Anemia

Compensatory mech- increased cardiac output (HR and SV), increased extraction ratio,
rightward shift of oxyhemoglobin curve, expansion of plasma volume
1 unit of pRBC=1 hb, 3hct; mix pRBC in saline not lactate Ringer (calcium causes coagulation),
give over 1.5 to 2hrs, check CBC after each infusion; FFP has all the clotting factors but no
RBcs/WBCs/platelets, give for high PT/PTT, coagulopathy, deficiency of clotting factors, cant
wait for vitamin K, liver failure, check PT/PTT after; cryoprecipitate contains factor VIII and
fibrinogen, for hemophilia A, DIC (fibrinogen) and vWD
1 unit of platelet= 10,000; whole blood only for massive blood loss and platelets:FFP:pRBCs is
1:1:1 and should be warmed to prevent drop in body temperature
patients with impaired cardiac function tolerate anemia less well
Dx- H/H, then MCV, reticulocyte index (prod vs. destruction or loss)

If unstable, give PRBCs before trying to find a cause

Transfusion reactions
Intravascular (acute)- ABO-mismatch with complement activation and C9
Sx- fever/chills, nausea/vomiting, pain in flanks/back, chest pain, dyspnea
comp- hypovolemic shock (hypotension, tachycardia), DIC, renal failure with hemoglobinuria
Tx- stop transfuoin, replace fluid to avoid shock and renal failure, epinephrine for anaphylaxis,
dopamine/norepi for BP
Extravascular (delayed; 3-4wks)- minor RBC antigens (Kell), removed by macrophages in spleen,
liver, and bone marrow
Tx- none; Px- good
Microcytic- both Fe and TIBC low (anemia of chronic disease), Fe low TIBC high (iron deficiency),
Fe and TIBC normal (lead poisoning, thalassemia)
Normocytic- aplastic anemia, BM fibrosis, tumor, anemia of chronic disease, renal failure
Macrocytic- normal B12 and folate (suspect liver disease)
liver disease causes altered metabolism of plasma lipoproteins into their membranes, altering
RBC shape and increasing their volume
stimulated erythropoiesis can cause macrocytic anemia because reticulocytes are larger than
mature RBCs, resulting in an increase in polychromatophilic RBCs
If retic>2, suspect blood loss (look for source of bleeding) and suspect hemolysis
RDW is usually abnormal in iron deficiency anemia, but normal in other microcytic anemias

Iron deficiency
In the absence of menstrual bleeding, GI blood loss is most likely for iron deficiency anemia
infants and toddlers, adolescents, and pregnant women are at increased need for iron
Sx- orthostatic lightheadedness, hypotension (if acute), tachycardia, dyspnea on exertion,
fatigue, pallor
Dx- labs and smear, bone marrow biopsy (gold; indicated if labs show iron deficiency anemia,
but no source of blood can be found)
Tx- PO Fe, IV or IM iron
PO Fe- SE constipation, nausea, dyspepsia

If iron deficiency is suspected, but not responsive to iron therapy, get a hemoglobin
electrophoresis
Give desferrioxamine along with transfusions to avoid secondary hemochromatosis
Thalassemias
Ex- b-thal: excess a-chains bind to and damage RBC membrane; a-thal: a-chains are necessary
for all hemoglobins
B-thal major (Cooley anemia)
Ex- homozygous b-chain thal, mainly Mediterranean populations
Sx- severe anemia, massive hepatosplenomegaly, growth retardation and failure to thrive,
progressive CHF (cause of death), crew-cut on skull xray
Dx- Hb electrophoresis- HbF and HbA2 are elevated; peripheral smear- target cells
Tx- frequent PRBCs needed to sustain life
B-thal minor
Ex-heterozygous b-chains
Sx-usually asx; Dx- hb electrophoresis
Tx- usually not necessary

A-thal
Silent carriers- one a-locus, asx, normal hb and hct level, no tx needed
a-thal trait (or minor)- two a-locus, mild anemia, African-Americans, no treatment needed
Hb H- three a-loci, significant anemia, HbH, treatment same as b-thal major
4-loci- hydrops fetalis

Sideroblastic anemia
Ex- abnormal RBC iron metabolism; acquired (drugs- chloramphenicol, INH, alcohol; exposure
to lead; collagen vascular disease, and neoplastic disease- myelodysplastic syndromes)
Sx- high serum iron and ferritin, normal TIBC (vs Fe def), ringed sideroblasts in bone marrow
Tx- consider pyridoxine
Anemia of Chronic disease
Dx- low serum iron, low TIBC, low serum transferrin levels, serum ferritin increased; usually
normocytic and normochromic, but microcytic and hypochromic possible
Tx- none needed, dont give iron

Aplastic anemia
Ex- radiation exposure, meds (chloramphenicol, sulfonamides, gold, carbamazepine), viral
infection (HPV, hep C, hep B, EPBV, CMV, HZV, HIV), chemicals (benzene, insecticides)
Dx- bone marrow biopsy (best; hypocellular marrow, absence of progenitors of all three lines)
Tx- bone marrow transplantation

Vit B12
Ex- stored in liver; pernicious anemia (MCC; no IF), gastrectomy, alcoholism, Crohn, disease, ileal resection
Sx- sore tongue (stomatitis and glossitis), neuropath (posterior columns, lateral corticospinal tracts,
spinocerenellar tracts- ataxia, upper motor neuron signs, decreased position/vibrator sensation in lower
extremities; urinary and fecal incontinence, impotence, dementia)
Dx- megaloblastic RBCs, hypersegmented neutrophils, MMA and Homocysteine, angtibodies against IF,
Schilling test (1. unlabled B12, then 2. radiolabeled B12; repeat with IFmalabsorption vs. pernicious
anemia)
Tx- B12 IM once a month

Folate
Ex- dietary (MCC), antibiotics, pregnancy, hemolysis, methotrexate, phenytoin, hemodialysis
Dx- MMA increased, not homocysteine
Tx- daily folic acid
Hemolytic anemias
Ex- normal bone marrow, but cant keep up with demands
1. Hemolsis due to causes external to RBC defects (most are acquired)
immune hemolysis; mechanical hemolysis (prosthetic valves, microangiopathic hemolytic
anemia- TTP, DIC); medications, burns, toxins (snake or brown recluse spider bite), infection
(malaria, clostridium)
2. Hemolysis due to intrinsic RBC defects (most are inherited)
hemoglobin (sickle cell, hemoglobin C, thalassemias); membrane defects (hereditary
spherocytosis, paroxysmal nocturnal hemogloinuria); enzyme defects (G6PD, pyruvate kinase)
Sx- dark urine color (hemogloniuria, not bilirubin) suggests intravascular process;
hepatosplenomegaly, cholelithiasis, lymphadenopathy (chronic cases)

Sickle Cell
Ex- normal Hb A replaced by mutant HbS; reduced oxygen conditions (acidosis, hypoxia, changes
in temperature, dehydration, infection)
Trait- not anemic, normal life expectancy, a/w isosthenuria (inability to concentrate or dilute
urinepaitients will have a constant osmolality on urinalysis testing)
Px- survival depends on frequency of vaso-occlusive crises
Comp- blood- chronic hemolytic anemia, aplastic crises; heart- high-output CHF due to anemia; CNS- stroke; GI- gallstones,
splenic infarctions (large in children, small after 4yo, abdominal crises; bones- painful crises (MC), osteomyelitis, avascular
necrosis (MC in hips-femoral head, and shoulders-humeral head); lungs- infections, acute chest syndrome (pulm
infarctions); kidneys-hematuria, papillary necrosis, renal failure; eyes- proliferative retinopathy, retinal infarcts, vitreous
hemorrhage, proliferative retinopathy, retinal detachment; genitalia-priapism (Px- hydralazine or nifedipine or antiandron
stilbestrol); Hand-foot syndrome (dactylitis- painful swelling of dorsa of hands and feet; often the first manifestation of
sickle cell; avascular necrosis of MC and MT bones), chronic leg ulcers esp lateral malleoli; abdominal crisis mimics acute
abdomen
Susceptible to H. flu and strep pneumo
Dx- hemoglobin electrophoresis is needed for diagnosis
Tx- avoid high altitudes (hypoxia), maintain fluid intake (dehydration), treat infections promptly
(fever)
crisis- hydration, morphine, warmth, supllemental oxygen if hypoxia present
Px- early vaccination for Strep pneumo, H. info, and N. meningitides; folic acid (chornic
hemolysis); Hydroxyurea (enhances HbF, which interferes with the sickling process; accelerates
healing of leg ulcers and reduces recurrence)

Hereditary Spherocytosis
Ex- AD; spectrin mutation or absence leading to loss of RBC surface area; extravascular hemolysis
(spherocytes cant adapt shape so gets trapped in spleen and removed by macrophages)
Sx- splenomegaly, gallstones, occasional hemolytic crisis
Dx- osmotic fragility to hypotonic saline (cell cant swell in higher oncotic pressure), elevated retic count,
eleated MCHC, direct Coombs negative (vs. AIHA)
Tx- splenectomy (then immunization against strep pneumo, Neisseria meningitides, h. flu)
Causes of spherocytosis- hereditary spherocytosis, G6PD, ABO incompatibility but not Rh, hyperthermia,
AIHA

G6PD
Ex- X-linked recessive that primarily affects men; sulfonamides, nitrofurantoin, primaquine, dimercaprol, fava
beans, infection; A-variant (milder; 10% of AAs) targets only older RBCs (younger RBCs have enough G6PD to
prevent RBC destruction); severe variant (Mediteranian)
Sx- episodic hemolytic anemia usually drug-induced; dark urine and jaundice
Dx- peripheral smear- bite cells (after Heinz body removal), deficient NADPH formation on G6PD assay;
measurement of G6PD levels is diagnostic
Tx- hydration, perform RBC transfusion when needed
Autoimmune Hemolytic Anemia
Ex- autoantibodies to RBC membrane antigens; IgM vs. IgG determines prognosis, site of
destruction, and response to treatment
Warm AIHA
Ex- IgG, extravascular hemolysis, splenomegaly; primary-idiopathic, secondary-lymphomas,
leukemias (CLL), collaen vascular diseases (esp SLE), drugs (a-methyldopa)
Cold AIHA
Ex- IgM, complement activation and intravascular hemolysis, liver; primary idiopathic (elderly),
secondary- infection (Mycoplasma or EBV)
Dx- Direct Coombs (RBCs wih IgG- positive Coombs and warm AIHA; RBCs with complement
alone, cold AIHA); positive cold agglutinin titer=cold AIHA; spherocytes may be present in warm
Tx- none usually because hemolysis is mild; otherwise, warm-steroids (main), splenectomy
immunosuppression (AZA/CPP), RBC, folic acid; cold- steroids not useful

Paroxyhsmal Nocturnal Hemoglinuria

Ex- all hematopoietic stem cells and cells of all lineages; deficiency of anchor proteins that link
complement inactivation proteins to cell mebranes
Sx- chronic intravascular hemolysis, normochromic normocytic anemia, thrombosis of venous
sytem (ex. hepatic vains Budd-Chiari), abdominal, back, musculoskeletal pain
Dx- Ham test- cells incubated in acidic serum which activates alternative complement pathway
and lysis abnormal cells; Sugar water test- triggers hemolysis in PNH; flow cytometry for CD55
and CD59
Tx- glucocorticoids; bone marrow tranplant
Comp- asplastic anemia, myelodysplasia, myelofibrosis, acute leukemia
Platelet Disorders
Thrombocytopenia
Ex- <150;
decreased production- bone marrow failure (acquired- aplastic anemia), congenital (Fanconi
syndrome), congenital intrauterine rubella; bone marrow invasion: tumors, leukemia, fibrosis;
bone marrow injury (drugs- ethanol, gold, chemotherapy; chemicals- benzene; radiation,
infection)
Increased destruction- immune (infection, drug-induced, immune thrombocytopenic purpura,
SLE, heparin-induced thrombocytopenia 2, HIV thrombocytopenia); nonimmune- DIC, TTP, HIT 1
Sequestration from splenomegaly; dilutional; pregnancy
Dx- cbc-plt count; bleeding time, PT, PTT

Immune (idiopathic) thrombocytopenic purpura

Ex- IgG, extravascular; acute- children, post-viral (most), self-limited; chronic- adults, women 20-
40, spontaneous remissions are rare
Sx- NO splenomegaly; only minimal bleeding symptoms despite extremely low platelet counts
(<5000)
Dx- plt usually <20,000, all other blood count is normal; peripheral smear- decreased plts; bone
marrow aspiration- increased megakaryocytes; increased platelet-associated IgG
Tx- corticosteroids; IVIG; splenectomy; romiplostim and eltrombopag (thrombopoietin receptor
agonists)

PT- prolonged by warfarin

PTT- prolonged by heparin
Thrombin time- measure of fibrinogen concentration
Thrombotic Thrombocytopenic Purpura
Ex- no functional ADAMTS13, a protease that cleaves vWF resulting in ultralarge vWF multimers;
microthrombi (plt thrombi) occlude small vessels leading to MAHA and mechanical RBC damage;
life-threatening
Sx- hemolytic anemia, acute renal failure, fever, fluctuating transient neurologic signs (AMS to
hemiplegia)
Tx- plasmapheresis, corticosteroids and splenectomy, platelet transfusion are contraindicated
TTP=HUS + Fever + AMS; HUS=MAHA+ thrombocytopenia+ renal failure
(thrombosis in brain-AMS)

Heparin-induced Thrombocytopenia
Ex- abs against heparin-platelet factor 4 complex
Sx- venous thrombosis, pulmonary embolism, decrease in plt by 50% after heparin suggests HIT
Dx- antiplatelet factor 4 antibody, serotonin release assay
Tx- stop heparin, lepirudin, argatroban, dabigatran (direct trhombin inhibitor)

Bernard-Soulier Syndrome
Ex- AR, GP1b-Ix deficiency, platelet cant adhere to subendothelium
Dx- LARGE platelets on smear, platelet count mildly low
Glanzmann Thrombasthenia
Ex- AR, GPIIb-IIIa deficiency, platelet cant aggregate, bleeding time prolonged, platelet count
normal

GPIIb: 2 platelets; oher causes of platelet disfunction- uremia, NSAIDs, and aspirin
Disorders of Coagulation
von Willebrand Disease
Ex- AD, deficient or defective vWF, MC inherited bleeding disorder; vWF enhances plt adhesion
AND aggregation
Type 1 (MC)- decreased vWF; Type 2- qualitative deformities of vWF; Type 3 (least common)-
absent vWF (very severe)
Sx- cutaneous and mucosal bleeding, menorrhagia, GI bleeding
Dx- prolonged bleeding time (but normal platelet count), PTT may be prolonged, decreased
plasma vWF, decresed factor 8 activity, reduced ristocetin-induced platelet aggregation (most
snsp)
Tx- DDAVP desmopressin, factor VIII concentrates (containing HMW vWF) given to all vWF type
after major trauma or during surgery
Cryoprecipitate not recommended because risk of viral transmission
Avoid aspirin/NSAIDs and intramuscular injections

Hemophilia A
Ex- X-inked recessive
Sx- hemarthrosis (MC of knee), progressive joint destruction, intracranial bleeding (any head
trauma is potentially life-threatening and requires urgent evaluation), intramuscular
hematomas, retroperitoneal hematomas, hematuria or hemospermia
Dx- prolonged PTT, low factor VIII with normal vWF levels
Tx- acute hemarthrosis- analgesia (codeine +/- acetaminophen; avoid aspirin and NSADs),
immobilize joint, ice packs, nonweight bearing
Factor VIII concentrate (main)- acute bleeding episodes and before surgery or dental work
Cryoprecipitate and FFP not recommended because risk of viral transmission
Hemophilia B
Tx- factor IX concentrates

Disseminated Intravascular Coagulation

Ex- abnormal activation of coagulation cascade, forming microthrombi throughout
microcirculation; consumption of platelets, fibrin, and coagulation factors; fibrinolytic
mechanisms are activated sleading to hemorrhage. Bleeding and thrombosis occur
simultaneously
-all critically ill patients are at risk for DIC; most common in ICU pateints
Causes- infection (MCC)- esp. gram-negative sepsis, but any infection can cause DIC
Obstetric complications (placenta and uterus have increased tissue factor)amniotic fluid
emboli, retained dead fetus, abruptio placentae
Major itissue injury- trauma, major surgery, burns, fractures
Malignancy, shock/circulatory collapse, snake venom
Sx- bleeding- oozing from sites of procedures, incisions; thrombosis- end-organ infarction may
develop in any organ, especially CNS and kidney
-normal/elevated fibrinogen rules out DIC
Tx- cryoprecipitate, FFP; platelet transfusion not recommended unless counts drop below
30,000; low-dose heparin only in thrombosis predominant clinical picture

Vitamin K deficiency
Ex- broad-spectrum antibiotics (suppresses gut floral production of vit K) in patients who are NPO, TPN,
malabsorption of fat-soluble vitamins (small bowel disease, IBD, obstructive jaundice), warfarin
Dx- PT initially prolonged, PTT follows
Tx- vitamin K replacement; FFP if bleeding is severe
Coagluapathy of Liver Disease
Ex- liver disease must be severe for coagulopathy to develop; and so overall prognosis is poor
Decreased synthesis of clotting factors, cholestasis (dereased vit K), hypersplenism
(splenomegaly due to portal hypertension causes thrombocytopenia
Sx- GI bleed is most common (mainly due to varices 2/2 portal HTN), prolonged PT and PTT (esp
PT)
Tx- FFP (contains all clotting factors), vitamin K (cholestasis), platelet transfusion (if
thrombocytopenia), cryoprecipitate (if fibrinogen deficiency)

Inherited Hypercoagulable States

Antithrombin (AT) III deficiency
Ex- AD, unresponsive to heparin
Antiphospholipid antibody syndrome
Ex- acquired, arterial or venous thrombosis, recurrent fetal loss, thrombocytopenia; antibody against lupus
anticoagulants, anticardiolipin, B2-microglobulin,
Protein C Deficiency
Ex- AD, unregulated fibrin synthesis; portien C inhibits factors V and VIII
Protein S deficiency
Ex- protein S is a cofactor of protein C
Factor V Leiden (activated protein C resistance)
Ex- MC hereditary hypercoagulability disorder aong whites; unregulated prothrombin activation
Prothrombin gene mutation
Hyperhomocysteinemia
Sx- DVT and PE are the MC sequelae
Suspect if family history of DVT, or PE; recurrent episodes; first episode before 40; unusual sites (mesenteric
veins, inferior vena cava, renal veins, cerebra veins)
Tx- standard treatment for DVT or PE ; if >2 events, place on warfarin indefinitely
Breast Cancer
PF-age, family history, thoracic radiation, smoking, alcohol, menstrual cycles
<35- fibroadenoma, cycs fibrocystic changes
DCIS and LCIS
-DCIS- Tx- lumpectomy or mastectomy
-LCIS- increased riskof breast cancer in either breast, removal of lesion does not reduce risk of
preogressio to invasive cacer
Invasive ductal carcinoma and invasive lobular carcinoma
Sx- palpable mass, lymph nodes, skin dimpling, nipple retraction
Dx- confirmed with tissue biopsy, and test for E/P receptor, and Her-2/neu amplification
Tx- surgery (+adjuvant radiotherapy if tumor has not spread to sentinel lymph nodes)
Plasma cell disroders
MGUS
Ex- elderly >75yo, asx premalignant clonal expansion of plasma cell
Dx- IgG spike <3.0g; less than 10% plasma cells in bone marrow; Bence Jones proteinuria
<1g/24h; no end-organ damage (lytic bone lesions, anemia, hypercacemia); most do not
develop multiple myeloma; all multiple myeloma came from MGUS
Tx- none

Multiple Myeloma
Ex- proliferation of a single plasma cell line that produces monoclonal immunoglobulin; >50yo;
blacks; as disease progresses, bone marrow gets replaced by malignant plasma cells leading to
pancytopenia
Sx- bone pain (osteolytic lesions, factures, and vertebral collapses), anemia, renal failure,
infections (MCC of death- lung or urinary tract infection)
Dx- at least 10% abnormal plasma cells in bone marrow + SPEP/UPEP/lytic punched out bone
lesions (mainly skull and axial)- monoclonal protein (M-protein) usually IgG
Tx- hematopoietic cell transplant (HCT) preferred; DO NOT start chemo if considering HCT;
systemic chemo if cant do HCT; radiation if unresponsive to chemo

Waldenstrom Macroglobulinemia
Ex- malignant proliferation of plasmacytoid lymphocytes that produce IgM (very large-
hyperviscosity)
Dx- IgM>5g/dL; NO bone lesions
Sx- neurologic symptoms, lymphadenopathy, splenomegaly, anemia, fatigue, weight loss
Tx- chemo and plasmapheresis for hyperviscosity syndromes
Lymphomas
-cancer of the lymphatic system: Hodgkin and NonHodgkin
-lymphadenopathy is usually the first finding in lymphomas
-chemo and radiation combo achieve cure rates of 70% in Hodgkins

Hodgkin Lymphoma
Ex- bimodal; Nodular sclerosis (70%-bands of collagen envelope pools of RS cells), Mixed
cellularity (25%-large numbers of RS cells in pleomorphic background), Lymphocyte predominat
(5%-few RS cells and many B cells), lymphocyte depletion (<1%-lacking ractive cells, worst
prognosis).
Staging- I-one node, II- >one node same side, III- both sides, IV- extralymphatic site
dissemination; A- no symptoms, B-fever, weight loss, night sweats (worse prognosis)
Sx- MC is painless lymphadenopathy- supraclavicular, cervical, axillary, mediastinal nodes;
continuous spread;
Dx- lymph node biopsy- RS cells needed to make diagnosis; presence of inflammatory cell
infiltrates that are reactive to the RS cells (distinguishes Hodgkin vs NHL)- plasma cells,
eosinophils, fibroblasts , T and B lymphocytes
CXR and CT to detect lymph node involvement; bone marrow biopsy to evaluate bone marrow
involvement
Tx- I, II, IIIA radiation; IIIB and IV- chemo
NonHodgkin Lymphoma
Ex- B cell lymphomas 85%, T cell lymphomas 15%; disease usually starts in lymph nodes and
amy spread to blood and bone marrow; primary tumor may be found in GI tract; 2x as common
as Hodgkin.
PF- HIV/AIDS, immunosuppression, viruses (EBV< HTLV), H.pylori gastritis/gastric lymphoma,
autoimmune disease (Hashimoto, Sjogren)-risk of MALT
Sx-lymphadenopathy (often rapid enlargement), supraclavicular, cervical, axillary;
hepatosplenomegaly, abdominal pain or fullness; pancytopenia
Dx- lymph node biopsy for definitive diagnosis (any node >1cm for more than 4wks not due to
infection need to be biopsied); LDH and B2-microglobulin are indirect indicators of tumor
burden; alk-phos suggests one or liver involvement; LFTs or bilirubin suggest liver involvement
Tx- CHOP therapy
Leukemia
Acute Leukemias (AML and ALL)
AML
Ex- 80% of adult leukemias; neoplasm of myelogenous precursors; APL t(15;17)- pancytopenia
common, Tx- all-trans retinoic acid (ATRA) before confirmation because patients end to be very
sick
PF- radiation, myeloproliferative syndromes, Down syndrome, chemotherapy (alkylating agents)
Tx- not as responsive as ALL
ALL
Ex- neoplasm of early lymphocytic precursors; histology- predomincance of lymphoblasts; MC
malignancy in children in the US; it is the leukemia most responsive to therapy; poor prognosis is
age <2 or >9, WBC 10^5, or CNS involvement
B-cell phenotype, increased LDH, rapid leukemic cell proliferation increases risk for CNS
involvement
Sx- pancytopenia (anemia, increased risk of bacterial infections pneumonia, UTI, cellulitis,
pharyngitis, esophagitis; abnormal bleeding), splenomegaly, hepatomegaly, lymphadenopathy;
bone and joint pain (invasion of periosteum); CNS- - diffuse or focal neurologic dysfunction
Testicular involvement (ALL); anterior mediastinal mass (T-cell ALL), skin nodules (AML)
Dx- bone marrow biopsy needed for diagnosis; ALL-proliferation of lymphoblasts in boen
marrow, AML- Auer rods
Tx- combination chemotherapy

Tumor Lysis Sundrome- hyperkalemia, hyperphosphatemeia, hyperuricemia; medical emergency

CLL
Ex- >60yo; monoclonal proliferation of lymphocytes that are morphologically mature but
nonfunctional; least aggressive type of leukemia
Sx- generalized painless lymphadenopathy, splenomegaly, asymptomatic in early stages
Dx- peripheral blood smear is diagnostic; absolute lymphocytosis with mature WBCs, small
lymphocytes, smudge cells fragile leukemic cells, flow cytometry shows clonal B cells; bone
marrow biopsy shows infiltrating leukemic cells in bone marrow
Tx- observe until symptoms develop
chemotherapy has little effect on overall survival, but provides symptomatic relief and reduction
of infection
Px- depends on number of lymph nodes sites are involved

CML
Ex- >40yo; indolent course before transforming into acute leukemia (blast crisis) which is an
accelerated phase of blast and promyelocyte production; a/w translocation t(9;22); patients
without the Philadelphia chromosome have shorter survival times and respond more poorly to
treatment
Sx- constitutional symptoms are common, asymptomatic in early stages
Dx- marked leukocytosis with left shift toward granulocytes; small numbers of blasts and
promyelocytes; myelocytes, metamyelocytes, bands, segmented form; decreased leukocyte
alkaline phosphatase activity; bone marrow biopsy- leukemic cells
Tx- imagtinib (tyrosine kinase inhibitor)

Leukemoid reaction vs. CML leukemoid reaction- usually no splenomegaly, increased leukocyte
alkaline phosphatase, history of precipitating event (infection)
Myeloproliferative Disorders
Polycythemia Vera
Ex- clonal proliferation of hematopoietic stem cells resulting in excessive erythrocyte production;
proliferation is independent of EPO; JAK2 tyrosine kinase mutations are found in >90% of cases
Sx- hyper viscosity (headache, dizziness, weakness, pruritus, visual impairment, dyspnea0, thrombosis,
bleeding (Gi or genitourinary), splenomegaly, hepatomegaly
Dx- R/O secondary polycythemia (hypoxemia, CO); CBC- elevated RBC, hgb, hct , reduced EPO levels,
hyperuricemia is common; bone marrow biopsy confirms diagnosis
Tx- repeated phlebotomy
-thromotic and hemorrhagic complications in p. vera can be life-threatening

Myelodysplastic syndromes
Ex- idiopathic clonal blood disorders, leading to ineffective hematopoiesis with apoptosis of myeloid
precursors resulting in pancytopenia despite normal or hypercellular bone marrow
PF- radiation, immunosuppressive agents, toxins
Sx- asymptomatic in early stages, incidental pancytopenia
Dx- bone marrow biopsy showing dysplastic marrow cells with blasts or ringed sideroblasts; CC shows
normal or mildly elevated MCV, low retic count
Tx- supportive; RBC and platelet transfusion are the mainstays of treatment; EPO, G-CSF, vitamins and folate;
bone marrow transplant is the only potential cure

Essential Thrombocythemia
Ex- splenomegaly, pseudohyperkalemia, elevated bleeding time; erythromelalgia-burning pain and erythema
of extremities due to microvascular occlusions; hypogranular abnormally shaped platelets, elevated
megakaryocytes; JAK2 tyrosine kinase mutation; Tx- anagrelide and low-dose aspirin; hydroxyurea
sometimes used for severe thromboytosis