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)

Thirty-three (75 per cent) of forty-four unselected children who had Legg-Perthes disease were found to have coagulation abnormalities. Twenty-three children had thrombophilia (a deficiency in antithrombotic factor C or S, with an increased tendency toward thrombosis); nineteen of the twenty-three children had protein-C deficiency and four had protein-S deficiency. Seven children had a high level (0.25 gram per liter or more) of lipoprotein(a), a thrombogenic, atherogenic lipoprotein associated with osteonecrosis in adults. Three children had hypofibrinolysis (a reduced ability to lyse clots). The mean age of the children when the Legg-Perthes disease was first diagnosed was 5.8 +/- 2.7 years, and the mean age at the time of the present study was 10.1 +/- 4.4 years. At least one of the first-degree relatives of eleven of the nineteen probands who had a low protein-C level had a low protein-C level as well; all of these low levels represented previously undiagnosed familial protein-C deficiency. The eleven probands who had familial protein-C deficiency were more likely to have early onset of Legg-Perthes disease (at or before the age of five years) than the eleven children who had normal levels of protein C, protein S, and lipoprotein(a) as well as normal fibrinolytic activity (chi-square = 6.6; p = 0.01). At least one first-degree relative of one of the four probands who had a low protein-S level had a low protein-S level and previously undiagnosed familial protein-S deficiency. At least one first-degree relative of six of the seven probands who had a high level of lipoprotein(a) had a familial high level of lipoprotein(a). Six of the seven children who had a high level of lipoprotein(a) also had a low level of stimulated tissue-plasminogen activator activity, the major initiator of fibrinolysis. At least one first-degree relative of one of the three probands who had normal levels of protein C, protein S, and lipoprotein(a) but low stimulated tissue-plasminogen activator activity also had low stimulated tissue-plasminogen activator activity (familial hypofibrinolysis). Legg-Perthes disease, thrombophlebitis, premature myocardial infarction, and stroke, which are ramifications of the familial thrombophilic-hypofibrinolytic disorders, were common in the first and second-degree relatives of the thirty-three children with Legg-Perthes disease who also had thrombophilic-hypofibrinolytic disorders.
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PMID:Association of antithrombotic factor deficiencies and hypofibrinolysis with Legg-Perthes disease. 956 92

Immunological and functional protein S, protein C and antithrombin III levels and anticoagulant responses to activated protein C were measured in 24 patients with stroke in childhood. No hereditary deficiencies were found. The protein S levels in healthy controls of younger age did not differ from the adult levels. For optimal screening of protein S deficiency, measurements using functional as well as immunological assays are recommended. Appropriate criteria for the diagnosis of the deficiencies must be carefully applied if unnecessary anxiety and inappropriate treatment of children are to be avoided.
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PMID:Physiological anticoagulants and activated protein C resistance in childhood stroke. 864 59

APC resistance, due to a point mutation in factor V at amino acid position Arg506, has been identified as a major cause of inherited thrombophilia. Here we report the presence of the factor V Arg506-->Gln mutation in 2 Italian families. In 1 family 3 subjects heterozygous and 2 subjects homozygous for the factor V Arg506-->Gln mutation were identified. The only subject who developed a thrombotic event was a 20-yr-old girl who was found to be homozygous for the factor V Arg506-->Gln mutation. In the second family 10 subjects were identified to be heterozygous for the factor V Arg506-->Gln mutation; among them 2 developed a thrombotic event. In the same family 2 individuals were found to be homozygous for the mutation: the first had a myocardial infarction at age 25 yr and the second suffered from multiple episodes of deep venous thrombosis and had a stroke at age 24 yr. These data show that the risk of developing deep venous thrombosis for the carriers of the factor V Arg506-->Gln mutation is high in the families investigated. Furthermore our data imply that the factor V Arg506-->Gln mutation in its homozygous form may relate to myocardial infarction and stroke.
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PMID:Arterial and venous thrombosis in two Italian families with the factor V Arg506-->Gln mutation. 869 38

Carbohydrate-deficient glycoprotein (CDG) syndrome type I is an autosomal recessive disease with multisystemic manifestations. During childhood the patients may suffer from hemorrhages, which may be lethal, venous thromboses and stroke-like episodes. In this study 15 patients with CDG syndrome type I were examined from the levels and isoform patterns of coagulation factors and inhibitors and fibrinolysis parameters. The screening assays APTT and PTC were unaffected in most cases. In spite of this reduced levels were found particularly for factors II, V, X and XI and for antithrombin and protein C. Low values tended to be associated with elevated liver enzyme levels in serum. The values were at potential clinical risk levels for protein C and/or antithrombin in more than half of the patients, and for factor V and/or factor XI in one third of them. There were no current differences in values between patients who had previously displayed clinical symptoms of coagulation disturbance and those without such symptoms. Partially carbohydrate-deficient isoforms were demonstrated in antithrombin, protein C, protein S and in alpha 2-antiplasmin, but not in factors II, X and fibrinogen. Abnormal isoforms did not appear to reduce the functional activity of the respective glycoproteins. Analysis of individual hemostatic parameters is recommended in these patients in connection with clinical symptoms or elective surgery. The observed variability of the carbohydrate defect in glycoproteins in this disease may be a clue to its pathogenesis.
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PMID:Complex functional and structural coagulation abnormalities in the carbohydrate-deficient glycoprotein syndrome type I. 873

Cerebrovascular accidents are rare but well documented in patients with Crohn's disease. Up to 10% of hypercoagulable state manifestations reported in association with inflammatory bowel disease are ischemic strokes. However, no clear mediating factor has thus far been suggested. A 44-year-old woman with Crohn's disease for 25 years developed a left temporal stroke associated with anticardiolipin antibody and lupus anticoagulant suggesting antiphospholipid syndrome. A thorough evaluation did not reveal any other risk factor for ischemic stroke. No possible sources of emboli were found in the carotids and heart, and no deficiencies of protein C and activated protein C, protein S, and anti-thrombin III leading to hypercoagulable state were present. There may be a possible association between antiphospholipid syndrome and hypercoagulable state in Crohn's disease.
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PMID:Antiphospholipid syndrome manifested by ischemic stroke in a patient with Crohn's disease. 874 56

Hereditary protein S deficiency (HSPD) is a predisposing factor to recurrent venous thrombosis but is not currently associated with stroke. We report two cases of HSPD revealed by stroke in young adults. The first one was a 36-year-old patient whith a pure motor hemiplegia, who gradually recovered without sequelae. Total and free protein S was decreased (55 and 10%). One of his brothers died from pulmonary embolism at 20 years and a sister had low protein S level without clinical signs. The second case was a 26-year-old patient who had a right hemiplegia with aphasia due to an infarction in middle cerebral artery area. He partially recovered, but the course of the illness was complicated by deep venous thrombosis of the lower limbs and pulmonary embolism. Total and free serum protein S level was severely decreased (25 and 0%). The patient's mother and one of his sisters also had low protein S but never had clinical complications. In both case, dupplex scanning, transcranial doppler, echocardiography, serum antithrombin III and protein C were normal. Cigarette smoking was the only risk factor for arterial disease. These two cases suggest that HSPD must be investigated in young patients with stroke, even in cases of lacunar stroke.
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PMID:[Cerebrovascular complications and hereditary protein S deficiency: 2 cases]. 876 59

To assess the risk of thromboembolism in women using oral contraceptives (OCs), we identified through computer search in the hospitals of the province of Parma, Italy, all women aged 15-44 who were resident in the province and had a documented thromboembolic event in the years 1989-93. The number of users and nonusers of OCs was estimated by the drug sale data for the province and by the demographic statistics. In cases with venous thromboembolism (VT) the prevalence of concomitant deficiency of antithrombin III, protein C, protein S, and of factor V gene mutation Arg506GIn was evaluated. The incidence rate of VT was 37/59,603 woman-years in users (0.62 per 1000) and 13/303,954 woman-years in nonusers (0.042 per 1000), for a relative risk (RR) of 14.5 (95% confidence interval: 7.8-27.1; P < 0.001); the rate of stroke per 1000 woman-years was 0.17 in users and 0.036 in nonusers (RR = 4.6; 2.9-10.7; P < 0.01). A congenital thrombophilia involving the protein C anticoagulant system was documented in about 25% of young women developing venous thromboembolism while on OCs.
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PMID:Risk of venous thromboembolism and stroke associated with oral contraceptives. Role of congenital thrombophilias. 883 Dec 53

This study was designed to prospectively evaluate haemostatic activation in 75 children undergoing cardiac catheterisation with intermittent flush heparin (10 IU/ml saline) and to relate these data to clinical findings and inherited risk factors for thrombophilia. In addition to flush heparin in infants < 6 months of age in whom additional arterial catheterisation was performed (n = 5) or patients with thrombophilia, heparin (300-400 IU/kg/d) was administered for a further 24 h. APTT was prolonged and anti Xa activity was significantly increased at the end of catheterisation and returned to normal 24 hours later. Whereas thrombin generation (F1 + 2) showed a significant coagulation activation at the end of catheterisation, no concomitant fibrinolytic activation (D-Dimer) was observed. Four children showed resistance to APC: one of them in whom stroke had occurred before and one additional child heterozygous for APCR received further prophylactic heparin. Two neonates with APCR and flush heparin only suffered from thrombosis after catheterisation. No further thrombotic events occurred. This study indicates that low-dose flush heparin during catheterisation may prevent long-term haemostatic activation in children without thrombophilia. Whether further heparin after cardiac catheterisation in children with APCR prevents vascular insults requires a more intensive study.
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PMID:Flush heparin during cardiac catheterisation prevents long-term coagulation activation in children without APC-resistance-preliminary results. 886 15

CDG syndrome (CDGS) type I is the most frequent form of a group of metabolic disorders characterised by a defect of the carbohydrate moiety of glycoproteins. A large number of plasma glycoproteins, including clotting factors and inhibitors, are decreased and stroke-like episodes have been described in about half of the reported patients. We studied blood coagulation factors, inhibitors and D-dimer plasma levels in four subjects, aged 12-23 years, with CDGS type I. Factors VIII, XI, antithrombin III activity, antigen plasma levels of antithrombin III, free protein S and protein C were decreased whereas protein C as activity was normal. In addition two patients had reduction of factors II, V, VII, IX, X reflecting the phenotypic heterogeneity associated with CDGS type I. D-dimer plasma concentrations were elevated in all subjects. The hypercoagulable state as consequence of the combined deficiencies of coagulation inhibitors could contribute to the stroke-like phenomena in CDGS type I.
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PMID:Haemostatic studies in carbohydrate-deficient glycoprotein syndrome type I. 890 85

We developed a simple and rapid amplification-refractory mutation system (ARMS) assay for the factor V mutation [R506Q] (factor VLeiden), which results in the autosomal dominant thrombotic tendency, resistance to activated protein C (rAPC). PCR primers within Exon 10 of the factor V gene were designed. A common upstream primer was paired with either a mutant or wild-type-specific downstream primer. The 3'-most nucleotide of the specific primers recognized either the mutant or normal allele, and the 3' penultimate nucleotide was mismatched to enhance specificity of the reaction. The assay was validated using authentic factor VLeiden DNA samples. Seven of 103 hematologically normal children (6.8%) were found to be heterozygotes. Among 27 patients studied by the rAPC assay, ARMS assay and rAPC results were concordant in 26. Among these were a 1-year-old child with a calcified clot in the inferior vena cava. Both the patient and his father were heterozygous for the mutation and both had abnormal rAPC assays. rAPC and factor VLeiden assays were discordant in a young girl with a history of stroke. Biochemical rAPC assay was abnormal, while ARMS assay revealed amplification only with wild-type primers, suggesting a non-[R506Q] mechanism for rAPC. This assay will be a valuable tool for studying subjects with thromboses and their family members.
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PMID:ARMS test for diagnosis of factor VLeiden mutation, a common cause of inherited thrombotic tendency. 895 12


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