Modulatory effect of erythrocytes on the platelet reactivity to collagen in IDDM patients.

Platelets participate in the atherothrombotic complications of diabetes. Recent data demonstrate that platelet reactivity can be modulated via cell-cell interactions with erythrocytes and neutrophils. In this study, platelet reactivity was evaluated in 30 IDDM patients. We used an analytical procedure that permits an independent evaluation of platelet activation (granule release, eicosanoid formation) and platelet recruitment (pro-aggregatory activity of cell-free releasates) after platelet stimulation with collagen in the presence or absence of other blood cells. The interaction between platelets and erythrocytes (hematocrit 40%) resulted in a marked enhancement of platelet activation (5HT, betaTG, TXA2 release) and recruitment in both patients and control subjects. The erythrocyte enhancement of platelet TXA2 synthesis and recruitment was significantly higher in the patients, while no differences were detected in platelet granule release. The elevated platelet recruitment in the IDDM patients was found to be due to 1) increased susceptibility of diabetic platelets to the prothrombotic effect of erythrocytes and 2) the greater response of diabetic platelets to their own cell-free releasate. Patients with poor metabolic control (elevated HbA1c) or longer evolution time had an even greater platelet recruitment. The presence of microalbuminuria is not related to the platelet recruitment. Since platelet recruitment is an essential step in thrombus growth, its enhancement may favor thrombotic complications in IDDM.

Ridogrel, a combined thromboxane synthase inhibitor and receptor blocker, decreases elevated plasma beta-thromboglobulin levels in patients with documented peripheral arterial disease.

The combination of thromboxane synthase inhibition with thromboxane receptor antagonism has been shown to result in a strong inhibition of platelet aggregation and a prolongation of the bleeding time (Gresele et al., J. Clin Invest 1987; 80: 1435-45). Ridogrel is a single molecule that efficiently achieves both inhibitions in human volunteers. The present study was performed in patients with obstructive peripheral arterial disease and elevated plasma beta-thromboglobulin levels. Patients were treated with either 2 x 300 mg ridogrel or 2 x 300 mg placebo per day for 2 1/2 days, according to a double blind randomised parallel design. Plasma beta-thromboglobulin decreased significantly throughout active treatment starting within 2 h after administration; serum and urinary immunoreactive TxB2 levels and urinary 11-dehydro-TxB2 excretion were significantly lower and serum PGE2 and 6-keto-PGF1 alpha levels significantly higher with ridogrel; no changes were observed in the placebo-treated group. In conclusion this study demonstrates a reduction of platelet activation in vivo by ridogrel.

A comparison between effects of estradiol valerate and low dose ethinyl estradiol on haemostasis parameters.

Ethinyl estradiol (EE) is still used to some extent as hormonal replacement therapy (HRT) in the climacteric period. As regards oral contraception, it is well known that the induced increase in cardiovascular disease is related to the estrogen component (invariably EE) in a dose-related fashion. Considerably lower doses of EE are needed in HRT compared to oral contraception. To delineate and compare effects of EE and estradiol valerate (E2V) in doses needed in HRT on haemostasis parameters, 24 postmenopausal women were engaged in a study with an open cross-over design. The doses compared (10 micrograms EE and 2 mg E2V daily) are the lowest which eliminate climacteric symptoms in a majority of women. Unlike E2V, EE caused increased levels of factor VII:Ag, factor VIII:C and beta-thromboglobulin, which may be changes towards hypercoagulability. Both estrogens decreased the AT III activity. Long-term administration (6 + 12 w) of the estrogens induced further changes in haemostatic parameters. 10 micrograms EE increased factor VII:Ag in contrast to 2 mg E2V. Furthermore both estrogens increased factor VIII:C and factor II-VII-X. A decrease in platelet count was induced by both EE and E2V. Oral contraception and adjuvant estrogen therapy in men with prostatic carcinoma are known to imply an increased cardiovascular risk. It is noteworthy that the pattern of changes in haemostatic parameters induced by as little as 10 micrograms of EE is the same as seen after the administration of combined oral contraceptives or the substantially higher doses of EE given as adjuvant therapy to men with prostatic carcinoma.

Anti-hypertensive drugs non-specifically reduce "spontaneous" activation of blood platelets.

Abnormal activation of blood platelets may be a contributory factor in the accelerated vascular disease which occurs in hypertension. We investigated the effects of lowering blood pressure in 12 patients with mild hypertension on several aspects of platelet function, initially in a placebo-controlled, double-blind, cross-over study with nisoldipine, and subsequently in the same patients comparing nisoldipine with the patients' usual anti-hypertensive therapy. Values were compared with those from an age, sex-matched control population. Seven hypertensive patients with renal failure were also studied. Administration of nisoldipine reduced ex vivo "spontaneous" aggregation of blood platelets significantly, and a similar significant effect was seen when blood pressure was lowered by the patients usual anti-hypertensive therapy. "Spontaneous" aggregation occurring in the control population was similar to that in the treated hypertensives. Blood platelet count, and aggregation in response to ADP and adrenalin were unaffected by treatment. Median plasma beta thromboglobulin levels were significantly higher in the untreated hypertensive patients (43 ng ml-1) than in the controls (30 ng ml-1), and there was a trend to reduced values for beta thromboglobulin on treatment of the hypertension. These results indicate that blood platelet activity is enhanced in hypertension and that function returns towards normal when blood pressure is lowered by treatment.

Heparin-coated cardiopulmonary bypass circuits: hemostatic alterations and postoperative blood loss.

This prospective, randomized study involving patients undergoing isolated coronary artery bypass grafting investigated whether the use of heparin-coated bypass circuits with an uncoated cardiotomy reservoir (n = 10) compared with standard uncoated bypass circuits (n = 10) resulted in differences in patient outcome and hemostatic alterations. There were no differences in postoperative blood loss, transfusion requirements, and routine coagulation test results between groups. Immunoassays for platelet alpha-granule constituents platelet factor 4 and beta-thromboglobulin, thrombin generation by-product F1.2, fibrinopeptide A, thrombin-antithrombin complex, and fibrinolysis by-product D-dimer also demonstrated no significant differences between groups, although trends for lower platelet secretion with heparin coating were noted. Increases were found in beta-thromboglobulin and platelet factor 4 concentrations at 10 (p < 0.03) and 30 minutes (p < 0.001) of CPB, respectively, and continuing throughout CPB (p < 0.001) for both groups versus values measured before incision. No significant differences were seen between levels 5 minutes prior to aortic cross-clamp release and those obtained 8 and 45 minutes after cross-clamp release. Conversely, no significant increases in F1.2, thrombin-antithrombin complex, and D-dimer were seen prior to release of the aortic cross-clamp, but afterward increases occurred that were highly significant (p < 0.001). The temporal data suggest that platelet activation occurs primarily as a result of contact with the cardiopulmonary bypass circuitry, whereas thrombin generation and fibrinolytic activity are not significant until reperfusion of the heart and lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of alcohol ingestion post-exercise on platelet aggregation.

The present study examined the influence of ingesting a moderate dose of alcohol on platelet count and platelet aggregation during recovery following exercise. Nineteen subjects (11 male and 8 female) were studied immediately after a standardised cycle ergometer test and during the 24-h period of recovery. In random order, alcohol (0.7 g/kg body mass) was given 1 h after exercise on one test occasion, while an equal volume of alcohol-free solution was administered on the other. Venous blood samples were obtained at baseline, post-exercise, and at 1, 5, and 22 h post-alcohol ingestion. Blood alcohol level increased significantly 1 h after the ingestion of alcohol, but decreased and returned to the resting baseline level at 5 h during recovery. Males and females subjects exhibited similar mean values of platelet count, platelet aggregation, and beta-thromboglobulin concentration at rest and following exercise and recovery. A significant increase in platelet count and a decrease in platelet aggregation using adenosine diphosphate (ADP) was found following exercise. Although plasma beta-thromboglobulin level (pooled data for males and females) showed an increase by 26.0% (from a mean pre-exercise value of 22.3-28.1 IU/ml), this rise was not significant (P>.05). The post-exercise increase in platelet count was mainly due to exercise-induced plasma volume loss. During recovery, while the increase in platelet count post-exercise returned to the baseline level in control and alcohol trials, the optical density of platelet aggregation remained significantly depressed at 5-h during recovery in the alcohol trial but not in the normal control condition. It is concluded that exercise induces significant reduction in platelet aggregation and the consumption of alcohol after physical exercise delays the normal return of platelet aggregation to the resting baseline levels during recovery.

A novel enzyme immunoassay for plasma thrombospondin. Comparison with beta-thromboglobulin as platelet activation marker in vitro and in vivo.

A novel enzyme immunoassay for plasma thrombospondin (TSP) based on commercially available monoclonal antibodies was established. The following conditions for correct collection and preservation of blood samples were required: venipuncture directly into a vacutainer containing citrate, theophylline, adenosine and dipyridamole, storage on ice, and separation of plasma within 30 minutes. Thereafter, the plasma TSP concentration remained constant at room temperature and after five times of freezing and thawing. Both inter- and intraassay variation coefficients were 5%. The lower detection limit was 20 microg/L. Median TSP concentration among 40 healthy blood donors was 43 microg/L, slightly lower than previously published. The assay is valid, reliable, and has certain advantages compared with previously published methods. TSP and beta-thromboglobulin (BTG) were then compared as platelet activation and biocompatibility markers in vivo: 23 patients undergoing cardiopulmonary bypass (CPB); and in vitro: effect of coating polyvinyl chloride with heparin. The kinetic patterns of TSP and BTG were markedly different in vivo but virtually identical in vitro, explained by different in vivo clearance mechanisms during CPB. We conclude that BTG is superior to TSP for evaluation of platelet activation during in vivo CPB, whereas TSP and BTG are virtually identical as markers in vitro.

Platelet activation during angiotensin II infusion in healthy volunteers.

The present study was undertaken to evaluate the effects of an intravenous infusion of angiotensin II (10 ng/kg per min) on platelet function and coagulation in vivo in 18 healthy males. The infusion increased mean arterial pressure by 23+/-2 mm Hg. Plasma beta-thromboglobulin levels, reflecting platelet secretion, increased by 66+/-24% during the infusion, as did also platelet surface expression of P-selectin as measured by flow cytometry. Platelet fibrinogen binding increased, whereas platelet aggregability, assessed by ex vivo filtragometry, was unaltered. Angiotensin II caused mild activation of the coagulation cascade with increases in plasma levels of thrombin-antithrombin complex and prothrombin fragment F1 + 2. In conclusion, angiotensin II has mild platelet-activating effects in vivo and also enhances coagulation. Markers of platelet secretion are significantly increased, whereas markers of platelet aggregability are less affected. The clinical relevance of these findings remains to be clarified.

Effects of ionic and non-ionic contrast media on platelet function as evaluated by plasma concentration of beta-thromboglobulin.

The aim of the study was to evaluate the effects of ionic and non-ionic contrast media on platelet function. In 44 patients who underwent angiography, the plasma concentration of beta-thromboglobulin (beta TG) was measured before and after ionic contrast medium (diatrizoate) administration in 22 patients and non-ionic contrast medium (iopromide) in the other 22 patients. A significant decrease in the plasma beta TG levels after intraarterial contrast medium injection occurred in both groups of patients. No significant beta TG level changes occurred in patients with normal pre-examination beta TG levels in both groups. In patients with elevated beta TG levels before arteriography, beta TG returned to normal values after contrast medium injection in both groups. There was no significant correlation between the amount of administered contrast medium and beta TG concentration after angiography. These results suggest that platelet function is not affected by either ionic or non-ionic contrast medium in patients with normal platelet activation. In patients with enhanced platelet activation, the activation became normal after contrast medium administration.

Effects on hemostasis after two-year use of low dose combined oral contraceptives with gestodene or levonorgestrel.

We studied 67 healthy women who were randomly allocated to receive third generation gestodene (Gynera) or second generation levonorgestrel (Microgynon 30) combination of low-dose estrogen oral contraceptives (OCs) for their hemostatic effects over 2 years. Hemostatic changes were apparent within 3 months of OC use. Hematocrit (Hct) was not affected, but hemoglobin (Hb) concentration decreased by 18 months. Shortened prothrombin time (PT) and activated plasma thromboplastin time (APTT) were associated with elevated fibrinogen within the 12-month use of both OCs. Factor VII was reduced only in Micro 30 during the 18 months of use. Enhanced thrombin-antithrombin (TAT)-complex level was seen at 18 months of Gynera use. Prothrombin fragment1+2 (F1+2) rise was seen at 3 months with Micro 30. Reduced antithrombin III (ATIII) activity was seen at 18 months with Gynera and at 24 months with Micro 30. Increased protein C activity was seen at 3 months and reduced protein S occurred at 18 months of Gynera use. Tissue plasminogen activator (t-PA) activity was enhanced for 6 months in both OCs with raised D-dimer levels for 12 months with Gynera and 6 months with Micro 30. Decreased t-PA antigen was seen at 18 months and decreased urokinaselike plasminogen activator (u-PA) antigen occurred throughout the 24 months of both OCs use. Enhanced u-PA activity was only seen in Gynera users. Elevated plasminogen levels were apparent throughout both OCs use. PAI-1 levels were significantly decreased with Micro 30. With Gynera, the decreased PAI-1 activity was seen only at 18 months and PAI-1 antigen at 12 months. No change in platelets and von Willebrand factor (vWF) were seen in long-term OC use except that beta-thromboglobulin (beta-TG) showed decreased trends reaching statistical significance by 18 and 24 months of Micro 30 use and by 24 months of Gynera use. A further significant decrease in beta-TG, u-PA antigen, ATIII, and protein S levels were seen 3 months after pill stoppage compared with pretreatment levels. Activated protein C resistance (APCR) was negative in all subjects before and during OC use. The study indicated dynamic balance between coagulation and fibrinolysis with no endothelial activation. However, because some hemostatic markers showed wide fluctuations during OC use, a longer term study is warranted to investigate any adverse hemostatic changes that might enhance the risks of venous thromboembolism in Asian subjects known to be less prone to thrombosis.

Platelet-derived growth factor release and antiplatelet treatment with low-dose acetylsalicylic acid.

Platelet-derived growth factor (PDGF) and beta-thromboglobulin (beta-TG) are released from alpha granules during platelet activation. PDGF may play a role in the development of atherosclerosis and the late restenosis after percutaneous transluminal coronary angioplasty (PTCA). The effect of acetylsalicylic acid (ASA) on PDGF release was studied in healthy volunteers before and twelve hours after ingestion of 300 mg ASA. PDGF, beta-TG, and thromboxane B2(TxB2) were measured by radioimmunoassay (RIA) in serum and in platelet rich plasma (PRP) after submaximal stimulation with collagen. TxB2 decreased significantly from 0.9 +/- 0.3 ng/(mL x 10(6) platelets) to 0.006 +/- 0.005 ng/(mL x 10(6) platelets) (mean +/- SD) in serum after ASA ingestion while PDGF and beta-TG remained unchanged. Measurements in PRP after stimulation with collagen showed a significant decrease in PDGF (from 21.5 +/- 1.4 pg/(mL x 10(6) platelets) to 1.8 +/- 4.1 (pg/mL x 10(6) platelets), in beta-TG (from 21.0 +/- 13.3 ng/(mL x 10(6) platelets) to 2.2 +/- 1.4 ng/(mL x 10(6) platelets)) and in TxB2 (from 143.6 +/- 80.7 pg/(mL x 10(6) platelets) to 0.5 +/- 0.6 pg/(mL x 10(6) platelets)) after treatment with ASA. In conclusion low-dose ASA inhibits collagen-induced release of both beta-TG and PDGF in PRP and TxB2-synthesis in PRP and serum.

Metabolic response of blood cells to synthetic graft-materials with special reference to a Fluoromer Passivated Dacron graft. An in vitro study using microcalorimetry.

Microcalorimetry was used to study in vitro the metabolic response from human platelets and leukocytes when incubated with three different synthetic graft-materials. The graft to be studied primarily was Fluoromer Passivated Dacron (FPD) which was compared with ePTFE and with a knitted Teflon graft. A rapid increase in the metabolic activity of platelets was observed, followed by a steady-state for more than one hour, while the platelet metabolism did not differ among the various graft-materials. Leukocytes incubated with FPD showed a high initial metabolism, with a peak after about 15 minutes. After 60 minutes the metabolic response had reached control values. ePTFE and Teflon grafts differed significantly from FPD, without causing any peak metabolic activity. It may be concluded that FPD and ePTFE grafts, as evaluated in vitro, activate platelets to the same extent, while FPD causes a more extensive leukocyte activation. Whether these findings can be interpreted as differences in thrombogenicity and inflammatory responses has not been proven, but seems probable. This in vitro method should make it possible to further study human responses to synthetic materials a method possibly more reliable than animal experiments.

[Ticlopidine and platelet function]. / Ticlopidina e funzione piastrinica.

In macular degeneration disease of the eye, we have studied the behaviour of vitro thrombocyte aggregation/deaggregation and ex vivo plasma beta-thromboglobulin level (Born aggregometer, RIA kit) during administration of an antiaggregant platelet drug (ticlopidine). We have observed the presence of a prothrombotic state that improves after 15 days of administration of drug. In fact platelet aggregation and beta-thromboglobulin level significantly decrease while thrombocyte deaggregation significantly increase. The correlations between deaggregation, aggregation and beta-thromboglobulin level suggest that the antiaggregant action of the ticlopidine is linked to the inhibition of platelet release reaction.

Mean platelet volume and ß-thromboglobulin levels in familial Mediterranean fever: effect of colchicine use?

BACKGROUND: Many studies have shown that subclinical inflammation persisted during remission period of Familial Mediterranean Fever (FMF) patients but long term effects of subclinical inflammation in these patients aren't clearly known. Besides, a few of the recent studies revealed that risk of atherosclerosis had increased in FMF patients. ß-Thromboglobulin (ß-TG) is considered as a sensitive marker of platelet activation. In this study Mean Platelet Volume (MPV) and ß-TG levels were evaluated in FMF patients. METHODS: Following the Local Ethics Committee's consent, 25 FMF patients were included in the study. Twenty eight age and sex matched healthy volunteers were recruited as a control group. Lipid profile, inflammatory parameters, hemogram, ß-TG, MPV were assessed. Statistical analysis was performed with SPSS for Windows 16.00. RESULTS: Group I consisted of 25 FMF cases (16 females, 9 males; mean age: 35.72 ± 12.34 years), Group II consisted of 28 cases (22 females, 6 males; mean age 31.78 ± 10.31 years). There was no statistically significant difference between the groups in terms of age and gender distribution, smoking status, total cholesterol, triglyceride, LDL and MPV (p>0.05). HDL levels were found to be statistically lower in Group I (p:0.04). Median ß-TG levels was significantly higher in Group II than Group I (129.50 (range:372.00) ng/mL versus 104.00 (range:212.80) ng/mL respectively; p:0.03). CONCLUSION: In this study MPV and ß-TG were evaluated for FMF cases and healthy controls, ß-TG levels were found significantly lower among patients; we hypothesized that this difference may have resulted from the effect of colchicine use on platelet functions.

Iohexol, platelet activation and thrombosis. I. Iohexol-induced platelet secretion does not affect thrombus formation in native blood.

BACKGROUND: The nonionic monomer iohexol triggers in vitro platelet secretion of beta-thromboglobulin (beta-TG). This iohexol platelet activation may promote intravascular thrombosis. We studied this relationship by employing a human model of collagen-induced platelet thrombus formation at arterial flow. The ionic dimer ioxaglate, the nonionic dimer iodixanol, and glucose were included. METHODS AND RESULTS: In vitro platelet activation as measured by beta-TG secretion following a 1-min incubation of native blood with 50 vol% of iohexol was significant. Glucose solutions of 300, 580 and 825 mosmol, corresponding to the osmolalities of respectively iodixanol, ioxaglate and iohexol, increased the beta-TG secretion in parallel with the osmolalities. Ioxaglate and iodixanol were virtually inert. Continuous infusion of iohexol or 580 or 825 mosmol glucose (40 vol%) into flowing native blood at an arterial wall shear rate of 2600 s-1 in an ex vivo collagen-induced platelet thrombus formation device triggered pronounced secretion of beta-TG. However, the platelet thrombus formation in blood mixed with iohexol was within the same range as that observed with ioxaglate or iodixanol. Increasing glucose osmolality induced increasing beta-TG secretion, which paralleled gradually decreasing platelet thrombus formation. CONCLUSION: Iohexol and 580 or 825 mosmol glucose trigger platelet secretion of beta-TG. This secretion is not associated with enhanced collagen-induced platelet thrombus formation at high arterial shear.

Dipyridamole specifically decreases platelet-derived growth factor release from platelets.

The authors have previously reported that dipyridamole decreased platelet-derived growth factor levels in human serum by lowering the release of this factor during blood clotting. In the present study, we have shown that this effect is specific to dipyridamole, and does not occur with other antiplatelet drugs such as aspirin, trapidil or ticlopidine. In addition, dipyridamole has been shown to decrease the PDGF level selectively, but not the levels of other factors from alpha granules in platelets (beta-thromboglobulin and platelet factor 4). These data indicate that dipyridamole may be an effective drug for the prevention of PDGF-related disorders.

In vitro platelet interactions in whole human blood exposed to biomaterial surfaces: insights on blood compatibility.

A short-term in vitro test to study platelet interactions with biomaterials is described. Using fresh human blood and a modified Chandler loop system, beta-thromboglobulin release was measured. Also, adherent platelets were observed by using scanning electron microscopy (SEM) and a colorimetric stain specific for human platelet GPIIIa. Materials studied in these experiments were polyethylene (PE), Biomer, poly(vinyl alcohol) (PVA), and a polyurethane prepared with octadecyl pendant groups (ODCE). Four blood reactions were observed: (1) Platelets continually adhere and activate on the Biomer; (2) platelets initially adhere and activate but then spread to a thin, passivating film on the PE; (3) platelets do not adhere to the PVA surface but continually react with it upon contact; and (4) platelets neither adhere to nor activate on the ODCE surface. Reactions (2) and (4) are considered characteristic of blood-compatible materials.

Effects of isradipine sustained release on platelet function and fibrinolysis in essential hypertensives with or without other risk factors.

The aim of this study was to assess the chronic effects of a highly selective dihydropiridine calcium channel blocker, israpidine, in its sustained release form (I-SRO), on platelet functions and fibrinolytic parameters in subjects with essential hypertension (EH) combined or not with other well-known cardiovascular risk factors, such as cigarette smoking (EH+S) and type II diabetes mellitus (EH+DM). Thirty-six patients with essential hypertension with sitting diastolic blood pressures of 96-104 mmHg without (EH, n = 12) or with other risk factors (EH+S, n = 12, EH+DM, n = 12) were enrolled. After a 4-week, single-blind, placebo run-in period, the subjects received I-SRO 5 mg once daily for 18 weeks. After both placebo and 6 and 18 weeks of I-SRO treatment, the following parameters were measured: sitting blood pressure by mercury sphygmomanometer; platelet aggregation, plasma beta-thromboglobulin (BTG), platelet factor-4 (PF4), and plasminogen activator inhibitor 1 (PAI-1) by means of ELISA methods; and euglobulin lysis time before (ELT) and after standardized (10 min) venous occlusion (ELT-VO). In the group of patients as a whole compared with placebo, I-SRO significantly reduced SBP/DBP platelet aggregation, BTG, PF4, ELT, and ELT-VO. Significant reductions in these parameters were also observed in each group. In addition to the antihypertensive effect, I-SRO chronic treatment may favorably affect the platelet function and fibrinolytic system in essential hypertension with or without other cardiovascular risk factors.

Iohexol, platelet activation and thrombosis. II. Iohexol-induced platelet secretion does not affect collagen-induced or tissue-factor-induced thrombus formation in blood that is anticoagulated with heparin and aspirin.

BACKGROUND: There is a dispute about the potential effects of radiographic contrast media (CM) on thrombogenesis. The nonionic CM iohexol triggers platelet beta-thromboglobulin (beta-TG) secretion, and thus may activate the platelets and promote thrombosis. We addressed this topic in a study employing a human model of arterial thrombus formation in the presence of aspirin and heparin. This was a follow-up to our initial study (on thrombus formation in native blood) which did not include antithrombotic drugs. The nonionic CM iohexol (monomer) and iodixanol (dimer) and the ionic CM ioxaglate (dimer) were compared. METHODS AND RESULTS: Thrombus formation was triggered by a surface rich in either collagen or tissue factor, positioned in a parallel-plate perfusion chamber device at an arterial wall shear rate of 2600 s-1. Blood from healthy volunteers, following ingestion of 1 g aspirin, was mixed with 40 vol% CM and 2.0 IU/ml heparin and passed over the surfaces. Thrombus formation in the presence of either CM showed no difference, despite the fact that iohexol triggered a pronounced platelet beta-TG secretion; iodixanol or ioxaglate were virtually inert. CONCLUSION: There was no association between iohexol-induced beta-TG secretion and thrombus formation on collagen (platelet-driven) or on tissue factor (thrombin-driven) in the presence of a standard antithrombotic regimen of aspirin and heparin as used in the clinic. The notion of a thrombotic risk due to platelet activation by iohexol was thus not substantiated by this study.