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

Management of thromboembolic disease involves administration of anticoagulants, thrombolytics or antiplatelet agents to lyse or prevent thrombus extension. Despite widespread use and decades of experience with some of these agents, much is unknown about the effects of dose and plasma concentration on patient response. Unfractionated heparin (UFH) improves outcome in many thromboembolic disorders when administered to a target activated partial thromboplastin time (aPTT) or plasma heparin concentration. UFH exhibits dose-dependency both with absorption from subcutaneous sites and elimination. Doses based on bodyweight or estimated blood volume attain therapeutic aPTTs faster than fixed or standard doses. Low molecular weight heparins (LMWHs) were developed to increase the anti-factor Xa:anti-factor IIa activities. Several different LMWHs are as effective as UFH in treating deep venous thrombosis. Evidence fails to support a relationship between anti-factor Xa activity and either thrombosis evolution or bleeding. No comparisons have been made between bodyweight-based and anti-factor Xa activity-based doses. The dose of orally administered warfarin is adjusted to achieve a target International Normalised Ratio (INR). Maintenance doses are estimated on the basis of the patient's INR during the first 3 days of therapy: the dose required to achieve an optimal INR decreases with age > 50 years. The thrombolytic agents are administered in standard doses to achieve rapid thrombolysis with minimal alteration in systemic haemostasis. Accelerated intravenous alteplase may result in the highest rate of coronary artery reperfusion. Nevertheless, standard doses of streptokinase, anisoylated plasminogen streptokinase complex and alteplase result in similar 1-month mortality rates. The minimal advantage seen with alteplase is offset by higher rates of stroke. Future trials will focus on administration strategies achieving rapid thrombolysis, while minimising the risk of serious bleeding. With the antiplatelet agents, unpredictability in the pharmacokinetic parameters of different products has confounded interpretation of published reports. Optimal aspirin (acetylsalicylic acid) administration would include administration of an initial dose of 160 to 325mg after an acute vascular event, followed by maintenance dosages of approximately 75 mg/day for prophylaxis or treatment. Ticlopidine does not exhibit a relationship between either plasma concentration or dose and adverse effects, while pharmacodynamic effects may be dose-, but not plasma concentration-, dependent. The correlation between the concentration of dipyridamole and some of its antiplatelet effects may be the strongest amongst all the antiplatelet agents. However, unfortunately all clinical trials used standard doses and the current consensus is that dipyridamole alone is not an effective antiplatelet agent.
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PMID:Pharmacokinetic optimisation of the treatment of embolic disorders. 771 62

Haemostatic measurements were undertaken in 132 patients diagnosed with heat stroke during the pilgrimage to Makkah, in two successive summers of 1989-90. The control group comprised 49 patients, all pilgrims, with a wide range of clinical conditions, but without hyperpyrexia or deranged haemostasis. Heat stroke patients showed (i) significant prolongation of the prothrombin (PT), activated partial thromboplastin (aPTT) and thrombin times (TT) but normal reptilase time (RT); (ii) significant reduction in plasma levels of antithrombin III (AT-III), factor V, proteins C and S, plasminogen activator inhibitor (PAI) and platelet count; (iii) increase in plasma factor VIII, tissue plasminogen activator (t-PA) and serum FDP; (iv) no significant changes in plasma fibrinogen, plasminogen, alpha 2-antiplasmin and factors VII and X. Heat stroke patients were then grouped into those with and those without bleeding symptoms. Bleeders showed greater prolongation of the PT, aPTT and TT and significant reductions in fibrinogen, AT-III, factors V, VIII and X, plasminogen, alpha 2-antiplasmin and platelet count. Logistic regression and discriminant analysis showed that AT-III was the parameter associated most with heat stroke and reliable enough to predict its occurrence, whether or not bleeding occurred. The results indicate that activation of the haemostatic mechanism, consumptive in nature, regularly accompanies heat stroke and highlights the physiological role of AT-III in checking this activation process.
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PMID:The coagulopathy of heat stroke: alterations in coagulation and fibrinolysis in heat stroke patients during the pilgrimage (Haj) to Makkah. 786 79

Cloricromen is a new drug that inhibits platelet aggregation in man and in experimental thrombosis. Twenty patients with a history of atherothrombotic stroke received cloricromen (100 mg, twice daily) for 30 days in order to evaluate its effects on plasma fibrinogen, antithrombin III, and other variables of the haemostatic system. A statistically significant decrease in the prothrombin time (P < 0.01) was found only after 30 days of therapy. This decrease was transient and disappeared 15 days after the end of treatment. No statistically significant changes in plasma fibrinogen levels, antithrombin III, partial thromboplastin time, or platelet count were observed compared with baseline values. No side-effects were reported. This study did not reveal an effect of cloricromen on coagulative variables in patients with cerebrovascular occlusive disease.
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PMID:No effect of cloricromen on some coagulation parameters in patients with ischaemic cerebrovascular disease. 786 74

Polymorphonuclear (PMN) and mononuclear (MN) leukocytes possess procoagulant and anticoagulant activity which could be involved in both formation and dissolution of thrombi. We investigated if coagulant properties of circulating leukocytes are altered in patients within three days after acute ischemic stroke (n = 22) as compared to a control group (n = 22) matched for sex and age. The recalcification time with autologous plasma did not differ between patients and control subjects. Circulating PMNs were procoagulant in all subjects, however, they were less procoagulant in patients (-18.1 [-13.4 - (-)22.8] % of control experiments; mean [95% confidence interval]) than in controls subjects (-31.9 [-27.4 - (-)36.4] %; p = 0.0002). In contrast, MNs were similarly procoagulant in both groups. In the activated partial thromboplastin time (aPTT), there was a non-significant trend to less procoagulant PMNs in patients (-6.7 [-5.1 - (-)8.2] %) than in control subjects (-8.4 [-6.4 - (-)10.5] %). The recalcification time with pooled human plasma showed similar results as with autologous plasma. The procoagulant activity of PMNs increased in follow-up measurements in patients. Upon stimulation with FMLP, the procoagulant activity of PMNs decreased in control subjects but did not change significantly in patients. In the acute stage after ischemic stroke, circulating PMNs exhibit a decreased capability to stimulate coagulation, a feature which reflects cell activation and which may be a reaction on thrombus formation and ischemic tissue damage.
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PMID:Altered influence of polymorphonuclear leukocytes on coagulation in acute ischemic stroke. 790 Jan 1

A summary of the recommendations for antithrombotic therapy after myocardial infarction appears in Table 1. The American College of Cardiology/American Heart Association Task Force used a three-tiered classification of therapeutic interventions after myocardial infarction. Class I includes interventions that are usually indicated, always acceptable, and considered useful and effective. Class II includes treatments that are considered acceptable but are of uncertain efficacy and possibly controversial. This class is further subdivided into class IIa (weight of evidence in favor of usefulness and efficacy) and IIb (not well established by evidence, can be helpful, and probably not harmful). Class III includes interventions that are not indicated and possibly harmful. None of the antithrombotic therapies under consideration in this review were in Class III; therefore, this category does not appear in Table 1. Contraindications to anticoagulation must, however, be considered before anticoagulant therapy is started. To prevent arterial embolism, immediate anticoagulation with heparin sufficient to prolong the activated partial thromboplastin time to 1.5 to 2.0 times control should be initiated in patients with large anterior myocardial infarctions. This should be followed by warfarin therapy for at least 3 months in patients with anterior or apical wall-motion abnormalities or demonstrated mural thrombus. Indefinite oral warfarin therapy may be considered in patients with diffusely dilated and poorly contracting left ventricles. For the prevention of reocclusion after thrombolytic therapy, aspirin and heparin should be initiated immediately. Aspirin should be continued indefinitely; the heparin may be discontinued after 24 to 72 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
Heart Dis Stroke
PMID:Indications for antithrombotic therapy after myocardial infarction. 813 61

A poor anticoagulant response to activated protein C (APC) in an activated partial thromboplastin time (aPTT) assay (APC resistance) was recently reported to be a cause of familial thrombophilia. The response to APC was measured in 30 patients suffering from juvenile or recurrent stroke, in 40 patients suffering from venous thromboembolism and in 50 healthy subjects. The prevalence of APC resistance was found to be significantly higher among patients with stroke (20%, P < 0.003) and venous thrombosis (17.5%, P < 0.02) compared with the prevalence of APC resistance among normal controls (2%). In one case of venous thrombosis, the proposita's family (A) could be investigated and in five out of nine investigated members (56%) a poor or borderline response to APC was detected. The family (B) of another APC-resistant patient revealed six subjects with poor coagulation response to APC out of eight family members studied (75%). Measuring protein S activity with an automated calcium-thromboplastin-based protein S activity assay, a significant correlation (P < 0.0001) between the results of this functional protein S assay and APC resistance (represented by the ratio (Rs value) of clotting time with and without addition of activated protein C) was observed. Nine out of 14 patients (64%) with poor APC response showed protein S activities below the normal range. Assessment of protein S activity with a second protein S clotting assay using factor Va as substrate confirmed only 47% of the decreased levels of the thromboplastin-based protein S clotting assay.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The prevalence of poor anticoagulant response to activated protein C (APC resistance) among patients suffering from stroke or venous thrombosis and among healthy subjects. 760 83

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

A highly sensitive automated method, fluorogenic prothrombin time (FPT) method, was developed by a combination of a fluorogenic peptide substrate for thrombin and a centrifugal autoanalyzer (Cobas Bio). Using plasmas from stroke patients, we showed that the second reagent containing fluorogenic peptide substrate should be mixed after the first reagent containing tissue factor and plasma were mixed, that is, two steps method, in order to detect hypercoagulable state. When the first and the second reagent were mixed with plasma at the same time, that is, one step method, FPT was not sensitive to hypercoagulable state. We also showed that patient plasmas should be stored at -80 degrees C and subjected to FPT analysis immediately after thawing, not leaving at 4 degrees C or room temperature. Good correlation was observed on FPT of stroke patients using human tissue factor and bovine tissue factor. Another fluorogenic method was developed by the same principle for the evaluation of factors X and VII concentrations in plasma using deficient plasma of factor X or factor VII. Good correlation was observed on factors X and VII concentrations of stroke patients using human tissue factor and bovine tissue factor.
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PMID:[A basic study on a highly sensitive automated method for hypercoagulable state in plasma, fluorogenic prothrombin time (FPT) method]. 825 61

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


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