PANCE Blueprint Hematology (3%)

Lessons

1. Hematology Comprehensive Exam
2. Hematology Flashcards (Members Only)
3. Anemias (PEARLS)
   1. Anemia of chronic disease

      6 mins

      Normal or ↓ MCV, ↓  TIBC, ↑ Ferritin (high iron stores) ↓ serum erythropoietin

      • Normochromic/microcytic (normocytic initially)
      • Diagnosis generally requires the presence of chronic infection
      • ↓ serum erythropoietin levels in anemia of renal failure
   2. Aplastic Anemia

      The only anemia where all three cell lines are decreased ↓ WBC, ↓ RBC, ↓ Platelets - will have normal MCV and ↓ Retic

      • Diagnostic studies: Pancytopenia
   3. Folate deficiency

      ↓ Folate, ↑ MCV (macrocytic anemia) looks like B12 but no neurologic symptoms

      • Population: Alcoholics
      • Megaloblastic anemia, elevated homocysteine
   4. Hemolytic anemia

      • Autoimmune Hemolytic Anemia (+ Direct Coombs Test) -  ↑ Retic, ↑ LDH, ↓ Haptoglobin, and ↑ Bilirubin (indirect) 
      • Hereditary Spherocytosis (+) osmotic fragility test. ↑ Retic, ↑ LDH, ↓ Haptoglobin, and ↑ Bilirubin (indirect) and presence of spherocytes
      1. G6PD deficiency

         After infection or medication (oxidative stress) in an African American male (x-linked) + Heinz Bodies and Bite Cells on smear (damaged hemoglobin - G6PD protects RBC membrane) 
      2. Sickle cell anemia (ReelDx)

         8 mins

         Very High Retic count + Pain in African American male, +  Sickled cells on peripheral smear + Diagnosis requires (+) HgbS on hemoglobin electrophoresis is definitive, howell-Jolly bodies, target cells
      3. Thalassemia

         Very ↓ MCV (microcytic and hypochromic) with a normal TIBC, Ferritin and ↑ elevated iron, normal to ↓ Retic count and a (+) HB Electrophoresis. Family history of blood cell disorder

   5. Iron deficiency

      13 mins

      ↓ MCV (microcytic), ↓ MCH (hypochromic), ↑ TIBC, ↓ Ferritin (best test, low iron stores), Target cells, pica and nail spooning
   6. Vitamin B12 deficiency

      ↑ MCV (macrocytic anemia), Hypersegmented Neutrophils and normal folate, decreased vibratory and position sense

      • Etiology: Pernicious anemia (antibody to intrinsic factor), gastrectomy, vegans
      • Smooth beefy, sore tongue and neurologic symptoms (poor balance, low proprioception)
      • Schilling test (pernicious anemia) less than 10% radiolabeled vitamin B12 in urine. Normal results when repeated with administration of intrinsic factor.
4. Coagulation Disorders (PEARLS)
   1. Clotting factor disorders

      9 mins

      Von Willebrand Disease (vWD)

      • Most common genetic bleeding disorder, autosomal dominant
      • ↑ PTT, prolonged bleeding time, ↓ Willebrand factor
      • Patients may present with excessive bleeding after a cut, or increased menstrual bleeding. 
      • Treat with DDAVP (desmopressin)

      Hemophilia is a hereditary bleeding disorder caused by a deficiency in one of two blood clotting factors: VIII or IX.  Presents with spontaneous hemarthrosis, ↑ aPTT and normal platelet count and function

      • Hemophilia A, which accounts for about 80% of all cases, is a deficiency in clotting factor VIII
      • Hemophilia B is a deficiency in clotting factor IX (Christmas disease)
   2. Hypercoagulable states

      • Factor V Leiden (the most common)
        • Mutated factor V resistant to breakdown by activated Protein C - results in hypercoagulability.
        • Increased DVT and PE especially in young patients.
        • Diagnosis with activated protein C resistance assay (factor V Leiden specific functional assay) - if positive, confirm with DNA testing. Normal PT/PTT.
        • Long-term antithrombotic therapy not recommended.
      • Protein C/S Deficiency
        • Protein C (with cofactor protein S) inactivates factors V and VIII. Deficiency of either protein C or S leads to active factors V and VIII, which leads to thrombosis.
        • DVT or PE at a young age. After warfarin initiation - skin necrosis. 
        • Diagnose with Protein C or S functional assay (preferred) - ↓ protein C or S activity levels.
        • Requires Heparin and oral anticoagulation for life.
      • Antithrombin III Deficiency
        • Antithrombin is a natural anticoagulant. It inhibits thrombin, factor Xa, and other serine proteases in the coagulation cascade such as factor IXa.
        • Antithrombin III activity is potentiated by Heparin.
        • Deficiency associated with DVT and PE.
        • Patients with thrombotic events require high-dose IV heparin then oral anticoagulation indefinitely. 
      • Antiphospholipid Syndrome
        • Autoimmune disorder, often associated with systemic lupus erythematosus (SLE), characterized by thromboses and recurrent spontaneous abortions.
        • Autoantibodies (lupus anticoagulant, anticardiolipin, and anti-β₂ glycoprotein antibodies) react against platelet membranes or prothrombin-platelet membrane complex, activating endothelial cells and platelets - this activates complement-mediated thrombosis.
        • Diagnose with lupus anticoagulant, prolonged dilute Russell viper venom time (DRVVT) test, prolonged (PTT), anti-β2 glycoprotein, and anticardiolipin antibody.
        • Patients with thrombotic events require high-dose IV heparin then oral anticoagulation indefinitely. 

       
   3. Thrombocytopenia
      1. Idiopathic thrombocytopenic purpura (ReelDx)

         Autoimmune reaction to platelets usually after a viral illness (ITP is insidious and chronic)

         • Diagnosis of exclusion
           • Associated with HIV, HCV, SLE, CLL
           • CBC normal except low platelets.  (+ Direct Coombs Test)
      2. Thrombotic thrombocytopenic purpura (TTP)

         Thrombotic Thrombocytopenia (TTP):↓ Platelets + anemia + schistocytes (RBC fragments) on smear and (-) Coombs test

         • After drugs: Quinidine, cyclosporine & pregnancy
           • Inhibition of ADAMTS13
         • Presentation: Adults
           • Purpura and “FAT RN”- Fever, Anemia, Thrombocytopenia, Renal failure, Neurological symptoms
         • Diagnostic studies: CBC normal except ↓ Platelets. Schistocytes (RBC fragments) on smear

         Hemolytic Uremic Syndrome (HUS): ↓ Platelets + anemia + renal failure (associated with E.coli O157: H7 and diarrheal illness in child)

         • Post-infection: E.coli or Shigella
         • Children, severe kidney problems
5. Hematologic Malignancies (PEARLS)

   6 mins
   1. Acute and chronic lymphocytic leukemia

      Acute lymphocytic leukemia (ALL): CHILD + Lymphadenopathy + bone pain + bleeding + fever in a CHILD, bone marrow > 20% blasts in bone marrow

      • Population: Children - most common childhood malignancy peak age 3-7
      • Highly responsive to chemotherapy (remission > 90%)

      Chronic Lymphocytic Leukemia (CLL): Middle age patient, often asymptomatic (seen on blood tests), fatigue, lymphadenopathy, splenomegaly

      • Population: Adults - most common form of leukemia in adults - peak age 50 y/o
      • Diagnostic studies: SMUDGE CELLS on peripheral smear, mature lymphocytes
      • Treatment with observation, if lymphocytes are > 100,000 or symptomatic treat with chemo
   2. Acute and chronic myelogenous leukemia

      9 mins

      Acute Myeloid Leukemia (AML): BLASTS + AUER RODS  in ADULT PATIENT

      • Population: Adults (80%) majority of patients > 50 y/o
      • Anemia, thrombocytopenia, neutropenia. Splenomegaly, gingival hyperplasia and Leukostasis (WBC > 100,000)
      • Auer Rods and > 20% blasts seen in bone marrow

      Chronic Myeloid Leukemia (CML): Strikingly Increased WBC count > 100,000 + hyperuricemia + Adult patient (usually > 50 years old)

      • Population: Adults - patient usually > 50 y/o
      • 70% asymptomatic until patient has blastic crisis (acute leukemia) 
      • Diagnostic studies: Philadelphia chromosome (translocation of chromosome 9 and 22) - "Philadelphia CreaM cheese", splenomega
   3. Lymphoma (ReelDx)

      Hodgkin's Lymphoma: painless lymphadenopathy + bimodal age distribution (15-35) and (>60)

      • Fever, chills, and night sweats for > 1 month. Painless enlarged posterior cervical and supraclavicular lymph nodes Virchow’s node. CXR - mediastinal adenopathy. Excisional biopsy of lymph node shows Reed-Sternberg cells

      Non-Hodgkin Lymphoma

      • Look for an immunocompromised (HIV) Patient with GI symptoms and painless peripheral lymphadenopathy
   4. Multiple myeloma

      Cancer of monoclonal plasma cells - produces large amounts of IgG (55% of cases) or IgA (25% of cases).

      • An older patient with bone and back pain refractory to treatments.
      • Presentation: “CRAB”- Calcium elevation, renal failure, anemia, and bone lesions.
      • Serum protein electrophoresis: Monoclonal (M protein) Spike (IgG or IgA).
      • Urinalysis: Monoclonal proteinuria (Bence Jones Protein).
      • Blood smear: Rouleaux formation (stacked RBCs).
      • Radiograph: X-ray showing lytic "punched-out" bone lesions of skull, spine, long bones.
      • Bone marrow biopsy: > 10% clonal plasma cells.