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)

This double-blind, randomised, multicentre trial in 513 patients having elective surgery for intra-abdominal or intrathoracic malignancy compared the efficacy and safety of venous thrombosis (VT) prophylaxis using 750 anti-factor Xa units of Orgaran (a mixture of low molecular weight heparinoids) given subcutaneously (sc) twice-daily with that of twice-daily injections of 5,000 units standard heparin. The main study endpoints were the development of postoperative VT detected by 125I-fibrinogen leg scanning, and the onset of clinically significant venous thromboembolism or bleeding. "Intent to treat" analysis showed a statistically non-significant trend towards less VT during Orgaran prophylaxis (10.4%) than after heparin (14.9%) and there was no difference in bleeding complications between the two study groups. Results remained similar if only patients who completed the intended course of therapy ("compliant patients") were analysed. Other trials have shown that Orgaran prevents VT after hip surgery and stroke. We now show it is also safe and effective in patients having major surgery for cancer.
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PMID:Orgaran (Org 10172) or heparin for preventing venous thrombosis after elective surgery for malignant disease? A double-blind, randomised, multicentre comparison. ANZ-Organon Investigators' Group. 750 9

A 22-year-old female presented to the Emergency Department after the acute onset of left hemiparesis. Marked prolongation of the partial thromboplastin time, mild thrombocytopenia, a history of syphilis, and recent spontaneous abortion suggested the diagnosis of antiphospholipid antibody syndrome, an unusual cause of ischemic stroke. This case illustrates the clinical and laboratory features of this uncommon disorder.
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PMID:Antiphospholipid antibody syndrome: an unusual cause of stroke in a 22-year-old female. 759 66

We prospectively studied 81 consecutively identified patients with antiphospholipid antibodies (aPLs) who developed focal cerebral ischemia over a 7-year period. The mean age of this cohort was approximately a decade younger than the average atherothromboembolic stroke victim and women were more commonly involved than men. The frequency of conventional stroke risk factors was lowest in the group of stroke patients with the highest levels of IgG cardiolipin immunoreactivity. Other serological abnormalities associated with aPL (false-positive Venereal Disease Research Laboratory test, thrombocytopenia, prolonged activated partial thromboplastin time [aPTT]) were more common in the group with over 100 GPL units (high positive). Patients with the highest IgG anticardiolipin titers had the shortest times to subsequent thrombo-occlusive events. The most common recurrent event was cerebral infarction, often occurring within the first year of follow-up during a mean prospective follow-up of 3 years. Over one-half of the cohort had at least one recurrent thrombo-occlusive event during follow-up. This distinct syndrome of cerebral ischemia should be recognized for its younger age at onset, predominance of women, high risk of recurrent thrombo-occlusive events, and the possible use of the IgG anticardiolipin antibody titer for prognosis.
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PMID:Recurrent stroke and thrombo-occlusive events in the antiphospholipid syndrome. 761 14

For four decades, warfarin has been used extensively to treat thromboembolic disorders. Major advances in monitoring have been achieved through recognition of thromboplastin variability and implementation of the international normalized ratio (INR). Recommended INR ranges have shifted to lower intensity, and new clinical information has led to the potential for increased use of warfarin to prevent venous thromboembolism, to treat patients with prosthetic heart valves, to prevent stroke in patients with atrial fibrillation, and to prevent death and recurrent events after myocardial infarction. Optimal management of the patient who requires a drug that has a narrow therapeutic index, such as warfarin, remains challenging. Strategies to enhance patient outcomes with these drugs attempt to improve the risk-benefit ratio of such therapies, which requires optimizing the agent's effectiveness, improving its safety profile, or both.
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PMID:Oral anticoagulation: improving the risk-benefit ratio. 765 May 6

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


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