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Difficulty: MediumInterpreting Laboratory Results

A 34-year-old woman is evaluated during a preoperative assessment prior to an elective laparoscopic cholecystectomy. She has a history of systemic lupus erythematosus, which is currently well-controlled on hydroxychloroquine. She reports no history of heavy menses, excessive bruising, or abnormal bleeding following a dental extraction 5 years ago. Vital signs are within normal limits. Physical examination is unremarkable.

Laboratory results are as follows:

Laboratory TestResultReference Range
Hemoglobin12.8 g/dL12.0-16.0 g/dL
Platelet count210,000/mm³150,000-400,000/mm³
Prothrombin time (PT)12 seconds11-15 seconds
Activated partial thromboplastin time (aPTT)58 seconds25-40 seconds

Due to the isolated prolonged aPTT, a mixing study is performed using equal parts of the patient's plasma and normal pooled plasma. The repeat aPTT on the mixture is 54 seconds.

Which of the following is the most likely underlying cause of this patient's laboratory findings?

  1. Presence of an inhibitor directed against phospholipid-binding proteinsAnswer
  2. B
    Deficiency of coagulation factor VIII
  3. C
    Defective platelet adhesion and reduced carrier protein for factor VIII
  4. D
    Impaired gamma-carboxylation of coagulation factors
  5. E
    Systemic consumption of coagulation factors and platelets

Answer

Presence of an inhibitor directed against phospholipid-binding proteins
The correct answer accurately describes the pathophysiology of a lupus anticoagulant (an antiphospholipid antibody). In a mixing study, the patient's plasma is mixed 1:1 with normal pooled plasma. If the patient has a factor deficiency (e.g., Hemophilia A, von Willebrand disease), the normal plasma will replace the missing factors, and the aPTT will correct to a normal range. If the patient has an inhibitor (e.g., lupus anticoagulant), the inhibitor will bind to the phospholipids in the normal plasma reagent as well, and the aPTT will remain prolonged (fail to correct). Given this patient's history of SLE and the failure of the aPTT to correct, a lupus anticoagulant is the most likely cause.

Step-by-Step Solution

1
Interpret the baseline coagulation panel.
The patient has an isolated prolonged aPTT with a normal PT and normal platelet count.
An isolated prolonged aPTT indicates a defect in the intrinsic or common coagulation pathway.
2
Analyze the results of the mixing study.
The aPTT remains prolonged (54 seconds) after adding normal pooled plasma.
Failure to correct on a mixing study differentiates a coagulation inhibitor (which neutralizes factors in the normal plasma) from a factor deficiency (which is replenished by the normal plasma).
3
Correlate the laboratory findings with the patient's clinical history.
The patient has SLE, no bleeding history, and an inhibitor pattern on the mixing study, pointing to a lupus anticoagulant.
Lupus anticoagulants are antiphospholipid antibodies that bind to phospholipids in the assay, artifactually prolonging the aPTT in vitro despite promoting a prothrombotic state in vivo.

Key Concept

Interpretation of Coagulation Mixing Studies
Estimated Time:1m 0s
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Topics

Interpreting Laboratory Results

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