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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombogenesis is increasingly recognised as an immediate cause of most major clinical episodes of ischaemic heart disease (IHD) and the haemostatic system makes a significant contribution to the development of atheroma. It is therefore important to consider how far concepts of increased thrombotic tendency and hypercoagulability can be demonstrated in reality. A number of general observations do suggest that characteristics of the circulating blood influence the course of events in IHD--for example, the occurrence of IHD or stroke in young women using oral contraceptives in whom advanced arterial wall changes are not a feature. Epidemiologically, the coagulation system has been more rewarding than the study of platelets. The Northwick Park Heart Study (NPHS) has demonstrated a strong relationship between the level of factor VII activity and the later incidence of IHD. Several biochemical characteristics of factor VII suggest that this relationship may well be one of cause and effect. There is growing evidence that high levels of factor VII activity lead to high levels of thrombin production. In addition to NPHS, three other prospective studies have shown an association between high levels of plasma fibrinogen and IHD incidence. Again, there are several reasons for believing that this association, too, is of pathogenetic significance. Dietary fat intake is a major determinant of the factor VII activity level, and smoking of the fibrinogen level. Hypercoagulability determining IHD is best defined, on present evidence, as over-activity of procoagulatory influences (whereas hypercoagulability leading to venous thrombosis is predominantly manifested as underactivity of natural defence mechanisms).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypercoagulability and ischaemic heart disease. 333 83

The plasma concentrations of protein C, an anticoagulant protein, and fibrinopeptide A were measured in 37 patients with acute hemispheric stroke and in age-matched controls with nonvascular neurologic diseases. In 11 stroke patients who died within 15 days after the onset (nonsurvivors) protein C antigen concentration on admission was lower than in the control group (p less than 0.005), with a mean value of 63% of the concentrations found in the 26 survivors (p less than 0.001). The difference in protein C concentrations was not associated with different prothrombin time ratios and serum albumin concentration in survivors and nonsurvivors of stroke and was independent of the size of the cerebral lesion. Increased fibrinopeptide A concentration on admission was found in all stroke patients (p less than 0.001), but it was higher in nonsurvivors than in survivors (p less than 0.01), suggesting that lower protein C concentrations in nonsurvivors might be due to increased thrombin-dependent protein C activation. In survivors, protein C concentration was slightly but significantly higher than in controls (p less than 0.05) and was unchanged 2 months after stroke, a time when fibrinopeptide A concentrations had returned to normal. These results show that protein C is involved in the hemostatic derangement caused by stroke and provide a rationale for clinical trials evaluating the therapeutic supplementation with protein C of patients with acute ischemic stroke.
Stroke 1988 May
PMID:Protein C in acute stroke. 336 90

The thrombin-induced secretion of [14C]-serotonin and adenine nucleotides from stroke-prone spontaneously hypertensive rats (SHRSP) platelets was markedly reduced with the development of hypertension accompanying hypo-aggregability compared with that from age-matched Wistar Kyoto rats (WKY) platelets. Calcium Ionophore A23187-induced secretion and aggregation were also attenuated in SHRSP platelets. Additionally, an enhancement of platelet secretion as well as aggregation by extracellular Ca2+ was less in SHRSP platelets than in WKY platelets. The platelet contents of adenine nucleotides and serotonin were not different between SHRSP and WKY at 5-16 weeks of age whereas they became significantly lower in SHRSP beginning at 22 weeks. The serotonin content in SHRSP platelets at 36 weeks of age was only 55% of that in WKY platelets. It is suggested that the reduced platelet aggregation and secretion observed in SHRSP platelets at ages lower than approximately 20 weeks are not secondary phenomena to the circulation of degranulated platelets, but the primary defect of SHRSP platelets appears to be an impaired function of Ca2+.
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PMID:Primary dysfunction in aggregation and secretion of SHRSP platelets: not secondary to the circulation of "exhausted" platelets. 363 11

Fibrinopeptide A (FPA), released from the fibrinogen A alpha-chain by thrombin, can be resolved by high-performance liquid chromatography (HPLC) into three forms, the intact peptide (A), a modified peptide phosphorylated at the serine in position 3 (AP), and an N-terminally degraded form (AY). A new method has been developed, using HPLC, that allows direct measurement of the proportions of AP, A, and AY released by thrombin from fibrinogen in plasma samples of 200 ul or less. The method was used to examine variations in the proportions of AP and AY expressed as a % of total FPA in a number of patient and control groups. The mean percentages of AP and AY of plasma fibrinogen were found to be 21.7 and 14.2%, respectively, in normal laboratory controls. In older, apparently normal, individuals these figures were 27.0 and 15.5%, respectively. Cord plasma exhibited very high AP and slightly reduced AY levels (41.6 and 12.4%, respectively) compared with normal adults. Patients with liver failure had low AP levels and high AY levels (11.6 and 21.1%, respectively). Patients recovering from major surgery or acute thrombotic stroke showed an acute-phase rise in fibrinogen level that was accompanied by an increase in AP and variable reduction in AY. Incubation of heparinized whole blood for 8 days in vitro demonstrated a gradual decrease in the proportion of AP and increase in AY of plasma fibrinogen. These results provide some support for the idea that an increased "aging" of fibrinogen in the circulation may result in a decrease in the AP content of fibrinogen accompanied by a more variable increase in AY.
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PMID:Direct analysis of plasma fibrinogen-derived fibrinopeptides by high performance liquid chromatography: investigation of A alpha-chain N-terminal heterogeneity. 364 63

Aggregation and secretion of washed platelets from stroke-prone spontaneously hypertensive rats(SHRSP) were greatly reduced by the development of hypertension in comparison with age-matched normotensive WKY platelets. In an attempt to clarify the mechanism of the defective functions, Ca2+ transport in platelets from SHRSP and WKY were studied. Changes of cytoplasmic free Ca2+ concentration ([Ca2+]i) were examined by using Quin 2. [Ca2+]i increase in response to thrombin(0.028 - 0.11 U/ml) was significantly delayed in SHRSP platelets compared with that of age-matched WKY platelets. The time(sec) to peak in [Ca2+]i was about two times longer in SHRSP platelets than in WKY platelets. [Ca2+]i levels at resting state were significantly lower in SHRSP platelets while there was no difference in maximal [Ca2+]i level in response to thrombin (0.031 - 0.125 U/ml) between the two strains. In addition thrombin-induced 45Ca2+ uptake was significantly delayed in SHRSP platelets. This delay of [Ca2+]i increase following thrombin stimulation might be associated with the hypofunctions of SHRSP platelets.
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PMID:Defective calcium transport in platelets from stroke-prone spontaneously hypertensive rats. 370 15

Aggregation and secretion of washed platelets from stroke-prone spontaneously hypertensive rats (SHRSP) were greatly reduced by the development of the hypertension compared with those of platelets from age-matched normotensive Wistar-Kyoto rats (WKY). Concomitantly, thrombin-induced phosphorylation of the 47 kDa protein in SHRSP platelets was significantly decreased. However, TPA-induced aggregation, secretion and 47 kDa protein phosphorylation in SHRSP platelets were similar to those in WKY platelets. These results suggest that protein kinase C activity and its substrate were normally present in SHRSP platelets and that defects in the receptor-mediated activation of protein kinase C. This defective protein phosphorylation may be an underlying mechanism for the dysfunction of SHRSP platelets.
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PMID:Defects of thrombin-induced protein phosphorylation in platelets from stroke-prone spontaneously hypertensive rats. 394 26

Stroke was induced in stroke-prone spontaneously hypertensive rats (SHRSP) by NaCl loading. They were killed at 3 weeks and cerebral lesion was confirmed by autopsy. About 2/3 of them had strokes. Platelet count and thrombin-induced aggregation were reduced to 36% and 66%, respectively, compared with the level of those in the healthy SHRSP group which did not have stroke with the same treatment. ADP and serotonin content in platelets diminished by 45% and by 65%, respectively, due to stroke while plasma thiobarbituric acid reacting substances (TBARS, lipid peroxides) in the stroke group was two-fold that in the healthy group. Blood TBARS levels were significantly higher in rats with lower platelet serotonin content than in rats with normal serotonin content. These results suggest that marked activation of platelets has occurred due to vascular injuries at the time of stroke with a consequent decrease in platelet serotonin content and increase in plasma TBARS.
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PMID:The appearance of "exhausted" platelets at the time of stroke in stroke-prone spontaneously hypertensive rats. 408 11

When the human blood coagulation and fibrinolytic systems are activated thrombin cleaves fibrinopeptide A (FPA) and plasmin cleaves b beta1 leads to 42 from fibrin(ogen). Elevated plasma concentrations of FPA and B beta 1 leads to 42 are evidence for enhanced thrombin and plasma activities in plasma. We have determined the plasma concentrations of FPA and B beta 1 leads to 42 in patients who have had thrombotic stroke. Patients who were studied immediately following stroke were found to have greatly elevated plasma FPA and B beta 1 leads to 42 levels, but these decreased to the concentrations found in an apparently healthy age-matched control group 1 month after the infarct. In contrast, the plasma concentrations of the platelet release product beta-thromboglobulin (beta TG) were slightly, but significantly, elevated immediately following the stroke and these did not alter with time after the infarct. It is concluded that following thrombotic stroke increased thrombin and plasmin activities are to be found in plasma. These increased protease activities are probably not directly associated with an increased in vivo platelet release reaction and may be useful in deciding which patients are at risk of reinfarction or stroke progression.
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PMID:Activation of coagulation and fibrinolytic systems following stroke. 621 94

The aggregation properties of washed SHRSP platelets were investigated in comparison with normotensive WKY platelets at prehypertensive (4 weeks), early hypertensive (11 weeks) and late hypertensive (17 weeks) ages in the absence of plasma factors. The number of platelets in SHRSP was markedly lower with the development of hypertension than that in WKY. The thrombin- and collagen-induced aggregation was markedly reduced in the platelets from 11 and 17 week old SHRSP compared with that of age-matched WKY, whereas the degree of platelet aggregation in 4 week old SHRSP showed a tendency to be even greater than that in WKY. The changes in blood pressure and platelet aggregability were correlated inversely. ADP did not induce aggregation in the same system used for thrombin and collagen stimulation but in another system it aggregated washed rat platelets. Aggregation responses to ADP and ionophore A23187 were also significantly lower in 14 week old SHRSP platelets than age-matched WKY platelets. Together with other evidence, these results suggest that defective Ca2+ function, rather than the presence of exhausted platelets, is responsible for hypoaggregability in SHRSP platelets.
Stroke
PMID:Hypoaggregability of washed platelets from stroke-prone spontaneously hypertensive rats (SHRSP). 642 Sep 47

Aggregation of washed platelets from stroke-prone spontaneously hypertensive rats(SHRSP) was markedly reduced with the development of hypertension in comparison with age-matched normotensive Wistar Kyoto rats(WKY) (Tomita et al. Stroke 15, 70-75, 1984). The mechanism of the hypoaggregability of SHRSP platelets was studied. Ca2+-dependence of thrombin-induced aggregation and MDA formation, and Ionophore A23187-induced aggregation of the platelets from SHRSP at a hypertensive age(16-weeks) was similar to that of the aggregation of platelets from age-matched WKY. Optimum Ca2+ concentration for aggregation and MDA formation was 1-2 mM. There was no difference in aggregation in Ca2+-free medium between the two strains. The enhancement by Ca2+ of both thrombin- and Ionophore A23187- induced aggregation, however, was markedly less in SHRSP than in WKY, whereas their MDA formation was equally enhanced by Ca2+. At a prehypertensive age (4-weeks) the degree of enhancement of aggregation by Ca2+ did not differ in the two strains. The magnitude of phospholipid(PI, PC, PE) degradation, and MDA formation IN SHRSP at early- and late- hypertensive ages(11- and 17-weeks) were either the same as or greater than that of age-matched WKY. A linear correlation line between the amount of MDA formed and the degree of platelet aggregation of SHRSP shifted to the right of WKY. In addition, thrombin-induced thromboxane B2 formation in SHRSP platelets was similar to that in WKY in the concentration range of 0.22 - 0.44 U/ml, and became significantly higher at 0.65 U/ml despite severe hypoaggregability of SHRSP platelets in all the concentrations examined. The overproduction of MDA or thromboxane B2 appears to be a compensatory mechanism. These results suggest that abnormalities of SHRSP platelets at hypertensive ages are due to an impaired function of thromboxane A2 and/or calcium concerned in aggregation and secretion but not due to a defect in cyclo-oxygenase and thromboxane synthetase pathway.
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PMID:Impaired function of TXA2 and/or calcium in the platelets from SHRSP at hypertensive ages. 647 18


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