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Difficulty: MediumOrdering Laboratory Tests

A 3232-year-old woman comes to the clinic for a preoperative evaluation prior to an elective laparoscopic cholecystectomy. She has a history of symptomatic gallstones but is otherwise healthy. The patient has never undergone surgery before and has no history of heavy menstrual bleeding, easy bruising, or frequent epistaxis. She does not take any prescription or over-the-counter medications. Her family history is unremarkable for any bleeding or clotting disorders. Physical examination shows normal vital signs and no petechiae, ecchymoses, or hepatosplenomegaly.

Routine preoperative laboratory tests show:

TestResultReference Range
Hemoglobin13.5 g/dL13.5 \text{ g/dL}12.0−16.0 g/dL12.0-16.0 \text{ g/dL}
Platelet count250,000/mm3250,000/\text{mm}^3150,000−400,000/mm3150,000-400,000/\text{mm}^3
Prothrombin time (PT)11 seconds11 \text{ seconds}11−15 seconds11-15 \text{ seconds}
Activated partial thromboplastin time (aPTT)58 seconds58 \text{ seconds}25−40 seconds25-40 \text{ seconds}

Which of the following is the most appropriate next step in laboratory evaluation?

  1. Plasma mixing studyAnswer
  2. B
    Dilute Russell viper venom time
  3. C
    Factor VIII activity assay
  4. D
    Thrombin time
  5. E
    Platelet function analysis

Answer

Plasma mixing study
The correct answer is a plasma mixing study. This patient presents with an isolated prolonged aPTT and no personal or family history of bleeding. An isolated prolonged aPTT indicates an issue with the intrinsic coagulation pathway (factors VIII, IX, XI, XII) or the presence of a circulating inhibitor (such as a lupus anticoagulant). The necessary initial step in evaluating an unexplained prolonged aPTT is a mixing study, in which the patient's plasma is mixed 1:1 with normal plasma. If the aPTT corrects, a factor deficiency is present, and specific factor assays are the next step. If it fails to correct, an inhibitor is present. In an asymptomatic patient with no bleeding diathesis, a lupus anticoagulant (an inhibitor) or a factor XII deficiency is the most likely cause. The mixing study is the critical branch point to guide further evaluation.

Step-by-Step Solution

1
Identify the isolated laboratory abnormality in the context of the clinical presentation.
The patient has an isolated prolonged aPTT with a normal PT and platelet count, and is entirely asymptomatic with no bleeding history.
Establishing the specific pattern of coagulation abnormality narrows the differential diagnosis to the intrinsic pathway or the presence of an inhibitor.
2
Determine the standard algorithmic approach to an isolated prolonged aPTT.
The initial diagnostic step is to perform a 1:1 plasma mixing study.
A mixing study is necessary to differentiate between a coagulation factor deficiency (which corrects upon mixing with normal plasma) and a circulating inhibitor (which fails to correct).

Key Concept

The evaluation of an isolated prolonged aPTT in an asymptomatic patient begins with a plasma mixing study to differentiate between a coagulation factor deficiency and a circulating inhibitor.
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Ordering Laboratory Tests

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