Huub H. D. M. Van Vliet
Erasmus University Rotterdam
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Featured researches published by Huub H. D. M. Van Vliet.
Annals of Internal Medicine | 1985
Jan Jacques Michiels; Abels Johannes; Johan Steketee; Huub H. D. M. Van Vliet; Vojislav D. Vuzevski
Erythromelalgia was the presenting symptom in 26 of 40 patients with thrombocythemia in its primary form or when associated with polycythemia vera. The localized painful burning, redness, and warm congestion in the extremities could be accurately documented with thermography. Skin punch biopsy samples taken from the affected areas showed typical arteriolar inflammation, fibromuscular intima proliferation, and thrombotic occlusions. Erythromelalgia often progressed to ischemic acrocyanosis or necrosis in toes or fingers. Complete relief of pain and restoration of microvascular circulation disturbances was obtained with the cyclo-oxygenase inhibitors aspirin and indomethacin, but not with sodium-salicylate or the platelet inhibitors dipyridamole, sulfinpyrazone, ticlopidine, and dazoxiben. The erythromelalgia was alleviated during busulfan-induced remissions of thrombocythemia and its recurrence coincided with relapsing thrombocythemia. These observations suggest a causal relationship between erythromelalgia and thrombocythemia, in which platelet-mediated inflammatory and occlusive arteriolar changes play a part in the etiology of erythromelalgia.
British Journal of Haematology | 1996
Perry J. J. Van Genderen; Ulrich Budde; Jan Jacques Michiels; Roel van Strik; Huub H. D. M. Van Vliet
We have investigated the relationship between platelet count and large VWF (von Willebrand factor) multimers in the plasma of 36 patients with essential thrombocythaemia (ET) and 26 patients with reactive thrombocytosis (RT). In both ET and RT patients an inverse relationship could be established between platelet count and large VWF multimers in plasma as well in relatively decreased ristocetin cofactor/von Willebrand factor antigen and collagen binding activity/von Willebrand factor antigen ratios. A normalization of the platelet count was accompanied by restoration of a normal plasma VWF multimeric distribution. Our data suggest that increasing numbers of platelets circulating in blood result in increased removal of large VWF multimers from plasma.
Leukemia & Lymphoma | 1996
Jan Jacques Michiels; Perry J. J. Van Genderen; Jan Lindemans; Huub H. D. M. Van Vliet
Fifty consecutive patients with thrombocythemia (35 men and 15 women) were diagnosed as primary thrombocythemia (PT) in 30 and thrombocythemia associated with polycythemia vera (PV) in 20. The symptoms were platelet-mediated erythromelalgia in 16 PT and 15 PV, coronary artery disease in 3 PT and 2 PV, atypical cerebral ischemic attacks in 8 PT and 3 PV, paradoxical thrombosis and bleeding in 3 PT and 2 PV and hemorrhages alone in 6 PT and 2 PV patients. Erythromelalgia was localized in the forefoot sole and toes in 28, the fingertips in 9, the handpalm in 2. Untreated erythromelalgia progressed to acrocyanosis or peripheral ischemia with necrosis in a toe or fingertip in 14 cases. Painful red, warm and indurated erythromelalgic hot spots in the skin of the upper legs were misdiagnosed as superficial thrombophelebitis in 5 PT and 2 PV patients. Erythromelalgia in thrombocythemia already occurred at slightly increased platelet counts above 400 x 10(9)/l. The curative effect of aspirin on erythromelalgia in thrombocythemia was consistently accompanied by a significant increase of platelet counts. Erythromelalgia and bleeding paradoxically occurred in 5 patients at platelet counts between 1000 and 2000 x 10(9)/l. In this situation aspirin prevents erythromelalgic and microcirculatory circulation disturbances, but further increases the risk of serious bleeding complications. Presenting hemorrhagic manifestations in thrombocythemia were observed at platelet counts in excess of 1000 x 10(9)/l in 9 PT and 4 PV patients as severe epistaxis in 5, atypical ecchymoses in 3, gastrointestinal bleeding in 2 and secondary bleeding in 3. The concept of platelet-mediated erythromelalgia, thrombosis and hemorrhages in thrombocythemia is discussed.
British Journal of Haematology | 1997
Perry J.J. van Genderen; Fransisco J. Prins; Irene S. Lucas; Desiree Van De Moesdijk; Huub H. D. M. Van Vliet; Roel van Strik; Jan Jacques Michiels
Patients with essential thrombocythaemia (ET) exhibit a decrease of large von Willebrand factor (VWF) multimers in plasma, which is inversely related to the platelet count. In the present study we investigated whether the decrease of large VWF multimers in plasma with increasing platelet counts is the consequence of increased turnover of large VWF multimers in vivo. To that end we measured the half‐life times of endogenously released VWF:Ag and VWF:CBA (collagen binding activity) after intravenous administration of desmopressin (DDAVP) to nine ET patients and nine control subjects (N). In addition, the half‐life times of VWF:Ag and VWF:CBA were also measured in four ET patients after cytoreduction of the increased platelet count to normal or nearly normal values. Estimated half‐life times of VWF:Ag did not differ between ET patients and normals (11.0 ± 4.0 h v 12.4 ± 2.5 h, P > 0.05). Estimated half‐life times of VWF:CBA were significantly lower in ET patients as compared with normal individuals (6.1 ± 2.0 h v 8.4 ± 2.5 h, P < 0.05). After cytoreduction of the increased platelet count to (nearly) normal values in all four ET patients the half‐life time of VWF:CBA significantly (P = 0.014) increased from 5.2 ± 1.2 h to 8.7 ± 2.0 h. Our data suggest that platelets may play a role in the homeostasis of circulating von Willebrand factor, which may compromise normal haemostasis at fairly increased platelet counts.
Clinical and Applied Thrombosis-Hemostasis | 2006
Jan Jacques Michiels; Zwi N. Berneman; Alain Gadisseur; Marc van der Planken; Wilfried Schroyens; Ann Van de Velde; Huub H. D. M. Van Vliet
All variants of type 2 von Willebrand disease (VWD) patients, except 2N, show a defective von Willebrand factor (VWF) protein (on cross immunoelectrophoresis or multimeric analysis), decreased ratios for VWF:RCo/Ag and VWF:CB/Ag and prolonged bleeding time. The bleeding time is normal and FVIII:C levels are clearly lower than VWF:Ag in type 2N VWD. High resolution multimeric analysis of VWF in plasma demonstrates that proteolysis of VWF is increased in type 2A and 2B VWD with increased triplet structure of each visuable band (not present in types 2M and 2U), and that proteolysis of VWF is minimal in type 2C, 2D, and 2E variants that show aberrant multimeric structure of individual oligomers. VWD 2B differs from 2A by normal VWF in platelets, and increased ristocetine-induced platelet aggregation (RIPA). RIPA, which very likely reflects the VWF content of platelets, is normal in mild, decreased in moderate, and absent in severe type 2A VWD. RIPA is decreased or absent in 2M, 2U, 2C, and 2D, variable in 2E, and normal in 2N. VWD 2M is usually mild and characterized by decreased VWF:RCo and RIPA, a normal or near normal VWF multimeric pattern in a low resolution agarose gel. VWD 2A-like or unclassifiable (2U) is distinct from 2A and 2B and typically featured by low VWF:RCo and RIPA with the relative lack of high large VWF multimers. VWD type 2C is recessive and shows a characteristic multimeric pattern with a lack of high molecular weight multimers, the presence of one single-banded multimers instead of triplets caused by homozygosity or double hereozygosity for a mutation in the multimerization part of VWF gene. Autosomal dominant type 2D is rare and characterized by the lack of high molecular weight multimers and the presence of a characteristic intervening subband between individual oligimers due to mutation in the dimerization part of the VWF gene. In VWD type 2E, the large VWF multimers are missing and the pattern of the individual multimers shows only one clearly identifiable band, and there is no intervening band and no marked increase in the smallest oligomer. 2E appears to be less well defined, is usually autosomal dominant, and accounts for about one third of patients with 2A in a large cohort of VWD patients.
British Journal of Haematology | 2003
Kirill Skomorovski; Hila Harpak; Anton Ianovski; Moshe Vardi; Trudi P. Visser; Simone C. C. Hartong; Huub H. D. M. Van Vliet; Gerard Wagemaker; Zvia Agur
Summary. Thrombopoietin (TPO) immunogenicity hampers its development as a therapeutic agent for attenuating thrombocytopenia and improving platelet harvest in donors. This work was aimed at validating, in mouse and in monkey experiments, a thrombopoiesis computer‐model prediction that platelet counts, similar to those obtained with accepted TPO dose scheduling, can also be achieved by new and safer schedules of significantly reduced doses. To this end we compared, in a two‐arm mouse experiment, platelet increases obtained with a single intraperitoneal dosing of recombinant mouse TPO (17·5 μg/kg), with those obtained by the model‐suggested protocol of a significantly reduced dose (2 μg/kg on 4 consecutive days). The two TPO regimens generated similar platelet profiles, peaking at ca. 2700 × 109/l platelets. In rhesus monkeys, treated by rhesus monkey recombinant TPO (5 μg/kg on 4 consecutive days), the suggested protocol yielded effective platelet stimulation with significantly reduced immunogenicity. The models ability to predict individual monkey responses to several new TPO administration protocols was further validated, proving sufficient robustness in providing good predictions with limited input data. The simulation tool could be used for testing the effects of different therapeutic agents on thrombopoiesis. Human trials are warranted for testing the suggested improved TPO protocol, possibly in conjunction with chemotherapy.
Blood Coagulation & Fibrinolysis | 2004
Jan Jacques Michiels; Zwi N. Berneman; Marc van der Planken; Wilfried Schroyens; Ulrich Budde; Huub H. D. M. Van Vliet
The parameters to diagnose von Willebrand disease (vWD) include factor VIII coagulant activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), von Willebrand factor ristocetin cofactor activity (vWF:RCo), and von Willebrand factor collagen binding activity (vWF:CB). Type 2 vWD is associated with a moderate bleeding diathesis due to low levels of vWF:RCo and vWF:CB as compared with near normal or normal values for FVIII:C and vWF:Ag. As the factor VIII/von Willebrand factor (vWF) concentrate, Haemate-P, is featured by a vWF:RCo/FVIII:C ratio of about 2.2, the recommended loading dose of 50 U/kg FVIII:C followed by 25 U/kg FVIII:C every 12 h for several days for bleeding prophylaxis in type 2 vWD patients undergoing major surgery demonstrated a predicted significant over-treatment reaching vWF:RCo levels above 2 U/ml. Therefore, we restricted Haemate-P substitution for major surgery to one loading dose of 40–50 U/kg FVIII:C (88–110 U/kg vWF:RCo) followed by 15–20 U/kg FVIII:C (33–44 U/kg vWF:RCo) every 12 h for several days and evaluated this strategy in a prospective pharmacokinetic and efficacy study for bleeding prophylaxis in five type 2 vWD patients. Pre-treatment and peak levels (1 h after Haemate-P loading dose) rose from 0.43–0.66 to 1.5–2.5 U/ml for FVIII:C, from 0.23–0.45 to 1.5–2.5 U/ml for vWF:Ag, from 0.10–< 0.20 to 1.5–2.5 U/ml for vWF:RCo, and from < 0.05–0.10 to 1.0–2.0 U/ml for vWF:CB. Mean in vivo recoveries per transfused IU FVIII:C/kg body weight were 3.2% for FVIII:C, 3.9% for vWF:RCo, and 2.8% for vWF:CB. Mean in vivo recoveries per transfused IU vWF:RCo/kg were 1.45% for FVIII:C, 1.7% for vWF:RCo and 1.25% for vWF:CB. The biological half-life times after transfused Haemate-P were about 12 h for both vWF:RCo and vWF:CB. Based on these pharmacokinetic data, we propose to adapt the loading dose factor VIII/vWF concentrate (Haemate-P) to 60–80 U/kg vWF:RCo followed by 30–40 U/kg vWF:RCo every 12 h for no longer than several days (less than 1 week) for bleeding prophylaxis during major surgery or trauma, and to one loading dose of 40–60 U/kg vWF:RCo for minor surgery, trauma or mucotaneous bleedings in patients with type 2 vWD unresponsive to DDAVP.
Clinical and Applied Thrombosis-Hemostasis | 2007
Jan Jacques Michiels; Huub H. D. M. Van Vliet; Zwi N. Berneman; Alain Gadisseur; Marc van der Planken; Wilfried Schroyens; Ann van der Velden; Ulrich Budde
The current standard set of von Willebrand factor (VWF) parameters used to differentiate type 1 from type 2 VWD include bleeding times (BTs), factor VIII coagulant activity (FVIII:C), VWF antigen (VWF:Ag), VWF ristocetine cofactor activity (VWF:RCo), VWF collagen binding activity (VWF:CB), ristocetine induced platelet aggregation (RIPA), and analysis of VWF multimers in low and high resolution agarose gels and the response to DDAVP. The BTs and RIPA are normal in asymptomatic carriers of a mutant VWF allele, in dominant type 1, and in recessive type 2N VWD, and this category has a normal response of VWF parameters to DDAVP. The response of FVIII:C is compromised in type 2N VWD. The BTs and RIPA are usually normal in type Vicenza and mild type 2A VWD, and these two VWD variants show a transiently good response of BT and VWF parameters followed by short in vivo half life times of VWF parameters. The BTS are strongly prolonged and RIPA typically absent in recessive severe type 1 and 3 VWD, in dominant type 2A and in recessive type 2C (very likely also 2D) VWD and consequently associated with low or absent platelet VWF, and no or poor response of VWF parameters to DDAVP. The BTs are prolonged and RIPA increased in dominant type 2B VWD, that is featured by normal platelet VWF and a poor response of BT and functional VWF to DDAVP. The BTs are prolonged and RIPA decreased in dominant type 2A and 2U, that all have low VWF platelet, very low VWF:RCo values as compared to VWF:Ag, and a poor response of functional VWF to DDAVP. VWD type 2M is featured by the presence of all VWF multimers in a low resolution agarose gel, normal or slightly prolonged BT, decreased RIPA, a poor response of VWF:RCo and a good response of FVIII and VWF:CB to DDAVP and therefore clearly in between dominant type 1 and 2U. The existing recommendations for prophylaxis and treatment of bleedings in type 2 VWD patients with FVIII/VWF concentrates are mainly derived from pharmocokinetic studies in type 3 VWD patients. FVIII/VWF concentrates should be characterised by labelling with FVIII:C, VWF:RCo, VWF:CB and VWF multimeric pattern to determine their safety and efficacy in prospective management studies. As the bleeding tendency is moderate in type 2 and severe in type 3 VWD and the FVIII:C levels are near normal in type 2 and very low in type 3 VWD patients. Proper recommendations of FVIII/VWF concentrates using VWF:RCo unit dosing for the prophylaxis and treatment of bleeding episodes are proposed and has to be stratified for the severity of bleeding, the type of surgery either minor or major and for type 2 and type 3 VWD as well.
Clinical and Applied Thrombosis-Hemostasis | 1999
Jan Jacques Michiels; Huub H. D. M. Van Vliet
The reported underlying lymphoproliferative dis orders associated with acquired von Willebrand disease (AvWD) include benign monoclonal gammapathy, multiple myeloma, Waldenström disease, chronic lymphocytic leuke mia, non-Hodgkin lymphoma, and hairy cell leukemia. The AvWD in patients with a monoclonal gammapathy and/or a lymphoproliferative disorder is featured by a prolonged bleed ing time, normal platelet count, and a decreased or absent ris tocetine-induced platelet aggregation in combination with a prolonged aPTT and normal PT due to low levels of factor VIII/von Willebrand factor (vWF) parameters in the absence of a factor VIII inhibitor in the Bethesda assay. In vitro and vivo experiments consistently showed that the anti-vWF autoanti bodies in monoclonal gammapathies cause a rapid clearance of the factor VIII/vWF complex from the circulation after DDAVP and factor VIII/vWF concentrate infusion. Multimeric analysis of the vWF usually show a type 11-like AvWD due to the absence of large vWF multimers as the consequence of the rapid clearance of the anti-vWF-factor VIII/vWF complex from the circulation. There is a poor response to intravenous DDAVP and factor VIII/vWF concentrate infusion, but high dose intravenous gamma globulin (1 g/kg for 2 days) usually induces a transient correction of the factor VIII/vWF param eters for 1 to a few weeks.
Clinical and Applied Thrombosis-Hemostasis | 2006
Jan Jacques Michiels; Zwi N. Berneman; Alain Gadisseur; Marc van der Planken; Wilfried Schroyens; Ann van de Velde; Huub H. D. M. Van Vliet
Recessive type 3 von Willebrand disease (VWD) is caused by homozygosity or double heterozygosity for two non-sense mutations (null alleles). Type 3 VWD is easy to diagnose by the combination of a strongly prolonged bleeding time (BT), absence of ristocetine-induced platelet aggregation (RIPA), absence of von Willebrand factor (VWF) protein, and prolonged activated partial thromboplastin time (aPTT) due to factor VIII:coagulant (FVIII:C) deficiency. VWD type 3 is associated with a pronounced tendency to mucocutaneous and musculoskeletal bleedings since early childhood. Carriers of one null allele are usually asymptomatic at VWF levels of 50% of normal. Recessive severe type 1 VWD is caused by homozygosity or double heterozygosity for a missense mutation. Recessive type 1 VWD differs from type 3 VWD by the presence of detectable von Willebrand factor: antigen VWF:Ag and FVIII:C levels between 0.09 and 0.40 U/mL. Patients with recessive type 1 VWD show an abnormal VWF multimeric pattern in plasma and/or platelets consistent with severe type 2 VWD. Carriers of a missense mutation may have mild bleeding and mild VWF deficiency and can be diagnosed by a double VWF peak on cross immunoelectrophoresis (CIE). There will be cases of mild and moderate recessive type 1 VWD due to double heterozygosity of two missense mutations, or with the combination of one missense mutation with a non-sense or bloodgroup O. Mild deficiency of VWF in the range of 0.20 to 0.60 U/mL, with normal ratios of von Willebrand factor: ristocetine cofactor/antigen VWF:RCo/Ag and VWF:collagen binding/antigen (VWF:CB/Ag), normal VWF multimers, and a completely normal response to desmopressin acetate (DDAVP) with VWF level rising from below to above 1.00 U/mL are very likely cases of so-called pseudo-VWF defienciecy in individuals with normal VWF protein and gene. Autosomal dominant type 1 VWD variants are in fact type 2 variants caused by a heterozygous missense mutation in the VWF gene that produces a mutant VWF protein that has a dominant effect on normal VWF protein produced by the normal VWF allele with regard to the synthesis, processing, storage, secretion, and/or proteolysis of VWF in endothelial cells. A DDAVP challenge test clearly differentiates between dominant type 1 VWD phenotype and dominant type 2 M VWD.