Factor VIII Levels Measured at the Time of Diagnosis of Acute Idiopathic Venous Thromboembolism Are Higher Then When Measured Six-Months Post Diagnosis.

Background: Thrombophilia screens are performed frequently in persons with a history of acute venous thromboembolism especially in those for whom the etiology is unprovoked or idiopathic. The optimal timing of the thrombophilia screen is controversial. Elevation of Factor VIII levels are a more recently described thrombophilia that is felt to be hereditary, however, the exact mode of inheritance is not certain. Factor VIII is also known to be elevated as an acute phase reactant. The accuracy of assessing Factor VIII levels at the time of diagnosis of acute venous thromboembolism is not known. The purpose of this study was to determine if there is a difference in Factor VIII levels measured at the time of diagnosis of acute venous thromboembolism as compared to six months later while patients are on oral anticoagulation.

Methods: Consecutive patients with a first episode of idiopathic acute venous thromboembolism were eligible. Patients were excluded if they were <18 years of age or had already been started on oral anticoagulants. Plasma was collected within 48 hours of diagnosis in.105 mmol sodium citrate, double spun at 1,500 G and frozen at −70 Celsius for batch testing. Factor VIII levels were assessed with a three point assay on an ACL 9000 (Beckman Coulter, Mississauga). A seven-point reference curve was used for all factor assays. Linear regression showed r² values were always > 0.99 on calibration lines. Controls at two levels, 1.00 U/mL normal pooled plasma and 0.32 U/mL were run with all assays. All patients were treated with dalteparin at 200u/kg sc daily for 5–7 days and simultaneously initiated on warfarin for six months. At the six-month point repeat Factor VIII assessments were performed while the patients were still receiving oral anticoagulation with warfarin.

Results: There were 61 patients (37 male) and the mean age was 50.4 years (18–85 years). Thirty patients had deep vein thrombosis, 23 pulmonary embolism and 8 patients had both diagnoses. The patients’ Factor VIII levels at baseline and six months were compared. At baseline the mean Factor VIII level was 1.77 units/ml and at six months it was 1.59 units/ml. The 95% confidence interval for difference in means was 0.04 – 0.32. These results were statistically significant, (paired t-test p=.01).

Conclusion: This study confirms that caution should be used in interpreting Factor VIII levels drawn as part of a thrombophilia screen at the time of diagnosis of acute idiopathic venous thromboembolism. Factor VIII levels will be lower six-months later when patients are stable on oral anticoagulation.