Abnormal aPTT? Perform an inhibitor mixing study

Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 37-year-old woman undergoes preoperative evaluation prior to a hysterectomy for worsening menstrual bleeding of several years’ duration caused by uterine fibroids. She has a recent history of recurrent epistaxis and bleeding after recent dental work but denies thromboembolism and a family history of unusual bleeding. The patient is otherwise healthy. Her only medication is an occasional aspirin.

The pelvic examination reveals a slightly enlarged, irregular uterus. The remainder of the physical examination is normal.

Laboratory studies:

Hemoglobin	11 g/dL (110 g/L)
Platelet count	182,000/µL (182 × 10⁹/L)
INR	1.1
Activated partial thromboplastin time (aPTT)	52 s

Which of the following is the most appropriate next diagnostic test?

A) Anticardiolipin antibody assay
B) aPTT mixing study
C) Factor VIII assay
D) von Willebrand factor assay

MKSAP Answer and Critique

The correct answer is B) aPTT mixing study. This item is available to MKSAP 15 subscribers as item 33 in the Hematology and Oncology section. MKSAP 16 will release Part A on July 31. More information is available online.

This patient has a prolonged activated partial thromboplastin time (aPTT). The first diagnostic step in determining the cause of an abnormal aPTT or prothrombin time (PT) is to perform an inhibitor mixing study. In a mixing study, the patient’s plasma is mixed in a 1:1 ratio with normal pooled plasma, and the clotting tests with abnormal results are repeated. A mixing study that corrects to normal indicates a factor clotting deficiency, whereas one that does not correct (or only poorly corrects) indicates the presence of a clotting inhibitor or antibody. Once the results of the inhibitor mixing study are established, other assays to identify the deficient clotting factor or the type of clotting inhibitor can be done.

Although this patient might have von Willebrand’s disease, hemophilia A, or the antiphospholipid antibody syndrome with a mild factor VIII deficiency causing an elevated aPTT, understanding the mechanism responsible for the elevated aPTT is necessary before performing tests to rule out these diagnoses.

Key Point

Performing an inhibitor mixing study is the first step in identifying the cause of an abnormal activated partial thromboplastin time or prothrombin time.

Learn more about ACP’s MKSAP 16.

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