The Action Mechanism of the Purified Platelet Aggregation Principle of Trimeresurus mucrosquamatus Venom

1979 ◽  
Vol 41 (03) ◽  
pp. 475-490 ◽  
Author(s):  
Chaoho Ouyang ◽  
Che-Ming Teng
Keyword(s):  
Platelet Aggregation ◽  
Adenine Nucleotides ◽  
Muscle Relaxants ◽  
Prostaglandin Synthesis ◽  
Action Mechanism ◽  
Crude Venom ◽  
Platelet Factor ◽  
Induce Platelet Aggregation ◽  
Minimal Concentration ◽  
Aggregation Principle

SummaryThe minimal concentration of the platelet aggregation principle (Platelet Aggregoserpen- tin, PAS) necessary to induce platelet aggregation was 10 ng/ml, about one-hundredth of that of the crude venom. PAS induced the release of platelet factors 3 and 4 from platelets, but the released platelet factor 3 was easily inactivated by the anti-phospholipid effect of PAS. Pretreatment of platelets with neuraminidase potentiated PAS-induced platelet aggregation. PAS-induced platelet aggregation was independent on released ADP; it could occur in the ADP-removing systems, such as apyrase or a combination of phosphoenolpyruvate and pyruvate kinase. However, PAS-induced platelet aggregation could be inhibited by adenine nucleotides and adenosine.PAS-induced platelet aggregation was inhibited by some anti-inflammatory agents, antimalarial drugs, local anesthetics, antihistamine and smooth muscle relaxants. After deaggregation of PAS-treated platelets, thrombin and sodium arachidonate could further induce platelet aggregation, but ADP and second dose of PAS could not. It is concluded that PAS-induced platelet aggregation is due to prostaglandin synthesis. Recent literatures on the mechanism of platelet aggregation were surveyed and the actions of PAS were discussed.

Increased Ristocetin Induced Binding of Factor VIII to Platelets in Von Willebrand’s Disease (vWd)

1979 ◽  
Author(s):  
Z.M. Ruggeri ◽  
F.I. Pareti ◽  
P.M. Mannucci ◽  
T.S. Zimmerman
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Bleeding Time ◽  
Human Platelet ◽  
Bleeding Tendency ◽  
Platelet Factor ◽  
Induce Platelet Aggregation ◽  
Prolonged Bleeding Time ◽  
Crossed Immunoelectrophoresis ◽  
Ristocetin Cofactor

Initial reports of ristocetin-induced platelet aggregation (RIPA) demonstrated it to be decreased in some patients with vWd. We now report 20 patients (from five unrelated families) in whom RIP A was increased, apparently as the result of an increased ristocetin-induced binding of Factor VIIIrelated antigen (VIIIR:Ag) to platelets. All the patients had a life-long bleeding tendency, with prolonged bleeding time, and an abnormal two-dimensional crossed immunoelectrophoresis (2DCIE). Increased RIPA was demonstrated by measuring the minimum ristocetin concentration necessary to induce platelet aggregation. This was 0.42 mg/ml á 0.11 SD in the patients, and 0.91 á 0.097 SD in 17 normals (t = 13.83; P < 0.001). VIIIR:Ag binding to platelets occurred at ristocetin concentrations (0.4 mg/mI) which were ineffective in normals (who required >0.6 mg/mI). In contrast, the VIIIR:Ag of other patients with abnormal 2DCIE and markedly decreased RIP A did not bind to platelets at ristocetin concentrations as high as I mg/ml. It has been previously demonstrated that 30% to 60% of normal VIIIR:Ag binds to isolated human platelet membranes in the absence of ristocetin or any other agent, and that binding is restricted to the larger forms of VIIIR:Ag. However, VIIIR:Ag from the patients with increased RIPA, including two with normal ristocetin cofactor activity, showed decreased or undetectable binding as did all other patients with abnormal 2DCIE. This study suggests that ristocetin induced platelet Factor VIII interaction does not accurately reflect the “bleeding time factor” defect in vWd.

In Vitro and In Vivo Effects of Adrenaline and Phentolamine on Platelet Function

1978 ◽  
Vol 40 (02) ◽  
pp. 428-438 ◽  
Author(s):  
Oreste Ponari ◽  
Emilio Civardi ◽  
Alessandro Megha ◽  
Mario Pini ◽  
Raffaele Poti’ ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Threshold Concentration ◽  
Two Phase ◽  
Platelet Factor ◽  
Induce Platelet Aggregation ◽  
In Vivo Effects ◽  
In Vivo Administration

Summary In vitro and in vivo effects of adrenaline (ADR) on platelet aggregation, on platelet factor 3 (PF3) availability and on platelet factor 4 (PF4) release were studied in man. Inhibitory action of an alpha-blocker, phentolamine (PHEN) was investigated in the same conditions.The threshold concentration (TC) of ADR inducing the typical two-phase response in aggregation tests when added to platelet-rich plasma (PRP) varied in different pools of plasma, but always induced an evident PF4 release and increased PF3 availability. A further increase in both parameters was obtained with higher concentrations but without any significant dose/response correlation.Adding PHEN alone to PRP did not induce platelet aggregation or modify PF4 release induced by stirring, but it reduced PF3 availability. On the other hand, PHEN prevented the effects of ADR in different platelet tests, at appropriate concentrations.Intravenous infusion of ADR lowered the TC, and increased PF3 availability and PF4 release. In vivo administration of PHEN, in contrast, increased TC and reduced PF3 availability, while PF4 remained unchanged.

Inhibition of Virus-Induced Platelet Aggregation by Treatment of Platelets with Neuraminidase

1975 ◽  
Author(s):  
M. A. Chernesky ◽  
R. P. B. Larke
Keyword(s):  
Sialic Acid ◽  
Platelet Aggregation ◽  
Sendai Virus ◽  
Adenine Nucleotides ◽  
Lactic Dehydrogenase ◽  
Human Platelets ◽  
Induce Platelet Aggregation ◽  
Platelet Surface ◽  
Thin Sections ◽  
Virus Attachment

Washed suspensions of rabbit or human platelets aggregate and release their constituents (adenine nucleotides, serotonin and lactic dehydrogenase) when mixed with Newcastle disease virus (NDV) or Sendai virus (paramyxoviruses) in a stirred system at 37° C. Treatment of rabbit platelets with chromatographically purified neuraminidase which removed 10–20 ug of sialic acid/101 platelets reduced, by more than 95%, platelet aggregation and release of constituents by virus; treated platelets were as responsive to stimulation with ADP or thrombin as were control platelets. Virus, which normally becomes associated with aggregated platelets, failed to attach to neuraminidase-treated platelets and was recovered in platelet supernatant fluids. Subsequent aggregation of these mixtures of virus and neuraminidase-treated platelets with thrombin failed to trap NDV in platelet aggregates. Electron microscopy (carbon replica and thin-sections) revealed an absence of virus attachment on surfaces of platelets treated with neuraminidase.These data indicate that a receptor substance containing sialic acid present on the platelet surface is necessary to enable paramyxoviruses to attach and induce platelet aggregation and release of platelet constituents.

Release of Platelet Factor 4 (PF 4) During Repeatedly Induced Platelet Aggregation in Vivo

1975 ◽  
Author(s):  
J. Vaage ◽  
K. Gjesdal
Keyword(s):  
Platelet Aggregation ◽  
Vasoactive Agents ◽  
Platelet Factor ◽  
Induce Platelet Aggregation ◽  
Vasoactive Substances ◽  
Pulmonary Vasoconstriction ◽  
Reversible Aggregation ◽  
Aggregation Of Platelets ◽  
Lung Response

After induced intravascular platelet aggregation a pulmonary vasoconstriction occurs due to the release of vasoactive substances from platelets (Acta physiol. scand. 92, 546-556, 1974). PF 4 has been suggested to be a marker of the platelet release reaction. In the present experiments the release of PF 4 and the vasoactive effects of induced platelet aggregation were compared in cats.Successive i. v. infusions of either ADP or collagen were given to induce platelet aggregation. The plasma level of PF 4 was measured by electroimmuno assay immediately before each infusion and at the maximal ensuing lung response. The initial infusion of either ADP or collagen increased PF 4 in plasma by about 25%. After several ADP-infusions neither lung responses nor PF 4 release could be elicited by further infusions, although reversible aggregation of platelets was still induced. At this stage collagen infusions gave profound lung responses, but no release of PF 4. Another group of animals were given 3 successive collagen infusions. The lung responses were similar after each infusion, but the release of PF 4 became gradually reduced.These data suggest that the release of PF 4 from platelets is dissociated from that of the vasoactive agents.

Single-Dose Effect of Enteric-Coated Aspirin on Platelet Function and Thromboxane Generation in Middle-Aged Men

1993 ◽  
Vol 27 (4) ◽  
pp. 405-410 ◽  
Author(s):  
Hiroshi Mohri ◽  
Takao Ohkubo
Keyword(s):  
Single Dose ◽  
Platelet Aggregation ◽  
Bleeding Time ◽  
Adenine Nucleotides ◽  
Adenosine Diphosphate ◽  
Platelet Factor 4 ◽  
Middle Aged ◽  
Platelet Factor ◽  
Enteric Coated Aspirin ◽  
Enteric Coated

OBJECTIVE: To evaluate the effect of a single dose of enteric-coated aspirin (ECA) in three different dosages on platelet function and thromboxane generation in middle-aged men. DESIGN AND METHODS: In a nonblind, nonplacebo-controlled, crossover study, a single dose of ECA (50, 250, or 1000 mg) was given in a tablet form to a group of healthy, middle-aged men. Ten subjects, aged 50–67 years, volunteered to participate in this study. Platelet functions including bleeding time, platelet aggregation, adenine nucleotides, beta-thromboglobulin, platelet factor 4, thromboxane generation, and aspirin measurement were determined. RESULTS: Before ECA ingestion, the intracellular adenine nucleotides (adenosine triphosphate, adenosine diphosphate) were decreased, and both beta-thromboglobulin and platelet factor 4 were increased. These observations suggested that platelets were activated in vivo in middle-aged men. These findings returned to normal within 8 hours after the ingestion of ECA, and maintained normal for at least two days. Bleeding time was significantly prolonged at 8 and 24 hours compared with that before ingestion of ECA 1000 mg (p<0.05). The generation of platelet thromboxane was maximally inhibited by approximately 40 percent in the samples 8 hours after ECA ingestion. Abnormal values of adenine nucleotides, beta-thromboglobulin, and platelet factor 4 returned to normal within 8 hours. Arachidonic acid-induced platelet aggregation was inhibited compared with that before treatment (p<0.01) and the inhibitory effect was maintained for at least three days. Adenosine diphosphate- and epinephrine-induced aggregations were less inhibited than those induced by arachidonic acid. Inhibitory effects of ECA on platelet aggregation were dose dependent. CONCLUSIONS: Our study indicates that platelets are activated in middle-aged men and that a single dose of ECA 50 mg is safe and can inhibit thromboxane synthesis and platelet aggregation. These results suggest that a daily dose of ECA 50 mg may be useful for blocking platelet activation and preventing thrombosis.

scholarly journals ADP and epinephrine-induced release of platelet fibrinogen

Blood ◽  
1981 ◽  
Vol 58 (4) ◽  
pp. 797-802 ◽  
Author(s):  
KL Kaplan ◽  
MJ Dauzier ◽  
S Rose
Keyword(s):  
Platelet Aggregation ◽  
Bovine Serum Albumin ◽  
Adenine Nucleotides ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Dense Granule ◽  
Fibrinogen Concentration ◽  
Platelet Factor ◽  
Granule Proteins ◽  
Induced Aggregation

Abstract Human platelets gel-filtered into Tyrode's buffer containing 1 mM Mg++ and 0.35% bovine serum albumin were studied to determine whether they would undergo biphasic aggregation and release of alpha-granule proteins in response to adenosine diphosphate (ADP) or epinephrine without addition of exogenous fibrinogen. Fibrinogen concentration in the supernatant of unaggregated gel-filtered platelets was less than 1 pmole/ml. With addition of ADP or epinephrine, biphasic aggregation was seen, with release of platelet fibrinogen, beta-thromboglobulin, and platelet factor 4. Fibrinogen concentration in the supernatant after aggregation ranged from 15 to 70 pmole/ml. Release of the alpha-granule proteins by epinephrine was coincidental with release of the dense granule adenine nucleotides. Aggregation and alpha-granule protein release by both ADP and epinephrine were inhibited by added Ca++ at 1-- 2 mM. The ability of gel-filtered platelets to undergo ADP- and epinephrine-induced aggregation and release in the absence of exogenous fibrinogen suggests that released platelet fibrinogen may be able to fulfill the requirement for fibrinogen in ADP- and epinephrine-induced platelet aggregation and release.

scholarly journals Incorporation of3H-Glycerol into Phospholipids of Normal and abnormal Platelets

1977 ◽  
Author(s):  
R. A. Hutton ◽  
R. M. Hardisty ◽  
D. Deykin
Keyword(s):  
Platelet Aggregation ◽  
Adenine Nucleotides ◽  
Membrane Damage ◽  
Phosphatidyl Inositol ◽  
Adenosine Diphosphate ◽  
Platelet Factor ◽  
Pi Turnover ◽  
Minute Period ◽  
Phospholipid Distribution ◽  
Glycerol Uptake

Glycerol-2-3H uptake into phospholipids separated by unidirectional chromatography on silica gel H plates, was measured in normal platelets and those from patients with Glanzman’s thrombasthenia (GT), Bernard-Soulier syndrome (B-S), Storage pool deficiency (SPD) or aspirinlike release defect . The results were compared with the release of adenine nucleotides (AN) and with changes in platelet factor 3 availability (PF3a). In normal platelets, secondary aggregation induced by adenosine diphosphate (ADP), Epinephrine (EPI) , Collagen (COL) or Ristocetin (RI) led to a marked stimulation of glycerol uptake over a 60 minute period of incubation, the most striking increase being in the phosphatidyl inositol (PI) fraction.No quantitative differences in phospholipid distribution were noted in any of the patients tested. In all cases, the uptake of glycerol was proportional to the degree of platelet aggregation, being minimal where no aggregation was observed (GT platelets mixed with ADP or EPI) , of intermediate level where primary aggregation alone occurred (SPD platelets with all agents or with GT platelets with RI), and similar to normal where secondary aggregation was induced (B-S platelets stirred with ADP or EPI). The results suggest that the defective 3H-glycerol uptake by abnormal platelets is a consequence rather than a cause of the decrease in platelet aggregation. Enhanced PI turnover most probably reflects the cells response to membrane damage or distortion incurred during aggregation and the release reaction.

scholarly journals Inhibition of coagulation and thrombin-induced platelet activities by a synthetic dodecapeptide modeled on the carboxy-terminus of hirudin

Blood ◽  
1990 ◽  
Vol 75 (2) ◽  
pp. 399-406 ◽  
Author(s):  
JA Jakubowski ◽  
JM Maraganore
Keyword(s):  
Platelet Aggregation ◽  
Antithrombin Iii ◽  
Thromboxane A2 ◽  
Serotonin Release ◽  
Dependent Manner ◽  
Thrombin Time ◽  
Platelet Factor ◽  
Induce Platelet Aggregation ◽  
Apparent Lack

A synthetic, tyrosine-sulfated, dodecapeptide (BG8865) modeled on residues 53–64 of hirudin was found to elevate the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) of human plasma in a dose-dependent manner. The most sensitive assay was the TT, which was prolonged 2 and 3 times control values at 2.2 and 4.1 micrograms/mL hirudin peptide, respectively. The sulfated dodecapeptide exhibited no dependency on antithrombin III as monitored by the APTT in the presence of sheep anti-human antithrombin III antibodies, and its activity was not neutralized by platelet releasates or platelet factor 4. In studies of thrombin-induced platelet activation, the hirudin peptide was found to block aggregation, serotonin release and thromboxane A2 generation. At thrombin concentrations of 0.25 U/mL, the IC50 (concentration resulting in 50% inhibition) for inhibition of platelet aggregation was 0.72 micrograms/mL peptide. Inhibition of TXA2 generation and serotonin release correlated closely with inhibition of aggregation. Using platelets from patients with clinically documented heparin-induced thrombocytopenia anticoagulant doses of heparin were found to induce platelet aggregation and thromboxane A2 generation. In sharp contrast, anticoagulant-equivalent doses of hirudin peptide had no effect on patient platelets, as evidenced by a lack of platelet aggregation and thromboxane A2 generation. These data provide compelling in vitro evidence that the hirudin peptide has several potential advantages over heparin, namely effective inhibition of thrombin-induced platelet activities, co-factor independence, insensitivity to endogenous heparin- neutralizing factors, and an apparent lack of direct or immune-mediated platelet stimulating properties.

Effect of Heparin:PMX60056 Complexes on Platelet Aggregation Induced by ADP or HIT Antibody

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4386-4386
Author(s):  
Walter Jeske ◽  
R. Eric McAllister ◽  
Jeanine M. Walenga ◽  
Michelle Paulus ◽  
Jawed Fareed
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Anticoagulant Activity ◽  
Platelet Factor ◽  
Induce Platelet Aggregation ◽  
Heparin Induced Thrombocytopenia ◽  
Platelet Aggregometry ◽  
Positively Charged

Abstract Abstract 4386 Introduction: A neutralization of anticoagulant activity occurs when heparin binds to a variety of positively charged substances such as protamine and platelet factor 4 (PF4). PMX60056 (PolyMedix, Radnor, PA) is a novel compound that is being developed as a heparin antagonist. Since heparin-PF4 complexes are antigenic, with antibodies against this complex activating platelets to trigger thrombin generation, thrombus formation and associated morbidities, it is of interest to determine whether heparin:PMX60056 complexes affect platelet function. This study compares the effect of PMX60056 and protamine, alone and complexed to heparin, on platelet function as assessed by platelet aggregometry. Materials and Method: Whole blood, collected from 10 healthy individuals, was anticoagulated with 3.2% sodium citrate and centrifuged to make platelet rich plasma (PRP). PRP was supplemented with 10 μ g/ml heparin (~1.5 IU/ml), 10 μ g/ml heparin antagonist (protamine or PMX 60056) or a complex of 10 μ g/ml heparin and 10 μ g/ml heparin antagonist. Platelet aggregation was stimulated by the addition of ADP (5 or 10 μ M final concentration) or serum from a patient with heparin-induced thrombocytopenia. Result: ADP-induced platelet aggregation was not affected by the addition of heparin, protamine, PMX 60056, or complexes of heparin with heparin antagonist. In the HIT system, heparin + HIT serum led to a significant increase in platelet aggregation vs. saline (46.7 ± 3.2 % vs. 8.2 ± 2.9%). HIT serum + heparin antagonist did not induce platelet aggregation (PMX60056: 10.2 ± 4.4%; protamine: 11.6 ± 3.5%). The aggregation responses to HIT serum + heparin (46.7 ± 3.2%), HIT serum + heparin:PMX60056 (43.6 ± 5.8%) and HIT serum + heparin:protamine (47.8 ± 3.8%) were not significantly different. Conclusion: When mixed at equigravimetric amounts, protamine and PMX60056 do not prevent formation of immune complexes consisting of HIT antibody and heparin which lead to platelet activation. Previous data from human trials has suggested that smaller amounts of PMX60056 (less than equigravimetric) may effectively neutralize heparin. Thus, it is speculated that smaller heparin:PMX60056 complexes may induce less antibody formation than larger heparin:protamine complexes. Validation of this hypothesis in animal models or clinical studies is warranted. Disclosures: McAllister: PolyMedix, Inc.: Employment.

Inhibition of Platelet Aggregation by a New Agent, Ticlopidine

1978 ◽  
Vol 40 (02) ◽  
pp. 542-550 ◽  
Author(s):  
Shin-Ichiro Ashida ◽  
Yasushi Abiko
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Life Span ◽  
Thromboxane A2 ◽  
Prostaglandin Synthesis ◽  
Half Time ◽  
Platelet Adhesiveness ◽  
Clot Retraction ◽  
Platelet Factor ◽  
Inhibition Of Platelet Aggregation

SummaryEffect of Ticlopidine, 5-(2-chlorobenzyl)-4, 5, 6, 7-tetrahydro[3,2-C]pyridine hydrochloride, on platelet aggregation was studied in the rat. Ticlopidine was found to be a potent, long-lasting inhibitor of platelet aggregation. It inhibited the aggregation induced by any of ADP, collagen, thrombin, arachidonic acid and prostaglandin endoperoxides and/or thromboxane A2-like substance. Ticlopidine was effective at doses as low as 30 mg/kg when orally given to rats, and the effect lasted as long as the life span of the circulating platelets (half time: about 48 hours).Ticlopidine inhibited also nucleotide release from and prostaglandin synthesis in the platelets, but did not significantly affect platelet adhesiveness to glass, platelet factor 3 availability and clot retraction.

Sign in / Sign up

Export Citation Format

Share Document