hematology-oncology review session pete voorhees
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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 Coomb’s test (direct antiglobulin test or DAT).– Indirect Coomb’s 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, + 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).
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 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).
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.