LETTER
Response to Activated Protein C and Cerebrovascular Disease
Matthew P. Jones, MD, and
Barbara Alving, MD
15 May 1997 | Volume 126 Issue 10 | Pages 832-833
TO THE EDITOR:
The most common inherited hypercoagulable state results from a mutation in factor V (factor V Leiden, 1691G 
A), which causes factor Va to be "resistant" to inhibition by activated protein C (APC). This disorder is evaluated by a plasma assay that measures the ratio of the activated partial thromboplastin time with and without APC or by DNA analysis for the single point mutation of the factor V gene. A major goal of hemostasis laboratories has been to develop a plasma assay for resistance to APC that is sensitive and specific for factor V Leiden, as assessed by the genomic assay. The current recommendation is to perform all assays by premixing patient plasma with factor V-deficient plasma in order to enhance sensitivity and specificity [1, 2].
In a recent study, van der Bom and colleagues [3] showed that the incidence of factor V Leiden was not increased in patients with myocardial infarction or cerebrovascular disease, findings that confirm an earlier report [4]. However, the authors found that a low response to APC, measured in an assay that did not include factor V-deficient plasma, was associated with an increased risk for cerebrovascular disease and suggested that such an assay could be used clinically. However, they did not describe the reproducibility of their assay, nor did they fully discuss the variables that can influence test results, such as choice of instrumentation and lupus anticoagulants. We urge that the test for resistance to APC be performed with factor V-deficient plasma and be used only as an adjunct to the detection of factor V Leiden with a DNA-based assay. Other uses for the assay for resistance to APC, according to the methods that van der Bom and colleagues have described, are nonspecific and are not of proven clinical value.
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Author and Article Information
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Walter Reed Army Medical Center, Washington, DC 20307-5001
Washington Hospital Center, Washington, DC 20010
1. Dahlback B. Factor V: Q506 and a negative APC-resistance test: Modified APC-resistance test offers increased sensitivity and specificity for the FV:Q506 allele [Letter]. Thromb Haemost. 1995; 74:1380-1.
2. Trossaert M, Conard J, Horellou MH, Elalamy I, Samama MM. The modified APC resistance test in the presence of factor V deficient plasma can be used in patients without oral anticoagulant [Letter]. Thromb Haemost. 1996; 75:521-2.
3. van der Bom JG, Bots ML, Haverkate F, Slagboom E, Meijer P, de Jong PT, et al. Reduced response to activated protein C is associated with increased risk for cerebrovascular disease. Ann Intern Med. 1996; 125:265-9.
4. Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. N Engl J Med. 1995; 332:912-7.
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