Monitoring of von Willebrand Factor Inhibitors in Patients with Type 3 von Willebrand Disease Using a Quantitative Assay

Details

• Alternative Title:
  Haemophilia
• Personal Author:
  Miller, Connie H.
• Description:
  Background:
  
  Antibodies inhibiting von Willebrand factor (VWF) develop in a subset of patients with Type 3 von Willebrand disease (VWD3) and may be detected by their inhibition of ristocetin cofactor activity (VWF:RCo). Some also inhibit factor VIII activity (VIII:C).
  
  Aim:
  
  To describe monitoring of ten VWD3 patients for VWF inhibitors using a quantitative assay.
  
  Methods:
  
  VWF inhibitor was measured by comparing VWF:RCo activity of a mix of patient and pooled normal plasma (PNP) with a mix of buffer and PNP, using agglutination of fixed normal platelets in microtiter plates or lyophilized platelets in an aggregometer. VIII:C inhibitor was measured by Bethesda assay. Preanalytical heat treatment of patient plasma was used during treatment episodes.
  
  Results:
  
  Four of 10 patients monitored developed VWF inhibitors, 2 detected during bleeding episodes refractory to treatment and 2 on routine screening. Data from the first 5 patients were used to establish an arbitrary unit, VWU, defined as the amount of inhibitor per mL of patient plasma inactivating 25% of the activity of 1 mL of PNP. In 3 of 4 patients, both VWF:RCo and VIIII:C were inhibited at some time points, although VIII:C inhibition sometimes disappeared. In one patient, no VIII:C inhibition was seen. Two patients remained inhibitor positive more than 15 years after inhibitor detection, one became negative following immune tolerance induction, and one was deceased.
  
  Conclusions:
  
  VWF inhibitors can be quantitatively monitored in VWD3 patients. Preanalytical heat treatment may be required for their detection post infusion.
  
  
• Subjects:
  Antibodies Article Blood Platelets Factor VIII Humans Inhibitor Von Willebrand Disease Von Willebrand Disease, Type 3 Von Willebrand Diseases Von Willebrand Factor
• Source:
  Haemophilia. 27(5):823-829
• Pubmed ID:
  34089550
• Pubmed Central ID:
  PMC8667261
• Document Type:
  Journal Article
• Funding:
  CC999999/ImCDC/Intramural CDC HHSUnited States/
• Volume:
  27
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:621cf5f22881e87c99863dc7f87c92f4521ad4572da7271245b5e60f5a2fd9e1
• Download URL:
  https://stacks.cdc.gov/view/cdc/112553/cdc_112553_DS1.pdf
• File Type:
  [PDF - 353.12 KB ]