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

In order to clarify the coagulation profile accompanying ischemic stroke, which may have implications on therapeutic strategies, we performed a prospective study to evaluate the hemostatic parameters in the first 24 h after the onset of cortical atherothrombotic infarct and lacunar infarction. Twenty-seven patients with cortical atherothrombotic infarction and 27 patients with lacunar infarction, diagnosed on clinical and CT-scan criteria, had blood samples taken within the first 24 h after onset of the stroke, and before anticoagulant treatment had been started. Levels of fibrinogen, von Willebrand factor, D-dimers, prothrombin factors 1 + 2, anti-thrombin III, and C-protein and S-proteins, were measured. Laboratory tests detected the following abnormalities: a protein C deficiency was observed in 1 case of cortical infarction and in 1 case of lacunar infarction; a decrease in S-protein was observed in 1 case of cortical infarction, and the presence of lupus anticoagulant in 4 cases (2 in cortical and 2 in lacunar infarction). Various degrees of coagulation activation were observed. Statistically significant activation of the coagulation was observed in the patients with cortical infarction, compared to normal patients adjusted for age: the levels of DDI were significantly raised (2298 +/- 2221 ng ml-1 vs. 750 +/- 400 ng ml-1) (p < 0.03) as were F1 + 2 levels (3.9 +/- 2.8 nmol l-1 vs. 1.5 +/- 0.9 nmol l-1). (p < 0.01). In the lacunar infarction group, there was a significant rise in F1 + 2 compared with normal patients adjusted for age (2.2 +/- 1.7 nmol l-1 vs. 1.5 +/- 0.9 nmol l-1) (p < 0.01), while the DDI level was in the normal range, when age was taken into account. In the cortical infarction group, we observed a significantly raised fibrinogen level (4.8 +/- 1.7 g l-1 vs. 3.7 +/- 1.0 g l-1) (p < 0.05) and von Willebrand factor level (271 +/- 104% vs. 178 +/- 103%) (p < 0.01) compared to the lacunar infarction group. In addition, we observed a significantly low level of S-protein in the cortical infarction group (105 +/- 29%) compared to the lacunar infarction group (127 +/- 28%) (p < 0.01). Confirmation of the role of enhanced thrombin activity in the pathogenesis of acute stroke may be an important determinant in its therapeutic management.
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PMID:Coagulation abnormalities in lacunar and cortical ischemic stroke are quite different. 947 Oct 97

This paper presents the role of inhibitory protein C in the haemostatic processes, types of its deficiency and current opinions concerning the role of protein C deficiency in the pathogenesis of stroke. Deficiency of protein C (PC) or activated protein C resistance (both hereditary and acquired) play a role in pathogenesis of stroke, but not so great as it was thought until quite lately. Isolated protein C deficiency in old patients does not increase the risk of stroke. But in children hereditary deficiency of PC or activated PC resistance are of great importance in pathogenesis of ischaemic or venous stroke. In the presence of additional risk factors both in children and in adults deficiency of PC may be an important condition leading to stroke occurrence.
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PMID:[The role of protein C in the pathogenesis of stroke]. 976 May 56

Today, more than 40% of all patients who develop a thrombosis are found to have inherited thrombophilia. The most common cause of this is APC resistance, which can usually be traced back to factor V-Leiden. In the commonly heterozygous patients the risk of thrombosis is increased about 7-fold (life-long risk of thrombosis 10 to 15%). In most cases, however, additional thrombogenic stimuli are required (oral contraception, pregnancy, surgery, immobilization). In combination with oral contraceptives, the risk is increased roughly 30-fold. In contrast, APC resistance does not present an increased risk for thrombosis in the arterial system (myocardial infarction, stroke). Four further inherited or acquired disorders of the hemostatic system are known: prothrombin dimorphism, antithrombin, protein C and protein S deficiencies. Prothrombin dimorphism, the second most common form of inherited thrombophilia, has been known only for the past two years and elevates the risk of thrombosis only to a moderate degree. Today, a search for thrombophilic factors should be carried out not only in young patients with spontaneous development of thrombosis, but also in elderly patients, even when an additional risk for the occurrence of thrombosis such as traumatization or immobilization is present. Therapeutic consequences are discussed.
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PMID:[Thrombophilia caused by congenital disorders of blood coagulation]. 984 71

The anticoagulant transmembrane glycoprotein thrombomodulin (TM) is expressed at the luminal surface of vascular endothelial cells. Recently, we showed that TM antigen and TM mRNA are expressed in brain microvessels in several species and that brain capillaries have the capability to activate protein C. The activation of protein C in brain microcirculation was greatly impaired by major stroke risk factors in rats due to downregulation of TM. In this study, a partial sequence of TM was determined from TM mRNA from brain capillaries examined in brain capillaries of the rat, a species that provides a useful model to investigate stroke mechanisms in relation to brain hemostasis. The predicted deduced amino acid sequences for rat TM were compared with other TM sequences. Particularly high homology (77-100%) among functional domains of the protein, i.e., the epidermal growth factor repeats (EGFRs) 1-6 and the transmembrane region, was observed between mice and rats. Somewhat less degree of homology was observed for bovine and human EGFRs 1-6, while the homology of the transmembrane region was 92-96%. All cysteine residues were conserved among the TM sequences, and specific amino acids previously suggested to be essential for activation of protein C by thrombin TM were highly conserved. We conclude that the highly conserved mRNA and protein sequences may reflect a similar anticoagulant role of TM in brain endothelial and systemic vascular endothelial cells across different species.
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PMID:Rat brain capillary thrombomodulin: structure and function. 985 12

Migraine, particularly migraine with aura (MA), may be a risk factor for ischemic stroke (IS). The reasons for this association are unknown. We investigated the presence of genetic abnormalities of the protein C system in 83 MA patients, 31 IS patients, and 124 healthy controls, all aged under 45 years. We found an increased frequency of activated protein C resistance due to Arg506Gln factor V mutation, and of protein S deficiency in both disorders, with figures higher than those reported in the general population and significantly different from those found in controls. These prothrombotic genetic abnormalities may be shared risk factors in IS and MA, and may play a role in increasing the risk of cerebrovascular disease in migraineurs.
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PMID:Genetic abnormalities of the protein C system: shared risk factors in young adults with migraine with aura and with ischemic stroke? 987 85

Experimental evidence suggests a stimulatory effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on both platelets and coagulation. RhG-CSF is increasingly used to stimulate healthy volunteer donors for blood stem cell mobilization. We therefore assessed 25 healthy donors receiving rhG-CSF for changes in in vitro bleeding test (IVBT), coagulation parameters and cerebral microembolism by transcranial Doppler (TCD) ultrasound. A significant shortening of IVBT was found on day 4 of rhG-CSF administration together with increased levels of fibrinogen and factor VIII and reduced activities of protein C and protein S. Although these changes are quite small it is possible that they may lead to a hypercoagulable state especially in donors with other risk factors for thromboembolism. However, TCD examination failed to detect any signs of microembolism. We therefore conclude that rhG-CSF leads to significant changes in coagulation parameters, but has no effect on TCD detectable microembolism as a stroke risk factor. However donors receiving rhG-CSF should be examined carefully to detect pre-existing changes in the coagulation system and we would like to suggest a routine thrombophilia screen.
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PMID:Analysis of rhG-CSF-effects on platelets by in vitro bleeding test and transcranial Doppler ultrasound examination. 987 71

The carbohydrate-deficient glycoprotein syndromes are a group of recently described autosomal recessive, metabolic defects affecting multiple systems. The disorder is caused by inefficient posttranslational glycosylation of glycoproteins. Patients with the syndrome present early in life with psychomotor retardation, seizures, hypotonia, and stroke-like episodes. They also have dysmorphic features including almond-shaped eyes, constant squint, inverted nipples, and buttock fat pads. One of the features of the syndrome is coagulopathy, and we report here a patient who presented with a prolonged activated partial thromboplastin time, and was subsequently diagnosed with the carbohydrate-deficient glycoprotein syndrome. We also summarize the results of five previously published studies of the coagulation system in these patients. Most of the reported patients are deficient in factor XI, protein C, antithrombin III, and protein S. Other coagulation proteins are less frequently affected. Both bleeding and thrombosis have been observed, yet the cause of the stroke-like episodes remains speculative. The carbohydrate-deficient glycoprotein syndrome is an increasingly recognized multisystem disorder affecting hemostasis, and thus will involve clinical hematologists as part of a multidisciplinary team caring for patients with the syndrome.
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PMID:Coagulation abnormalities in the carbohydrate-deficient glycoprotein syndrome: case report and review of the literature. 988 8

Vascular occlusion has a central role in the pathophysiology of sickle cell disease (SCD) and, although there is little evidence that thrombosis alone is responsible, patients with sickle cell disease are known to have an ill-defined but increased thrombotic risk. The most serious complication of this in childhood is stroke which occurs in 7-10% of children and a further 14% have asymptomatic cerebrovascular disease (CVD) on imaging. We have performed a comprehensive profile of coagulation inhibitors and markers of thrombin generation in 96 children (83 nontransfused [NTx] and 13 transfused [Tx]) with steady-state SCD and 18 healthy sibling controls. The levels of protein S (free and total) and heparin cofactor II were reduced in both the NTx and Tx groups compared to controls and protein C and APC resistance ratios were reduced in the NTx group only. Antithrombin levels were not different from controls. Thrombin-antithrombin complexes and prothrombin fragment F1+2 were increased in both patient groups. In the NTx subgroups with or without CVD there were no differences for any of the parameters measured except for lower haemoglobin levels and higher white cell counts in those with asymptomatic CVD. We conclude that children with SCD have a reduction in levels of the majority of the coagulation inhibitors and increased thrombin generation in the steady-state and these are only partially reversed by transfusion. However, these abnormalities do not appear to play a primary role in the development of cerebrovascular disease.
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PMID:Prothrombotic changes in children with sickle cell disease: relationships to cerebrovascular disease and transfusion. 988 16

Carbohydrate-deficient glycoprotein syndrome type 1 (CDGS-1) is an autosomal recessive hereditary metabolic disorder, the gene locus of which is chromosome 16p13. The disorder is characterised by genetic heterogeneity, and by decrease in the gene product, phosphomannomutase 2, though the heterogeneity is far less manifest in affected Swedish families. Its incidence is 1/80,000 live births, and the under-5 mortality rate over 30 per cent. The causes of death are liver failure, cardiac tamponade, haemorrhaging, and severe infection. The characteristic biochemical aberration is the occurrence of deficient carbohydrate chains in many but not all circulating glycoproteins, and the serum and blood concentrations of some glycoproteins may be above or below normal. These changes may improve over time, but never normalise. The clinical picture is generally more problematic during the first years of life when psychomotor retardation is complicated by failure to thrive, liver dysfunction, pericardial effusions, and stroke-like episodes. In addition, strabismus, lipocutaneous anomalies, and gluteal fat pads are always present, and muscular hypotonia and restricted joint mobility are common. Failure to thrive is common, with vomiting and diarrhoea and subsequent slow growth. Inflammation is a constant finding in the liver, and very common in the small bowel. Pancreatic function is also affected. Pericardial effusion has been reported in 50 per cent of the youngest children, requiring pericardectomy in 30 per cent of cases. Haemorrhaging and thromboembolic complications may occur, and the serum concentrations of several factors and inhibitors are low, particularly those of factors V and XI, protein C and antithrombin. Stroke-like episodes occur in about 30 per cent of cases, often following an infection, with coma lasting for hours to several days. Such sequelae as hemiplegia, blindness, and other focal neurological pathology have been observed transiently. Diagnosis is based on the serum carbohydrate-deficient transferrin level, verified by isoelectric focusing. Molecular genetic procedures enable point mutations to be identified and prenatal diagnosis to be performed in many families.
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PMID:[CDGS-1--a recently discovered hereditary metabolic disease. Multiple organ manifestations, incidence 1/80,000, difficult to treat]. 988 93

We report a patient who had an ischemic stroke aged 22 years, an inherited type I protein C deficiency and a heterozygous genotype of prothrombin gene 20210A. In view of recent reports of an increased risk for ischemic cerebral vascular disease in patients with the prothrombin 20210A mutation, we suggest that many of the reported cases of ischemic stroke and protein C deficiency may have had additional prothrombotic disorders such as the prothrombin mutation. The current data concerning the magnified risk for stroke in patients with the prothrombin 20210A mutation suggests the need to study all patients with premature stroke for this mutation and the other risk factors for thrombosis. This would include homocysteine, lupus inhibitor, anticardiolipin antibodies, and possibly the natural inhibitors of coagulation. It is possible that patients with the prothrombin 20210A mutation and ischemic cerebral vascular disease would benefit from long-term anticoagulation therapy in a similar way to patients with the antiphospholipid syndrome.
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PMID:Ischemic stroke in a young patient with protein C deficiency and prothrombin gene mutation G20210A. 989 Jul 20


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