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

Studies of 11 patients with haemorrhagic stroke revealed no significant change in kaolin cephalin clotting time, prothrombin time, thrombin time, PF 3 availability, platelet count and factor V and VIII during the first week. Plasma fibrinogen was significantly increased while factors VII + X were decreased (borderline significance). Prolongation of plasma recalcification time and decrease in heparin tolerance reached borderline significance. There was moderate, but significant, increase in serum antithrombin activity and plasma (euglobulin fraction) fibrinolytic activity.
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PMID:Blood coagulation and fibrinolysis in haemorrhagic stroke. 58 May 8

A marked pleocytosis and increase in the levels of prostaglandin F2a (PGF2a) and prostaglandin E2 (PGE2) were noted in cerebrospinal fluid of dogs within two hours following the intracisternal injection of thrombin. Quantitation of the prostaglandins (PG's) was done by gas chromatography-mass spectroscopy using deuterated PGF2a and PGE2 as internal standards. Whereas the levels of these prostaglandins were below the sensitivity of the method in control animals, a marked increase was noted following thrombin. PGF2a levels were 15-21 ng/ml and the PGE2 levels were 55-72 ng/ml. This concentration of the PG's is adequate to cause spasm of the cerebral vessels and could explain the spasm which occurs following the intracisternal injection of thrombin. These two effects, a pleocytosis and elevation of PG levels, may be specific to thrombin.
Stroke
PMID:Pleocytosis and elevation of prostaglandins F2a and E2 in cerebrospinal fluid following intracisternal injection of thrombin. 84 88

To examine the influence of atrial fibrillation (Af) on stroke onset, we measured the plasma D-dimer level, thrombin antithrombin III complex and plasmin alpha 2 antiplasmin complex (PAP) in 46 stroke patients with Af and 87 stroke patients without Af. These marker levels were significantly higher in Af patients with stroke than in those without stroke (n = 16), and thus do not seem to be affected by Af alone. Abnormal values were also more frequent in acute Af stroke patients with visible occlusion of the major cerebral artery than in those without Af. The D-dimer and PAP levels in all Af stroke patients in the younger-aged patients (< or = 64 years) were significantly higher than those without Af, but not noted in the older-aged group (> or = 75 years). These results suggest that the D-dimer and PAP levels in younger-aged patients with Af indicate the existence of cerebral emboli due to Af.
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PMID:Influence of atrial fibrillation on coagulo-fibrinolytic markers in patients with cerebral infarction. 128 51

Platelets from stroke-prone spontaneously hypertensive rats (SHRSP) show severe hypofunctions accompanied by defective protein (P47) phosphorylation. To examine the mechanism of platelet hypofunctions, phospholipid metabolism in SHRSP was compared with that in Wistar Kyoto rats (WKY). Phosphatidylinositol (PI) content was 20% less in SHRSP than in WKY, but no changes were observed in other phospholipids. Incorporation of [3H]-arachidonic acid (AA) into PI and phosphatidylethanolamine (PE) was 12% and 11% lower, and that into phosphatidylcholine (PC) was 6% higher in SHRSP than in WKY. Thrombin-induced diacylglycerol and phosphatidic acid formation were similar in both groups of platelets. Thrombin-induced release of [14C]-AA from the labeled platelets and its metabolism to eicosanoids occurred at similar rates. These results suggest that reduced formation of diacylglycerol, an activator of protein kinase C (PKC), does not cause defective phosphorylation of P47, a substrate of PKC, in SHRSP. However it remains unclear how the lower PI content and the altered distribution of AA in PC and PE is related to SHRSP platelet hypofunctions.
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PMID:Phospholipid metabolism in platelets from stroke-prone spontaneously hypertensive rats and Wistar Kyoto rats. 132 96

Plasma crosslinked fibrin polymers (XLFP) are formed as a result of in vivo hemostatic activation and are elevated in thrombotic disease. We have investigated the plasmic degradation of plasma XLFP in vitro to provide information regarding the pattern of crosslinking and the composition of degradation products. Plasma XLFP were identified by sodium dodecyl sulfate (SDS)-agarose electrophoresis and Western blotting and quantitated by gel scanning. D-dimer was measured by enzyme-linked immunosorbent assay and the results were verified by SDS-polyacrylamide gel electrophoresis and Western blotting of the digests. Complete degradation of XLFP occurred only after supplementation of plasma with plasminogen (5 U/mL) and incubation with recombinant tissue plasminogen activator (rt-PA), indicating that the normal plasma plasminogen concentration limits plasmic degradation in vitro. Gel electrophoresis showed that the principal terminal degradation products of XLDP were fragments D, DD, and E, indicating that crosslinking occurred primarily through gamma chain dimers. After adding a low concentration of thrombin to plasma in vitro, XLFP increased progressively before clotting, and the concentration correlated with the increase in the D-dimer concentration after degradation (r = .98). Plasma XLFP and D-dimer concentrations in plasmic digests were significantly elevated in patients with stroke (150 +/- 83 micrograms/mL and 88 +/- 32 micrograms/mL), myocardial infarction (217 +/- 110 micrograms/mL and 84 +/- 30 micrograms/mL), and venous thrombosis (187 +/- 80 micrograms/mL and 86 +/- 19 micrograms/mL) compared with normals (28 +/- 12 micrograms/mL and 25 +/- 7 micrograms/mL). There was a strong correlation between the plasma concentration of XLFP and the D-dimer immunoreactivity of plasma after plasmic degradation (r = .87). The results indicate that XLFP in plasma are crosslinked primarily through gamma chains and degrade to fragment DD with plasminogen activation. Also, the immunoreactivity of in vitro plasmic digests of plasma reflects the concentration of XLFP and may provide a useful indirect measure of in vivo hemostatic activation in patients with thrombotic disease.
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PMID:Plasma crosslinked fibrin polymers: quantitation based on tissue plasminogen activator conversion to D-dimer and measurement in normal and patients with acute thrombotic disorders. 138 60

Aggregation, secretion and 47kDa protein (P47) phosphorylation by various agonists such as thrombin, ADP and ionophore A23187 were markedly reduced in platelets from stroke-prone spontaneously hypertensive rats (SHRSP) compared with those of age-matched Wistar Kyoto rat (WKY) platelets, suggesting defective functions of intracellular Ca2+ in SHRSP platelets (Tomita et al. Hypertension 1989; 14: 304-315). To clarify the mechanism of the platelet hypofunctions, saponin permeabilized platelets were prepared to compare the responses of platelets from both rats in varying concentrations of extracellular Ca2+. The leakage of lactate dehydrogenase from saponin (15 micrograms/ml)-treated platelets was approx. 5% of total activity; the degree of the leakage in both platelets did not differ. In saponin-treated platelets, extracellular Ca2+ alone did not induce either aggregation or secretion in both strains. However, in the presence of 1-oleoyl-2-acetylglycerol (10 micrograms/ml), Ca2+ dose dependently stimulated both aggregation and secretion. Under this condition, Ca2+ sensitivity of aggregation, secretion and P47 phosphorylation in SHRSP platelets were significantly reduced compared with those in WKY platelets. These results strongly suggest that intracellular Ca2+ functions are impaired in SHRSP platelets.
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PMID:Reduced functions of intracellular Ca2+ in aggregation, secretion and protein phosphorylation of permeabilized platelets from stroke-prone spontaneously hypertensive rats. 144 May 31

The amounts of tissue factor (TF) expressed by brain microvascular endothelial cells (BMECs) from normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were compared after stimulating the cells with different doses of lipopolysaccharide (LPS), thrombin, phorbol myristic acid (PMA), Ca(2+)-ionophore (A23187), or tumor necrosis factor (TNF) and interleukin-1 (IL-1). Treatment of cultured BMECs from WKY and SHR with all of these factors dose-dependently increased their total amount of TF; no substantive differences in the levels of enhanced TF expression were observed between WKY and SHR BMECs. We conclude that stimulated endothelium from rats with hypertension, a major stroke risk factor, is not hyperresponsive with respect to TF expression when compared to normotensive controls.
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PMID:Comparison of stimulated tissue factor expression by brain microvascular endothelial cells from normotensive (WKY) and hypertensive (SHR) rats. 147 6

Thrombotic or thromboembolic occlusion of a cerebral artery is the most common pathophysiologic mechanism of acute ischemic stroke. An antithrombotic agent would therefore appear to be an ideal medication for treatment of this condition. Heparin is an effective anticoagulant, but it has poor bioavailability and effects on thrombin and platelets that predispose it to life-threatening complications such as hemorrhage and thrombocytopenia. Low-molecular-weight (LMW) heparins have better bioavailability, a higher anti-Xa:anti-IIa ratio, and less effect on platelets than heparin; yet their heterogeneity has hampered their proper investigation in clinical trials and it has not yet been proven that they exhibit less tendency toward hemorrhage and thrombocytopenia than conventional heparin. The LMW heparinoid, Org 10172, is superior to standard heparin in terms of its bioavailability, anti-Xa:anti-IIa ratio, and lack of effect on platelets. It is less likely than heparin and many LMW heparins to induce thrombocytopenia. Like the various heparins, Org 10172 exhibits dose-dependent hemorrhagic tendencies, yet preliminary studies have found doses that are safe for use in patients with acute ischemic stroke. These studies also suggest that Org 10172 may improve outcome and lessen mortality in this population. A prospective, randomized, double-blind, controlled trial is needed to establish the potential efficacy of Org 10172 in patients who suffer acute or progressing ischemic stroke.
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PMID:Low-molecular-weight heparins and heparinoids and their use in acute or progressing ischemic stroke. 170 55

Binding of iodine-125-labeled thrombin to fibrin clots from two siblings with juvenile stroke was 30% of normal, and abnormally high amounts of the radioligand (not adsorbed by fibrin) were found in the supernatant. In concordance with this finding, supernatants from the patients' fibrin clots caused abnormal enhancement of platelet aggregation, ATP secretion, and binding of 125I-fibrinogen to platelets exposed to subthreshold concentrations of ADP or epinephrine. Hirudin suppressed the enhancing effect of the patients' supernatants, and substitution of gamma-thrombin for alpha-thrombin led to normalization of platelet responses. Under some experimental conditions, degradation of the patients' fibrinogen by plasmin was impaired. However, the euglobulin lysis time, the rate of fibrin degradation by plasmin, and the lysis of the patients' plasma clots by human melanoma tissue-type plasminogen activator were normal. Patients' plasmas, as well as purified fibrinogen, showed a prolonged thrombin time (partially corrected by 10 mM CaCl2) and an impaired release of fibrinopeptide A in response to thrombin. However, the release in response to reptilase was normal, and the reptilase, ancrod, and thrombin coagulase times were within control (normal) values. In addition, the patients' fibrinogen showed normal polymerization of preformed fibrin monomers, normal sialic acid content, and normal binding to ADP or epinephrine-stimulated platelets. Our studies support the concept that thrombin and platelets play an important role in the occurrence of stroke in these patients and suggest a direction to be followed to identify the mechanism(s) contributing to thrombosis in subjects with abnormal fibrinopeptide release.
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PMID:A role for platelets and thrombin in the juvenile stroke of two siblings with defective thrombin-adsorbing capacity of fibrin(ogen). 182 31

Recent evidence suggests that sickle cell disease (SCD) can be considered a hypercoagulable state, in which both platelet activation and thrombin generation are abnormally increased. Although thrombosis is now known to play an important role in at least one of the vasocclusive complications of SCD, namely stroke, the significance of hypercoagulability in the pathogenesis of vascular occlusion in SCD remains unclear. This review summarizes current evidence regarding platelet, coagulation, and fibrinolytic abnormalities in SCD and their possible role in vascular occlusion. Potential implications for therapy are also discussed.
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PMID:Platelets, coagulation, and fibrinolysis in sickle cell disease: their possible role in vascular occlusion. 189 65


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