carriers had an odds ratio for elevated blood pressure of 1.93 (95%CI: 1.30-2.86). Finally, women... more carriers had an odds ratio for elevated blood pressure of 1.93 (95%CI: 1.30-2.86). Finally, women double heterozygous for Thr164Ile and Gln27Glu versus non-carriers at all 3 loci had an odds ratio for elevated blood pressure of 2.49 (1.28-4.85). In men, blood pressure was not influenced consistently by this genetic variation.
The role of plasminogen activator inhibitor-1 (PAI-1) in the plasma, blood platelets, and vessel ... more The role of plasminogen activator inhibitor-1 (PAI-1) in the plasma, blood platelets, and vessel wall during acute arterial thrombus formation was investigated in gene-deficient mice. Photochemically induced thrombosis in the carotid artery was analyzed via transillumination. In comparison to thrombosis in C57BL/6J wild-type (wt) mice (113 +/- 19 x 10(6) arbitrary light units [AU] n = 15, mean +/- SEM), thrombosis in PAI-1(-/-) mice (40 +/- 10 x 10(6) AU, n = 13) was inhibited (P <.01), indicating that PAI-1 controls fibrinolysis during thrombus formation. Systemic administration of murine PAI-1 into PAI-1(-/-) mice led to a full recovery of thrombotic response. Occurrence of fibrinolytic activity was confirmed in alpha(2)-antiplasmin (alpha(2)-AP)-deficient mice. The sizes of thrombi developing in wt mice, in alpha(2)-AP(+/-) and alpha(2)-AP(-/-) mice were 102 +/- 35, 65 +/- 8.1, and 13 +/- 6.1 x 10(6) AU, respectively (n = 6 each) (P <.05), compatible with functional plasmin...
Congenital disorders of glycosylation (CDG) type I are mostly due to a deficient phosphomannomuta... more Congenital disorders of glycosylation (CDG) type I are mostly due to a deficient phosphomannomutase activity, called CDG Ia. CDG IIa (mutations in the MGAT2 gene) results from a deficient activity of the Golgi enzyme N-acetylglucosaminyltransferase II. CDG Ia patients predominantly have a thrombotic tendency, whereas our CDG IIa patient has an increased bleeding tendency, despite similar coagulation factor abnormalities in both types. We have investigated whether abnormally glycosylated platelet membrane glycoproteins are involved in the haemostatic complications of both CDG groups. In flow cytometry, the binding of Ricinus communis lectin (reactive with beta-galactose primarily) to control platelets increased after neuraminidase treatment: this increase was smaller (p < 0.01) in CDG Ia patients (3.1 +/- 0.08 times) than in control platelets (8.5 +/- 1.8 times) and did not occur in the CDG IIa patient. Platelet-rich plasma from CDG Ia patients, but not a CDG IIa patient. aggregat...
MK-383 (L-tyrosine, N-(n-butylsulfonyl)-O-[4-butyl(4-piperidinyl)], monohydrochloride monohydrate... more MK-383 (L-tyrosine, N-(n-butylsulfonyl)-O-[4-butyl(4-piperidinyl)], monohydrochloride monohydrate) is a potent and specific platelet fibrinogen receptor antagonist that may be useful in preventing processes that lead to occlusive thrombus formation in the lumen of the blood vessel. Two placebo-controlled phase I trials were completed in 56 healthy volunteers to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of MK-383 administered as 1- and 4-hour infusions in the presence and absence of aspirin. When administered to healthy male subjects by constant infusions up to 0.4 microgram/kg/min over 1 hour or up to 0.2 microgram/min over 4 hours, it provided a well-tolerated reversible means of inhibiting platelet function. At infusion rates of 0.25 and 0.15 microgram/kg/min for 1 and 4 hours, respectively, MK-383 extended baseline bleeding time by 2.0- to 2.5-fold and inhibited adenosine diphosphate (ADP)-induced platelet aggregation by at least 80%. The pharmacokinetics of MK-383 include a mean plasma clearance of 329 ml/min, steady-state volume of distribution of 76 L, and half-life of 1.6 hours. The percentage of dose excreted in the urine was 37%. Correlations between MK-383 plasma concentration (C) and inhibition of platelet aggregation were examined by fitting with a sigmoid maximum-effect model. The plasma concentration yielding 50% inhibition (C50) for MK-383 in healthy volunteers is approximately 13 ng/ml, with a Hill coefficient &gt; 5. Based on a naive pooled analysis, an exponential empirical model best describes the MK-383 C-extension of template bleeding time (BTE) relationship. The model indicates that the MK-383 plasma concentration necessary to double BTE is approximately 30 ng/ml (i.e., 2.5-fold greater than the C50 for ADP-induced inhibition of platelet aggregation). The pharmacokinetics of MK-383 was unaffected by pretreatment with 325 mg aspirin 1 day before and 1 hour before infusion. Conversely, aspirin pretreatment reduced C50 and increased bleeding time extension, suggesting that aspirin may have an additive effect with respect to inhibition of platelet function. Based on the putative role of the fibrinogen receptor in thrombotic processes and an acceptable human pharmacokinetic-pharmacodynamic profile, MK-383 should be evaluated in patients with unstable angina.
Several reports describing outbreaks of hepatitis A in hemophilia A patients transfused with solv... more Several reports describing outbreaks of hepatitis A in hemophilia A patients transfused with solvent/detergent-treated factor VIII concentrates have raised concern about possible transmission of hepatitis A by these concentrates. We recently witnessed such an outbreak of hepatitis A in 6 hemophilia A patients; review of the clinical data did not disclose any increased risk factor for community-acquired hepatitis A. A case-control study comparing the prevalence of anti-hepatitis A IgG antibodies in hemophiliacs and age-matched controls showed a lower seroprevalence in hemophiliacs. This might be due to passive protection acquired through transfusion of the previously used immunoglobulin-containing cryoprecipitate. The outbreak of hepatitis A could be explained as a catch-up phenomenon linked to the loss of passive protection with the use of purer factor VIII concentrates.
It has been shown by several authors (1, 2, 3, 4, 5) that bovine plasma and different preparation... more It has been shown by several authors (1, 2, 3, 4, 5) that bovine plasma and different preparations of purified bovine fibrinogen aggregate human platelets. This activity was absent in bovine serum and in the supernatants of either bovine plasma or purified bcvine fibrinogen heated at 56°C for 30 minutes (5). Furthermore, bovine fibrinogen preparations, rendered incoagulable by extensive plasmin degradation, no longer produced platelet aggregation (6). All these findings suggested that bovine fibrinogen itself was respcnsible for the aggregation. However, fcllcwing gel filtration on 6% agarose, purified bovine fibrinogen was eluted as a single protein peak, which, although clottable, was devoid of aggregating activity (7). Forbes et al. (8) have reported that commercial preparations of bovine and porcine antihemophilic globulin had a platelet aggregating activity, which appeared to be related to the fibrinogen fraction. Very recently, however, the same authors (9) have suggested that animal factor VIII, separated by gel filtration on Sepharose 4B a would be responsible for the observed aggregation. X ResearchFellow of the Katholieke Universiteit te Leuven, 1972.
Human platelet-rich plasma clotted by reptilase does not retract. This seems to be due to the lac... more Human platelet-rich plasma clotted by reptilase does not retract. This seems to be due to the lack of activation of platelets exposed to this enzyme rather than to the incomplete hydrolysis of fibrinogen. Indeed, when aggregating agents such as ADP, collagen, adrenaline or Thrombofax are preincubated with unstirred PRP before adding reptilase, strong clot retraction occurs. A number of antiaggregating compounds has been evaluated in this test system.
It was the aim of the present study to perform a systematic review of the published studies that ... more It was the aim of the present study to perform a systematic review of the published studies that estimated the prevalence of non-responders to aspirin, as assessed by the closure time of PFA-100, a point-of-care device, and to analyse: 1) some major clinical and methodological factors that can influence it and 2) its possible association with vascular outcomes. The prevalence of non-responders to aspirin in 64 populations from 53 studies, comprising 6,450 subjects, had a median value of 0.27. A higher number of aspirin non-responders was found among older patients, those with acute vascular events, or those treated for more than one month. Aspirin non-response was more frequently associated with the use of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;home-established&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; cut-offs or when closure time was only assessed after aspirin (rather than both before and after). Among risk factors, type 2 diabetes appeared to be associated with a higher prevalence of aspirin non-responders. The latter was also higher in less recent publications and in studies that used 3.2% rather than 3.8% Na-citrate as an anticoagulant. In eight studies comprising 847 subjects, aspirin non-responders were more likely to have vascular events than responders (relative risk: 1.63; 95% CI 1.16-2.28). In conclusion, although there appears to be heterogeneity among the studies analysed, this review indicates that about one quarter of people receiving aspirin would be identified--as an average--as aspirin non-responders by PFA-100. As this is a simple, widely available point-of-care test, efforts to better standardize it and to control for its major methodological variables might be useful to improve monitoring of platelet performance under aspirin treatment and to firmly establish the observed association with clinical vascular events.
Patients with a microdeletion on chromosome 22q11 demonstrate the clinical picture of the velocar... more Patients with a microdeletion on chromosome 22q11 demonstrate the clinical picture of the velocardiofacial syndrome. We report on three members of the same family with this microdeletion and velocardiofacial syndrome, all having an increase in platelet size and a mild decrease in platelet number. Their platelet function, however, tested by aggregation and by adherence to collagen in a whole blood perfusion system, was normal. We retrospectively studied the files of 35 other patients with 22q11 deletion and also found that their platelets had an increased size compared with cardiac controls. Moreover, their platelet size correlated negatively with platelet number. Knowing that patients with 22q11 deletion are obligate carriers for a heterozygous glycoprotein Ib beta deletion, these patients can be considered to be heterozygous Bernard-Soulier patients. In addition, a significant increase in platelet size may be a positive predictor for the clinical diagnosis of the velocardiofacial syndrome.
The case of an 11-year-old boy with grey platelet syndrome is described. Platelets had the typica... more The case of an 11-year-old boy with grey platelet syndrome is described. Platelets had the typical grey and ghostly appearance on May-Grünwald/Giemsa staining, caused by the absence of alpha granules confirmed by electron microscopy. Alpha granule protein content, i.e., beta-thromboglobulin and platelet factor 4, was less than 3% of normal and alpha granule secretion in response to thrombin was not detectable photometrically. The plasminogen activator inhibitor-1 pool in the patient&#39;s platelets was 5% of normal, confirming previous indirect evidence for the storage of this protein within the alpha-granule. Dense body secretion of adenosine triphosphate and 5-hydroxytryptamine was normal. Aggregation occurred normally in response to adenosine diphosphate and there was a slight delay in response to collagen.
Pathophysiology of Haemostasis and Thrombosis, 1981
10 male Wistar rats were made diabetic by an intravenous injection of streptozotocin. 10 sex and ... more 10 male Wistar rats were made diabetic by an intravenous injection of streptozotocin. 10 sex and age-matched rats served as control animals. 5 of the diabetic and 5 of the control rats received Bay g 6575 (20 mg/kg orally) for 6 days each week throughout the whole study period (9-11 months). From these animals aorta was removed for prostacyclin bioassay based upon its platelet aggregation inhibitory effect. The diabetic rats treated with Bay g 6575 released significantly more prostacyclin than the controls (p less than 0.005). Our study suggests further experiments in other animal models more susceptible to diabetic vascular lesions than the rat model to evaluate the possible beneficial role of the treatment with Bay g 6575.
We report the use of bilateral thalamic stimulation in a case of primary erythromelalgia with imm... more We report the use of bilateral thalamic stimulation in a case of primary erythromelalgia with immediate and important pain relief for 3 years. A 12-year-old boy experiencing primary erythromelalgia had a 4-year history of recurrent attacks of severe burning pain in both feet, accompanied by local reddening, swelling, and heating of the skin. The attacks were triggered by warmth and exercise. The pain was relieved only by elevation and cooling of the lower limbs, which he achieved by immersing his legs in a bucket of ice water, resulting in severe ulceration of the skin. Because of the gradual aggravation of the signs and symptoms and resistance of the patient&amp;amp;amp;amp;amp;amp;amp;amp;#39;s condition to several medical therapies, the patient received spinal cord stimulation. The implants were removed twice because of recurrent infection. Finally, the patient was treated with bilateral electrical stimulation of the ventral posterolateral thalamic nucleus, which resulted in important pain control until 3 years later. The patient was able to avoid water immersions, and all ulcerations disappeared. We conclude that thalamic stimulation was successful in this case of primary erythromelalgia.
To cite this article: Ulrichts H, Harsfalvi J, Bene L, Matko J, Vermylen J, Ajzenberg N, Baruch D... more To cite this article: Ulrichts H, Harsfalvi J, Bene L, Matko J, Vermylen J, Ajzenberg N, Baruch D, Deckmyn H, Tornai I. A monoclonal antibody directed against human von Willebrand factor induces type 2B-like alterations. J Thromb Haemost 2004; 2: 1622-28.
This review briefly describes the development of the concepts of antiphospholipid antibody and of... more This review briefly describes the development of the concepts of antiphospholipid antibody and of antiphospholipid syndrome. It focuses on the two main antigenic targets, beta2 glycoprotein I and prothrombin. An excessive production of natural antibodies rather than an immune response to exogenous antigen is proposed as pathogenetic for the development of these antibodies. The review attempts to explain how some of these antibodies are anticoagulant in vitro yet prothrombotic in vivo. The final section discusses when to test for such antibodies, how to test and how to consider treatment of patients with the antiphospholipid syndrome.
Journal of the American College of Cardiology, 1986
Further progress in the search for more effective but safe antithrombotic agents is coupled to an... more Further progress in the search for more effective but safe antithrombotic agents is coupled to an improved understanding of the factors involved in arterial and venous thrombogenesis. Although arterial thrombosis is initiated by formation of a layer of platelets on modified endothelium or subendothelial constituents and subsequent recruitment of passing-by platelets, this phenomenon is not sufficient to lead to a full thrombus. Further growth of such a platelet mass depends, to a large extent, on the presence of free thrombin. Thrombin is mainly generated by activation of factor XI on the platelet contact with collagen. In addition, thrombin leads to formation of fibrin, which maintains the stability of the arterial platelet thrombus and is the main component of the venous thrombus. The search for agents that inhibit platelet activation and thrombin formation is, therefore, a logical endeavor.
We compared the dietary habits, fatty acid composition of plasma and platelet phospholipids, and ... more We compared the dietary habits, fatty acid composition of plasma and platelet phospholipids, and platelet function in two groups of healthy Belgian male subjects, known to differ in their mortality rate from coronary heart disease (CHD). In the Walloon subjects, there was a larger intake of saturated and a lower intake of (n-6) polyunsaturated fats, confirmed by the fatty acid composition of plasma and platelet phospholipids. While plasma HDL and total cholesterol were similar in the present samples of the two communities, platelet aggregation to epinephrine was significantly higher in the Walloon subjects. When the two populations were divided into younger (28-54 years) and older (55-73 years) age groups, the older Walloon subjects exhibited platelet hyper-aggregability to most of the agonists, compared to the other three groups. In addition to dietary fats, alcohol and smoking habits, age was an important determinant of platelet phospholipid fatty acids and platelet reactivity. The present results reinforce those of previous studies, indicating that platelet behaviour is significantly affected by the main risk factors for CHD.
Background The regulator of G-protein signalling-2 (RGS2) is a key factor in adipogenesis. We hyp... more Background The regulator of G-protein signalling-2 (RGS2) is a key factor in adipogenesis. We hypothesized that the metabolic syndrome, of which obesity is an important component, might be related to genetic variation in RGS2.
carriers had an odds ratio for elevated blood pressure of 1.93 (95%CI: 1.30-2.86). Finally, women... more carriers had an odds ratio for elevated blood pressure of 1.93 (95%CI: 1.30-2.86). Finally, women double heterozygous for Thr164Ile and Gln27Glu versus non-carriers at all 3 loci had an odds ratio for elevated blood pressure of 2.49 (1.28-4.85). In men, blood pressure was not influenced consistently by this genetic variation.
The role of plasminogen activator inhibitor-1 (PAI-1) in the plasma, blood platelets, and vessel ... more The role of plasminogen activator inhibitor-1 (PAI-1) in the plasma, blood platelets, and vessel wall during acute arterial thrombus formation was investigated in gene-deficient mice. Photochemically induced thrombosis in the carotid artery was analyzed via transillumination. In comparison to thrombosis in C57BL/6J wild-type (wt) mice (113 +/- 19 x 10(6) arbitrary light units [AU] n = 15, mean +/- SEM), thrombosis in PAI-1(-/-) mice (40 +/- 10 x 10(6) AU, n = 13) was inhibited (P <.01), indicating that PAI-1 controls fibrinolysis during thrombus formation. Systemic administration of murine PAI-1 into PAI-1(-/-) mice led to a full recovery of thrombotic response. Occurrence of fibrinolytic activity was confirmed in alpha(2)-antiplasmin (alpha(2)-AP)-deficient mice. The sizes of thrombi developing in wt mice, in alpha(2)-AP(+/-) and alpha(2)-AP(-/-) mice were 102 +/- 35, 65 +/- 8.1, and 13 +/- 6.1 x 10(6) AU, respectively (n = 6 each) (P <.05), compatible with functional plasmin...
Congenital disorders of glycosylation (CDG) type I are mostly due to a deficient phosphomannomuta... more Congenital disorders of glycosylation (CDG) type I are mostly due to a deficient phosphomannomutase activity, called CDG Ia. CDG IIa (mutations in the MGAT2 gene) results from a deficient activity of the Golgi enzyme N-acetylglucosaminyltransferase II. CDG Ia patients predominantly have a thrombotic tendency, whereas our CDG IIa patient has an increased bleeding tendency, despite similar coagulation factor abnormalities in both types. We have investigated whether abnormally glycosylated platelet membrane glycoproteins are involved in the haemostatic complications of both CDG groups. In flow cytometry, the binding of Ricinus communis lectin (reactive with beta-galactose primarily) to control platelets increased after neuraminidase treatment: this increase was smaller (p < 0.01) in CDG Ia patients (3.1 +/- 0.08 times) than in control platelets (8.5 +/- 1.8 times) and did not occur in the CDG IIa patient. Platelet-rich plasma from CDG Ia patients, but not a CDG IIa patient. aggregat...
MK-383 (L-tyrosine, N-(n-butylsulfonyl)-O-[4-butyl(4-piperidinyl)], monohydrochloride monohydrate... more MK-383 (L-tyrosine, N-(n-butylsulfonyl)-O-[4-butyl(4-piperidinyl)], monohydrochloride monohydrate) is a potent and specific platelet fibrinogen receptor antagonist that may be useful in preventing processes that lead to occlusive thrombus formation in the lumen of the blood vessel. Two placebo-controlled phase I trials were completed in 56 healthy volunteers to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of MK-383 administered as 1- and 4-hour infusions in the presence and absence of aspirin. When administered to healthy male subjects by constant infusions up to 0.4 microgram/kg/min over 1 hour or up to 0.2 microgram/min over 4 hours, it provided a well-tolerated reversible means of inhibiting platelet function. At infusion rates of 0.25 and 0.15 microgram/kg/min for 1 and 4 hours, respectively, MK-383 extended baseline bleeding time by 2.0- to 2.5-fold and inhibited adenosine diphosphate (ADP)-induced platelet aggregation by at least 80%. The pharmacokinetics of MK-383 include a mean plasma clearance of 329 ml/min, steady-state volume of distribution of 76 L, and half-life of 1.6 hours. The percentage of dose excreted in the urine was 37%. Correlations between MK-383 plasma concentration (C) and inhibition of platelet aggregation were examined by fitting with a sigmoid maximum-effect model. The plasma concentration yielding 50% inhibition (C50) for MK-383 in healthy volunteers is approximately 13 ng/ml, with a Hill coefficient &gt; 5. Based on a naive pooled analysis, an exponential empirical model best describes the MK-383 C-extension of template bleeding time (BTE) relationship. The model indicates that the MK-383 plasma concentration necessary to double BTE is approximately 30 ng/ml (i.e., 2.5-fold greater than the C50 for ADP-induced inhibition of platelet aggregation). The pharmacokinetics of MK-383 was unaffected by pretreatment with 325 mg aspirin 1 day before and 1 hour before infusion. Conversely, aspirin pretreatment reduced C50 and increased bleeding time extension, suggesting that aspirin may have an additive effect with respect to inhibition of platelet function. Based on the putative role of the fibrinogen receptor in thrombotic processes and an acceptable human pharmacokinetic-pharmacodynamic profile, MK-383 should be evaluated in patients with unstable angina.
Several reports describing outbreaks of hepatitis A in hemophilia A patients transfused with solv... more Several reports describing outbreaks of hepatitis A in hemophilia A patients transfused with solvent/detergent-treated factor VIII concentrates have raised concern about possible transmission of hepatitis A by these concentrates. We recently witnessed such an outbreak of hepatitis A in 6 hemophilia A patients; review of the clinical data did not disclose any increased risk factor for community-acquired hepatitis A. A case-control study comparing the prevalence of anti-hepatitis A IgG antibodies in hemophiliacs and age-matched controls showed a lower seroprevalence in hemophiliacs. This might be due to passive protection acquired through transfusion of the previously used immunoglobulin-containing cryoprecipitate. The outbreak of hepatitis A could be explained as a catch-up phenomenon linked to the loss of passive protection with the use of purer factor VIII concentrates.
It has been shown by several authors (1, 2, 3, 4, 5) that bovine plasma and different preparation... more It has been shown by several authors (1, 2, 3, 4, 5) that bovine plasma and different preparations of purified bovine fibrinogen aggregate human platelets. This activity was absent in bovine serum and in the supernatants of either bovine plasma or purified bcvine fibrinogen heated at 56°C for 30 minutes (5). Furthermore, bovine fibrinogen preparations, rendered incoagulable by extensive plasmin degradation, no longer produced platelet aggregation (6). All these findings suggested that bovine fibrinogen itself was respcnsible for the aggregation. However, fcllcwing gel filtration on 6% agarose, purified bovine fibrinogen was eluted as a single protein peak, which, although clottable, was devoid of aggregating activity (7). Forbes et al. (8) have reported that commercial preparations of bovine and porcine antihemophilic globulin had a platelet aggregating activity, which appeared to be related to the fibrinogen fraction. Very recently, however, the same authors (9) have suggested that animal factor VIII, separated by gel filtration on Sepharose 4B a would be responsible for the observed aggregation. X ResearchFellow of the Katholieke Universiteit te Leuven, 1972.
Human platelet-rich plasma clotted by reptilase does not retract. This seems to be due to the lac... more Human platelet-rich plasma clotted by reptilase does not retract. This seems to be due to the lack of activation of platelets exposed to this enzyme rather than to the incomplete hydrolysis of fibrinogen. Indeed, when aggregating agents such as ADP, collagen, adrenaline or Thrombofax are preincubated with unstirred PRP before adding reptilase, strong clot retraction occurs. A number of antiaggregating compounds has been evaluated in this test system.
It was the aim of the present study to perform a systematic review of the published studies that ... more It was the aim of the present study to perform a systematic review of the published studies that estimated the prevalence of non-responders to aspirin, as assessed by the closure time of PFA-100, a point-of-care device, and to analyse: 1) some major clinical and methodological factors that can influence it and 2) its possible association with vascular outcomes. The prevalence of non-responders to aspirin in 64 populations from 53 studies, comprising 6,450 subjects, had a median value of 0.27. A higher number of aspirin non-responders was found among older patients, those with acute vascular events, or those treated for more than one month. Aspirin non-response was more frequently associated with the use of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;home-established&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; cut-offs or when closure time was only assessed after aspirin (rather than both before and after). Among risk factors, type 2 diabetes appeared to be associated with a higher prevalence of aspirin non-responders. The latter was also higher in less recent publications and in studies that used 3.2% rather than 3.8% Na-citrate as an anticoagulant. In eight studies comprising 847 subjects, aspirin non-responders were more likely to have vascular events than responders (relative risk: 1.63; 95% CI 1.16-2.28). In conclusion, although there appears to be heterogeneity among the studies analysed, this review indicates that about one quarter of people receiving aspirin would be identified--as an average--as aspirin non-responders by PFA-100. As this is a simple, widely available point-of-care test, efforts to better standardize it and to control for its major methodological variables might be useful to improve monitoring of platelet performance under aspirin treatment and to firmly establish the observed association with clinical vascular events.
Patients with a microdeletion on chromosome 22q11 demonstrate the clinical picture of the velocar... more Patients with a microdeletion on chromosome 22q11 demonstrate the clinical picture of the velocardiofacial syndrome. We report on three members of the same family with this microdeletion and velocardiofacial syndrome, all having an increase in platelet size and a mild decrease in platelet number. Their platelet function, however, tested by aggregation and by adherence to collagen in a whole blood perfusion system, was normal. We retrospectively studied the files of 35 other patients with 22q11 deletion and also found that their platelets had an increased size compared with cardiac controls. Moreover, their platelet size correlated negatively with platelet number. Knowing that patients with 22q11 deletion are obligate carriers for a heterozygous glycoprotein Ib beta deletion, these patients can be considered to be heterozygous Bernard-Soulier patients. In addition, a significant increase in platelet size may be a positive predictor for the clinical diagnosis of the velocardiofacial syndrome.
The case of an 11-year-old boy with grey platelet syndrome is described. Platelets had the typica... more The case of an 11-year-old boy with grey platelet syndrome is described. Platelets had the typical grey and ghostly appearance on May-Grünwald/Giemsa staining, caused by the absence of alpha granules confirmed by electron microscopy. Alpha granule protein content, i.e., beta-thromboglobulin and platelet factor 4, was less than 3% of normal and alpha granule secretion in response to thrombin was not detectable photometrically. The plasminogen activator inhibitor-1 pool in the patient&#39;s platelets was 5% of normal, confirming previous indirect evidence for the storage of this protein within the alpha-granule. Dense body secretion of adenosine triphosphate and 5-hydroxytryptamine was normal. Aggregation occurred normally in response to adenosine diphosphate and there was a slight delay in response to collagen.
Pathophysiology of Haemostasis and Thrombosis, 1981
10 male Wistar rats were made diabetic by an intravenous injection of streptozotocin. 10 sex and ... more 10 male Wistar rats were made diabetic by an intravenous injection of streptozotocin. 10 sex and age-matched rats served as control animals. 5 of the diabetic and 5 of the control rats received Bay g 6575 (20 mg/kg orally) for 6 days each week throughout the whole study period (9-11 months). From these animals aorta was removed for prostacyclin bioassay based upon its platelet aggregation inhibitory effect. The diabetic rats treated with Bay g 6575 released significantly more prostacyclin than the controls (p less than 0.005). Our study suggests further experiments in other animal models more susceptible to diabetic vascular lesions than the rat model to evaluate the possible beneficial role of the treatment with Bay g 6575.
We report the use of bilateral thalamic stimulation in a case of primary erythromelalgia with imm... more We report the use of bilateral thalamic stimulation in a case of primary erythromelalgia with immediate and important pain relief for 3 years. A 12-year-old boy experiencing primary erythromelalgia had a 4-year history of recurrent attacks of severe burning pain in both feet, accompanied by local reddening, swelling, and heating of the skin. The attacks were triggered by warmth and exercise. The pain was relieved only by elevation and cooling of the lower limbs, which he achieved by immersing his legs in a bucket of ice water, resulting in severe ulceration of the skin. Because of the gradual aggravation of the signs and symptoms and resistance of the patient&amp;amp;amp;amp;amp;amp;amp;amp;#39;s condition to several medical therapies, the patient received spinal cord stimulation. The implants were removed twice because of recurrent infection. Finally, the patient was treated with bilateral electrical stimulation of the ventral posterolateral thalamic nucleus, which resulted in important pain control until 3 years later. The patient was able to avoid water immersions, and all ulcerations disappeared. We conclude that thalamic stimulation was successful in this case of primary erythromelalgia.
To cite this article: Ulrichts H, Harsfalvi J, Bene L, Matko J, Vermylen J, Ajzenberg N, Baruch D... more To cite this article: Ulrichts H, Harsfalvi J, Bene L, Matko J, Vermylen J, Ajzenberg N, Baruch D, Deckmyn H, Tornai I. A monoclonal antibody directed against human von Willebrand factor induces type 2B-like alterations. J Thromb Haemost 2004; 2: 1622-28.
This review briefly describes the development of the concepts of antiphospholipid antibody and of... more This review briefly describes the development of the concepts of antiphospholipid antibody and of antiphospholipid syndrome. It focuses on the two main antigenic targets, beta2 glycoprotein I and prothrombin. An excessive production of natural antibodies rather than an immune response to exogenous antigen is proposed as pathogenetic for the development of these antibodies. The review attempts to explain how some of these antibodies are anticoagulant in vitro yet prothrombotic in vivo. The final section discusses when to test for such antibodies, how to test and how to consider treatment of patients with the antiphospholipid syndrome.
Journal of the American College of Cardiology, 1986
Further progress in the search for more effective but safe antithrombotic agents is coupled to an... more Further progress in the search for more effective but safe antithrombotic agents is coupled to an improved understanding of the factors involved in arterial and venous thrombogenesis. Although arterial thrombosis is initiated by formation of a layer of platelets on modified endothelium or subendothelial constituents and subsequent recruitment of passing-by platelets, this phenomenon is not sufficient to lead to a full thrombus. Further growth of such a platelet mass depends, to a large extent, on the presence of free thrombin. Thrombin is mainly generated by activation of factor XI on the platelet contact with collagen. In addition, thrombin leads to formation of fibrin, which maintains the stability of the arterial platelet thrombus and is the main component of the venous thrombus. The search for agents that inhibit platelet activation and thrombin formation is, therefore, a logical endeavor.
We compared the dietary habits, fatty acid composition of plasma and platelet phospholipids, and ... more We compared the dietary habits, fatty acid composition of plasma and platelet phospholipids, and platelet function in two groups of healthy Belgian male subjects, known to differ in their mortality rate from coronary heart disease (CHD). In the Walloon subjects, there was a larger intake of saturated and a lower intake of (n-6) polyunsaturated fats, confirmed by the fatty acid composition of plasma and platelet phospholipids. While plasma HDL and total cholesterol were similar in the present samples of the two communities, platelet aggregation to epinephrine was significantly higher in the Walloon subjects. When the two populations were divided into younger (28-54 years) and older (55-73 years) age groups, the older Walloon subjects exhibited platelet hyper-aggregability to most of the agonists, compared to the other three groups. In addition to dietary fats, alcohol and smoking habits, age was an important determinant of platelet phospholipid fatty acids and platelet reactivity. The present results reinforce those of previous studies, indicating that platelet behaviour is significantly affected by the main risk factors for CHD.
Background The regulator of G-protein signalling-2 (RGS2) is a key factor in adipogenesis. We hyp... more Background The regulator of G-protein signalling-2 (RGS2) is a key factor in adipogenesis. We hypothesized that the metabolic syndrome, of which obesity is an important component, might be related to genetic variation in RGS2.
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Papers by Jos Vermylen