Hematology-Oncology Review

Session
Pete Voorhees
 Iron Deficiency Anemia
Symptoms of anemia (fatigue /
weakness, SOB / DOE).
Ice pica and koilonychia are
specific for iron deficiency!
Microcytic (low MCV),
hypochromic (low MCHC) RBCs.
Other causes of microcytosis
include thalassemias,
sideroblastic anemias.
Ferritin is low, Serum Fe low, TIBC
or transferrin normal or high, Fe
saturation (serum Fe / TIBC) low.
Causes: chronic blood loss,
malabsorption, decreased intake,
pregnancy.
Treatment: Give iron, fix source of
blood loss.
 Vitamin B12 Deficiency
Symptoms of anemia.
Peripheral neuropathy (decreased
proprioception, vibratory sense).
Macrocytic (high MCV) RBCs.
Other causes of macrocytic
anemias include liver disease,
folate deficiency, anemias ass.
with a high retic. ct.,
hypothyroidism, HIV therapy
(AZT), chemotherapy.
Hypersegmanted neutrophils.
Dx: low B12 levels.
Causes: pernicious anemia (Ab to
IF), malabsorption (ileal resection),
pancreatic insufficiency.
Treatment: replace B12.
 Folate Deficiency
Same symptoms as B12
deficiency but no neuropathy.
Macrocytic RBCs and
hypersegmanted neutrophils.
Dx: low folate or RBC folate
level.
Causes: Decreased intake
(alcoholic), malabsorption,
increased utilization (depletion)
of body stores (chronic
hemolytic anemia)
Treatment: Replace folate.
 Hereditary Spherocytosis
Symptoms of waxing /
waning anemia, jaundice.
Hemolysis accelerated by
infection.
Splenomegaly
(hyperplasia secondary to
increased workload),
pigmented gallstones (h/o
cholecystectomy), ankle
ulcers.
Family history
AD. 1 : 5000 people of
european descent affected.
 Hereditary Spherocytosis
Blood smear: spherocytes,
polychromatophilia (increased
reticulocytes).
Labs: Increased retic. ct.,
increased LDH, increased
indirect bilirubin, increased
osmotic fragility.
Treatment: folate replacement,
splenectomy in some
circumstances).
Genetic defect: Spectrin,
ankyrin mutations.
Pearl: Parvovirus B19 infection
in patients with hemolytic
anemis in general = aplastic
crisis.
 G6PD Deficiency
Episodic hemolytic
anemia.
Triggered by oxidant
stress: drugs, infection.
Occurs in males
X-linked, 10 14% of
males of African descent
carry an unstable A- variant
of G6PD.
More severe, chronic
form seen in men of
Mediterranean descent.
Think fava beans in a
Mediterranean pt.
 G6PD Deficiency
G6PD is required to generate
NADPH and ultimately
reduced glutathione.
Glutathione required to prevent
oxidative damage to
hemoglobin.
Deficient glutathione leads to
oxidized, methemoglobin
which precipitates out as Heinz
bodies.
Macrophages of the RES
phagocytose bits of RBC
membrane with underlying
precipitated hemoglobin.
 G6PD Deficiency
Smear: Bite cells and blister cells.
Diagnosis: Smear, G6PD level, heinz body prep.
G6PD levels may be normal in the acute setting due
to selective removal of older RBCs with lower
baseline G6PD levels.
Treatment: Get rid of offending oxidant stress
(drug, infection).
Important drugs to know that may precipitate
hemolysis in these folks: SULFA, anti-malarial drugs,
dapsone, vitamin K, fava beans.
 Warm Autoimmune Hemolytic
Anemia
Symptoms of anemia,
jaundice, splenomegaly.
Smear: spherocytes,
polychromatophilia.
Labs: Increased retic. ct., high
LDH, high indirect bilirubin, +
direct Coombs test (direct
antiglobulin test or DAT).
Indirect Coombs usually
positive as well.
Treatment: immune-
suppression (steroids,
spenectomy), treat / remove
underlying trigger.
 Warm Autoimmune Hemolytic
Anemia
Causes: Idiopathic, SLE,
lymphoproliferative disorder (lymphoma,
CLL).
Drugs
Innocent bystander: quinine, quinidine, INH
Hapten: PCNs, cephs
Autoimmune: alpha-methyldopa,
procainamide
 Cold Agglutinin Disease
Symptoms of anemia,
acrocyanosis.
Smear, RBC agglutination,
polychromatophilia.
Labs: Increased retic. ct., LDH,
bilirubin, + Coombs test (C3 +.
IgG -), + cold agglutinin titer.
Treatment: avoidance of cold,
treat underlying disease,
immune-suppression
(chemotherapy).
Associated diseases:
lymphoproliferative diseases
(lymphoma, CLL) or after
infectious mononucleosis or
mycoplasma infection
(walking pneumonia).
 Hemophilia A and B
X-linked.
Factor VIII (Hemo A) > Factor IX (Hemo B) deficiency.
Manifests as soft tissue and joint bleeds, provoked and
spontaneous as well as other bleeding (intracranial, GU).
Long-term complications: Joint destruction from repeated
bleeds, pseudotumors.
Labs: Prolonged aPTT, normal PT, normal TCT, normal
platelet function screen and bleeding time.
Treatment: recombinant Factor VIII or IX replacement,
ddAVP for mild hemophilia A (leads to release of
endothelial stores of FVIII).
 Von Willebrands Disease
Autosomal dominant.
The most common inherited bleeding disorder.
Mucocutaneous bleeding (epistaxis, gum bleeding,
GU/GI bleeding, menorrhagia).
Types 1 (mild deficiency) , 2 (qualitative abnormality),
and 3 (severe deficiency).
Labs: Prolonged bleeding time / platelet function screen,
slightly prolonged aPTT (due to low FVIII levels), low von
Willebrand activity level, +/- low vWF antigen levels.
Treatment: Type 1: ddAVP. Type 2 and 3: vWF and FVIII-
containing plasma product (Humate-P).
 Venous Thrombosis
Causes
Acquired
Cancer
Myeloproliferative disorders (P. Vera, Essential
thrombocytosis)
Antiphospholipid antibody syndrome
Hyperhomocysteinemia
Pregnancy
OCPs, HRT
Prior venous thrombosis
Age
Immobilization
Surgery
 Venous Thrombosis
Inherited causes
Factor V Leiden mutation!!!!
Prothrombin gene mutation
Protein C def.
Protein S. def.
Antithrombin def.
Dysfibrinogenemias, elevated FVIII, IX, XI
levels
 Venous Thrombosis
Symptoms: pain / swelling in leg, chest
pain, SOB (pulmonary embolism).
Diagnosis:
Duplex ultrasonography (doppler ultrasound)
IPG
Contrast venography
Magnetic resonance venography
D-dimer
 Venous Thrombosis
Treatment
Heparin or low-molecular weight heparin
Potentiates anticoagulant effect of endogenous
anti-thrombin.
Warfarin
Depletes vitamin K-dependent coagulation factors
(II, VII, IX, and X).
Fibrinolytics (tPA) if patient clinically unstable
with extensive clot burden.
Activates the fibrinolytic enzyme, plasmin.
 Pseudothrombocytopenia
Lab artifact!
The patient will have no
bleeding history.
Clumps of platelets will
be seen on the fringes of
the smear.
Due to presence of EDTA
in tube.
Diagnosis: smear, re-
check plt count in citrated
or heparin-anticoagulated
tube.
 Disseminated Intravascular
Coagulation
Diffuse, abnormal activation of
coagulation, leading to consumption of
clotting factors, and thrombocytopenia.
Clinically manifests as bleeding but the
clinical picture is typically dominated
by the disease that led to the DIC.
Prolonged PT, aPTT, TCT, and low
platelets, low fibrinogen, low
antithrombin, elevated D-dimer.
MAHA may be seen on the smear.
Causes: Severe infection, AML (esp.
APL or M3 AML), obstetrical
complications (eclampsia), severe
burns.
Treatment: replacement (platelets,
clotting factors with FFP, fibrinogen
with cryoprecipitate), treat underlying
disease.
 Thrombotic Thrombocytopenic
Purpura (TTP)
Abnormal activation of platelets and endothelium leading to fibrin
deposition in the microvasculature and destruction of RBCs and
consumption of platelets.
Pentad
MAHA
Thrombocytopenia
Fever
Renal failure
Neurologic deficits
Smear shows MAHA
Labs: PT, aPTT, TCT, fibrinogen, d-dimer are normal.
Cause: Primary (idiopathic) TTP due to autoantibodies to ADAMTS-
13; secondary causes: pregnancy, drugs (mitomycin-C, quinine,
ticlopidine, cyclosporine), HIV
Treatment
Plasma exchange
 Hemolytic Uremic Syndrome
Similar to TTP but renal failure dominates the
clinical picture.
The blood smear will look the same and the lab
work will be the same.
More common in children after diarrheal illness
(esp. E. Coli O157/H7 and shigella).
Treatment: Supportive care +/- plasma
exchange (less effective here than in TTP).
 Idiopathic Thrombocytopenic
Purpura
The platelet equivalent of warm AIHA.
Symptoms: mucocutaneuos bleeding.
PE: petechiae.
Smear: absent / few platelets.
Causes: idiopathic, drugs (PCNs, sulfa (TMP-
sulfamethoxazole, quinine), SLE, HIV,
lymphoproliferative disorders.
Heparin causes an immune-mediated thrombocytopenia
paradoxically associated with excessive clotting.
Treatment: Corticosteroids +/- IVIG, splenectomy for
relapse, anti-D immune globulin, immunosuppressants.
 Polycythemia Vera
Symptoms of increased viscosity: decreased mental
acuity, blurred vision, tinnitus, headache, dizziness,
paresthesias.
PV specific findings: post-bathing pruritus, erythromelalgia,
thrombosis, hemorrhage, hypermetabolic symptoms.
PE: plethora, retinal vein distention,
hepatosplenomegaly.
Labs: Increased WBCs, HCT, and platelets. Basophilia,
high LAP score, high uric acid and vitamin B12, low
erythropoietin level.
Treatment: phlebotomy, hydroxyurea, interferon-alpha,
busulfan, P32.
Aspirin reduces the incidence of thrombosis.
 Essential Thrombocytosis
Similar to P. Vera.
Asymptomatic or excessive
bleeding and / or clotting,
splenomegaly.
Smear: large platelets. Labs:
thrombocytosis, leukocytosis.
Must r/o CML.
Treatment: age < 60, no
clotting risk factors (smoking,
HTN, etc.), plts < 1 1.5
million, no h/o clotting /
bleeding observation.
Otherwise, hydroxyurea,
anagrelide, or interferon-alpha.
ASA alleviates symptoms of
microvascular occlusion (e.g..
erythromelalgia).
 Idiopathic Myelofibrosis
Symptoms of hypermetabolism (weight
loss, fevers, sweats), splenomegaly
(abd. pain, early satiety), anemia, +/-
thrombocytopenia.
Leukoerythroblastic blood smear
Tear drop shaped RBCs, nucleated
RBCs.
Left-shifted WBCs.
WBC count normal or high at
diagnosis but eventually drops, HCT
usually low at diagnosis, plts may be
up, down or low.
Dry tap on bone marrow aspirate.
Increased fibrosis on bone marrow
biopsy.
P. Vera and ET can evolve into a
spent, myelofibrotic stage.
Treatment largely supportive, bone
marrow transplant has been tried in
younger patients.
 CML
Symptoms of
hypermetabolism,
splenomegaly, anemia.
Smear with increased numbers
of WBCs (granulocytes of all
stages of maturation).
Labs: Increased WBCs, +/-
anemia, low LAP score, low
vitamin B12 level.
Cytogenetics: t(9;22), BCR-
ABL.
Treatment: Bone marrow
transplant, Gleevec.
Monitoring disease:
cytogenetics, FISH for t(9;22),
PCR for BCR-ABL.