Search PubMed⌕ Search

Biomedical subjects

R L Kinlough-Rathbone

Publications and source records attributed to R L Kinlough-Rathbone.

At least 55 records · Page 3Linked to original sources
PubMed1990

Released adenosine diphosphate stabilizes thrombin-induced human platelet aggregates.

Normal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, chymotrypsin, and prostaglandin E1 (PGE1). In contrast, thrombin-induced aggregates of platelets from patients with delta-storage pool deficiency (delta-SPD), which lack releasable nucleotides, are readily deaggregated by the same combination of inhibitors. The ease with which delta-SPD platelets are deaggregated is caused by the lack of stabilizing effects of released ADP, since: (1) exogenous adenosine diphosphate (ADP) (10 mumol/L), but not serotonin (2 mumol/L), abolishes the ability of these inhibitors to deaggregate delta-SPD platelets; (2) thrombin-induced aggregates of platelets from a patient (V.R.) (whose platelets have a severe, selective impairment of sensitivity to ADP, but normal amounts of releasable nucleotides) can be readily deaggregated, and addition of ADP does not stabilize the platelet aggregates; (3) apyrase or creatine phosphate (CP)/creatine phosphokinase (CPK), added before thrombin, make control platelets more easily deaggregated by hirudin, chymotrypsin, and PGE1, and do not change the deaggregation response of delta-SPD platelets and of V.R.'s platelets. Thrombin-induced aggregation and release of beta-thromboglobulin in control, delta-SPD, and in V.R.'s platelets was similar and not inhibited by apyrase or CP/CPK. The stabilizing effect of ADP on platelet aggregates is specific, since epinephrine in the presence of apyrase to remove traces of released ADP does not stabilize the aggregates of control, delta-SPD, or of V.R.'s platelets. Because epinephrine increases fibrinogen binding to thrombin-stimulated platelets to a greater extent than ADP, but does not stabilize the aggregates, it is unlikely that the additional fibrinogen binding sites induced by ADP have a major role in inhibiting deaggregation by the combination of inhibitors.

Adenosine Diphosphate↗
PubMed1990

The relation among vessel injury, thrombus formation, and platelet survival in rabbits.

Continuous or repeated injury of rabbit aortae by indwelling vascular catheters caused the deposition of platelets on the injured vessels and the formation of thrombi rich in platelets and fibrin at sites where flow was most disturbed and injury was most extensive. Incorporation of 51Cr platelets into the thrombi reached a maximum between 3 and 24 hr. The platelet-fibrin-rich thrombi remained reactive to circulating platelets for at least 14 days. Continuing reactivity of thrombi and the turnover of platelets in the thrombi were accompanied by an increase in the proportion of platelets that separated in the least dense fraction on Stractan density gradients. Platelet survival was also shortened (43.5 +/- 5.9 hr in animals with catheters, compared with 62.6 +/- 4.5 hr in animals with a sham operation), indicating that some platelets that had taken part in thrombus formation or had interacted with the injured vessel wall were rapidly cleared from the circulation. Platelets from rabbits that had had indwelling aortic catheters in place for 3 or 6 days survived significantly longer than those from animals with a sham operation upon injection of the platelets into normal animals; thus, continuous turnover of platelets on injured vessels and thrombi, and the clearance of altered platelets, leads to a population of younger platelets that survive longer. The continuing reactivity of thrombi may in part account for repeated occlusive episodes in vascular disease. The contribution of thrombin generation and fibrin formation to the platelet-rich thrombi is substantial and warrants the ongoing evaluation of treatment with a combination of anticoagulant and antiplatelet agents in arterial thrombosis and in thrombus formation on vascular catheters.

Animals↗
PubMed1990

Survival of rabbit platelets exposed to immune complexes.

Rabbits injected with human serum albumin (HSA) formed detectable immune complexes after 5 days; complex formation was maximal between 11 and 14 days after which the complexes were cleared from the circulation. Platelets from control rabbits or HSA-injected rabbits had a reduced survival upon injection into rabbits in which complexes were forming. Platelets from HSA-animals tended to survive for a longer period upon injection into control rabbits than when they were injected into HSA-rabbits, raising the possibility that some of the immune complexes may have eluted from their surface. Platelets prepared from either control animals or from HSA-treated animals at the time when complexes were being cleared from the circulation (14-21 days) did not have a shortened life span in HSA- or control rabbits. When platelet survival was reduced, it could not be attributed to platelet accumulation at sites of vessel wall injury or to accumulation in kidneys damaged by immune complexes, since the tissues (aorta and kidney) appeared to be morphologically normal and free of thrombi. The reduction in platelet survival likely results from the interactions of immune complexes with the surface of platelets leading to the platelets being recognized as "foreign" and cleared from the circulation by the reticuloendothelial system.

Animals↗
PubMed1990

Localization of fibrinogen during ADP- or thrombin-induced aggregation of washed rabbit platelets.

In contrast to human platelets, which aggregate poorly in response to ADP unless fibrinogen is present in the external medium, washed rabbit platelets form large aggregates in response to ADP without fibrinogen in the suspending medium. Addition of fibrinogen to the suspending medium of rabbit platelets frequently has little or no effect on the extent of ADP-induced platelet aggregation. We examined washed rabbit platelets by immunocytochemistry during ADP-induced aggregation and deaggregation and during thrombin-induced aggregation when the external medium did not contain added fibrinogen to determine if (a) fibrinogen was expressed on the surface of rabbit platelets that could support aggregation when the platelets were stimulated, or (b) fibrinogen secreted from the alpha granules supports platelet aggregation. Glutaraldehyde-fixed samples were prepared at different times after addition of ADP or thrombin, embedded in Lowicryl K4M, sectioned, incubated with sheep anti-rabbit fibrinogen, washed, reacted with gold-labeled anti-sheep IgG, and prepared for electron microscopy. The alpha granules of rabbit platelets were heavily labeled with immunogold; the platelet membrane was not labeled. During platelet aggregation and deaggregation in response to ADP, fibrinogen was not detectable on the platelet surface. In response to thrombin, large aggregates formed before fibrinogen was secreted from the alpha granules; fibrinogen was detectable focally at sites of granule discharge by 30-60 sec and fibrin formed by 3 min. Therefore, stimulated washed rabbit platelets can adhere to each other without large amounts of fibrinogen taking part in the close platelet-to-platelet contact, since aggregation occurs before detectable secretion, and large areas where the platelets are in contact are devoid of fibrinogen between the adherent membranes. Adhesion mechanisms not involving fibrinogen may support the aggregation of washed rabbit platelets.

Adenosine Diphosphate↗
PubMed1990

Reduced membrane fluidity in platelets from diabetic patients.

Platelets from diabetic patients are hypersensitive to agonists in vitro. Membrane fluidity modulates cell function, and reduced membrane fluidity in cholesterol-enriched platelets is associated with platelet hypersensitivity to agonists, including thrombin. Decreased membrane fluidity of these platelets is attributed to an increased cholesterol-phospholipid molar ratio in platelet membranes. We examined the response of platelets from diabetic subjects to thrombin, platelet membrane fluidity, and platelet cholesterol-phospholipid molar ratio. Twelve poorly controlled diabetic subjects were compared with 12 age- and sex-matched control subjects. In response to a low concentration of thrombin, mean values for release of [14C]serotonin from washed prelabeled platelets were not significantly different between diabetic and control subjects, but in 8 of 12 diabetic subjects, the release response was greater than in their paired control subjects. Mean steady-state fluorescence polarization values in 1,6-diphenyl-1,3,5-hexatriene-labeled platelets prepared from diabetic subjects were significantly greater than in control subjects; this indicates a decreased membrane fluidity in platelets from diabetic subjects. Total or very-low-density (VLDL), low-density (LDL), or high-density (HDL2, HDL3) lipoprotein cholesterol concentrations in plasma were not significantly different between groups; however, the ratio of VLDL + LDL to HDL2 + HDL3 was significantly greater in diabetic than in control subjects. There was no difference in the total platelet cholesterol-phospholipid molar ratio between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Acute administration of ethanol to rabbits inhibits thrombus formation induced by indwelling aortic catheters.

Platelet aggregation and secretion of granule contents in response to specific agonists are inhibited by acute ethanol (1 to 4 mg/ml in vitro or 4 to 5 mg/ml ex vivo). However, acute administration of ethanol, giving blood levels of 4 to 5 mg/ml, does not affect platelet adherence to de-endothelialized rabbit aortae in vivo, which is the initial step in thrombus formation. Whether ethanol inhibits subsequent reactions in thrombus formation induced by indwelling catheters in rabbit aortae was investigated. Before insertion of the catheters, the rabbits received injections of 51Cr-labeled platelets (and, in some experiments, [125I]fibrinogen), and were given ethanol by stomach tube, to achieve blood levels of approximately 4 mg/ml. Thrombus formation after 3 hours was assessed by determining the number of platelets and the amount of radiolabeled fibrin(ogen) associated with the aortae, and by determining the thrombus weights; all three measurements indicated a 64 to 84% reduction in thrombosis. Thus, experimentally induced thrombus formation in the aorta is significantly reduced by ethanol.

Animals↗
PubMed1990

Thrombin-induced inositol phosphate production by platelets from rats with diet-induced or genetically determined hypercholesterolemia.

Platelets from rats with diet-induced or genetically determined hypercholesterolemia are hypersensitive to thrombin through a pathway that is independent of the effects of released ADP or formation of thromboxane A2. We examined production of inositol phosphates by platelets from these hypercholesterolemic rats to determine whether the enhanced responsiveness to thrombin is associated with increased production of inositol trisphosphate (IP3). The opportunity to study rats with hypercholesterolemia determined genetically or induced by diet makes it possible to determine whether any differences in inositol phosphate production are caused by hypercholesterolemia alone rather than to any other effect of the diet used to induce hypercholesterolemia. Platelets were prelabeled with [3H]inositol so that increases in inositol phosphates (IP, IP2, and IP3) upon stimulation with thrombin could be assessed by measuring the amount of label in these compounds. Platelets were preincubated with CP/CPK, to inhibit effects of released ADP, and aspirin, to inhibit formation of thromboxane A2/endoperoxides. In platelets from rats with either form of hypercholesterolemia, the percentage increase in labeling of IP3 was significantly greater 30 seconds after stimulation with low concentrations of thrombin than in platelets from control rats. Increased IP3 formation in platelets from hypercholesterolemic rats indicates that there is increased activity of a pathway(s) leading to IP3 formation and that this may be a mechanism responsible for the thrombin-induced hypersensitivity of these platelets.

Animals↗
PubMed1990

Platelets, blood flow, and the vessel wall.

Vessel wall injury and lipid deposition in the walls of arteries can contribute to the development of atherosclerotic lesions. The mitogen (platelet-derived growth factor) for smooth muscle cells that is released from platelets that adhere to the sites of injury contributes to vessel wall thickening, as does the organization of mural thrombi. Although many arterial thrombi result from fissure or rupture of the fibrous cap of lipid-rich atherosclerotic plaques, thrombi that result from shear-induced platelet aggregation and disturbed blood flow at stenotic lesions also contribute to the thromboembolic clinical complications of atherosclerosis. Prevention of thrombus initiation requires a better understanding of platelet interaction with injured vessel walls and of the ways in which this process may be inhibited. A crucial factor in the management of thrombus formation in severely injured vessels is restoration of a normal pattern of blood flow. Theoretically, it may be possible to use angioplasty (to remove atherosclerotic lesions and to dilate stenosed vessels) and to use new therapeutic interventions (to prevent the accumulation of an initial layer of platelets on the acutely injured surface) to reduce the probability of restenosis and thrombosis at these sites.

Animals↗
PubMed1989

Eicosapentaenoic acid interferes with U46619-stimulated formation of inositol phosphates in washed rabbit platelets.

Eicosapentaenoic acid (EPA) inhibits platelet responsiveness to aggregating agents. To investigate the reactions that are affected by EPA, we examined the effect of preincubating aspirin-treated rabbit platelets with EPA on stimulation of inositol phosphate formation in response to the TXA2 analogue U46619. Stimulation of platelets with U46619 (0.5 microM) caused aggregation and slight release of dense granule contents; aggregation and release were inhibited by preincubation of the platelets with EPA (50 microM) for 1 h followed by washing to remove unincorporated EPA. Incubation with EPA (50 microM) for 1 h did not cause a detectable increase in the amount of EPA in the platelet phospholipids. When platelets were prelabelled with [3H]inositol, stimulation with U46619 of control platelets that had not been incubated with EPA significantly increased the labelling of inositol phosphates. The increases in inositol phosphate labelling due to U46619 at 10 and 60 s were partially inhibited by preincubation of the platelets with 50 microM EPA. Since the activity of cyclo-oxygenase was blocked with aspirin, inhibition of inositol phosphate labelling in response to U46619 indicates either that there may be inhibition of signal transduction without a detectable change in the amount of EPA in platelet phospholipids, that changes in signal transduction require only minute changes in the fatty acid composition of membrane phospholipids, or that after a 1 h incubation with EPA, activation of phospholipase C is affected by a mechanism that is not directly related to incorporation of EPA.

Animals↗
PubMed1989

Effect of the concentration of Ca2+ in the suspending medium on the responses of human and rabbit platelets to aggregating agents.

The effect of the concentration of Ca2+ in the suspending medium of human and rabbit platelets on aggregation, release of 14C-serotonin, and TXB2 formation in response to ADP, thrombin, 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (PAF), collagen and arachidonic acid was studied in either platelet-rich plasma anticoagulated with D-phenylalanyl-prolyl-arginyl chloromethylketone (PPACK) or citrate, or suspensions of washed platelets in modified Tyrode-albumin solutions containing 1 mM Mg2+ and concentrations of added Ca2+ ranging from 0 to 5 mM. In response to ADP, thrombin, or PAF, human platelets were stimulated to form TXA2 by close platelet contact in a low-Ca2+ medium; at physiological concentrations of Ca2+, TXB2 formation was much less and declined progressively as the concentration of Ca2+ was raised. When the formation of TXA2 was blocked with aspirin or indomethacin, aggregation and release by human platelets were strongest at physiological concentrations of Ca2+. Rabbit platelet responses differed markedly from those of human platelets because close contact of rabbit platelets in a low-Ca2+ medium did not promote TXA2 formation. Rabbit platelet responses were more strongly inhibited by the lack of added Ca2+ in the medium than the responses of human platelets, possibly because rabbit platelets do not contain releasable Ca2+. In all studies of human platelets in media with low concentrations of Ca2+, the additional contribution to platelet responses of TXA2 formed because of close platelet contact should be considered because TXA2 formation is not usually stimulated in this way at physiological concentrations of Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1989

Platelet function and survival in rats with genetically determined hypercholesterolaemia.

Platelets from rats with genetically determined hypercholesterolaemia are hypersensitive to aggregation induced by thrombin compared with platelets from their genetic controls without hypercholesterolaemia. Aggregation or release induced by thrombin of platelets from hypercholesterolaemic and control rats correlated significantly with plasma cholesterol concentrations. Platelet responses to ADP or collagen were not different between the groups. The hypersensitivity to thrombin-induced aggregation was independent of released ADP or products of arachidonic acid metabolism. The changes in platelet sensitivity occurred with only moderate increases in plasma cholesterol concentration and with no detectable changes in total platelet cholesterol. The hypersensitivity of platelets from hypercholesterolaemic rats was not associated with a reduction in platelet survival or any significant injury to the aortic endothelium in these animals. Platelets from hypercholesterolaemic rats were smaller than platelets from controls. Thus, platelets from rats with genetically determined hypercholesterolaemia have alterations in function similar to those found with platelets from rats with diet-induced hypercholesterolaemia indicating that this strain can be used to study the mechanisms by which cholesterol can change platelet function without the possible complicating effects of dietary factors. Since platelet hypersensitivity occurred in rats with genetically determined hypercholesterolaemia without a reduction in platelet survival, these studies are also consistent with the reduced platelet survival found in animals with diet-induced hypercholesterolaemia being independent of platelet changes.

Animals↗
PubMed1989

Platelet accumulation and turnover on de-endothelialized aortae in rats.

Previous studies indicate that the subendothelium of rabbit aortae de-endothelialized with a balloon catheter rapidly becomes covered with a monolayer of platelets; after 60 min few additional platelets accumulate and although most platelets are lost from the injured surface by 4 days, there is a substantial delay before re-endothelialization. We examined the dynamics of platelet accumulation on rat aortae de-endothelialized with a balloon catheter to determine if the response to this type of injury is similar to rabbit aortae. When 51Cr-platelets were injected prior to aortic de-endothelialization, 25,500 +/- 2,750 platelets/mm2 accumulated on rat subendothelium in the first 15 min. After 60 and 92 h, fewer platelets remained on the surface (13,740 +/- 2,400 and 5,020 +/- 1,330 platelets/mm2, respectively). When 51Cr-platelets were injected into rats 30 min after injury, platelet accumulation in a 30-min period was 8,610 +/- 1,230 platelets/mm2. By 4 days rat aortae did not accumulate newly injected platelets significantly in a 30-min period, but in a 24-h period 20,600 +/- 3,490 platelets/mm2 accumulated. Morphologically, the non-endothelialized areas of rat aortae were almost completely covered with platelets 4 days after injury. Fourteen days after injury, rat aortae did not accumulate newly injected platelets and, morphologically, no platelets were present on the surface which was almost re-endothelialized. Thus, in rats, as with rabbits, platelets rapidly accumulate on de-endothelialized aortae and the ability to attract newly introduced platelets is considerably reduced shortly after injury. In contrast to rabbits, however, de-endothelialized aortae in rats remain attractive to new platelets up to 4 days following injury, but less so than at the time of injury. Also, in contrast to rabbits, 14 days after injury to rat aortae the surface is almost completely re-endothelialized. Thus, there are species differences in platelet interactions with de-endothelialized vessels.

Animals↗
PubMed1989

Association of fibrinogen with human platelets pretreated with chymotrypsin or aggregated with ADP or thrombin: an immunocytochemical study.

Although platelets can be induced to aggregate in the absence of external fibrinogen, the response is greatly potentiated by fibrinogen and fibrinogen becomes associated with the surface of stimulated platelets. We compared the aggregation response and association of fibrinogen with the surface of platelets aggregated by ADP or thrombin, and of chymotrypsin-treated platelets aggregated by fibrinogen. The association of fibrinogen with the surface of the platelets was visualized using an electron microscope immunocytochemical method. The aggregation response and the pattern of fibrinogen association was different with each of the three agonists studied. ADP-induced aggregation was associated with pseudopod formation and fibrinogen binding; granule contents were not released and aggregation and fibrinogen binding were reversible. Thrombin-induced aggregation was associated with extensive pseudopod formation and the release of granule contents, but platelet-to-platelet adherence did not appear to involve fibrinogen binding at sites remote from regions of granule discharge; disaggregation did not occur, and visible fibrin did not form rapidly in the absence of added fibrinogen. Fibrinogen-induced aggregation/agglutination of chymotrypsin-treated platelets was similar to ADP-induced aggregation in that fibrinogen binding was required and granule contents were not released; it differed from ADP-induced aggregation in that pseudopod formation did not occur and the aggregates were irreversible. Fibrinogen-induced aggregation of chymotrypsin-treated platelets differed from thrombin-induced aggregation of untreated platelets in every respect except irreversibility. Thus neither pseudopod formation, fibrinogen binding nor the release of granule contents is essential for platelet-to-platelet adherence, although one or other or all may occur in association with it. If platelets are not stimulated to release their granule contents, fibrinogen binding appears to be necessary for extensive platelet aggregation.

Adenosine Diphosphate↗
PubMed1988

Conditions affecting the responses of human platelets to epinephrine.

Conditions affecting the responses of human platelets to epinephrine were examined. In platelet-rich plasma prepared from blood anticoagulated with hirudin or PPACK (D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone), epinephrine did not cause shape change or aggregation. In a Tyrode-albumin-apyrase solution containing a concentration of Ca2+ in the physiological range, and fibrinogen, epinephrine in concentrations as high as 40 microM did not induce platelet shape change, caused either no primary aggregation or very slight primary aggregation, and did not induce thromboxane formation, release of dense granule contents, or secondary aggregation. In contrast, in citrated platelet-rich plasma, epinephrine induced two phases of aggregation. This is not attributable to the generation of traces of thrombin since the same effects were evident when blood was taken into a combined citrate-hirudin anticoagulant or a combined citrate-PPACK anticoagulant. In a modified Tyrode-albumin-apyrase solution containing approximately 20 microM Ca2+, 1 mM Mg2+, and fibrinogen, epinephrine induced extensive aggregation after a lag phase, but no primary phase was evident; thromboxane formation and release of dense granule contents accompanied the aggregation response. These responses were also observed when PPACK was included with the acid-citrate-dextrose anticoagulant, and in the washing and resuspending fluids. In the presence of aspirin or the thromboxane receptor blocker BM 13,177 a few small aggregates were detected by particle counting and by scanning electron microscopy; with the latter inhibitor, the platelets in the aggregates retained their disc shape; secondary aggregation and the responses associated with it did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1988

Effects of ethanol on pathways of platelet aggregation in vitro.

Ethanol, at physiologically tolerable concentrations, did not affect the primary phase of ADP-induced aggregation of human or rabbit platelets, which is not associated with the secretion of granule contents. Potentiation by epinephrine of the primary phase of ADP-induced aggregation of rabbit platelets was also not inhibited by ethanol. However, ethanol did inhibit the secondary phase of ADP-induced aggregation which occurs with human platelets in citrated platelet-rich plasma and is dependent on the formation of thromboxane A2. Inhibition by ethanol of thromboxane production by stimulated platelets is likely due to inhibition of the mobilization of arachidonic acid from membrane phospholipids, as ethanol had little or no effect on aggregation and secretion induced by arachidonic acid or the thromboxane mimetic U46619. Rabbit platelet aggregation and secretion in response to low concentrations of collagen, thrombin, or PAF were inhibited by ethanol. Inhibition of the effects of thrombin and PAF was also observed with aspirin-treated platelets. Thus, in addition to inhibiting the mobilization of arachidonate for thromboxane formation that occurs with most agonists, ethanol can also inhibit aggregation and secretion through other effects on platelet responses.

Adenosine Diphosphate↗
PubMed1988

Thrombin-induced inositol trisphosphate production by rabbit platelets is inhibited by ethanol.

Ethanol has an inhibitory effect on some platelet functions, but the mechanisms by which it exerts this effect are not known. Using suspensions of washed platelets, we observed that ethanol (1-9 mg/ml) did not affect the aggregation of rabbit platelets stimulated with ADP (0.5-10 microM). When platelets were prelabelled with 5-hydroxy[14C]tryptamine, aggregation and secretion of granule contents in response to thrombin (0.01-0.10 unit/ml) were not inhibited by ethanol, but these responses to thrombin at lower concentrations (less than 0.01 unit/ml) were inhibited by ethanol (2-4 mg/ml). Platelets were prelabelled with [3H]inositol so that increases in inositol phosphates upon stimulation could be assessed by measuring the amount of label in these compounds. ADP-induced increases in IP (inositol phosphate) and IP2 (inositol bisphosphate) were not affected by ethanol. IP3 (inositol trisphosphate) was not changed by ADP or ethanol. Although ethanol did not affect the increases in IP, IP2 and IP3 caused by stimulation of platelets with thrombin at concentrations greater than 0.01 unit/ml, ethanol did inhibit the increases observed at 2 and 3 min in these inositol phosphates caused by lower concentrations of thrombin (less than 0.01 unit/ml). Since ADP did not cause formation of IP3 in rabbit platelets, and since no thromboxane B2 was detected in platelets stimulated with the lower concentrations of thrombin, it is unlikely that the inhibitory effect of ethanol in IP3 formation was due to effects on further stimulation of platelets by released ADP or by thromboxane A2. Ethanol may inhibit platelet responses to thrombin by inhibiting the production of the second messenger, IP3.

Adenosine Diphosphate↗
PubMed1988

Thrombin binding to platelets from hypercholesterolaemic rats.

Platelets from rats made hypercholesterolaemic with a diet enriched with milk fat and cholesterol and containing taurocholate to promote hypercholesterolaemia aggregated more extensively to a low concentration of thrombin than platelets from rats given a milk fat-enriched diet containing sitosterol. Total and specific binding of thrombin to platelets from hypercholesterolaemic rats was significantly greater than in controls when expressed per mg platelet protein, per mumol platelet cholesterol, or per unit relative surface area. Total and specific binding of thrombin per platelet were not different between the groups. However, platelets from hypercholesterolaemic rats had less protein and cholesterol, were smaller and had less surface area than control platelets; platelet cholesterol content expressed per mg platelet protein was not different. Thus, the increase in thrombin-binding to the smaller platelets from hypercholesterolaemic rats during the first 10 s after its addition may be responsible, at least in part, for the hypersensitivity of these platelets to thrombin.

Animals↗