Pioglitazone Inhibits Platelet Function and Potentiates the Effects of Aspirin

Abstract Abstract 1228 BACKGROUND: Thiazolidinediones (TZDs) are agonists of PPARγ which favorably modify metabolic parameters and markers of atherosclerosis among type 2 diabetics. Enucleate platelets express PPARγ protein, and PPARγ agonists blunt release of CD40L and thromboxane B2 (TXB2) from thrombin-activated platelets. (Abbiyik, F et al, Human bone marrow megakaryocytes and platelets express PPARγ and PPARγ agonists blunt platelet release of CD40 ligand and thromboxanes. Blood, 2004 104(5):p.1361–8.) Diabetic subjects disproportionately experience arterial thromboses despite aspirin therapy. We assessed platelet function after pioglitazone in two risk groups in the presence and absence of aspirin to characterize its range of antiplatelet effect. SUBJECTS: 20 diabetic and 20 non-diabetic subjects were enrolled in a prospective study. Exclusion criteria among all subjects included current use of antiplatelet, anticoagulants, or pioglitazone, bleeding disorder, renal or liver disease, congestive heart failure, pregnancy or hypersensitivity to aspirin or pioglitazone. Non-diabetic subjects were excluded for BMI > 30 kg/m2, cardiovascular disease or risk factors. All subjects previously on aspirin underwent a 7 day minimum “wash-out” period. METHODS: Four separate blood samples from each subject were collected on 2 separate days separated by a 7 day interval. On day 1, a baseline blood sample was obtained followed by a second blood sample 3 hours after ingestion of 30 mg pioglitazone. Subjects returned 1 week later after having taken a single 81 mg aspirin 2–3 hours before arrival. Samples 3 and 4 were collected in the same manner as during week 1. Platelet rich plasma (PRP) was immediately prepared and platelet aggregation performed by the turbidometric method of Born with simultaneous measurement of ATP release. ADP (5M and 10M), arachidonic acid (0.5mM) and collagen (2g/mL) were used as agonists. PRP was activated with 0.8 unit/ mL thrombin for subsequent ELISA assays of TXB2 (Thromboxane B2), TGF-β (Transforming Growth Factor-Beta) and CD40L (CD 40 Ligand). RESULTS: By Diabetic Status: a.) Baseline platelet aggregations, ATP release and ELISAs were similar between diabetic and non-diabetic subjects, with the exception of platelet aggregation using 5 uM and 10uM as agonist. b.) Mean maximum platelet aggregation after aspirin alone was 20% higher among diabetic subjects. lp;&0.5qAmong all Subjects: a.) Mean TXB2 release among all subjects was reduced from a baseline of 42,075 ± 4,479 pg/ml to 32,719 ± 3,589pg/ml after pioglitazone alone (p = 0.0004). b.) Mean TXB2 release after aspirin alone was 20,829 ± 2,753 pg/ml which was reduced to 9,569 ± 1,653 pg/ml after the addition of pioglitazone (p = 0.0001). (Figure 1) c.) Twenty-five of 40 subjects (63%) had aggregation of greater than 20% using arachidonic acid as agonist despite ingestion of 81 mg aspirin. This decreased to 11 /40 (28%) after the administration of 30 mg of pioglitazone (p < 0.0001). (Figure 2) No significant effects were observed on release of CD40L or TGFβ. Conclusion: Pioglitazone has a direct platelet stabilizing effect and potentiates the effect of aspirin irrespective of underlying cardiovascular risk. Disclosures: Francis: Takeda Pharmaceuticals North America, Inc.: Research Funding.

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The Effects Of Chemical Alterations Of The Benzoic Acid Nucleus On Platelet Function And Prostacyclin Activity In The Arterial Wall

10.1055/s-0038-1653369 ◽

1981 ◽

Author(s):

B A Killackey ◽

J J Killackey ◽

R B Philp

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Benzoic Acid ◽

Platelet Function ◽

Platelet Rich Plasma ◽

Atp Release ◽

Rabbit Aorta ◽

Arachidonic Acid Metabolism ◽

Second Phase ◽

Benzoic Acid Derivatives

The effects of a series of benzoic acid derivatives (ASA analogs) on prostacyclin (PGI2) synthesis by rabbit aorta rings and on human platelet function were examined to determine if antiplatelet activity could be separated from anti-PGI2 activity.Rings of rabbit aorta were incubated with or without drugs in Tris 0.05 M, pH 7.5 for 6 m at room temperature (R.T.). Supernatant was then transferred to platelet-rich plasma incubated at 37°C for 3 m. ADP was added 60 s later and aggregation was measured and compared to controls. Rings were also incubated with 14C-arachidonic acid (14C-AA) for 60 m at R.T. in Tris with or without drugs. Products were extracted and measured by radio-T.L.C. along with known standards. Platelet aggregation and release of ATP were measured using a ChronoLog Lumi aggregometer. The effects of these agents on PGI2 activity were similar to their effects on platelet aggregation. ASA however did not exhibit the marked inhibitory potency that it had on the second phase of platelet aggregation and ATP release. Changing the 2-acetoxy group of A.S.A. to a 2-acetyl or 3-propionyloxy resulted in a loss of inhibitory activity in both systems. 2-Propionyloxy substitution resulted in a similar spectrum of activity to ASA. The effects of these agents on the metabolism of 14C-AA by rabbit aorta rings generally confirmed the bioassay results although some of the agents had novel effects on blood vessel arachidonic acid metabolism.Despite potential species differences, this study demonstrates an inability to separate antiplatelet and anti-PGI2 effects with this series of benzoic acid derivatives. Further study of the effects of these agents on the metabolism of 14C-AA by rings of rabbit aorta may lead to a better understanding of PGI2 formation.

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Inhibition of Platelet Thromboxane Formation and Phosphoinositides Breakdown by Osthole from Angelica pubescens

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651041 ◽

1989 ◽

Vol 62 (03) ◽

pp. 996-999 ◽

Cited By ~ 38

Author(s):

Feng-Nien Ko ◽

Tian-Shung Wu ◽

Meei-Jen Liou ◽

Tur-Fu Huang ◽

Che-Ming Teng

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Inositol Phosphates ◽

Platelet Rich Plasma ◽

Chinese Herb ◽

Atp Release ◽

Inhibitory Effect ◽

Thromboxane B2 ◽

Ionophore A23187 ◽

Thromboxane Formation

SummaryOsthole, isolated from Chinese herb Angelica pubescens, inhibited platelet aggregation and ATP release induced by ADP, arachidonic acid, PAF, collagen, ionophore A23187 and thrombin in washed rabbit platelets. It showed a weak activity in platelet-rich plasma. Osthole inhibited the thromboxane B2 formation caused by arachidonic acid, collagen, ionophore A23187 and thrombin in washed platelets, and also the thromboxane B2 formation caused by the incubation of lysed platelet homogenate with arachidonic acid. The generation of inositol phosphates in washed platelets caused by collagen, PAF and thrombin was suppressed by osthole. These data indicate that the inhibitory effect of osthole on platelet aggregation and release reaction was due to the inhibition of thromboxane formation and phosphoinositides breakdown.

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Stimulated Platelet Aggregation, Thromboxane B2 Formation and Platelet Sensitivity to Prostacyclin - A Critical Evaluation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650170 ◽

1981 ◽

Vol 45 (03) ◽

pp. 204-207 ◽

Cited By ~ 42

Author(s):

Wolfgang Siess ◽

Peter Roth ◽

Peter C Weber

Keyword(s):

Arachidonic Acid ◽

Platelet Count ◽

Platelet Aggregation ◽

Reliable Method ◽

Platelet Rich Plasma ◽

Critical Evaluation ◽

Vascular Diseases ◽

Thromboxane B2 ◽

Test Time ◽

Stimulation Of

SummaryPlatelets have been implicated in the development of atherosclerotic and thrombotic vascular diseases. Evaluation of platelet aggregation in relation to endogenously formed compounds which affect platelet function may provide information of clinical and pharmacological relevance. We describe a method in which thromboxane B2 (TXB2) formation was analyzed following stimulation of platelet-rich plasma (PRP) with ADP, 1-epinephrine, collagen, and arachidonic acid. In addition, we determined platelet sensitivity to prostacyclin following ADP- and collagen-induced platelet aggregation. The parameters under study were found to depend on the platelet count in PRP, on the type and dose of the aggregating agent used, and on the test time after blood sampling. By standardization of these variables, a reliable method was established which can be used in clinical and pharmacological trials.

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Comparison of Rapid Platelet Function Assay with Whole Blood Platelet Impedance Aggregometry for the Definition of Aspirin Resistance.

Blood ◽

10.1182/blood.v106.11.4018.4018 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4018-4018

Author(s):

Anna M. Dyszkiewicz-Korpanty ◽

Anne Kim ◽

James D. Burner ◽

Eugene P. Frenkel ◽

Ravindra Sarode

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Platelet Function ◽

Whole Blood ◽

Platelet Rich Plasma ◽

Blood Platelet ◽

Aspirin Resistance ◽

Impedance Aggregometry ◽

Definition Of ◽

Induced Aggregation

Abstract The reported incidence of aspirin (ASA) resistance ranges from 5 to 30%. Various platelet function assays have been employed to detect aspirin resistance in patients with cardio- and cerebrovascular disease. Such a high proposed incidence of ASA resistance poses a critical need for a rapid point-of -care (POC) platelet function test. Unfortunately, no uniformly accepted definition of ASA resistance exists. Platelet aggregation studies that have been used to define ASA resistance are time consuming and require special technical expertise. The Ultegra Rapid Platelet Function -ASA (RPFA-ASA) has been developed as a POC test that is performed without sample processing. This optical method measures agglutination of fibrinogen-coated beads upon platelet activation with arachidonic acid. In the presence of aspirin effect, however, the agglutination of the beads is inhibited. The described cutoff of ≥ 550 Aspirin Reaction Units (ARU) is termed non-responsiveness to ASA based on a preclinical study and subsequent correlation with epinephrine-induced platelet aggregation in platelet rich plasma. Since RPFA-ASA uses whole blood, we validated its performance characteristics against a classic whole blood platelet aggregation assay (WBA). We studied 50 healthy volunteers, aged 25–75 (24 men, 26 women) with normal CBC, who had not ingested anti-platelet drugs for 14 days prior to the study. Baseline studies included WBA (dual channel aggregometer, Chrono-log Inc., Havertown, PA) using both arachidonic acid (AA -0.5; 0.25 mM) and collagen (1; 2 μg/mL) as well as an RPFA-ASA assay (Accumetrics Inc., San Diego, CA). These studies were repeated after 3 days of ASA (325 mg/d) intake. Based on a review of the literature, we defined an adequate ASA response as a completely inhibited AA-induced platelet aggregation and at least 30% inhibition of collagen-induced aggregation (both concentrations of the agonist). Thus, those with < 30% inhibition of aggregation response to collagen were considered ASA resistant. Eleven subjects were ASA resistant by WBA (20%; 8 females and 3 males (aged 25–63). In contrast, since all 50 subjects achieved ARU values of < 550 ARU, none were recognized as an ASA non-responder by the RPFA-ASA. While the current cutoff of < 550 ARU posed by the Ultegra RPFA-ASA does identify those who have taken ASA, the assay is unable to recognize ASA non-responders. Thus, based on these data, the appropriate cutoff for the recognition of ASA resistance by the RPFA-ASA should be re-adjusted to a significantly lower level to ensure appropriate assay results.

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Investigation of Platelet Functions in Chronic Myeloproliferative Disorders by Optical and Luminesance Method.

Blood ◽

10.1182/blood.v104.11.4766.4766 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4766-4766

Author(s):

Meltem O. Akay ◽

Fezan S. Mutlu ◽

Zafer Gulbas

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Reference Range ◽

Platelet Rich Plasma ◽

Atp Release ◽

Adenosine Diphosphate ◽

Myeloproliferative Disorders ◽

Test Results ◽

Chronic Myeloproliferative Disorders ◽

Significant Difference

Abstract Background: Bleeding and thrombosis are common causes of morbidity and mortality in patients with myeloproliferative disorders (MPD). Qualitative platelet abnormalities are frequently found in these patients and range from platelet hypofunction as demonstrated by defective invitro platelet aggregation, acquired storage pool disease and/or platelet membrane defects, in addition to enhanced platelet aggregation, increased plasma beta thromboglobulin levels or shortened platelet survival. In this study we aimed to perform platelet aggregation studies by optical method (on platelet rich plasma=PRP) and luminesance method (on whole blood) in chronic myeloproliferative disorders. Methods:A total of twenty-five patients with MPD (17 chronic myeloid leukemia, 6 polycythemia vera, 2 essential thrombocytosis) were enrolled. Median age was 54,4 (29–76). Platelet aggregation was measured using the optic and luminesance method. The agonists used were adenosine diphosphate (ADP), arachidonic acid (AA) ristocetin and collagen. Platelets were considered to be hyperactive if at least one result (i.e. aggregation or ATP release with one agonist) was above the reference range, and hypoactive if at least one result (i.e. aggregation or ATP release) was below the reference range. Mixed hypo- and hyperactive platelets were considered present when at least one result (i.e. aggregation or ATP release) was below and above the reference range respectively. Results:Platelet aggregation test results by two methods in myeloproliferative disorders were shown in Table 1. The percent for detection of platelet function abnormality by luminesance method was found to be higher than the optic method and a significant difference was shown between two methods (p<0,05). Conclusion Our findings suggest that;1. Luminesance platelet aggregation study is more valuable than optic platelet aggregation study for invitro assessment of platelet function in patients with MPD. 2. The use of luminesance platelet aggregation study appears useful to select patients for antiplatelet therapy. Platelet aggregation test results in myeloproliferative disorders (n=25) Normal Hypofunction Hyperfunction Mix Total abnormality Luminesance method 1(%4) 4(%16) 8(%32) 11(%44) 24(%96) Optic method 9(%36) 11(%44) 2(%8) 3(%12) 16(%64)

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Effect of Diltiazem and Low-Dose Aspirin on Platelet Aggregation and ATP Release Induced by Paired Agonists

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649575 ◽

1993 ◽

Vol 70 (02) ◽

pp. 332-335 ◽

Cited By ~ 12

Author(s):

Marjorie L Zucker ◽

Susan E Budd ◽

Lawrence E Dollar ◽

Steven B Chernoff ◽

Raul Altman

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Low Dose ◽

Atp Release ◽

Thromboxane B2 ◽

Platelet Response ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Significant Difference

SummaryThe authors studied the effects of diltiazem, administered alone and together with low-dose aspirin, on the platelet response to paired agonists. After a baseline period, 25 healthy volunteers were given oral diltiazem for 1 week (120, 240, or 360 mg/day), and then crossed over randomly between 1 week on diltiazem plus aspirin (81 mg/day), and 1 week on aspirin (81 mg/day) alone. Platelet function was tested on 2 consecutive days in each period. Synergistic platelet aggregation and ATP release were obtained at baseline using a subthreshold concentration of arachidonic acid combined with platelet activating factor, ADP, or epinephrine. Diltiazem resulted in a significant decrease from baseline in platelet aggregation and ATP release using the arachidonic acid-epinephrine combination (35% and 40% decrease, respectively, p <0.01) and a significant decrease in aggregation using the arachidonic acid-ADP combination (22% decrease, p <0.01). The effects were neither dose-related, nor accompanied by any significant change in serum thromboxane B2 levels or bleeding times. There was no significant difference between the effects of aspirin alone and aspirin plus diltiazem on the synergistic platelet aggregation and ATP release induced by the paired agonists, or on thromboxane B2 levels or bleeding times. Diltiazem administered in vivo partially inhibits the synergistic platelet aggregation and ATP release induced by paired agonists; however, in contrast to a previous in vitro study it does not potentiate the platelet-inhibitory effect of aspirin.

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Role of Cyclic Amp in Platelet Function : Evidence from Inhibition of Adenylate Cyclase in Intact Platelets by Adenosine Analogues

10.1055/s-0039-1680345 ◽

1977 ◽

Author(s):

R. J. Haslam ◽

M. M. L. Davidson ◽

J. V. Desjardins

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Cyclic Amp ◽

Adenylate Cyclase ◽

Platelet Function ◽

Platelet Rich Plasma ◽

Inhibitory Effects ◽

Adenosine Analogues ◽

Inhibitory Activities

Adenosine exerts independent stimulatory and inhibitory effects on the adenylate cyclase activity of platelet particulate fractions (Haslam & Lynham, 1972). Two adenosine analogues, 9-(tetrahydro-2-furyl) adenine (SQ 22536) and 2′, 5′-dideoxyadenosine (DDA) have now been found to show marked non-competitive inhibitory activities only. Basal and PGE1-stimulated adenylate cyclase activities were inhibited ~50% and ~70% respectively by 100 μM SQ 22536 and ~60% and ~80% respectively by 100 μM DDA. Both compounds also inhibited adenylate cyclase in intact platelets, when this was measured as the increase in cyclic [3H]AMP in platelets labelled with [3H] adenine and then incubated with papaverine. At the concentrations tested (10-500 μM), neither SQ 22536 nor DDA induced platelet aggregation or potentiated aggregation and release of [14C] 5-HT induced by suboptimal concentrations of ADP, Arg8-vasopressin, arachidonic acid or collagen added to heparinized or citrated platelet-rich plasma. However, both compounds partially blocked the inhibition by PGE1 or papaverine of aggregation induced by ADP or Arg8-vasopressin. From the concentrations exerting equal effects, DDA was ~3 times as potent in this regard as SQ 22536. Above 100 μM, the anti-inhibitory effects of both compounds decreased. The actions of these compounds in overcoming inhibition of aggregation by PGE1 were correlated with decreases in platelet cyclic [3H]AMP in platelets labelled with [3H] adenine. The results show that cyclic AMP plays no role in the responses of platelets to aggregating agents unless the platelet cyclic AMP level is elevated above the resting level and confirm that the effects of PGE1 on platelet function are mediated by cyclic AMP.

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Assessment Of a Novel Synthetic Collagen Reagent By Platelet Aggregometry

Blood ◽

10.1182/blood.v122.21.3645.3645 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3645-3645

Author(s):

Walter Jeske ◽

Vicki Escalante ◽

Jeanine M. Walenga ◽

Mamdouh Bakhos

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Platelet Function ◽

Platelet Rich Plasma ◽

Critical Role ◽

Patient Specific ◽

Blood Draw ◽

Drug Concentrations ◽

Platelet Aggregometry ◽

Induced Aggregation

Abstract Platelets play a critical role in hemostasis and depending on the physiological balance can have either decreased (bleeding) or increased (thrombosis) activity. The monitoring of platelet function is important to diagnose congenital and acquired platelet dysfunctions, predict surgical bleeding, identify the need for antiplatelet therapy and to monitor anti-platelet therapy efficacy. A growing concern today is that many anti-platelet drugs used with a one dose fits all protocol, may not achieve optimal clinical efficacy and safety in all patients. It may be desirable to dose to a targeted level of platelet function inhibition. Additionally, a subpopulation of patients treated with anti-platelet drugs may exhibit ‘anti-platelet drug resistance’ due to non-compliance, biochemical factors, genetic polymorphisms, concomitant therapies or patient-specific factors. Because platelets can be activated through a number of pathways, the sensitivity of current platelet agonists is not always optimal. This study evaluated the ability of a novel synthetic collagen reagent to detect the anti-platelet activity of ticagrelor, cilostazol and abciximab in normal and aspirinized human platelets. Whole blood was drawn from 6 healthy volunteers from the antecubital vein using a double-syringe technique and was anticoagulated by the addition of 1 part 3.2% sodium citrate to 9 parts blood. Citrated blood was centrifuged for platelet rich plasma (PRP) and platelet poor plasma (PPP). The platelet count of the PRP was measured using an ICHOR II Analyzer (Helena, Beaumont, TX) and adjusted to 250,000-300,000/µl by the addition of homologous PPP. Each donor was drawn on separate days for the ‘non-aspirinized’ and ‘aspirinized’ portions of the protocol. For the ‘aspirinized’ portion of the protocol, three donors had ingested aspirin (325 mg)< 48 hours prior to blood draw. For the other three donors, solubilized aspirin was supplemented to the PRP in vitro at a final concentration of 100 µM. All PRPs were supplemented with abciximab (1.25-5 µg/ml; Eli-Lilly, Indianapolis, IN), ticagrelor (5-50 µg/ml; AstraZeneca, London, UK) and cilostazol (5-25 µM; Otsuka, Tokushima, Japan). Platelet aggregation was measured using a PAP-8 platelet aggregometer (BioData, Horsham, PA) in response to ADP (10 µM; BioData), arachidonic acid (AA) (500 µg/ml; BioData), biologic collagens (0.19 mg/ml; BioData or 10 µg/ml; Chronolog) and synthetic collagen (8-64 ng/ml; JNC, Tokyo, Japan). In non-aspirinized PRP, ticagrelor strongly inhibited ADP- and AA-induced aggregation. Whereas the two biologic collagens were not able to identify the anti-platelet effect of ticagrelor, a clear anti-platelet effect was seen with the synthetic collagen at concentrations ≤ 32 ng/ml. In the presence of aspirin, the anti-platelet effect of ticagrelor was no longer observed with AA or 8 ng/ml synthetic collagen. Although the effect with 16 and 32 ng/ml synthetic collagen was reduced, ticagrelor could still be detected. In non-aspirinized PRP, the most marked effect of cilostazol was on AA-induced aggregation, where aggregation levels of ∼20% were observed at drug concentrations ≥ 12.5 µM (vs. 95% in the absence of cilostazol). Cilostazol at concentrations up to 25 µM did not inhibit aggregation induced by either biologic collagen, but at lower concentrations of synthetic collagen, the anti-platelet effect of higher concentrations of cilostazol could be observed. Addition of aspirin to the PRP negated the ability to detect cilostazol. Arachidonic acid and synthetic collagen (8 and 16 ng/ml) were the most sensitive for detecting abciximab. Inhibition of biologic collagen-induced aggregation was only observed at the 5 µg/ml drug concentration. Although the synthetic collagen reagent produced lower levels of aggregation in aspirinized plasma than in non-aspirinized plasma, abciximab was readily detectable in the presence of aspirin using the synthetic collagen reagent. Low concentrations of the synthetic collagen reagent induced platelet aggregation that is inhibited by several classes of anti-platelet drugs (ADP receptor antagonists, GPIIb/IIIa antagonists, PDE inhibitors), and in addition combined anti-platelet effects with aspirin could be measured. Because such effects are not observed with standard biologic collagens, the new synthetic collagen may be a useful addition to clinical laboratory testing for platelet function. Disclosures: Jeske: BioData Corporation: Research Funding.

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Chlorobutanol, a Preservative of Desmopressin, Inhibits Human Platelet Aggregation and Release In Vitro

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647339 ◽

1990 ◽

Vol 64 (03) ◽

pp. 473-477 ◽

Cited By ~ 4

Author(s):

Shih-Luen Chen ◽

Wu-Chang Yang ◽

Tung-Po Huang ◽

Shiang Wann ◽

Che-ming Teng

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Atp Release ◽

Free Calcium ◽

Dependent Manner ◽

Antiplatelet Effect ◽

Human Platelet Aggregation ◽

Acid Pathway ◽

Arachidonic Acid Pathway

SummaryTherapeutic preparations of desmopressin for parenteral use contain the preservative chlorobutanol (5 mg/ml). We show here that chlorobutanol is a potent inhibitor of platelet aggregation and release. It exhibited a significant inhibitory activity toward several aggregation inducers in a concentration- and time-dependent manner. Thromboxane B2 formation, ATP release, and elevation of cytosolic free calcium caused by collagen, ADP, epinephrine, arachidonic acid and thrombin respectively were markedly inhibited by chlorobutanol. Chlorobutanol had no effect on elastase- treated platelets and its antiplatelet effect could be reversed. It is concluded that the antiplatelet effect of chlorobutanol is mainly due to its inhibition on the arachidonic acid pathway but it is unlikely to have a nonspecitic toxic effect. This antiplatelet effect of chlorobutanol suggests that desmopressin, when administered for improving hemostasis, should not contain chlorobutanol as a preservative.

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Effects of Halothane on Platelet Function

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650105 ◽

1980 ◽

Vol 44 (03) ◽

pp. 143-145 ◽

Cited By ~ 19

Author(s):

J Dalsgaard-Nielsen ◽

J Gormsen

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Platelet Rich Plasma ◽

Human Platelets ◽

Halothane Anaesthesia ◽

Inhibition Of Platelet Aggregation ◽

Transient Impairment ◽

High Concentrations ◽

Uptake And Release ◽

Platelet Functions

SummaryHuman platelets in platelet rich plasma (PRP) incubated at 37° C with 0.3–2% halothane for 5–10 min lost the ability to aggregate with ADP, epinephrine and collagen.At the same time uptake and release of 14C-serotonin was inhibited. When halothane supply was removed, platelet functions rapidly returned to normal. However, after high concentrations of halothane, the inhibition of platelet aggregation was irreversible or only partially reversible.The results suggest that halothane anaesthesia produces a transient impairment of platelet function.

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