Article CommentaryClinical Case Study

Commentary

Alice D. Ma
DOI: 10.1373/clinchem.2011.174177 Published October 2012

This is a classic case of a patient with a hemorrhagic presentation and an isolated prolonged activated partial thromboplastin time (aPTT).

Lessons to be learned:

  1. Don't blame the dabigatran. Although the patient had discontinued anticoagulation therapy 5 days prior, his prolonged aPTT value was erroneously attributed to dabigatran. If there is concern about dabigatran presence, a thrombin time (TT), which is very sensitive to the presence of direct thrombin inhibitors, can be performed to avoid the delay in appropriate evaluation.

  2. Do a mixing study. That will determine whether the prolongation is due to a factor deficiency (in which case the normal plasma will complement the patient's plasma and the aPTT will normalize) or to an inhibitor (the patient's plasma will “anticoagulate” the normal plasma, and the aPTT will be prolonged).

  3. Do an incubated mixing study. Acquired factor VIII inhibitors exhibit time- and temperature-dependent binding to factor VIII. Thus, a mixing study done immediately may show substantial correction of the clotting time, but after a 2-h incubation at 37°C, the aPTT will become reprolonged. This reprolongation after incubation is highly suggestive of acquired hemophilia.

  4. Check a factor VIII activity level and a Bethesda titer. A bleeding patient with an isolated prolonged aPTT should have his or her activity levels for factors VIII, IX, and XI measured, but factor VIII inhibitors are the most common acquired (nonpharmacologic) bleeding disorder. This individual had an expectedly low factor VIII activity level, and a Bethesda assay to quantify the strength of the inhibitor is required.

  5. Ignore factor XII. Low factor XII levels can be found in samples that have been frozen and thawed, and factor XII deficiency is not a hemorrhagic disorder.

This patient had an acquired autoantibody to factor VIII. These are function-blocking antibodies rather than clearing antibodies. Treatment requires treating bleeding with bypassing agents and inhibitor eradication by immunosuppression.

Footnotes

  • Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.

  • Authors' Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest:

  • Employment or Leadership: None declared.

  • Consultant or Advisory Role: A.D. Ma, Novo Nordisk, Bayer, and CSL Behring.

  • Stock Ownership: None declared.

  • Honoraria: A.D. Ma, Novo Nordisk.

  • Research Funding: None declared.

  • Expert Testimony: None declared.

  • Received for publication September 8, 2011.
  • Accepted for publication September 13, 2011.