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  How to work up hypercoagulability

 

January 2000
Coagulation Case Study

Michael Laposata, MD, PhD
Elizabeth M. Van Cott, MD

Figure 1 | Figure 2 | Figure 3 | Figure 4 | Figure 5 | Figure 6

This is the fifth in a periodic series of articles written by members of the CAP Coagulation Resource Committee and focusing on laboratory evaluation of coagulation disorders.

A 28-year-old man was repairing a sink in his home when he became acutely short of breath. He was taken to the emergency room, where medical personnel established a diagnosis of pulmonary embolism.

Two years earlier, the patient had suffered a deep vein thrombosis and was anticoagulated with warfarin for six months. He was evaluated around the time of his deep vein thrombosis and found to have normal values for what his primary care physician believed was the full battery of laboratory tests appropriate for identifying acquired or congenital hypercoagulation risk factors. However, the patient was tested only for antiphospholipid antibodies, protein C, protein S, and antithrombin. He was not evaluated for factor V Leiden, the prothrombin G20210A mutation, or homocysteine. Because the patient’s antiphospholipid antibody tests and protein C, protein S, and antithrombin levels were normal, his physician terminated his Coumadin therapy at six months, in accordance with published guidelines for treating a spontaneous venous clot in the absence of identifiable risk factors.1

After his second thrombotic event (the pulmonary embolism), the patient was referred to our practice for further evaluation. We tested for activated protein C resistance, the prothrombin G20210A mutation, and obtained a homocysteine level. In this evaluation, the patient was found to be heterozygous for the prothrombin G20210A mutation and heterozygous for factor V Leiden and had no evidence of hyperhomocysteinemia.

The published recommendation for patients with one spontaneous thrombosis and a congenital risk factor (such as factor V Leiden in combination with the prothrombin G20210A mutation) is lifelong warfarin therapy.1 Had the warfarin not been discontinued after his first thrombotic event, the second, more life-threatening clot may have been prevented.

Primary care physicians are now confronted with an array of new diagnostic tests at a faster rate than ever before, particularly in the area of thrombophilia. This poses an educational challenge to physicians. Featured in this area are six algorithms for selecting and interpreting tests that lead to a diagnosis of activated protein C resistance, the prothrombin G20210A mutation, hyperhomocysteinemia, protein C deficiency, protein S deficiency, and antithrombin deficiency. (Antiphospholipid antibodies were the focus of the coagulation case study published in the March 1999 issue of CAP TODAY, page 84.) These flowcharts are evolving rapidly. They represent one current approach to diagnosing hypercoagulable states associated with these six laboratory abnormalities. The current case illustrates the diagnosis of two of the more common risk factors for thrombosis. Future coagulation case studies published as part of this series will refer to the diagnostic algorithms in this article.

Reference
1. Fifth ACCP Consensus Conference on Antithrombotic Therapy. Hyers TM, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease. Chest. 1998;114:561S–578S.

Dr. Laposata is director of clinical laboratories, Massachusetts General Hospital, Boston. He is a member of the CAP Coagulation Resource Committee. Dr. Van Cott is director of the coagulation laboratory, Massachusetts General Hospital.