22 A short Dilute Russel Viper Venom Time is not always a benign finding: Association with thrombophilias

The Dilute Russel Viper Venom Time (DRVVT) is considered one of the most sensitive and specific tests for detecting a lupus anticoagulant (LA). A prolonged DRVVT (greater than 99% of the normal population), is indicative of a positive screening LA result. However, occasionally we observed unexpected shorter-than-reference range results in the DRVVT screen instead of prolonged results. Unlike the Activated Partial Thromboplastin Time, the other common LA screening test, which can be short due to elevated levels of the acute phase reactant factor VIII, the DRVVT is unaffected by intrinsic factor levels or other acute phase reactants. Thus, we hypothesize that a short DRVVT may reflect impaired inactivation of coagulation factors in the common pathway, rather than increased levels of common pathway coagulation factors. We aimed to investigate a possible association of a short DRVVT with thrombophilias. We studied all the cases in which a hypercoagulable panel and DRVVT were performed within the same collection from January 2018 to February 2022 at our institute (n = 1385). We sorted the data into 3 cohorts based on our reference range: short (<32 seconds), normal (32- 45.7 seconds), and prolonged DRVVT (>45.7 seconds, with the prolonged cohort excluded to avoid interference by lupus anticoagulants, drugs, or factor deficiencies). We calculated the odds ratios (OR) of thrombophilias in the short and normal DRVVT cohorts, excluding cases with liver disease, multiple anticoagulation deficiencies, elevated factor VIII, and prolonged PT. Our results show that the prevalence of thombophilias was 42.5% in the short DRVVT cohort (20 known thrombophilias within 47 short DRVVT cases; 20/47) vs. 18.0% in the normal DRVVT cohort (84 /466) (OR of 3.37; 95% CI 1.8-6.29, p = 0.0001). Isolated protein S deficiency was the most common thrombophilia within these cohorts, with a higher prevalence in the short DRVVT cohort (10 cases) compared to the normal DRVVT cohort (28 cases) (OR 4.23, 95% CI 1.90-9.37, p = 0.0004). The other thrombophilias did not show significant individual ORs (22 Factor V Leiden heterozygous, 4 in short DRVVT; 19 Prothrombin gene heterozygous, 5 in short DRVVT; 9 isolated protein C deficiency, 1 in short DRVVT; 16 isolated antithrombin deficiencies, none in short DRVVT). To conclude, there seems to be an association of increased thrombophilias in cases with short DRVVT. The association is stronger with protein S deficiency, however, an association with all other thrombophilias was limited due to the low incidence of inherited thrombophilias and the small sample size. In summary, a short DRVVT should not always be deemed normal. Recommendation of thrombophilia testing in patients with a short DRVVT within an LA panel may be warranted in cases with high pretest probability (young adult patients with unprovoked venous thromboembolism and/or recurrent miscarriage).