(Stroke. 1996;27:1731-1733.)
© 1996 American Heart Association, Inc.
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the Departments of Neurology (D.A.D., C.C.L., H.S.S.) and Medicine (E.C.W.), University of Wisconsin-Madison Medical School.
Correspondence to Henry S. Schutta, Department of Neurology, University of Wisconsin Medical School, 600 Highland Ave, Madison, WI 53792. E-mail schutta@neurology.wisc.edu.
| Abstract |
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Case Descriptions We describe three women who had superior sagittal and lateral sinus thrombosis while taking oral contraceptives and had a number of additional risk factors for CVT. Each had APC-R for different reasons.
Conclusions Inherited thrombophilia, including APC-R, should be looked for in all patients with CVT. Functional APC-R is a highly prevalent coagulopathy, but the reasons for this abnormality are diverse; abnormal and borderline functional APC-R results should be supplemented by DNA analysis for the presence of factor V Leiden.
Key Words: cerebral embolism and thrombosis contraceptives, oral protein C protein S deficiency sinus thrombosis
| Introduction |
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The methods used for the detection of functional APC-R and of factor V Leiden have been previously described.6 The test for functional APC-R is a modification of the original method of Dahlback and Svensson.5 It is less influenced by the presence of anticoagulants and is more sensitive and specific. Functional APC-R is expressed as the ratio of APTT in the presence of APC to APTT in the absence of APC (Chromogenic Pharmacia Hepar, product No. 822908). Protein C and protein S antigen levels were measured before anticoagulants with ELISA and are expressed as a percentage of the value found in pooled normal plasma.
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| Discussion |
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Although it is now well established that APC-R associated with factor V Leiden is an important risk factor for CVT, the clinical significance of functional APC-R, and particularly borderline APC-R, in the absence of factor V Leiden is not clear. In a family study of 50 Swedish families with thrombophilia and inherited APC-R, the factor V Leiden was lacking in three families and was absent in some members of families that had the factor V Leiden gene mutation.4 Patients with borderline abnormal functional APC-R results (2.1 to 2.5) appear to be common among patients with CVT. In a recent study, 12 of 40 patients had APC-R results in that range. Factor V Leiden was demonstrated in only one of those patients.10
In our cases, patient 1 had an unequivocally abnormal functional APC-R (1.5) and factor V polymorphism. Patient 2 had APC-R results in the high abnormal range (1.9 and 2.0) without factor V Leiden. Because the patient was euthyroid at the time that APC-R was demonstrated, thyrotoxicosis cannot account for this abnormality, and in this case the mechanism of APC-R remains unknown. Patient 3 with borderline APC-R (2.3 and 2.4), who was Chinese, did not carry the factor V Leiden mutation but had protein S deficiency. Intact factor V is synergistic with protein S as cofactor to APC.14 The possibility that thrombophilia in patients who have protein S deficiency may be the result of factor V mutations other than Arg506 substitution has been suggested.4
Table 2
lists the acquired risk factors in CVT patients with APC-R or borderline APC-R published to date. All but two patients with factor V Leiden and all but one patient with borderline APC-R without factor V Leiden had one or more acquired risk factors for thrombosis, including thyrotoxicosis.15 This suggests that, as is the case in other types of inherited thrombophilia, additional risk factors are required in most cases to precipitate CVT in patients with APC-R. APC-R with or without factor V Leiden appears to augment the risk for CVT from oral contraceptives, and patients should be counseled accordingly. Our cases again demonstrate that in patients with abnormal and borderline results the functional APC resistance test should be supplemented by DNA analysis for factor V Leiden and that other types of inherited thrombophilia must be looked for.6
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All patients were treated with intravenous heparin followed by warfarin anticoagulation, which resulted in prompt recovery without complications, demonstrating again that hemorrhage resulting from CVT is no contraindication to anticoagulation.1 On the other hand, the decision to provide anticoagulation for patients with APC-R and a single thrombotic event indefinitely must be made on a case-by-case basis. This decision would be influenced by the ability to remove other risk factors for thrombosis.16
| Selected Abbreviations and Acronyms |
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| Acknowledgments |
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Received May 2, 1996; revision received August 2, 1996; accepted August 7, 1996.
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