Diagnostic workup of patients with acquired von Willebrand syndrome: a retrospective single-centre cohort study.
BACKGROUND
Diagnosis of acquired von Willebrand syndrome (AVWS) remains challenging. Diagnostic algorithms suggest the use of factor VIII (FVIII:C), von Willebrand factor antigen (VWF:Ag), ristocetin cofactor (VWF:RCo), and collagen-binding capacity (VWF:CB), but the sensitivity of these and other laboratory tests for the diagnosis of AVWS is unknown.


OBJECTIVE
To analyze the capacity of laboratory tests, including point-of-care testing (POCT), for the identification of patients with AVWS.


METHODS
Thirty-five consecutive patients were enrolled with AVWS diagnosed because of a history of recent onset of bleeding, a negative family history of von Willebrand disease, and abnormal plasma VWF multimers.


RESULTS
According to our inclusion criteria, all patients had bleeding symptoms, and the VWF high molecular weight multimers were either decreased or absent. Regarding POCT, PFA-100 was inconclusive, due to anemia or thrombocytopenia, in 29%; the sensitivity was 80% in the remaining patients. The sensitivity of VWF:Ag (23%), VWF:RCo/Ag ratio < 0.7 (26%), VWF:CB/Ag ratio < 0.7 (46%), anti-VWF antibodies (15%) and VWF propeptide/Ag ratio (22%) was too low to rule out the disease. A combination of VWF:Ag < 50 IU dL(-1), VWF:RCo/Ag ratio < 0.7 and VWF:CB/Ag ratio < 0.8 yielded a sensitivity of 86%. Patients diagnosed only because of abnormal VWF multimers showed similar clinical characteristics as other patients.


CONCLUSIONS
Early diagnosis of AVWS is difficult, due to lack of sensitivity of the tests used. A substantial number of patients present with normal or increased test results, emphasizing the importance of multimer analysis in all patients with suspected AVWS.
Tiede
A
A
Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany. tiede.andreas@mh-hannover.de
Priesack
J
J
Werwitzke
S
S
Bohlmann
K
K
Oortwijn
B
B
Lenting
P
P
Eisert
R
R
Ganser
A
A
Budde
U
U
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000941:Antigens / Q000032:analysis*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D001704:Biopolymers; D015331:Cohort Studies; D003094:Collagen / Q000378:metabolism; D005169:Factor VIII / Q000032:analysis*; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D010979:Platelet Function Tests / Q000295:instrumentation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D019095:Point-of-Care Systems; D011498:Protein Precursors / Q000032:analysis*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D014842:von Willebrand Diseases / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D014841:von Willebrand Factor / Q000032:analysis* / Q000737:chemistry / Q000627:therapeutic use
D000941:Antigens; D001323:Autoantibodies; D001704:Biopolymers; D019038:Platelet Glycoprotein GPIb-IX Complex; D011498:Protein Precursors; C029417:Von Willebrand antigen; D014841:von Willebrand Factor; C067003:von Willebrand factor propolypeptide; D005169:Factor VIII; D003094:Collagen