Anti-phosphatidyl-serine/prothrombin antibodies (aPS/PT) in isolated lupus anticoagulant (LA): is their presence linked to dual test positivity?

Abstract Objectives Anti phosphatidylserine/prothrombin antibodies (aPS/PT) are often present in patients with antiphospholipid syndrome (APS) and might be relevant in the pathogenesis of this condition. They are major determinant of lupus anticoagulant (LA) in triple-positive antiphospholipid (aPL) profile. Whether they are present and pathogenic in patients with isolated LA [negative anticardiolipin (aCL) and anti β2-glycoprotein I (aβ2GPI) antibodies] is a matter of debate. Methods We measured aPS/PT in a large number of isolated LA with the aim to ascertain whether there is a link between the way isolated LA is assessed and the presence of these antibodies. APS/PT were measured in 86 patients with isolated LA (aCL- and abeta2GPI-). LA was assessed by two test systems, the dilute Russell Viper Venom Time (dRVVT) and the Silica Clotting Time (SCT). Results Sixty-six (77%) individuals with isolated LA were positive for aPS/PT (IgM 44, IgG and IgM 15, IgG in 7). Diagnosis of LA was made based on positive results in both dRVVT and SCT in 40 patients (Group 1) and based on only one positive test in the remaining 46 patients (Group 2). The rate of positive aPS/PT antibodies was significantly higher in Group 1 (OR=7.2, 95% CI 1.9–27.0, p<0.002). Moreover, the titre of IgM aPS/PT was significantly increased in Group 1 as compared to Group 2 (137 U, IQR 64–179 vs. 43 U, IQR 11–120, p=0.008). Conclusions These data indicate an association between LA based on two positive coagulation tests and the presence of aPS/PT antibodies, especially of IgM isotype

Lupus anticoagulant identifies two distinct groups of patients with different antibody patterns

Background: Whether antibodies directed to β2-Glycoprotein I (aβ2GPI) are responsible for LA activity is not well defined. However, in the absence of such antibodies the molecule responsible for LA phenomenon is unknown. Objective: The aim of this study was the biochemical identification of the target antigen epitope of aPL responsible of LA activity in the absence of aβ2GPI antibodies together with the biological and clinical characteristics of these patients in comparison with classical triple positive patients. Patients/methods: A comparison of patients with LA without (LA+/aβ2GPI−) and those with (LA+/aβ2GPI+) associated aβ2GPI antibodies was performed. Size exclusion chromatography and analytical chromatography were used to identify the molecule with LA activity in patients LA+/aβ2GPI-. Results and conclusions: Analytical size-exclusion chromatography revealed a peak of 996Kd with LA activity perfectly overlapping that of IgM anti phosphatidylserine/prothrombin (aPS/PT) antibodies. Similarly, all the 25 LA+/aβ2GPI− patients were positive for aPS/PT antibodies. LA+/aβ2GPI− compared to 33 LA+/aβ2GPI+ patients turned out to be significantly older, with a lower rate of previous thromboembolic events and a weaker LA activity. Search for aPS/PT and aβ2GPI antibodies in patients with LA is useful to identify two subgroups of LA at different risk of thromboembolic event

Two novel mutations (Pro864His, Val867Glu) causing type 2A von Willebrand disease and affecting a single restriction site in exon 28.

We detected two transversions in two unrelated Italian patients with type 2A von Willebrand disease (VWD): a C to A at nucleotide 8821 and a T to A at nucleotide 8830, resulting in the missense mutations Pro864His and Val867Glu respectively. Both mutations were in the heterozygous form and abolished the BstXI restriction site in exon 28 of the VWF gene. In both mutations plasma VWF multimer pattern improved by antiproteases. Moreover, DDAVP normalized plasma VWF multimers in the Pro864His patient, especially when protease inhibitors were present. These new mutations appear to be of the 2A VWD subtype due to the increased susceptibility to proteases

Combined hemophilia A and type 2 von Willebrand's disease: defect of both factor VIII level and factor VIII binding capacity of von Willebrand factor.

We describe a family in which hemophilia A and von Willebrand’s disease (VWD) were simultaneously present. von Willebrand’s disease and hemophilia A are the most common inherited bleeding disorders, having factor VIII (FVIII) deficiency in common, albeit of different origin. In hemophilia A, the FVIII defect is associated with abnormalities in the FVIII gene, with an X-linked pattern of transmission, whereas in VWD the deficiency is related to an abnormality in von Willebrand factor (VWF), encoded by a gene located in chromosome 12. VWF carries FVIII and its reduction/absence reduces FVIII plasma concentration. Type 2N is a VWD variant characterized by a defect in the FVIII binding function of VWF, (with reduced FVIII but normal VWF levels. It may be misdiagnosed as hemophilia A

Re-evaluation of the therapeutic efficacy of DDAVP in type IIB von Willebrand's disease.

With few exceptions, 1-desamino-8-D-arginine vassopressin (DDAVP) has been shown to be useful in securing haemostasis in patients with von Willebrand's disease (vWd). In type IIB vWd, DDAVP has been reported to have no beneficial effects and to be contraindicated because it causes or worsens thrombocytopenia, due to in vivo platelet aggregation. Nevertheless, it was previously demonstrated that DDAVP may have clinical utility in some patients with type IIB vWd. Additional findings obtained in seven type IIB vWd patients of different kindreds undergoing minor surgical procedures are now reported. It was observed that DDAVP corrected the bleeding time in every case, with effects lasting for 2 h. Mean platelet counts decreased 30 min after DDAVP to variable degrees, depending on the anticoagulant used for blood collection, but were normal 2 h later. Furthermore DDAVP normalized FVIII, von Willebrand factor (vWf) antigen (vWf:Ag), and to a lesser extent, vWf ristocetin cofactor activity (vWf:RCoF). Intermediate and large vWf multimers appeared after 30 min. There were no bleeding complications during or after surgery, nor evidence of thrombosis. It was thus confirmed that DDAVP has clinical utility in the prevention of bleeding symptoms in different type IIB vWd patients. Therefore, despite the transitory thrombocytopenia and the incomplete restoration of larger vWf multimers, the use of this drug should be reconsidered for patients with type IIB vWd