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Biomedical subjects

H K Breddin

Publications and source records attributed to H K Breddin.

At least 37 records · Page 2Linked to original sources
PubMed2000

Prophylaxis and treatment of deep-vein thrombosis.

In 1980, unfractionated heparin (UFH) was the established agent for the prophylaxis of venous thromboembolic (VTE) disease in patients undergoing general surgery. VTE prophylaxis was the first indication in which low-molecular-weight heparins (LMWHs) were tested. Approximately 40 trials have demonstrated that LMWHs are at least as effective and safe as UFH. LMWHs exhibit a number of advantages over UFH, including ease of administration, convenient once-daily dosing, and facilitation of outpatient management. The ideal time of administration and the dose of the initial one or two injections of LMWH remain unresolved issues. LMWHs are used with increasing frequency in the treatment of acute deep vein thrombosis (DVT), having been studied in comparison to UFH in 16 major clinical trials. LMWHs are at least as effective as UFH in the prevention of VTE, but higher doses than those used for prophylaxis are required. There is still an ongoing debate about whether the daily dose should be administered in one or two subcutaneous injections. In some recent studies, symptomatic new DVTs or pulmonary emboli (PE) were the primary end points, which had to be verified by objective methods, but such end points may be not be sensitive enough to detect major differences in the efficacy of different LMWHs.

Clinical Trials as Topic↗
PubMed2000

Ex vivo--in vitro interaction between aspirin, clopidogrel, and the glycoprotein IIb/IIIa inhibitors abciximab and SR121566A.

OBJECTIVES: To assess the interaction between aspirin and clopidogrel in healthy male volunteers and the interaction of the glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors abciximab and SR121566A with blood from those pretreated subjects (ex vivo-in vitro). METHODS: Aspirin (300 mg/day), clopidogrel (75 mg/day), or the combination of both drugs were administered orally for 8 days. Group 1 (n = 5) started with aspirin and group 2 (n = 5) with clopidogrel. From day 4 to day 8, subjects of both groups received the combined treatment. Blood from these subjects was spiked with abciximab (0.5 and 1.5 microg x mL(-1)) and SR121566A (31 and 62 ng x mL(-1)). RESULTS: In vivo, average bleeding times were 6.8 minutes at baseline, 20.3 minutes for clopidogrel alone (P < .01), 10.9 minutes for aspirin alone (difference not significant), and 24.0 minutes (P < .01) for the combined treatment. Fibrinogen binding to the platelet GPIIb/IIIa receptor was reduced for aspirin to 69% (difference not significant), to 63% for clopidogrel (difference not significant), and to 63% for the clopidogrel plus aspirin combination (P < .01). CD62 expression as a marker of platelet granular secretion was reduced to 66% by clopidogrel (P < .01) and to 41% by the combination of clopidogrel and aspirin; aspirin alone had no effect. In vitro, with pretreatment with aspirin and clopidogrel, inhibitory effects of the GPIIb/IIIa inhibitors on fibrinogen binding were additive to changes observed with aspirin or clopidogrel alone. No effect on CD62 expression was observed with either GPIIb/IIIa inhibitor. Aspirin and clopidogrel reinforced effects of the GPIIb/IIIa inhibitors on adenosine diphosphate (5 micromol/L)-induced aggregation in an additive manner, a supra-additive effect was observed with collagen (2 microg x mL(-1))-induced aggregation. CONCLUSION: The augmentation of the antiaggregatory effects of GPIIb/IIIa inhibitors by aspirin and clopidogrel and the lack of antisecretory effects of GPIIb/IIIa inhibitors may favor their combination with clopidogrel.

Abciximab↗
PubMed1999

Pharmacokinetics and pharmacodynamic effects of a new antibody glycoprotein IIb/IIIa inhibitor (YM337) in healthy subjects.

BACKGROUND: This study describes the first administration of YM337, the Fab fragment of a humanized monoclonal antibody against the fibrinogen GP IIb/IIIa receptor, in healthy male humans. METHODS AND RESULTS: Platelet aggregation (20 micromol/L ADP), platelet adhesion, fibrinogen binding, bleeding time, and YM337 concentrations in plasma were studied in substudy 1 after single boluses of 0.025, 0. 05, 0.1, 0.2, and 0.4 mg/kg YM337 and in substudy 2 after a bolus (0. 35 mg/kg) plus 6 hours of infusion at different dose levels of YM337 (0.5, 0.75, 1.0, 1.5 microg. kg(-1) x min(-1)), with abciximab as reference drug (n=5 or 6 subjects per group). After the 0.2-mg/kg and 0.4-mg/kg boluses, fibrinogen binding was reduced by >80% and bleeding time was prolonged to approximately 60 minutes. Bolus followed by infusion of 1.0 and 1.5 microg x kg(-1) x min(-1) YM337 maintained inhibition of platelet aggregation >80%. Aggregation and bleeding time returned to normal within 24 hours. A bolus of 0.25 mg/kg of abciximab followed by an infusion of 0.125 microg x kg(-1) x min(-1) showed effects similar to those observed with the 0.5- and 0. 75-microg x kg(-1) x min(-1) infusion of YM337. In 53 subjects exposed to YM337, 1 case of transient thrombocytopenia and 3 minor bleeding events occurred. No human anti-chimeric antibodies were detected 2 weeks and 2 months after administration. CONCLUSIONS: YM337 effectively inhibits IIb/IIIa-mediated platelet aggregation and adhesion in humans. The results of this phase 1 study will give rise to further clinical evaluation of YM337.

Abciximab↗
PubMed1999

Spontaneous platelet aggregation as a predictive risk factor for vascular occlusions in healthy volunteers? Results of the HAPARG Study. Haemostatic parameters as risk factors in healthy volunteers.

The HAPARG Study (haemostatic parameters as risk factors in healthy volunteers) was performed in a subset of volunteers taking part in the MARISK Study (Mainzer Risikoindikatoren Studie für die koronare Herzkrankheit) sponsored by the German Ministry of Research and started in 1984. A previous study (Yamanishi et al., Thromb Haemostas 1985;54:539-543) had shown that spontaneously enhanced platelet aggregation as measured with the PAT-III-test and higher fibrinogen concentrations are significant risk factors for new vascular occlusions in diabetic patients. It was the aim of the HAPARG Study to establish whether spontaneous platelet aggregation and other hemostatic variables are independent risk factors for vascular occlusions in healthy volunteers. Employees of a chemical/pharmaceutical company aged 40-65 years and personnel of the University of Mainz, aged 30-60 years were included in this prospective study. Besides anamnestic data such as on smoking, hypertension and diabetes, blood pressure, the ankle/arm Doppler-index and an ECG were recorded and serum cholesterol, HDL, LDL, triglycerides, uric acid and glucose were measured. Men (1884) and women (989) entered the study and were followed for 4-6 years. In the age group of 30-50 years, more women than men were included. During the observation period 53 vascular occlusions occurred (36 coronary and nine cerebral events and eight peripheral vascular occlusions). Only three of these endpoints occurred in women. Besides age (odds ratio = 1.7, P = 0.02) and gender as expected risk factors, the multivariate logistic stepwise regression analysis revealed smoking (odds ratio = 2.2, P = 0.008), lower HDL-levels (odds ratio = 2.2, P = 0.013), elevated diastolic blood pressure (odds ratio = 1.4. P = 0.004) followed by spontaneous platelet aggregation (odds ratio = 1.1, P = 0.037), and slightly elevated blood glucose (P = 0.0047) as significant risk factors for men. Higher fibrinogen levels missed significance in this analysis (P = 0.059). None of the other hemostatic parameters showed a significant correlation with the vascular events. To our knowledge, this has been the first prospective trial in a large population of healthy individuals in which a platelet function parameter has been studied together with other possible risk factors. Spontaneously enhanced platelet aggregation is probably an independent risk factor and, like elevated fibrinogen and other haemostatic variables, an indicator of an ongoing active atherosclerotic process.

Adult↗
PubMed1999

Comparative study on the in vitro and in vivo activities of heparinoids derivative investigated on the animal model.

In this study we compared the antithrombotic and anticoagulant properties of sodium and calcium derivatives of pentosan polysulfate (Na-PPS, Ca-PPS), unfractionated heparin (UFH), and low-molecular-weight heparin (Fraxiparin). The antithrombotic effects of these agents have been investigated in an experimental thrombosis model in which rat mesenteric venules with a diameter of 20-30 microm were injured by well-defined argon laser lesions. Furthermore, the in vivo and in vitro anticoagulant activities [activated partial thromboplastin time (aPTT), Heptest] of these agents have been studied. Thrombus formation was significantly inhibited after s.c. injection of Na-PPS and Ca-PPS in doses >10 mg/kg. The duration of the antithrombotic effect lasted 8 h for Na-PPS and 12 h for Ca-PPS. After oral administration of Na-PPS, an antithrombotic effect was not observed. Oral application of Ca-PPS in doses >20 mg/kg significantly inhibited thrombus formation. Na-PPS and Ca-PPS markedly prolonged clotting time in aPTT and Heptest in concentrations ranging from 0.01 to 0.2 mg/ml rat PTT. Two h after s.c. administration of these agents in a dose of 10 mg/kg, the aPTT increased threefold and the Heptest 2.5-fold compared with controls. After oral application of 50 mg/kg Na-PPS and Ca-PPS, no effect on the coagulation test could be measured. Intravenous injection of UFH prolonged the Heptest after 1 min and the aPTT after 30 min. In ex vivo studies of aPTT and Heptest performed in rat plasma between 2 and 24 h after s.c. injection of 0.2 mg/kg Fraxiparin, no inhibition of any coagulation test was measured. The antithrombotic effect of 0.2 mg/kg Fraxiparin after s.c. injection was significant. Intravenous injection of 20 U/kg UFH significantly inhibited thrombus formation. The smallest antithrombotic effect was after i.v. injection of UFH.

Animals↗
PubMed1999

Effects of aprosulate, a novel synthetic glycosaminoglycan, on coagulation and platelet function parameters: a prospective, randomized phase I study.

In a phase I clinical trial the effect of the highly sulfated polyanion "Aprosulate" was studied in healthy volunteers using different coagulation and platelet function parameters. Eighteen healthy volunteers aged 21 to 30 years received two single subcutaneous doses of aprosulate (0.5 mg/kg body weight; 1.0 mg/kg body weight), or unfractionated heparin (Calciparin 7,500 IU). The washout period between the different drugs/doses was at least 7 days. Coagulation and platelet function parameters (activated partial thromboplastin time, Heptest, fibrinogen, von Willebrand factor, ristocetin cofactor, platelet adhesion to siliconized glass, and platelet-induced thrombin generation time [a new method for measuring thrombin generation in platelet-rich plasma in the presence of platelets]) were assessed during 24 hours after each injection. Aprosulate led to a significant and dose-dependent prolongation of activated partial thromboplastin time and Heptest. This effect lasted for 4 hours (activated partial thromboplastin time) to 8 hours (Heptest). Activated partial thromboplastin time was not prolonged after the injection of unfractionated heparin (7,500 IU). Fibrinogen, von Willebrand factor, and ristocetin cofactor remained unchanged with both drugs. Platelet induced thrombin generation time was slightly prolonged and platelet adhesion was slightly diminished up to 2 hours using 0.5 mg/kg aprosulate, and up to 4 hours using 1.0 mg/kg aprosulate while the platelet induced thrombin generation time system was not influenced by the subcutaneous injection (7,500 IU) of unfractionated heparin. Both drugs and doses were well tolerated. Plasma transaminase concentrations alanin aminotransferase and aspartate aminotransferase serum values were slightly increased in some volunteers but returned to normal during or after the study (< 4 weeks). Further clinical trials will have to establish whether aprosulate is an effective drug for the prophylaxis of deep venous thrombosis.

Adolescent↗
PubMed1999

Experimental studies on the anticoagulant and antithrombotic effects of sodium and calcium pentosan polysulphate.

In the present study we have compared the antithrombotic and anticoagulant properties of sodium and calcium derivatives of pentosan polysulphate (Na-PPS, Ca-PPS). The antithrombotic effect of these agents have been investigated in an experimental thrombosis model in which rat mesenteric venules diameter of 20-30 microm were injured by well defined Argon laser lesions. Furthermore, the in vivo and in vitro anticoagulant activities (aPTT, Heptest) of these agents have been studied. Thrombus formation was significantly inhibited after s.c. injection of Na-PPS and Ca-PPS in doses above 10 mg/kg. The duration of the antithrombotic effect lasted 8 h for Na-PPS and 12 h for Ca-PPS. After oral administration of Na-PPS an antithrombotic effect was not observed. Oral application of Ca-PPS in doses higher than 20 mg/kg significantly inhibited thrombus formation. Na-PPS and Ca-PPS markedly prolonged clotting time in aPTT and Heptest in concentrations ranging from 0.01 to 0.2 mg/ml rat PTT. Two h after s.c. administration of these agents in a dose 10 mg/kg, the aPTT increased 3-fold and Heptest 2.5-fold compared to controls. After oral application of 50 mg/kg Na-PPS and Ca-PPS no effect on coagulation test could be measured.

Animals↗
PubMed1999

Preclinical biochemistry and pharmacology of low molecular weight heparins in vivo--studies of venous and arterial thrombosis.

Low molecular weight heparins (LMWHs) are effective agents in both venous and arterial thrombosis. Extensive preclinical studies in various animal models show that there are substantial differences in antithrombotic efficacy between LMWHs, and that the relative efficacy of individual agents depends on the thrombogenic stimulus used. Relative efficacy cannot be predicted on the basis of molecular weight, nor on the basis of anti-factor Xa or anti-factor IIa potency. This suggests that other mechanisms of action, e.g., the release of tissue factor pathway inhibitor (which differs among the LMWHs), are important. Data obtained with a specific LMWH cannot be extrapolated to other compounds within the same class and their substitution in the clinical setting is, therefore, inappropriate.

Animals↗
PubMed1999

Low molecular weight heparins in the prevention of deep-vein thrombosis in general surgery.

Unfractionated heparin (UFH) was the established treatment in the early 1980s for the prophylaxis of venous thromboembolic disease (VTED) in patients undergoing general surgery. This was one of the earliest indications in which low molecular weight heparins (LMWHs) were tested, and about 40 trials have revealed that these agents are at least as effective and safe as UFH with a tendency of superiority when higher dosages are used. In most trials, the fibrinogen uptake test has been used to assess the frequency of deep vein thrombosis. LMWHs exhibit a number of improved features over UFH, including ease of administration and convenient once daily dosing, facilitating outpatient management. A still open question is the ideal time and dose of the first one or two injections of a LMWH. To determine the clinical relevance of product differentiation further, clinical trials, directly comparing different LMWHs, are required.

Dalteparin↗
PubMed1999

[Antithrombotic therapy and follow-up of peripheral arterial occlusive disease].

In patients with arterial occlusive disease the following antithrombotic drugs are used to prevent new arterial thromboses: Unfractionated heparin (UFH) and low molecular weight heparins (LMWH): UFH is frequently used perioperatively in patients with vascular reconstructions and after peripheral percutaneous transluminal angioplasty (PTA). Only one study on the longterm use of a LMWH after operative revascularization has been published, where LMWH led to an increased patency rate in comparison to acetylsalicylic acid + dipyridamol. Vitamin-K-antagonists were effective in the prevention of new vascular occlusions in studies published in the 1970ies. Platelet function inhibitors (aspirine, ticlopidine and clopidogrel): Aspirine reduced reocclusions after vascular surgery and PTA. Ticlopidine was effective in the Swedish Ticlopidine-Multicenter-Trial in the prevention of ischemic heart disease and also reduced the need for vascular surgery. In the CAPRIE-study clopidogrel reduced myocardial infarctions in patients with peripheral arterial disease in comparison to aspirine.

Angioplasty, Balloon↗
PubMed1998

A supersulfated low-molecular-weight heparin (IK-SSH) increases plasma levels of free and total tissue factor pathway inhibitor after intravenous and subcutaneous administration in humans.

Unfractionated as well as low-molecular-weight heparins (LMWH) are known to cause an increase in blood levels of tissue factor pathway inhibitor (TFPI). To study the effect of a newly developed supersulfated LMWH (IK-SSH, Iketon Farmaceutici) on TFPI concentrations in human plasma, the compound was injected into volunteers at doses of 0.14, 0.33 and 0.66 mg/kg intravenously or 0.33, 0.66 and 1.0 mg/kg subcutaneously. At certain known times blood was drawn and plasma levels of both total and free TFPI were measured using enzyme-linked immunosorbent assay methodology. Baseline plasma concentrations of TFPI were 72.2+/-3.1 ng/ml for total and 10.8+/-0.8 ng/ml for free TFPI. Intravenous or subcutaneous injection of IK-SSH led to a strong and long-lasting rise in TFPI levels which were increased more than 5-fold for total TFPI and more than 30-fold for free TFPI. Maximum TFPI levels were reached 5-10 min after intravenous and 60 min after subcutaneous administration. IK-SSH caused prolongation of ex-vivo clotting times in the APTT and Heptest assay, whereas thrombin time was not affected. Anticoagulant actions of IK-SSH showed a significant correlation to plasma concentrations of TFPI and they are thought to be based at least partially on the release of TFPI from vascular sites.

Adult↗
PubMed1998

Efficacy of a low molecular weight heparin administered intravenously or subcutaneously in comparison with intravenous unfractionated heparin in the treatment of deep venous thrombosis. Certoparin-Study Group.

BACKGROUND: The main objective of the study presented was to test if thrombus regression can be improved by treatment with an intravenously or subcutaneously administered low molecular weight heparin (LMWH). Patients with acute deep vein thrombosis were randomly assigned to receive either intravenous UFH (131 patients), intravenous (i.v.) LMWH (128 patients), or 8000 IU of the same LMWH bid subcutaneously (s.c.) (128 patients). All patients were treated with heparin for 14 to 16 days. Vitamin-K-antagonist prophylaxis was started between Day 12 and Day 14 after enrollment into the study. METHODS: Phlebographies and perfusion/ventilation lung scans were performed at baseline and on Days 12 to 16. Primary endpoint of the study was a reduction of the phlebographic Marder score. Secondary endpoints were recurrent thrombosis and pulmonary embolism (PE), major and minor bleedings and the rate of PE at inclusion and at the end of the study assessed by ventilation/perfusion scans. RESULTS: The Marder score improved by at least 30% in 32.4% (95% CI: 22.6 ... 42.2) of the patients receiving UFH, in 34.0% (95% CI: 24.9 ... 44.0) receiving LMWH i.v. and in 42.6% (95% CI: 32.8 ... 52.8) treated with the low molecular weight heparin s.c. The difference between LMWH s.c. and UFH was 10.2% (95% CI: -3.7% ... +24.5%) (p = 0.11). PE with clinical signs confirmed by objective methods occurred in three patients of the UFH group, one of whom died and was not observed in patients of the i.v. or s.c. LMWH-groups. During the first 15 days no patient receiving UFH or i.v. LMWH, and one patient on s.c. LMWH had a recurrent thrombosis. Major bleedings were observed in four patients receiving i.v. UFH compared to nine patients on i.v. LMWH (one of these patients died) and one patient on s.c. LMWH. Perfusion ventilation lung scans were obtained from 287 patients at baseline and from 246 patients on Days 12-16. PE, defined according to PIOPED-criteria as intermediate or high probability scans, was observed in 38.0% of the patients entering the study and in 18.3% on Days 12 to 16. New asymptomatic PE occurred less frequently in the groups on LMWH (7.1%, 7.5%, respectively) than in the UFH-group (12.6%) (not significant). CONCLUSIONS: S.c. treatment with a LMWH (certoparin) (b.i.d.) is at least as effective as UFH i.v. The hypothesis of increased efficacy of subcutaneous LMWH in resolving venous thrombi will have to be confirmed by an independent study comparing s.c. LMWH with UFH. The i.v. continuous infusion of the LMWH for 12 to 16 days does not result in a higher venous re-opening rate than intravenous standard heparin.

Adolescent↗
PubMed1997

Treatment of deep vein thrombosis: is thrombosis regression a desirable endpoint?

Recent studies on the treatment of acute deep vein thrombosis (DVT) with low-molecular-weight heparins have demonstrated that a certain degree of early recanalization of thrombosed veins can be obtained which is higher than that observed under standard heparin treatment. Thrombolytic treatment of DVT is mainly advocated because a reduction of late sequelae of DVT is expected from early thrombolysis. It has been made likely by several small long-term studies that this expectation is true, but conclusive evidence is still missing. There are also large differences in the reported incidence of late postthrombotic syndrome after acute DVT. It seems likely that there is a minimal reopening rate which is required to be of possible clinical value to the individual patient. A 30% or higher reduction of the Marder score is at present used in several clinical trials as a sign of individual response to the treatment and may prove to be a useful clinical endpoint in these and in future studies. Validated methods to predict the late sequelae of acute DVT, mainly severe postthrombotic syndrome, do not yet exist. Foot plethysmography, air plethysmography, duplex sonography (peak velocity of venous reflux, valve competence), and venous pressure reduction under exercise are possible candidates to be used in future prospective trials. From the existing evidence it is very likely that a marked or total reduction of thrombi will reduce the incidence of postthrombotic syndromes. Clinical studies aiming at a high rate of venous recanalization by prolonged treatment with low-molecular-weight heparins are ongoing.

Heparin, Low-Molecular-Weight↗
PubMed1996

Coronary heart disease, unstable angina, PTCA: new indications for low molecular weight heparins?

Unstable angina in patients with coronary heart disease carries a high risk of myocardial infarction (MI) and death. Partial thrombotic occlusions of coronary arteries are a major causal factor in the development of unstable angina and consecutive thrombotic occlusions may lead to MI. Treatment with unfractionated heparin (UFH) has been shown to significantly reduce the frequency of anginal attacks, but not to affect the frequency of MI, PTCA and death within one month. Prolonged treatment with low molecular weight heparins (LMWHs) may improve the outcome in patients with unstable angina. New clinical studies in this area seem promising. In the prevention of early reocclusions after PTCA LMWHs may be more effective than UFH. Late restenosis after PTCA within 6 months occurs in 25-35% of patients. To date, no effective prophylaxis exists. In a recent trial, short-term treatment with a LMWH had no preventive effect on late restenoses. Ongoing trials with long-term treatment may lead to better results. In the near future long-term treatment, up to six months, with a LMWH alone or in combination with a platelet function inhibitor, possibly with reduced doses of both drugs, may reduce the frequency of restenosis.

Angina, Unstable↗
PubMed1996

Pathophysiology of thromboembolism and its modulation by low-molecular-weight heparins.

Vessel wall damage and changes in hemostatic mechanisms are important factors in thrombogenesis. Vascular damage may be encountered in trauma, inflammatory processes, and other forms of vascular disease. Systemic changes in platelets and in certain coagulation constituents also contribute to thrombus formation. The generation of thrombin seems to be a pivotal event in thrombogenesis, and inactivation of this enzyme has been attempted for many years with heparin, low-molecular-weight heparin, and other glycosaminoglycans. Different forms of heparin may act differently, and the future must more clearly elucidate the role of the endothelium in all of these processes.

Animals↗
PubMed1996

The role of monocytes in the platelet release of von Willebrand factor.

Circulating blood monocytes, which are a source of foam cells contribute to the vascular lesions. Von Willebrand factor (vWF) is an adhesive multimeric glycoprotein that is synthesized only by endothelial cells and megakaryocytes. In the present study we assessed the ability of human platelets to secrete vWF after incubation with blood monocytes in vitro. Monocytes derived from blood of healthy adults were cultured and next incubated with washed platelets. von Willebrand factor antigen (vWF:Ag) was measured in the supernatant by Laurell immunoelectrophoresis. The study showed that Triton X-100 treated platelets released 82-112% of vWF:Ag. The levels of vWF:Ag in the supernatant with untreated platelets and incubated with monocytes without LPS were respectively 36-48% and 45-72%. After incubation washed platelets with LPS stimulated monocytes a significant decrease in vWF:Ag level was observed (7-11%).

Adult↗
PubMed1995

Two different inhibitory effects of pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid on adenosine diphosphate-induced human platelet aggregation.

In the present study, the novel compound pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), which has been shown to inhibit P2x-purinoceptor-mediated contractions in smooth muscle, was investigated for its antagonistic effects on adenosine diphosphate (ADP)-induced human platelet aggregation in platelet-rich plasma (PRP) and in washed platelets, respectively. Suramin served as reference compound. In PRP, suramin (1 mmol/l) was inactive whereas PPADS (1 mmol/l) considerably reduced the extent of aggregation. In contrast, both suramin (1 mmol/l) and PPADS (500 mumol/l) markedly depressed the aggregation of washed platelets. In addition, there was a peculiarity in washed platelets: a delay of onset of platelet aggregation up to 15 min in the presence of PPADS (10-500 mumol/l) and suramin (0.1-1 mmol/l). Thus, in the present study washed platelets were more suited to detect an influence of PPADS and suramin as inhibitors of ADP-induced aggregation, and a delay of onset of aggregation was the most sensitive parameter in this regard. Comparing the effective threshold concentration of PPADS at P2x (1 mumol/l)- and the platelet P2t-purinoceptor, PPADS proves to be P2x-selective.

Adenosine Diphosphate↗