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Difficulty: HardOrdering Laboratory Tests

Match each clinical vignette describing a patient with an unexplained bleeding diathesis or abnormal coagulation profile to the most appropriate targeted laboratory test to establish the diagnosis.

  • A 68-year-old man presents with sudden onset of large, spontaneous hematomas on his torso. Coagulation studies show a normal PT and a prolonged aPTT that fails to correct after a 1:1 mixing study with normal plasma.Factor VIII inhibitor assay (Bethesda assay)
  • A 28-year-old woman with a history of two second-trimester miscarriages and a recent deep vein thrombosis is found to have a prolonged aPTT that fails to correct after a 1:1 mixing study with normal plasma.Dilute Russell viper venom time (dRVVT) and anti-cardiolipin antibodies
  • A 34-year-old woman presents with heavy menstrual bleeding and frequent epistaxis since adolescence. Coagulation studies reveal a normal PT, normal aPTT, and a normal platelet count.Von Willebrand factor antigen and ristocetin cofactor activity
  • A 22-year-old man presents with a swollen, painful right knee after minor trauma. He has a history of prolonged bleeding after tooth extraction. Coagulation studies show a normal PT and a prolonged aPTT that fully corrects immediately after a 1:1 mixing study.Factor VIII and Factor IX activity assays

Answer

The elderly man with non-correcting aPTT and bleeding requires a Bethesda assay. The young woman with non-correcting aPTT and thrombosis requires dRVVT. The woman with mucocutaneous bleeding and normal labs requires VWF testing. The young man with a correcting aPTT requires Factor VIII/IX activity assays.
Each matching pair correctly links a distinct hematologic clinical presentation with its definitive diagnostic laboratory test based on the interpretation of standard screening coagulation studies and mixing tests.

Step-by-Step Solution

1
Analyze the baseline coagulation screening tests (PT and aPTT).
Determines whether the defect lies in the extrinsic pathway (prolonged PT), intrinsic pathway (prolonged aPTT), or common pathway (both prolonged).
This localizes the potential factor deficiencies or inhibitors to specific cascades.
2
Interpret the results of the 1:1 mixing study for cases with prolonged aPTT.
Correction of the aPTT indicates a factor deficiency. Failure to correct indicates the presence of a circulating inhibitor (autoantibody).
A mixing study replaces missing factors. If an inhibitor is present, it will neutralize the factors in the normal plasma, keeping the aPTT prolonged.
3
Synthesize the laboratory findings with the clinical phenotype.
Differentiates between bleeding vs. thrombotic presentations (e.g., lupus anticoagulant causes in vitro aPTT prolongation but in vivo thrombosis) and mucocutaneous vs. deep tissue bleeding.
Clinical context dictates which specific factor or inhibitor test to order when the screening lab pattern overlaps.
4
Select the appropriate targeted confirmatory laboratory test.
Leads to the ordering of the Bethesda assay, dRVVT, VWF panel, or Factor activity assays.
Confirms the exact diagnosis to guide highly specific patient management.

Key Concept

Diagnostic approach to abnormal coagulation profiles and mixing studies
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Topics

Ordering Laboratory Tests

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