Differences In Thrombogenicity Research Articles

Safety and efficacy of biodegradable polymer biolimus-eluting stents in patients with non-ST-elevation acute coronary syndrome: a pooled analysis of GLASSY and TWILIGHT

Abstract Background Biodegradable polymer (BP) drug-eluting stents (DES) have shown similar safety and efficacy compared with second-generation durable polymer (DP)-DES in several randomized trials and meta-analyses. However, study participants were generally maintained on a standard dual antiplatelet therapy (DAPT) for at least 6 months after percutaneous coronary intervention (PCI). Therefore, the differences in thrombogenicity between these two stent technologies may have been unappreciated, especially among patients with acute coronary syndrome (ACS). Purpose We aimed to compare the safety and efficacy of BP Biolimus-Eluting Stent (BP-BES) versus 2nd generation DP-DES among ACS patients undergoing PCI and receiving ticagrelor alone or in combination with aspirin. Methods We pooled individual patient-level data from two randomized controlled trials, the Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention (TWILIGHT, n=9,006) (1) and the GLOBAL LEADERS Adjudication Sub-Study (GLASSY, n=7,585) (2). In order to reduce biases related to trial design differences, only NST-ACS patients not fulfilling any exclusion criterion of both studies were included and 2 separate analysis for short (0 to 3 months after PCI) and long-term (3 to 12 months after PCI) outcomes were performed. Patients were stratified according to the stent used at index PCI (BP-BES vs 2nd generation DP-DES). In both analysis, the primary outcome was major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction and definite or probable stent thrombosis); the key secondary outcomes were target-vessel failure (TVF) and BARC 2, 3 or 5 bleeding. Events rate and risk were assessed separately for the two study periods and subsequently 12-months risk estimates were derived by pooling the results of the two analysis. Results Out of 7,729 and 6,572 NST-ACS patients included in the two analysis, 2,321 (30%) and 2,211 (33.6%) received a BP-BES, respectively. Among patients treated with BP-BES versus DP-DES, the occurrence of MACE was similar at 3 months after PCI (1.1% vs 1.4%, adjusted HR 0.81, 95% CI 0.51–1.29), while it was significantly lower in the former group between 3 and 12 months (1.7% vs 3.1%, adj. HR 0.46, 95% CI 0.32–0.67) and in the overall period (pooled adjusted HR estimate 0.58, 95% CI 0.43–0.77). Similarly, significant differences were observed for TVF and BARC 2, 3, or 5 bleeding, whose risk at 12 months was lower among BP-BES than DP-DES patients (pooled adj. HR estimate 0.49, 95% CI 0.38–0.63 and 0.79, 95% CI 0.79, 95% CI 0.65–0.97, respectively). Conclusion As compared to 2nd generation DP-DES, BP-BES was associated with a lower risk of MACE, TVF and bleeding among NST-ACS patients undergoing PCI and treated with ticagrelor with or without aspirin. The findings of this analysis are exploratory and need further confirmation. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Biosensors (Singapore)

Platelet activation and aggregation in different centrifugal-flow left ventricular assist devices

Left-ventricular assist devices (LVADs) improve outcomes in end-stage heart failure patients. Two centrifugal-flow LVAD systems are currently approved, HeartMate 3 (HM3) and Medtronic/Heartware HVAD (HVAD). Clinical findings suggest differences in thrombogenicity between both systems. We compared markers of platelet activation and aggregation between HM3 and HVAD. We prospectively included 59 LVAD patients (40 HM3, 19 HVAD). Platelet P-selectin expression, activated glycoprotein (GP) IIb/IIIa and monocyte-platelet aggregates (MPA) were assessed by flow-cytometry. Platelet aggregation was measured by light-transmission aggregometry (LTA) and multiple-electrode aggregometry (MEA). Von-Willebrand factor (VWF) antigen (VWF:Ag), VWF activity (VWF:Ac), and VWF multimer pattern analysis were determined. Soluble P-selectin (sP-selectin) was measured with an enzyme-linked immunoassay. P-selectin, GPIIb/IIIa and MPA levels in vivo and in response to arachidonic acid, adenosine diphosphate, and thrombin receptor activating peptide were similar between HM3 and HVAD (all p > .05). Likewise, agonist-inducible platelet aggregation by LTA and MEA did not differ between HM3 and HVAD (all p > .05). VWF:Ag levels and FVIII:C were similar between both systems (both p > .05), but patients with HVAD had significantly lower VWF:Ac (p = .011) and reduced large VWF multimers (p = .013). Finally, sP-selectin levels were similar in patients with HVAD and HM3 (p = .845). In conclusion, on-treatment platelet activation and aggregation are similar in HM3 and HVAD patients. Potential clinical implications of observed differences in VWF profiles between both LVAD systems need to be addressed in future clinical trials.

Ethnic Difference of Thrombogenicity in Patients with Cardiovascular Disease: a Pandora Box to Explain Prognostic Differences.

Arterial and venous atherothrombotic events are finely regulated processes involving a complex interplay between vulnerable blood, vulnerable vessel, and blood stasis. Vulnerable blood ('thrombogenicity') comprises complex interactions between cellular components and plasma factors (inflammatory, procoagulant, anticoagulant, and fibrinolytic factors). The extent of thrombogenicity may determine the progression of atheroma and the clinical manifestation of atherothrombotic events, with the highest thrombogenicity in African Americans and lowest in East Asians. Inherent thrombogenicity may influence clinical efficacy and safety of specific antithrombotic treatments in high-risk patients, which may in part explain the observation that East Asian patients have reduced anti-ischemic benefits and elevated bleeding risk with antithrombotic therapy compared to Caucasian patients. In this review, we discuss available evidence regarding the racial differences in thrombogenicity and its impact on clinical outcomes among patients with atherosclerotic cardiovascular disease.

Assessment of a Siloxane Poly(urethane‐urea) Elastomer Designed for Implantable Heart Valve Leaflets

Synthetic polymer leaflets in prosthetic cardiac valves hold the potential to reduce calcification and thrombus, while improving blood flow, durability, and device economics. A recently developed siloxane poly(urethane‐urea) (LifePolymer, LP) exhibits properties essential for heart valve leaflets, including low dynamic modulus, high tensile strength, minimal creep, and excellent biostability. LP's properties result from carefully designed “linked co‐macrodiol” chemistry that maximizes silicone content and virtual crosslinks between soft and hard phases. Characterization of multiple commercial batches demonstrates a robust synthesis process with minimal variation. Extensive ISO 10993–based biocompatibility testing results in no observable toxicity or other adverse reactions. An ex vivo AV shunt thrombogenicity investigation reveals nearly undetectable levels of platelet attachment and thrombus formation on LP surfaces. Chronic ovine implantation of prototype heart valves with LP leaflets shows no differences in thrombogenicity or systemic tissue response when compared to a clinically standard tissue‐based valve. Toxicological risk assessment, based on extractables and leachables analysis of LP‐based heart valves, confirms minimal toxicological risk. Lastly, 24‐week, strain‐accelerated in vivo LP biostability testing confirms previous favorable in vitro biostability findings. These studies demonstrate that this newly developed elastomer exhibits ideal biomaterial properties for the flexible leaflets of a totally synthetic heart valve replacement.

Race-Related Differences in Thrombogenicity: An Explanation for Disparities in COVID-19 Outcomes?

Background: As COVID-19 infection continues to spread, there are increasing reports about its differential impact on racial/ethnic minorities in the United States. African Americans have worse clinical outcomes including hospitalization and mortality compared to Caucasians or Asians. Role of racial/ethnic differences in inherent thromboinflammatory milieu with COVID-19 infection remains unexplored. Methods: Medline, Cochrane Central Register of Controlled Trials, Embase, EBSCO, Web of Science, and CINAHL databases were searched for articles elaborating on COVID-19 pathophysiology and racial/ethnic differences in thrombotic biomarkers from inception through June 14, 2020. Data were used for qualitative analysis. Findings: A total of 98 articles were included in the qualitative analysis. COVID-19 infection is characterized as an immuno-thrombo-inflammatory syndrome with thrombotic microangiopathy strongly influencing clinical outcomes. Several biomarkers have been associated with severe COVID-19 including markers of thrombosis/coagulation (e.g. D-dimer, prothrombin time, etc.) and inflammation (C-reactive protein, ferritin, etc.). In this review, we summarize the reported genetic differences in the inherent thromboinflammatory milieu among different populations with increased risk of thrombosis in African Americans and increased bleeding risk particularly in Asian populations. We elaborate on the limitations of the traditional coagulation biomarkers and propose thromboelastography and rotational thromboelastometry to determine the dynamic functional clot characteristics. Interpretation: Hemostasis profiling may provide clinically relevant information of thrombotic risk used to understand the racial disparities and could be used in personalizing antithrombotic treatment strategies in COVID-19 infection.Funding Statement: NoneDeclaration of Interests: Dr. Kreutz has received consulting fees from Haemonetics. Dr. Jeong has received honoraria for lectures from AstraZeneca, Sanofi-Aventis, Daiichi Sankyo/Lilly, Haemonetics, Otsuka, Han-mi Pharmaceuticals and Yuhan Pharmaceuticals; and research grants or support from AstraZeneca, Korean Society of Interventional Cardiology, Han-mi Pharmaceuticals, Yuhan Pharmaceuticals, Otsuka and Haemonetics. Dr. Gurbel reports serving as a consultant fees/receiving honoraria from Daiichi Sankyo, Bayer, AstraZeneca, Merck, Boehringer, New Haven Pharmaceuticals, Janssen, and CSL and receiving grants from the National Institutes of Health, Daiichi Sankyo, CSL, AstraZeneca, Harvard Clinical Research Institute, Haemonetics, New Haven Pharmaceuticals, Duke Clinical Research Institute, Sinnowa, and Coramed. Dr Gurbel has patents in the field of platelet function testing. Other authors report no disclosure.

Gender differences in thrombogenicity among patients with angina and non-obstructive coronary artery disease.

Women more often present with angina and non-obstructive coronary artery disease (ANOCA) and have poorer clinical outcomes than men. These findings may be related to sex associated differences in inflammation and thrombogenicity. Consecutive patients (n = 134) with ANOCA (luminal diameter stenosis < 50%) undergoing elective cardiac catheterization were included in post hoc analysis of Multi-Analyte, thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA, NCT01276678) study. Patients with prior revascularization, coronary artery bypass grafting or myocardial infarction were excluded. Blood for thromboelastography, oxidized LDL β2-glycoprotein complex (AtherOx), oxidized-LDL, lipid profile, and urine for 11-dehydrothromboxane B2 (dTxB2) were obtained before catheterization. All women (n = 75) were post-menopausal and tended to be older than men (61.4 ± 10.6 vs. 58.6 ± 9.9year, p = 0.12), and were significantly more thrombogenic with higher thrombin-induced platelet-fibrin strength (TIP-FCS, mm) (68.0 ± 4.5 vs. 64.5 ± 6.2mm, p = 0.001), clotting index (0.35 ± 2.22 vs. - 0.72 ± 2.75, p = 0.02), K (measure of the speed to reach 20mm of clot strength from an amplitude of 2mm) (2.2 ± 1.6 vs. 1.7 ± 0.5min, p = 0.01), and fibrinogen activity (degrees) (66.6 ± 7.1 vs. 62.9 ± 7.5, p = 0.009). Markers of inflammation were not significantly different between the two groups. Women had higher total cholesterol, total LDL, LDL subtypes 1 and 2, total HDL, HDL subtypes 2 and 3, and ApoA1 (p < 0.05 for all). On multivariate regression, TIP-FCS remained significantly higher in women (p < 0.0001). Women with ANOCA are more thrombogenic than men. This fundamental difference in thrombogenicity may affect gender-related outcomes and warrants further investigation.

Thromboembolic Events with Enterprise Versus Pipeline: Porcine In Vivo Experiment

Thromboembolic complications are serious adverse events associated with stenting of intracranial aneurysms. For the development of novel devices, currently no practical model exists to evaluate distal embolic events. The purpose of the current study was 2-fold: 1) assess the feasibility of a porcine carotid bifurcation model for invivo testing of stent thrombogenicity and 2) compare the thrombogenicity of the Enterprise vascular reconstruction device versus the Pipeline embolization device (PED). Six Yorkshire pigs underwent implantation of size-matched devices across the carotid bifurcation. Each animal received 1 Enterprise and 1 PED contralaterally. Baseline and 2-week follow-up angiography were performed. Images were analyzed including detailed measurements of the rete mirabile, a small-vessel conglomerate supplied by branches of the common carotid artery. In the absence of thromboembolic events at 2 weeks (n= 8), the perfused rete area measured 134.4 ± 6.9 mm2. In the presence of thromboembolic events (n= 4), theperfused rete was reduced to an area covering 37.1 ± 8.6 mm2 (P < 0.01). There was no difference in thrombogenicity between Enterprise and PED with a thromboembolic event rate of 33.3% for both devices (P > 0.99). The swine carotid stent model allows invivo analysis of device-related thrombogenicity and distal embolic event rates. Size reduction of the perfused rete mirabile indicates the presence of thromboembolic events. Both Enterprise and PED were associated with similar thrombogenicity in this experiment.

Potential Mechanisms of Vascular Thrombosis after Microwave Ablation in an in Vivo Liver

PurposeTo evaluate potential biologic and thermal mechanisms of the observed differences in thrombosis rates between hepatic vessels during microwave (MW) ablation procedures. Materials and MethodsMW ablation antennae were placed in single liver lobes of 2 in vivo porcine liver models (n = 3 in each animal; N = 6 total) in the proximity of a large (> 5 mm) portal vein (PV) and hepatic veins (HVs). Each ablation was performed with 100 W for 5 minutes. Conventional ultrasound imaging and intravascular temperature probes were used to evaluate vessel patency and temperature changes during the ablation procedure. Vascular endothelium was harvested 1 hour after ablation and used to characterize genes and proteins associated with thrombosis in PVs and HVs. ResultsTargeted PVs within the MW ablation zone exhibited thrombosis at a significantly higher rate than HVs (54.5% vs 0.0%; P = .0046). There was a negligible change in intravascular temperature in PVs and HVs during the ablation procedure (0.2°C ± 0.4 vs 0.6°C ± 0.9; P = .46). PVs exhibited significantly higher gene expression than HVs in terms of fold differences in thrombomodulin (2.9 ± 2.0; P = .0001), von Willebrand factor (vWF; 7.6 ± 1.5; P = .0001), endothelial protein C receptor (3.50 ± 0.49; P = .0011), and plasminogen activator inhibitor (1.46 ± 0.05; P = .0014). Western blot analysis showed significantly higher expression of vWF (2.32 ± 0.92; P = .031) in PVs compared with HVs. ConclusionsLarge PVs exhibit thrombosis more frequently than HVs during MW ablation procedures. Biologic differences in thrombogenicity, rather than heat transfer, between PVs and HVs may contribute to their different rates of thrombosis.

Race and sex differences in thrombogenicity: risk of ischemic events following coronary stenting

Race and sex affect thrombogenicity. We have demonstrated that platelet-fibrin clot characteristics can be used to stratify patients for risk of ischemic events following percutaneous coronary intervention. We investigated race and sex differences in thrombogenicty and the relation to ischemic risk in 252 consecutive African-American and Caucasian men and women undergoing elective percutaneous coronary intervention. Platelet-fibrin clot characteristics were measured using the Thrombelastograph Hemostasis System. The incidence of adverse ischemic events was assessed over a 6-month follow-up period. Overall, 40 ischemic events (15.9%) occurred. Adverse events were higher in African-Americans than Caucasians (P = 0.14), and in women than men (P = 0.004). The incidence was highest in African-American women (37.5%) and lowest in African-American men (6.5%). Measured Thrombelastograph parameters were significantly different between ischemic and nonischemic patients (P < 0.05). African-American women in the ischemic group exhibited higher thrombogenicity than the other race and sex groups (P < 0.05). Multivariate logistic regression identified platelet-fibrin mediated clot strength (relative risk 2.52, P = 0.017) and sex (relative risk 2.56, P = 0.009) as significant independent predictors of ischemic events 6 months postpercutaneous coronary intervention. Thrombogenicity is a novel measurable cardiovascular risk factor that varies by race and sex, is highest in African-American women, and independently predicts the frequency of ischemic events following percutaneous coronary intervention. Point-of-service measurements of platelet-fibrin clot characteristics may lead to more intensified antithrombotic therapy and reduced mortality in selected patients.

The use of a balloon angioplasty model of arterial injury to compare the thrombogenicity of dietary anhydrous milkfat, fish oil and hydrogenated coconut oil in pigs

Three groups each of 16 pigs were fed for 70 days on a diet containing one of three test fats/oils (anhydrous milkfat, fish oil (MaxEPA TM) or hydrogenated coconut oil) at a level of 100 g/kg. On day 70, a balloon catheter was inserted under anaesthesia into each femoral artery and inflated to 620.5 kPa for five 30 sec intervals. One h after angioplasty, while still anaesthetised, the pigs were killed by exsanguination. The injured segments of femoral artery were perfused in vivo with 0.9% saline and 10% neutral buffered formalin before being harvested. Thrombus size was determined by the counts of technetium-99m-labelled platelets in the injured arteries and by morphometry of the thrombus area in microscopic sections. Of 91 arteries subjected to angioplasty, mural thrombi were seen macroscopically in all nine arteries that had deep injury with exposure of the tunica media, as well as in 19 of the remaining 82 arteries (23%) in which there was no evidence of a medial tear. Many small platelet-rich thrombi, attached to the denuded endothelium, were also detected microscopically. There was no statistically significant effect of diet on either thrombus area or platelet deposition at sites of arterial injury. Failure to show significant differences may have been due to the large within-group variation in thrombus size, a factor which may limit the use of this model in studies aimed at detecting differences in thrombogenicity between different dietary fats and oils.

Randomized trial of vein versus Dacron patching during carotid endarterectomy: Influence of patch type on postoperative embolization

Purpose: A recent overview indicated that although routine patching is safer than routine primary closure after carotid endarterectomy (CEA), there is no systematic evidence that patch type influences outcome. However, most surgeons still believe that prosthetic patches are probably more thrombogenic than vein patches. This study tested the hypothesis that there was no difference in thrombogenicity between the different patch types. Methods: A total of 274 patients undergoing 276 CEAs were randomized to either Dacron-patch closure (n = 137) or vein-patch closure (n = 139). All patients with an accessible cranial window were monitored for 3 hours postoperatively with transcranial Doppler scanning (TCD). The number of emboli and rate of embolization were quantified with the requirement for selective dextran therapy to control high rates of postoperative embolization. All patients were assessed postoperatively and again at 30 days by a neurologist, and all patients underwent a duplex examination at 30 days. Results: The 30-day death/any stroke rate was 2.2% for patients in the Dacron-patch group and 3.6% for patients in the vein-patch group (P =.72). Patients in the Dacron-patch group had a higher incidence of postoperative emboli (median, 5; interquartile range, 0-10.5) than patients in the vein-patch group (median, 3; interquartile range, 1-17; P =.028). However, the incidence of detecting more than 50 emboli was virtually identical, and patch type had no effect on the incidence of high-rate, sustained embolization that required dextran therapy (5.3% for Dacron, 3.7% for vein). No patient had a carotid thrombosis at 30 days. Conclusion: Sustained, high-rate embolization, previously shown to be highly predictive of progression to carotid thrombosis, appears to be patient dependent, rather than related to patch type. (J Vasc Surg 2001;33:994-1000.)

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.

Studies of activated GPIIb/IIIa receptors on the luminal surface of adherent platelets. Paradoxical loss of luminal receptors when platelets adhere to high density fibrinogen.

The accessibility of activated GPIIb/IIIa receptors on the luminal surface of platelets adherent to damaged blood vessels or atherosclerotic plaques is likely to play a crucial role in subsequent platelet recruitment. To define better the factors involved in this process, we developed a functional assay to assess the presence of activated, luminal GPIIb/IIIa receptors, based on their ability to bind erythrocytes containing a high density of covalently coupled RGD-containing peptides (thromboerythrocytes). Platelets readily adhered to wells coated with purified type I rat skin collagen and the adherent platelets bound a dense lawn of thromboerythrocytes. With fibrinogen-coated wells, platelet adhesion increased as the fibrinogen-coating concentration increased, reaching a plateau at about 11 micrograms/ml. Thromboerythrocyte binding to the platelets adherent to fibrinogen showed a paradoxical response, increasing at fibrinogen coating concentrations up to approximately 4-6 micrograms/ml and then dramatically decreasing at higher fibrinogen-coating concentrations. Scanning electron microscopy demonstrated that the morphology of platelets adherent to collagen was similar to that of platelets adherent to low density fibrinogen, with extensive filopodia formation and ruffling. In contrast, platelets adherent to high density fibrinogen showed a bland, flattened appearance. Immunogold staining of GPIIb/IIIa receptors demonstrated concentration of the receptors on the filopodia, and depletion of receptors on the flattened portion of the platelets. Thus, there is a paradoxical loss of accessible, activated GPIIb/IIIa receptors on the luminal surface of platelets adherent to high density fibrinogen. Two factors may contribute to this result: engagement of GPIIb/IIIa receptors with fibrinogen on the abluminal surface leading to the loss of luminal receptors, and loss of luminal filopodia that interact with thromboerythrocytes. These data provide insight into the differences in thrombogenicity between surfaces, and may provide a mechanism for purposefully passivating platelet-reactive artificial surfaces.

A fiberoptic compatable midinfrared laser with CO 2 laser-like effect: Application to atherosclerosis

In theory, pulses of laser light in the 2-μm range should ablate tissue in a manner similar to that of the 10.6-μm CO 2 laser with the added advantage of efficient transmission through flexible quartz fibers. Using 200-μsec pulses of 2.15-μm thulium—holmium—chromium:YAG (THC:YAG) laser light, we were able to create 700-μm-diameter holes through calcific atherosclerosis in vitro. In vivo evaluation of thrombogenicity and healing was accomplished by exposing the luminal surface of rabbit aortas to the THC:YAG laser. Serial histologic examinations of laser-treated rabbit aortae revealed a time course of resolution of the lesions which was very similar to that observed with like-sized lesions created with the same amount of continuous wave CO 2 energy. No significant differences in thrombogenicity nor healing response were noted. The excellent in vivo response observed is due in part to the pulsed nature of the THC:YAG laser output as well as to the efficient tissue absorption at the 2.15-μm wavelength. We feel that excellent ablative effects with minimal collateral thermal damage can be obtained through fiberoptic delivery systems by taking advantage of laser wavelengths corresponding to the infrared absorption peak of water in the 2-μm region and pulsed delivery of the laser energy.

Indium 111-labeled platelet deposition in woven and knitted Dacron bifurcated aortic grafts with the same patient as a clinical model

A study was designed to compare platelet deposition between knitted and woven Dacron grafts in the same patient. Twenty patients received aortoiliac or aortofemoral bifurcated Dacron grafts, each composed of one woven and one double-velour knitted limb. External nuclear graft imaging was carried out after injection of autologous platelets labeled with indium 111. The patients were studied postoperatively in time periods ranging from 6 days to 42 months. Platelet accumulation was almost identical in knitted and woven limbs in all patients. This study appears to indicate that there is no difference in thrombogenicity between knitted and woven bifurcated Dacron grafts in the aortoiliac or aortofemoral positions measured by platelet accumulation.

Effects of roughness on the thrombogenicity of a plastic.

Tubings extruded from one batch of polyvinylchloride resin at five temperatures ranging from 110 to 205 degrees C were tested for thrombogenicity in the saphenous vein and aorta of sheep. There was more thrombus in both the vein and aorta on tubings extruded at lower temperatures. The surface areas of renal infarction were smaller when lower temperature tubings were inserted into the aorta. Scanning electron microscopy showed that lower extrusion temperatures caused greater roughness on the tubings. This greater roughness was confirmed by roughness measurements. It is suggested that the association which has been demonstrated between roughness and thrombus formation might be due to the degree of adhesion of the thrombus to the surface rather than to differences in thrombogenicity.

Thrombus formation in the artificial kidney. Platelet and fibrin(ogen) content of experimental thrombi detected by radioisotope technique.

In vitro studies in a "mini-Kiil" dialyser showed that, in spite of presumably adequate heparinization (2.5 IU/ml plasma), 51Cr-labelled platelets and 125I-labelled fibrin(ogen) deposited on membranes and blood lines, when freshly drawn human blood was dialyzed for 30 min. Platelet retention dominated, with a Cr/I ratio 3 times that of blood. Increasing the heparin concentration led to a reduction both of 51Cr- and 125I-activity, with a slight fall in the Cr/I ratio. Heparin was unable to prevent platelet retention in the dialyser, but the platelet aggregating effect of heparin was shown to be of minor importance compared to its anticoagulant activity and effect on thrombin induced platelet aggregation. Platelet retention by the blood lines exceeded that of the dialyser, in spite of a much smaller surface area. Differences in thrombogenicity between cuprophane and silicone rubber as well as different flow characteristics in the two situations were probably contributory. When heparinized tubing was used, the radioactivity retained was negligible, but membrane radioactivity was unaltered. A considerable reduction in blood radioactivity during dialysis, not accounted for by the deposits above, suggests the additional formation of more loosely attached platelet/fibrin(ogen) masses.

Measurement of thrombus formation on intravascular catheters.

Relative thrombogenicities of several brands of intravascular catheters were measured in the saphenous and cephalic veins of sheep. Differences in thrombogenicity between brands of up to eleven fold were found. At least one brand contained an ingredient which was locally toxic to sheep and which caused phlebitis in cannulated vessels. The brands tested were made from six types of plastics. It is suggested that differences in manufacturing technique may be more important than the type of plastic in determining the thrombogenicity of catheters.