The Effect of Anaesthetic Agents on Platelet Function

This paper reviews studies which have investigated the effect of anaesthetic agents on platelet function The results of these studies suggest that halothane is the only agent in current use which inhibits platelet function in concentrations used clinically. Nitrous oxide appears to cause only a modest inhibition, while enflurane and isoflurane appear to have minimal or negligible effects. There is no current evidence that intravenous induction agents opiates, or muscle relaxants affect platelet function. Reports indicate that local anaesthetic agents inhibit platelet aggregation, but only at concentrations far greater than peak plasma concentrations found during clinical use. Epidural anaesthesia may be associated with a reduction in platelet aggregation through a mechanism unrelated to direct local anaesthetic inhibition. The clinical significance of the effect of halothane on platelet function is not known. However, it is possible that halothane may affect bleeding or thrombotic complications in a similar manner to other ‘anti-platelet’ drugs.

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Multiplate® Platelet Aggregation Findings Are Dependent on Platelet Count but Can Be Corrected by Use of a Ratio

Applied Sciences ◽

10.3390/app10227971 ◽

2020 ◽

Vol 10 (22) ◽

pp. 7971

Author(s):

Mohamed Soliman ◽

Matthias Hartmann

Keyword(s):

Platelet Count ◽

Platelet Aggregation ◽

Platelet Function ◽

Platelet Rich Plasma ◽

Platelet Aggregation Inhibitors ◽

Impedance Aggregometry ◽

Aggregation Inhibitors ◽

Thrombotic Complications ◽

Highly Correlated ◽

Bedside Method

Impedance aggregometry (Multiplate®) detects the effects of platelet aggregation inhibitors and can predict thrombotic complications after coronary and cerebrovascular stent interventions. The bedside method uses whole blood samples not corrected for platelet count. It is claimed but not proved that the findings are unrelated to platelet count in the physiological range. We therefore investigated in the experimental study: (1) whether impedance aggregometry findings and platelet count are correlated and (2) whether the aggregation/platelet count ratio expresses platelet function independent of platelet count. Following ethics committee approval, platelet-rich plasma from healthy probands was diluted with platelet-poor plasma to obtain different platelet counts. Thereafter, platelet count was measured and samples were subjected to impedance aggregometry using thrombin receptor activating peptide (TRAP) for platelet activation. In all probands, impedance aggregometry findings and platelet count were highly correlated (r = 0.88 to 0.94; p < 0.05). The combination of all experiments revealed the proportionality between impedance aggregometry findings and platelet count (n = 31, r = 0.78, p = 0.0001). In contrast, the ratio of impedance aggregometry findings and platelet count was not significantly correlated with platelet count (r = 0.017; p = 0.3) and thus constitutes a specific measure for platelet function. In conclusion, impedance aggregometry findings subsequent to the activation with TRAP are dependent on both platelet function and platelet count. Normalization of impedance aggregometry findings for platelet count can be achieved by a ratio resulting in more specific results.

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Inhibitory Effect of Piracetam on Platelet-rich Thrombus Formation in an Animal Model

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614243 ◽

1998 ◽

Vol 79 (01) ◽

pp. 222-227 ◽

Cited By ~ 8

Author(s):

F. Stockmans ◽

W. Deberdt ◽

Å. Nyström ◽

E. Nyström ◽

J. M. Stassen ◽

...

Keyword(s):

Platelet Aggregation ◽

Ex Vivo ◽

Peak Plasma ◽

Thrombus Formation ◽

Plasma Concentrations ◽

Inhibitory Effect ◽

Human Platelets ◽

Cell Deformability

SummaryIntravenous administration of piracetam to hamsters reduced the formation of a platelet-rich venous thrombus induced by a standardised crush injury, in a dose-dependent fashion with an IC50 of 68 ± 8 mg/kg. 200 mg/kg piracetam also significantly reduced in vivo thrombus formation in rats. However, in vitro aggregation of rat platelets was only inhibited with piracetam-concentrations at least 10-fold higher than plasma concentrations (6.2 ± 1.1 mM) obtained in the treated animals. No effects were seen on clotting tests.In vitro human platelet aggregation, induced by a variety of agonists, was inhibited by piracetam, with IC50’s of 25-60 mM. The broad inhibition spectrum could be explained by the capacity of piracetam to prevent fibrinogen binding to activated human platelets. Ex vivo aggregations and bleeding times were only minimally affected after administration of 400 mg/kg piracetam i.v. to healthy male volunteers, resulting in peak plasma levels of 5.8 ± 0.3 mM.A possible antiplatelet effect of piracetam could be due to the documented beneficial effect on red blood cell deformability leading to a putative reduction of ADP release by damaged erythrocytes. However similarly high concentrations were needed to prevent stirring-induced “spontaneous” platelet aggregation in human whole blood.It is concluded that the observed antithrombotic action of piracetam cannot satisfactorily be explained by an isolated direct effect on platelets. An additional influence of piracetam on the rheology of the circulating blood and/or on the vessel wall itself must therefore be taken into consideration.

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Sequential changes in platelet function and coagulation in leukemic children treated with L-asparaginase, prednisone, and vincristine.

Journal of Clinical Oncology ◽

10.1200/jco.1983.1.6.380 ◽

1983 ◽

Vol 1 (6) ◽

pp. 380-385 ◽

Cited By ~ 31

Author(s):

C H Pui ◽

C W Jackson ◽

C Chesney ◽

S A Lyles ◽

W P Bowman ◽

...

Keyword(s):

Platelet Function ◽

Antithrombin Iii ◽

Lymphoblastic Leukemia ◽

Plasma Concentrations ◽

Adenosine Diphosphate ◽

Remission Induction ◽

Induction Treatment ◽

Aggregation Response ◽

Thrombotic Complications

Coagulation and platelet function in 13 children with acute lymphoblastic leukemia were studied sequentially during a remission induction with L-asparaginase, prednisone, and vincristine. In the first weeks of therapy, which included four doses of L-asparaginase coagulation was characterized by significant decreases in plasma concentrations of plasminogen, antithrombin III alpha 2-macroglobulin, and fibrinogen. All measures gradually returned to normal after complication of L-asparaginase therapy. In the latter part of induction treatment, clotting times, especially partial Thromboplastin time, decreased significantly, while levels of factors V and VIII increased with recovery of platelet counts. At this time, 6 patients had an increased in vitro platelet aggregation response to adenosine diphosphate, and their partial thromboplastin times were significantly shorter than those of patients without increased aggregation. Concurrent abnormalities in coagulation and platelet function may account for the thrombotic complications that develop in some children receiving induction therapy with these agents.

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Peptides affecting coagulation

British Journal Of Nutrition ◽

10.1017/s0007114500002312 ◽

2000 ◽

Vol 84 (S1) ◽

pp. 99-102 ◽

Cited By ~ 47

Author(s):

Kay J. Rutherfurd ◽

H. S. Gill

Keyword(s):

Amino Acid ◽

Platelet Aggregation ◽

Platelet Function ◽

Bioactive Peptides ◽

Thrombus Formation ◽

Milk Proteins ◽

Inhibit Platelet Aggregation ◽

Considerable Effort ◽

Sequence Similarities ◽

Proteins And Peptides

Based on amino acid sequence similarities that exist between the fibrinogen γ-chain and κ-casein, and also functional similarities between milk and blood coagulation, considerable effort has been made to investigate the effects of milk proteins and peptides on platelet function and thrombosis. In particular, a number of peptides derived from the glycomacropeptide segment of κ-casein, have been shown to inhibit platelet aggregation and thrombosis. KRDS, a peptide from lactoferrin has also been shown to inhibit platelet aggregation but to a lesser extent than its fibrinogen analogue RGDS. Despite their functional and structural similarities they do not act in the same way on platelet function and are thought to affect thrombus formation differently. Further investigation is needed to determine if these milk-derived bioactive peptides are released naturally following ingestion and might therefore be useful as the basis for milk-based products with anti-thrombotic properties.

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THE EFFECT OF ACETYLSALICYLIC ACID ON PLATELET FUNCTION

Journal of Experimental Medicine ◽

10.1084/jem.128.5.877 ◽

1968 ◽

Vol 128 (5) ◽

pp. 877-894 ◽

Cited By ~ 198

Author(s):

Geoffrey Evans ◽

Marian A. Packham ◽

Edward E. Nishizawa ◽

James F. Mustard ◽

Edmund A. Murphy

Keyword(s):

Platelet Aggregation ◽

Acetylsalicylic Acid ◽

Platelet Function ◽

Gamma Globulin ◽

Sodium Salicylate ◽

Adenosine Diphosphate ◽

The Other ◽

Inhibit Platelet Aggregation ◽

Coated Particles ◽

Antigen Antibody

Acetylsalicylic acid (ASA, aspirin) and sodium salicylate inhibit platelet aggregation induced by collagen, antigen-antibody complexes, gamma globulin-coated particles or thrombin. These compounds suppress the release of platelet constituents, such as adenosine diphosphate (ADP) and serotonin, induced by such stimuli. Since ASA and sodium salicylate do not inhibit ADP-induced platelet aggregation, it appears that their effect on the action of the other stimuli is due to a decrease in the amount of ADP released. The administration of ASA to rabbits (in doses which inhibited collagen-induced platelet aggregation) impaired hemostasis, prolonged platelet survival, and diminished the amount of deposit formed in an extracorporeal shunt.

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The Effects of a Combined Alpha- and Beta-Blocking Drug, Labetalol, on Some Aspects of Platelet Function

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648676 ◽

1978 ◽

Vol 40 (02) ◽

pp. 423-427 ◽

Cited By ~ 6

Author(s):

Knut Lote ◽

Birgit J Svenson ◽

Unni Ånstad ◽

Arne Nordøy

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Blood Platelets ◽

Plasma Concentrations ◽

Blocking Agent ◽

Platelet Function Test ◽

Platelet Factor ◽

Human Blood Platelets

SummaryThe effects of the combined alpha- and beta-adrenoreceptor blocking agent labetalol on human blood platelets as estimated by platelet aggregation, platelet count, bleeding time and platelet factor 3 activity were studied in 5 patients. The drug reduced adrenaline - induced platelet aggregation in vitro. However, it did not influence the above platelet function test in therapeutic plasma concentrations in vivo.

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MECHANISMS FOR THE IN VIVO ANTIPLATELET EFFECTS OF ORGANIC NITRATES

10.1055/s-0038-1643435 ◽

1987 ◽

Author(s):

R De Caterina ◽

D Giannessi ◽

W Bernini ◽

A Mazzone

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Isosorbide Dinitrate ◽

Platelet Rich Plasma ◽

Secondary Wave ◽

Organic Nitrates ◽

Inhibit Platelet Aggregation ◽

Threshold Doses

Organic nitrates (nitroglycerin, isosorbide dinitrate) are inhibitors of platelet function more effective in vivo than in vitro (Am J Cardiol 1984; 53:1683), the in vivo effect requiring concentrations 10-100 times lower than in vitro. We have previously excluded that such difference is due to elicitation by nitrates of prostacyclin synthesis in human endothelial cells or vascular fragments (Circulation 1985; 71:176). In the present study we evaluated alternative explanations: that the difference is due (1) to generation of more active drug metabolites; (2) to synergism between nitrates and prostacyclin in the inhibition of platelet function. Isosorbide dinitrate (ISDN) and its two main in vivo metabolites, isosorbide-2-mononitrate (IS-2-MN) and isosorbide-5-mononitrate (IS-5-MN), were compared in their ability to inhibit platelet aggregation and thromboxane (TX) B2 formation (RIA) in respone to threshold doses of ADP, adrenaline, collagen, arachidonic acid and thrombin in citrated platelet-rich plasma. The same tests were performed in 10 healthy volunteers before, during (at 5, 15 and 30 min) and after infusion of the three drugs at 8 mg/h for 30 min in 3 different days. Finally, the concentration of prostacyclin (and its stable analogue Iloprost) added in vitro to platelets, and required to inhibit platelet aggregation by 50% (IC50) after 5 min pre-incubation of platelets with nitrates was determined. In vitro incubation of platelets with IS-2-MN resulted in greater inhibition of both aggregation and TX formation (by ADP and adrenaline) than with ISDN and IS-5-MN. At 10−7M, only IS-2-MN significantly inhibited aggregation (−12%, P< 0.05) and TX formation (from 9.2±1.8 to 5.9± 0.6 ng/ml) by ADP, while minimum effective concentrations were 10−7M for ISDN and 10−7m for IS-5-MN. These in vitro differences are unlikely to be the explanation of in vivo findings, since IS-2-MN, ISDN and IS-5-MN were equipotent when administered in vivo (complete abolition of secondary wave after ADP and adrenaline at 30 min of infusion). At supra-threshold doses of all the aggregating agents, all three drugs, at 10−7M, decreased IC50 for prostacyclin from 2.9± 1.3 to 0.32± 0.18 nM (P< 0.01). Synergim with prostacyclin is most likely to account, at least partially, for in vivo antiplatelet effects by organic nitrates.

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Glycoprotein Ia C807T: Polymorphisms and Their Association with Platelet Function in Patients with the Acute Coronary Syndrome

Cardiology ◽

10.1159/000435906 ◽

2015 ◽

Vol 132 (4) ◽

pp. 213-220 ◽

Cited By ~ 1

Author(s):

Qiang Zhang ◽

Yiqi Jin ◽

Dongmin Shi ◽

Junrong Gong ◽

Jing Liu ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Platelet Aggregation ◽

Platelet Function ◽

Plasma Concentrations ◽

Adenosine Diphosphate ◽

Coronary Intervention ◽

Antiplatelet Treatment ◽

Coronary Syndrome ◽

Granule Membrane ◽

Dual Antiplatelet Treatment

Objectives: In the current study, we explored the relationship between glycoprotein Ia (GPIa) C807T polymorphisms and platelet function, and the sensitivity to dual antiplatelet treatment after percutaneous coronary intervention. Materials and Methods: We conducted a case-control study in 220 patients diagnosed with acute coronary syndrome (ACS) and 220 healthy controls. The platelet GPIa C807T genotypes of patients and controls were determined, and platelet aggregation and plasma concentrations of α-granule membrane protein (GMP-140) were assessed following stimulation with arachidonic acid and adenosine diphosphate. Results: The frequency of the GPIa T allele was higher in the ACS group than in controls. In the ACS group, platelet aggregation was significantly higher in individuals with the T allele than in those with the C allele. Dual antiplatelet treatment reduced platelet aggregation in all three genotypes, and patients carrying the CC genotype were more sensitive to antiplatelet treatment than those with the T allele, particularly the ones with the TT genotype. There were no differences in plasma GMP-140 levels. Conclusions: The GPIa C807T polymorphism might be a risk factor for the development and relapse of ACS. The GP Ia T allele may help to identify a group of patients who need more aggressive antithrombotic treatment.

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Platelet Activation and Aggregation Induced by Recombinant von Willebrand Factors Reproducing Four Type 2B von Willebrand Disease Missense Mutations

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614241 ◽

1998 ◽

Vol 79 (01) ◽

pp. 211-216 ◽

Cited By ~ 13

Author(s):

Lysiane Hilbert ◽

Claudine Mazurier ◽

Christophe de Romeuf

Keyword(s):

Platelet Aggregation ◽

Platelet Activation ◽

Von Willebrand Disease ◽

Platelet Glycoprotein ◽

Missense Mutations ◽

Inhibit Platelet Aggregation ◽

Wild Type ◽

A1 Domain ◽

Von Willebrand ◽

Willebrand Factor

SummaryType 2B of von Willebrand disease (vWD) refers to qualitative variants with increased affinity of von Willebrand factor (vWF) for platelet glycoprotein Ib (GPIb). All the mutations responsible for type 2B vWD have been located in the A1 domain of vWF. In this study, various recombinant von Willebrand factors (rvWF) reproducing four type 2B vWD missense mutations were compared to wild-type rvWF (WT-rvWF) for their spontaneous binding to platelets and their capacity to induce platelet activation and aggregation. Our data show that the multimeric pattern of each mutated rvWF is similar to that of WT-rvWF but the extent of spontaneous binding and the capacity to induce platelet activation and aggregation are more important for the R543Q and V553M mutations than for the L697V and A698V mutations. Both the binding of mutated rvWFs to platelets and platelet aggregation induced by type 2B rvWFs are inhibited by monoclonal anti-GPIb and anti-vWF antibodies, inhibitors of vWF binding to platelets in the presence of ristocetin, as well as by aurin tricarboxylic acid. On the other hand, EDTA and a monoclonal antibody directed against GPIIb/IIIa only inhibit platelet aggregation. Furthermore, the incubation of type 2B rvWFs with platelets, under stirring conditions, results in the decrease in high molecular weight vWF multimers in solution, the extent of which appears correlated with that of plasma vWF from type 2B vWD patients harboring the corresponding missense mutation. This study supports that the binding of different mutated type 2B vWFs onto platelet GPIb induces various degrees of platelet activation and aggregation and thus suggests that the phenotypic heterogeneity of type 2B vWD may be related to the nature and/or location of the causative point mutation.

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Increased Response to Arachidonic Acid and U-46619 and Resistance to Inhibitory Prostaglandins in Patients with Chronic Myeloproliferative Disorders

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642568 ◽

1988 ◽

Vol 59 (01) ◽

pp. 073-076 ◽

Cited By ~ 9

Author(s):

Sergio Cortelazzo ◽

Monica Galli ◽

Donatella Castagna ◽

Piera Viero ◽

Giovanni de Gaetano ◽

...

Keyword(s):

Bone Marrow ◽

Arachidonic Acid ◽

Platelet Aggregation ◽

Myeloproliferative Disorders ◽

Bone Marrow Stem Cell ◽

Healthy Controls ◽

Aggregation Response ◽

Thrombotic Complications ◽

Cyclic Endoperoxide ◽

Marrow Stem Cell

SummaryIn patients with myeloproliferative disorders (MPD) a group of related diseases of the bone marrow stem cell and recurrent haemorrhagic and/or thrombotic complications, the production of aggregating prostaglandins (PGs) may be normal or slightly reduced, while PGI2 production is normal. However, MPD platelet sensitivity to antiaggregatory PGs is still unknown.We studied the potency of PGD2, PGI2 and PGEi as inhibitors of platelet aggregation induced by threshold aggregating concentrations of arachidonic acid and U-46619-analogue of the cyclic endoperoxide PGH2 in 20 patients with MPD in comparison with healthy controls, with the aim of evaluating the sensitivity of MPD platelets to antiaggregatory PGs. In these patients platelet prostanoid metabolism was normal. However, the functional response of platelets to aggregating and antiaggregating prostanoids was shifted towards potentially increased platelet aggregation response. These findings could have a clinical relevance in view of the haemostatic and thrombotic complications so frequent in MPD.

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