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High-Yield Hematology for the PANCE

The hematologic system is a smaller but consistently tested domain (~5% of the current NCCPA PANCE blueprint), dominated by anemias, hemoglobinopathies, and coagulation/platelet disorders. Master the smear-and-index pattern recognition and first-line workups below for reliable points.

Microcytic & Macrocytic Anemias

  • ◆Iron deficiency (most common): low ferritin (<15-30), high TIBC, low iron/sat, high RDW; in adult men/postmenopausal women, evaluate for GI blood loss/colon cancer. Treat with oral ferrous sulfate (e.g., 325 mg = 65 mg elemental) given ONCE daily or every-other-day — 2024 ACG/EHA guidance favors alternate-day dosing to lower hepcidin, improve absorption, and reduce GI side effects.
  • ◆Anemia of chronic disease: low iron and low TIBC but NORMAL or HIGH ferritin (acute-phase reactant); hepcidin-mediated. Distinguishes from IDA by the ferritin/TIBC pattern.
  • ◆Thalassemia: microcytosis with NORMAL/high RBC count, low Mentzer index (MCV/RBC <13), target cells; beta-thal shows elevated HbA2 on electrophoresis. Do NOT give iron unless deficiency is proven.
  • ◆B12 deficiency: macrocytic, hypersegmented neutrophils, glossitis, plus NEUROLOGIC signs (subacute combined degeneration, paresthesias). Check methylmalonic acid (elevated). Pernicious anemia → anti-intrinsic factor antibodies.
  • ◆Folate deficiency: macrocytic with hypersegmented PMNs but NO neurologic findings; normal MMA, high homocysteine. Always rule out B12 before repleting folate.

Hemolytic Anemias & Hemoglobinopathies

  • ◆Hemolysis labs: elevated LDH and indirect bilirubin, LOW haptoglobin, reticulocytosis. Direct Coombs (DAT) positive = autoimmune.
  • ◆Sickle cell disease: vaso-occlusive pain crises, acute chest syndrome (fever/hypoxia/infiltrate - leading cause of death), splenic sequestration, functional asplenia. Hydroxyurea raises HbF and reduces crises; ensure pneumococcal/meningococcal vaccination and penicillin prophylaxis in kids.
  • ◆G6PD deficiency: X-linked; episodic hemolysis with oxidative stress (fava beans, sulfa/dapsone/primaquine, infection); bite cells and Heinz bodies on smear.
  • ◆Hereditary spherocytosis: spherocytes, elevated MCHC, positive osmotic fragility/EMA binding; splenomegaly, pigmented gallstones; treat with splenectomy in severe cases.
  • ◆G6PD: check enzyme level AFTER the acute hemolytic episode resolves (young reticulocytes have higher enzyme and falsely normalize the assay).

Platelet & Bleeding Disorders

  • ◆ITP: isolated thrombocytopenia, otherwise normal counts; often post-viral in kids (self-limited). Treat if platelets <30k or bleeding: corticosteroids (short course, e.g., prednisone 0.5-2 mg/kg/day or dexamethasone 40 mg/day x4) first-line; add IVIG for severe bleeding or when a rapid rise is needed.
  • ◆TTP: pentad (thrombocytopenia, microangiopathic hemolytic anemia with schistocytes, fever, renal, neuro) from ADAMTS13 deficiency. EMERGENT treatment is plasma exchange PLUS corticosteroids; caplacizumab is now added first-line and rituximab is commonly used. Do NOT transfuse platelets.
  • ◆von Willebrand disease: most common inherited bleeding disorder; mucocutaneous bleeding, prolonged bleeding time/PFA, often prolonged aPTT (low factor VIII). Treat with desmopressin (DDAVP) for type 1.
  • ◆Hemophilia A (factor VIII) / B (factor IX): X-linked; hemarthrosis and deep muscle bleeds, isolated prolonged aPTT that corrects with mixing study. Replace the specific factor.
  • ◆HIT: platelet drop >50% typically 5-10 days after heparin, paradoxical thrombosis; STOP all heparin, start a non-heparin anticoagulant (argatroban), avoid warfarin acutely and platelet transfusion.

Coagulation Cascade & Anticoagulation

  • ◆PT/INR reflects extrinsic pathway (factor VII, warfarin/vit K); aPTT reflects intrinsic (VIII, IX, XI, XII, heparin). Both elevated in DIC and vitamin K deficiency/liver disease.
  • ◆DIC: prolonged PT/aPTT, LOW fibrinogen and platelets, HIGH D-dimer, schistocytes; treat the underlying cause (sepsis, malignancy, obstetric).
  • ◆Warfarin: bridge with heparin initially due to transient protein C/S drop (procoagulant window); reverse with vitamin K plus 4-factor PCC for major bleeding.
  • ◆DOACs (apixaban, rivaroxaban, dabigatran): preferred over warfarin for most nonvalvular AFib and VTE; idarucizumab reverses dabigatran. Andexanet alfa is the specific factor Xa inhibitor reversal agent but was voluntarily withdrawn from the US market in 2025, so 4-factor PCC is the practical alternative for Xa-inhibitor major bleeding.
  • ◆Provoked VTE: anticoagulate 3 months; unprovoked or recurrent VTE often warrants extended/indefinite therapy.

White Cell & Malignant Disorders

  • ◆ALL: most common childhood cancer; blasts, fever, bone pain, lymphadenopathy; high cure rate.
  • ◆AML: adults, Auer rods; DIC classically with acute promyelocytic leukemia (APL, t(15;17)) treated with ATRA (often with arsenic trioxide).
  • ◆CLL: most common adult leukemia; older adults, smudge cells, absolute lymphocytosis; often asymptomatic and observed.
  • ◆CML: t(9;22) Philadelphia chromosome/BCR-ABL, massive splenomegaly, marked leukocytosis; treat with imatinib (tyrosine kinase inhibitor).
  • ◆Hodgkin lymphoma: Reed-Sternberg cells, contiguous nodal spread, bimodal age, B symptoms; Non-Hodgkin: more common, noncontiguous/extranodal spread.
  • ◆Multiple myeloma: CRAB (hyperCalcemia, Renal failure, Anemia, Bone lytic lesions), monoclonal M-spike, Bence Jones proteins, rouleaux; older adults with back pain.
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