Influence of storage temperature on the responsiveness of human platelets to agonists

To investigate the effects of storage temperature on the responsiveness to agonists of human platelets prepared from stored blood, we measured the aggregability and acid-base status of platelets from 96 healthy subjects before and after storage of whole blood at 4 degrees C and room temperature (RT) up to 48 hr. After 24 hr storage at 4 degrees C, there were no significant differences in agonist-induced platelet aggregability, compared to fresh specimens. When blood was kept at RT for 24 hr, all of the platelet samples showed non-responsiveness (< 20% aggregability) to epinephrine and 70% (67/96) revealed impaired responsiveness (20 to 60% aggregability) to adenosine diphosphate (ADP); there were no samples that showed impaired- or non-responsiveness to collagen or ristocetin. Among the 67 samples that showed impaired responsiveness to ADP after RT storage, 62 (93%) exhibited the loss of a secondary wave of aggregation in response to ADP. After storage of blood at RT for 48 hr (pH 6.81 +/- 0.06), mean values of maximal platelet aggregability to epinephrine, ADP, collagen, and ristocetin were 8%, 16%, 19%, and 70%, which were significantly lower than the corresponding mean values after storage of blood at 4 degrees C for 48 hr (pH 7.04 +/- 0.04) (ie, 66%, 69%, 102%, and 91%, p < 0.01). In summary, refrigerated storage of human blood improves the stability of platelet responsiveness to agonists. Storage at RT causes platelet non-responsiveness to epinephrine and disturbs the release reaction of endogenous ADP.     

Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death

We have previously reported that the frequencies of myocardial infarction and of sudden cardiac death are highest during the period from 6 a.m. to noon. Since platelet aggregation may have a role in triggering these disorders, we measured platelet activity at 3-hour intervals for 24 hours in 15 healthy men. In vitro platelet responsiveness to either adenosine diphosphate (ADP) or epinephrine was lower at 6 a.m. (before the subjects arose) than at 9 a.m. (60 minutes after they arose). The lowest concentration of these agents required to produce biphasic platelet aggregation decreased (i.e., aggregability increased) from a mean +/- SEM of 4.7 +/- 0.6 to 3.7 +/- 0.6 microM (P less than 0.01) for ADP and from 3.7 +/- 0.8 to 1.8 +/- 0.5 microM (P less than 0.01) for epinephrine. The period from 6 to 9 a.m. was the only interval in the 24-hour period during which platelet aggregability increased significantly. We subsequently studied 10 subjects on alternate mornings after they arose at the normal time and after delayed arising. The morning increase in platelet aggregability was not observed when the subjects remained supine and inactive. Thus, there is a temporal association between increased platelet aggregability in the morning and an increased frequency of myocardial infarction and of sudden cardiac death. Demonstration of this association does not establish a cause--effect relation, but together with other evidence linking platelets to these disorders, it may provide insight into the mechanisms precipitating myocardial infarction and sudden cardiac death and aid in the design of more effective preventive measures.     

Tirofiban administration attenuates platelet and platelet-neutrophil conjugation but not neutrophil degranulation during in vitro VAD circulation

Ventricular Assist Devices (VADs) have been used as bridges to heart transplantation. However, VAD circulation is complicated by the incidence of thromboembolism, prolonged bleeding, and activation of the inflammatory cascade. We hypothesize that platelet and neutrophil activation are interrelated and linked to the activation of the glycoprotein (GP) IIb/IIIa platelet receptor. The purpose of this study is to evaluate the effects of Tirofiban, a platelet GP IIb/IIIa receptor inhibitor, on platelet and neutrophil activation during simulated VAD circulation. Two groups of five in vitro VAD circuits were simulated with and without Tirofiban using 450 cc of human blood. Blood samples were drawn at specific time intervals up to 72 hours, measuring leukotriene C4 (LTC4), platelet factor four (PF4), and neutrophil elastase. Tirofiban decreased serum levels of PF4 and LTC4 during VAD circulation. Neutrophil elastase secretion was not affected by Tirofiban administration. Preconditioning of VAD circulation with Tirofiban attenuated platelet activation as demonstrated by a decrease in serum PF4 levels. Tirofiban administration ameliorates the inflammatory response by altering platelet-neutrophil interaction as demonstrated by a decrease in LTC4 production. Continued elastase secretion indicates that the inflammatory response is not completely inhibited by Tirofiban administration. These results suggest that neutrophils may be activated by alternative mechanisms. Early complement activation has been demonstrated during in vivo and in vitro VAD circulation and may play a role in mediating inflammatory and thromboembolic reactions during VAD use.     

Extensive coagulation monitoring in patients after implantation of the MicroMed Debakey continuous flow axial pump

Ventricular assist device (VAD) implantation is associated with impaired primary hemostasis and thromboembolic complications. Recently, a new generation of implantable continuous flow axial pumps was introduced into clinical application. To study the potential thrombogenic properties of this type of pump, we applied extensive platelet monitoring was applied. In our institution, 13 patients received the MicroMed DeBakey VAD as a bridge to transplantation. Routine coagulation tests (platelet count, activated partial thromboplastin time, prothrombin time, antithrombin III activity) and platelet function tests (whole blood aggregometry, thrombelastography, flow cytometry) were performed. No clinically relevant thromboembolic events were detected. No correlation was found between global function tests, platelet aggregation, and thrombelastography. No correlation was detected between platelet activation and hemolysis parameters. Platelet aggregation and coagulation index were significantly suppressed early after operation. A subsequent phase of hyper-aggregability, starting around day 6, suggested the initiation of antiaggregation therapy. Platelet activation markers were upregulated in the postoperative period but were returned to preoperative levels after initiation of aspirin. In contrast to routine coagulation monitoring, platelet function tests reflect in detail the coagulation status of blood pump recipients and the efficiency of antiaggregation therapy. Aspirin and dipyridamole therapy in addition to oral anticoagulation using phenprocoumon may contribute to platelet function and clot mechanics restoration and is, therefore, recommended for patients after VAD implantation.     

17Beta-estradiol rapid stimulation of rat aorta NOS activity is prevented by oestrogen deficiency

OBJECTIVES: The purpose of this study was to determine the effects of chronic oestrogen deficiency on rat aorta rapid response to 17beta-estradiol treatment. METHODS: Rat aortic strips (RAS) were isolated from Wistar female rats of three different groups: rats 6-7-month old with normal oestrogen levels (NER); aged rats, 24-month old, with low oestrogen levels (LER); and young rats after 2 months of bilateral ovariectomy (OVX). Platelet aggregation was measured after incubation of RAS in a platelet rich plasma by addition of 10 microM ADP. NO production by RAS was measured by 3H-citrulline technique. RESULTS: RAS obtained from NER treated with 17beta-estradiol produced an inhibition of platelet aggregation specific for ovarian hormones, since testosterone was devoid of any effect. In aortic tissue isolated from male rats no increment in nitric oxide (NO) production was found. RAS from LER and OVX treated with 1-10 nM failed to induce a significant inhibition of platelet aggregation compared with NER (5 and 17%; 6 and 20% vs. 45 and 77% inhibition of platelet aggregation respect to control, respectively). In contrast to NER, 5 min treatment of LER and OVX aortic tissue with 1 nM 17beta-estradiol did not incremented NO production (NER 1.14 vs. 2.3 (P < 0.05); LER 1.14 vs. 1.42; OVX 1.24 vs. 1.52 pmol NO per mg protein). CONCLUSIONS: These results suggest that chronic oestrogen deprivation impairs the inhibition of platelet aggregation and suppresses the rapid stimulation of aortic NOS induced by acute 'in vitro' treatment with 17beta-estradiol.     

Species variability in platelet aggregation response to different agonists

Conflicting data on platelet function in animal species are reported in the literature. In this study, the response of buffalo, horse, pig and sheep platelets to different agonists was assessed. Blood samples were collected from the jugular vein of six healthy subjects of each species and platelet-rich plasma was obtained by centrifugation. Platelet aggregation responses to increasing doses of adenosine 5'-diphosphate (ADP), arachidonic acid, collagen, platelet activating factor (PAF) and ristocetin were measured by a turbidimetric method. Horse platelets were the most responsive to ADP, collagen and PAF, whereas sheep platelets were the most responsive to ristocetin. The response to arachidonic acid varied least between species. PAF was the most effective agonist, inducing a maximum aggregation response at a concentration of 1 micro M for platelets of each species. Conversely, concentrations of ristocetin higher than 1mg/ml induced a maximum aggregation response only with sheep and horse platelets. The different responses of platelets from the four animal species to various agonists may reflect either (1). structural differences (including composition of the platelet membrane and presence of specific agonist receptors), or (2). activation of distinct signalling pathways by the agonist.     

Fibrinogen degradation products generation is the major determinant of platelet inhibition induced by plasminogen activators in platelet-rich plasma

The platelet function defect induced by thrombolytic agents has been referred either to the degradation of platelet surface receptors or to the anti-aggregatory effect of fibrinogen degradation products (FgDPs).In the present study we have evaluated platelet aggregation induced by ADP, collagen and ristocetin after incubation of washed platelets or platelet-rich plasma (PRP) with plasmin (1.1–3.4IU/ml), plasminogen activators (PAs) (streptokinase 250–1000 IU/ml; urokinase, 10–1000 IU/ml; t-PA 0.5–10 μg/ml) or FgDPs (0.062–2 mg/ml). In parallel the surface levels of platelet GP lb and IIb/IIIa complex were determined by fluorescence flow cytometry using specific monoclonal antibody.Washed platelets treated with plasmin (1.1IU/ml) for 10 to 90 min showed a progressive reduction of ristocetin-induced platelet agglutination and a progressive reduction of surface GP Ib. Surface expression of GP IIb/IIIa complex was significantly increased after plasmin exposure.The addition of PAs to PRP resulted in a marked reduction of ADP-induced platelet aggregation. Collagen-induced platelet aggregation was only slightly affected. Similar changes were observed when PRP was preincubated with high concentrations of FgDPs. In PRP treated with PAs platelet surface levels of GP Ib and GP IIb/IIIa complex did not show any significant changes.In conclusion our results show that in plasma no proteolysis of platelet adhesive receptors occurs after plasminogen activation. The platelet inhibition observed after incubation of PRP with PAs is likely to be caused by FgDPs generation.     

Evaluation of platelet aggregability during left ventricular bypass using a MedTech MagLev VAD in a series of chronic calf experiments

The impact of continuous flow left ventricular assist device (LVAD) pumping on platelet aggregation was investigated in animal experiments utilizing six calves. A single-use MagLev centrifugal blood pump, MedTech MagLev, was used to bypass the calves’ hearts from the left atrium to the descending aorta at a flow rate of 50 ml/kg/min. The LVAD’s impact on blood coagulation activities was evaluated based on the platelet aggregability, which was measured with a turbidimetric assay method during the preoperative, operative, and postoperative periods. Heparin and warfarin were used for anticoagulation, while aspirin was used for the antiplatelet therapy. A decrease in platelet aggregation immediately after the pump started was observed in the cases of successful long-term pump operation, while the absence of such a decrease might have caused coagulation-related complications to terminate the experiments. Thus, the platelet aggregability was found to be significantly affected by the pump, and its initial trend may be related to the long-term outcome of the mechanical circulatory support.     

Platelet aggregation and platelet function analyzer 100 (PFA-100) closure time in camels—a comparative study with humans

Despite the very active coagulation system in camels, there are no previous studies on camel platelet functions. It is our aim to study camel platelet function using aggregometry, Platelet Function Analyzer (PFA100), and flow cytometry. A total of 103 camels, 19 males and 84 females, were studied. Their ages ranged from 5 to 20 years (mean±SD: 6.4±4.4 years). The results obtained were compared with healthy humans. Platelet aggregometry was undertaken in platelet-rich plasma in response to adenosine diphosphate (ADP), adrenaline, collagen, arachidonic acid, and ristocetin. Camel platelet function in whole blood was also tested using the PFA-100 and by flow cytometry using three human monoclonal antibodies (CD42, CD61, and CD62). Camel platelets failed to respond to arachidonic acid, adrenaline, and ristocetin. However, responses to ADP and collagen were obtained but were less than the human values. The addition of human plasma caused some enhancement of the aggregation responses to adrenaline and collagen but not ristocetin or arachidonic acid. However, the presence of human serum or heparin resulted in a very marked enhancement of the camel platelet aggregation responses to all agonists, except arachidonic acid. PFA-100 closure times of the collagen–ADP and the collagen–epinephrine cartridges were markedly longer than in humans. In the flow cytometry studies, camel platelets failed to respond to any of the human monoclonal antibodies with or without activation by ADP, thrombin, human plasma, or serum. This first study on camel platelet functions uncovered the distinction between camel and human platelet functions. The lack of platelet responses to certain aggregating agonists, their enhancement with human plasma and serum, as well as the prolongation of the PFA-100 closure times, add other unique characteristics to the biology of this interesting creature.     

Mechanism of hypocoagulative effect of low-intensity laser radiation

Aggregation of platelets and their role in the hypocoagulation syndrome was studied afterin vitro irradiation of blood with a laser. Thromboelastography was performed in platelet-rich and platelet-free plasma. Low-intensity laser radiation affected the coagulation system via platelets. It decreased platelet aggregation induced by ADP, collagen, epinephrine, ristocetin, platelet activating factor, and fibrinogen. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 7, pp. 36–38, July, 1998     

大鼠脑血栓形成时心功能不全发生机制的探讨

以脑水含量、局部脑血液、全血血小板聚集、心输出量、每搏出量、心率、平均血压、外周总阻力及心、肝、脾。肾和肾上腺局部血流量为指标，探讨 光化学法诱导的实验性血栓形成性局部脑缺血时全血血小板功能改变对心功能的影响及其机理。结果表明，光化学反应后４小时，全血血小板聚集明显增强（Ｐ＜０．０１），ＣＯ、ＳＶ降低（Ｐ＜０．０５）；２４小时ｒＣＢＦ，ＣＯ，Ｓ及心肌ｒＢＦ均明显减少，ＴＰＲ及脑水含量明显增加（Ｐ＜     

Role of immunoglobulin G in platelet aggregation by viridans group streptococci.

The aggregation of human platelets by the viridans group streptococci requires both direct platelet-bacterium binding and plasma components. Some of these extracellular constituents (e.g., fibrinogen) are cofactors for ADP, which mediates the terminal events in platelet activation by these organisms. In addition, other plasma components which are specific for viridans group streptococci are necessary. To better define these latter cofactors, we examined the role of immunoglobulin G (IgG) in platelet aggregation by two strains of viridans group streptococci. The addition of either strain to washed human platelets suspended in normal plasma resulted in a 5- to 12-min lag phase, followed by brisk and irreversible platelet aggregation. In contrast, neither strain aggregated platelets suspended in IgG-depleted plasma (IgG concentration, less than or equal to 6.7 micrograms/ml). The addition of IgG (1.0 mg/ml) to the platelet suspension restored normal aggregation. Absorption of the IgG with intact bacteria abolished its ability to support aggregation. Preincubation of washed platelets with a murine monoclonal antibody to the 40,000-Mr platelet Fc receptor blocked aggregation by both strains, but had no effect on aggregation by ADP (5 microM) or collagen (200 micrograms/ml). Neither strain aggregated gel-filtered platelets supplemented with fibrinogen (100 micrograms/ml), whereas ADP induced a maximal platelet response. When IgG (1.0 mg/ml) was added to the suspension of gel-filtered platelets, both strains produced normal aggregation. These results indicate that specific IgG is required for platelet aggregation by viridans group streptococci and that platelet activation is mediated through the 40,000-Mr Fc receptor on the platelet surface.     

Effects of poly(ethyleneglycol)-modified hemoglobin vesicles on agonist-induced platelet aggregation and RANTES release in vitro

We studied the effects of hemoglobin-vesicles modified with PEG (PEG-HbV), a type of liposome-encapsulated hemoglobin (LEH), on human platelet functions in vitro. The effect of a low concentration of PEG-HbV (Hb; 5.8 mg/dl) was assessed by examining an agonist-induced aggregation response, and that of relatively high concentrations of PEG-HbV (Hb; 0.29, 1 and 2 g/dl) by measuring the release of RANTES (Regulated upon activation, normal T-cell expressed and presumably secreted) from platelets, which is regarded as a marker of platelet activation. The preincubation of platelets with PEG-HbV at 5.8 mg/dl of Hb did not affect platelet aggregation induced by collagen, thrombin and ristocetin. The pretreatment of platelet-rich plasma (PRP) with PEG-HbV at concen trations up to 2 g/dl of Hb had no aberrant effects on the collagen-induced RANTES release. Furthermore, the collagen-induced release of RANTES from PRP was not affected by longer incubation with PEG-HbV at 2 g/dl of Hb. The basal levels of RANTES from PRP were unchanged in the presence of PEG-HbV. These results suggest that PEG-HbV, at the concentrations studied, have no aberrant effects on platelet functions in the presence of plasma.     

Platelet dysfunction in Noonan's syndrome. A case with a platelet cyclooxygenase-like deficiency and chronic idiopathic thrombocytopenic purpura

Individuals with Noonan's syndrome are likely to have one or more coagulation abnormalities: complex platelet function defects, partial Factor XI deficiency, or von Willebrand's disease. A distinctive platelet function defect has not been identified. The authors describe a 24-year-old women with Noonan's syndrome, chronic idiopathic thrombocytopenic purpura (ITP), and a platelet function defect characterized by a greater than 15-minute bleeding time, failure of aggregation and release with 10 microM ADP, 10 microM epinephrine, 750 microM arachidonic acid or 0.019 g/L collagen. A mixture of aspirin-treated platelets with the patient's platelets failed to correct the defect. Addition of 2.5 microM U46619 (a PGG2 analogue) corrected the aggregation and release defect. An electron microscopic analysis failed to reveal structural abnormalities. Thus, the platelet function defect in this patient appears to be a functional deficiency of cyclooxygenase. The presence of autoantiplatelet antibodies in a clinical setting consistent with chronic ITP raises the possibility that the defect may be acquired.     

C1 inhibitor infusion modifies platelet activity in hereditary angioedema patients

CONTEXT: C1 inhibitor (C1-INH) is an alpha2-globulin that blocks esterolytic activity of the first component of the classic complement cascade. The alpha-granules of normal human platelets also contain C1-INH, which is expressed on the platelet surface during platelet secretion in healthy patients, but it is clearly reduced in patients with hereditary angioedema (HAE). OBJECTIVE: To evaluate the effects of in vivo C1-INH concentrate infusion on platelet responsiveness and coagulation system activity in patients with HAE. DESIGN: Assessment of the platelet activity and plasma levels of C1-INH, activated factor XII (XIIa), and prothrombin fragment F1.2 (F1.2) before and after infusion of 15 U/kg of C1-INH concentrate. PATIENTS: In 6 patients (4 men and 2 women), HAE was diagnosed according to the accepted clinical and laboratory criteria. MEASUREMENTS: Platelet aggregation (final concentrations: adenosine diphosphate, 0.5, 1.25, and 2.5 microM; collagen, 5 microg/mL), C1-INH antigen (radial immunodiffusion), C1-INH activity (chromogenic substrates), and XIIa and F1.2 (enzyme-linked immunosorbent assay). RESULTS: After C1-INH infusion, we observed a prompt increase of C1-INH level and a slow return toward its plasma preinfusion values within 4 to 7 days, a significant decrease of both adenosine diphosphate- and collagen-induced platelet aggregation versus preinfusion values (maximum after 1-2 days; P <.001), and a rapid decrease of high basal values of XIIa and F1.2 in 30 and 120 minutes, respectively. CONCLUSIONS: These data show a role of C1-INH in the control of platelet activity and that its deficiency increases platelet aggregability and plasma levels of XIIa and F1.2 in patients with HAE.     

The platelet reactivity of vascular graft prostheses: an in vitro model to test the effect of preclotting

An in vitro perfusion system was used to study the platelet reactivity of the following vascular graft materials when tested with human blood: expanded polytetrafluoroethylene (ePTFE), crimped Dacron Bionit (DB) and preclotted Dacron Bionit (DB/PC). These materials were simultaneously compared to silicone rubber (SR) using an identical perfusion circuit with the same donor's blood. All vascular graft materials tested in this in vitro perfusion system caused some degree of platelet activation as shown by a decrease in platelet count, an increase in platelet factor 3 activity, elevation of plasma levels of both platelet factor 4 and β-thromboglobulin and decreased platelet aggregability. The observed platelet activation was striking for Dacron and especially preclotted Dacron, with ePTFE showing low levels of platelet activation. Platelet activation fay Dacron was initially rapid and then levelled off, whereas the platelet activation with preclotted Dacron began more slowly, but reached much greater levels after three hours of in vitro perfusion.     

Intraglomerular thrombotic tendency and glomerular ADPase. Unilateral impairment of ADPase elicits a proaggregatory microenvironment in experimental glomerulonephritis

It has been proposed, predominantly from ex vivo studies, that glomerular ADPase may function as an antithrombotic principle within the rat kidney. Therefore, intraglomerular platelet aggregation was studied in vivo in rats after impairment of glomerular ADPase activity using local X-irradiation (20 Gy). Biochemical assays in suspensions of glomeruli obtained from rats 24 hours after local X-irradiation (group I) demonstrated a significant reduction in ADPase activity as compared to sham treated rats (group II; p less than 0.01). Cytochemical observations at the ultrastructural level showed that this reduction in glomerular enzyme activity represents in particular ADPase activity detectable in the basement membrane. Following X-irradiation, intraglomerular platelet aggregation was quantitatively studied in two groups of rats. Both groups received X-irradiation of the left kidney (20 Gy). Twenty-four hours after X-irradiation, animals received an intravenous injection of either 0.5 ml of saline (group III; N = 6) or 0.5 ml of heterologous nephrotoxic serum (NTS; group IV; N = 6). Subsequently, 24 hours after this injection, platelet aggregation in left kidneys was compared with aggregation in contralateral non-X-irradiated kidneys. The results showed that while X-irradiation per se did not induce intraglomerular platelet aggregation as compared with the contralateral kidney (0.20 +/- 0.08% versus 0.17 +/- 0.06% platelet aggregation/glomerulus), a significant increase in platelet aggregation could be demonstrated in X-irradiated kidneys in the early phase of nephrotoxic serum nephritis as compared with the contralateral nephritic kidney (2.45 +/- 0.66% versus 1.37 +/- 0.35% platelet aggregation per glomerulus; p less than 0.005). A potential effect of altered influx of inflammatory cells after X-irradiation could be excluded since no difference in H2O2 producing cells was observed between left and right kidneys. Thus, while ADPase impairment by X-irradiation does not induce platelet aggregation per se, it is clear that in proaggregatory conditions, like in NTS nephritis, the thrombotic tendency, due to decreased glomerular ADPase, is enhanced. These results demonstrate the functional significance of glomerular ADPase activity as an antithrombotic principle following platelet activation in vivo.     

Platelet function: aggregation by PAF or sequestration in lung is not modified during immediate or late allergen-induced bronchospasm in man

Among the mediators involved in the pathophysiologic mechanisms that underly the reactions of the acute and delayed phases of bronchospasm induced by allergens in man, platelet-activating factor (PAF) could play an important role, in particular by its effects on platelets. In animals, inhalation or injection of PAF causes a platelet-dependent bronchoconstriction that is blocked by prior administration of an antiplatelet antiserum and accompanied by platelet accumulation in the pulmonary vessels. In man, inhalation of PAF causes a bronchospasm and induces a bronchial hyperreactivity. Abnormalities of platelet aggregation and the secretion into plasma of platelet factor 4 and beta-thromboglobulin have been described in patients with asthma during induced bronchospasm. Platelet functions have been studied in 15 patients with asthma before and after allergen bronchial provocation tests. There was no difference between platelet counts, plasma concentrations of platelet factor 4 and beta-thromboglobulin, and platelet aggregation induced by several agonists (adrenaline, arachidonic acid, or PAF) before and immediately after the allergen bronchial provocation test. There was no platelet pulmonary sequestration as studied with 111Indium-labeled platelets during 24 hours after the antigen challenge, and the life span of circulating platelets was normal. Our results do not support an important direct role for PAF in the pathophysiology of asthma. It is still possible that the current methodology is too insensitive to detect amounts of PAF in the circulation or that PAF is acting locally.     

Improved biocompatibility of heparin surface-coated ventricular assist devices.

Heparin surface coated ventricular assist devices (VADs) and cannulas were evaluated in comparison to uncoated VADs in 10 bovine experiments (body weight 77 +/- 6 kg). All systems were primed with cristalloid solution. No systemic heparin was given. Left ventricular assist was started with a blood flow of 4.2 +/- 0.4 l/min and maintained over 6 hours. Besides hemodynamic monitoring, blood samples were taken at regular intervals for blood gas, hematological, biochemical and coagulation studies. All animals in the study group (coated) were assisted for the scheduled 6 hours without device failure. In the control group, however, total occlusion occurred in 1 VAD after 1 hour of left ventricular assist whereas the other 4 VADs remained functional throughout the protocol. Mixed venous oxygens saturation was preassist 56 +/- 12% for coated versus 63 +/- 11% for uncoated and the final value at 60 minutes after weaning was 58 +/- 16% versus 59 +/- 5% (NS). Mean hematocrit dropped from a baseline value of 33 +/- 4% for coated versus 29 +/- 8% for uncoated to 29 +/- 7% versus 30 +/- 5% (NS) after 6 hours of assist. There was no significant difference between the baseline values (5.7 +/- 3.0 mumol/l for coated versus 4.6 +/- 3.1 mumol/l for uncoated) and the 6-hour values (3.8 +/- 3.7 mumol/l versus 7.6 +/- 6.4 mumol/l) for mean plasma hemoglobine. The normalized platelet levels dropped after 10 minutes of assist to 91 +/- 21% for coated versus 94 +/- 49% for uncoated (NS) and 89 +/- 29% versus 65 +/- 44 at 6 hours (NS).(ABSTRACT TRUNCATED AT 250 WORDS)