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)

The role of endogenous tissue-type plasminogen activator (tPA) on focal cerebral ischemic injury (FII) after middle cerebral artery (MCA) occlusion was studied by using tPA gene deficient (KO) mice and wild type (WT) mice. MCA was occluded by thrombosis induced by 3 different intensities of photochemical damage of MCA. FII size in KO mice was smaller than in WT mice in mild damage whereas it was larger in severe damage. These results suggested that endogenous tPA protected FII through its thrombolytic action on transient occlusion with mild damage, but deteriorated on persistent occlusion with severe damage. Cerebral hemorrhage associated with antithrombotic and thrombolytic therapy in acute stroke is a major clinical problem. We investigated the roles of endogenous tPA and MMPs in hemorrhagic cerebral infarction associated with heparin. We demonstrated that heparin administration caused cerebral hemorrhage in WT but not in KO. Heparin administration increased tPA activity and its mRNA expression in WT. We also observed an induction of MMP9 and its mRNA expression by heparin administration in WT but not in KO. Our findings suggest that endogenous tPA plays an important role in heparin-produced cerebral hemorrhage via MMP9 induction and activation.
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PMID:[Role of endogenous tPA in stroke]. 1619 Mar 67

Heparin remains the most commonly used anticoagulant in the treatment of patients with acute vascular syndromes, including myocardial infarction, unstable angina and ischaemic stroke. However, heparin therapy is not always associated with a significant improvement of clinical outcomes, is linked with enhanced bleeding risk and can occasionally provoke the development of heparin-induced thrombocytopaenia, the most devastating complication of conventional therapy with unfractioned heparin. Understanding the key role of thrombin in clot formation and platelet activation has stimulated the development of a new class of drugs - direct thrombin inhibitors. The direct thrombin inhibitor argatroban has been known for decades. Similar to the unfractioned heparin, argatroban requires intravenous administration and activated partial prothrombin time-dependent dose adjustment; however, this pharmacological agent has a relatively short half-life that broadens its safety margins, as well as its low antigenic potential due to the small molecular weight of the compound. The efficacy of argatroban has been demonstrated among patients with acute coronary syndromes and stroke. However, this drug is currently approved by the FDA only for the treatment of patients with heparin-induced thrombocytopaenia. Indeed, in such patients, argatroban significantly improves clinical outcomes, and is associated with reduced mortality. Further clinical studies are needed to present more clinical evidence necessary to broad the indication spectrum of this agent.
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PMID:Argatroban, a direct thrombin inhibitor for heparin-induced thrombocytopaenia: present and future perspectives. 1637 Sep 25

Cardiopulmonary bypass (CPB) poses great risks for hypercoagulable patients and requires management techniques to ensure an optimal outcome free from thrombotic events. This case report reviews perfusion management techniques that may contribute to a safer CPB experience for a patient deficient in both protein C and protein S. A patient with heterozygous protein C deficiency is at increased risk of thrombosis, especially in the venous circulation. Since it is an essential cofactor for activated protein C, deficiency of free protein S is also linked to a hypercoagulable condition. A 52-year-old male presented to our institution with a past medical history of hypercoagulable state, multiple deep vein thromboses, pulmonary embolisms, and stroke. He was scheduled for two-vessel coronary artery bypass graft surgery to be followed by right carotid endarterectomy (RCEA) before discharge. The anesthesia and perfusion teams worked closely together to ensure that fresh frozen plasma (FFP) was given intraoperatively at appropriate times. Heparin dose response and protamine dosage was determined with hemostasis management system (HMS) analysis. The closed CPB circuit and cannulae were Carmeda bonded. Rapid autologous priming, along with the use of a hemoconcentrator, kept the hematocrit above 21 during CPB. Zero-balance ultrafiltration and leukocyte depletion were initiated during rewarming to aid in attenuation of the inflammatory response. To conserve coagulation factors, all pump blood was ultrafiltrated post-CPB and returned to the patient. Laboratory samples drawn on postoperative day (POD) one measured normal protein C activity with subnormal protein S activity. On POD six, the patient underwent RCEA and he was discharged on POD eight without complications.
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PMID:Cardiopulmonary bypass for a coronary artery bypass graft patient with heterozygous protein C deficiency and protein S deficiency. 1661 90

Heparin induced thrombocytopenia is a serious side effect of a drug that is widely used in clinical practice. All patients exposed to heparin, administered by any route or at any dose, are at varying risk of developing HIT and its potentially devastating thrombotic complications. There are two clinical forms of HIT, type I and type II. Type I HIT, is a non-immunologic response, while type II HIT is an immunologic response to heparin therapy. Type I HIT is not associated with an increased risk of thrombosis and is characterized by reversible thrombocytopenia. Type II HIT occurs in approximately 1 to 3% of patients receiving unfractionated heparin. Type II HIT is more severe because of the increased risk of thrombotic events. Venous and arterial thromboembolic complications may lead to amputation, stroke, myocardial infarction, and death.
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PMID:Heparin-induced thrombocytopenia (an overview). 1683 45

Cerebral venous thrombosis (CVT) is a rare type of cerebrovascular disease that can occur at any age, including in neonates, and it accounts for 0.5% of all stroke. The widespread use of neuroimaging now allows for early diagnosis and has completely modified our knowledge on this disorder. CVT is more common than previously thought and it is recognised as a non-septic disorder with a wide spectrum of clinical presentations, numerous causes, and usually a favourable outcome with a low mortality rate. MRI with T1, T2, fluid-attenuated inversion recovery, and T2* sequences combined with magnetic resonance angiography are the best diagnostic methods. D-dimer concentrations are raised in most patients but normal D-dimers do not rule out CVT, particularly in patients who present with isolated headache. Heparin is the first-line treatment, but in a few cases more aggressive treatments, such as local intravenous thrombolysis, mechanical thrombectomy, and decompressive hemicraniectomy, may be required.
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PMID:Cerebral venous thrombosis: an update. 1723 3

There are few data regarding the use of enoxaparin in children undergoing myelosuppressive therapy for malignancies even though thrombosis is a known risk in pediatric patients with malignancies. Low-molecular-weight heparin such as enoxaparin has become widely used in adult patients with thrombosis. The purpose of this study was to review the utilization of low-molecular-weight heparin, enoxaparin (Lovenox), in children with cancer at our institution who had thrombosis while undergoing myelosuppressive chemotherapy. In particular we were interested in the efficacy of enoxaparin in these patients, and in whether these children were able to continue their chemotherapy without adjustment or interruption secondary to bleeding complications. We conducted a retrospective review from 1999 through April 1, 2004. Seven patients (4-17 years of age) were identified. Diagnosis included B-precursor acute lymphoblastic leukemia (ALL) (n=three), T-ALL, Hodgkin's disease, anaplastic large cell lymphoma, and rhabdomyosarcoma (n=one each). Six patients had a deep vein thrombus (DVT) or clot of the vena cava. One of these six patients also had a pulmonary embolus. One patient presented with manifestations of a unilateral cerebral vascular accident without evidence of DVT. Most patients were screened for known hypercoaguable abnormalities. Treatment was enoxaparin, 1-1.5 mg/kg/dose twice daily to maintain a heparin anti-Xa level of 0.5-1.5 IU/mL till clot resolution. The dose was then decreased to daily for a total of 3-6 months of therapy. All patients had resolution of their thrombosis within 1-2 months of initiation of enoxaparin, and none required delays or dose reduction of their chemotherapy regimens while on anticoagulation, though some were supported by blood and platelet transfusions. Enoxaparin was safely administered to this series of seven patients for thrombotic complications in children undergoing cancer chemotherapy.
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PMID:Treatment of deep vein thrombosis with enoxaparin in pediatric cancer patients receiving chemotherapy. 1745 25

Heparin is a classic anticoagulant that is commonly used in the treatment of acute ischemic stroke (AIS). Its use remains controversial, however, due to the risk of cerebral hemorrhagic transformation. In addition to anticoagulant effects, diverse effects on transcription factors can be caused by heparin. Among the transcription factors potentially affected is nuclear factor kappa B (NF-kappaB), a protein that is reportedly related to the survival of cerebral endothelial cells. We investigated the effect of heparin on NF-kappaB activation and cell death following oxygen-glucose deprivation (OGD), an experimental model of AIS. We subjected bEnd.3 cells from a murine cerebral microvascular endothelial cell line to OGD. We examined the effect of heparin on OGD-induced NF-kappaB activation and its mechanism of action, using electrophoretic mobility shift assays, reporter gene analysis, real-time RT-PCR, Western blot analysis, and confocal microscopy. We also measured the effect of heparin on OGD-induced cell death using an MTT assay. Heparin inhibited both tumor necrosis factor alpha- and OGD-induced NF-kappaB activation. Heparin was taken up by endocytosis and then entered the nucleus. Heparin did not affect the nuclear translocation of NF-kappaB, but instead inhibited the DNA binding of NF-kappaB in the nucleus. Cells were more susceptible to OGD-induced cell death after heparin treatment. Besides producing an anticoagulation effect, heparin also inhibits NF-kappaB activation, resulting in increased susceptibility to OGD-induced cell death. This effect may be responsible for hemorrhagic transformation in patients following heparin treatment for AIS.
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PMID:Heparin inhibits NF-kappaB activation and increases cell death in cerebral endothelial cells after oxygen-glucose deprivation. 1787 98

Heparin and low-molecular-weight heparin have long been proposed for stroke treatment. This study was conducted to demonstrate the antagonistic effects of ultra-low-molecular-weight heparin (ULMWH) on cerebral ischemic injury in rats and the mechanisms underlying the effects. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2h followed by reperfusion for 24h. ULMWH (0.5, 1 mg kg(-1), i.v.) was administered after the MCAO and reperfusion. Twenty-four hours after the reperfusion, neurological deficit scores, body weight and infarct volume were assessed. Spectrophotometric assay was used to determine the activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) of the brain. Furthermore, the intracellular Ca(2+) concentration ([Ca(2+)]i) was measured. The results showed that vein injection of ULMWH at doses of 0.5 and 1.0 mg kg(-1) exerted significant neuroprotective effects on rats with focal cerebral ischemic injury via significantly decreasing neurological deficit scores, increasing body weight, reducing the infarct volume. At the same time, ULMWH significantly decreased MDA content, and increased SOD activity in ischemic brain. Compared with model group, ULMWH decreased the intracellular calcium concentration remarkably. All these findings suggest that ultra-low-molecular-weight heparin might act as a neuroprotective agent useful in the treatment in focal cerebral ischemia.
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PMID:Antagonistic effects of ultra-low-molecular-weight heparin against cerebral ischemia/reperfusion injury in rats. 1790 59

In acute ischemic stroke and transient ischemic attack (TIA), aspirin is recommended to all patients (except immediately following thrombolysis). Heparin and anticoagulant therapy using vitamin K antagonists should be avoided in the acute phase. Secondary preventive antithrombotic treatment includes anticoagulation in patients with cardioembolic stroke and antiplatelet agents aspirin possibly combined with dipyridamole or clopidogrel alone in patients with non-cardioembolic stroke. Other individual risks may modify this treatment regimen.
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PMID:[Antithrombotic therapy in ischemic stroke and transient ischemic attack]. 1795 58

Heparin is the standard of care in cerebral venous thrombosis. Local thrombolysis is believed to better restore venous blood flow than heparin. Thrombolysis is also used when the patient's condition worsens despite heparin and symptomatic treatment. The most frequently described cause of worsening is inadequate anticoagulation. Clinical deterioration due to thrombosis progression in properly anticoagulated patients is rarely observed. When it is observed, thrombolytic treatment should be considered as a valid option. This is so, even in the absence of clear evidence from randomized trials that clinical outcome is superior. Furthermore, in theory, hemorrhagic risk is higher in thrombolysis compared to heparin, especially when a pretreatment hemorrhage is already present. Thus, this fear that hemorrhagic stroke can deteriorate due to thrombolysis treatment leads to the development of improved mechanical techniques that lower the risk of bleeding. One of these devices is rheolytic thrombectomy, which utilizes the Venturi effect which creates a negative pressure fragmenting and aspirating the cerebral venous thrombus. These devices can be utilized in combination with thrombolysis. The interventional neuroradiology data published until now are promising. However, whether interventional radiology is more effective or safer than heparin therapy even in patients who can be treated by heparin can only be answered by randomized controlled trials. There is no reason to recommend interventional radiology in these patients who are likely to have a good outcome unless proven superior in a trial.
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PMID:Interventional neuroradiology in the treatment of cerebral venous thrombosis. 1800 60


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