PANCE Blueprint Hematology (5%)

Lessons

1. 2019 PANCE Hematologic System Content Blueprint
2. Hematology Comprehensive Exam
3. Hematology Flashcards (Members Only)

4. Hematologic System With Joe Gilboy PA-C (Video Lecture)

   45 mins

5. Autoimmune hematologic disorders (PEARLS)
6. Coagulation Disorders (PEARLS)
   1. Clotting factor disorders (Lecture)

      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 + Lecture)

         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 (Lecture)

         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
7. Cytopenias (PEARLS)
   1. Anemias (PEARLS)
      1. Anemia of chronic disease (Lecture)

         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 (Lecture)

         • 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) 

      5. Iron deficiency (Lecture)

         13 mins

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

         ↑ 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.

   2. Leukopenia
8. Cytoses (PEARLS)
   1. Polycythemia
   2. Thrombocytosis
9. Hemoglobinopathies (PEARLS)
   1. Hemochromatosis
   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 (Lecture)

      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
10. Immunologic disorders (PEARLS)
    1. Transfusion reaction
11. Neoplasms, premalignancies, and malignancies (PEARLS)

    6 mins

    1. Acute and chronic lymphocytic leukemia (Lecture)

       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 (Lecture)

       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 + Lecture)

       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 (Lecture)

       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.
    5. Myelodysplasia