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Difficulty: HardHematology and Oncology

Match each clinical and laboratory presentation with its most likely underlying pathophysiologic mechanism.

  • A 32-year-old woman presents with heavy menses and mucosal petechiae. Labs show a platelet count of 12,000/mm³, normal PT, normal aPTT, and large platelets on peripheral smear without schistocytes.IgG autoantibodies directed against platelet membrane glycoproteins IIb/IIIa or Ib/IX
  • A 45-year-old man presents with fever, confusion, and petechiae. Labs show a platelet count of 22,000/mm³, normal PT, normal aPTT, abundant schistocytes on smear, and a creatinine of 2.6 mg/dL.Severe deficiency of ADAMTS13 leading to uncleaved ultra-large von Willebrand factor multimers
  • A 28-year-old pregnant woman with abruptio placentae develops diffuse oozing from venipuncture sites. Labs show a platelet count of 45,000/mm³, prolonged PT, prolonged aPTT, and elevated D-dimer.Systemic activation of the coagulation cascade leading to widespread consumption of clotting factors and platelets
  • A 55-year-old man presents with an unprovoked deep vein thrombosis. Labs show a normal platelet count, normal PT, and a prolonged aPTT that fails to correct when his plasma is mixed with normal plasma.Presence of autoantibodies directed against phospholipid-binding proteins that prolong phospholipid-dependent coagulation assays in vitro

Answer

Patient 1 matches with IgG autoantibodies (ITP). Patient 2 matches with ADAMTS13 deficiency (TTP). Patient 3 matches with systemic activation of the coagulation cascade (DIC). Patient 4 matches with autoantibodies against phospholipid-binding proteins (Antiphospholipid Syndrome).
Each clinical vignette provides pathognomonic laboratory findings that differentiate these hematologic disorders. ITP is defined by isolated autoantibody-mediated platelet destruction. TTP is driven by uncleaved von Willebrand factor multimers creating platelet microthrombi (normal coags, schistocytes). DIC involves systemic factor consumption (prolonged coags). Lupus anticoagulant acts as an inhibitor, artificially prolonging aPTT while causing thrombosis.

Step-by-Step Solution

1
Analyze the first presentation (isolated severe thrombocytopenia with normal coagulation times and large platelets).
Identified as Immune Thrombocytopenic Purpura (ITP).
The absence of schistocytes rules out microangiopathic processes, and normal PT/aPTT rules out consumptive coagulopathies.
2
Analyze the second presentation (thrombocytopenia, schistocytes, renal injury, neurologic symptoms, and normal coagulation times).
Identified as Thrombotic Thrombocytopenic Purpura (TTP).
The presence of microangiopathic hemolytic anemia with normal coagulation studies points strictly to ADAMTS13 deficiency causing platelet-rich microthrombi.
3
Analyze the third presentation (bleeding diathesis following obstetric complication, thrombocytopenia, prolonged PT/aPTT, and elevated D-dimer).
Identified as Disseminated Intravascular Coagulation (DIC).
Prolongation of both PT and aPTT alongside thrombocytopenia indicates systemic consumption of both coagulation factors and platelets.
4
Analyze the fourth presentation (venous thrombosis with isolated, non-correcting prolonged aPTT).
Identified as Antiphospholipid Syndrome (specifically lupus anticoagulant).
Failure of the aPTT to correct during a mixing study confirms the presence of an inhibitor (rather than a factor deficiency) which paradoxically causes in vivo thrombosis.

Key Concept

Pathophysiology and laboratory differentiation of thrombocytopenia and coagulation disorders
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Topics

Hematology and Oncology

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