title: Clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients with von Willebrand disease type 2B: a cohort study of 67 patients.
abstract: Type 2B von Willebrand disease (VWD2B) is caused by an abnormal von Willebrand factor (VWF) with increased affinity for the platelet receptor glycoprotein Ib-alpha (GPIb-alpha) that may result in moderate to severe thrombocytopenia. We evaluated the prevalence and clinical and molecular predictors of thrombocytopenia in a cohort of 67 VWD2B patients from 38 unrelated families characterized by VWF mutations. Platelet count, mean platelet volume, and morphologic evaluations of blood smear were obtained at baseline and during physiologic (pregnancy) or pathologic (infections, surgeries) stress conditions. Thrombocytopenia was found in 20 patients (30%) at baseline and in 38 (57%) after stress conditions, whereas platelet counts were always normal in 16 patients (24%) from 5 families carrying the P1266L/Q or R1308L mutations. VWF in its GPIb-alpha-binding conformation (VWF-GPIb-alpha/BC) was higher than normal in all except the 16 cases without thrombocytopenia (values up to 6-fold higher than controls). The risk of bleeding was higher in patients with thrombocytopenia (adjusted hazard ratio = 4.57; 95% confidence interval, 1.17-17.90) and in those with the highest tertile of bleeding severity score (5.66; 95% confidence interval, 1.03-31.07). Prediction of possible thrombocytopenia in VWD2B by measuring VWF-GPIb-alpha/BC is important because a low platelet count is an independent risk factor for bleeding.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia Thrombosis Center, Department of Medicine and Medical Specialties, Istituti di Ricovero e Cura a Carattere Scientifico Maggiore Hospital, University of Milan, Italy. augusto.federici@unimi.it
authors.forename: Augusto B
authors.initials: AB
authors.lastname: Federici
authors.forename: Pier M
authors.initials: PM
authors.lastname: Mannucci
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Castaman
authors.forename: Luciano
authors.initials: L
authors.lastname: Baronciani
authors.forename: Paolo
authors.initials: P
authors.lastname: Bucciarelli
authors.forename: Maria T
authors.initials: MT
authors.lastname: Canciani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pecci
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lenting
authors.forename: Philip G
authors.initials: PG
authors.lastname: De Groot
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology* / Q000209:etiology; D006801:Humans; D007239:Infections / Q000097:blood; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010976:Platelet Count; D011247:Pregnancy; D015995:Prevalence; D020836:Protein Structure, Quaternary; D012307:Risk Factors; D013312:Stress, Physiological / Q000502:physiology; D013921:Thrombocytopenia / Q000453:epidemiology* / Q000209:etiology; D014842:von Willebrand Diseases / Q000097:blood* / Q000150:complications* / Q000235:genetics*; D014841:von Willebrand Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor