Hematoma growth occurs in 38% of intracerebral hemorrhage (ICH) patients scanned by computed tomography (CT) within 3 hours of onset. Activated recombinant factor VII (rFVIIa) promotes hemostasis at ...sites of vascular injury and may minimize hematoma growth after ICH.
In this randomized, double-blind, placebo-controlled, dose-escalation trial, 48 subjects with ICH diagnosed within 3 hours of onset were treated with placebo (n=12) or rFVIIa (10, 20, 40, 80, 120, or 160 microg/kg; n=6 per group). The primary endpoint was the frequency of adverse events (AEs). Safety assessments included serial electrocardiography (ECG), troponin I and coagulation testing, lower extremity Doppler ultrasonography, and calculation of edema:ICH volume ratios.
Mean age was 61 years (range, 30 to 93) and 57% were male. At admission, mean National Institutes of Health Stroke Scale (NIHSS) score was 14 (range, 1 to 26), median Glasgow Coma Scale score was 14 (range, 6 to 15), and mean ICH volume was 21 mL (range, 1 to 151). Mean time from onset to treatment was 181 minutes (range, 120 to 265). Twelve serious AEs occurred, including 5 deaths (mortality 11%). Six AEs were considered possibly treatment-related, including rash, vomiting, fever, ECG T-wave inversion, and 2 cases of deep vein thrombosis (placebo and 20-microg/kg groups). No myocardial ischemia, consumption coagulopathy, or dose-related increase in edema:ICH volume occurred.
This small phase II trial evaluated a wide range of rFVIIa doses in acute ICH and raised no major safety concerns. Larger studies are justified to determine whether rFVIIa can safely and effectively limit ICH growth.
Oral anticoagulant-associated intracerebral hemorrhage (OAC-ICH) accounts for nearly 20% of all ICH. The number of patients with an indication for oral anticoagulant therapy (OAT) increases with ...increasing age. OAT became less complicate with the introduction of non-vitamin K oral anticoagulants (NOAC) OAT because of easier handling, favorable risk-benefit profile, reduced rates of ICH compared to vitamin K antagonists and no need for routine coagulation testing. Consequently, despite a better safety profile of NOAC the number of patients with OAC-ICH will increase. The mortality and complication rates of OAC-ICH are high and therefore they are the most feared complication of OAT. Immediate normalization of coagulation is the main goal and therefore knowledge of pharmacodynamics and coagulation status is essential. Laboratory measurements of anticoagulant activity in NOAC patients is challenging as specific tests are not widely available. More accessible tests such as the prothrombin time and activated partial thromboplastin time have important limitations. In dabigatran-associated ICH 5 g Idarucizumab should be administered. In rivaroxaban and apixaban-associated ICHs administration of andexanet alpha should be considered. Prothrombin complex concentrate may be considered if andexanet alpha is not available or in case of an ICH associated with edoxaban.
Warfarin-related intracerebral hemorrhage carries a particularly high risk of neurologic deterioration and death because of a high rate of hematoma expansion of about 50%. Novel oral anticoagulants ...(NOACs)—apixaban, dabigatran, and rivaroxaban—have a significantly smaller risk of intracerebral hemorrhage (ICH). However, two facts make this situation complicated: First, the risk of hematoma expansion is unknown for NOACs. Second, there is no specific antidote for neither of the NOACs. We present a case that suggests that hematoma expansion may occur after NOAC-related ICH.
Abstract Purpose Because of the immune-suppressive effect of cerebral damage, stroke patients are at high risk for infections. These might result in sepsis, which is the major contributor to ...intensive care unit (ICU) mortality. Although there are numerous studies on infections in stroke patients, the role of sepsis as a poststroke complication is unknown. Methods We retrospectively analyzed incidence of and risk factors for sepsis acquisition as well as outcome parameters of 238 patients with ischemic or hemorrhagic strokes consecutively admitted to the neurologic ICU in a tertiary university hospital between January 1, 2009, and December 31, 2010. Basic demographic and clinical data including microbiological parameters as well as factors describing stroke severity (eg, lesion volume and National Institute of Health stroke scale score) were recorded and included into the analysis. The diagnosis of sepsis was based on the criteria of the German Sepsis Society. Results We identified 30 patients (12.6%) with sepsis within the first 7 days from stroke onset. The lungs were the most frequent source of infection (93.3%), and gram-positive organisms were dominating the microbiologic spectrum (52.4%). Comorbidities (chronic obstructive pulmonary disease and immunosuppressive disorders) and Simplified Acute Physiology Score II but none of the factors describing stroke severity were independent predictors of sepsis acquisition. Sepsis was associated with a significantly worse prognosis, leading to a 2-fold increased mortality rate during in-hospital care (36.7% vs 18.8%) and after 3 months (56.5% vs 28.5%), but only in the subgroup of supratentorial hemorrhages, it was an independent predictor of in-hospital and 3-month mortality. Other factors significantly associated with death in a multivariate analysis were chronic obstructive pulmonary disease, malignancies (in-hospital mortality only), and Simplified Acute Physiology Score II (3-month mortality only) for ischemia and heart failure (in-hospital mortality only), National Institute of Health stroke scale score (in-hospital mortality only), and stroke volume for hemorrhages, respectively. Conclusions Sepsis seems to be a frequent complication of stroke patients requiring neurologic ICU treatment. Predictors of sepsis acquisition in our study were comorbidities and severity of deterioration of physiological status, but not stroke severity. A better understanding of risk factors is important for prevention and early recognition, whereas knowledge of outcome may help in prognosis prediction. Further studies are needed to clarify the optimal preventive treatment for these patients.
Acute critical bleeding is one of the most feared complications during treatment with oral anticoagulating agents. As more patients undergo treatment with anticoagulating agents, critically bleeding ...episodes in patients with vitamin K antagonists, thrombin inhibitor, or factor Xa inhibitor-inducted coagulopathy will be encountered frequently by physicians. Hence, an effective treatment capable of reversing the iatrogenic coagulopathy in the acute setting is needed. In randomised clinical trials and observational studies, prothrombin complex concentrate has been reported to be superior to other acute interventions, and many guidelines recommend prothrombin complex concentrate in treatment of critically bleeding patients. The aim of this systematic review is to synthesise the evidence of the effects of prothrombin complex concentrate compared with placebo, no intervention, or other treatment options in critically bleeding patients treated with oral anticoagulants.
A comprehensive search for relevant published literature will be undertaken in Cochrane Central Register of Controlled Trials, MEDLINE, Embase, WHO International Clinical Trials Registry Platform, Science Citation Index, regulatory databases, and trial registers. We will include randomised clinical trials comparing prothrombin complex concentrate versus placebo, no intervention, or other interventions in critically bleeding patients with oral anticoagulant-induced coagulopathy. Data extraction and risk of bias assessment will be handled by two independent review authors. Meta-analysis will be performed as recommended by Cochrane Handbook for Systematic Reviews of Interventions, bias will be assessed with domains, and trial sequential analysis will be conducted to control random errors. Certainty will be assessed by GRADE.
As critical bleeding in patients treated with oral anticoagulants is an increasing problem, an up-to-date systematic review evaluating the benefits and harms of prothrombin complex concentrate is urgently needed. It is the hope that this review will be able to guide best practice in treatment and clinical research of these critically bleeding patients.
PROSPERO CRD42018084371.
Different aspects of acute stroke management and strategies for stroke prevention derive from two viewpoints: specific traditional and historical backgrounds and evidence-based medicine from modern ...randomized controlled trials (RCTs), meta-analysis and authorized clinical practice guidelines (GLs). Regarding intracerebral hemorrhage (ICH), Cerebrovascular Diseases published the 2006 European stroke initiative recommendations for the management of ICH. In 2009, the revised Japanese GLs for the management of stroke, including that of ICH, appeared in Japanese. Whereas GLs for the prevention and treatment of ischemic stroke were presented in detail, recommendations with regard to ICH are relatively rare both in Japan and Europe.
Since 2011, the authors have met repeatedly and have compared the latest versions of published European and Japanese GLs for ischemic and hemorrhagic strokes. Many aspects have only been addressed in one but left out in the other GLs, which consequently founded the basis for the comparison. Classification of evidence levels and recommendation grades defined by the individual committees differed between both original GLs.
Aspects of major importance were similar and hence did not need extensive interpretation, mostly due to a lack of evidence from appropriate RCTs worldwide. The target level to which systolic blood pressure should be lowered is quite high; <170 mm Hg for patients with known hypertension in Europe and <180 mm Hg in Japan. The results of ongoing clinical trials are awaited for the optimal target level and optimal medications. Concerning ICH associated with oral anticoagulant therapy, both guidelines give similar recommendations, namely that anticoagulation should be discontinued and the international normalized ratio of prothrombin time should be normalized with prothrombin complex concentrate or fresh-frozen plasma and additional vitamin K. Patients with ICH were treated surgically, often based on individual decisions - more frequently in Japan, depending on the association with hypertension. Patients with large or intraventricular bleedings were only treated if a life-saving performance was considered, irrespective of the neurological outcome. Infra- and supratentorial differences were similarly addressed in both GLs.
This brief survey - when compared with the lengthy original recommendations - provides a stimulating basis for an extended interest among Japanese and European stroke clinicians to learn from their individual experiences and to strengthen efforts for joint cooperation in treating and preventing stroke all around the globe.
Intracranial aneurysm with and without subarachnoid haemorrhage (SAH) is a relevant health problem: The overall incidence is about 9 per 100,000 with a wide range, in some countries up to 20 per ...100,000. Mortality rate with conservative treatment within the first months is 50-60%. About one third of patients left with an untreated aneurysm will die from recurrent bleeding within 6 months after recovering from the first bleeding. The prognosis is further influenced by vasospasm, hydrocephalus, delayed ischaemic deficit and other complications. The aim of these guidelines is to provide comprehensive recommendations on the management of SAH with and without aneurysm as well as on unruptured intracranial aneurysm.
We performed an extensive literature search from 1960 to 2011 using Medline and Embase. Members of the writing group met in person and by teleconferences to discuss recommendations. Search results were graded according to the criteria of the European Federation of Neurological Societies. Members of the Guidelines Committee of the European Stroke Organization reviewed the guidelines.
These guidelines provide evidence-based information on epidemiology, risk factors and prognosis of SAH and recommendations on diagnostic and therapeutic methods of both ruptured and unruptured intracranial aneurysms. Several risk factors of aneurysm growth and rupture have been identified. We provide recommendations on diagnostic work up, monitoring and general management (blood pressure, blood glucose, temperature, thromboprophylaxis, antiepileptic treatment, use of steroids). Specific therapeutic interventions consider timing of procedures, clipping and coiling. Complications such as hydrocephalus, vasospasm and delayed ischaemic deficit were covered. We also thought to add recommendations on SAH without aneurysm and on unruptured aneurysms.
Ruptured intracranial aneurysm with a high rate of subsequent complications is a serious disease needing prompt treatment in centres having high quality of experience of treatment for these patients. These guidelines provide practical, evidence-based advice for the management of patients with intracranial aneurysm with or without rupture. Applying these measures can improve the prognosis of SAH.
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