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

Specific treatment in the acute phase after cerebral haemorrhage is still not available. Corticosteroids and early surgical evacuation have been proven to be ineffective. In the initial 3 hours after a cerebral haemorrhage, the haematoma volume increases in one-third of all patients. Arresting this enlargement may be an effective strategy to improve outcome. Recombinant activated factor VII (rFVIIa) is used to treat bleeding in patients with haemophilia and has also been reported to reduce bleeding in patients without coagulopathy. In a recently published phase-II trial totalling 399 patients given placebo or one of three doses of rFVIIa, treatment with rFVIIa reduced haematoma volume 24 hours after administration. Treatment with rFVIIa was also superior to placebo for several secondary endpoints, including death, handicap and neurological deficits. However, more thromboembolic complications, including myocardial infarction and ischaemic stroke, occurred in the groups given rFVIIa. A new trial, with death or dependency as the primary outcome, has recently been started. The results are expected early in 2007.
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PMID:[Acute treatment with recombinant factor VII is probably indicated for intracerebral haematoma]. 1612 78

Apart from management in a specialised stroke or neurological intensive care unit, until very recently no specific therapies improved outcome after intracerebral haemorrhage (ICH). In a recent phase II trial, recombinant activated factor VII (eptacog alfa) reduced haematoma expansion, mortality, and disability when given within 4 h of ICH onset; a phase III trial (the FAST trial) is now in progress. Ventilatory support, blood-pressure reduction, intracranial-pressure monitoring, osmotherapy, fever control, seizure prophylaxis, and nutritional supplementation are the cornerstones of supportive care in intensive care units. Ventricular drainage should be considered in all stuporous or comatose patients with intraventricular haemorrhage and acute hydrocephalus. Given the lack of benefit seen in a the recent STICH trial, emergency surgical evacuation within 72 h of onset should be reserved for patients with large (>3 cm) cerebellar haemorrhages, or those with large lobar haemorrhages, substantial mass effect, and rapidly deteriorating condition.
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PMID:Treatment of intracerebral haemorrhage. 1616 35

Intracerebral hemorrhage (ICH), which constitutes 10 to 15% of all strokes and affects approximately 65,000 people each year in the United States, has the highest mortality rate of all stroke subtypes. Hypertension, cerebral amyloid angiopathy, and anticoagulation underlie the majority of cases of ICH. Warfarin not only increases the risk but also increases the severity of ICH by causing hematoma expansion. With the advent of gradient-echo magnetic resonance imaging, patients with underlying cerebral amyloid angiopathy or hypertensive vasculopathy can be identified, and measures can be taken to prevent ICH. Initiating an antihypertensive regimen in a patient with nonlobar microbleeds suggestive of hypertensive vasculopathy, and withholding warfarin in patients with lobar microbleeds suggestive of cerebral amyloid angiopathy, are emerging prevention strategies. Although a treatment for cerebral amyloid angiopathy does not exist, agents targeting beta-amyloid metabolism and bioactivity are promising candidates. Strategies for preventing warfarin-associated hemorrhage include strict monitoring of anticoagulation levels and using agents such as direct thrombin inhibitors. The future of ICH management lies in therapies targeted at the pathophysiological steps in ICH. Potential treatments include glutamate receptor antagonists for preventing glutamate excitotoxicity, matrix metalloproteinase and thrombin inhibitors for preventing perihematomal edema, and recombinant activated factor VII for preventing hematomal expansion.
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PMID:Treatment and prevention of primary intracerebral hemorrhage. 1634

Intracerebral hemorrhage (ICH) is the least treatable form of stroke, and causes high mortality, severe disability, and a staggering economic burden. ICH accounts for 15% of stroke cases in the United States and Europe, and up to 30% in Asian populations. Computed tomography-based studies suggest that ICH growth within the first few hours of onset is common, and the principal cause of early neurological deterioration. Hematoma volume is also a well-established predictor of 30-day mortality. Intervention with ultra-early hemostatic therapy could minimize or prevent this early dynamic bleeding process, and might improve outcome. Recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) is approved for the treatment of bleeding in patients with hemophilia and inhibitors, but it may also promote hemostasis in patients with normal coagulation by acting locally at the bleeding site without activation of systemic coagulation. In a randomized, double-blind, placebo-controlled trial of 399 ICH patients treated with a single dose of 40, 80, or 160 microg/kg of rFVIIa or placebo within 4 hours of onset, subsequent hematoma growth was reduced by approximately 50% with rFVIIa. This was associated with a significant reduction (38%) in mortality, and improved functional outcomes among survivors. A phase III trial comparing 20 and 80 microg/kg rFVIIa with placebo is now in progress to confirm these results.
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PMID:Ultra-early hemostatic therapy for acute intracerebral hemorrhage. 1642 89

Stroke is a major health problem worldwide, causing high morbidity and mortality. Intracerebral hemorrhage (ICH) accounts for 10% of stroke cases in the United States and Europe and up to 30% in Asian populations. Intracerebral hemorrhage is less treatable than other forms of stroke and causes higher morbidity and disability. Data suggest that early hematoma growth is the principal cause of early neurological deterioration after ICH. Prospective and retrospective studies indicate that early hematoma growth occurs in 18-38% of patients scanned within three hours of ICH onset, and that hematoma volume is an important predictor of 30-day mortality. Recombinant activated factor VII (rFVIIa, NovoSeven), a powerful initiator of hemostasis, is approved for the treatment of bleeding in patients with hemophilia and inhibitors, and can also promote hemostasis in patients with normal coagulation. A Phase-IIB randomized, double-blind, placebo-controlled, dose-ranging trial has been conducted in 399 patients with ICH to investigate the potential of rFVIIa as an ultra-early hemostatic therapy. A reduction in hematoma growth in non-coagulopathic ICH patients was evident with reduced mortality and improved clinical outcome at three months. The significance of these findings for neurocritical care is discussed.
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PMID:Ultra-early hemostatic therapy for primary intracerebral hemorrhage: a review. 1645 Aug 6

Haemorrhagic stroke is frequent and associated with a high mortality and morbidity. Less than 30% of patients are still alive five years after onset and few patients regain functional independence. The worsening effect of anticoagulation has been demonstrated and the failure to rapidly normalize coagulation further increases haematoma expansion. In a recent phase II trial, recombinant activated factor VII given within 4 hours of stroke onset, reduced haematoma growth, mortality and disability. An aggressive blood pressure and intracranial pressure control early after the haemorrhage seems beneficial. A large prospective randomized study (the STICH trial) did not demonstrate any beneficial effect of surgery.
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PMID:[Intracerebral haemorrhage, what's new?]. 1669 32

Recombinant activated factor VII (rFVIIa /Novoseven) has been used in a wide variety of circumstances as a treatment for uncontrolled bleeding. We present a retrospective report of the use of rFVIIa in 40 consecutive patients without inherited bleeding disorders in a single centre. Twenty-one (68%) of the 31 patients whose response to rFVIIa was documented showed a reduction or cessation in bleeding; in nine patients (29%) bleeding was unchanged and in one patient (3%) bleeding increased despite rFVIIa. One person suffered a thrombotic stroke after rFVIIa treatment. There were no other adverse events directly attributable to rFVIIa. Twenty-four patients (60%) died during the hospital admission in which the rFVIIa was administered. Twelve patients (30%) who received rFVIIa had bleeding secondary to haematological malignancy and 21 patients (53%) had bleeding complicating a surgical procedure. There were 11 deaths (92%) in the haematological malignancy group and 10 deaths (48%) in the surgical group. Patients with haematological malignancy received a significantly greater median number of doses of rFVIIa than patients with surgical bleeding complications (three versus one dose, P = 0.04). We conclude that rFVIIa can be used safely in uncontrolled haemorrhage and the majority of patients show a response.
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PMID:Efficacy of recombinant activated factor VII in unselected patients with uncontrolled haemorrhage: a single centre experience. 1678 16

Despite the highest mortality and morbidity of all forms of stroke, few advances have been made in the management of intracerebral hemorrhage (ICH). Besides specialized care in the stroke or neurologic intensive care unit, until very recently no specific therapies have been shown to improve outcome after ICH. Ventilatory support, blood pressure reduction, intracranial pressure monitoring, osmotherapy, fever control, seizure prophylaxis, and nutritional supplementation are the cornerstones of supportive care in the intensive care unit. Recently, a phase II trial of recombinant activated factor VII (NovoSeven; Novo Nordisk, Bagsvaerd, Denmark) reduced hematoma expansion, mortality, and disability when given within 3 hours of ICH onset. A phase III trial to confirm these results is now in progress.
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PMID:Hemostatic therapy for intracerebral hemorrhage. 1682 96

A thorough review of the literature and of personal files has allowed the gathering of 81 patients with rare congenital bleeding disorders and thrombotic phenomena. Sixteen of these patients had congenital afibrinogenemia, eight involved factor V deficiency, 20 factor VII defects, 33 factor XI deficiencies and only one, a factor XIII defect. Altogether 42 patients showed arterial thrombosis (myocardial infarction [MI] in 28 cases; ischemic stroke in 4; arterial occlusion in 8; 2 patients with disseminated intravascular coagulation (DIC)). Ages varied between 13 and 74. Twenty-two patients were males and 16 females. In four cases, sex was not reported. There were three fatalities: two after a MI and one because of heart failure. With regard to venous thrombosis: 9 patients had pulmonary embolism, 15 patients had deep vein thrombosis, 9 patients had both pulmonary embolism and deep vein thrombosis; 1 patient had superficial vein thrombosis, whereas, 5 cases had an unusual site venous thrombosis (two portal systems, two cerebral sinuses, one inferior vena cava) for a total of 39 cases. Age varied between 3 and 86. In this case, 20 patients were males and 17 were females. In two cases, sex was not reported. There were three fatalities: two because of pulmonary embolism and one because of inferior vena cava thrombosis. The fact that thrombosis has never been described in patients with factor II or factor X seems to underscore the central antithrombotic role that these two factors have in the coagulation system.
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PMID:Arterial and venous thrombosis in rare congenital bleeding disorders: a critical review. 1683 33

To explore the role of the the tissue factor (TF) pathway in ischemic stroke. We measured blood concentrations of markers of the TF pathway [TF antigen, free tissue factor pathway inhibitor antigen (TFPIf) and activity (TFPIac), and activated factor VII (FVIIa)] within 7 days (acute phase) and after 3-6 months (convalescence) in 150 patients with first-ever ischemic stroke and 150 community controls. During the acute phase, TF antigen and TFPIf were not significantly altered but TFPIac was increased (mean 1.27 versus 1.13 U/ml, P = 0.04) and FVIIa was decreased in cases compared with controls (mean 43.3 versus 57.9 mU/ml, P = 0.0004). After adjusting for baseline differences between cases and controls, increasing quartiles of TFPIf were independently associated with reduced odds of stroke, and reducing quartiles of FVIIa and increasing quartiles of TFPIac with increased odds of stroke. During the convalescent phase, FVIIa and TFPIac returned to normal but TF antigen and TFPIf were significantly decreased compared with controls [median TF antigen, 110 (follow-up) versus 155 pg/ml (controls), P = 0.0008; median TFPIf, 15.5 (follow-up) versus 23.3 ng/ml (controls), P = 0.002]. Alterations of blood concentrations of TF pathway markers are common in patients with acute ischemic stroke. The mechanisms are unclear but may relate to enhanced formation of TF-FVIIa complexes and upregulation and release of TFPI during the acute phase, and ongoing consumption of TF antigen and TFPIf during the chronic phase as the atherosclerotic plaque heals.
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PMID:The tissue factor pathway in ischemic stroke. 1698 46


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