hematology-oncology review session pete voorhees

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Hematology-Oncology Review Session Pete Voorhees

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Page 1: Hematology-Oncology Review Session Pete Voorhees

Hematology-Oncology Review Session

Pete Voorhees

Page 2: 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.

Page 3: Hematology-Oncology Review Session Pete Voorhees

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.

Page 4: Hematology-Oncology Review Session Pete Voorhees

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.

Page 5: Hematology-Oncology Review Session Pete Voorhees

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.

Page 6: Hematology-Oncology Review Session Pete Voorhees

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.

Page 7: Hematology-Oncology Review Session Pete Voorhees

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.

Page 8: Hematology-Oncology Review Session Pete Voorhees

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.

Page 9: Hematology-Oncology Review Session Pete Voorhees

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.

Page 10: Hematology-Oncology Review Session Pete Voorhees

Warm Autoimmune Hemolytic Anemia

• Symptoms of anemia, jaundice, splenomegaly.

• Smear: spherocytes, polychromatophilia.

• Labs: Increased retic. ct., high LDH, high indirect bilirubin, + direct Coomb’s test (direct antiglobulin test or DAT).– Indirect Coomb’s usually

positive as well.

• Treatment: immune-suppression (steroids, spenectomy), treat / remove underlying trigger.

Page 11: Hematology-Oncology Review Session Pete Voorhees

Warm Autoimmune Hemolytic Anemia

• Causes: Idiopathic, SLE, lymphoproliferative disorder (lymphoma, CLL).

• Drugs– Innocent bystander: quinine, quinidine, INH– Hapten: PCNs, cephs– Autoimmune: alpha-methyldopa,

procainamide

Page 12: Hematology-Oncology Review Session Pete Voorhees

Cold Agglutinin Disease• Symptoms of anemia,

acrocyanosis.• Smear, RBC agglutination,

polychromatophilia.• Labs: Increased retic. ct., LDH,

bilirubin, + Coomb’s 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).

Page 13: Hematology-Oncology Review Session Pete Voorhees

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).

Page 14: Hematology-Oncology Review Session Pete Voorhees

Von Willebrand’s 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).

Page 15: Hematology-Oncology Review Session Pete Voorhees

Venous Thrombosis

• Causes– Acquired

• Cancer• Myeloproliferative disorders (P. Vera, Essential

thrombocytosis)• Antiphospholipid antibody syndrome• Hyperhomocysteinemia• Pregnancy• OCPs, HRT• Prior venous thrombosis• Age• Immobilization• Surgery

Page 16: Hematology-Oncology Review Session Pete Voorhees

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

Page 17: Hematology-Oncology Review Session Pete Voorhees

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

Page 18: Hematology-Oncology Review Session Pete Voorhees

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.

Page 19: Hematology-Oncology Review Session Pete Voorhees

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.

Page 20: Hematology-Oncology Review Session Pete Voorhees

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.

Page 21: Hematology-Oncology Review Session Pete Voorhees

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

Page 22: Hematology-Oncology Review Session Pete Voorhees

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).

Page 23: Hematology-Oncology Review Session Pete Voorhees

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.

Page 24: Hematology-Oncology Review Session Pete Voorhees

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.

Page 25: Hematology-Oncology Review Session Pete Voorhees

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).

Page 26: Hematology-Oncology Review Session Pete Voorhees

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.

Page 27: Hematology-Oncology Review Session Pete Voorhees

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.