RESUMO
Background: Individuals with von Willebrand disease (VWD) require desmopressin testing because of interindividual response differences. However, testing is burdensome, while not all patients may need extensive testing. Objectives: To provide von Willebrand factor (VWF) cutoffs that predict desmopressin nonresponse and thereby identify individuals who do not need extensive testing in a retrospective cohort. We validated these cutoffs in a prospective cohort. Patients and Methods: We included 376 patients (Type 1 VWD with VWF activity [VWF:Act] <0.30 IU/ml: n = 112; with VWF:Act 0.30-0.50 IU/ml: n = 206; Type 2 VWD: n = 58; ages, 5-76 years) from January 2000 to July 2020. We collected VWF:Act and factor VIII activity (FVIII:C) at baseline and several time points after desmopressin (T1-T6). We defined response as VWF:Act and FVIII:C 0.50 IU/ml or greater at T1 and T4. We compared VWF:Act and FVIII:C distribution (historically lowest level, baseline, and T1) between responders and nonresponders and determined cutoffs discriminating between these groups. Results were validated in a group of 30 individuals. Results: All individuals with Type 1 VWD and Type 2 VWD, respectively, with baseline VWF:Act 0.34 IU/ml or greater or 0.28 IU/ml or greater were responders. In individuals with T1 VWF:Act ≥0.89 IU/ml (Type 1 VWD) or T1 VWF:Act 1.10 IU/ml or greater (Type 2 VWD), response remained at T4. Conclusion: Desmopressin testing is not needed when lowest historical VWF:Act is 0.30 IU/ml or greater. In patients with Type 1 VWD who require testing, measurements after T1 are often not needed. In patients with Type 2 VWD who require testing, we advise performing T1 and T4 measurements.
RESUMO
BACKGROUND: Important diagnostic and clinical aspects of moderately reduced von Willebrand factor (VWF) levels are still unknown. There is no clear evidence which cutoff value (0.50 vs 0.60 IU/ml) should be used to diagnose "low VWF." Also, the incidence of bleeding after the diagnosis has been made, and risk factors for bleeding are unknown yet. OBJECTIVES: To investigate the incidence of postsurgical bleeding, postpartum hemorrhage (PPH), and traumatic and spontaneous bleeding after low VWF diagnosis, and to develop a risk score to predict future bleeding. METHODS: We performed a cohort study in patients with historically lowest VWF levels of 0.31 to 0.60 IU/ml. Clinical data of patients were retrospectively collected. RESULTS: We included 439 patients with low VWF. During a follow-up of 6.3 ± 3.7 years, 259 surgical procedures, 81 deliveries, and 109 spontaneous and traumatic bleeding episodes were reported. The incidence of postsurgical bleeding was 2.7%, whereas 10% of deliveries was complicated by PPH. Overall, 65 patients (14.8%) had bleeding requiring treatment, which was not different between patients with historically lowest VWF levels of 0.31-0.50 and 0.51-0.60 IU/ml (p = .154). Age <18 years, abnormal bleeding score at diagnosis, and being referred for bleeding symptoms at the time of diagnosis were independent risk factors for bleeding during follow-up, and therefore included in the risk score. CONCLUSIONS: The cutoff value of low VWF diagnosis should be set at 0.60 IU/ml. Furthermore, a risk score is developed to identify individuals with a high risk for bleeding after low VWF diagnosis.