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The Journal of Bone and Joint Surgery (American) 84:2161-2167 (2002)
© 2002 The Journal of Bone and Joint Surgery, Inc.

Scientific Article

Correlation of Thrombophilia and Hypofibrinolysis with Pulmonary Embolism Following Total Hip Arthroplasty

An Analysis of Genetic Factors

Geoffrey H. Westrich, MD, Babette B. Weksler, MD, Charles J. Glueck, MD, Brianne F. Blumenthal, BA and Eduardo A. Salvati, MD

Investigation performed at The Hospital for Special Surgery-Weill Medical College of Cornell University, New York, NY

Geoffrey H. Westrich, MD
Brianne F. Blumenthal, BA
Eduardo A. Salvati, MD
The Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for G.H. Westrich: westrichg{at}hss.edu

Babette B. Weksler, MD
New York Presbyterian Hospital, 525 East 68th Street, New York, NY 10021. E-mail address: babette@med.cornell.edu

Charles J. Glueck, MD
Molecular Diagnostics Laboratory, 3130 Highland Avenue, 3rd Floor, Cincinnati, OH 45219. E-mail address: glueckch@healthall.com

In support of their research or preparation of this manuscript, one or more of the authors received donations from Dr. and Mrs. Alberto Foglia. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Background: The increased thromboembolic risk associated with total hip arthroplasty is multifactorial. We assessed whether the prevalence of abnormalities shown by newer genetic screening tests for thrombophilia and hypofibrinolysis was higher in patients in whom pulmonary embolism had developed after total hip arthroplasty than it was in matched control patients.

Methods: Fourteen patients with documented pulmonary embolism after total hip arthroplasty and fourteen matched control patients who had undergone total hip arthroplasty without any clinical indication of thromboembolism were evaluated for risks of thrombophilia and hypofibrinolysis. Functional tests of hemostasis included evaluations of prothrombin time; activated partial thromboplastin time; levels of fibrinogen, serum homocysteine, protein C and S, and antithrombin III; activated protein-C resistance; and dilute Russell viper venom time. Molecular genetic testing was performed for factor-V Leiden, prothrombin promoter G20210A, methylenetetrahydrofolate reductase C677T, plasminogen activator inhibitor-1 4G/4G, and platelet glycoprotein IIb/IIIa A1/A2 or A2/A2 mutations.

Results: The total number of genetic thrombophilic abnormalities identified was higher in the pulmonary embolism group (twenty-four abnormalities) than in the control group (fifteen abnormalities). Only patients with pulmonary embolism were found to have heterozygosity or homozygosity for the prothrombin G20210A mutation (four of fourteen patients; p = 0.05 compared with the control group) and a decreased antithrombin-III level (three of thirteen patients; p = 0.10 compared with the control group). Patients with pulmonary embolism were much more likely than control patients to have at least one thrombophilic abnormality: seven of fourteen patients with pulmonary embolism had a low antithrombin-III level or the prothrombin G20210A gene mutation compared with none of the fourteen in the control group (Fisher exact test, p < 0.01). The presence of the prothrombin G20210A gene mutation was significantly correlated with pulmonary embolism (r = 0.41, p = 0.03), as was the presence of least one abnormality (a low antithrombin-III level or the presence of the prothrombin G20210A gene mutation) (r = 0.58, p = 0.001).

Conclusions: Genetic thrombophilia and hypofibrinolysis were more frequent in patients who had had pulmonary embolism after total hip arthroplasty than in those who had not. The presence of multiple genetic thrombophilic polymorphisms, particularly prothrombin G20210A and antithrombin III, rather than any single genetic prothrombotic abnormality, appears to signal an increased thromboembolic risk in patients undergoing total hip arthroplasty. Future refinements and availability of these tests will likely allow preoperative identification of patients with an increased genetic predisposition for thromboembolism.


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