TY - JOUR
T1 - Clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients with von Willebrand disease type 2B
T2 - A cohort study of 67 patients
AU - Federici, Augusto B.
AU - Mannucci, Pier M.
AU - Castaman, Giancarlo
AU - Baronciani, Luciano
AU - Bucciarelli, Paolo
AU - Canciani, Maria T.
AU - Pecci, Alessandro
AU - Lenting, Peter J.
AU - Groot, Philip G De
PY - 2009/1/15
Y1 - 2009/1/15
N2 - Type 2B vonWillebrand disease (VWD2B) is caused by an abnormal von Willebrand factor (VWF) with increased affinity for the platelet receptor glycoprotein Ib-γ (GPIb-γ) 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-γ-binding conformation (VWF-GPIb-γ/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-γ/BC is important because a low platelet count is an independent risk factor for bleeding.
AB - Type 2B vonWillebrand disease (VWD2B) is caused by an abnormal von Willebrand factor (VWF) with increased affinity for the platelet receptor glycoprotein Ib-γ (GPIb-γ) 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-γ-binding conformation (VWF-GPIb-γ/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-γ/BC is important because a low platelet count is an independent risk factor for bleeding.
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U2 - 10.1182/blood-2008-04-152280
DO - 10.1182/blood-2008-04-152280
M3 - Article
C2 - 18805962
AN - SCOPUS:60249092963
VL - 113
SP - 526
EP - 534
JO - Blood
JF - Blood
SN - 0006-4971
IS - 3
ER -