Adriana I. Woods

Antithrombotic therapy in children and adolescents

This report documents our experience with long term antithrombotic therapy (acenocoumarol plus aspirin) in 31 children and adolescents, from 5 months to 16 years of age. The valves replaced were mitral in 20 patients, aortic in 4, mitral-aortic in 4 and tricuspid in 3; the overall follow-up time was of 1336 months. Anticoagulant requirement in each children was not in correlation with age, but a significant increase (p less than 0.01) was found in association with sexual development. Our total incidence of embolic episodes was 1.49/1000 patient-months. The embolic incidence on adequate anticoagulated patients was 0.74/1000 patient-months and 93.7% of all patients were free of thrombo-embolic accidents up to 96 months of follow-up. Minor haemorrhage in relation to an excess of anticoagulant was 1.49/1000 patient-months. There has been only one major bleeding episode associated with severe sepsis, with an incidence of 0.74/1000 patient-months. No major difficulties were found in the management of anticoagulant treatment and its association with antiplatelet drugs in children.

Intraplatelet levels of vWF:Ag and fibrinogen in myeloproliferative disorders

Several platelet function abnormalities have been described in the myeloproliferative syndromes. We have measured the intraplatelet vWF:Ag and fibrinogen (FI) in the platelet lysates by Laurell technique in 11 patients with polycythemia vera (PV), 10 with essential thrombocythemia (ET), 14 with chronic myelocytic leukaemia (CML) and 3 with myelofibrosis (MF) and these results were correlated with platelet function abnormalities. Decreased intraplatelet levels of vWF:Ag and FI were found in all the patients with ET and MF, in 8 out of 11 PV and 3 out of 14 CML. A statistical significant correlation was observed between the intraplatelet levels of vWF:Ag and FI in the control group and in CML and PV, but no correlation was found in ET and MF. No correlation was observed between the plasmatic and the intraplatelet levels of vWF:Ag and FI in any group. Evidences of platelet activation (spontaneous platelet aggregation or circulating platelet aggregates) were observed in 40% of the cases with ET and PV, and all these cases had low intraplatelet levels of both antigens. None of the cases with MF had evidences of platelet activation and 2 out of 14 patients with CML had platelet activation. The deficiency of the dense bodies was less frequent than the depletion of the alpha granules (5 out of 11 PV, 4 out of 10 ET, 6 out of 14 CML and 2 out of 3 MF). The low intraplatelet contents of vWF: Ag and FI, more frequently observed in ET and PV, may be the result of platelet activation and in vivo release, but megakaryocyte dysfunction is more likely in myelofibrosis.

Visualization of the multimeric structure of von Willebrand factor by immunoenzymatic stain using avidin-peroxidase complex instead of avidin-biotin peroxidase complex

Description dune methode permettant de visualiser les formes multimeres des facteurs de Willebrand, sans recours aux radioisotopes. Cette methode trouve application dans la classification de la maladie de Willebrand

Aspirin effect on platelet antiplasmins release

Abstract Euglobulins of platelet poor plasma containing resuspended washed platelets produced a significant decrease of the lysis areas with regard to euglobulins of platelet poor plasma alone:this decrease correlated with the number of platelets. Euglobulins of platelet poor plasma containing washed platelets activated with collagen (2 and 20 ug/ml) showed lower lysis areas on fibrin plates compared with euglobulins containing non-activated platelets (p 0.001). The higher number of platelets,the lower the lysis area. Aspirin had no effect upon antiplasmin activity either in non-activated or in activated platelets. We must consider the possibility that platelet antiplasmins could be released by different metabolic pathways than via the cyclooxygenase pathway or that they are not stored in-granules

Aspirin effect on the release of plasminogen activators inhibitors by human platelets

Intrinsic plasminogen activators (PA) were tested in euglobulins (eug) of platelet poor plasma (PPP) with and without washed platelets (WP), treated or not with urokinase (UK), streptokinase (SK), collagen (Col) and aspirin (ASA) using fibrin plates method. A significant decrease of the fibrinolytic activity related to the presence and number of platelets was observed. We confirm the presence of platelet anti-UK and anti-SK activities. The former appears to be higher than the other activity. Low and high concentrations of Col stimulated the release of plasminogen activator-inhibitors (PA-I) from platelets, and ASA could not modify this release. Besides ASA might inhibit some PA release. The high concentration of Col was capable to release anti-UK and anti-SK activities from platelets and perhaps other intrinsic PA-I. The low concentration of Col was only capable to release intrinsic PA-I, suggesting that anti-UK and anti-SK needed a stronger stimuli to be released than intrinsic PA-I. We must consider the possibility that the PA-I and/or activators could be released by different metabolic pathways other than cyclooxygenase pathway.

A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy.

A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura diagnosed during pregnancy -

Combined effects of two mutations in von Willebrand disease 2M phenotype

Essentials Compound heterozygosity causes a VWD2M phenotype in a child with severe bleeding symptoms. p.P1648fs*45 changes the folding of A2 domain altering VWF binding to GPIbα and type VI collagen. p.P1648fs*45 was considered as an apparent de novo mutation; AS‐PCR revealed paternal mosaicism. Bleeding score and DDAVPs response were worse than those seen in VWD2M heterozygous controls.

Phenotypic Parameters in Genotypically Selected Type 2B von Willebrand Disease Patients: A Large, Single-Center Experience Including a New Novel Mutation.

&NA; von Willebrand disease type 2B (VWD2B) expresses gain‐of‐function mutations that enhance binding of an individuals von Willebrand factor (VWF) to its platelet ligand, glycoprotein Ib (GPIb), and which are usually identified by increased ristocetin‐induced platelet aggregation (RIPA). We describe here the phenotypic profile of 38 genotypically selected VWD2B‐affected family members (AFMs) belonging to 19 unrelated families. Major bleeding was observed in 68.4% of AFMs (previous to their diagnosis and registered by lifetime interviews), with a total of 46 episodes (1.21/patient), and was found to be highly related to the individual bleeding score and presence of thrombocytopenia, but otherwise unrelated to other laboratory parameters. Excessive muco‐cutaneous bleeding symptoms were often reported, the most frequent of which comprised menorrhagia, epistaxis, easy bruising, and bleeding after teeth extraction/in oral cavity. Eight unaffected family members were also studied. The prevalence of VWD2B within families was 0.826, and the penetrance of mutations was complete, making it mandatory to study entire family sets to complete diagnostic profiles. Seven heterozygous missense mutations were found, the most common being p.V1316M. In the p.R1308C group, 75% of the AFMs showed absence of RIPA at 0.5 mg/mL, 66.6% of whom had VWF:RCo < 10 IU/dL, and 50% of whom had VWF:CB < 10 IU/dL. In the p.S1310F group, none of the AFMs had VWF:RCo/VWF:Ag < 0.6 (RCo/Ag), but 100% had VWF:CB/VWF:Ag < 0.6/(CB/Ag). Patients with p.P1266L and p.R1304V were characterized as atypical VWD2B. Two de novo mutations were found in four AFMs belonging to two families. We also describe a novel mutation: p.Y1258C. Of our patients, 70.5% had O blood group. In conclusion, a normal RCo/Ag and a negative RIPA at 0.5 mg/mL do not necessarily rule out a diagnosis of VWD2B.

The effect of venous occlusion on the PAI and antiplasmins release from platelets.

The aim of this work is to study the effect of venous occlusion upon the antiplasmins and plasminogen activator-inhibitors (PAI) release from human platelets which could modify fibrinolytic response