Hematology-Oncology Review Session

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Hematology-Oncology Review Session

• Pete Voorhees

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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.

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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.

4
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.

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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.

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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.

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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.

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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.

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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.

10
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.

11
Warm Autoimmune Hemolytic Anemia

• Causes Idiopathic, SLE, lymphoproliferative
  disorder (lymphoma, CLL).
• Drugs
• Innocent bystander quinine, quinidine, INH
• Hapten PCNs, cephs
• Autoimmune alpha-methyldopa, procainamide

12
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).

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Hemophilia A and B

• X-linked.
• Factor VIII (Hemo A) gt 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).

14
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).

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Venous Thrombosis

• Causes
• Acquired
• Cancer
• Myeloproliferative disorders (P. Vera, Essential
  thrombocytosis)
• Antiphospholipid antibody syndrome
• Hyperhomocysteinemia
• Pregnancy
• OCPs, HRT
• Prior venous thrombosis
• Age
• Immobilization
• Surgery

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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

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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

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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.

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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.

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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.

21
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

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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).

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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.

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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.

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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 lt 60, no clotting risk factors
  (smoking, HTN, etc.), plts lt 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).

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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.

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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(922), BCR-ABL.
• Treatment Bone marrow transplant, Gleevec.
• Monitoring disease cytogenetics, FISH for
  t(922), PCR for BCR-ABL.