Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Defibrotide, a deoxypolyribonuclide, has been found to modulate endothelial cell function causing increase in t-PA and decrease in PAI levels and also increase in PGI2 production. In addition, it increases platelet c-AMP levels and decreases MDA and TXB2 formation in human. Defibrotide inhibits platelet aggregate formation in vitro experiments as well as end-to-end anostomosis in rats. So, defibrotide inhibits the activation of platelets. Besides an increase of protein C and S levels a synergic action of heparin was observed in animal experiments. A strong antithrombotic effect has been observed in animal models. The drug has a beneficial effect in the cases of DVT, POVD, stroke and thromboembolism. Through its action we may say that the drug acts in a novel fashion in contrast to the other drugs used in this area. Defibrotide is a single-stranded polydeoxyribonucleotide obtained from deoxyribonucleic acid of mammalian lungs by controlled depolimerization. Since 1981 in our laboratory and in the clinical department we have been investigating a newly developed agent defibrotide in vitro experiments, animal experiments, and also its clinical pharmacology and clinical application. Some of our findings are already published and compared with literature (40, 43, 46). Because of the limited space we are not going to review the literature in detail but we are going to summarize our observations on this compound in the following order. I--in vitro experiments, II--Animal experiments, III--clinical pharmacology in human.
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PMID:The pharmacology and clinical pharmacology of defibrotide: a new profibrinolytic, antithrombotic and anti-platelet substance. 210 24

Lipodermatosclerosis of the lower extremity, with or without ulceration, is a common manifestation of severe venous disease and the result of sustained venous hypertension. The latter is generally a sequela of deep vein thrombosis. Factors that enhance clot formation or impair fibrinolysis contribute to the pathogenesis of venous disease. It is already established that faulty fibrinolysis may play a pathogenic role in patients with venous disease. We examined the possibility that patients with venous disease have abnormally low plasma levels of proteins C and S, two proteins whose deficiencies have been reported to cause an increased frequency of thromboembolic disease. Using immunologic and functional assays for plasma proteins C and S, we found that 4 (21%) of 19 patients with lipodermatosclerosis and leg ulcers had abnormally low levels of protein C or protein S. One of 7 patients with lipodermatosclerosis without ulceration had a profoundly depressed level of protein C and a history of cerebral stroke at a young age. Plasma levels of protein C were normal in five patients with arterial insufficiency severe enough to cause leg ulceration. We conclude that abnormally low plasma levels of proteins C and S may be found in patients with lipodermatosclerosis and venous ulceration. As with the abnormally low fibrinolytic activity in these patients, our findings indicate a possible propensity for increased thrombotic disease.
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PMID:Protein C and protein S plasma levels in patients with lipodermatosclerosis and venous ulceration. 203 43

Plasma protein C exerts anticoagulatory effects by inactivating factors V and VIII. Hereditary protein C deficiency is transmitted as an autosomal dominant disorder. Homozygous individuals usually develop purpura fulminans as newborns; heterozygous protein C-deficient individuals are at increased risk for venous thrombosis and pulmonary embolism. However, arterial thrombosis has been only rarely observed. We describe a young patient with heterozygous protein C deficiency who experienced a severe stroke due to thrombotic occlusion of the left middle cerebral artery.
Stroke 1990 Jul
PMID:Ischemic stroke due to protein C deficiency. 219 15

More than a dozen primary hematologic disorders have been associated with ischemic stroke. Inherited deficiencies of antithrombin III, protein C, and protein S have been linked with stroke in case reports; optimal screening requires functional as well as antigenic assays. Antiphospholipid antibodies and lupus anticoagulants are the most frequently identified acquired states associated with ischemic stroke. Polycythemia vera, sickle cell anemia, sickle-C disease, and essential thrombocythemia are the major disorders of formed blood elements causing stroke. Special, step-wise screening for occult prothrombotic entities in stroke patients is recommended for young persons with stroke of uncertain cause, for those with prior venous thrombosis, for those with a family history of unusual thrombosis, and for those with no other explanation for recurrent stroke. Acquired, perhaps transient, abnormalities of platelets, coagulation inhibition, and fibrinolysis may contribute importantly to brain ischemia in synergy with other mechanisms, but at present these remain ill-defined. The contribution of prothrombotic diatheses to stroke is probably underrecognized and warrants further investigation.
Stroke 1990 Aug
PMID:Hematologic disorders and ischemic stroke. A selective review. 186 63

A congenital deficiency of protein C (PC) is reported in a 42-year-old male, suffering from his first spontaneous episode of deep venous thrombosis in the left lower limb. The only defect found in laboratory assays for hemostasis and hepatic function was half normal level of PC, measured by both immunological and functional assays. To confirm congenital PC deficiency, the functional activity levels of PC were compared with those of other vitamin K-dependent factors during stabilized anticoagulant therapy under stable conditions. Although the patient's father had a history of a cerebral vascular accident, his PC level was found to be within normal levels. The patient's mother, free from thromboembolic events, also had a normal PC level. So the patient seemed to be a sporadic case. However, the patient's 14-year-old son, who has been asymptomatic to this time, has the same PC deficiency state.
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PMID:[A sporadic case of protein C deficiency]. 228 72

Anticardiolipin antibodies and, rarely, protein C deficiency have been described in patients with stroke. The familial coexistence of these two prothrombotic defects has not been previously reported. We describe a family with debilitating strokes occurring at an early age in whom both anticardiolipin antibodies and protein C deficiency were found. The propositus and her deceased mother both suffered a stroke at age 50 years. The propositus had both anticardiolipin antibodies and protein C deficiency. After a detailed study of the remainder of the family, the tendency to form anticardiolipin antibodies appeared to be inherited independently of the protein C deficiency. The simultaneous occurrence of these abnormalities in one family suggests that it may be useful to test for both anticardiolipin antibodies and inherited anticoagulant protein deficiencies in patients with unusual or unexplained stroke. The differential expression of both protein C deficiency and anticardiolipin antibody production in various members of the described family may allow insight into the relative contributions of these two prothrombotic abnormalities for the development of thrombotic complications, including stroke.
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PMID:Protein C deficiency and anticardiolipin antibodies in a family with premature stroke. 201 79

The well-known coagulation inhibitors antithrombin and protein C, and the more recently described inhibitors, heparin cofactor II and extrinsic pathway inhibitor, were measured in plasma during a 7-day observation period, from patients with pneumonia (n = 13), and in stroke patients with infarction (n = 9) and haemorrhage (n = 9). In patients with pneumonia, elevated fibrinopeptide A levels and subnormal antithrombin and protein C levels suggested some degree of consumption of the inhibitors. Later, an increase was observed for all the inhibitors, but was most conspicuous for heparin cofactor II which reached high normal values. C-reactive protein, initially markedly elevated, decreased rapidly. This finding suggests that heparin cofactor II might act as a delayed acute phase reactant. In stroke patients only small, not statistically significant, changes occurred during the observation period, except for heparin cofactor II which increased in patients with haemorrhagic stroke.
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PMID:Coagulation inhibitor levels in pneumonia and stroke: changes due to consumption and acute phase reaction. 247 68

Serial determinations of beta-thromboglobulin (BTG), platelet factor 4 (PF4), fibrinopeptide A (FPA), antithrombin III (ATIII), protein C (PC), fibrin (ogen) degradation product (FDP), FDP D-dimer, activated partial thromboplastin time (APTT), prothrombin time (PT), and euglobulin lysis time (ELT) were performed in 18 patients with non-progressing stroke and 14 patients with progressing stroke in order to predict the development of progressing stroke. Increasing levels of BTG, PF4 and FDP with frequent fluctuation were noted in both kinds of stroke. Fluctuation of FPA levels was also noted but was less pronounced. PC levels were found to be slightly decreased with fluctuation but the mean was still in the lower normal limit. BTG, PF4 and PC all elevated at the time of deterioration of physical condition in patients with progressing stroke, whereas FPA had no definite change at that time. From our study, we conclude that both platelet activation and coagulation process do occur in both kinds of stroke. But the latter plays a minor role in the formation of thrombosis. The hemostasis change, especially concerning the thrombosis formation, probably plays a role in the development of progressing stroke, but we cannot predict their development even by the detections of the newly known molecular substances appearing in various steps of the hemostatic mechanism. Development of new tests for understanding the whole dynamic change of the thrombosis process is necessary for accurate prediction of the progressing stroke in the future.
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PMID:The serial hemostasis-related changes in patients with cerebral infarction: comparison between progressing and non-progressing stroke. 253 1

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 authors investigated the behaviour of some markers of the haemostatic balance in a group of patients with acute focal cerebral vasculopathy. The series consists of 70 female patients (mean age: 61 +/- 5), 25 of whom suffering from TIA and 45 from thrombotic stroke; 40 normal controls (mean age 43 +/- 5) were also considered. For each patient after an overnight fasting a withdrawal of venous blood was done within 24-36 hours after the admission. For each sample the determination of seven prothrombotic markers [(fibrinogen (F), factor VII (F VII), antithrombin III (AT III), protein C (PC), protein S (PS) (coagulometric method IL), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) (ELISA method Boehringer)] and of three prethrombotic markers [(fibrinopeptide A (FPA), beta-thromboglobulin (BTG) and D-dimer (D-D) (ELISA method, Boehringer)] was performed. The results obtained in the group of the cerebrovasculopathic patients compared to the controls showed a significant increase of F (p < 0.001), F VII (p < 0.005), BTG (p < 0.05) and D-D (p < 0.01), whereas significant differences regarding AT III, PC, PS, t-PA, PAI and FPA were not observed. The authors hypothesized that the increased levels of fibrinogen and factor VII in the cerebrovascular subjects, globally considered, may depend on a marked prothrombotic state, linked in a pathogenetic sense to the vascular disease; the existence of a prethrombotic state is also documented by the increase of betathromboglobulin and D-dimer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Haemostatic balance in patients with acute focal cerebral vasculopathy. 760 35


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