Significant Decrease In Platelet Aggregation Research Articles

Adverse effects of trazodone in dogs on primary hemostasis and electrocardiogram: A single-blinded placebo-controlled crossover study.

Trazodone is a serotonin antagonist/reuptake inhibitor medication commonly used for anxiety in dogs. Therapy with selective serotonin reuptake inhibitors in humans is associated with bleeding disorders and increased arrhythmogenesis. To evaluate markers of primary hemostasis and corrected QT (cQT) interval in dogs before and after oral administration of standard dosages of trazodone or placebo. Fifteen apparently healthy, client-owned dogs. A single-blinded, randomized placebo-controlled crossover study was performed. Dogs were administered trazodone (5 to 7.5 mg/kg PO Q12h) or placebo. [Correction added after first online publication on 14 October 2023. In the abstract (methods) section (57.5 mg/kg PO Q12h) changed as (5 to 7.5 mg/kg PO Q12h).] Buccal mucosal bleeding time (BMBT), platelet count, platelet aggregation via Plateletworks, PFA-100 closure time and cQT interval were measured. A Shapiro-Wilk test was performed followed by either a paired t test or a Wilcoxon signed-rank test. No significant difference was detected in the BMBT, PFA-100 closure times, platelet counts, and cQT interval between trazodone or placebo. However, using Plateletworks, there was a significant decrease in platelet aggregation after administration of trazodone (95%; 81-97 vs 62%; 39-89, P = .002) and not placebo (95%; 81-97 vs 91%; 81-96, P = .21). It is unknown if this represents a clinically relevant change or if dogs with preexisting impairment in primary hemostasis or receiving higher dosages or longer durations of trazodone could have a more substantial change in hemostatic variables.

The study of platelet microparticles and P-selectin expression in patients with the peripheral arterial diseases

BACKGROUND: High platelet reactivity leads to the progression of atherosclerosis and its complications. Activated platelets adhere to the site of endothelium damage on the vessel wall and initiate the formation of an arterial thrombus, followed by acute ischemia of the organ. Biochemical and cellular marker such as platelet microvesicles and P-selectin can be analyzed using flow cytometry, which is based on a specific antigen-antibody interaction. Patients with peripheral arterial disease are at significantly greater risk of cardiovascular and cerebrovascular complications than individuals of the same age and sex. The use of antiplatelet agents is an important part of pathogenetic therapy and prevention of cardiovascular diseases and their complications.
 AIM: This study was to evaluate the level of platelet microparticles and P-selectin expression in patients with peripheral arterial disease receiving antiplatelet therapy.
 MATERIALS AND METHODS: The study included 49 people, which included three study groups: patients with obliterating disease of the arteries of the lower extremities (n = 14) on the background of long-term use (more than 14 days) of double (75 mg clopidogrel and 100 mg Acetylsalicylic acid) antiplatelet therapy, patients with COVID-19 (n = 15), who made up the positive control group in the determination of microparticles of platelet origin, and healthy volunteers (n = 20) without signs of acute respiratory disease, without a history of cardiovascular and thromboembolic episodes, not taking antiplatelet drugs. The functional activity of platelets was assessed by two methods: using light aggregometry and analysis of P-selectin expression on platelet surface by flow cytometry. The number of platelets microparticles in blood plasma was also determined using flow cytometry.
 RESULTS: A significant decrease in platelet aggregation was found in patients with peripheral arterial disease taking antiplatelet agents, compared with controls by used light aggregometry. Similar changes were obtained when analyzing the expression of P-selectin on platelets. A higher percentage of platelets microparticles with the CD9+CD41+ phenotype was found in patients with severe inflammation compared with peripheral arterial disease patients treated with antiplatelet agents and compared with the healthy controls.
 CONCLUSIONS: Thus, our study reflects the consistency of the results of three different laboratory tests in assessing the platelets reactivity in patients with the peripheral arterial diseases taking antiplatelet drugs.

A Systematic Review on the Effect of Common Medications on Platelet Count and Function: Which Medications Should Be Stopped Before Getting a Platelet-Rich Plasma Injection?

Background:Platelet-rich plasma (PRP) exerts its effect through the release of growth factors and cytokines from the platelet concentrate. Certain medications may affect platelet count or function, resulting in decreased efficacy of PRP injections.Purpose:To systematically review the literature regarding common medications and their effects on platelets to establish guidelines for which medications should be stopped before obtaining a PRP injection.Study Design:Systematic review; Level of evidence, 2.Methods:This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search for studies assessing the effect of common medications on platelet count or platelet function was performed of the PubMed, Cochrane Library, Web of Science, and OpenGrey databases. Inclusion criteria were as follows: drug studied was aspirin, acetaminophen, a nonsteroidal anti-inflammatory drug (NSAID), a statin, or gabapentin; human participants; and article in the English language. Risk of bias was assessed using the Cochrane Risk of Bias tool and the Risk of Bias in Non-randomised Studies—of Interventions tool.Results:A total of 1711 studies were identified through the initial search, with 20 studies meeting all inclusion criteria. No studies involving gabapentin met all inclusion criteria. Patients treated with aspirin (268 patients) or acetaminophen (13 patients) showed a significant decrease in platelet aggregation. Statin therapy (73 patients) did not result in a significant decrease in platelet aggregation. Patients who took NSAIDs (172 patients) demonstrated significantly decreased platelet aggregation only when treated with nonselective formulations. Those treated with cyclooxygenase (COX)-2–selective NSAIDs showed no significant difference in platelet aggregation. Treatment with aspirin, acetaminophen, statins, or NSAIDs did not lead to a significant decrease in platelet count.Conclusion:Aspirin, acetaminophen, and nonselective NSAIDs should be considered for suspension before a PRP injection because of their potential to diminish the effects of the injection. COX-2–selective NSAIDs and statins do not need to be withheld before a PRP injection.

Effect of lactic acid addition to equine whole blood on platelet aggregation measured by impedance aggregometry

Acidemia in sick or injured horses is often due to lactic acid accumulation. Alterations in platelet function and hemostasis are among numerous deleterious effects caused by decreased physiologic pH. We aimed to evaluate the effect of hyperlactatemia and resultant acidemia on platelet aggregation in equine whole blood using impedance aggregometry. Platelet aggregation was measured using the Multiplate analyzer in whole blood from 34 healthy horses at baseline and after in vitro addition of lactic acid to adjust the pH. Platelet aggregation of each sample was quantified by the area under the curve measurement reported by the Multiplate system. The association between platelet aggregation and pH was analyzed using a linear mixed-effects model. The association of baseline platelet aggregation with hematocrits (Hcts), white blood cell (WBC) counts, and platelet counts was evaluated using Pearson's correlations. There was a significant association between acidemia and decreased platelet aggregation. No significant correlations were detected between platelet aggregation and Hct, WBC count, or platelet count. Platelet aggregation measured in healthy horses using the Multiplate analyzer showed substantial variation between animals. Acidemia caused by the addition of lactic acid to equine whole blood was associated with a mild though statistically significant decrease in platelet aggregation. In conjunction with other factors, this change may contribute to morbidity-related disorders of hemostasis, although its precise clinical relevance is uncertain.

The effect of adding lactic acid to canine whole blood on platelet aggregation as measured by impedance aggregometry.

Acidemia in sick dogs often results from the accumulation of lactic acid. The resulting decrease in blood pH can have many physiologic effects, including alteration of platelet function. We aimed to evaluate the effect of hyperlactatemia and subsequent acidemia on platelet aggregation in canine blood using impedance aggregometry. Platelet aggregation was measured in blood from 27 healthy dogs using the Multiplate analyzer at baseline and after in vitro addition of two different volumes of lactic acid to adjust the pH. The area under the curve (AUC), reported by the Multiplate analyzer, was used to assess the extent of platelet aggregation in each sample. A linear mixed effects model was used to test for the association between platelet aggregation and pH. The association of baseline platelet aggregation with HCTs, platelet counts, and WBC counts was assessed using Pearson's correlations. Acidemia was associated with a significant decrease in platelet aggregation. No significant correlations were detected between platelet aggregation and HCT, platelet count, or WBC count. Platelet aggregation measured using the Multiplate analyzer showed substantial individual variation. Worsening acidemia due to the addition of lactic acid caused a mild but significant decrease in platelet aggregation in canine blood. The clinical significance of this change is uncertain but could be important when combined with other abnormalities of hemostasis associated with illness.

Treprostinil treatment decreases circulating platelet microvesicles and their procoagulant activity in pediatric pulmonary hypertension.

Pulmonary arterial hypertension (PAH) results from pulmonary vascular disease and may eventually lead to right heart failure and death. Vasodilator therapy has greatly improved PAH prognosis. Circulating microvesicles are considered as surrogate markers of endothelial and hematopoietic cell activation. Thus, our purpose was to determine if MVs are upregulated in pediatric PAH such as reported in adult patients, and to analyze the impact of vasodilator therapies on MV count and function. Population study consisted of 26 patients of median age 6.09 years, with Congenital Heart Disease (CHD) and elevated pulmonary vascular resistance (CHD-PAH) or idiopathic PAH (iPAH). Compared to healthy controls, all circulating MV subpopulations were found higher in untreated PAH patients. No significant differences of annexin-V+ total MV, endothelial, or leukocyte derived-MV counts were found between untreated patients and those receiving oral vasodilator therapies. Conversely, platelet MVs were significantly lower in the group treated with SC-treprostinil compared with both untreated PAH and oral therapy groups (P = 0.01), and exhibited a significant decrease of phospholipid procoagulant activity. Control samples treated in vitro with treprostinil at therapeutic concentrations showed as expected a significant decrease of platelet aggregation but also a reduced spontaneous MV generation. Our results suggest that treprostinil, besides vasodilation, might exert its beneficial effect through an inhibition of platelet activation, resulting in a decreased number and procoagulant activity of circulating MVs.

Study of pharmacodynamic interaction of Phyllanthus emblica extract with clopidogrel and ecosprin in patients with type II diabetes mellitus

BackgroundDiabetes mellitus is associated with oxidative stress which impairs the platelet function. Phyllanthus emblica extract a rich source of vitamin C plays an important role in scavenging free radicals. The effect of vitamin C on platelet aggregation in healthy and coronary artery disease patients has been demonstrated. The present study attempts to study the pharmacodynamic interactions of P. emblica extract with clopidogrel and ecosprin. Materials and methodsThis was a randomized open label crossover study of 10 type II diabetic patients. The dosage schedules were either single dose of 500mg P. emblica extract or 75mg clopidogrel or 75mg ecosprin or 500mg P. emblica+75mg clopidogrel or 500mg P. emblica+75mg ecosprin. After single dose study and washout period, patients received either 500mg P. emblica extract twice daily or 75mg clopidogrel or 75mg ecosprin once daily or combinations for 10 days. Platelet aggregation was measured at baseline and at 4h of treatment after single and multiple dose study along with recording of bleeding and clotting time. ResultsAfter single and multiple dose administration of the three treatments and with combinations there was statistically significant decrease of platelet aggregation compared to baseline. Further, the mean percent inhibition of platelet aggregation was significant, when compared between single and multiple doses of P. emblica. The bleeding and clotting time was prolonged with single and multiple dose administration of all treatments compared to baseline. All treatments were well tolerated. ConclusionP. emblica extract demonstrated significant antiplatelet activity with both single and multiple dose administration.

Point-of-Care Assessment of Hypothermia and Protamine-Induced Platelet Dysfunction with Multiple Electrode Aggregometry (Multiplate®) in Patients Undergoing Cardiopulmonary Bypass

Coagulopathy is common after cardiopulmonary bypass (CPB), and platelet dysfunction is frequently considered to be a major contributor to excessive bleeding. Exposure to hypothermia may exacerbate the platelet function defect. We assessed platelet function during and after deep hypothermia with multiple electrode aggregometry (Multiplate(®); Verum Diagnostica GmbH, Munich, Germany). Twenty adult patients undergoing pulmonary endarterectomy for chronic pulmonary hypertension were cooled on CPB to 20°C and deep hypothermic arrest was used to facilitate surgery. We analyzed platelet aggregation in whole blood samples at 12 measuring points during and after the procedure. Platelet aggregation was stimulated via the thrombin receptor (TRAPtest) at the patient's actual body temperature (AUC-CT) and after rewarming the samples to 37°C (AUC-37). In addition, we tested samples at 2 time points after 2 minutes of in vitro incubation with 20 μg protamine (0.067 μg/μL). Results are expressed as area under the aggregation curve (AUC). Cooling resulted in a marked decrease of platelet aggregation to a minimum AUC-CT of 20.5 (95% confidence interval [CI] 8.9-32.1) at 20°C body temperature. AUC-CT was significantly different from baseline (92.8, 95% CI 82.5-103.1) for temperatures of ≤28°C (P < 0.001), whereas the change in AUC-37 only became significant at the lowest body temperature (59.4, 95% CI 41.3-77.4). After rewarming to 36°C, AUC-CT and AUC-37 had recovered to 67.6 (95% CI 53.9-81.3) and 71.7 (95% CI 52.5-90.8), respectively. The mean AUC-CT was significantly lower than the mean AUC-37 from cooling at 28°C to warming at 24°C inclusive, and the relationship with temperature during cooling was significantly different between AUC-CT and AUC-37 (regression coefficients 4.7 [95% CI 4.2-5.2] vs 1.3 [95% CI 0.7-1.9]; P < 0.0001). After administration of protamine, mean aggregation decreased significantly for both measurements by 38.2 (95% CI -27.9 to -48.5; P < 0.001) and 44.5 (95% CI -58.5 to -30.5; P < 0.001), respectively. Similarly, adding protamine in vitro resulted in a decrease of mean aggregation by 35.1 (95% CI -71.0 to 0.8; P = 0.055) when measured after administration of heparin, and 56.5 (95% CI -94.5 to -18.5; P = 0.005) at the end of CPB. Platelet aggregation, assessed by multiple electrode aggregometry (Multiplate), was severely affected during deep, whole-body hypothermia. This effect was partially reversible after rewarming, and was distinct from a general decline of platelet aggregation during CPB. Protamine also caused a significant decrease in platelet aggregation in vivo and in vitro.

An Assessment of Cardiopulmonary Bypass-Induced Changes in Platelet Function Using Whole Blood and Classical Light Transmission Aggregometry: The Results of a Pilot Study

In this study, we explored whether antiplatelet medications impair whole blood impedance aggregometry after cardiac surgery and cardiopulmonary bypass (CPB) compared with classical light transmission aggregometry (LTA). Multiplate (M) assays measuring changes in electrical resistance as aggregation units over time, and LTA assays (% aggregation) induced by collagen (COL), adenosine diphosphate (ADP), or arachidonic acid were performed simultaneously using arterial blood samples obtained before induction of anesthesia, 15 min and 3 h after neutralization of heparin in 70 consecutive patients scheduled for elective coronary artery bypass grafting. Patients in Group A (n = 48) discontinued intake of antiplatelet drugs for at least 7 days and served as controls, patients in Group B (n = 11) received aspirin 100 mg/d and those in Group C (n = 11) aspirin 100 mg/d and clopidogrel 75 mg/d (dual antiplatelet therapy) until the day before surgery. In patients without antiplatelet therapy, 15 min and 3 h after protamine a significant decrease in platelet aggregation was observed with all three agonists and both aggregation methods. In patients receiving aspirin alone, LTA-COL, LTA-ADP and M-ADP changed significantly over time, and ADP assays of both aggregation methods showed a significant decrease in platelet aggregation 15 min after protamine in patients receiving dual antiplatelet therapy. When calculating the areas under the receiver-operating characteristic curves for discrimination of antiplatelet agents, LTA-COL was able to discriminate between controls and patients receiving aspirin or dual antiplatelet therapy 15 min and 3 h after CPB and the M-ADP assay was able to discriminate between controls and patients receiving dual antiplatelet therapy 3 h after protamine. Whole blood and classical LTA performed with all commonly used agonists enable detection of CPB-induced changes in platelet aggregation in patients not taking antiplatelet medication, whereas in patients receiving antiplatelet therapy, ADP-induced antiplatelet assays are preferable for detecting CPB-induced impairment of platelet aggregation.

In Vitro Inhibition of Platelet Aggregation in Response to Increasing Concentrations of Tirofiban in Patients with Significant Renal Insufficiency

Patients with impaired renal function are a growing subset at higher risk for cardiovascular complications due to vasculopathic state, inducing accelerated atherosclerosis and arteriosclerosis. These patients are at increased risk for complications after coronary interventions, especially major bleeding events. As a result, this at-risk population of patients has not been well studied in most of the major clinical trials evaluating coronary interventions. Of particular interest is the optimal dosing of glycoprotein IIb-IIIa inhibitors in the setting of acute myocardial infarction. In this study, we attempted to find the in vitro concentration of tirofiban required to inhibit platelet aggregation to <10% in patients with moderate to severe renal insufficiency. A total of 21 patients were divided into two groups based on estimated creatinine clearance (group 1 <46ml/min; group 2 >46ml/min). Platelet-rich plasma from each subject was then incubated in vitro with increasing concentrations of tirofiban (25, 37.5, and 50ng/ml), and light transmission aggregometry assay was used to assess the degree of platelet aggregation in response to adenosine diphosphate (ADP). Patients in group 1 had a baseline platelet aggregation of 45%, which decreased to 10% at a 25.0ng/ml concentration of tirofiban; the effect was enhanced to a platelet aggregation of <5% at higher doses. In contrast, subjects in group 2 with creatinine clearance >or=46ml/min had an average platelet aggregation inhibition of 12% with 50ng/ml of tirofiban.We found a significant decrease in platelet aggregation in group 2 at 25, 37.5, and 50ng/ml of tirofiban (p<0.05) in comparison with group 1. Our data indicate that patients with moderate to severe renal dysfunction suppress their platelet aggregation to <10% with 25ng/ml of tirofiban, one-third of the standard effective dose for patients with normal renal function.We suggest further clinical trials to define an objective means to calculate proper renal dosing of glycoprotein IIb-IIIa inhibitors in these patients to prevent potentially fatal complication of major hemorrhagic events.

Effects of oxypolygelatin and dextran 70 on hemostatic variables in dogs

ObjectiveTo evaluate and compare coagulation variables following the administration of oxypolygelatin and dextran 70 to clinically healthy dogs. Study designRandomized cross–over experimental study. AnimalsA total of eight healthy adult female Beagles aged 2–4 years old and weighing 11.8 ± 2.7 kg. MethodsThe dogs received a 15–minute intravenous (IV) infusion of 5 mL kg−1 oxypolygelatin or 10 mL kg−1 6% dextran 70. Before (PRE) and at 2, 5, and 24 hours after administration, packed cell volume (PCV), total solids concentration (TS), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen concentration (FIB), platelet numbers (Plat), factor VIII coagulant activity (VIII:C), von Willebrand factor antigen concentration (vWf:Ag) and platelet function and buccal mucosal bleeding time (BMBT) were measured. Platelet function was assessed using aggregation and by measuring ATP release from aggregating platelets over 6 minutes, with 20, 10, and 5 μm ADP and 5 and 10 μg of collagen mL−1 as platelet activation agonists. ResultsAll baseline values were within our normal ranges, except for one dog that had low vWf:Ag PRE values prior to both dextran and oxypolygelatin administration. Following dextran and oxypolygelatin administration, the PCV and TP were significantly (p < 0.05) decreased. Plat, FIB, and vWf:Ag decreased, while BMBT and VIII:C increased following dextran administration. Dextran also caused a significant decrease in platelet aggregation in response to ADP. Oxypolygelatin caused a significant decrease in vWf:Ag, Plat, and FIB compared to PRE values. The total amount of ATP released, standardized to platelet number, did not vary significantly for either group at any sampling time from PRE values. No significant changes from PRE values were noted at any time in either group for PT or APTT. ConclusionAt the doses administered, both dextran and oxypolygelatin can interfere with hemostatic variables in healthy dogs, but dextran's effect is more profound and prolonged when compared to oxypolygelatin. Clinical relevanceOxypolygelatin causes fewer hemostatic abnormalities when compared to dextran, making it a superior colloid for administration at the doses tested.

The Effect of Clopidogrel (Plavix) on Platelet Function in Patients with Peripheral Vascular Disease ‐ Comparison with Aspirin

Aims: To establish if clopidogrel (Plavix) is a more effective platelet inhibitor than aspirin in patients with peripheral vascular disease (PVD). Introduction:PVD is a common condition that is associated with a considerable increase in the risk of vascular events, like myocardial infarction (MI) and stroke. Aspirin resistance has been reported in PVD patients. These patients tend to have hyperactive platelets. Aspirin is an inhibitor of the synthesis of thromboxane A2 (TXA2), a promoter of platelet aggregation. In contrast, clopidogrel acts at the level of the platelet ADP receptor. ADP is released by activated platelets to further induce aggregation on other platelets. The rationale behind combination therapy is that aspirin and clopidogrel act by different mechanisms. Methods: Twenty PVD patients (14 men; 6 women: mean age 70 years) took part in this study. Citrated venous blood was collected at baseline (visit 1, n = 20), 10 days after clopidogrel (75 mg/day) or aspirin (75 mg/day) (visit 2, n = 10 for each drug), and then 10 days after combination therapy with aspirin plus clopidogrel, (visit 3, n = 20). Platelet aggregation was measured in whole blood using a MD18 Coulter counter, after adding ADP (5–10 μmol/l) or 5HT (serotonin, 5.0 μmol/l). Spontaneous platelet aggregation (SPA) was followed for up to 15 min. Platelet shape change (PSC) was assessed after adding agonists (5-HT, 0.5 μmol/l; ADP, 0.4-0.8 μmol/l -in platelet rich plasma) using a high-resolution (0.07 fl) channelyzer (ZM34 coupled to a Coulter counter). Median platelet volume (MPV) was measured at various time points. Results: There was a significant decrease in platelet aggregation, induced with ADP (measured as% free platelet count, FPC), after taking clopidogrel for 10 days, P = 0.0001. In contrast taking aspirin for 10 days showed no significant increase in FPC after adding ADP. The combination of clopidogrel plus aspirin significantly decreased SPA (P = 0.001) and also ADP-induced aggregation (P = <0.0001). SPA was not significantly altered by either drug used alone. The effect of either drug or both combined on 5HT-induced platelet aggregation was not significant. ADP-induced PSC (using% increase in MPV) was more significantly inhibited by clopidogrel (P = 0.004) than by aspirin (P = 0.01). This was also true for 5HT-induced PSC (clopidogrel P = 0.01, aspirin P = 0.03). However, with combination therapy the PSC effect was more marked (ADP, P = 0.0002, 5HT, P = 0.0006) than with either drug alone. Conclusions:In patients with PVD, clopidogrel is a more potent inhibitor of ADP-induced platelet activation than aspirin. There appears to be a beneficial combined effect of clopidogrel plus aspirin on platelet activation in PVD.

Effects of nonionic contrast media on platelet aggregation: assessment by particle counting with laser-light scattering.

Intravascular radiographic contrast media used in angiography, particularly nonionic contrast media, may cause activation of platelets. This study was designed to determine which properties of nonionic contrast media were potentially responsible for this action. Platelet aggregation after adenosine diphosphate stimulation was studied in the platelet rich plasma obtained from 37 patients who underwent left ventriculography using the highly sensitive method of particle counting with laser-light scattering. Platelet activation by contrast media was studied in the platelet rich plasma from healthy volunteers using flow cytometric analysis to detect platelet degranulation as P-selectin expression. There was a significant decrease in platelet aggregation in patients injected with ioxilan or iomeprol compared with patients injected with iohexol. There was a significant increase in P-selectin expression with the three groups of contrast media compared to control. The platelet activation with ioxilan or iomeprol was significantly less compared to the activation with iohexol. The comparison showed that previous generalization regarding platelet activation by nonionic contrast media might not be valid. It is presumed that the higher osmolality of iohexol may contribute to the increase in platelet aggregation and activation.

Effects of cephalothin, cefazolin, and cefmetazole on the hemostatic mechanism in normal dogs: implications for the surgical patient.

Twenty-six female beagles were used to evaluate the effects of intravenous and long-term subcutaneous administration of cephalothin, cefazolin, and cefmetazole on platelet function and the coagulation cascade. Platelet aggregation in response to an adenosine diphosphate (ADP) agonist, bleeding time, platelet count, platelet size, prothrombin time (PT), and activated partial thromboplastin times (aPTT) were evaluated before and 90 minutes after two intravenous doses (22 mg/kg) of cephalothin, cefazolin, and cefmetazole given at 90-minute intervals. Dogs given saline injections were used as controls. Platelet count, platelet size, PT, and aPTT were evaluated after 7 days of subcutaneous administration of saline, cefazolin, and cefmetazole (22 mg/kg every 8 hours). A significant decrease in platelet aggregation in response to ADP was detected 90 minutes after intravenous administration of cephalothin. Bleeding time was increased significantly 90 minutes after intravenous administration of cefmetazole. Platelet size was decreased significantly 24 hours after onset of the study in all animals, including controls. No significant changes in platelet count, platelet size, PT, or aPTT were detected after 7 days of subcutaneous administration. Cefazolin had no adverse effects on platelet aggregation in response to ADP, bleeding time, platelet count, platelet size, PT, or aPTT. Therefore, cefazolin should be considered as a perioperative antibiotic in dogs with conditions predisposing to hemostatic complications.

Hemorheological and cardiovascular responses to beta-endorphin and naloxone in healthy subjects and in patients with essential hypertension.

The purpose of the present study was to determine if opioid agonism (beta-endorphin) and antagonism (Naloxone) exert rheological and cardiovascular effects in normal humans and in patients with essential hypertension. Eight hypertensive patients were matched for age, sex, and body habitus (body mass index, waist to hip ratio) with eight normotensive healthy subjects. In all subjects, heart rate and blood pressure (continuous automatic recording), blood and plasma viscosity, fibrinogen, hematocrit, and platelet aggregation to ADP were evaluated during an infusion of human synthetic beta-endorphin (0.5 mg/h). On a different day and in randomized order, the subjects were submitted to another beta-endorphin infusion preceded by an i.v. naloxone bolus (5 mg in 5 min). beta-Endorphin and naloxone failed to significantly alter heart rate or blood pressure in both normotensive and hypertensive subjects. In hypertensive patients, beta-endorphin significantly increased blood viscosity and ADP-induced platelet aggregation, but only the former effect was naloxone-sensitive. In normotensive subjects, beta-endorphin caused a transient but significant decrease of platelet aggregation that was reversed by naloxone. These data suggest that beta-endorphin may play some role in the inhibitory control of platelet aggregation in normal subjects. An altered responsiveness of some rheological determinants to beta-endorphin seems to be present in human hypertension.

Hyperaggregation of platelets detected by whole blood platelet aggregometry in newly diagnosed noninsulin-dependent diabetes mellitus.

Twenty-five newly diagnosed cases of noninsulin-dependent diabetes mellitus were studied at the time of diagnosis and again after metabolic control of diabetes was achieved (approximately 3 months later) for platelet aggregation abnormalities in whole blood by the impedance method. Adenosine diphosphate in 10 and 20 mumol/L final concentrations and arachidonic acid in 25 and 50 mmol/L final concentrations were used as agonists. Patients had a significant hyperaggregation of platelets (P < 0.01) at the time of diagnosis compared with age-matched healthy control subjects. After metabolic control of blood glucose was achieved using oral hypoglycemic agents (n = 20) and diet regulation alone (n = 5), there was a significant decrease in platelet aggregation (P < 0.01). There was a positive relationship between blood glucose levels and whole blood platelet aggregation with adenosine diphosphate (P < 0.02 and < 0.05, with 10 mumol/L and 20 mumol/L, respectively), but there was no relationship between aggregation and glycosylated hemoglobin levels. Thus, platelet hyperaggregation was present even at the time of diagnosis in patients with diabetes mellitus in the absence of any vascular complications, and there was significant improvement in platelet hyperaggregation after metabolic control of blood glucose levels was achieved.

N−3 Polyunsaturated fatty acids raise low-density lipoproteins, high-density lipoprotein 2, and plasminogen-activator inhibitor in healthy young men

The effects of a moderate supplementation in n-3 polyunsaturated fatty acids (PUFAs) were investigated in 36 young healthy adult males. Factors investigated were lipoprotein (including HDL subfractions and apolipoproteins) and hemostasis indexes, assessed by platelet aggregation and plasminogen-activator-inhibitor (PAI) activity. Fat-controlled diets were prescribed, one with and one without a fish-oil supplement (control diet), successively during 3 wk in random order. Total calorie, fat, and cholesterol intakes were similar in the two diets. Triglycerides in serum and very-low-density lipoproteins were lower and high-density-lipoprotein 2 cholesterol was higher with the n-3 PUFA-supplemented diet. These effects as well as a significant decrease in platelet aggregation can be considered beneficial in terms of cardiovascular risk. However, significant increases in low-density-lipoprotein cholesterol and PAI activity occurred and were correlated. This latter effect could be detrimental.

Inhibition of platelet function during in vivo infusion of isosorbide mononitrates: Relationship between plasma drug concentration and hemodynamic effects

Isosorbide monitrates (IS-2-MN and IS-5-MN), hepatic metabolites of isosorbide dinitrate, inhibit platelet function in vitro very differently, with IS-2-MN being much more potent than IS-5-MN. To assess their antiplatelet properties in vivo and to compare time and dosage requirements, we infused both IS-2-MN and IS-5-MN for 30 minutes, on 2 separate days, into nine patients with stable coronary artery disease, at rates of 4 mg/hr (n = 4) and 8 mg/hr (n = 5). Two additional patients received IS-5-MN at 16 mg/hr. Platelet aggregation and thromboxane (TX) B2 generation in response to various agonists, drug plasma concentrations, and blood pressure were monitored throughout the study. A significant decrease in platelet aggregation and TXB2 production by adenosine diphosphate and adrenaline occurred in seven of nine patients receiving IS-2-MN and in 7 of 11 patients receiving IS-5-MN. Response was dose related, with more patients responding at 8 mg/hr to IS-2-MN (five of five) than to IS-5-MN (three of five), and was maximum at the end of the infusion time, corresponding to peak plasma levels. Patients responding to drug infusions with an inhibition of platelet function were characterized by a greater vascular responsiveness compared to nonresponders, since the decrease in systolic blood pressure (mean +/- SEM) was significantly greater in the former (15.4 +/- 3.2) than in the latter (2.5 +/- 2.1, p less than 0.05). Therefore both mononitrates, when administered at infusion rates between 8 and 16 mg/hr, are accompanied by a consistent inhibition of adenosine diphosphate- and adrenaline-induced aggregation and TX generation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Ticlopidine on Platelet Function and Blood Coagulation

A double blind study was performed on 20 atherosclerotic patients. A placebo was administered to one group of 10 patients (group A) and ticlopidine (500 mg/day) was administered to another group of 10 patients (group B) for one month. ADP and collagen-induced platelet aggregation (PA), platelet malondialdehyde (MDA) produced by thrombin stimulation and plasma beta-thromboglobulin (beta TG) levels, prothrombin time, activated partial thromboplastin time (APTT) fibrinogen, antithrombin (AT) III fibrin(ogen) degradation products, alpha 2-antiplasmin and plasminogen were evaluated in both groups before and after treatment. No changes in PA, MDA and beta TG were seen in group A. Group B showed a significant decrease of PA, beta TG and a significant increase of MDA. No changes on blood coagulation data were seen in either group. This study suggests that ticlopidine is able to inhibit platelet function in vivo.

Inhibition of platelet aggregation by contrast media.

The effect of 30% Urografin on platelet aggregation induced by adenosine diphosphate (ADP), epinephrine, and arachidonic acid was examined. In vivo and in vitro experiments in 10 nondiabetic subjects and in vitro experiments in 7 diabetic-uremic patients showed a statistically significant decrease in platelet aggregation 20 minutes after in vitro incubation or in vivo infusion with Urografin. Urografin concentration was about 2.4-2.5%. The possibility of bleeding induced by contrast media and the connection with acute renal failure in diabetic-uremic patients are discussed.