Dominique Meyer

San Bortolo Hospital, Vicenza, Veneto, Italy

Are you Dominique Meyer?

Claim your profile

Publications (42)178.12 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The relationships between the Platelet Function Analyzer (PFA)-100 and von Willebrand factor (VWF) levels and bleeding score (BS) were evaluated within a multicentre project on Molecular and Clinical Markers for the Diagnosis and Management of type 1 von Willebrand disease (MCMDM-1VWD). PFA-100 closure time, either with epinephrine (EPI) or adenosine diphosphate (ADP)-cartridges, was measured in 107 index cases, 105 affected and 71 unaffected family members, and 79 healthy controls. By regression analysis VWF levels were strongly related to both closure times, with a non-linear progression. In a multiple stepwise regression model, age- and sex-adjusted PFA-100 ADP and VWF ristocetin cofactor activity (VWF:RCo) were independently associated with BS. Most of the variation of BS was predicted by PFA-100 ADP and VWF:RCo alone. In the subgroup of patients with subtle abnormalities of the multimeric pattern, VWF was invariably reduced and closure time prolonged in almost all of them. Neither PFA-100 ADP nor EPI closure times appeared to significantly improve the diagnostic capability of VWF antigen (VWF:Ag) measurement. Thus, in an unselected population a normal PFA-100 would be useful to exclude VWD, but whether it could replace the more specific VWF assay in patients with significant mucocutaneous bleeding symptoms remains to be investigated prospectively.
    British Journal of Haematology 11/2010; 151(3):245-51. · 4.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The decreased survival of von Willebrand factor (VWF) in plasma has been implicated as a mechanism in a subset of type 1 von Willebrand disease (VWD) patients. We have previously reported that the ratio of plasma levels of VWF and its propeptide (VWFpp) can be used to identify patients with reduced VWF survival. In this study, we report the assay of VWFpp and VWF:Ag in 19 individuals recruited from 6 European centers within the MCMDM-1VWD study. Eight individuals had a VWF:Ag level less than 30 IU/dL. Seven of these patients had a robust desmopressin response and significantly reduced VWF half-life that was predicted by a markedly increased steady-state plasma VWFpp/VWF:Ag ratio. VWF mutations previously associated with reduced VWF survival were identified in each of the 7 individuals. Thus, a substantially increased ratio of steady-state VWFpp/VWF:Ag predicted a reduced VWF half-life in patients with markedly decreased VWF:Ag levels. These data indicate that a reduced VWF survival is found in a subpopulation of patients with type 1 VWD. The systematic assay of both plasma VWF and the VWF propeptide in moderately severe type 1 VWD patients may identify patients with a reduced VWF survival phenotype.
    Blood 06/2008; 111(10):4979-85. · 9.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We have prospectively evaluated the biologic response to desmopressin in 77 patients with type 1 von Willebrand disease (VWD) enrolled within the Molecular and Clinical Markers for the Diagnosis and Management of type 1 VWD project. Complete response to desmopressin was defined as an increase of both ristocetin cofactor activity (VWF:RCo) and factor VIII coagulant activity (FVIII:C) to 50 IU/dL or higher and partial response as VWF:RCo or FVIII:C lower than 50 IU/dL after infusion, but at least 3-fold the basal level. Complete response was observed in 83% of patients; partial in 13%; and no response in 4%. Patients with some abnormality of VWF multimeric pattern had significantly lower basal FVIII:C and VWF, lower VWF:RCo/Ag ratio, and less complete responses to desmopressin than patients with a normal multimeric pattern (P=.002). Patients with mutations at codons 1130 and 1205 in the D'-D3 domain had the greatest relative increase, but shortest FVIII and VWF half-lives after infusion. Most partial and nonresponsive patients had mutations in the A1-A3 domains. Response to desmopressin in these VWD patients seemed to be associated with the location of the causative mutation. The presence of subtle multimeric abnormalities did not hamper potential clinically useful responses, as in typical type 1 VWD.
    Blood 05/2008; 111(7):3531-9. · 9.78 Impact Factor
  • Edith Fressinaud, Dominique Meyer
    Textbook of Hemophilia, 10/2007: pages 272 - 278; , ISBN: 9780470987124
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To study both the pathophysiologic and the prognostic value of ADAMTS13 in thrombotic microangiopathies (TMAs), we enrolled a cohort of 35 adult patients combining a first acute episode of TMA, an undetectable (below 5%) ADAMTS13 activity in plasma, and no clinical background such as sepsis, cancer, HIV, and transplantation. All patients were treated by steroids and plasma exchange, and an 18-month follow-up was scheduled. Remission was obtained in 32 patients (91.4%), and 3 patients died (8.6%) after the first attack. At presentation, ADAMTS13 antigen was decreased in 32 patients (91.4%), an ADAMTS13 inhibitor was detectable in 31 patients (89%), and an anti-ADAMTS13 IgG/IgM/IgA was present in 33 patients (94%). The 3 decedent patients were characterized by the association of several anti-ADAMTS13 Ig isotypes, including very high IgA titers, while mortality was independent of the ADAMTS13 inhibitor titer. In survivors, ADAMTS13 activity in remission increased to levels above 15% in 19 patients (59%) but remained undetectable in 13 patients (41%). Six patients relapsed either once or twice (19%) during the follow-up. High levels of inhibitory anti-ADAMTS13 IgG at presentation were associated with the persistence of an undetectable ADAMTS13 activity in remission, the latter being predictive for relapses within an 18-month delay.
    Blood 05/2007; 109(7):2815-22. · 9.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Two versions of conformation sensitive gel electrophoresis, fluorescent (F-CSGE) and manual (M-CSGE) techniques, were compared for mutation analysis of the von Willebrand factor gene. 56 PCRs were used to amplify all 52 exons of the gene in seven type 1 von Willebrand disease cases, plus a healthy control. One hundred and ninety-two samples were analyzed on each F-CSGE gel, compared with 40 on M-CSGE. 125 amplicons revealed bandshifts using F-CSGE, but only 101 by M-CSGE. Five mutations were detected by both techniques. F-CSGE detected 45 different polymorphisms whereas M-CSGE detected only 39. F-CSGE is high-throughput and more sensitive than M-CSGE.
    Haematologica 05/2007; 92(4):550-3. · 5.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Type 1 von Willebrand disease (VWD) is characterized by a personal and family history of bleeding coincident with reduced levels of normal plasma von Willebrand factor (VWF). The molecular basis of the disorder is poorly understood. The aims of this study were to determine phenotype and genotype and their relationship in patients historically diagnosed with type 1 VWD. Families were recruited in 9 European countries based on previous type 1 VWD diagnosis. Bleeding symptoms were recorded, plasma phenotype analyzed, and VWF mutation analysis performed in all index cases (ICs). Phenotypic and molecular analysis stratified patients into those with or without phenotypes suggestive of qualitative VWF defects (abnormal multimers) and with or without mutations. A total of 105 of 150 ICs (70%) had mutations identified. A subgroup with abnormal multimers (38% of ICs, 57 of 150) showed a high prevalence of VWF gene mutations (95% of ICs, 54 of 57), whereas in those with qualitatively normal VWF, fewer mutations were identified (55% of ICs, 51 of 93). About one third of the type 1 VWD cases recruited could be reconsidered as type 2. The remaining group could be considered "true" type 1 VWD, although mutations were found in only 55%.
    Blood 02/2007; 109(1):112-21. · 9.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In type 2B von Willebrand disease, there is spontaneous binding of mutated von Willebrand factor (VWF) multimers to platelets. Here we report a family in which severe thrombocytopenia may also be linked to abnormal megakaryocytopoiesis. A heterozygous mutation in the VWF A1 domain gave a R1308P substitution in an interactive site for glycoprotein Ibalpha (GPIbalpha). Electron microscopy showed clusters of platelets in close contact. Binding of antibodies to the GPIbalpha N-terminal domain was decreased, whereas GPIX and GPV were normally detected. In Western blotting (WB), GPIbalpha, alphaIIb, and beta3 were normally present. Proteins involved in Ca(2+) homeostasis were analyzed by quantitating platelet mRNA or by WB. Plasma membrane Ca(2+) ATPase (PMCA)-4b and type III inositol trisphosphate receptor (InsP(3)-R3) were selectively increased. The presence of degradation products of polyadenosine diphosphate (ADP)-ribose polymerase protein (PARP) suggested ongoing caspase-3 activity. These were findings typical of immature normal megakaryocytes cultured from peripheral blood CD34(+) cells with TPO. Significantly, megakaryocytes from the patients in culture produced self-associated and interwoven proplatelets. Immunolocalization showed VWF not only associated with platelets, but already on the megakaryocyte surface and within internal channels. In this family, type 2B VWD is clearly associated with abnormal platelet production.
    Blood 11/2006; 108(8):2587-95. · 9.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Type 2N von Willebrand disease (VWD) is characterized by a markedly decreased affinity of von Willebrand factor (VWF) for factorVIII (FVIII) and is caused by mutations in the D' or D3 domain of mature VWF. We now report a French patient with an atypical 2N VWD phenotype associating FVIII deficiency with plasmaVWF unable to bind FVIII (undetectableVWF:FVIIIB) but with an abnormal multimeric profile. This patient is heterozygous for both the frequent R854Q type 2NVWD mutation and a novel R763G mutation at the cleavage site between VWF propeptide and mature VWF. Four children of the patient displayed moderately decreased VWF:FVIIIB of plasma VWF and were heterozygous for either the R763G or the R854Q mutation. Children with the R763G mutation displayed the same abnormal multimeric profile as their father. Recombinant VWF (rVWF) expression studies performed in COS-7 cells showed that the R763G mutation subtly affects its multimeric profile and dramatically impairs its FVIII binding function. Furthermore, the characteristics of hybrid G763/Q854 rVWF resulting from cotransfection experiments were in agreement with the type 2N VWD diagnosis of the patient. We conclude that R763G is a new type 2N VWD mutation located in the VWF propeptide which alters the proteolytic processing of VWF and consequently its binding to FVIII.
    Thrombosis and Haemostasis 10/2006; 96(3):290-4. · 5.76 Impact Factor
  • Thrombosis and Haemostasis 07/2006; 95(6):1049-51. · 5.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The CK domain of von Willebrand factor (VWF) is involved in the dimerization of the protein. We identified the homozygous substitution A2801D of the CK domain in two siblings. Patients had low levels of VWF in plasma, abnormal ristocetin-induced binding to platelets and abnormal multimeric pattern with a lack of high molecular weight (HMW) forms and the presence of intervening bands between normal multimers. Accordingly, they were classified in type 2A, subtype IID, von Willebrand disease (VWD). Both asymptomatic parents carried the mutation at the heterozygous state. Their plasmaVWF exhibited the full range of multimers found in normal plasma. When analyzed by high resolution gel electrophoresis, very faint bands corresponding to the position of intervening bands of the propositus can be observed. The mutated recombinant (r)VWF-D2801, the hybrid rVWF-A/D2801 and the mutated C-terminal VWF fragment rSPII-D2801 were expressed in COS-7 cells. rVWF-D2801 showed an abnormal multimeric distribution similar to that of the propositus'VWF with intervening bands and a lack of HMW species. rVWF-A/D2801 exhibited the full range of multimers and the aberrant sized forms observed both in propositus'VWF and in rVWF-D2801. rSPII-WT assembled correctly into a dimer of 220 kDa. rSPII-D2801 appeared as a mixture of monomeric and dimeric forms which may be related to the abnormal multimeric pattern of the propositus and both mutated rVWF. We concluded that mutation A2801D disturbs the folding of the CK domain, which may result in a mixture of monomers and dimers of VWF. Multimers containing either an odd or even number of mature subunits are produced, and the presence of monomers appears to limit the degree of multimerization. In the heterozygousVWF, the presence of normal dimers improves the multimerization process. In conclusion, the mutation A2801D appears to be responsible for a recessive type 2A, subtype IID, VWD.
    Thrombosis and Haemostasis 06/2006; 95(5):776-81. · 5.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The physiopathology of thrombotic thrombocytopenic purpura (TTP) has been clarified since 1998, when it was shown that TTP in adults was most often associated with an acquired deficiency of von Willebrand factor-cleaving protease (ADAMTS13) due to autoantibodies, whereas TTP in children was most often associated with a hereditary autosomal recessive severe deficiency of ADAMTS13. The hereditary form of TPP (Upshaw-Schulman syndrome) is a very rare but life-threatening disease if adequate treatment (plasma therapy) is not administered. First manifestations occur before age 10 in two thirds of cases and as soon as birth in most cases. The subsequent course is characterized by recurrent hemolytic and thrombocytopenic crises, with intervals between relapses from every 3 to 4 weeks in two thirds of cases to several months or years in one third of cases. TTP crises are associated with cerebral vascular accidents in at least 30% of patients, with a risk of neurologic sequelae in approximately 20% of patients. Renal involvement includes frequent acute renal failure due to hemoglobinuria and/or thrombotic microangiopathy during hemolytic crisis and progressive renal deterioration in approximately 50% of cases, leading to chronic or end-stage renal failure in approximately 20% of patients. The clinical phenotype may vary from the typical congenital recurrent TTP. Some mild forms are limited to a fluctuating thrombocytopenia and may be misdiagnosed as idiopathic thrombocytopenic purpura. Phenotypic variability may be observed within a single family, which suggests a role of modifier genes. Fresh frozen plasma (FFP) replaces active ADAMTS13. Ten milliliters per kilogram FFP every 2 to 4 weeks suffices to maintain remission. FFP infusions are best used preventively, given that rescue infusions may not prevent central nervous system and renal involvement. It is hoped that plasmatic or recombinant purified ADAMTS13 will be available in the years to come.
    Seminars in Thrombosis and Hemostasis 04/2006; 32(2):90-7. · 4.22 Impact Factor
  • Edith Fressinaud, Dominique Meyer
    [Show abstract] [Hide abstract]
    ABSTRACT: Von Willebrand disease is the most frequent bleeding disorder caused by inherited defects in the concentration, structure, or function of von Willebrand factor (VWF). The genetic defects are essentially located in the VWF gene, but can potentially be located within other genes, and induce an heterogeneous clinical pattern inherited as an autosomal trait, mostly dominant. Three main categories are distinguished; type 1 includes partial quantitative deficiency of VWF, type 3 (recessive form) includes virtually complete deficiency of VWF, and type 2 includes variants with either a defective VWF-dependent platelet function or a defective binding of VWF to factor VIII. These categories correlate with important clinical features and therapeutic requirements. In type 1, the mildest form, desmopressin, which induces secretion of VWF from endothelial cells, is most effective with a variable-lasting response. In type 2, responsiveness to desmopressin is variable (contraindicated in type 2B) with the persistence of the qualitative abnormality, and replacement therapy with blood products containing VWF is often necessary. Patients with type 3, the severe form, are unresponsive to desmopressin since they lack VWF in storage compartments, and the treatment or the prophylaxis of bleeding require replacement therapy.
    La Revue du praticien 01/2006; 55(20):2209-18.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Calcium (Ca2+) ionophores are the most effective agents able to elicit rapid membrane remodeling in vitro. This process exposes aminophospholipids at the surface of platelets and blood cells, thus providing a catalytic surface for coagulation. To explore the underlying mechanism, we examined if cytosolic Ca2+ ([Ca2+]i) increase through store-operated Ca2+ entry (SOCE) was necessary for the potent effect of ionophores. Recent studies have demonstrated that the Ca2+-ATPase inhibitor thapsigargin, although able to elevate [Ca2+]i through SOCE, does not trigger the rapid membrane remodeling. However, it was not known if the additional effect of ionophores to promote the process required SOCE or could it occur independently. We took advantage of two mutant B lymphoblast cell lines, characterized either by defective SOCE or altered membrane remodeling, to simultaneously assess [Ca2+]i increase and membrane remodeling in the presence of ionophores or thapsigargin. Results imply that ionophores trigger membrane remodeling without the requirement for a functional SOCE.
    Biochemical and Biophysical Research Communications 03/2005; 327(1):335-41. · 2.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In contrast to other agents able to induce apoptosis of cultured cells, Ca2+ ionophore A23187 was shown to elicit direct activation of intracellular signal(s). The phenotype of the cells derived from patients having the hemorrhagic disease Scott syndrome, is associated with an abnormally high proportion of apoptotic cells, both in basal culture medium and upon addition of low ionophore concentrations in long-term cultures. These features are presumably related to the mutation also responsible for the defective procoagulant plasma membrane remodeling. We analyzed the specific transcriptional re-programming induced by A23187 to get insights into the effect of this agent on gene expression and a defective gene regulation in Scott cells. The changes in gene expression upon 48 hours treatment with 200 nM A23187 were measured in Scott B lymphoblasts compared to B lymphoblasts derived from the patient's daughter or unrelated individuals using Affymetrix microarrays. In a similar manner in all of the B cell lines, results showed up-regulation of 55 genes, out of 12,000 represented sequences, involved in various pathways of the cell metabolism. In contrast, a group of 54 down-regulated genes, coding for histones and proteins involved in the cell cycle progression, was more significantly repressed in Scott B lymphoblasts than in the other cell lines. These data correlated with the alterations of the cell cycle phases in treated cells and suggested that the potent effect of A23187 in Scott B lymphoblasts may be the consequence of the underlying molecular defect. The data illustrate that the ionophore A23187 exerts its pro-apoptotic effect by promoting a complex pattern of genetic changes. These results also suggest that a subset of genes participating in various steps of the cell cycle progress can be transcriptionally regulated in a coordinated fashion. Furthermore, this research brings a new insight into the defect in cultured Scott B lymphoblasts, leading to hypothesize that a mutated gene plays a role not only in membrane remodeling but also in signal transduction pathway(s) leading to altered transcriptional regulation of cell cycle genes.
    BMC Genomics 02/2005; 6:146. · 4.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Arterial thrombotic events, thrombocytopenia, and hemolytic anemia with schistocytes may be encountered in the setting of both thrombotic thrombocytopenic purpura (TTP) and primary antiphospholipid syndrome (APS). We report 2 cases of TTP occurring in patients with definite primary APS. We also describe the results of tests for ADAMTS-13 activity in 20 consecutive patients with primary APS, as well as tests for antiphospholipid antibodies in 26 patients who had TTP, severe ADAMTS-13 deficiency, and ADAMTS-13-inhibiting antibodies. In both of the patients with primary APS and TTP, ADAMTS-13 activity was undetectable, and ADAMTS-13-inhibiting antibodies were present. None of the 26 patients with TTP and severe ADAMTS-13 deficiency was positive for the lupus anticoagulant. One of these patients had a low level of anticardiolipin antibodies (22 IgG phospholipid units). In the 20 patients with primary APS, mean ADAMTS-13 activity was 116% (range 44-250%), and no severe deficiency (< 5%) was observed. Our findings suggest that primary APS must be added to the list of autoimmune disorders that can be complicated by TTP.
    Arthritis & Rheumatology 11/2004; 50(10):3260-4. · 7.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To explore the molecular basis of von Willebrand factor (VWF) clearance, an experimental model employing VWF-deficient mice was developed. Biodistribution was examined by the injection of radiolabeled VWF, which was primarily directed to the liver with minor amounts in other organs. Disappearance of VWF from plasma was characterized by a rapid initial phase (t((1/2))alpha = 13 min) and a slow secondary phase (t((1/2))beta = 3 h), with a mean residence time (MRT) of 2.8 h. A similar clearance was observed for VWF consisting of only high or low molecular weight multimers, indicating that, in our experimental model, clearance is independent of multimeric distribution. This allowed us to compare the survival of full-length VWF to truncated variants. Deletion of both the amino-terminal D'-D3 and carboxyl-terminal D4-CK domains resulted in a fragment with a similar clearance to wild-type VWF. Deletion of only the D'-D3 region was associated with an almost 2-fold lower recovery and increased clearance (MRT = 1.6 h), whereas deletion of only the D4-CK region resulted in a significantly reduced clearance (MRT = 4.5 h, p < 0.02). These results point to a role of the D'-D3 region in preventing clearance of VWF. Furthermore, replacement of D3 domain residue Arg-1205 by His resulted in a markedly increased clearance (MRT = 0.3 h; p = 0.004). Therefore, this mutation seems to abrogate the protective effect of the D'-D3 region. In vitro analysis of this mutant also revealed a 2-fold reduced affinity for VWF propeptide at low pH, showing that mutation of Arg-1205 results not only in an increased clearance rate but is also associated with an impaired pH-dependent interaction with VWF propeptide.
    Journal of Biological Chemistry 03/2004; 279(13):12102-9. · 4.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Glycogen storage disease type Ia (GSD-Ia), a congenital deficiency of hepatic glucose-6-phosphatase activity, is often associated with hyperproteinemia. To document the mechanism of hyperproteinemia, the proteins of the hemostatic system were analyzed according to their site of synthesis: hepatocyte, endothelial cell, or both. The role of inflammation was investigated by the measurement of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels in plasma. Twenty-seven patients with GSD-Ia were evaluated, as were 14 patients with other types of GSD and 30 healthy control subjects. Of the 41 patients with GSD, 15 also had hepatic adenoma (14 patients with GSD-Ia and 1 with GSD type III). In patients with GSD-Ia, there was a two-fold increase in all hepatocyte-synthesized proteins (i.e., factor VII, protein C, C4b binding protein) compared with control subjects and patients with other types of GSD. The proteins with mixed endothelial and hepatocyte origin (i.e., antithrombin and protein S) also were significantly increased but to a lesser extent. In contrast, the mean concentration of von Willebrand factor, which is exclusively synthesized in endothelial cells, was normal, as was the concentration of TNF-alpha and IL-6. These results suggest that the hyperproteinemia of GSD-Ia (including hemostatic proteins) is attributable to hepatocyte dysfunction and not related to an inflammatory process.
    Journal of Pediatric Gastroenterology and Nutrition 12/2003; 37(5):566-70. · 2.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Antibodies to heparin–PF4 (H-PF4) complexes have been tested and isotyped in 38 patients who developed severe heparin-induced thrombocytopenia (type II HIT). All the patients had a platelet count < 120 × 109/l or a reduction of >30% of the initial value, occurring at least 5 d after the onset of heparin. Thrombocytopenia, which rapidly reversed following the withdrawal of heparin, was associated with thrombosis in nine patients. Although IgG isotypes were found in most cases (n = 26), the presence of only IgM and/or IgA was observed in 12 patients, including three cases showing a thrombotic complication. Our results indicate that type II HIT may be induced by IgA and/or IgM anti-H-PF4 antibodies even in the absence of IgG isotypes. This finding demonstrates that platelet Fc receptors (FcγRII) are not necessarily involved in the pathogenicity of heparin-dependent antibodies and emphasizes the major role of platelet PF4 receptors. The increased expression of the latter following a slight activation by thrombin, and the subsequent binding of IgM and IgA antibodies to H-PF4 on the platelet surface, may directly trigger platelet activation, aggregation and thrombosis. Alternatively, thrombocytopenia could be indirectly induced through the mediation of neutrophils, monocytes and lymphocytes which expose receptors for IgA (FcαR) or IgM (FcμR). IgM–platelet complexes may also bind and activate complement, leading to platelet activation or destruction. Moreover, the reactivity of the antibodies with glycosaminoglycans–PF4 complexes present on the endothelial surface could also induce endothelial lesions and promote procoagulant activity and predisposition to thrombosis.
    British Journal of Haematology 11/2003; 92(4):954 - 959. · 4.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The von Willebrand factor-cleaving protease (VWF-cp) activity has been reported to be deficient in adults with thrombotic thrombocytopenic purpura (TTP) and generally normal in adults with hemolytic uremic syndrome (HUS). The goal of this study was to determine VWF-cp activity in children with typical postdiarrheal (d+) HUS or atypical non-postdiarrheal (d-) HUS. Study design We measured VWF-cp activity in the plasma of 64 children with either (d+) HUS (n = 41) or (d-) HUS (n = 23). In the acute phase of HUS, VWF-cp activity was normal (>50%) in 54 children and undetectable (<5%) in one (d+) HUS and in 6 (d-) HUS children. After a 3-month remission, the (d+) HUS patient recovered a 100% VWF-cp activity, and the 6 (d-) HUS patients kept an undetectable level. In these 6 (d-) HUS patients, the disease was characterized by a neonatal onset and several relapses (hemolytic anemia, thrombocytopenia, transient acute renal failure, cerebral ischemia), and sometimes the development of arterial hypertension or end stage renal failure. A subgroup of pediatric patients with atypical (d-) HUS, with hematologic symptoms starting at birth and a recurrent course progressively involving kidney and brain, is related to VWF-cp deficiency and actually corresponds to Upshaw-Schulman syndrome revisited as congenital TTP.
    Journal of Pediatrics 03/2003; 142(3):310-7. · 4.04 Impact Factor

Publication Stats

947 Citations
178.12 Total Impact Points

Institutions

  • 2008–2010
    • San Bortolo Hospital
      Vicenza, Veneto, Italy
  • 2003–2010
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
    • Hôpital Antoine-Béclère – Hôpitaux universitaires Paris-Sud
      Clamart, Île-de-France, France
  • 2006
    • Hôpital Universitaire Robert Debré
      • Service de Néphrologie Pédiatrique
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Universitaire de Nantes
      Naoned, Pays de la Loire, France
  • 2002
    • Unité Inserm U1077
      Caen, Lower Normandy, France