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)

Cerebral infarction in the young is likely to be non-atheromatous. While in previous studies no cause has been found in 40% to 50% of patients, an increasing role for haemorheological factors is becoming apparent. Among these, an association between antiphospholipid antibodies (aPLs) and ischaemic cerebrovascular disease is now well-recognised. This entity has not been previously reported in Malaysian patients. In a study of 80 patients with stroke below the age of 50 years who were seen at the University Hospital, Kuala Lumpur, between January 1982 and May 1992, 3 patients with ischaemic cerebral infarction were found to have aPLs. aPLs was detected using ELISA method for anticardiolipin antibodies (aCLs), and presence of lupus anticoagulant (LA) was established by kaolin clotting time, thromboplastin inhibition test and platelet neutralisation procedure. Only 1 patient had active systemic lupus erythematous. Cerebrovascular events were recurrent in one of the 2 non-lupus patients. aPL-related stroke should be considered in young patients who have cerebral ischaemia occurring without obvious cause. More cases are likely to emerge in Malaysia with active screening.
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PMID:Antiphospholipid antibodies and stroke in the young--a study of three cases. 818 47

Primary antiphospholipid syndrome (PAS) is characterized by the isolated presence of antiphospholipid antibodies in the absence of other immunological changes. Its association with ischemic cerebrovascular disease is rarely reported. This study analyzes this association in 10 patients (8 women) first presenting with ischemic cerebrovascular accident (ICVA) that met the criteria for PAS. The average age of the patients was 50.4 years. Two patients had Sneddon's syndrome. Prolonged thromboplastin partial activation time was found in only three patients. Eight started aspirin therapy. The average time of follow-up was 17.2 months, during which there was one relapse. PAS should be included as a possible cause when examining individuals with ICVA, particularly when patients are young, when abortion has occurred or when no other cause is evident. Acetylsalicylic acid is effective for preventing relapse when other vascular risk factors are carefully controlled.
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PMID:[Primary antiphospholipid syndrome and cerebrovascular disease]. 820 46

The use of first generation plasminogen activators, urokinase, streptokinase and tissue plasminogen activator has revolutionized thrombolytic therapy for myocardial infarction and ischaemia, and potentially stroke. However, thrombolytic therapy employing these activators is limited by reocclusion of the very arteries being opened, which follows in a small but significant number of patients. The development of second generation plasminogen activators, e.g. staphylokinase and anisoylated plasminogen streptokinase activator complex, has not alleviated the problems encountered with classical plasminogen activators. It is now widely recognized that aberrant platelet aggregation induced primarily by thrombin, rather than plasmin, is one of the major causes of recurrent thrombosis following pharmacologic thrombolysis. Agents that (a) inhibit enzymatic and/or coagulant activity of thrombin, (b) block binding of thrombin to its receptor, and (c) interfere with the generation of thrombin by the prothrombinase complex may compromise haemostasis resulting in haemorrhage. We recently demonstrated that thrombin-induced platelet aggregation is accompanied by cleavage of aggregin, a putative ADP-receptor on the platelet surface, and that these events are indirectly mediated by intracellularly activated calpain expressed on the surface. In this review, we discuss the known mechanisms of thrombin-induced platelet aggregation and suggest relative advantages of potential pharmacological agents, being developed in our laboratory, over those that have been previously developed and tested. These inhibitors selectively prevent aggregation of platelets induced by thrombin by inhibiting calpain expressed on the surface. Moreover, one of these inhibitors which blocks thrombin-induced platelet aggregation does not interfere with other platelet responses mediated by thrombin or platelet aggregation induced by other agonists, such as, ADP, collagen, phorbol myristate acetate and thromboxane A2 mimetics. This selectivity could reduce the chances of perturbing the formation of a haemostatic plug.
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PMID:Reocclusion after thrombolytic therapy: strategies for inhibiting thrombin-induced platelet aggregation. 832 74

Primary antiphospholipid syndrome (PAPS) is an autoimmune disorder manifested by recurrent thrombosis in the venous and arterial system. We report a group of seven patients with lower limb ischaemia associated with PAPS. Four were male patients and three were females, with a mean age of 37 years. All had a previous deep vein thrombosis and the majority, five out of seven, had a prior cerebrovascular accident (CVA). Prolonged activated thromboplastin time was demonstrated in all our patients and PAPS was established by positive thromboplastin titration index, circulating anticoagulant index and increased anticardiolipin levels. Symptoms included claudication in three, rest pain in four and gangrene in five patients. Angiography demonstrated thrombosis of various segments of the arterial tree including: aorta, iliac, femoral and popliteal arteries. Two patients were treated conservatively and one by percutaneous transluminal angioplasty (PTA) of the distal aorta. A total of eleven vascular surgical procedures were performed in four patients resulting in early postoperative thrombosis (2h-30 days) in 10 cases. Only one graft remained patent, when full heparinisation (1000 units/h) was used perioperatively. We conclude that PAPS patients are at high risk for graft thrombosis and should only be operated upon on full anticoagulation, starting at operation and proceeding indefinitely.
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PMID:Lower limb ischaemia in primary antiphospholipid syndrome. 835 98

We reviewed the results of 68 consecutive Fontan procedures from 1978 to 1993 to determine the frequency of late central neurologic complications of the Fontan procedure in patients living at a mean altitude of 4500 feet. Two surviving patients had transient neurologic symptoms or signs with no corresponding evidence of brain injury by magnetic resonance imaging (MRI), whereas six surviving patients had strokes defined by sustained neurologic symptoms or signs with areas of brain injury identified by MRI [8.8% (6.0-13.0%; 70% confidence limits)]. Collectively, patients with neurologic symptoms had normal hemoglobin values, platelet counts, partial thromboplastin times, and prothrombin times at the onset of clinical neurologic findings. Two patients were taking antiplatelet agents, and one patient was taking warfarin. One of the patients with transient neurologic findings and all of the stroke patients had residual right-to-left shunts. Thus strokes were not uncommon in our patients after the Fontan procedure. Brain injury may result from thromboembolic events associated with residual right-to-left shunts, but our total number of asymptomatic patients with a residual shunt or brain abnormalities by MRI is not known.
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PMID:Factors associated with stroke following the Fontan procedure. 865 12

Seasonal influence on mortality from cardiovascular and cerebrovascular diseases is well documented. Understanding the seasonal variations in cardiovascular risk factors can shed light on this phenomenon. Elevation of coagulation factors during cold weather may in part explain the higher mortality from myocardial infarction and stroke in winter. The Cardiovascular Disease Risk Factors Community Study (CVDFACTS) included subjects belonging to 2 cohorts located in northern and southern Taiwan. This study included 2877 subjects aged 18 and above whose blood levels were examined for various coagulating factors. Besides measuring conventional cardiovascular risk factors including: blood pressure, body mass index and total cholesterol, values for blood fibrinogen, factor VII activity, factor VIII activity, plasminogen, antithrombin III, prothrombin time and activated partial thromboplastin time were determined for all subjects. Of these hemostatic parameters, levels of all, except prothrombin time, were statistically different between days with mean temperature > 20 degrees C and days with temperature < or = 20 degrees C (P < 0.01). In cold weather, a greater tendency to clot in circulatory system was demonstrated in this study, indicating seasonal variations may be demonstrated in this subtropical region.
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PMID:Values of blood coagulating factors vary with ambient temperature: the Cardiovascular Disease Risk Factor Two-Township Study in Taiwan. 890 10

The aim of the study is to determine if a novel thrombophilia mechanism (factor V Leiden) that is associated with resistance to activated protein C (APC) is in itself a risk factor for the development of ischemic stroke (IS). Sixty-six controls and 66 patients with IS were included in an unmatched case-control study. In the group of patients selected for this study, other causes of IS were ruled out. APC resistance was considered if activated partial thromboplastin time (aPTT) measured in the presence of APC was less than 2.2 times prolonged when compared to aPTT in the absence of APC (APC ratio < 2.2). Digestion with a restriction enzyme of a previously amplified exon 10 of the gene that encodes for factor V was used to detect the presence of the factor V mutation. We identified 5 patients (prevalence: 7.5%) with APC resistance (mean age: 31 years, range: 6-52 years). Mutation in factor V gene was confirmed in three of them. In the control group we detected 3 (4.5%) low APC ratios, all of them carrying specific factor V mutation. We cannot conclude a significant association between APC resistance and IS [odds ratio: 1.72; chi 2 Mantel and Haenszel was 0.53 (p = 0.4673) and exact Fisher's test p = 0.3589] but these 5 young adults suffered an episode of IS having APC resistance as the only prothrombotic condition. In conclusion, these results cannot prove a statistical association between APC resistance and IS. Further studies must be done in order to confirm that there is no relationship between APC resistance and IS in young adults when major risk factors are excluded.
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PMID:Low prevalence of the factor V Leiden among patients with ischemic stroke. 909 81

Nadroparin (nadroparin calcium) is a low molecular weight heparin with a mean molecular weight of 4.5 kD. Compared with unfractionated heparin (UFH), nadroparin has a greater ratio of anti-factor Xa to anti-factor Ha activity, greater bioavailability and a longer duration of action, allowing it to be administered by subcutaneous injection for prophylaxis or treatment of thromboembolic disorders. In clinical trials conducted in older patients (mean age usually > 60 years), nadroparin was at least as effective as UFH in preventing deep vein thrombosis (DVT) and pulmonary embolism after major general or orthopaedic surgery, and in bedridden medical patients. Nadroparin was also at least as effective as dalteparin or oral acenocoumarol in preventing thromboembolic events following general and orthopaedic surgery, respectively. When used for treatment of established DVT, nadroparin was at least as effective as intravenous UFH. Subcutaneous nadroparin, at dosages similar to those used for the treatment of DVT, produced promising results in older patients with pulmonary embolism, acute ischaemic stroke or unstable angina. In 1 study, 75% of nadroparin-treated patients were able to complete their treatment at home and 36% did not require admission to hospital; the potential pharmacoeconomic implications of these results deserve further evaluation. Overall treatment costs (drug acquisition and monitoring costs) were similar for nadroparin and UFH in a French study, but nadroparin was associated with significantly less nursing time spent on treatment delivery. Nadroparin is well tolerated by older patients. The most frequently reported adverse events in a large (n approximately 4500) placebo-controlled study in general surgical patients were wound and injection site haematoma (11.8 and 10.2%, respectively, vs approximately 6.5% for placebo). When used as prophylaxis, no significant differences in bleeding complications were noted between nadroparin and UFH or acenocoumarol recipients. Prophylactic nadroparin was associated with significantly fewer withdrawals because of adverse events than UFH in elderly bedridden medical patients. When used as treatment for DVT, nadroparin was generally associated with lower occurrences of major bleeding than intravenous UFH (0.5 to 2.3% vs 2 to 5%); however, trials were not large enough to demonstrate any significant differences between the 2 agents. Similarly, the incidence of thrombocytopenia was slightly, but generally not significantly, lower in nadroparin (< 1%) than in UFH (< or = 3.5%) recipients. Thus, nadroparin should be considered an effective and well tolerated alternative to UFH for prophylaxis and treatment of DVT in older patients, with the advantage of more convenient administration and decreased monitoring requirements.
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PMID:Nadroparin calcium. A review of its pharmacology and clinical use in the prevention and treatment of thromboembolic disorders. 910 90

Bone marrow necrosis (BMN) is a relatively rare entity and has been associated with a poor prognosis. It is most commonly found in patients with neoplastic disorders, severe infections and sickle cell anemia. An unusual case of antiphospholipid syndrome (APS) with extensive bone marrow necrosis is described in a 27 year old woman. The patient presented with severe pancytopenia, some cognitive impairment resulting from a previous cerebrovascular accident, fever, hypertension, dyspnoea, tachycardia, hepatosplenomegaly, and vaginal bleeding. Her laboratory findings included a strongly positive Coombs' test (anti-IgG and anti-C3d), a prothrombin time of 23 seconds and an activated partial thromboplastin time of 45 seconds. Anticardiolipin antibody tests were positive. Antinuclear and anti-DNA antibodies were negative but the anti-SM test was positive. A bone marrow biopsy specimen was reported as showing extensive necrosis. The patient was treated with steroids, transfusion, and plasma exchange with some clinical improvement but her pancytopenia did not respond and necessitated frequent transfusions. This case lends further support to the association between APS and BMN.
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PMID:Bone marrow necrosis in antiphospholipid syndrome. 915 83

Lupus anticoagulants (LAs) represent a diverse group of antibodies directed against phospholipids. Patients with LAs may be free of symptoms but can have thrombotic complications including stroke, placental infarction, and fetal loss. Rarely hemorrhagic symptoms have been reported. We describe six previously healthy children who were first seen with clinical bleeding and prolonged activated partial thromboplastin time. Laboratory evaluation revealed positive results on mixing studies and evidence of phospholipid dependence of the anticoagulant, suggesting LAs. Four of six patients had anticardiolipin antibodies, and all four who were tested had reduced factor II activity levels. In all patients, bleeding symptoms resolved spontaneously within 3 months, and laboratory findings returned to normal within 6 months. The hemorrhagic LA syndrome should be considered in previously healthy children with new-onset bleeding and prolonged activated partial thromboplastin time. This clinical entity probably represents pathogenic mechanism distinct from thrombotic LA syndromes.
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PMID:Transient lupus anticoagulants associated with hemorrhage rather than thrombosis: the hemorrhagic lupus anticoagulant syndrome. 920 27


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