A 48-year-old man is status posttraumatic gunshot wound to the abdomen, requiring

an emergent diverting colostomy with Hartmann pouch. His intraoperative course

was uneventful, requiring only crystalloid during the procedure. His hematocrit is
23%. The decision to transfuse is made; 2 U of type-specific packed red blood cells
are ordered. Approximately 5 minutes after the transfusion has begun, the patient
begins to develop a fever to 38.9 C (102 F), back pain, and some minimal difficulty
breathing. Current vital signs are: blood pressure 85/55 mm Hg, pulse 110/minute,
and oxygen saturation 99% on room air. A Foley catheter in place begins to produce
red-tinged urine. The site around his intravenous line and his wound staples appears
to be oozing with blood. There are no surgeons around and since you are his
primary care physician, you are paged to assess what is going on. Which of the
following is the most likely etiology for this reaction?

A. ABO typing
B. Antileukocyte antibodies
C. Bacterial contamination
D. Histamine release
E. Reaction to blood preservative

The correct answer is A. This patient has developed a hemolytic transfusion

reaction, characterized by fever, back pain, and respiratory difficulties. Such patients
may develop hypotension, disseminated intravascular coagulation, and acute renal
failure with severe reactions. These reactions are most commonly caused by
ABO-blood type incompatibility. The most important step in treating this patient is to
stop the offending agent (the blood) and send the blood back to the blood bank with
a sample of the patients blood for retesting. Supportive measures should be
instituted to treat the consequent symptoms of the transfusion (oxygen and
bronchodilators for respiratory difficulties, mannitol and furosemide for maintenance
of urine output, etc.).

Antileukocyte antibodies (choice B) are the causative agents for febrile reactions
that occur usually within 6 hours of a transfusion. These are usually not associated
with the hemolytic symptoms seen in this case. Some physicians would pretreat
their patients before transfusion with acetaminophen to prevent the febrile reactions;
others would not to be able to diagnose a febrile reaction.

Bacterial contamination (choice C) is a possibility in this patient and would present

similarly with regard to signs and symptoms, but its incidence is very rare and it is
not the most likely etiology in this patient.

Histamine release (choice D) is the classic mechanism for patients who develop
allergic reactions to transfusions, which usually presents with a rash, pruritus, and
bronchospasm without adverse effects of the hematologic system, as seen with this
patient. Treatment usually involves stopping the transfusion, treating with
diphenhydramine, and restarting the transfusion after symptoms abate.

Reaction to blood preservative (choice E) is not a known common adverse reaction

to administered blood products.
 A 19-year-old black man with sickle cell anemia comes to the emergency
department with a painful, persistent erection for the past 3 hours. He explains that
for the last 3 days before presentation he had a cold and had not been eating or
drinking very much. He did vomit a couple times yesterday but began feeling better
this morning. After lunch he got an erection and it has not gone away. He denies any
bone or joint pain. On examination he is uncomfortable. His temperature is 37.3 C
(99.1 F), blood pressure is 146/88 mm Hg, pulse is 108/min, and respirations are
26/min. Heart, lung, and abdominal examinations are noncontributory. Genital
examination displays an erect phallus that is diffusely edematous. The penis is
tender to palpation along its entire course and although examination is limited
because of tenderness there does not seem to be any sign of infection or trauma.
There is no urethral discharge. The corporal bodies are aspirated of dark, old blood
and then injected with an alpha-adrenergic agent. The priapism responds minimally.
Analgesics are administered. Which of the following is the most appropriate next
step in management?

A. Consider emergent arteriography and embolization of the internal pudendal

artery
B. Perform a corporal-glandular shunt
C. Provide intravenous hydration and oxygenation
D. Send the corporeal blood for a blood gas
E. Transfuse packed red blood cells emergently

The correct answer is C. This patient with known sickle cell disease is suffering
from low-flow priapism. There are two categories of priapism, low-flow and
high-flow. In low-flow priapism there is decreased venous outflow that results in
increased intracavernosal pressure, resulting in an erection. Increased
intracavernosal pressure leads to decreased arterial inflow and stasis of blood,
causing local hypoxia and acidosis. On examination the penis is fully erect with a
rigid corporal cavernosum but a soft glans and corpus spongiosum. A blood gas of
this corporal body will show a pH <7.25, pO2 <30, and pCO2 >60. Irrigation and
injection of the corporal bodies with an alpha-adrenergic agent helps decrease
arterial inflow and increase venous outflow. In patients with sickle cell disorder,
approximately 40% of adults and 64% of children eventually develop priapism.
Almost all cases of priapism in patients with sickle cell disease are of the low-flow
type. Treatment, once other possible causes have been ruled out, should be
prompt. Patients should be well hydrated, provided with supplemental oxygenation,
and have alkalinization with bicarbonate in intravenous fluids to prevent further red
blood cell sickling. These patients also should be given sufficient analgesics, usually
in the form of morphine.

High-flow priapism is caused by a sustained increased arterial inflow without

increased venous outflow resistance, resulting in high inflow and high outflow. This
produces an erection without local hypoxia or acidosis. On examination the penis is
not painful and has 60-100% rigidity of the corporal bodies with a soft glans and
corpus spongiosum. The etiology is penile or perineal trauma causing injury to the
cavernosal artery, resulting in a cavernous artery to corporal tissue fistula.
Treatment is not an emergency and if the erection does not subside with
observation then arteriography with embolization of the internal pudendal artery is
required (choice A).

Performing a shunt (choice B) between the corpora cavernosum and the corpus
spongiosum creates a fistula between the two structures that allows for the drainage
of old blood in patients with low-flow priapism. It is the final step in the treatment
algorithm of low-flow priapism because it is invasive, requires anesthesia, and leads
to erectile dysfunction.

Sending the corporeal blood for blood gas (choice D) at this stage is unhelpful. The
patients history, physical examination, and character of the blood on aspiration
confirm that this is a low-flow priapism. Sending the aspirate for blood gas is only
beneficial when the etiology is questioned.

The measures mentioned previously should be initial treatment algorithm. If they are
unsuccessful, the packed red blood cells may be transfused (choice E) until the
hemoglobin is >10, thereby reducing the percentage of hemoglobin S.
 You are performing a presurgical consultation on a 32-year-old man about to
undergo elective cholecystectomy for gallstones. The patient reports that he has had
several episodes in the past of turning yellow accompanied by mild fatigue. He has
never sought medical care because these episodes lasted only 2-3 days, with
complete resolution of his symptoms. The ultrasound report provided by the
surgeons states that there are gallstones within the gallbladder. In addition, the
report states that the spleen is enlarged, which you confirm on physical examination.
His laboratory studies show a hemoglobin of 11.9 g/dL, hematocrit of 32%, MCHC of
37 g/dL, MCV of 101, reticulocyte index 5%, and studies are Coombs negative.
Peripheral smear shows:

Which of the following is the most likely underlying abnormality?

A. Amino acid substitution leading to hemoglobin defect

B. Autoantibodies directed against components of the red cell membrane
C. Nutritional deficiency
D. Red cell enzyme defect
E. Red cell membrane defect

The correct answer is E. The patient has hereditary spherocytosis. Inheritance is

usually autosomal dominant. A membrane protein abnormality leads to quantitative
reduction in spectrin, leading to the spherical shape and increased permeability to
sodium. Hemolysis occurs predominantly in the spleen. The clinical picture is one of
compensated hemolytic anemia with mild to severely decreased hemoglobin and
sustained reticulocytosis. Pigment gallstones frequently are found. Splenomegaly is
evident. The MCHC is increased. The diagnosis is based on performing an osmotic
fragility test that demonstrates increased hemolysis when the red cells are placed in
hypotonic saline. Splenectomy is curative.

Hemoglobinopathies, such as sickle cell anemia and thalassemia, in addition to

having somewhat different CBC indices (such as low MCV), also would have
different peripheral blood picture (sickle cells, target cells) (choice A).

The patients blood is Coombs negative. Coombs positive hemolytic anemia, which
also is associated with spherocytes, occurs in autoimmune hemolytic anemia,
lymphoproliferative disorders (lymphoma, CLL), and collagen vascular disorders
(SLE) (choice B).

Fe deficiency anemia would result in microcytic hypochromic cells in the periphery

(smaller red cells with increased central pallor). Vitamin B12 or folate deficiency
would result in macro-ovalocytes (larger red cells) with megaloblastosis (neutrophils
with hypersegmented nuclei) (choice C).

Red cell enzyme defects (choice D), such as glucose-6-phosphatase deficiency,

although characterized by red cell hemolysis subjected to oxidant stress, are not
associated with splenomegaly or spherocytosis.
 A 28-year-old woman with known human immunodeficiency virus (HIV) infection is
brought to the clinic by a concerned friend. The friend tells you that over the past
week the patient has been at times disoriented, has suffered from a low-grade fever,
and seems to be getting worse. Examination reveals a confused young woman who
is slow to answer questions and is oriented only to person and place. She has a
temperature of 37.9 C (100.2 F), blood pressure of 108/62 mm Hg, pulse of 104/min,
and respirations of 20/min. Physical examination is unremarkable. Laboratory
studies show:

The staff hematologist reviews the blood smear and reports polychromatophilic red
cells, schistocytes, helmet cells, and rare nucleated red blood cells. This patient is
most likely to benefit from which of the following therapies?

A. Activated protein C
B. Broad-spectrum antibiotics
C. Intravenous immunoglobulin
D. Plasma exchange
E. Platelet transfusion

The correct answer is D. This patient has thrombotic thrombocytopenia purpura

(TTP), a disease characterized by the pentad of fever, anemia, thrombocytopenia,
renal insufficiency, and neurologic findings. The blood smear is consistent with a
microangiopathic hemolytic anemia (TTP, disseminated intravascular coagulation,
and hemolytic-uremic syndrome), while the rest of the laboratory work points toward
TTP. The current treatment of TTP is exchange transfusion.

Sepsis and disseminated intravascular coagulation (DIC) are treated with

broad-spectrum antibiotics (choice B) and, in certain cases, with activated protein C
(choice A). If this were DIC from sepsis, one would expect increased PT and aPPT,
a leukocytosis, and a higher D-dimer level. TTP is a disease caused by
larger-than-usual von Willebrand factor proteins that cause abnormal platelet
activation. Patients with TTP become transiently deficient in a plasma enzyme that
depolymerized ultra-high-molecular weight vWF released from endothelial cells.
Exchange therapy may remove abnormal forms of vWF and replenish the deficient
enzyme. Because the coagulation cascade is not activated (due to minimal
microvascular trauma), coagulation studies are not as altered as in DIC.

Intravenous immunoglobulin (IVIG) (choice C) is not a proven treatment of TTP.

Platelets should not be transfused (choice E) in TTP. Platelets will fuel the fire by
binding to abnormal von Willebrand protein. These platelets will be activated and
release further platelet activating factors, furthering thrombosis formation.
 You are asked by your secretary to consult on her father, who has been to several
physicians who have not been able to discern the cause of his anemia. The father is
a 67-year-old, well-nourished, talkative man who is in no apparent distress. He is not
taking any medications. He has been drinking a fifth of whiskey per day for the last
20 years, and smokes 10 cigarettes per day. He has palmar erythema and spider
angiomata on his upper chest area. A recent gastrointestinal workup including
esophagogastroduodenoscopy, push enteroscopy of the small bowel, and
colonoscopy revealed: 1+ esophageal varices; no bleeding lesions, ulcers, or
gastritis in the stomach; normal small bowel; and no lesions, polyps, diverticula, or
hemorrhoids in the colon. Serum protein electrophoresis and immunofixation did not
reveal a monoclonal protein. Laboratory studies show: BUN 12 mg/dL, creatinine 0.8
mg/dL, hemoglobin 10.5 g/dL, MCV 75, serum iron 226 microgram/dL, TIBC 330
microgram/dL, transferrin saturation 75%. Cytogenetics show normal male 46,XY.
Hemoglobin electrophoresis shows HbA 97%, HbA2 2%, and HbF 1%. You decide
to perform a bone marrow biopsy, which is shown.

Which of the following is the most likely underlying cause of this patients anemia?

A. Hemoglobinopathy
B. Myelodysplastic syndrome
C. Iron deficiency
D. Erythropoietin deficiency
E. Chronic alcoholism
The correct answer is E. The patient has sideroblastic anemia due to chronic
alcoholism. Sideroblastic anemias are a group of diseases in which heme synthesis
is abnormal. The main characteristic is the presence of ringed sideroblasts in
marrow smears stained for iron. Ringed sideroblasts result from the accumulation of
iron in the mitochondria of erythroid precursors. Primary sideroblastic anemias occur
as hereditary disorders that can be X-linked or autosomal. Secondary sideroblastic
anemias are caused by drugs (isoniazid, pyrazinamide, chloramphenicol), by other
marrow toxins (alcohol, lead poisoning), or by primary marrow disorders
(neoplasms, myeloid leukemia). The bone marrow stain shows erythroid
hyperplasia, increased sideroblasts, and numerous ring sideroblasts where the iron
granules tightly ring the nucleus. Sideroblastic anemia is characterized by high
serum iron, decreased or normal TIBC, and increased transferrin percent saturation.

Hemoglobinopathy (choice A) is incorrect. The patients hemoglobin electrophoresis

reveals a normal adult hemoglobin pattern.

Myelodysplastic syndrome (choice B) is incorrect; this patient has normal

cytogenetics.

Iron deficiency (choice C) is incorrect. If it were the correct choice, the iron
deficiency workup would reveal decreased or absent marrow iron stores, decreased
serum iron, increased TIBC, and decreased transferrin percent saturation.

Erythropoietin deficiency (choice D) is incorrect. Erythropoietin is secreted by the

kidneys, but this patients renal function is normal.
 You are called by emergency room physicians to evaluate a 21-year-old Mexican
migrant worker who comes in complaining of several days of profound fatigue,
dyspnea on exertion, and spontaneous nosebleeds. Laboratory studies on arrival
show the following: white blood cell count 2,100/ mm3, absolute neutrophil count
1,100, Hgb 5g/dL, and platelets 9,000/ mm3. The emergency room physicians have
proceeded with transfusion of 4 units of packed red cells and 5 units of random
pooled platelets. The patient reports that for the last 7 years he has been working as
an assistant pesticide sprayer in various farming communities throughout northern
Mexico. He denies ever using intravenous drugs, and has not engaged in sexual
intercourse with anyone. On examination there is no hepatosplenomegaly, no
lymphadenopathy, and no bone tenderness. He has no complaints of joint
symptoms or rashes. He is thin and well-developed, but his conjunctivae are pale
and dry and he has petechiae and large ecchymoses on his lower extremities, as
well as crusted blood in his right nares. He is now being admitted to the general
medicine service. While you are evaluating him, further studies return including
reticulocyte index of 0.3%. Peripheral smear shows:

The next morning the hematology service performs a bone marrow biopsy which
shows the following:
Which of the following is the most likely underlying cause of his condition?

A. Acute leukemia
B. Hypersplenism
C. Aplastic anemia
D. Lymphoma
E. Systemic lupus erythematosus

The correct answer is C. The patient has acquired aplastic anemia secondary to
pesticide/insecticide exposure. Pancytopenia and a marked decrease in the
cellularity of the bone marrow are characteristic. The etiologies of aplastic anemia
are idiopathic, secondary to drugs, chemicals, radiation, viral infections (hepatitis),
or the immune destruction or suppression of stem cells. Anemia leads to symptoms
of weakness and fatigue. Neutropenia causes susceptibility to bacterial infections.
Thrombocytopenia results in mucosal and skin bleeding. There should be no
hepatosplenomegaly, lymphadenopathy, or bone tenderness. Anemia can be
severe and is always associated with decreased reticulocytes. The bone marrow
aspirate and the biopsy appear hypocellular with only scant numbers of normal
hematopoietic progenitors. No abnormal cells are seen.

Acute leukemia (choice A) is incorrect as there are no circulating myelo- or

lymphoblasts seen in the peripheral smear. In acute leukemia one would expect the
bone marrow to be hypercellular and filled with abnormal elements.

Hypersplenism (choice B) can result in pancytopenia from trapping of cells;

however, this patient does not have splenomegaly.

The patient does not have lymphoma (choice D). The bone marrow would be
expected to have malignant appearing cells as well.

Systemic lupus erythematosus (choice E) can rarely cause aplastic anemia by

suppressing the hematopoietic stem cell by an IgG autoantibody directed against
the stem cell. This patient does not appear to have the clinical picture of a
rheumatologic disorder.
 You are on staff at the student health services center for a nearby college. A
20-year-old sophomore complains of a 1-month history of early satiety and fullness
in her left upper quadrant. She does not smoke but drinks a six-pack of beer every
weekend. She states that she has been depressed since breaking up with her
boyfriend several weeks ago. Review of systems reveals a mild upper respiratory
illness 2 months ago and two episodes of cystitis within the last year. On
examination, she is in no apparent distress. The only thing remarkable is
splenomegaly 4 cm below the left costal margin. There is no lymphadenopathy.
Laboratory studies reveal a white cell count of 120,000/microL (diff: 65,000
neutrophils, 26,000 metamyelocytes, 10,000 promyelocytes, 11,000 myeloblasts,
4,000 basophils, 2,000 eosinophils, 2,000 monocytes), hemoglobin of 14.2 g/dL,
hematocrit of 42%, and platelets 250,000/microL. Peripheral smear shows:

Further diagnostic testing most likely will reveal which of the following?

A. Auer rods in the peripheral smear

B. (8;21) translocation
C. High LAP (leukocyte alkaline phosphatase) score
D. (9;22) translocation
E. Reed-Sternberg cells in the bone marrow
The correct answer is D. This patient has CML (chronic myelogenous leukemia). It
is one of the myeloproliferative syndromes, with abnormal proliferation of immature
granulocytes, neutrophils, eosinophils, and basophils in blood, bone marrow,
spleen, and liver. Patients typically present with early satiety and left upper quadrant
fullness. Workup reveals leukocytosis and splenomegaly. The smear shows the
entire spectrum of granulocytic precursors. There is also an absolute increase in
basophils and eosinophils. More than 95% of patients have the Philadelphia
chromosome, t(9;22), which is formed by the translocation of the abl oncogene from
chromosome 9 to the bcr region of chromosome 22, thus creating a new gene
(bcr/abl). The leukocyte alkaline phosphatase (LAP) score is low or absent.

Auer rods (choice A) are specific for AML and are especially prominent in the M3
(promyelocytic) subtype. Splenomegaly is uncommon in AML.

The (8;21) translocation is one of the good prognostic indicators in AML (choice B).

CML is associated with a low LAP score, not a high LAP score (choice C).

Reed-Sternberg cells (choice E) are found in Hodgkin disease. Patients frequently

present with B symptoms (fever, weight loss, and night sweats) with
lymphadenopathy.
 A 30-year old woman is being evaluated for a cramping abdominal pain that has
been occurring for the past 6 months. She has intermittent vomiting, constipation,
difficulty urinating, and leg weakness. She presents again with similar symptoms in
the emergency department. She has no other medical issues or allergies and does
not take any medications. Her temperature is 37 C (98.6 F). Examination is
unremarkable and she does not have any abdominal rebound tenderness. An
extensive evaluation is initiated and findings include a normal white blood cell count,
urinalysis, liver function tests, amylase, lipase, and beta-hCG. A prior evaluation has
showed normal abdominal imaging, endoscopy and angiography. Urinary
porphobilinogen excretion is elevated. Which of the following is the appropriate
management?

A. Aspirin administration
B. Intravenous heme administration
C. Intravenous narcotic analgesics administration
D. Pyridoxine administration
E. Sunlight avoidance

The correct answer is B. This patient has a porphyria--an inherited or acquired

disorder of heme biosynthesis. Acute intermittent porphyria (AIP) is caused by a
deficiency of HMB synthase. Heterozygotes for the condition are prone to recurrent
abdominal pain. The test of choice is increased urinary porphobilinogen level. Heme
therapy causes feedback inhibition of early heme biosynthesis and reduces attacks.

Aspirin administration may cause some resolution in the pain, but will not treat the
underlying condition in this patient (choice A).

Narcotics may ameliorate some of the pain but will not prevent recurrent attacks
(choice C).

The severe anemia may respond to pyridoxine supplementation (choice D).

Porphyria cutanea tarda (PCT) is the most common porphyria and involves
cutaneous photosensitivity. Neurologic manifestations are not seen (choice E).
 A 45-year-old woman comes to the emergency department because of acute
shortness of breath and hemoptysis. Pulmonary angiography confirms a pulmonary
embolus. On further questioning, the patient denies smoking or using birth control
pills. She has not been on a prolonged journey during which she was immobilized.
She denies recent trauma. She had a recent negative mammogram and Pap smear.
She reports a strong family history of miscarriages. She had a deep venous
thrombosis when she was pregnant at ages 23 and 28 years. Her mother died of
pulmonary embolus at age 48 years. The patient has no other medical history. She
denies having allergies. Laboratory studies are positive for a high D-dimer. Which of
the following is the most appropriate additional study at this time?

A. Activated protein C level

B. Activated protein S level
C. Factor V Leiden mutation
D. Lactate dehydrogenase level
E. Lupus anticoagulant level

The correct answer is C. This patient has a hereditary thrombophilia and a

predisposition to thrombosis. The most likely cause of this condition is a factor V
mutation. This is seen in 4% of the general population presenting with such
thrombosis.

Activated protein C deficiency (choice A) is very rare and less common than
conditions such as hyperhomocysteinemia.

Similarly, activated protein S deficiency is very rare (choice B).

Any patient presenting with an unexplained thrombosis should be worked up for a

malignancy. This includes a mammogram, pelvic examination, colonoscopy, and
testicular examination. This patient also has had a thrombosis more than 20 years
ago. This makes a malignancy unlikely. Furthermore, the family history leads to a
diagnosis of a hereditary thrombophilia. Lactate dehydrogenase level (choice D)
seeks to determine if there might be a lymphoma.

Lupus anticoagulant level (choice E) seeks to determine if the patient has an

antiphospholipid syndrome. This should be on the differential diagnosis. Given the
presentation, however, the aforementioned syndromes should be ruled out first.
 A 70-year-old man comes to the clinic complaining of worsening back pain. The
pain has had an insidious onset, becoming progressively more painful over the past
8 months. The pain is mainly lumbar in nature, with no radiation, and is improved
when recumbent. Initially the pain was controlled with ibuprofen and acetaminophen.
As these no longer work to control the pain, he has decided to seek treatment. He
denies any heavy lifting or trauma to the area. A full review of systems reveals a
10-lb weight loss over the past 6 months but is otherwise unremarkable. Past
medical history is significant for controlled hypertension, gout, and osteoarthritis that
has manifested mainly as knee pain. Vital signs are within normal limits. Physical
examination reveals mild pain when the lumbar spine is palpated but is otherwise
normal. A radiograph of the spine is ordered, which reveals a dime-sized lucency
with a surrounding rim of sclerosis present in the L5 vertebra. Concerned about this
lesion, you order a full set of laboratory panels, including complete blood count, liver
function tests, and a set of chemistries. Significant findings include a hematocrit of
32%, a calcium level of 11.2 mg/dL, and a creatinine of 1.7 mg/dL. A urine dipstick
reveals no proteinuria or other abnormalities, but a serum protein level is elevated at
10 g/dL. Serum protein electrophoresis reveals a monoclonal pattern found to be
IgG kappa-chain M protein. A radiographic skeletal series is ordered and the patient
is consented for a bone marrow biopsy. Which of the following is an additional
appropriate test to order in the workup of this patient?

A. Full body CT scan

B. Interleukin (IL)-6 blood level
C. Magnetic resonance imaging (MRI)
D. Nuclear medicine bone scan
E. Urine electrophoresis

The correct answer is E. This patient likely has multiple myeloma, a common
cause of monoclonal gammopathy in elderly patients. If this patient does indeed
have multiple myeloma, the bone marrow biopsy is likely to show more than 10%
plasma cells, whereas the radiographic series may show other bone lesions.
Multiple myeloma can cause serious renal damage (myeloma kidney), which
should be screened for, particularly in a patient with an elevated creatinine. The
urine dipstick detects only albumin and misses the secreted Bence-Jones proteins.
A serum electrophoresis will provide more information.

Full body CT scan (choice A) and MRI (choice C) can complement a skeletal
survey if the radiographs are difficult to interpret. Neither needs to be ordered
routinely, however, and in this case the decision to order either test should be
deferred until the skeletal series is complete.

IL-6 (choice B) is secreted by myeloma cells and is believed to activate osteoclasts,

resulting in the lytic punched out lesions of multiple myeloma, as seen in this
patient. To date, measuring IL-6 levels has not been proven to be a useful test in
diagnosing the disease.

Bone scans (choice D) are of low yield in finding occult lesions, as the lesions of
multiple myeloma are osteoclastic, not blastic. As there is no new cell growth, there
will be little radioactive tracer uptake.
 A 70-year-old man comes to the urgent care clinic complaining of massive bruising
and bleeding from his gums when he brushes his teeth. He is known to have a
history of atrial fibrillation, which is treated with metoprolol and warfarin. He has
been stable on his current dose of warfarin, so it is surprising that he is now suffering
from increased bleeding. None of his other medications have recently been
changed, and he denies using any NSAID or other recent use of over-the-counter
medications. The patient reports that he is taking his warfarin as prescribed, and has
been recently trying to live a healthy life. Upon further questioning, he reports trying
to exercise more often, taking daily vitamins, and eating more vegetables. His new
diet includes a lot of vegetables, such as spinach, Brussels sprouts, and broccoli, as
well as copious amounts of green tea for its anticancer effects. A prothrombin time is
ordered, but will not be available for another hour. Which of the following dietary
changes is most likely responsible for this patients increased bleeding?

A. Brussels sprouts
B. Green tea
C. Spinach
D. Unrelated to diet
E. Vitamins

The correct answer is E. Vitamins, particularly vitamin E, can increase the risk of
bleeding in patients taking warfarin. Patients taking warfarin need to be educated on
the risks of drug interactions from over-the-counter drugs, particularly analgesics
and the risk of drug interactions from other prescription medications; and should
also be cautioned not to radically change their diets. Dietary change, which may
alter the amount of vitamin K consumed, can reduce the efficacy of warfarin. Foods
high in vitamin K include Brussels sprouts (choice A), green tea (choice B), and
spinach (choice C), as well as organ meat, alfalfa, asparagus, broccoli, cabbage,
cauliflower, kale, turnip greens, and watercress.

Given that the patient has no obvious drug interactions, compliance issues, or
illness to explain the sudden bleeding, it is reasonable to assume the problem may
be related to diet. While there are numerous causes of increased bleeding while on
a previously stable regimen of warfarin, there is no reason to think this patients
situation is unrelated to diet (choice D).
 A 59-year-old man has several medical problems, including hypertension,
hyperlipidemia, and chronic atrial fibrillation. He has had atrial fibrillation for
approximately 4 years. His ventricular response rate is well controlled, and he has
never experienced any embolic phenomenon. His medications include
hydrochlorothiazide (25 mg daily), lovastatin (40 mg daily), atenolol (50 mg daily),
and warfarin (7.5 mg alternating with 5.0 mg, every other day). He has been on
warfarin for approximately 5 years and on a stable dose for the past 3 years. He
calls you because he has developed some dental problems and his dentist is
planning to extract five mandibular teeth and possibly perform a partial alveolectomy
(subtotal excision of the alveolar process of the mandible). The patient is worried
about the possibility of bleeding during the dental surgery, and his dentist told him to
call you for advice about whether the warfarin should be continued or discontinued
before surgery. Laboratory studies obtained this week include the following:

What recommendation should you make regarding warfarin therapy in relation to the
dental surgery?

A. Continue warfarin therapy at current dose; do not discontinue warfarin before

surgery
B. Stop warfarin and hospitalize patient for intravenous heparin therapy until the INR
has normalized, at which point surgery can be scheduled; stop intravenous
heparin shortly before surgery; perform surgery and then resume intravenous
heparin after surgery; restart warfarin and continue heparin until INR has returned
to therapeutic range
C. Stop warfarin before surgery and resume warfarin after surgery

D. Stop warfarin before surgery and substitute aspirin; discontinue aspirin after
surgery and restart warfarin
E. Stop warfarin; begin subcutaneous low-molecular weight heparin (e.g.,
enoxaparin) and continue it until INR has normalized, at which point surgery can
be scheduled; stop low-molecular weight heparin shortly before surgery; perform
surgery and then restart warfarin and low-molecular weight heparin after surgery;
discontinue heparin when INR has returned to therapeutic range
The correct answer is A. It is not necessary to stop chronic warfarin therapy when
patients undergo dental surgery, assuming the INR is in the therapeutic range as it
is in this case (therapeutic range for atrial fibrillation is 2.0-3.0). The risk for serious
bleeding during dental surgery with a therapeutic INR is very low, only 0.2% based
on studies involving several thousand patients. Stopping the warfarin, on the other
hand, exposes the patient to the risk for thromboembolic complications, which occur
in 0.4% of patients. Other procedures for which it is unnecessary to stop warfarin
therapy are arthrocentesis and cataract surgery. Warfarin also can be continued
during upper or lower gastrointestinal endoscopy (with or without biopsy), unless a
polypectomy is to be performed. Note that it is not appropriate to continue warfarin
therapy for any of these procedures if the patients INR is supra therapeutic.

Temporarily stopping warfarin and substituting heparin (choice B) is unnecessary,

based on the explanation given in the previous paragraph. This approach would be
appropriate for patients who are undergoing surgical procedures that have a higher
risk for bleeding than those mentioned in the previous paragraph, and who have a
high risk for thromboembolic events (e.g., mechanical mitral valve, atrial fibrillation
with a history of stroke).

Simply stopping warfarin (choice C) without substituting heparin is unnecessary for

the reasons noted in the discussion of choice A. The approach of stopping warfarin
without substituting heparin would be an appropriate approach for a patient who is
undergoing a procedure with a higher risk for bleeding than dental surgery, when the
patient has a low risk for thromboembolic events (e.g., atrial fibrillation without a
history of stroke).

Temporarily stopping warfarin and substituting aspirin (choice D) is not appropriate.

As noted, it is not necessary to stop warfarin for dental surgery, and aspirin therapy
impairs platelet function and likely increases the risk for bleeding.

Temporarily stopping warfarin and substituting low-molecular weight heparin

(choice E) is not necessary for dental surgery. It is, however, an alternate approach
to that outlined in choice C for a patient undergoing surgery that has a higher risk for
bleeding than dental surgery, and who also has a substantial risk for
thromboembolic events.
A 33-year-old business executive comes into the office for her yearly checkup. She
had gone to the lab for routine blood tests ordered by her primary physician. On
evaluation of her laboratory results, it is noted that she has a hematocrit of 35%. She
denies feelings symptoms of fatigue, malaise, or lethargy. She is physically active,
eats three meals a day, and is not involved in substance use. Her vital signs and
physical examination are unremarkable. Which of the following is the most likely
etiology of this laboratory finding?

A. Hemochromatosis anemia
B. Iron deficiency anemia
C. Macrocytic anemia
D. Megaloblastic anemia
E. Sideroblastic anemia

The correct answer is B. Healthy women who are still menstruating are at very
high risk for developing iron deficiency anemia because of monthly blood loss from
menses. Presenting symptoms are usually insidious and mild, involving a
generalized decrease in energy levels, but patients can also be asymptomatic
during this period. Treatment of iron deficiency anemia is usually increased intake of
iron-rich foods, as well as iron supplementation.

Hemochromatosis anemia (choice A) is an inherited disorder resulting in the excess

absorption and utilization of iron from foods. It usually results in an increased
hematocrit, the treatment for which is chronic phlebotomy

Macrocytic anemias (choice C) are most commonly seen in patients who are
deprived of cyanocobalamin (B12) or folate. Both of these are usually seen in
patients who are nutritionally deprived or take medications that can interfere with the
absorption or metabolism of B12 or folate. Patients with surgical procedures can
also have an inability to absorb B12 or folate (such as in the case of patients with
pernicious anemia or massive ileal resection).

Megaloblastic anemia (choice D) is seen in patients who have impaired DNA

synthesis of red blood cell precursors. The most common megaloblastic anemias
are those caused by B12 and folate deficiency.

Sideroblastic anemia (choice E) is a heterogenous disease but is most commonly

an X-linked disease resulting in ineffective red blood cell formation. It is
characterized by abnormal deposits of iron in red blood cell mitochondria with
formation of a ring around the red blood cell nucleus. It is usually caused by
ingestion of drugs or toxins; it can also be secondary to cancer (usually
myelodysplastic disorders).
 You are called to the emergency room to evaluate a 37-year-old Hispanic woman
with a history of polysubstance abuse and HIV, current CD4 count 130 cells/L, who
was brought in by her family because she has been acting funny for several days.
The triage nurse tells you that upon arrival the patient was fully alert and oriented,
answering all questions appropriately, but by the time you see her, the patient is
lying down on the stretcher, mumbling softly and appearing lethargic. When you
attempt to ask her questions, she does not make eye contact nor does she respond
to you. Her family reports that she has been complaining of headaches and blurry
vision the last few days, and states that she keeps becoming sleepy many times
each day. The family also reports that the patient has been complaining of
weakness and poor appetite. Her temperature is 39.5 C (103.1 F). A noncontrast
head CT scan performed on arrival has been read out as unremarkable. Her
leukocyte count is 2.5/mm3, hemoglobin is 3.5 g/dL, hematocrit is 10.8%, platelets
are 16,000/mm3, creatinine is 1.8 mg/dL, LDH is 1675 U/L, PT is 12.5 seconds,
aPTT is 33 seconds, and reticulocyte index is 6.3%. Coombs test is negative. The
medical student rotating in the emergency department asks you to quickly look at the
peripheral smear shown.

Which of the following is the most likely diagnosis?

A. AIDS dementia complex

B. Disseminated intravascular coagulation
C. Evans syndrome
D. Hemolytic-uremic syndrome
E. Thrombotic thrombocytopenic purpura
The correct answer is E. The patient has thrombotic thrombocytopenic purpura
(TTP), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and
a very high serum LDH. Noninfectious fever, neurologic problems, and renal
abnormalities are less commonly seen. TTP is seen mainly in young adults between
20 and 50 years of age, and there is a slight female predominance. It is sometimes
precipitated by estrogen use or pregnancy, and is increasingly encountered in the
setting of HIV disease. The neurologic symptoms wax and wane over minutes, and
include headache, confusion, aphasia, and alterations in consciousness from
lethargy to coma. More advanced cases may present with hemiparesis and
seizures. Anemia may be marked. There is usually marked reticulocytosis and
sometimes circulating nucleated red cells. The hallmark is a microangiopathic blood
picture with a significant number of fragmented red cells (schistocytes, helmet cells)
on the smear. Thrombocytopenia may be severe. The Coombs test is negative.
Treatment is emergent large volume plasmapheresis.

AIDS dementia (choice A) is the most common cause of mental status changes in
HIV-infected patients. However, it would not present acutely with the clinical picture
and lab findings noted above.

Disseminated intravascular coagulation (choice B) is excluded by normal

coagulation results.

Evans syndrome (choice C) is the combination of autoimmune thrombocytopenia

and autoimmune hemolytic anemia, but the peripheral smear should show
spherocytes, not red cell fragments. Further, the Coombs test will be positive.

Hemolytic-uremic syndrome (choice D) is certainly a possibility, but the presence of

neurologic abnormalities in this patient rules this out.
 A 62-year-old man comes to the emergency department with 3 hours of substernal
chest pain. He has a past medical history that includes peripheral vascular disease,
hypertension, diabetes mellitus, and coronary artery disease. His medications
include metoprolol, lisinopril, aspirin, and insulin. He has no known drug allergies.
His blood pressure is 100/60 mm Hg and pulse is 72/min. Lungs are clear to
auscultation. Cardiac examination is unremarkable. Cardiac enzymes are consistent
with an acute myocardial infarction. All other laboratory results are normal. His
electrocardiogram reveals ST elevations in the anterior leads. The patient is taken to
the cardiac catheterization laboratory and a stent is placed in the left anterior
descending artery. He is then monitored in the intensive care unit. He is started on a
heparin infusion, metoprolol, aspirin, nitroglycerin, and ranitidine. The next day he
complains of numbness in his right hand. Examination reveals that he has no pulse
in the right hand. His platelet count is 32,000/mm3. Which of the following is the
most likely diagnosis?

A. Emboli from aortic atherosclerosis

B. Heparin-induced thrombocytopenia
C. Idiopathic thrombocytopenia
D. Paradoxic embolus
E. Ranitidine-induced thrombocytopenia

The correct answer is B. This patient recently was started on heparin. Twenty-four
hours later he has severely low platelet counts. He most likely has heparin-induced
thrombocytopenia. Treatment would include stopping the heparin and starting an
alternative agent. As a result of platelet aggregation caused by the heparin, the
patient has developed a thrombus in the arterial circulation of the right hand that is
causing the pulseless presentation.

This patient has atherosclerosis and is certainly at risk for emboli from this disease
(choice A). Furthermore, when heparin was started, it is possible that an atheroma
broke away and embolized downstream. His acute presentation and low platelet
counts, however, lead to a diagnosis of heparin-induced thrombocytopenia.

Idiopathic thrombocytopenia (choice C) is a hematologic disorder. Findings include

low platelet counts. The combination of a low platelet count and an embolus,
however, leads away from this diagnosis.

If this patient had a patent foramen ovale and a DVT, a paradoxic embolus (choice
D) would be very high on the differential diagnosis.

Ranitidine can cause thrombocytopenia (choice E). In fact, in any patient who has
thrombocytopenia, the medication list should be reviewed, because several
medications can cause a low platelet count.
 You are currently the staff physician for the student health center of a nearby
college. A 21-year-old junior comes to see you today for follow-up from his first visit
a few days ago. He had originally stated that for the last 2 weeks has had easy
fatigability and can no longer work out at the gym. He had noted that he had become
very pale, and a complete blood count performed on the first visit revealed a
hemoglobin of 7.7 g/dL, platelet count of 86,000/ mm3, and white blood cell count of
56,000/ mm 3. Peripheral smear shows:

Bone marrow examination reveals a hypercellular marrow with similar-appearing

lymphoid cells for the most part replacing and crowding out normal hematopoietic
cells. Flow cytometry of the marrow aspirate is typical for immature B cells (CD10+,
19+, 34+ without cytoplasmic or surface immunoglobulins). Cytogenetics reveals the
t(4;11) balanced translocation. Upon making the diagnosis, which is the most
appropriate intervention?

A. Anthracycline and cytarabine

B. All-trans retinoic acid
C. Combination of daunorubicin, vincristine, prednisone, and L-asparaginase
D. Splenectomy
E. Thalidomide and dexamethasone

The correct answer is C. The patient has acute lymphoblastic leukemia (ALL). The
standard induction therapy includes prednisone, vincristine, daunorubicin, and
L-asparaginase. The peripheral smear shows many lymphoblasts. ALL accounts for
one-fifth of adult acute leukemias. The enzyme terminal deoxyribonucleotidyl
transferase (TdT) is found in high concentration in normal immature thymocytes but
not in mature lymphoid cells. TdT is present in practically all patients with ALL.
PreB-ALL cells are typically CD19+, CD10+, and 34+. B-ALL cells are typically
CD19+ and positive for surface immunoglobulin. T-ALL cells are typically CD2+ and
CD7+. Poor prognostic factors include high initial white count; certain chromosome
abnormalities such as t(9;22), t(8;14), and t(4;11); male sex; and CNS involvement.

The combination of an anthracycline and cytarabine (choice A) is used as induction

regimen for acute myeloblastic leukemia(AML).

All-trans retinoic acid (choice B) is used in acute promyelocytic leukemia (APL) with
the (15;17) translocation.

Splenectomy (choice D) would not be curative for ALL.

Thalidomide and dexamethasone (choice E) is currently used for multiple myeloma

refractory to standard therapy.
 A previously healthy 34-year-old advertising executive comes to your office
concerned about abnormal laboratory values discovered during a routine travel
physical. The patient plans to travel to Tunisia to visit his grandparents, but wishes
to have a clean bill of health before traveling. A complete blood count, the first this
patient has ever had, revealed a mild anemia, and he returns today seeking advice
on his condition. He denies any weakness or fatigue. He plays racquetball at least
twice a week and consumes a normal diet. A complete review of symptoms is
unremarkable. Aside from this mild anemia, this patient has been in good health.
Vital signs and physical examination are within normal limits. Complete blood count
shows:

A review of the blood smear reveals small, hypochromic red cells, with numerous red
cells with a dark center surrounded by a light band that again is encircled by a darker
ring, intracellular inclusions attached to some red cell membranes, and occasional
basophilic stippling. Which of the following is the most appropriate test to diagnose
and document the cause of this patients anemia?

A. Hemoglobin electrophoresis
B. Iron panel
C. Lead level
D. Trial of iron supplementation
E. Vitamin B12 and folate levels

The correct answer is A. This patient likely has beta-thalassemia minor, a

common cause of microcytic anemia in adult populations. One of the beta-globulin
polypeptide chains is defective, resulting in abnormal ratios of alpha- and
beta-globulin polypeptides. Failure to produce adequate quantities of one globulin
chain creates a surplus of the other, which can precipitate, forming Heinz bodies
(intracellular inclusions attached to red-cell membranes). The resultant blood cell is
unstable and prone to lysis. Beta-thalassemia minor is often asymptomatic, usually
mild (hematocrit greater than 30%), but with severe microcytosis. It is common in
Mediterranean (such as this patient), African, Middle Eastern, Indian, and central
Asian patients. The electrophoresis should reveal an elevated level of hemoglobin
A2 and fetal hemoglobin. It is important to document thalassemia and inform the
patient, to avoid inadvertent administration of iron by other health care practitioners.

If the electrophoresis is negative, or the clinical and laboratory picture is unclear, an

iron panel (choice B) can help clarify this patients condition. It is unlikely that this
healthy male patient also has iron deficiency anemia. However, if the patient were a
woman with heavy menses, an iron panel would be appropriate to look for
concomitant iron deficiency anemia, which can complicate the interpretation of a
hemoglobin electrophoresis. This condition is often mistakenly diagnosed as iron
deficiency anemia, and an empiric trial of iron supplementation (choice D) is given.
This is risky, inasmuch as patients with thalassemia are at risk for iron overload from
constant hemolysis as well as iron supplementation.

Lead (choice C) does cause basophilic stippling and microcytic anemia, but is a
rare cause of anemia in adult males. Children who eat paint chips are the classic
victims of lead poisoning. If there were associated risk factors (occupation, mental
status changes, etc.) a blood lead level may be appropriate.

Vitamin B12 and folate (choice E) deficiencies cause a macrocytic, not microcytic,
anemia. There is no reason to check these levels, given this patients remarkably
reduced MCV.
 A 58-year-old woman comes to the emergency department with chest pain and
shortness of breath. The chest pain is pleuritic in nature, and, together with the
shortness of breath, began abruptly earlier in the day. Given the patients known
metastatic breast cancer, there is concern that she is hypercoagulable and has a
pulmonary embolus. Furthermore, she has had one episode of deep venous
thrombus years ago when she was pregnant, which was treated with heparin. A
ventilation perfusion scan confirms the presence of segmental perfusion defects.
The patient refuses admission to the hospital, stating, If I am going to die, it is going
to be at home. After evaluation by the psychiatry service, the patient is given a
10-mg dose of warfarin and discharged with low-molecular weight heparin for
self-injection. She returns 2 days later for a coagulation clinic appointment with
large, purple, necrotic appearing patches across her breasts and extremities. She
states that she took the warfarin as instructed, but did not take any of the
low-molecular weight heparin after the first injection because of the pain of
self-injection. The patient understands the severity of her situation and accepts
admission to the hospital, as well as having a skin biopsy performed by the
dermatology service. The biopsy demonstrates fibrin thrombi within cutaneous
vessels with large areas of interstitial hemorrhage. A heparin-induced antibody panel
is negative, and the patients platelet level is normal. Which of the following is the
most likely condition contributing to this patients skin lesions?

A. Idiosyncratic reaction to heparin

B. Inadequate anticoagulation
C. Pre-existing vitamin K deficiency
D. Tumor invasion of dermal skin layers
E. Underlying protein C deficiency

The correct answer is E. This patient is likely to have an underlying clotting factor
deficiency. Patients with underlying coagulopathies, most commonly protein C
deficiency, are at an increased risk for warfarin-induced skin necrosis. It is
presumed that patients with a relative deficiency of protein C are at risk for a
paradoxic hypercoagulable state when given warfarin. Warfarin inhibits production
of factors II, V, VII, X, and the anticoagulants protein C and protein S. Protein C has
a short half-life, and in patients with a reduced concentration to begin with, it may be
cleared from the blood before the vitamin K-dependent procoagulants. The resulting
hypercoagulable state results in diffuse thrombosis and skin lesions.

Heparin (choice A) also can cause skin lesions. This patient has tolerated heparin
in the past, however, and has no antibodies. Low-molecular weight heparin,
particularly if only one dose was given, is less likely to induce adverse events than
unfractionated heparin.

This patient likely had inadequate anticoagulation (choice B) in that she did not
receive low-molecular weight heparin as a bridge to warfarin therapy. The two
should overlap until the patient has a therapeutic INR. Recurrent clots are unlikely to
manifest as skin lesions, however. This diffuse, superficial pattern is more
consistent with warfarin-induced skin necrosis, which is more common with
high-loading doses of warfarin (as occurred here).

Vitamin K deficiency (choice C) would make this patient more prone to bleeding,
not thrombosis.

Tumor invasion (choice D) can cause an inflammatory breast cancer that may look
like mastitis but is unlikely to produce these large necrotic patches.
 A 72-year-old woman is brought to see you by her granddaughter. The
granddaughter is worried because her grandmother has had difficulty walking over
the last 3 months. The grandmother states that, although she has been unstable on
her feet, what really bothers her is numbness and tingling, as well as occasional
burning pain in her hands and feet, symptoms that have become worse over the last
year. Review of systems reveals some mild fatigue, a 10-lb weight loss over the last
year, and some mild dyspepsia, but is otherwise unremarkable. She states that her
appetite and diet, although minimal, are unchanged over the previous year. Past
medical history is significant for hypertension, iron deficiency anemia before
menopause, and diverticulosis. Her medications include hydrochlorothiazide, a daily
baby aspirin, fiber supplements, and a stool softener. Vital signs today are:
temperature 37.0 C (98.6 C), blood pressure 135/88 mm Hg, pulse 78/min, and
respirations 20/min. Physical examination reveals a thin, elderly woman in no
apparent distress. Although her physical examination is normal aside from some
patchy areas of vitiligo on her torso, neurologic examination is grossly irregular. Her
gait is ataxic and broad-based, requiring her to steady herself with a cane. Lower
extremity strength is 4 of 5, and upper extremity strength is 5 of 5. Deep tendon
reflexes are 2+ and symmetric, and toes flex downward when the lateral planter
aspect of the foot is scraped with a reflex hammer. Sensation is intact to light touch
and pinprick, but markedly reduced to proprioception. Her cranial nerves are intact,
though you do notice some mild atrophy of her tongue. When asked to stand still
and extend her arms, the patient is stable. On closing her eyes, however, she
becomes unstable and nearly falls. Laboratory studies show:

A manual review of the blood smear confirms the macrocytosis and notes that 6% of
the neutrophils are hypersegmented. Based on these results, a vitamin B12 level is
checked, which is 210 pg/mL (normal greater than 200 pg/mL). Which of the
following is the most appropriate next step in evaluating this patients anemia?

A. Bone marrow biopsy

B. Empiric trial of oral multivitamin
C. Folate level
D. Iron panel
E. Methylmalonate level

The correct answer is E. This patient has the signs and symptoms of vitamin B12
deficiency and may have pernicious anemia, hinted at by the vitiligo and atrophic
tongue. Although hypersegmented neutrophils, neurologic findings, and macrocytic
anemia are practically pathognomonic for vitamin B12 deficiency, it should be
confirmed. Low normal range values of vitamin B12 deficiency and normal blood
smears (without anemia or hypersegmented neutrophils) can occur in up to 25% of
patients, necessitating further testing. If vitamin B12 levels are borderline normal,
vitamin B12 deficiency can be confirmed by documenting elevations in
methylmalonic acid and homocysteine. Serum methylmalonic acid and
homocysteine levels are elevated in vitamin B12 deficiency, while elevated levels of
homocysteine but not methylmalonic acid are seen in folate deficiency. These tests
measure tissue vitamin stores and may demonstrate a deficiency even when the
more traditional but less reliable folate and cobalamin levels are borderline or even
normal. Patients (particularly older patients) without anemia and with normal serum
vitamin B12 levels but elevated levels of serum methylmalonic acid may develop
neuropsychiatric abnormalities.

Bone marrow biopsy (choice A) is invasive and painful and is not indicated. This
patients mild pancytopenia likely is caused by her vitamin B12 deficiency. More
information is unlikely to be found on a bone marrow stain.

An empiric trial of therapy (choice B) is a poor choice for two reasons. First, if this
patient has pernicious anemia, a common cause of vitamin B12 deficiency, oral
vitamin B12 will not be absorbed. Second, it takes months to see improvement from
this therapy, making it a difficult diagnostic test that will delay treatment if the wrong
diagnosis is suspected.

Folate deficiency, checked with a folate level (choice C), is unlikely, given the
neurologic findings in this patient. Folate deficiency is a cause of megaloblastic
anemia. Vitamin B 12 deficiency needs to be ruled out, as folate will cure the anemia,
but allow the neurologic disease to progress unchecked.

An iron panel (choice D) is not useful in this patient. Iron deficiency anemia is
microcytic and is extremely unlikely in a patient with macrocytosis.
 A 65-year-old woman is seeing you in the office for the first time. Her primary
complaint is of intense pruritus after taking a shower. She has no other complaints.
She smokes 12 cigarettes per day. She has no known chronic medical problems.
Physical examination shows distant sounding breath sounds and splenomegaly.
ABG on room air shows pH of 7.37, pCO2 44 mm Hg, and pO2 91 mm Hg. Her white
blood cell count is 11,000/microL, hemoglobin is 16 g/dL, and hematocrit is 50%.
Peripheral smear shows:

Which of the following is the most appropriate next step in management to prevent
morbidity?

A. Anticoagulation because thrombosis is the only problem with this disease

B. Continuing further workup to rule out an erythropoietin-secreting gynecologic
malignancy
C. Phlebotomy as needed to keep her hematocrit <45%
D. Quitting smoking will resolve her symptomatology
E. Starting therapy with chlorambucil if her platelets are increased greatly

The correct answer is C. The patient almost certainly has polycythemia vera, as
indicated by the high hemoglobin/hematocrit, splenomegaly, and normal pO2.
Polycythemia vera is a myeloproliferative disease with increased erythropoiesis
independent of erythropoietin. Generally all counts are elevated: white count,
hematocrit, and platelet count. Patients may have a history of cerebrovascular
accidents, myocardial infarction, angina, or venous thrombosis. Approximately 75%
have splenomegaly and 50% report history of pruritus after bath or shower.
Elevation in red cell mass results in an increased frequency of thrombotic
complications. Increased platelet count and platelet function abnormalities result in
an increased incidence of hemorrhage and thrombosis. Treatment is usually
phlebotomy as needed to keep HCT <45%

Thrombosis is not the only complication (choice A). Bleeding can be a complication
of thrombocytosis.

Gynecologic cancers (choice B) generally do not secrete erythropoietin and would

not cause splenomegaly.

Secondary polycythemia can be a result of COPD/chronic smoking; however, the

relatively normal pO2 on ABG and the splenomegaly suggest primary polycythemia.
Quitting smoking can never hurt (choice D).

Chlorambucil (choice E) is not used anymore because 6% of patients treated with it

eventually converted to acute leukemia. Hydroxyurea or anagrelide is used as an
adjunct to phlebotomy if the platelet count is increased greatly.
 A 76-year-old man comes to the clinic for his routine health examination. He reports
feeling healthy and is physically active in his assisted living community, requiring
minimal assistance with activities of daily living. His medical problems, which include
gout, hypertension, and osteoarthritis, are all under control, as are his healthcare
screening examinations. Vital signs and physical examination are within normal
limits. Laboratory studies show:

Because there is concern about this patients elevated protein levels, serum and
urine protein electrophoresis tests are ordered. The urine electrophoresis is
negative. The serum protein electrophoresis confirms the presence of elevated
gamma globulin levels, however, and detects a monoclonal pattern identified as IgG
kappa-chain M protein. A bone marrow biopsy is performed that shows 8% plasma
cells in the marrow blood smear. Radiographs of the axial skeleton show no bony
lesions. Which of the following is the most appropriate management?

A. CT of chest, abdomen, and pelvis to evaluate for malignancy

B. Follow immunoglobulin levels every 6 months for at least 2 years
C. Full quantification of immunoglobulins, including IgA and IgG
D. Normal nonpathologic finding, no additional intervention necessary
E. Nuclear medicine bone scan to evaluate for occult bony lesions
The correct answer is B. This patient has MGUS, or monoclonal gammopathy of
undetermined significance. This condition needs to be differentiated from multiple
myeloma, a similar condition that also has elevated globulins. Multiple myeloma,
however, has some combination of anemia, hypercalcemia, renal dysfunction,
light-chain proteinuria, and has greater than 10% plasma cells in the marrow. Within
the 20 years following diagnosis of MGUS, about 25% of patients will evolve
towards myeloma or other malignant lymphoproliferative disorders. No factor has
been identified to date which can efficiently predict this evolution. Recent data
concerning immunophenotype, cytogenetics and molecular biology of plasma cells
demonstrate the link between MGUS and multiple myeloma. Careful periodic
followup is recommended.

CT scanning is not necessary at this time (choice A). Blood smears and bone
marrow biopsy are better tests to look for evidence of multiple myeloma, particularly
because there are no lytic lesions on this patients radiographs. Likewise, a bone
scan (choice E) is not likely to provide more information. Most lesions in multiple
myeloma, the disease that needs to be ruled out in this patient, are lytic lesions
mediated by increased osteoclast activity from plasma cell-released IL-6. These lytic
lesions, unlike blastic lesions, do not pick up tracer and thus do not appear on a
bone scan.

Full quantification of globulin levels (choice C) is not necessary to differentiate

MGUS from multiple myeloma.

Although this condition is common, it is not normal (choice D) and should be

treated as a possible premalignant condition.
 A 35-year old woman comes to the urgent care clinic with a 3-day history of right
lower extremity swelling. She first noticed the swelling after returning from Spain via
a transatlantic flight. She also reports mild shortness of breath, exacerbated with
ambulation. At baseline, she leads an active lifestyle and enjoys bowling and sailing.
Her past medical history is significant only for tobacco abuse, with a 20-pack-year
history. Her only medication is oral contraceptive pills. Her vitals signs are: blood
pressure 132/61 mm Hg, pulse 71/min, respiratory rate 14/min, temperature 37.0 C
(98.6 F), and room air saturation of 94% on ambient air. Physical examination
reveals lungs clear to auscultation bilaterally and 2+ right lower extremity edema to
her knee.. Her chest x-ray is unremarkable. Her d-dimer is significantly elevated.
You obtain a V/Q scan that demonstrates a segmental pulmonary embolism. You
admit the patient and begin an unfractionated heparin drip and warfarin. On hospital
day 5 with continued heparin and warfarin, you notice that her platelet count has
decreased from an admission count of 250,000/ml to the current value of 50,000/ml.
Her hematocrit remains stable at 38%, her stool guaiac continues to be negative,
she has negative orthostatics, and she has no evidence of bleed. The patient has
not been started on any other medications. Which of the following is the mechanism
that accounts for the thrombocytopenia?

A. Bleed from an undetermined site because of the heparin and warfarin

B. Decreased megakaryocyte production in the bone marrow
C. Direct effect of heparin on platelet activation
D. Formation of antibodies against platelet factor 4 complex
E. Formation of antibodies against platelet factor 8 complex

The correct answer is D. There are two types of heparin-induced

thrombocytopenia (HIT), HIT I and HIT II. HIT I is the more benign form and occurs
from a direct effect of heparin on platelet activation. Additionally, HIT I occurs in 10
to 20% of patients exposed to heparin and occurs 1 to 4 days after exposure to
heparin. The nadir platelet count is typically around 100,000/ml. In contrast, HIT II is
mediated by the formation of antibodies against platelet factor complex 4, not
platelet factor 8 (choice E) complex. The Fc portion of these antibodies then binds
to receptors present on platelets, leading to further release of factor 4 and further
positive feedback. Additionally, HIT II is characterized by an incidence of 1 to 3% of
patients exposed to unfractionated heparin and a nadir platelet count of 35,000 to
55,000/ml. Further, HIT II occurs after 5 to 10 days of exposure to heparin. In this
case the presentation is classical for HIT II, with thrombocytopenia developing after
5 days of heparin exposure and the patient having a platelet count of 50,000/ml.

Bleed from an undetermined site with the overlap of heparin and warfarin (choice
A) is unlikely given a stable hematocrit, stable orthostatics, guaiac-negative stool,
and otherwise no evidence of bleed.

HIT II occurs by the formation of antibodies against platelet factor complex 4, not by
decreased megakaryocyte production in the bone marrow (choice B).

As stated previously, HIT I, not HIT II, occurs from a direct effect of heparin on
platelet activation (choice C).
 You have been conducting routine physicals and health screenings for an Internet
technology firm. On a routine physical, a healthy 45-year-old female marketing
manager was found by you to have a moderately enlarged spleen 3 cm below the
left costal margin (the spleen size was confirmed on ultrasound to be 19 cm). She
has two glasses of wine per day and does not smoke. In addition, her laboratory
studies submitted last week revealed mild pancytopenia: white blood cell count
4,200/microL, hemoglobin 10.1 g/dL, hematocrit 30.4%, platelet count
128,000/microL. You have attempted a bone marrow examination, but there was no
marrow aspirable. You did obtain a core biopsy, and the touch preparations had
stained positively for tartrate-resistant cytoplasmic acid phosphatase. The
examination of the peripheral smear shows:

Which of the following is the most appropriate management at this time?

A. Alcohol abstention
B. High-dose chemotherapy with allogeneic bone marrow transplant
C. Signal transduction inhibitor (e.g., Imatinib) because the molecular pathogenesis
involves the translocated abl oncogene in the t(9;23) mutation
D. Splenectomy
E. 2-chlorodeoxyadenosine (2-CDA)
The correct answer is E. The patient has hairy cell leukemia, which is found
incidentally on routine evaluations in 25% of patients with this condition. She has
peripheral blood pancytopenia and splenomegaly that immediately should arouse
suspicion for the disease. The diagnostic cell is a mature lymphocyte with prominent
cytoplasmic projections. Finding a dry tap caused by increased marrow reticulin is
typical, and TRAP-positive cells in the marrow is diagnostic. Hairy cell leukemia is a
B cell disorder. It is highly responsive to 2-CDA or cladribine. A single 5 to 7-day
course produces remissions that last for years in >90% of patients.

It is possible that her splenomegaly might be caused by cirrhosis and that alcohol
abstention might be helpful. The clinical picture, however, is more consistent with
hairy cell leukemia (choice A).

High-dose chemotherapy (choice B) with allogeneic transplant is not the standard

therapy for hairy cell leukemia.

The t(9;23) mutation that results in a translocated abl oncogene is the

pathophysiology behind CML (chronic myelogenous leukemia), for which a novel
therapy is Imatinib (choice C).

Before the nucleoside analogs (such as cladribine), splenectomy was the only
treatment option. Now it is rarely the first-line treatment (choice D).
 A 17-year-old African American boy comes to the emergency department
complaining of severe pain in his back, legs, and sternum. He tells you that the pain
is 10/10 in intensity, sharp, and not relieved by the over-the-counter analgesics that
he was taking at home. He denies any chest pain, shortness of breath, fever, or
chills. The pain started after the patient spent a day skiing in especially cold weather
2 days before presentation. He reports similar pain in the past and is requesting
narcotics. His temperature is 37.0 C (98.6 F), blood pressure is 120/70 mm Hg,
pulse is 103/min, and respirations are 18/min. His physical examination is
unremarkable except for pain in the stated areas. Laboratory studies show:

You are concerned about these findings so you request a peripheral blood smear
and see the following:
Which of the following is the most appropriate initial management?

A. Bone marrow biopsy

B. Emergent blood transfusion
C. Genetic counseling
D. Narcotic pain medication, oxygen, and intravenous fluids
E. Vaccination against pneumococcus and influenza

The correct answer is D. This patient has sickle cell anemia. The peripheral smear
reveals sickle cells. This patient is having a painful vasoocclusive crisis. This crisis is
managed with narcotic pain medication, oxygen, and intravenous hydration.

A bone marrow biopsy (choice A) is not necessary to make a diagnosis of sickle

cell anemia. Rather, the diagnosis can be made with hemoglobin electrophoresis. A
sickle prep can be used as a screening test.

This patient is hemodynamically stable and therefore doesnt require a blood

transfusion (choice B). Although there are some occasions when blood transfusions
are necessary, generally patients with sickle cell anemia can tolerate a low
hemoglobin. Transfusion usually is not part of the management of a vasoocclusive
(painful) crisis.

Genetic counseling (choice C) is important for this patient. It can be offered when
his acute crisis resolves or when he is considering having children. At this time, it is
more important to treat his severe pain than it is to give counseling.

Vaccinations against pneumococcus and influenza (choice E) is extremely

important in patients with sickle cell anemia. It should be offered to this patient
before discharge if he has not received them.
 An 80-year-old man is brought from an assisted living facility after developing an
altered mental status. According to the nurse supervisor at the facility, he developed
fever and flank pain earlier in the afternoon and appeared to become more ill and
confused as the day progressed. The nurse states that his only medical conditions
except for mild dementia are hypertension and benign prostatic hyperplasia (BPH).
She also notes that his family, who is supposed to bring the patients medications
that are distributed by the nurse, is a few days late, and that the patient has run out
of his prostate pills. In the emergency department, he has a temperature of 39.5 C
(103.0 F), a blood pressure of 82/40 mm Hg, a pulse of 128/min, and respirations of
30/min. Physical examination reveals a disoriented, elderly gentleman. Except for
diffuse, direct abdominal tenderness, the examination is nonrevealing. Laboratory
studies show a leukocyte count of 2,000 cells/mm3, a hematocrit of 29%, and a
platelet count of 12,000/mm3. His PT and PTT are elevated. A urinalysis dipstick is
positive for leukocyte esterase, nitrites, and ketones. Which of the following is the
most appropriate treatment at this time?

A. Aminocaproic acid
B. Antibiotics and activated protein C
C. Intravenous unfractionated heparin
D. Large volume blood transfusion
E. Platelets and fresh frozen plasma (FFP)

The correct answer is B. This patient has disseminated intravascular coagulation

(DIC), most likely from urosepsis. The most important determinant of survival is the
early administration of broad-spectrum antibiotics. Activated protein C also has been
shown to have a survival benefit in sepsis, particularly among the most ill patients,
and should be considered in this patient if it is available. Aminocaproic acid (choice
A) is a procoagulant and should not be used in DIC, a condition characterized by
uncontrolled clotting.

Heparin (choice C), which may seem to make sense intuitively, has not been shown
beneficial in DIC. The additional risk for bleeding and its low level of activity because
of reduced antithrombin levels (consumed by clot formation), the substrate on which
heparin acts, limit its effectiveness.

Blood transfusion (choice D) may be necessary if this patients hematocrit

continues to drop, but it would be unlikely to reverse his coagulopathy. Likewise,
platelets and FFP (choice E) would be useful if this patient bleeds, but would not
reverse the underlying coagulopathy. There is no reason to transfuse these factors if
the patient is not bleeding.
 A 63-year-old woman has been diagnosed with idiopathic autoimmune
thrombocytopenic purpura (ITP). Her platelet count has been consistently below
10,000/mm3, and she has not responded to prednisone or other medical
management. She has repeatedly refused splenectomy. Which of the following is
the most likely outcome in this situation?

A. High risk of death from intracranial bleeding

B. High risk of death from gastrointestinal tract bleeding
C. Multiple repeated bruises but no significant risk of death
D. Severe disability from intraarticular bleeding
E. Spontaneous resolution

The correct answer is A. The severity of the bleeding correlates with the degree of
thrombocytopenia and the age of the patient. Spontaneous, serious bleeding is
reported in approximately 40% of those with platelet counts below 10,000/mm3 and
<5% of those with platelet counts above 10,000/mm3. The estimated rate of fatal
hemorrhage in adults is approximately 5%, mostly from intracranial hemmorhage.

The GI tract (choice B) is not the main source of lethal bleeding. Bleeding volume
in these cases is not sufficient to produce exsanguination, but more than enough to
be lethal if it occurs inside the cranial cavity.

As pointed out above, younger patients have lower mortality. At age 63, multiple
repeated bruises but no significant risk of death (choice C) is incorrect because, as
stated above, this patient is at significant risk of death from an intracranial bleed.

Intraarticular bleeding (choice D) occurs in untreated hemophilia. Platelet counts

below 10,000 are more lethal and, as noted, they are associated with intracranial
bleeding.

Spontaneous resolution (choice E) is seen in children with immune

thrombocytopenic purpura. It should not be expected in a 63-year-old woman.
 A 76-year-old man with a known history of chronic alcohol abuse and a partial
gastrectomy for peptic ulcer disease is brought into your office by his wife for several
months of cognitive impairment, weakness, dyspnea on exertion, and numbness in
his hands and feet. Physical examination reveals a pale, withdrawn man who
appears slightly icteric. There is no hepatomegaly or splenomegaly. Neurologic
examination reveals decreased vibratory and position sensation. His hemoglobin is
6.5 g/dL, hematocrit is 19.5%, mean corpuscular volume is 135 fL, and reticulocyte
count is 1.3%. Other laboratory findings include those seen on the blood smear
shown, an LDH of 800 U/L, haptoglobin of 253 mg/dL, and indirect bilirubin of 4.5
mg/dL.

Which of the following is the most likely additional laboratory finding?

A. A low serum vitamin B 12 level

B. A low serum iron level and high total iron binding capacity level
C. Positive direct Coombs test
D. Positive osmotic fragility test
E. A serum ferritin level of 5 ng/mL

The correct answer is A. The history and physical exam are characteristic of a
vitamin B12 deficiency with subacute combined degeneration of the spinal cord,
peripheral neuropathy, dementia, and jaundice from increased indirect bilirubin. The
anemia is macrocytic with a low reticulocyte production index. After being ingested,
vitamin B12 becomes bound to intrinsic factor, a protein secreted by gastric parietal
cells. Gastrectomy will eliminate the site of intrinsic factor production. The hallmark
of vitamin B12 deficiency is megaloblastic anemia. The anemia may be severe, with
hematocrits as low as 10 to 15%. Vitamin B12 deficiency also leads to a complex
neurologic syndrome. Peripheral nerves are usually affected first, and patients
complain initially of paresthesias. The posterior columns become impaired next, and
patients complain of difficulty with balance. In more advanced cases, cerebral
function may be altered as well. A characteristic finding in the peripheral smear is
the macro-ovalocyte. Neutrophils are hypersegmented. The reticulocyte count is
reduced. Other laboratory abnormalities include elevated serum LDH and an
increase in indirect bilirubin. These reflect intramedullary destruction of developing
abnormal erythroid cells.

A high TIBC (choice B) and a serum ferritin of 5 ng/mL (choice E) are incorrect.
Iron studies and ferritin are not indicated because of the elevated mean corpuscular
volume.

A positive direct Coombs test (choice C) is incorrect. Although the elevated LDH
and indirect bilirubin suggest a hemolytic process, such as autoimmune hemolytic
anemia, the low reticulocyte count and normal haptoglobin level make immune
hemolysis unlikely.

A positive osmotic fragility test (choice D) is incorrect. The osmotic fragility test is
used to detect the presence of spherocytes. The increase in indirect bilirubin and
the patients jaundice may suggest hereditary spherocytosis, but there are no
spherocytes seen on the smear; further, the patient does not have an enlarged
spleen and his reticulocyte index is low.
 You are asked by the cardiology service to consult on an 84-year-old WW II veteran
inpatient for persistent leukocytosis. He has a known history of coronary artery
disease and underwent a two-vessel bypass graft 5 years ago. He was admitted 2
weeks ago for new onset atrial fibrillation. He has responded well clinically to
appropriate cardiac therapy and his atrial fibrillation is currently rate-controlled. He
also was discovered to have a double lobe pneumonia found to be secondary to
Streptococcus pneumoniae. Although he rapidly defervesced after institution of
antibiotics, his white blood cell count has remained high at 84,000/microL. The
patient now feels well and his peripheral edema has resolved almost completely,
and he has no complaints, is ambulating independently, and is eagerly awaiting
discharge to home. You review his laboratory studies and find a white blood cell
count of 84,000/microL (differential: 9,000 neutrophils, 1,000 bands, 72,000
lymphocytes, 1,000 monocytes, 500 eosinophils, 500 basophils), hemoglobin 12.4
g/dL, hematocrit 37.5%, and platelet count 225,000/microL; chemistry panel is within
normal limits. A review of his peripheral smear reveals:

On physical examination, you find a thin, elderly, Caucasian man sitting up in bed in
no apparent distress. His conjunctivae are pink and moist, sclerae anicteric, and
neck examination reveals palpable but nontender lymphadenopathy in his cervical
and supraclavicular areas. Cardiopulmonary examination reveals wet crackles at the
bases of his lungs, and his pulse is 75/min and irregularly irregular. He also has
palpable but nontender lymphadenopathy in his axillae and inguinal regions
bilaterally. His spleen does not appear to be enlarged. You already have advised the
primary team to send a sample of his peripheral blood for flow cytometry. The
daughter of the patient is at the bedside and is very anxious. She tells you, The
heart doctors told me that my father might have leukemia and he might die from
this. Which of the following is the most appropriate response?

A. His pneumonia probably had more to do with his age than with his blood
condition.
B. His prognosis is very poor and he most certainly will die from his leukemia.
C. We will need to institute chemotherapy immediately, otherwise he will die.
D. We will need to monitor your father as an outpatient; no therapy is indicated at
this time.
E. We will need to perform a bone marrow biopsy now.

The correct answer is D. This patient has CLL (chronic lymphocytic leukemia), a
B-cell lineage neoplasm. The smear shows a smudge cell (partially fractured
lymphocytes that appear as amorphous shapes), classic for CLL. Generalized
lymphadenopathy also is found commonly in CLL. CLL cells are B cells, and
although they have a marker seen on activated T cells, CD5, most of the surface
markers are typical for B cells (CD19, CD20). There is an accumulation of small,
well differentiated lymphocytes in blood, marrow, lymph nodes, spleen, and liver.
Anemia and thrombocytopenia portend a poor prognosis. This disease is incurable,
and treatment generally is withheld until the disease progresses.

Serum protein electrophoresis commonly shows deficiency of normal

immunoglobulins, and CLL patients are susceptible to infections with encapsulated
organisms such as Streptococcus pneumoniae and Haemophilus influenzae
because of the deficiency in opsonizing antibodies (choice A).

The patient does not have anemia or thrombocytopenia. Many patients have an
indolent, almost benign course and live for 10-20 years or more without major
complications from CLL. Because CLL tends to occur in elderly patients, death often
results from other unrelated illnesses in this age group (choice B).

Conventional full-dose chemotherapy is never curative in this disease (choice C).

Neither a lymph node biopsy nor a marrow aspirate is necessary for confirmation of
diagnosis (choice E).
 A 42-year-old woman comes to the office complaining of increased lower
extremities movement. She complains of motor restlessness, including floor pacing
and leg rubbing. The symptoms are worse at rest and relieved with activity. The
symptoms are worse in the evening and at night, although the symptoms have not
been keeping her awake. She denies daytime somnolence or fatigue. She has no
prior medical history and is not taking any medications. She has no known drug
allergies. On examination, vital signs are stable. Cardiac, lung, abdomen, and
musculoskeletal examinations are all within normal limits. Laboratory studies show a
microcytic anemia and a low iron level. Which of the following is the most
appropriate management at this time?

A. Prescribe amitriptyline
B. Prescribe iron replacement
C. Prescribe levodopa
D. Prescribe pramipexole
E. Schedule a sleep apnea study

The correct answer is B. This patient has restless leg syndrome (RLS). The
symptoms are commonly worse in the evening and can cause insomnia. Although
the cause is unknown, it can be precipitated by medications such as tricyclic
antidepressants and has been associated with several diseases, including renal
failure, iron deficiency anemia, and peripheral neuropathy. Because this patient has
iron deficiency anemia, it would be advisable to replete the iron and see if the
symptoms resolve.

Tricyclic antidepressants such as amitriptyline can worsen RLS symptoms (choice

A).

Other drug choices for treatment include dopaminergic agonists such as levodopa
(choice C).

There is preliminary evidence that pramipexole may be particularly effective (choice

D). If iron replacement were not successful, this medication should be considered.

This patients symptoms have not been keeping her awake. A sleep apnea study is
not necessary at this time (choice E).
 You are treating a 42-year-old man with epistaxis in the emergency department. He
was hit with a softball at the company picnic and the bleeding started immediately.
He reports that he has had approximately 6 ounces of blood loss. Vital signs are
normal. You control the epistaxis with placement of pre-made, specially designed
sponges in each nasal cavity. Your plan is to leave those in place for 5-7 days until
the patient can return for removal. The patient also should receive which of the
following?

A. Antibiotics effective against gram-positive flora as prophylaxis against toxic

shock syndrome
B. Broad-spectrum antibiotics to treat underlying infection, which plays a major role
in epistaxis
C. Coagulation studies to rule out bleeding diathesis
D. CT scan to ensure that there is no neoplasm as the source of the bleeding
E. X-rays to rule out nasal fracture

The correct answer is A. Specially designed sponges and catheters with inflatable
balloons are used frequently in the control of epistaxis refractory to topical
decongestants and conservative measures. Because they are foreign bodies that
remain in place for several days, there is the potential for colonization with
Staphylococcus capable of producing toxic shock syndrome toxin. In fact, toxic
shock syndrome has been reported from nasal packing. All patients with nasal
packing (even sponges specially designed for control of epistaxis) therefore should
receive coverage with antibiotics directed at Staphylococcus.

Broad-spectrum antibiotics (choice B) are unnecessary, because infection does not

play a major role in epistaxis.

Epistaxis after nasal trauma is very common, and coagulation studies (choice C)
and CT scan (choice D) are not necessary for this patient.

X-rays (choice E) have limited or no role in the treatment of possible nasal fracture;
regardless, nasal fracture is a secondary concern in the acute setting for this
patient.
 A 34-year-old woman is noted to have an apical scar in the right upper lung lobe
while undergoing health clearance for a job at a nursing home. Her PPD is 10 mm
and she is started on isoniazid, prophylactically. She is otherwise healthy with no
fever, chills, weight loss, or hemoptysis. She has no allergies. Three months after
starting this treatment, she complains of weakness, nausea, and feet tingling. Her
examination and laboratory results are normal. One week later she has a grand mal
seizure. She is noted to have dermatitis, glossitis and absent knee reflexes.
Laboratory studies at this time reveal a microcytic anemia. Which of the following is
the appropriate management?

A. Administer phenytoin
B. Administer pyridoxine
C. Obtain a brain computerized tomogram
D. Obtain an electroencephalogram
E. Perform a lumbar puncture

The correct answer is B. The peripheral neuritis, dermatitis, glossitis, microcytic

anemia and seizure in the setting of isoniazid treatment indicates that the patient is
suffering from a pyridoxine deficiency. Isoniazid can inhibit various enzymes that
use pyridoxine as a cofactor.

The patient is suffering from a seizure that probably is the result of pyridoxine
deficiency and should be corrected once the deficiency is reversed. Phenytoin
should not be required (choice A).

If the source of seizures is not determined and continue after the correction of
pyridoxine deficiency, a head CT may be necessary (choice C).

An electroencephalogram may be needed if the pyridoxine does not reverse the

seizures and the head CT is unremarkable (choice D).

The patient is afebrile and has a probable source for the seizure, which should first
be corrected. A lumbar puncture is not necessary now (choice E).