Antonio Girolami

Von Willebrand factor (vWF) was purified from the plasma of a patient with type IIB von Willebrand disease (vWF from such a patient, IIB vWF) who had a normal platelet count and showed no evidence of spontaneous platelet aggregation. Large multimers of IIB vWF were absent from purified preparations and from plasma. Ristocetin-induced platelet aggregation was enhanced by purified IIB vWF. The aggregation of washed normal platelets mixed with IIB vWF (0.4 microgram/ml) required lower ...

The capability of von Willebrand factor (VWF) to bind platelet glycoprotein Ib (GPIb) and promote platelet plug formation is currently evaluated in vitro using the ristocetin co-factor activity (VWF:RCo) assay. The replacement of this cumbersome and not always reproducible test with the collagen binding activity of VWF (VWF:CBA) has been attempted with controversial results. To evaluate the capacity of VWF:CBA to identify classic and variant von Willebrand disease (VWD) compared with ...

Inherited activated protein C (APC) resistance is a newly described pathological condition associated with familial thrombophilia. A recent report on family with APC resistance showed increased levels of prothrombin fragment 1 + 2 (F1 + 2) in the affected individuals. No data concerning thrombin-antithrombin complex (TAT) levels in patients with inherited APC resistance are presently available. The aim of this study was to assess the plasma levels of F1 + 2 and TAT in patients with ...

Three preparations of purified von Willebrand factor (vWF), obtained from unrelated patients affected by type IIB von Willebrand disease, were found to have normal sialic acid content (between 129 and 170 nmol/mg of vWF, as compared with 158 +/- 17 nmol/mg in four normal preparations) and to induce platelet aggregation in the presence of physiologic levels of divalent cations and without addition of ristocetin. A monoclonal antibody that blocks the vWF binding domain of the platelet ...

A small proportion of patients with deep vein thrombosis develop recurrent venous thromboembolic complications or bleeding during anticoagulant treatment. These complications may occur more frequently if these patients have concomitant cancer. This prospective follow-up study sought to determine whether in thrombosis patients those with cancer have a higher risk for recurrent venous thromboembolism or bleeding during anticoagulant treatment than those without cancer. Of the 842 included ...

We have studied the interaction of the congenitally abnormal type IIA and IIB von Willebrand factor (vWF) molecules, both lacking the larger multimeric forms, with the two vWF binding sites on platelets, the glycoprotein (GP) Ib-IX and GP IIb-IIIa complexes. Variant as well as normal (N) vWF were purified from plasma. Estimates for binding of subunit molecules per platelet at saturation (Bmax) and dissociation constant in moles/liter (Kd), respectively, were obtained from binding ...

von Willebrand factor (vWF) is necessary for the initial attachment of platelets to exposed subendothelium, particularly under flow conditions like those prevailing in the microcirculation. Little is known about its possible participation in subsequent events leading to formation of platelet thrombi at sites of vascular injury. We addressed this question by studying the mechanisms by which desialylated vWF induces platelet aggregation in the absence of any other stimulus. Asialo vWF, ...

One of the functions of von Willebrand factor (vWF) is to serve as a carrier of clotting factor VIII (FVIII). Deficiency of this function results in the von Willebrand disease (vWD) variant type 2N, which resembles hemophilia A. We describe a new sandwich enzyme-linked immunosorbent assay (ELISA) to study the ability of vWF to bind exogenous recombinant FVIII (rFVIII), in which anti-vWF-coated plates are incubated with plasma vWF, followed by exogenous FVIII and a peroxidase-coupled ...

BACKGROUND: A recently discovered mutation in coagulation factor V (Arg506-->Gln, referred to as factor V Leiden), which results in resistance to activated protein C, is found in approximately one fifth of patients with venous thromboembolism. However, the risk of recurrent thromboembolism in heterozygous carriers of this genetic abnormality is unknown.

METHODS: We searched for factor V Leiden in 251 unselected patients with a first episode of symptomatic deep-vein thrombosis diagnosed ...

In a prospective cohort study, we assessed the incidence of spontaneous and risk period-related venous thromboembolism (VTE) in asymptomatic family members of patients who experienced VTE and had the factor V Leiden mutation. In all, 561 family members of 131 probands were included, 313 of whom were carriers (299 heterozygous and 14 homozygous) and 248 of whom were noncarriers of the factor V Leiden mutation. Average follow-up was 4 years (range, 4 months-6 years). There were 1255 and ...

A deletion/insertion polymorphism (4G or 5G) in the promoter of the plasminogen activator inhibitor type 1 gene has been suggested to be involved in regulation of the synthesis of the inhibitor, the 4G allele being associated with enhanced gene expression. A relationship between 4G/5G polymorphism and PAI-1 levels was found in patients with cardiovascular and metabolic diseases, but not in healthy subjects. In the present work we studied the distribution of PAI-1 4G/5G genotype and its ...

The risk of spontaneous or risk-period related venous thromboembolism in family members of symptomatic carriers of antithrombin (AT), protein C (PC) or protein S (PS) defects, as well as of the Factor V Leiden mutation is still undefined. We performed a retrospective cohort study in family members (n = 793) of unselected patients with a documented venous thromboembolism and one of these deficiencies to make an estimate of this risk. The annual incidences of total and spontaneous venous ...