TREATMENT OF THROMBOPHILIC DISORDERS
Some individuals with thrombophilic disorders will never develop VTE; however, some physicians believe that the presence of any thrombotic disorder produces a 1% to 10% lifetime increase in risk of VTE.10 The risk is higher for persons with a combination of genetic disorders, and it is also higher if a genetic disorder is superimposed on an acquired risk factor.1 When oral contraceptive use precipitates the thrombosis, such as in the case presented in this article, significant lifestyle changes are necessary, including the use of an alternative contraceptive method.
Long-term decisions regarding thrombophilia are complex and outside the realm of primary care providers. However, the initial treatment of VTE when a thrombophilic disorder is suspected is the same as when no disorder is suspected and is within the scope of primary care. Combination of a standard low molecular weight heparin and warfarin plus bed rest should be used. PAs should consult the American Academy of Family Physicians Anticoagulation Worksheet for a detailed treatment protocol.21 As a general rule, an INR of 2.0 to 3.0 should be maintained.22 The decision regarding long-term anticoagulant therapy should be made with a hematology specialist and is based on several factors, including whether the patient has acquired or reversible risk factors versus genetic or irreversible ones.23,24
RISKS FOR RECURRENCE
Multiple studies have examined the risk of VTE recurrence for the thrombophilias in order to determine the need for long-term or lifelong anticoagulation. One recent study followed approximately 300 patients with VTE and an underlying thrombophilic disorder and approximately 200 patients with VTE who do not have thrombophilia for several years. The overall results revealed that although the risk of VTE recurrence was slightly higher for patients with thrombophilia, the difference was not significant.25 Furthermore, the risk of VTE recurrence was not significantly increased for patients with factor V Leiden or prothrombin 20210/20210A mutation; risk was only slightly increased in patients with protein C, protein S, and antithrombin deficiencies; and risk was not significantly increased in patients with elevated factor VIII or hyperhomocysteinemia.25 Risk for recurrence was slightly increased for patients with more than one genetic disorder. As a result of these findings, researchers concluded that a complex interaction between acquired or environmental factors and intrinsic or genetic factors is responsible for any increased propensity toward thrombosis formation and recurrence.25
The evidence presented in this review suggests that persons with a single known thrombophilia are better suited to simply avoiding conditions and/or medications that are known to increase the risk of thrombosis (ie, smoking, use of oral contraceptives or hormone replacement therapy, etc) rather than embark on long-term anticoagulation therapy. On the other hand, persons with multiple thrombophilias will probably benefit from long-term anticoagulation therapy, similar to that prescribed for the case patient. Her hematologist recommended that she remain on lifelong warfarin therapy, refrain from smoking, and avoid all medications containing estrogen. In the event that she becomes pregnant, she will be switched to low molecular weight heparin to avoid the teratogenic effects of warfarin.
REFERRALS FOR PATIENTS WITH THROMBOPHILIA
Patients with thrombophilic disorders require long-term follow-up by a hematologist, and women of reproductive age should be counseled by a maternal/fetal medicine specialist or perinatologist regarding the risks of pregnancy, anticoagulation therapy, miscarriage, stillbirth, intrauterine growth retardation, preeclampsia, and placental abruption. Table 3 lists aspects of patient counseling for persons with thrombophilia. Genetic counseling concerning the long-term consequences of the disorder and the need for other family members and future offspring to be tested is also recommended. Local resources and physicians familiar with the implications of thrombophilia are generally available and should be consulted for the proper management of these patients.
SUMMARY
Genetic thrombophilic disorders are variably common and primary care clinicians must be aware of them because of the increased risk of VTE. A physical examination will not be able to determine if a given VTE resulted from a genetic predisposition or not. In some instances, a patient's personal and family history will alert a clinician to the existence of a thrombophilic disorder, but diagnosis of the specific thrombophilia will require laboratory evaluation and referral to a specialist. The acute management of VTE is the same regardless of the presence of a genetic thrombophilia; therefore, laboratory testing or evaluation by a specialist is not cause to delay treatment of the acute thrombotic event. After the initial treatment and stabilization of the patient, ample time exists to perform a thrombophilia workup. Long-term management of thrombophilia disorders is complicated and needs to be individualized, so referral to specialists is necessary. Primary care clinicians need to keep abreast of the studies being conducted on thrombophilia because numerous families continue to be plagued by VTEs without a recognizable cause. Undoubtedly, new causes of inherited thrombophilias are yet to be unveiled. JAAPA
Herb Ridings works in the Department of Clinical & Diagnostic Sciences, The University of Alabama at Birmingham. Lynn Holt works in the Department of Genetics; Rebecca Cook works in the Department of Pediatrics, Hematology- Oncology; and Marisa Marques works in the Department of Pathology, Division of Laboratory Medicine, also at The University of Alabama at Birmingham. They have indicated no relationships to disclose relating to the content of this article.
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