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BACKGROUND: Assessment of bleeding phenotype is critically important in the diagnosis of von Willebrand disease (VWD). Despite advances in bleeding assessment tools (BATs), standardized tools to evaluate bleeding following diagnosis (interim bleeding) are lacking. OBJECTIVES: We assessed the clinical utility of an interim bleeding protocol in a multicenter, international study involving patients with VWD. METHODS: The enrolment ISTH BAT formed the original bleeding score (0 BS). At follow-up, the International Society on Thrombosis and Haemostasis BAT was repeated but included only interval bleeding (Interim BS, 1 BS). Both scores were annualized (0 BS/yr, 1 BS/yr). BS were analyzed by VWD subtype, plasma VWF level, sex, and age. RESULTS: Interim BS discriminated by subtype, with significantly increased 0 BS and 1 BS in patients with type 3 VWD. In patients with type 1 VWD, a positive or negative 0 BS did not predict future bleeding, with similar 1 BS/yr (median 1.0 vs. 0.7, p = .2). Despite significantly higher 0 BS in females with type 1 VWD than males (median 7 vs. 5, p = .0012), 1 BS were not significantly different (median 4 vs. 4, p = .16). While 0 BS were lower in children than adults with type 1 VWD, interim BS were similar (median 5 vs. 3, p = .5; 1BS/yr, median 1 vs. 0.8, p = .7). Interestingly, in those with plasma von Willebrand factor:ristocetin cofactor levels >50 IU/dl, interim BS rates were similar to those 30–50 IU/dl (1 BS/yr 0.8 vs. 1.3, p = .5). CONCLUSION: This study provides both a new approach to longitudinal bleeding assessment and insights into the evolution of bleeding in VWD.

von Willebrand Disease (VWD) is associated with significant morbidity because of excessive bleeding. Early diagnosis and treatment are important to prevent and treat these symptoms. We systematically reviewed the accuracy of any von Willebrand factor (VWF) activity assay in the diagnosis and classification of patients for VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 and the certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity. The review included 77 studies that evaluated the use of newer tests of VWF platelet binding activity (VWF:GPIbR, VWF:GPIbM) and VWF:RCo for the diagnosis of VWD (13 studies), VWF propeptide to VWF:Ag ratio, and desmopressin trial for the diagnosis of type 1C VWD (5 studies), VWF multimer analysis and VWF:CB/VWF:Ag ratio for the classification of type 2 VWD (11 studies), genetic testing and ristocetin-induced platelet aggregation to diagnose type 2B VWD (14 studies), genetic testing and FVIII:VWF binding to diagnose type 2N VWD (17 studies). Based on available diagnostic test accuracy, there appear to be comparable test accuracy results between newer tests of platelet binding activity of VWF function and VWF:RCo. The findings of these reviews support VWF multimer analysis or VWF:CB/VWF:Ag to diagnose type 2 VWD. The desmopressin trial test with 1- and 4-hour postinfusion blood work is the test of choice to confirm increased VWF clearance in patients with suspected VWD type 1C. Additionally, genetic testing is most useful in diagnosing type 2B VWD and has a role in the diagnostic algorithm of suspected type 2N VWD.

Introduction: von Willebrand disease (VWD) is an inherited bleeding disorder caused by a quantitative or qualitative dysfunction of von Willebrand factor. Clinicians, patients and other stakeholders have many questions about the diagnosis and management of the disease. Aim: To identify topics of highest importance to stakeholders that could be addressed by guidelines to be developed by the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF) and the World Federation of Hemophilia (WFH). Methods: A survey to determine and prioritize topics to be addressed in the collaborative development of guidelines for VWD was distributed to international stakeholders including patients, caregivers and healthcare providers (HCPs). Representatives of the four organizations coordinated the distribution strategy. The survey focused on both diagnosis and management of VWD, soliciting 7-point Likert-scale responses and open-ended comments, in English, French and Spanish. We conducted descriptive analysis with comparison of results by stakeholder type, gender and countries' income classification for the rating questions and qualitative conventional content data analysis for the open-ended responses. Results: A total of 601 participants responded to the survey (49% patients/caregivers and 51% healthcare providers). The highest priority topics identified were diagnostic criteria/classification, bleeding assessment tools and treatment options for women and surgical patients. In contrast, screening for anaemia and differentiating plasma-derived therapy versus recombinant therapies received lower ratings. Conclusion: This survey highlighted areas of importance to a diverse representation of stakeholders in the diagnosis and management of VWD, providing a framework for future guideline development and implementation.

Thiol compounds, such as glutathione, 2,3-dimercaptopropanol (BAL), propane-1,3-dithiol, and N-phenylaminopropanedithiol, were readily oxidized by x-rays, beta rays, and gamma rays. The ionic yield for this oxidation was about the same, 3 at pH 7, on irradiation with x-rays and with beta rays; it was 23 per cent less on irradiation with gamma rays. The ionic yield varied with the hydrogen ion concentration, increasing as the pH value increased. There was no reduction of oxidized glutathione on irradiation with dosages of x-rays and gamma rays which produced oxidation of the reduced compound. In the absence of oxygen, the oxidation of thiols by ionizing radiations was only 33 per cent of that obtained in the presence of dissolved oxygen. When the thiol solutions were irradiated in the presence of dissolved oxygen, catalase protected them from oxidation by 17 to 27 per cent.

Hydrogen peroxide at a concentration of 0.001 M produced almost complete inhibition of the respiration of sea urchin sperm suspended in sea water. At a concentration of 0.0005 M it had no effect. When the concentration was diminished to 0.0001 M it increased the respiration from 60 to 100 per cent.When sperm was added to sea water irradiated with 200,000 r, there was a marked inhibition of respiration (about 60 per cent). Sea water irradiated with 50,000 r produced small inhibition (10 per cent). Addition of catalase previous to the addition of sperm had no effect at all on this inhibition. Furthermore, sea water irradiated with 200,000 r gave no positive test for H2O2. It is postulated that inhibition is due to the action of stable organic peroxides produced on irradiation of sea water.

The respiration of sea urchin (Arbacia punctulata) sperm increased with dilution up to a dilution of 1:200, where maximum values were found. At this dilution the average Qo2 value was 19.6 ± 3.9. When the dilution was increased to 1:1000 the respiration dropped sharply to 2.0. A dilution of 1:1600 gave no measurable respiration.The respiration of dilute suspensions of sea urchin sperm (1:200) was inhibited by x-ray irradiation. A dose of 20,000 r produced an inhibition of 66 per cent which was further increased during the second hour; 10,000 r inhibited 30 per cent; 1000 r, 22 per cent; 500 r, 14 per cent; and 100 r, 10 per cent. When sperm was irradiated with 1000 r there was no recovery of respiration five hours after irradiation. Inhibition of respiration cannot be attributed to hypothetical H2O2 formation, for sperm suspensions contain catalase. The catalase value of sperm is 33 c.mm. O2 formed by 1 mg. dry weight per hour, i.e., 3 micromoles H2O2 destroyed. On addition of succinate and of acetate to ...