When to Evaluate for a Hypercoagulable State

This risk management article is designed to call attention to those settings associated with an increased risk for thromboembolic events.

The Doctors Company has medical consultants who review all claims filed against insured physicians. In a significant number of medical and surgical claims, deep venous thrombosis (DVT) and pulmonary embolism (PE) are complications that contribute directly or indirectly to alleged patient injury.

Hypercoagulability is any alteration in the coagulation pathway that predisposes to thrombosis; it can be divided into primary (genetic) and secondary (acquired) disorders.

Acquired conditions known to predispose to DVT and PE include knee and hip surgery, abdominal surgery, brain surgery, geriatric and obstetrical surgery, prolonged immobility or bed rest, congestive heart failure, and obesity. Malignancies, especially of the lung, prostate, pancreas, and GI tract, also predispose to thromboembolism. In addition, risk for DVT and PE increases with the use of oral contraceptives and postmenopausal hormones. Other rarer conditions, such as myeloproliferative disorders and the nephrotic syndrome, also place the patient at increased risk for thromboembolic disease.

In each of these conditions, the presence of a primary (genetic) disorder or additional acquired factor(s) significantly increases the likelihood of venous thrombosis or thromboembolism. Current thought is that inherited clotting disorders contribute to about 35 percent of thromboembolic events and may account for nearly 70 percent when circumstances lead one to suspect it.

Thromboembolic events that occur in unexpected circumstances should prompt a workup for primary (genetic) disorders contributing to hypercoagulability. Such circumstances include clots occurring in persons under age 50; clotting in an unusual site, such as mesenteric vein, cerebral vein, or axillary vein; a history of venous and arterial thromboses or recurrent venous thrombosis, particularly if unprovoked; and a history of multiple miscarriages or stillbirths.

Before prescribing oral contraceptives or hormone replacement therapy, the physician should ascertain that there is no personal or family history to suggest hypercoagulability. A positive history should lead to laboratory investigation, although even with a negative workup, caution should be used in prescribing hormonal therapy.

The number of positive workups has increased dramatically in recent years with the discovery of factor V Leiden mutation and the G20210A prothrombin gene mutation—which together may account for up to 40 percent of thromboembolic disease resulting from inherited disorders. A negative workup, however, is not a complete guarantee of safety if the history strongly suggests hypercoagulability.

Most authorities feel that the best time to do a workup after an episode of clotting is six months after the event, after completion of the anticoagulation treatment. Testing at this time avoids problems of test interpretation that could result from either the presence of a fresh clot or of Coumadin®. Since laboratory testing for hypercoagulable states can be confusing, complex, and expensive, it should be undertaken with the aid of a hematologist or knowledgeable pathologist.

The following table, abstracted from the excellent reference work of Seligsohn and Lubetsky, lists the most common inherited and acquired coagulation abnormalities leading to hypercoagulable states:

Genetic

Frequent

  • Factor V Leiden abnormality
  • G20210A prothrombin mutation
  • Mutations leading to elevated homocysteine levels

Less Frequent

  • Protein C deficiency
  • Protein S deficiency
  • Antithrombin III deficiency

Rare

  • Dysfibrinogenemia

Acquired

  • Elevated homocysteine related to dietary deficiency (folic acid, B12, B6)
  • Presence of lupus anticoagulant or anticardiolipin antibodies
  • Chronic DIC, especially in relation to cancer
  • Acquired resistance to activated Protein C (multiple causes)

 

 

Reference

Seligsohn, U., and Lubetsky, A.: Gentetic susceptibility to venous thrombosis, N Eng J Med 344(16):1222-31, 2001


 

 

About the Author

Richard Lanzerotti, M.D., practices internal medicine and oncology in San Francisco. He is former chair of the Department of Medicine and the Department of Oncology at St. Francis Memorial Hospital. Dr. Lanzerotti is an assistant clinical professor in the Department of Medicine at UCSF and a consultant for The Doctors Company.


David B. Troxel, M.D., is medical director of The Doctors Company. Dr. Troxel is clinical professor emeritus in the School of Public Health at the University of California at Berkeley. He is past president of the American Board of Pathology and the California Society of Pathologists.
 


The guidelines suggested here are not rules, do not constitute legal advice, and do not ensure a successful outcome. The ultimate decision regarding the appropriateness of any treatment must be made by each healthcare provider in light of all circumstances prevailing in the individual situation and in accordance with the laws of the jurisdiction in which the care is rendered.

J4244 5/03

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