Aspirin and fraxiparine in the prevention of laser induced thrombosis in the presence of iodinated contrast media

The purpose of this study was to investigate the thromboembolic properties of ionic and nonionic contrast media in rats pretreated with aspirin and/or fraxiparine using an experimental model of laser induced thrombosis in the mesenteric microvessels of 17 groups of five male Wistar rats each. Two ionic (ioxaglate and diatrizoate) and two nonionic contrast media (iopamidol and iohexol), alone or associated with antithrombotic drugs (aspirin and/or fraxiparine) were studied. To evaluate the effects of these substances in this model, the number of laser beams needed to induce platelet thrombus formation, the number of emboli detached from the thrombus and the duration of embolization were quantified. Platelet aggregation induced by ADP, induced hemorrhagic time (IHT) and haemoglobin loss level were also determined. Both contrast media injected at 3 ml/kg caused a significant increase in the number of emboli and the duration of embolization (p<0.05). Pretreatment with aspirin and/or fraxiparine in the presence of ionic contrast media showed antithrombotic activities equal to those obtained when they were tested alone (p<0.05), while in the presence of nonionic contrast media, these drugs only neutralised the prothrombotic effects. There were no differences with the NaCl treated group (p>0.05). The ionic contrast media, and to a lesser extent the nonionic contrast medium: iohexol, inhibited platelet aggregation, while iopamidol behaved as an activator. The antithrombotic drugs tested in this study prevent the prothrombotic activities of contrast media therefore suggesting their use before radiographic procedures.     

A comparison between the platelet activating properties of different contrast media used in radiology and MRI

Previous studies have demonstrated that some intravascular radiographic contrast media (CM) used in angiography, especially non-ionic monomers, may cause platelet activation. This study was designed to elucidate which properties of the CM were responsible for this activity. Platelet activation engendered by CM was studied using flow cytometry to detect platelet degranulation (as CD62 expression) and fibrinogen binding. In order to elucidate the relevant characteristics of the CM responsible, contrast agents of differing structures, properties, formulations and osmolalities were studied; ionic and non-ionic, monomeric and dimeric. Gadolinium chelate MR enhancing agents and saline solutions of differing osmolalities were also investigated. Ionic dimeric sodium meglumine ioxaglate, non-ionic dimeric iodixanol and non-ionic dimeric iotrolan did not produce increased degranulation compared with saline controls. However, all agents produced a mild increase in bound fibrinogen. Experiments using saline solutions demonstrated that these effects are not attributable to the high osmolality of some CM. The broad comparison facilitated by this study shows that previous generalizations regarding platelet activation by CM, based on an ionic-non-ionic division, are not valid. We presume that some chemical structural property of the compounds is responsible and it is of note that the chemically distinct gadolinium chelates, gadolinium DTPA and gadolinium DTPA-BMA, also caused platelet activation to a similar degree. CD62 expression correlated with fibrinogen binding suggesting that at least one common pathway of platelet activation is involved.     

Effects of cyclosporine and FK506 on in vitro high shear-induced platelet reactivity in rat and human non-anticoagulated blood

BACKGROUND: The immunosuppressants cyclosporine and FK506 have been used successfully in clinical transplantation, but both agents have various side effects. We have previously found that cyclosporine is prothrombotic and that FK506 is antithrombotic in an in vivo system. The aim of the present study was to assess the effects of these agents on platelet reactivity and coagulation using an in vitro shear-induced hemostatic platelet plug-forming instrument, the hemostatometer. METHODS: A purpose-built hemostatometer was constructed in our laboratory. The effects of cyclosporine and FK506 on platelet reactivity and coagulation were assessed under high shear stress using non-anticoagulated rat and human blood. RESULTS: FK506 significantly inhibited both platelet reactivity and coagulation. Cyclosporine also significantly inhibited coagulation, but a proaggregatory effect was observed at a final blood concentration of 0.05 mg/ml. CONCLUSIONS: The present in vitro results support our previous in vivo findings regarding the prothrombotic and antithrombotic effects of cyclosporine and FK506, respectively.     

Cerebral angiography with iohexol. A multicentre clinical trial

An open multicentre clinical trial with the new non-ionic contrast medium iohexol is reported. A total of 38 adult patients were included in the series. No serious side effects or complications occurred. The impression was that subjective reactions were less marked with iohexol than what is usually observed with conventional ionic contrast media.     

Prevention of carotid artery thrombosis by oral platelet GPIIb/IIIa antagonist in dogs

BACKGROUND AND PURPOSE: Current antithrombotic therapy in acute ischemic stroke and myocardial infarction in which a combination of antiplatelet agents (aspirin) and anticoagulants (heparin) was used led to partial reduction of acute thrombotic complications. Recent advances in antiplatelet research led to the discovery of the platelet glycoprotein IIb/IIIa complex (GPIIb/IIIa), the final common pathway for platelet aggregation. The present study was undertaken to determine the oral antithrombotic efficacy of a potent and specific platelet GPIIb/ IIIa antagonist, DMP728, in an electrically induced carotid artery thrombosis model in dogs. Based on the powerful antiplatelet efficacy of this mechanism in inhibiting all agonist-induced platelet aggregation as well as in inhibiting platelet procoagulant activity (thrombin generation and hence fibrin formation), an orally active antagonist for this integrin receptor might have potential benefits in stroke. METHODS: Anesthetized dogs were instrumented for monitoring of arterial blood pressure, heart rate, and carotid artery flow velocity. Animals were treated with saline or DMP728 (0.1 to 1.0 mg/kg PO). Thrombus formation (platelet-rich aggregate with fibrous coating and a few erythrocytes) by anodal electrolytic stimulation (300 microA) to the intimal surface of the right carotid artery was initiated 120 minutes after oral DMP728 administration and continued for 180 minutes. Whole blood cell counts, ex vivo platelet aggregation, and template bleeding time were determined at different time points throughout the study. RESULTS: DMP728 administered at 0.1 to 1.0 mg/kg PO exhibited dose-dependent antithrombotic efficacy in this model. DMP728 was shown to be significantly effective in inhibiting ex vivo platelet aggregation and in inhibiting thrombosis at 0.3 to 1.0 mg/kg PO. The antiplatelet, antithrombotic effects of DMP728 were demonstrated without any significant changes in the different hemodynamic or coagulation parameters. These data demonstrated the oral antithrombotic efficacy of DMP728 in dogs. CONCLUSIONS: Platelet GPIIb/IIIa blockade with an orally active antagonist was shown to be safe and effective in the prevention of carotid artery occlusive thrombosis.     

Management of intracoronary thrombosis complicating percutaneous transluminal coronary angioplasty

With technological advances in equipment and increased experience of operators, the success rates of percutaneous transluminal coronary angioplasty (PTCA) now exceed 90%. However, acute periprocural occlusion continues to complicate approximately 6% of all procedures, and many of these occlusions are due to intracoronary (IC) thrombus. Patients at highest risk for this complication include those with acute ischemic syndromes or with angiographically apparent thrombus. These individuals may be candidates for the use of prolonged heparin infusions prior to dilatation, intracoronary thrombolytic therapy, or monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor. All patients undergoing PTCA should receive adequate antiplatelet therapy, including aspirin, and heparin with dosing monitored by activated clotting times (ACT). In addition, some recommend the use of ionic contrast material. When IC thrombus accumulates following intervention, initial therapy should include IC nitroglycerin followed by a combination of redilatation and IC urokinase infusion. Prolonged balloon inflations may be useful, particularly with the use of autoperfusion catheters. Platelet glycoprotein IIb/IIIa receptor antagonists may prove to be beneficial in this situation as well. If the patient's clinical status deteriorates in spite of these measures, emergency coronary artery bypass graft surgery may be required.     

Coagulation/fibrinolytic system and platelet in acute coronary syndrome]

Coagulation/fibrinolytic system and platelet function play roles not only in the onset of acute coronary syndrome (ACS) but also in the development of atherosclerosis, which is a major underlying condition of ACS. In this paper we reviewed the involvement of coagulation/fibrinolytic system and platelet in coronary atherosclerosis and ACS. It is well known that hyperchoresterolemia and diabetes mellitus (DM) are the important risk factor for coronary atherosclerosis and ACS. Both oxidized LDL and advanced glycation endproduct (AGE) activate endothelial cells with down-regulating thrombomodulin and tissue plasminogen activator(t-PA) expression. Moreover the oxidized LDL and AGE up-regulate the expression of tissue factor, and t-PA inhibitor, PAI-1. Thus Ox-LDL and AGE impair the endothelial antithrombotic function and result ACS. These may explain the pathomechanism of coronary sclerosis and ACS. In the atherosclerotic lesion with narrowing the lumen, high shear stress may be occurred. Recent observations suggested that high shear stress induces platelets aggregation named as shear stress induced platelet aggregation (SIPA), which may also have very important role for the pathogenesis in ACS.     

Introduction to coronary artery stents and their pharmacotherapeutic management

OBJECTIVE: To provide an introduction to coronary artery stents and their pharmacologic management, including anticoagulant therapy and newer antiplatelet regimens. DATA SOURCES: A MEDLINE and current journal search of relevant articles that evaluated coronary stent success rates and anticoagulation or antiplatelet regimens. STUDY SELECTION: Data from the use of primarily the Palmaz-Schatz stent were included. Studies using vitamin K antagonists that are not commercially available in the US were excluded unless they compared an antiplatelet regimen with anticoagulation using the international normalized ratio (INR). DATA SYNTHESIS: Limitations with percutaneous transluminal coronary angioplasty (PTCA), such as ischemic complications and restenosis, have led to the advent of intracoronary stenting. However, the placement of a stent within the coronary artery lumen is associated with a risk of thrombotic events. Despite current postprocedural anticoagulation and antiplatelet regimens, thrombosis occurs at rates ranging from 0.6% to 21%. When anticoagulation is deemed appropriate, it should be used for 1-2 months and the INR should be maintained between 2 and 3.5. Anticoagulation appears to have no effect on the development of restenosis, but has been shown to cause significant hemorrhagic events in 5-13.5% of patients. Newer data continue to define the subsets of patients who may be managed with antiplatelet agents alone. Combinations of aspirin and ticlopidine or aspirin alone may be used to manage patients who fulfill the following criteria: optimal stent placement, high-pressure inflation, and adequate coronary size. CONCLUSIONS: Coronary artery stenting is a novel approach for the management of coronary artery disease, but is associated with the complication of stent thrombosis. Anticoagulation reduces the risk of stent thrombosis, but is associated with bleeding risk. Selected patients may be successfully managed with antiplatelet agents only. More data are needed to better define the optimal antithrombotic regimen.     

Current approach in antithrombotic treatment during coronary interventions: specific thrombocyte aggregation inhibitors and direct thrombin antagonists in high-risk patients

Patients undergoing angioplasty (PTCA) for unstable angina, postinfarction angina, or complex coronary lesions represent a high risk group for ischemic complications. High dose heparin and aspirin are used routinely to prevent thrombotic complications. However, new approaches designed to avoid platelet aggregation, including development of specific platelet GP IIb/IIIa receptor antagonists and specific thrombin inhibitors, demonstrate a significant reduction of thrombotic events following coronary interventions compared to heparin alone. Bleeding complications are not increased if conjunctive heparin administration is weight-adjusted. Pathophysiology of acute coronary closure, mechanisms of action of the new anti-thrombotic drugs, and current and future clinical applications are discussed.     

Delayed-type hypersensitivity to a nonionic, radiopaque contrast medium

BACKGROUND: True allergic reactions to iodinated radiocontrast media are rare, and only a few well-documented cases of delayed-type hypersensitivity reactions caused by contrast media have been described. METHODS: We report a 61-year-old patient in whom percutaneous transluminal coronary angioplasty (PTCA) was performed with iopamidol, a nonionic contrast medium. Seven days later, the patient developed generalized maculopapular exanthema. Repeated patch tests with several iodinated agents were performed. RESULTS: A first patch test with iopamidol was positive. Repetition of the patch tests showed positive results to iopamidol as well as to iohexol and ioversol, two other nonionic contrast media, but not to other iodinated substances. Three months later, PTCA was repeated, and iopamidol was used again. Despite premedication, pruritic macular exanthema developed 1 day later. Whether iopamidol or trometamol -- an additive substance in the contrast medium -- was causative could not be determined, since a third set of patch tests was negative. CONCLUSIONS: Delayed-type hypersensitivity reactions to iodinated contrast media are rare. We recommend that patients with delayed exanthematous reactions undergo patch or intradermal tests with different contrast media and their additives, and that readings be performed immediately and later at days 2 and 3.     

Enhanced effects of adriamycin by combination with a new ribonucleotide reductase inhibitor, trimidox, in murine leukemia

For invasive catheter procedures both ionic and nonionic contrast media (CM) with excellent tolerability are available. The governing practical factors for CM are X-ray opacity and biocompatibility. Tolerability of a contrast medium is governed among its physical properties by its viscosity, osmolality, and ionic concentration. In Germany the nonionic CM are currently preferred. Because of its low thrombotic complications, the ionic CM Ioxaglat is an important alternative in high risk interventions. In patients with known CM incompatibility, the prophylactic application of H1-receptor antagonists and corticosteroids allows catheterization safely without complications. In impaired renal function, hydration is the most effective prophylactic measure to be taken.     

Assessment of platelet activation by coronary sinus blood sampling during balloon angioplasty and directional coronary atherectomy

Three markers of platelet activation (platelet-derived microparticles, fibrinogen binding and expression of P-selectin) were assessed by flow cytometry during diagnostic coronary angiography and therapeutic coronary interventions. In 24 patients undergoing diagnostic angiography, blood was collected to determine if our sampling techniques or coronary angiography caused platelet activation. Changes during diagnostic angiography were used to establish baseline values and interpret changes during coronary interventions. In 21 patients, blood samples were obtained at 5 time points during percutaneous transluminal coronary angioplasty (PTCA) (n = 17) or directional coronary atherectomy (DCA) (n = 4). During coronary interventions, mean values for the percentage of platelets expressing P-selectin or binding fibrinogen increased, but with considerable variation among patients. Individual responses for platelet activation markers in each patient were characterized using a twofold increase to indicate elevation related to the intervention. Patients were classified as having complicated or uncomplicated procedures based on the presence of acute closure, dissection, or thrombus observed by angiography. There were no differences in the percentage of elevated markers between patients with uncomplicated (12.5%) and complicated (19%) PTCA procedures. However, patients treated with DCA had more elevated markers (38%) than those treated with PTCA (15%) (p = 0.04). Our data suggest that the extent of platelet activation in individual patients cannot be predicted by common angiographic findings or complications. More markers of platelet activation were present after DCA and may reflect a greater degree of vascular trauma associated with this procedure.     

Experimental kallikrein gene therapy in hypertension, cardiovascular and renal diseases

Argatroban, a direct thrombin inhibitor, is used clinically because of its safe and effective antithrombotic action. This drug of low molecular weight shows reversible inhibition of thrombin irrespective of whether thrombin is fibrin-bound or soluble. Optimal anticoagulant effects can easily be attained by monitoring with the activated partial thromboplastin time or whole-blood activated clotting time when a therapeutic range of argatroban equivalent to that of heparin is used. The antithrombotic action is simply detected with a chromogenic substrate assay. The clinical use of the drug in Japan was approved for the treatment of chronic peripheral arterial obstructive disease and acute ischemic stroke. For coronary artery disease in patients with deficiency of antithrombin activities attributable to either antithrombin III or heparin cofactor II deficiency, argatroban is effective as an anticoagulant. Acute coronary occlusion during and after percutaneous transluminal coronary angioplasty can be treated by argatroban as an alternative to heparin. The presence of platelets activated by a trace amount of thrombin is evidenced by modified methods of platelet aggregometry in acute ischemic stroke. Therefore, argatroban can render the platelets insensitive against the platelet hyperaggregation enhanced by thrombin.     

Relationship between the antithrombotic effect of YM-75466, a novel factor Xa inhibitor, and coagulation parameters in rats

The relationship between the antithrombotic effects of intravenous infusions of YM-75466 [N-[4-[(1-acetimidoyl-4-piperidyl)oxy]phenyl]-N-[(7-amidino-2-naph thyl)methyl] sulfamoyl]acetic acid monomethanesulfonate), a novel factor Xa (FXa) inhibitor, and various coagulation parameters (prothrombin time, activated partial thromboplastin time, thrombin-antithrombin III complex (TAT), anti-FXa activity and anti-thrombin activity) in rats was studied and compared with results for heparin. In the arterio-venous shunt model, both agents exerted antithrombotic effects in a dose-dependent manner. Coagulation parameters were studied simultaneously with antithrombotic effects. YM-75466 did not prolong coagulation time even at the dose which exerted significant antithrombotic effects, while it decreased TAT level in plasma in a dose-dependent manner. YM-75466 exerted anti-FXa activity but not anti-thrombin activity. In contrast, heparin prolonged activated partial thromboplastin time in a dose-dependent manner and decreased TAT level in plasma with increasing inhibition of thrombus formation. Heparin exerted both anti-FXa and anti-thrombin activity in a dose-dependent manner. These results suggest that TAT is a suitable parameter for monitoring the antithrombotic effect of YM-75466 in the arterio-venous shunt model in rats and that YM-75466, unlike heparin, exerts its antithrombotic effect through specific inhibition of FXa without any effect on thrombin.     

Subcutaneous administration of interleukin-2 in ambulatory treatment of patients with metastatic renal cancer. Three-year results of the SCAPP I program

Angina, myocardial infarction, and sudden cardiac death are associated with thrombus formation in coronary arteries. It is generally believed that these conditions benefit from long-term exercise. However, the evidence for such amelioration or prevention is inconclusive and so is the mechanism through which long-term exercise exerts its beneficial effect on various ischaemic conditions. Because of the thrombotic events, the effects of exercise on platelet reactivity, blood coagulation and fibrinolysis have been extensively studied, but the findings are not consistent (1-9). This is mainly due to methodological problems. Analysis of platelet response to a variety of agonists and the dozen of coagulation and fibrinolysis variables makes the assessment of the overall platelet function, coagulation and fibrinolysis status extremely difficult.     

Initial experience with the use of abciximab in the salvage treatment of acute coronary thrombosis in the Hemodynamics Laboratory

The optimal treatment of acute thrombotic complications in the Catheterization Laboratory has not been defined yet, due to the limited efficacy shown by various pharmacological regimens, even when associated to coronary angioplasty (PTCA). The aim of our study was therefore to evaluate the effects of abciximab (ReoPro), a new potent inhibitor of the platelet glycoprotein IIb/IIIa, when administered as a "rescue" treatment for acute thrombotic coronary occlusion during diagnostic or interventional procedures. Sixteen patients (12 males, 4 females, mean age 59.3 +/- 9.2 years, range 43-77 years), with unstable angina and consecutively treated with abciximab due to clinical instability attributable to coronary thrombosis angiographically proven during PTCA (9 cases) or diagnostic angiography (7 cases), were identified. The individual angiographic films and medical records were then reviewed in order to evaluate the effects of treatment on coronary flow, thrombus size and occurrence of in-hospital adverse events: death, non-fatal acute myocardial infarction (AMI), need for urgent myocardial revascularization and hemorrhage. The administration of abciximab, in association with PTCA (associated in turn with stent implantation in 8 cases), induced a significant increase of coronary TIMI flow grade (0.3 +/- 0.6 vs 2.4 +/- 0.9; p < 0.05) and a significant decrease of thrombus "score" (size) 2.4 +/- 0.9 vs 1.3 +/- 0.6; p < 0.01). No deaths nor need for urgent myocardial revascularization were observed; in 31% of cases (5 patients) evolution towards AMI occurred, while however 94% of cases (15 patients) had a coronary occlusion before treatment. No major hemorrhagic complications were observed, while in 12% of cases (2 patients) a groin hematoma associated with moderate hemoglobin drop, developed. In conclusion, the administration of abciximab, associated with the common "rescue" interventional procedures, in patients with acute thrombotic coronary occlusion in the Catheterization Laboratory, appears to be effective in restoring adequate coronary flow and reducing the thrombus size (limiting therefore the evolution towards AMI), and safe, not having been associated with significant hemorrhagic complications.     

Reduction of in-hospital complications after elective percutaneous transluminal coronary angioplasty using a combined pretreatment with ticlopidine and aspirin

OBJECTIVES: In a retrospective study the effect of a combined pretreatment using ticlopidine and aspirin (ASA) in patients undergoing elective PTCA procedures was investigated with respect to in-hospital complications of PTCA and with respect to the efficacy in avoiding a subacute stent thrombosis in case of stent implantation. The systematically performed pretreatment with ticlopidine and ASA takes the delayed begin of full antiplatelet effect of ticlopidine into account. METHODS: 1108 consecutive patients (group 1) underwent elective PTCA without pretreatment with ticlopidine. In case of stent implantation oral anticoagulation was initiated in this group. In 758 consecutive patients (group 2) with elective PTCA, a combined regimen with ticlopidine and ASA was initiated at least 24 h prior to PTCA and was continued in case of stent implantation. The rate of procedural success, necessary reinterventions, cardiac events (myocardial infarction, death) and complications as well as the rate of subacute stent thrombosis in the subgroups with stent implantation were evaluated. RESULTS: The number of patients without in-hospital cardiac complications (myocardial infarction, coronary artery bypass surgery, death) and without re-PTCA interventions was 92.8% in group 1 and 96.3% in group 2 (p < 0.005). Especially the rate of necessary reinterventions was significantly reduced in group 2 compared with group 1 (5.3% vs. 2.4%, p < 0.001). Cardiac events were reduced in group 2 (myocardial infarction: 2.0% vs. 1.1%, coronary artery bypass graft: 0.8% vs. 0.5%, exitus: 0.5% vs. 0%), the incidence of bleeding complications was similar in both groups (2.5% vs. 2.4%). The combined pretreatment with ticlopidine and ASA with a stent implantation rate of 16.4% in group 2 was effective to avoid a subacute stent thrombosis (1.6%, independent of the indication to stent implantation). One patient of 758 in group 2 had allergic reactions to ticlopidine. CONCLUSIONS: The "prophylactic" pretreatment with ticlopidine and ASA in combination with a higher rate of stent implantation reduces necessary reinterventions and cardiac events after PTCA and is effective to avoid subacute stent thrombosis without increase of complications, especially bleeding complications. Thus, this pretreatment can be proposed even in patients scheduled for elective PTCA without planned stent implantation to reduce the interval between a necessary unforeseen stent implantation and the full treatment effects of ticlopidine.     

Rapid platelet-function assay: an automated and quantitative cartridge-based method

BACKGROUND: The platelet glycoprotein (GP) IIb/IIIa receptor is important in mediating platelet thrombus formation, and the GP IIb/IIIa antagonist abciximab (c7E3 Fab; ReoPro) is effective in preventing thrombotic ischemic cardiovascular complications of unstable angina and percutaneous coronary interventions. Small-molecule antagonists of GP IIb/IIIa based on the Arg-Gly-Asp (RGD) sequence show similar benefit, and some of these agents are orally active. However, there may be significant interindividual variation in response to such antagonists, especially with chronic oral therapy. It will be essential to balance the beneficial antithrombotic effect of these drugs with their potential for causing bleeding. In response to this need, we have developed a rapid platelet-function assay (RPFA), a point-of-care system that provides a quantitative measure of the competence of the GP IIb/IIIa receptor as reflected in the ability of platelets to agglutinate fibrinogen-coated beads. METHODS AND RESULTS: Polystyrene beads were coated with fibrinogen and placed in a cartridge along with a lyophilized peptide that activates the thrombin receptor. Anticoagulated whole blood was added to the cartridge, and then a microprocessor-controlled operation mixed the reagents and detected agglutination between platelets and coated beads. Quantitative digital results were displayed within 3 minutes. Because there is no dilution of the blood, the assay can be used to measure platelet activity in samples that have been treated with GP IIb/IIIa antagonists with high dissociation rates. RPFA results of whole-blood samples treated with different GP IIb/IIIa antagonists correlated well with both conventional turbidimetric platelet aggregation (r2=0.95) and the percentage of free GP IIb/IIIa molecules in the sample (r2=0.96). The mean difference in measurements between RPFA and aggregometry was -4% (+/-4% SD), and the mean difference in measurements between RPFA and free GP IIb/IIIa receptors was -2% (+/-6% SD). CONCLUSIONS: The RPFA provides rapid information on platelet function that mirrors turbidimetric platelet aggregation and reflects GP IIb/IIIa receptor blockade.     

Oral verapamil inhibits platelet thrombus formation in humans

BACKGROUND: Calcium antagonists such as verapamil are potent coronary and systemic vasodilators that are used in the treatment of coronary disease. They have also been shown to inhibit platelet aggregation in vitro, but whether they have beneficial antithrombotic effects in humans is unclear, and whether they can potentiate the antithrombotic effects of aspirin is unknown. METHODS AND RESULTS: Platelet thrombus formation and whole blood platelet aggregation were measured in 18 stable coronary patients on three separate occasions: at baseline when receiving no active medications, after 7 days of receiving oral verapamil SR (240 mg/d), and after 7 days of receiving a combination of oral verapamil SR and aspirin (325 mg/d). Thrombus formation on porcine aortic media that were placed into cylindrical flow chambers and exposed to flowing antecubital venous blood for 3 minutes was assessed morphometrically at a shear rate of 2546 s-1, which is typical of arterial flow at sites of stenoses. Thrombus formation under basal conditions was 7.0 +/- 1.6 microns 2, and this was decreased to 3.1 +/- 0.5 microns 2 (P < .05) after 7 days of treatment with oral verapamil SR and to 2.6 +/- 0.5 microns 2 (P < .05) after 7 days of treatment with oral verapamil and aspirin. Whole blood platelet aggregation levels in response to 0.050 and 0.075 U of thrombin at baseline were 10.8 +/- 1.0 and 11.9 +/- 1.0 omega; aggregation was inhibited after 7 days of treatment with verapamil to 6.5 +/- 1.1 and 7.8 +/- 0.9 omega (P < .05 versus baseline) and after 7 days of treatment with verapamil and aspirin to 6.1 +/- 1.1 and 7.2 +/- 1.0 omega (P < .05), respectively. CONCLUSIONS: The present study demonstrates that part of the benefit of verapamil in ischemic heart disease may occur by inhibition of platelet aggregation and thrombus formation. This beneficial antithrombotic effect may be important in preventing acute coronary ischemic events resulting from thrombus formation at sites of plaque rupture.