vitamin-k-semiquinone-radical and Intracranial-Hemorrhages

Direct oral anticoagulants (DOACs) are a newer class of anticoagulants that inhibit factor Xa or factor IIa and include drugs such as rivaroxaban, apixaban, edoxaban, betrixaban, and dabigatran. Although vitamin K antagonists (VKAs) have been traditionally used to prevent thromboembolic events, DOACs have gained popularity because of their faster onset and offset of action and reduced need for monitoring. This study aimed to provide more data for anticoagulants in patients with atrial fibrillation with bioprosthetic heart valves by incorporating all available trials to date. A search was performed across 5 electronic databases to identify relevant studies. We analyzed the data using a pooled risk ratio for categorical outcomes and used the I

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Hemorrhages; Network Meta-Analysis; Stroke; Thromboembolism; Vitamin K

We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF).. A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting severe bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated.. Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1).. Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Network Meta-Analysis; Rivaroxaban; Stroke; Vitamin K

Patients with atrial fibrillation (AF) who take direct oral anticoagulants (DOACs) face the risk of intracranial hemorrhage (ICH), which can be serious and even life threatening, but the risk of ICH of anticoagulants is still controversial. In this meta-analysis, we compared the risk of ICH between vitamin K antagonists (VKAs) and DOACs. Furthermore, we also compared the risk of ICH in different DOACs. PubMed, Embase, Web of Science, and the Cochrane Library were searched for relevant randomized controlled trials. The outcome was ICH, shown as the odds ratio (OR) with a 95% confidence interval (CI). DOACs were ranked by calculating the surface under the cumulative ranking curve (SUCRA). We included a total of 82,404 patients with AF. DOACs reduced the ICH risk by nearly half compared with VKAs (OR 0.47, 95% CI 0.40 to 0.54, p <0.001). VKAs were the least safe among all oral anticoagulants (SUCRA 1.7). Dabigatran 110 mg was the safest DOAC (SUCRA 87.3) for ICH risk, whereas rivaroxaban 20 mg was a relatively unsafe DOAC (SUCRA 27.5). Compared with rivaroxaban 20 mg, dabigatran 110 mg presented 53% (OR 0.47, 95% CI 0.27 to 0.82) lower relative risk for ICH. In conclusion, DOACs present less ICH risk than VKAs in patients with AF. For patients with AF who are at high risk of ICH, dabigatran 110 mg may be the safest choice among the DOACs.

Topics: Atrial Fibrillation; Factor Xa Inhibitors; Humans; Intracranial Hemorrhages; Network Meta-Analysis; Stroke; Vitamin K

Observational studies have investigated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) used in nonvalvular atrial fibrillation. We performed a systematic review and meta-analysis assessing the risk of ischaemic stroke, thromboembolism (TE) and intracranial haemorrhage (ICH) associated with the use of DOACs and VKAs.. Medline and Embase were systematically searched until April 2021. Observational studies were gathered and hazard ratios (HRs) with 95% confidence intervals (CI) were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, exposure to VKA, age and sex were performed. A random-effects model was used.. We included 92 studies and performed 107 comparisons. Apixaban was associated with lower risk of stroke (HR: 0.82, 95% CI: 0.68-0.99) compared to dabigatran. Rivaroxaban was associated with lower risk of stroke (HR: 0.90, 95% CI: 0.83-0.98) compared to VKA. Dabigatran (HR: 0.85, 95% CI: 0.80-0.91), rivaroxaban (HR: 0.83, 95% CI: 0.77-0.89) and apixaban (HR: 0.75, 95% CI: 0.65-0.86) were associated with lower risk for TE/stroke compared to VKA. Apixaban (HR: 1.32, 95% CI: 1.03-1.68) and rivaroxaban (HR: 1.58, 95% CI: 1.31-1.89) were associated with higher risk of ICH compared to dabigatran. Dabigatran (HR: 0.48, 95% CI: 0.44-0.52), apixaban (HR: 0.60, 95% CI: 0.49-0.73) and rivaroxaban (HR: 0.73, 95% CI: 0.65-0.81) were associated with lower risk of ICH compared to VKA.. Our study demonstrated significant differences in the risk of ischaemic stroke, TE/stroke and ICH associated with individual DOACs compared to both other DOACs and VKA.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Dabigatran; Humans; Intracranial Hemorrhages; Ischemic Stroke; Pyridones; Rivaroxaban; Stroke; Thromboembolism; Vitamin K

Hypertension is common in patients with atrial fibrillation (AF) and carries an additional risk for complications, most notably stroke and bleeding. We assessed the history of hypertension, level of blood pressure control, and an interaction with the choice of oral anticoagulants on clinical outcomes.. We performed a systematic review and meta-analysis of studies that randomised patients to novel oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) and reported outcomes stratified by presence of hypertension. Collected outcomes were: ischaemic stroke or systemic embolism (SE), haemorrhagic stroke, intracranial haemorrhage and major bleeding. Log adjusted hazard ratios (HR) and corresponding standard error were calculated, and HRs were compared using Mantel-Haenszel random effects. Quality of the evidence was assessed with Cochrane risk of bias tool.. Five high-quality studies were eligible, including 71.527 participants who received NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) or VKAs, with median follow-up of 1.8-2.8 years. Compared with patients without hypertension, those with hypertension had higher adjusted risk for ischaemic stroke/SE (HR: 1.25, 95%-CI:1.09, 1.43) and haemorrhagic stroke (HR:1.98, 1.24-3.16). On a continuous scale, the risk of ischaemic stroke/SE increased 6-7% per 10 mmHg increase in systolic blood pressure. No interactions were found between the efficacy or safety of NOACs versus VKAs in the presence or absence of hypertension. In both groups, the use of NOACs led to a lower risk of ischaemic stroke/SE, haemorrhagic stroke and intracranial haemorrhage compared with patients that used VKAs.. Adequate blood pressure management is vital to optimally reduce the risk of stroke in patients with atrial fibrillation. The benefits of NOACs over VKAs, also apply to patients with elevated blood pressure.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Embolism; Hemorrhage; Hemorrhagic Stroke; Humans; Hypertension; Intracranial Hemorrhages; Ischemic Stroke; Stroke; Vitamin K

Several observational studies have compared the effectiveness and safety outcomes between nonvitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with a history of either stroke/transient ischemic attack (TIA) or intracranial hemorrhage. Therefore, our current meta-analysis aimed to address this issue. The Cochrane Library, PubMed, and Embase databases were systematically searched until December 2020 for all relevant observational studies. We applied a random-effects model to pool adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for this meta-analysis. A total of 10 studies were included. Among patients with a history of stroke/TIA, the use of NOACs versus VKAs was associated with decreased risks of stroke (HR, 0.82, 95% CI 0.69-0.97), systemic embolism (HR, 0.73, 95% CI 0.61-0.87), all-cause death (HR, 0.87, 95% CI 0.81-0.94), major bleeding (HR, 0.77, 95% CI 0.64-0.92) and intracranial hemorrhage (HR, 0.54, 95% CI 0.38-0.77). Among patients with a history of intracranial hemorrhage, the use of NOACs versus VKAs was associated with reduced risks of stroke (HR, 0.81, 95% CI 0.68-0.95), all-cause death (HR, 0.68, 95% CI 0.49-0.94), and intracranial hemorrhage (HR, 0.66, 95% CI 0.51-0.84). Compared with VKAs, the use of NOACs exhibited superior efficacy and safety outcomes in AF patients with previous stroke/TIA, and the use of NOACs was associated with reduced risks of stroke, all-cause death, and intracranial hemorrhage in patients with a history of intracranial hemorrhage.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Stroke; Vitamin K

Intracranial haemorrhage (ICH) in infancy is a rare life-threatening event. The aim of this review is to highlight the association of ICH and potentially preventable vitamin K deficiency and to describe risk factors, presentation and outcome.. Original published data on ICH related to vitamin K deficiency during 2008-2012 were extracted from records of participating centres in Egypt (Cairo and Delta region). Full data on 70 infants (0-24 weeks) have been reported in three publications.. The first study involved premature infants where ICH was potentially preventable with administration of parenteral vitamin K prophylactic doses to mothers ahead of imminent preterm delivery. The other 2 studies involved term newborns and infants. ICH due to early or classic vitamin K deficiency was reported in nine patients while 44 were due to late vitamin K deficiency. Main risk factors for late onset were exclusive breastfeeding, persistent diarrhoea and/or prolonged antibiotic therapy.. Vitamin K deficiency bleeding is a relatively frequent problem underlying ICH in infancy. Prophylactic vitamin K to mothers when anticipating preterm labour or a vitamin K boost in exclusively breast-fed infants with prolonged antibiotic usage and, or, persistent diarrhoea might have an impact on prevention and outcome.

Topics: Breast Feeding; Egypt; Female; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Vitamin K; Vitamin K Deficiency Bleeding

 In this study-level meta-analysis, we evaluated the clinical outcome with nonvitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with cancer..  Anticoagulation in AF patients with cancer is challenging given the coexistence of elevated thrombotic and bleeding risk. The efficacy and safety of NOACs in this setting remain unclear..  We included three randomized trials in our primary analysis (.  In AF patients with malignancy, NOACs appear at least as effective as VKAs in preventing thrombotic events and reduce intracranial bleeding. NOACs may represent a valid and more practical alternative to VKAs in this setting of high-risk patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Data Interpretation, Statistical; Embolism; Hemorrhage; Humans; Intracranial Hemorrhages; Neoplasms; Observational Studies as Topic; Odds Ratio; Patient Safety; Randomized Controlled Trials as Topic; Risk; Risk Factors; Stroke; Thromboembolism; Venous Thromboembolism; Vitamin K

Refusal of intramuscular Vitamin K at birth is an emerging public health issue resulting in increased rates of intracranial bleeding. Parents who refuse this intervention bear epidemiologic resemblance to vaccine-refusing parents, are geographically clustered and share a mistrust of public health interventions. We review the prevalence of Vitamin K refusal and discuss individual and societal recommendations that may reduce Vitamin K refusal, adapted from vaccine hesitancy literature. We note the prevalence of misinformation on social media as a contributor to refusal and explore how changes in healthcare practices may influence growing physician mistrust. We propose solutions to the issue including state-based mandates and a pervasive social media strategy to combat misinformation as a contributor to Vitamin K refusal.

Topics: Communication; Female; Health Knowledge, Attitudes, Practice; Humans; Infant, Newborn; Injections, Intramuscular; Intracranial Hemorrhages; Parents; Patient Acceptance of Health Care; Pregnancy; Public Health; Social Media; Treatment Refusal; Trust; Vaccination Refusal; Vitamin K; Vitamin K Deficiency Bleeding; Vitamins

This meta-analysis aimed to evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in secondary stroke prevention in atrial fibrillation (AF) patients.. PubMed and Embase electronic databases were systematically searched from January 2009 to July 2019 for relevant randomized clinical trials and observational studies. A random-effects model was applied in the pooled analysis.. A total of 14 studies (4 randomized clinical trials and 10 observational studies) were included. Based on the randomized clinical trials, compared with VKA use, the use of NOACs was associated with decreased risk of stroke and systemic embolism, major bleeding, and intracranial bleeding. Based on the observational studies, compared with VKAs, the subgroup analysis showed that dabigatran and rivaroxaban were associated with a reduced risk of stroke or systemic embolism, whereas dabigatran and apixaban were associated with a decreased risk of major bleeding.. Based on current data, the use of NOACs is at least non-inferior to the use of VKAs in AF patients for secondary stroke prevention irrespective of NOAC type.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Humans; Intracranial Hemorrhages; Observational Studies as Topic; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Secondary Prevention; Stroke; Thiazoles; Treatment Outcome; Vitamin K; Warfarin

In this pooled analysis of seven multicentre cohorts potential differences were investigated in the incidence, characteristics and outcomes between intracranial haemorrhages (ICHs) associated with the use of non-vitamin K antagonist oral anticoagulants (NOAC-ICH) or with vitamin K antagonists (VKA-ICH) in ischaemic stroke patients after oral anticoagulant treatment initiation for atrial fibrillation (AF).. Data from 4912 eligible AF patients who were admitted in a stroke unit with ischaemic stroke or transient ischaemic attack and who were treated with either VKAs or NOACs within 3 months post-stroke were included. Fatal ICH was defined as death occurring during the first 30 days after ICH onset. A meta-analysis of available observational studies reporting 30-day mortality rates from NOAC-ICH or VKA-ICH onset was additionally performed.. During 5970 patient-years of follow-up 71 participants had an ICH, of whom 20 were NOAC-ICH and 51 VKA-ICH. Patients in the two groups had comparable baseline characteristics, except for the higher prevalence of kidney disease in VKA-ICH patients. There was a non-significant higher number of fatal ICH in patients with VKAs (11 events per 3385 patient-years) than in those with NOACs (three events per 2623 patient-years; hazard ratio 0.32, 95% confidence interval 0.09-1.14). Three-month functional outcomes were similar (P > 0.2) in the two groups. The meta-analysis showed a lower 30-day mortality risk for patients with NOAC-ICH compared to VKA-ICH (relative risk 0.70, 95% confidence interval 0.51-0.95).. Non-vitamin K oral anticoagulants for intracranial haemorrhages and VKA-ICH occurring during secondary stroke prevention of AF patients have comparable baseline characteristics and outcomes except for the risk of fatal ICH within 30 days, which might be greater in VKA-ICH.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Humans; Intracranial Hemorrhages; Stroke; Vitamin K

Ischaemic stroke and systemic embolism are the major potentially preventable complications of atrial fibrillation (AF) leading to severe morbidity and mortality. Anticoagulation using vitamin K antagonists (VKA) or non-vitamin K oral anticoagulants (NOACs) is mandatory for stroke prevention in AF. Following approval of the four NOACs dabigatran, rivaroxaban, apixaban, and edoxaban, the use of VKA is declining steadily. Increasing age with thresholds of 65 and 75 years is a strong risk factor when determining annual stroke risk in AF patients. Current recommendations such as the "2016 Guidelines for the management of atrial fibrillation" of the European Society of Cardiology and the "2019 AHA/ACC/HRS Focused Update" by the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society strengthen the importance of anticoagulation and detection of bleeding risks, of which older age is an important one. While patients aged ≥ 75 years are usually underrepresented in randomised clinical trials, they represent almost 40% of the trial populations in the large NOAC approval studies. Therefore, a sufficient amount of data is available to assess the efficacy and safety for this patient cohort in that specific indication. In this article, the evidence for stroke prevention in AF using either VKA or NOACs is summarised with a special focus on efficacy compared to bleeding risk in patients aged ≥ 75 years. Specifically, we used a model of increased weighing of intracranial bleeding to illustrate the potential benefit of NOACs over VKA in the elderly population. In brief, there are at least two tested strategies with apixaban and edoxaban which even confer an additional clinical net benefit compared with VKA. Furthermore, elderly subgroups of trials for combined antithrombotic treatment following percutaneous coronary interventions in anticoagulated patients are analysed.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Pyrazoles; Pyridines; Pyridones; Risk Factors; Rivaroxaban; Stroke; Thiazoles; Treatment Outcome; Vitamin K; Warfarin

Oral anticoagulants (OAC) reduce stroke/systemic embolism and mortality risks in atrial fibrillation (AF). However, there is an inherent bleeding risk with OAC, where intracranial hemorrhage (ICH) is the most feared, disabling, and lethal complication of this therapy. Therefore, the optimal management of OAC-associated ICH is not well defined despite multiple suggested strategies.. In this review, the authors describe the severity and risk factors for OAC-associated ICH and the associated implications for using DOACs in AF patients. We also provide an overview of the management of OAC-associated ICH and treatment reversal strategies, including specific and nonspecific reversal agents as well as a comprehensive summary of the evidence about the resumption of DOAC and the optimal timing.. In the setting of an ICH, supportive care/measures are needed, and reversal of anticoagulation with specific agents (including administration of vitamin K, prothrombin complex concentrates, idarucizumab and andexanet alfa) should be considered. Most patients will likely benefit from restarting anticoagulation after an ICH and permanently withdrawn of OAC is associated with worse clinical outcomes. Although the timing of OAC resumption is still under debate, reintroduction after 4-8 weeks of the bleeding event may be possible, after a multidisciplinary approach to decision-making.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Coagulation Factors; Factor Xa; Humans; Intracranial Hemorrhages; Recombinant Proteins; Risk Factors; Stroke; Vitamin K

Urgent reversal of vitamin K antagonists (VKAs) is required for major bleeding or urgent surgery by intravenous vitamin K with either prothrombin complex concentrates (PCCs) or fresh frozen plasma (FFP). However, there is lack of consensus regarding the superiority of either reversal agent. We sought to compare the performance of PCC and FFP in urgent reversal of VKA.. A meta-analysis was conducted up to November 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model.. Seventeen studies comprising 2606 participants met the inclusion criteria. Compared with FFP treatment, PCC treatment led to a reduction in 90-day all-cause mortality (OR 0.60, 95% CI 0.40-0.90, p = 0.01), better reversal of INR (OR 7.36, 95% CI 4.18-12.98; p < 0.00001) and lower risk of at least one treatment-related adverse event (OR 0.45, 95% CI 0.26-0.80, p = 0.006). Among patients with VKA-associated intracranial haemorrhage, PCC treatment led to a reduction in 90-day all-cause mortality (OR 0.58, 95% CI 0.35-0.94, p = 0.03) and better reversal of INR (OR 6.52, 95% CI 1.66-25.59, p = 0.007). There were no differences between these two agents in thrombogenicity, requirement for and quantity of red blood cell transfusions, all adverse events, fluid overload or disability on discharge or at 90 days.. As an agent for urgent reversal of VKA, PCC outperforms FFP in 90-day all-cause mortality including those with VKA-related intracranial haemorrhage, INR reversal and treatment-related adverse events.

Topics: Anticoagulants; Blood Coagulation Factors; Erythrocyte Transfusion; Humans; Intracranial Hemorrhages; Plasma; Vitamin K

Prothrombin complex concentrate (PCC) is the treatment of choice in vitamin K antagonist-associated intracranial hemorrhage (VKA-ICH). However, the efficiency and safety associated with their use remain unclear.. This study aimed to assess the current evidence of the clinical outcomes in patients with VKA-ICH treated with or without PCC. A meta-analysis was conducted. Two randomized controlled trials and 19 observational studies were included. PCC use demonstrated a significant increased likelihood of international normalized ratio (INR) normalization (OR = 3.76; 95% CI 1.74-8.12), shortened time to INR correction (MD = - 1.30; 95% CI - 2.08 to - 0.53) and reduction of hematoma expansion (HE) rate (OR = 0.37; 95% CI 0.23-0.60). Although PCC use revealed a statistical reduction at 30-day mortality (OR = 0.62; 95% CI 0.50-0.78), the result was inconsistent with mortality at discharge (OR = 1.03; 95% CI 0.68-1.57) and 90-day follow-up (OR = 0.50; 95% CI 0.24-1.07), both of which yielded no significant difference. When subgroup analyses were performed focus on PCC only treatment with FFP, no statistically significant difference was observed in 30-day mortality (OR = 0.43; 95% CI 0.11-1.71) as well. Besides, significant difference was not found in neurologic improvement at discharge (OR = 1.85; 95% CI 0.32-10.75), 30-day follow-up (OR = 3.00; 95% CI 0.93-9.70), or 90-day follow-up (OR = 1.55; 95% CI 0.84-2.86). No statistically significant difference was noted in the risk of thromboembolism following PCC administration (OR = 0.61; 95% CI 0.23-1.63).. PCC use for VKA-ICH reversal was associated with a significant reduction in INR and HE rate, without an increased risk of thromboembolic events. However, this reduction was not associated with improvement in neurologic deficits or overall survival. Well-designed randomized trials with special considerations to the aspect are necessary.

Topics: Anticoagulants; Blood Coagulation Factors; Humans; Intracranial Hemorrhages; Vitamin K

Vitamin K is a key point for guarantee normal blood clotting and its level in newborns is commonly low, so a supplementation after delivery is mandatory. Vitamin K prophylaxis in newborns is still an open field of debate: many types of protocol have been proposed in different years and Countries, and sometimes with great variability inside the same Nation (for instance, in Italy a national consensus is not available, so different protocols are employed). Recommendations include different protocols for healthy newborns born at term, but the unpreventable presence of bleeding favouring factors (i.e. blood vessels malformations) or limiting intestinal absorption of liposoluble vitamins (i.e. cholestasis), which could be unrecognized or subclinical in the perinatal period, rises some concerning about the most precautionary route of administration and the timing of further doses after the first one given at birth. The purpose of this report is to underline the most recent evidences available in literature and to arise a debate about this topic, in order to stimulate the production of evidence-based guidelines concerning the prophylaxis with vitamin K1 in newborn infants, considering that many bleeding risk factors are not recognizable at birth.. We are hereby presenting an emblematic case concerning the risk of intracranial bleeding in an apparently healthy newborn: the described infant did not show any pathological elements in pregnancy history or perinatal life which suggest a possible increased risk of bleeding and the needing of a particular approach in the administration of vitamin K1, but at the end of the first week of life presented an intracranial bleeding with neurological symptoms that required treatment for vitamin K deficiency.. Univocal recommendations about vitamin K prophylaxis are not available and the contrast between oral and intramuscular routes persists unsolved. The difficulty to certainly identify an infant eligible for oral administration of vitamin K1 at birth suggests that the intramuscular route should be preferred. How to prosecute the supplementation in the first months of life is still an open topic of debate.

Topics: Evidence-Based Medicine; Female; Humans; Infant, Newborn; Injections, Intramuscular; Intracranial Hemorrhages; Italy; Magnetic Resonance Imaging; Needs Assessment; Neonatology; Practice Guidelines as Topic; Risk Assessment; Term Birth; Vitamin K; Vitamin K Deficiency Bleeding

The use of oral anticoagulant therapy for stroke prevention in atrial fibrillation has been transformed by the availability of the nonvitamin K antagonist oral anticoagulants. Real-world studies on the use of nonvitamin K antagonist oral anticoagulants would help elucidate their effectiveness and safety in daily clinical practice. Apixaban was the third nonvitamin K antagonist oral anticoagulants introduced to clinical practice, and increasing real-world studies have been published. Our aim was to summarize current evidence about real-world studies on apixaban for stroke prevention in atrial fibrillation.. We performed a systematic review and meta-analysis of all observational real-world studies comparing apixaban with other available oral anticoagulant drugs.. From the original 9680 results retrieved, 16 studies have been included in the final meta-analysis. Compared with warfarin, apixaban regular dose was more effective in reducing any thromboembolic event (odds ratio: 0.77; 95% confidence interval: 0.64-0.93), but no significant difference was found for stroke risk. Apixaban was as effective as dabigatran and rivaroxaban in reducing thromboembolic events and stroke. The risk of major bleeding was significantly lower for apixaban compared with warfarin, dabigatran, and rivaroxaban (relative risk reduction, 38%, 35%, and 46%, respectively). Similarly, the risk for intracranial hemorrhage was significantly lower for apixaban than warfarin and rivaroxaban (46% and 54%, respectively) but not dabigatran. The risk of gastrointestinal bleeding was lower with apixaban when compared with all oral anticoagulant agents (. Use of apixaban in real-life is associated with an overall similar effectiveness in reducing stroke and any thromboembolic events when compared with warfarin. A better safety profile was found with apixaban compared with warfarin, dabigatran, and rivaroxaban.

Topics: Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Female; Humans; Intracranial Hemorrhages; Male; Polymers; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Saliva, Artificial; Stroke; Vitamin K; Warfarin

Guidelines advise performing a computed tomography head scan for all anticoagulated head injured patients, but the risk of intracranial haemorrhage (ICH) after a minor head injury is unclear. We conducted a systematic review and meta-analysis to determine the incidence of ICH in anticoagulated patients presenting with a minor head injury and a Glasgow Coma Score (GCS) of 15. We followed Meta-Analyses and Systematic Reviews of Observational Studies guidelines. We included all prospective studies recruiting consecutive anticoagulated emergency patients presenting with a head injury. Anticoagulation included vitamin-K antagonists (warfarin, fluindione), direct oral anticoagulants (apixaban, rivaroxaban, dabigatran and edoxaban) and low molecular weight heparin. A total of five studies (including 4080 anticoagulated patients with a GCS of 15) were included in the analysis. The majority of patients took vitamin K antagonists (98·3%). There was significant heterogeneity between studies with regards to mechanism of injury and methods. The random effects pooled incidence of ICH was 8·9% (95% confidence interval 5·0-13·8%). In conclusion, around 9% of patients on vitamin K antagonists with a minor head injury develop ICH. There is little data on the risk of traumatic intracranial bleeding in patients who have a GSC 15 post-head injury and are prescribed a direct oral anticoagulant.

Topics: Anticoagulants; Craniocerebral Trauma; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Incidence; Intracranial Hemorrhages; Male; Prospective Studies; Vitamin K

Essentials Hemorrhagic risk of antiplatelet drugs is generally thought to be lower than anticoagulants. We systematically reviewed trials comparing antiplatelet and anticoagulant drugs in older patients. Overall, the risk of major bleeding was similar with antiplatelet and with anticoagulant drugs. In elderly patients, risks and benefits of antiplatelet drugs should be carefully weighted.. Background The hemorrhagic risk of antiplatelet drugs in older patients could be higher than is usually assumed. Objective To compare the bleeding risk of antiplatelet drugs and oral anticoagulants in elderly patients. Methods We carried out a systematic review and meta-analysis. We searched PubMed, EMBASE and the Cochrane Library up to January 2016 for randomized and non-randomized controlled trials (RCTs) and parallel cohorts comparing antiplatelet drugs and oral anticoagulants in patients aged 65 years or older. Two independent authors assessed studies for inclusion. The pooled relative risk (RR) of major bleeding was estimated using a random model. Results Seven RCTs (4550 patients) and four cohort studies (38 649 patients) met the inclusion criteria. The risk of major bleeding when on aspirin or clopidogrel was equal to that when on warfarin in RCTs (RR, 1.01; 95% confidence interval (95% CI), 0.69-1.48; moderate-quality evidence), lower than when on warfarin in non-randomized cohort studies (RR, 0.87; 95% CI, 0.77-0.99; low-quality evidence) and not different when all studies were combined (RR, 0.86; 95% CI, 0.73-1.01). Bleeding of any severity (RR, 0.70; 95% CI, 0.57-0.86) and intracranial bleeding (RR, 0.46; 95% CI, 0.30-0.73) were less frequent with antiplatelet drugs than with warfarin. All-cause mortality was similar (RR, 0.99). Subgroup analysis suggested that major bleeding might be higher with warfarin than with aspirin in patients over 80 years old. Conclusion Elderly patients treated with aspirin or clopidogrel suffer less any-severity bleeding but have a risk of major bleeding similar to that of oral anticoagulants, with the exception of intracranial bleeding.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Cohort Studies; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk; Stroke; Ticlopidine; Treatment Outcome; Vitamin K; Warfarin

Oral anticoagulation therapy has reduced the risk of ischaemic stroke and improved the outcomes for patients with atrial fibrillation considerably. The emergence of the non-vitamin K oral anticoagulants as alternatives to vitamin K antagonists has significantly changed the practice of stroke prevention in atrial fibrillation. As the main complication with antithrombotic therapy is bleeding, physicians should always balance the risk of ischaemic stroke against intracranial haemorrhage and intervene where appropriate to reduce both risks. Individual approach is often mandatory due to heterogeneity of the risks and patient preferences. The purpose of this review is to summarise the current knowledge of the oral anticoagulation therapy in atrial fibrillation patients and guide physicians with the management of anticoagulants based on data from clinical trials and systematic reviews.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Platelet Aggregation Inhibitors; Risk Assessment; Stroke; Vitamin K

The original non-vitamin K antagonist oral anticoagulant (NOAC) trials in nonvalvular atrial fibrillation (AF) enrolled patients with native valve pathologies. The object of this study was to quantify the benefit-risk profiles of NOACs versus warfarin in AF patients with native valvular heart disease (VHD).. Trials were identified by exhaustive literature search. Trial data were combined using inverse variance weighting to produce a meta-analytic summary hazard ratio (HR) and 95% confidence interval (CI) of efficacy and safety of NOACs versus warfarin. Our final analysis included 4 randomized controlled trials that enrolled 71 526 participants, including 13 574 with VHD. Pooling results from included trials showed that NOACs versus warfarin reduced stroke or systemic embolism (HR: 0.70; 95% CI, 0.60-0.82) and intracranial hemorrhage (HR: 0.47; 95% CI, 0.24-0.92) in AF patients with VHD. However, risk reduction of major bleeding and intracranial hemorrhage was driven by apixaban, edoxaban, and dabigatran (HR for major bleeding: 0.79 [95% CI, 0.69-0.91]; HR for intracranial hemorrhage: 0.33 [95% CI, 0.25-0.45]) but not rivaroxaban (HR for major bleeding: 1.56 [95% CI, 1.20-2.04]; HR for intracranial hemorrhage: 1.27 [95% CI, 0.77-2.10]).. Among patients with AF and native VHD, NOACs reduce stroke and systemic embolism compared with warfarin. Evidence shows that apixaban, dabigatran, and edoxaban also reduce bleeding in this patient subgroup, whereas major bleeding (but not intracranial hemorrhage or mortality rate) is significantly increased in VHD patients treated with rivaroxaban. NOACs are a reasonable alternative to warfarin in AF patients with VHD.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Chi-Square Distribution; Female; Heart Valve Diseases; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Odds Ratio; Risk Factors; Stroke; Treatment Outcome; Vitamin K; Warfarin

To perform a systematic review and meta-analysis of studies reporting recurrent intracranial hemorrhage (ICH) and ischemic stroke (IS) in ICH survivors with atrial fibrillation (AF) during long-term follow-up.. A comprehensive literature search including MEDLINE, EMBASE, Cochrane library, clinical trials registry was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We considered studies capturing outcome events (ICH recurrence and IS) for ≥3 months and treatment exposure to vitamin K antagonists (VKAs), antiplatelet agents (APAs), or no antithrombotic medication (no-ATM). Corresponding authors provided aggregate data for IS and ICH recurrence rate between 6 weeks after the event and 1 year of follow-up for each treatment exposure. Meta-analyses of pooled rate ratios (RRs) were conducted with the inverse variance method.. Seventeen articles met inclusion criteria. Seven observational studies enrolling 2,452 patients were included in the meta-analysis. Pooled RR estimates for IS were lower for VKAs compared to APAs (RR = 0.45, 95% confidence interval [CI] 0.27-0.74,. In observational studies, anticoagulation with VKA is associated with a lower rate of IS than APA or no-ATM without increasing ICH recurrence significantly. A randomized controlled trial is needed to determine the net clinical benefit of anticoagulation in ICH survivors with AF.

Topics: Atrial Fibrillation; Brain Ischemia; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Platelet Aggregation Inhibitors; Stroke; Vitamin K

Patients receiving vitamin K antagonists (VKAs) are at increased risk of bleeding. Intracranial hemorrhage (ICH) is a major cause of morbidity and mortality in this population, and is a particular concern among Japanese clinicians, given reports of an elevated risk of this bleeding type in patients of Asian ethnicity. Patients with VKA-associated ICH require rapid international normalized ratio (INR) reversal, and treatment guidelines suggest the use of prothrombin complex concentrates (PCCs) or plasma for this purpose. Although European and US guidelines recommend PCCs for the treatment of VKA-associated major bleeding, they do not make a specific recommendation in the setting of ICH, owing to the lack of comparative evidence. In contrast, Japanese guidelines recommend the use of PCCs rather than plasma for VKA reversal in patients with ICH; however, these agents are not currently licensed in Japan for this indication. Here we review the available evidence on the use of PCCs for the treatment of VKA-associated ICH, both globally and specifically in Japanese settings. Overall, the evidence reviewed here supports the use of PCC for rapid VKA reversal in these patients.

Topics: Blood Coagulation Factors; Humans; Intracranial Hemorrhages; Japan; Practice Guidelines as Topic; Vitamin K

Factor Xa (fXa)-inhibitors are as effective and safer than vitamin-K-antagonists (VKA) in the treatment of venous thromboembolism (VTE). We previously classified the severity of clinical presentation and course of all major bleeding events from the EINSTEIN, AMPLIFY and HOKUSAI-VTE trials separately. The current aim was to combine these findings in order to increase precision, assess a class effect and analyse presentation and course for different types of bleeding, i. e. intracranial, gastro-intestinal, and other. We classified the clinical presentation and course of all major bleeding events using pre-defined criteria. Both classifications comprised four categories; one being the mildest, and four the most severe. Odds ratios (OR) were calculated for all events classified as category three or four between fXa-inhibitors and VKA recipients. Also, ORs were computed for different types of bleeding. Major bleeding occurred in 111 fXa-inhibitor recipients and in 187 LMWH/VKA recipients. The clinical presentation was classified as category three or four in 35 % and 48 % of the major bleeds in fXa inhibitor and VKA recipients, respectively (OR 0.59, 95 % CI 0.36-0.97). For intracranial, gastro-intestinal and other bleeding a trend towards a less severe presentation was observed for patients treated with fXa inhibitors. Clinical course was classified as severe in 22 % of the fXa inhibitor and 25 % of the VKA associated bleeds (OR 0.83, 95 % CI 0.47-1.46). In conclusion, FXa inhibitor associated major bleeding events had a significantly less severe presentation and a similar course compared to VKA. This finding was consistent for different types of bleeding.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Transfusion; Chi-Square Distribution; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Logistic Models; Male; Middle Aged; Odds Ratio; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Venous Thromboembolism; Vitamin K

Intracranial hemorrhage (ICH) in cancer patients can result from tumor bleeding and from antitumor and anticoagulation therapy. The effect of anticoagulation on the incidence of ICH in cancer patients has not been quantified. Our objective was to determine the risk of intracranial hemorrhage associated with anticoagulation therapy for cancer-associated venous thromboembolism (VTE). Systematic review and meta-analysis of studies assessing the safety of anticoagulation therapy in patients with cancer-associated VTE. The primary endpoint of interest was the incidence of ICH and secondary outcomes included all major bleeding, and the time to ICH and major bleeding. After identifying 595 studies, five studies and 2089 patients were included in the analyses. We found that the relative risk (RR) for ICH was 0.494, 95 % CI (0.105-2.331) when low molecular weight heparin (LMWH) with vitamin K antagonist (VKA) anticoagulants were compared. No statistically significant differences in risk were measured. The risk of major bleeding using any type of anticoagulation therapy in patients with cancer-associated VTE was RR 0.853, 95 % CI (0.549, 1.327). After meta-analytic review of data published through August 2015, we conclude that therapeutic anticoagulation with LMWH given ≤6 months does not increase the risk of ICH in cancer patients compared to VKA. The risk of ICH in cancer patients is also similar to that of non-cancer patients. Available data were insufficient to determine if the ICH risk increase changes when the duration of anticoagulation is >6 months.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Intracranial Hemorrhages; Neoplasms; Risk; Venous Thromboembolism; Vitamin K

Vitamin K deficiency bleeding (VKDB) can cause prolonged and bleeding (intracranial hemorrhage) among newborns, which can be life-threatening or lead to long-term morbidity. The aim of this review article is to reiterate empirical evidence to support the argument that vitamin K should be mandatory for newborns in India and China, as well as in other countries with a high burden of neonatal deaths.. Studies were integrated from the PubMed/MEDLINE database search, as well as related literature available elsewhere.. Both India and China have been slow in adopting an effective program for administering vitamin K injections to newborns to prevent VKDB-related morbidity and mortality. VKDB cases in China and India have shown inadequate attention to routine use of vitamin K by injection.. While no reliable data are publicly available, the issue of VKDB is at last receiving some attention from the Chinese public health system as well as the Indian government. In both countries, routine vitamin K administration to newborns would prove to be a cost-effective intervention to reduce preventable neonatal morbidity and mortality. VKDB is a global neonatal care issue, including countries where parental resistance is preventing babies from defense against this life-threatening condition.

Topics: China; Dietary Supplements; Female; Humans; India; Infant; Infant Mortality; Infant, Newborn; Intracranial Hemorrhages; Male; Primary Prevention; Treatment Outcome; Vitamin K; Vitamin K Deficiency Bleeding

Until recently, vitamin K antagonists, warfarin being the most commonly used agent in the United States, have been the only oral anticoagulant therapies available to prevent stroke in patients with atrial fibrillation (AF). In the last 5 years four new, non-vitamin K oral anticoagulants, the so-called NOACs or novel oral anticoagulants, have come to market and been approved by the Federal Drug Administration. Despite comparable if not superior efficacy in preventing AF-related stroke, and generally lower risks of major hemorrhage, particularly intracranial bleeding, the uptake of these agents has been slow. A number of barriers stand in the way of the more widespread use of these novel agents. Chief among them is concern about the lack of antidotes or reversal agents. Other concerns include the need for strict medication adherence, since missing even a single dose can lead to a non-anticoagulated state; out-of-pocket costs for patients; the lack of easily available laboratory tests to quantitatively assess the level of anticoagulant activity when these agents are being used; contraindications to use in patients with severe chronic kidney disease; and black-box warnings about the increased risk of thromboembolic events if these agents are discontinued prematurely. Fortunately, a number of reversal agents are in the pipeline. Three reversal agents, idarucizumab, andexanet alfa, and aripazine, have already progressed to human studies and show great promise as either antidotes for specific drugs or as universal reversal agents. The availability of these reversal agents will likely increase the clinical use of the non-vitamin K oral anticoagulants. In light of the many complex and nuanced issues surrounding the choice of an optimal anticoagulant for any AF patient, a patient-centered/shared decision-making approach will be useful.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Decision Making; Humans; Intracranial Hemorrhages; Stroke; Thromboembolism; Vitamin K

Prior meta-analysis and observational studies have suggested that the bleeding risks associated with anticoagulation using vitamin K antagonists (VKA) or aspirin (ASA) are similar.. The aim of this systematic review was to provide the odds ratios (ORs) of major bleeding, intracranial bleeding or major extra-cranial bleeding of anticoagulation with VKA compared to low doses of ASA.. We conducted a systematic review of Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (RCT). Randomized controlled trials reporting bleeding rates in adult patients randomized to a VKA (INR 2-3) or to ASA alone (<325mg daily). Random effects OR were calculated.. Fifteen trials reporting the outcome of 2511 participants treated with VKA alone and 2471 treated with ASA alone were included; most common conditions evaluated were non-valvular atrial fibrillation (five trials) and heart failure (three trials). Overall, the use of VKA was associated with an increased risk of major bleeding (OR 1.76 (95% CI 1.33-2.33) when compared to ASA. The OR associated with VKA use for intracranial bleeding and extra-cranial bleeding were 1.74 (95% CI 0.83-3.62) and 1.66 (95% CI 0.94-2.92), respectively. In trials achieving good control of anticoagulation [time in therapeutic range (TTR) >65%], the risk of bleeding with VKA was similar to that of ASA [OR 1.16 (95% CI 0.79-1.71)].. Contrary to prior reports our results suggest that the risk of major bleeding with the use VKA is higher compared to those of patients treated with ASA alone. However, in patients achieving a good TTR, the risk of major bleeding with VKA or ASA is similar.

Topics: Anticoagulants; Aspirin; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Hemorrhages; Odds Ratio; Risk Assessment; Vitamin K

Several patients with non-valvular atrial fibrillation treated with warfarin or other vitamin-K antagonists (VKA) might benefit from switching to an oral non vitamin-K antagonist anticoagulant (NOAC). In the absence of randomised comparative trials of switching to NOACs versus maintaining VKA treatment, several considerations argue in favour of a switching strategy. First, there is conclusive evidence that haemorrhagic strokes and intracranial bleedings are much fewer in number with NOACs than with warfarin. The risk of intracranial bleeding is 52 % lower with NOACS than with warfarin, with extremes ranging from 33 to 70 %. Such benefit is applicable to different NOACs, and independent of the time-in-therapeutic range under warfarin. Patients at increased risk for intra-cranial bleeding (renal dysfunction, or prior stroke or intra-cranial bleeding) should benefit most from switching to NOACs. Patients with labile International Normalized Ratio are also considered good candidates for switching because of their increased risk of stroke, and the lack of interactions between the effects of NOACs versus warfarin and the time-in-therapeutic range. Furthermore, some NOACs proved to be superior to warfarin in reducing the risk of thromboembolic complications even in intention-to-treat analyses. As further advantage, NOACs show fewer drug-drug and drug-food interactions when compared with warfarin. Last, but not least, NOACs do not need frequent blood drawings except in patients with moderate renal dysfunction, in whom periodic controls of serum creatinine are generally advised. The higher cost remains a barrier to a wider use of NOACs, especially in low-income settings.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Evidence-Based Medicine; Female; Humans; Intracranial Hemorrhages; Male; Randomized Controlled Trials as Topic; Risk Assessment; Rivaroxaban; Severity of Illness Index; Survival Rate; Treatment Outcome; Vitamin K; Warfarin

While evidence supports resumption of vitamin K antagonists (VKAs) among mechanical heart valve (MHV) patients presenting with anticoagulant-associated intracranial hemorrhage (ICH), ideal timing of resumption is uncertain.. To determine the optimal timing of VKA re-initiation and its associated clinical outcomes.. We performed a systematic review and a meta-analysis of studies published from January 1950 to August 2015. We extracted data on the location of initial ICH, use of cranial surgery, presence of atrial fibrillation, MHV type and position, number of MHVs, and timing of VKA resumption. Outcomes including valve thrombosis, thromboembolic events or ICH recurrence were recorded. Meta-regression analysis was conducting with controlling for covariates. We calculated absolute risks, and assessed the effect of anticoagulant resumption timing on ICH recurrence.. 23 case-series and case-reports were identified. Overall ICH recurrence was 13% (95% confidence interval [CI], 7%-25%), while valve thrombosis and ischemic strokes occurred at 7% (95% CI, 3%-17%) and 12% (95% CI, 5%-23%) respectively. A trend towards lower ICH recurrence was observed with delayed VKA resumption (slope estimate -0.2154, p=0.10). Recurrence rate ranged from 50% with VKA resumption at 3days to 0% with resumption at 16days.. Among patients with MHV, there is inadequate data to suggest an optimal timing of VKA re-initiation following an ICH, though delayed restart appears to be protective against recurrence but is associated with higher risk of thrombosis. Our analysis suggests 4-7days might be an ideal time with least risk of thrombosis or ICH recurrence.

Topics: Anticoagulants; Heart Valve Prosthesis; Humans; Intracranial Hemorrhages; Thrombosis; Vitamin K; Warfarin

Atrial fibrillation is found in a third of all ischaemic strokes, even more after post-stroke atrial fibrillation monitoring. Data from stroke registries show that both unknown and untreated or under treated atrial fibrillation is responsible for most of these strokes, which are often fatal or debilitating. Most could be prevented if efforts were directed towards detection of atrial fibrillation before stroke occurs, through screening or case finding, and treatment of all patients with atrial fibrillation at increased risk of stroke with well-controlled vitamin K antagonists or non-vitamin K antagonist anticoagulants. The default strategy should be to offer anticoagulant thromboprophylaxis to all patients with atrial fibrillation unless defined as truly low risk by simple validated risk scores, such as CHA2DS2-VASc. Assessment of bleeding risk using the HAS-BLED score should focus attention on reversible bleeding risk factors. Finally, patients need support from physicians and various other sources to start anticoagulant treatment and to ensure adherence to and persistence with treatment in the long term.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Medication Adherence; Registries; Risk Assessment; Risk Factors; Stroke; Vitamin K; Warfarin

Several new anticoagulants have entered the clinical arena or are under clinical development. These drugs include indirect (fondaparinux) and direct oral factor Xa inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban), and the direct thrombin inhibitor dabigatran. Especially the oral direct FXa and FIIa inhibitors overcome many of the shortcomings of heparins and vitamin K antagonists (VKAs). They are administered orally at a fixed dose; regular monitoring is not necessary; interaction with other drugs or nutrition occur less than with VKAs and they are at least as effective as VKAs for most indications tested. They are associated with about 50 % less intracranial bleeding than VKAs. Nevertheless, they are still associated with bleeding complications. Bleeding can occur spontaneously or as a result of trauma or urgent surgery. In such situations rapid reversal of the anticoagulant effect is highly desirable. For unfractionated heparin protamine, and for VKAs prothrombin complex concentrates are available as specific antidotes. Under clinical development are: for the direct and indirect FXa inhibitors a modified recombinant FXa (andexanet alpha), which lacks enzymatic activity; and for dabigatran a Fab fragment of a monoclonal antibody (idarucizumab). In addition a small molecule (aripazine) has entered phase I clinical trials, which seems to inhibit nearly all anticoagulants but VKAs and argatroban. This review summarises the current options and strategies in development to antagonise anticoagulants with a focus on the status of the development of antidotes for the oral direct FXa and FIIa inhibitors.

Topics: Administration, Oral; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticoagulants; Antithrombins; Benzamides; Clinical Trials as Topic; Dabigatran; Factor Xa; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Hemostatics; Heparin; Humans; Infusions, Parenteral; Intracranial Hemorrhages; Polysaccharides; Protamines; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiazoles; Thrombosis; Vitamin K

Vitamin K is routinely administered after birth in the UK to prevent haemorrhagic disease of the newborn. Despite this, vitamin K-deficient coagulopathy still occurs in infants with high morbidity and mortality. Up to 50% of late onset bleeding presents with intracranial haemorrhage. The risk of developing vitamin K coagulopathy is higher in infants with cystic fibrosis (CF) and those that are exclusively breast fed due to low vitamin K levels in breast milk and intestinal changes in bacterial flora. Oral vitamin K supplementation is a simple addition to routine CF treatment during infancy to prevent complications from significant coagulopathy.

Topics: Administration, Oral; Cystic Fibrosis; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Male; Tomography, X-Ray Computed; Vitamin K; Vitamin K Deficiency; Vitamins

Central nervous system (CNS) hemorrhage is a potentially life-threatening condition, especially in patients with acquired coagulopathy. In this setting, treatment of CNS bleeding includes hemostatic therapy to replenish coagulation factors. There is currently a debate over the hemostatic efficacy of plasma in many clinical settings, alongside increasing concern about transfusion-associated adverse events. Despite these concerns, plasma is widely used. Moreover, plasma transfusion practice is variable and there is currently no uniform approach to treatment of traumatic, surgical or spontaneous CNS hemorrhage. This study addresses the need for guidance on the indications and potential risks of plasma transfusion in these settings. An Expert Consensus Panel was convened to develop recommendations guiding the use of plasma to treat bleeding and/or coagulopathy associated with CNS hemorrhage. The panel did not advise on the best treatment available but rather proposed recommendations to be used in the formulation of local procedures to support emergency physicians in their decision-making process.. Evidence was systematically gathered from the literature and rated using methods established by the Scottish Intercollegiate Guidelines Network. The evidence was used to develop graded consensus recommendations, which are presented along with the evidence-based rationale for each in this report.. Sixty-five articles were identified covering both vitamin K antagonist-anticoagulation reversal and treatment of bleeding/coagulopathy in non-anticoagulated patients. Recommendations were then developed in four clinical scenarios within each area, and agreed on unanimously by all members of the panel.. The Panel considered plasma to be reasonable therapy for CNS hemorrhage requiring urgent correction of coagulopathy, although physicians should be prepared for potential cardiopulmonary complications, and evidence suggests that alternative therapies have superior risk-benefit profiles. Plasma could not be recommended in the absence of hemorrhage or coagulopathy. Consideration of the absolute risks and benefits of plasma therapy before transfusion is imperative.

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Component Transfusion; Humans; Intracranial Hemorrhages; Plasma; Practice Guidelines as Topic; Vitamin K; Warfarin

Anticoagulants are effective at preventing and treating thrombosis, but can cause bleeding. For decades, vitamin K antagonists (VKAs) have been the only available oral anticoagulants. The development of non-VKA oral anticoagulants (NOACs), which inhibit either factor Xa or thrombin stoichiometrically, has provided alternatives to VKAs for several indications. The results of recent large-scale randomised controlled trials comparing NOACs with VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation (AF) have produced some unexpected results. As a group, NOACs showed similar efficacy as warfarin, but a reduced risk of major bleeding. The reduction in bleeding with NOACs was greatest with intracranial hemorrhage. In contrast, the relative risk of gastro-intestinal bleeding was increased with some NOACs. In this review, we explore the potential mechanisms as well as the implications of these organ-specific bleeding patterns.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation Factors; Endothelium, Vascular; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hemorrhage; Humans; International Normalized Ratio; Intestinal Absorption; Intracranial Hemorrhages; Organ Specificity; Randomized Controlled Trials as Topic; Stroke; Thrombophilia; Thromboplastin; Vitamin K; Warfarin

The incidence of intracranial bleeding is known to be markedly higher in Japan and other East Asian countries than in countries outside of East Asia. Non-vitamin K antagonist oral anticoagulants (NOACs) have much lower risk of intracranial bleeding than warfarin, so we reviewed the effect of this class of drugs on intracranial bleeding in Asian patients with non-valvular atrial fibrillation (NVAF). Warfarin therapy in Asian or East Asian populations appears to be associated with lower efficacy, poorer safety and a much greater risk of intracranial bleeding when compared with non-Asian or non-East Asian groups. Reflecting the higher incidence of intracranial bleeding in Asia and East Asia, Asian physicians in charge usually keep the prothrombin time-international normalized ratio (PT-INR) lower than is the case in Western countries. Irrespective of the lower PT-INR of warfarin, the incidence of intracranial bleeding is still high in Asia and East Asia. Because each NOAC strongly reduces the incidence of intracranial bleeding when compared with warfarin, use of dabigatran, rivaroxaban, apixaban or edoxaban would seem the best option for stroke prevention when treating Asian patients, including Japanese with NVAF.

Topics: Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Humans; Incidence; International Normalized Ratio; Intracranial Hemorrhages; Japan; Stroke; Vitamin K

The usefulness of anticoagulation in patients with atrial fibrillation (AF) is well known. However, the inherent limitations of vitamin K antagonists (VKAs) have made the development of new oral anticoagulants necessary. Drugs directed against thrombin or the factor Xa are currently available.. These molecules, being administered at fixed doses and not requiring laboratory monitoring, overcome one crucial problem associated with the use of VKAs. However, data about the bleeding risk related to the use of these molecules should be further analyzed.. The efficacy of direct anticoagulants (DACs) in AF-related stroke prevention has been considered the primary outcome in all Phase III published trials. On the other hand, the reduction of the bleeding risk is an important goal achieved by the DACs as compared with VKAs. Besides data deriving from randomized trials, when talking about new drugs, the need of evidences from the 'everyday clinical practice' are often requested. The aim of this literature revision is to report and analyze data from specific subgroups about which little is known. In particular, information about the use of DACs in oncologic patients, in patients receiving concomitant antiplatelet drugs and in the perioperative period is currently lacking. The parallel evaluation of all these data may lead to the identification of clinical and demographical criteria to choose when to switch to DACs.

Topics: Animals; Anticoagulants; Antimetabolites; Antithrombins; Atrial Fibrillation; Clinical Trials as Topic; Drugs, Investigational; Humans; Intracranial Hemorrhages; Stroke; Vitamin K

Seizures and intracranial hemorrhage are possible medical diseases that any obstetrician may encounter. This article reviews the cause, treatment, and medical management in pregnancy for seizures and intracranial hemorrhage, and how the two can overlap into preeclampsia or eclampsia. This article also highlights some challenging management issues from the obstetrician's perspective.

Topics: Anticonvulsants; Carbamazepine; Congenital Abnormalities; Eclampsia; Epilepsy; Female; Folic Acid; Heparin; Humans; Infant, Newborn; Intracranial Hemorrhages; Lamotrigine; Monitoring, Physiologic; North America; Phenobarbital; Phenytoin; Pregnancy; Risk Factors; Seizures; Subarachnoid Hemorrhage; Triazines; Valproic Acid; Vitamin K

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Fibrinolytic Agents; Hemostatics; Humans; Intracranial Hemorrhages; Intraoperative Period; Perioperative Care; Platelet Aggregation Inhibitors; Preoperative Care; Vitamin K

Non-valvular AF is the most common cardiac arrhytmia. Its incidence increases with age. AF is an independent risk factor for ischaemic stroke, representing a five times higher risk for it, associated with a high mortality rate. Beside AF, there are several other risk factors which influence the risk of stroke. Stroke risk calculator can be used to assess the risk of patient having a stroke. The most endangered group of patients with AF are those who have already suffered from cerebrovascular event. The only effective medication for prevention of stroke due to AF had been the application of vitamin K antagonists (VKA) which considerably decrease the rate of ischaemic event in a patient with AF providing that the INR is in the therapeutic range. VKA have several limitations of use in clinical practice and the fear of bleeding complications results an underusing of these drugs. Only 50% of all patients treated with VKA reaches the therapeutic range of INR. The breakthrough of prevention of stroke in recent years is undisputedly the coming out of novel oral anticoagulants (NOACs, thrombin and Xa-factor inhibitors). Recent studies suggest that these novel drugs prove the same efficacy as VKA drugs, furthermore dabigatran in a dose of 2 x 150 mg or apixaban in 2 x 5 mg was statistically superior to warfarin in the prevention of stroke. NOACs have shown a large reduction in intracranial hemorrhage compared with warfarin. They are given as a fixed dose and do not require persistent monitoring making them much more convenient. NOACs at guidelines of European Society of Cardiology act as a preferable drugs in case of ischaemic stroke with AF Probably the extended use of NOACs in clinical practice will be the mainstream of stroke prevention in the future.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Brain Ischemia; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Humans; International Normalized Ratio; Intracranial Hemorrhages; Pyridines; Risk Assessment; Risk Factors; Stroke; Vitamin K

The new oral anticoagulants (NOACs) dabigatran etexilate, rivaroxaban, and apixaban have been extensively studied for prevention and treatment of venous thromboembolic disease and for stroke prevention in atrial fibrillation. Elderly patients have the highest incidence of thrombotic complications but also have the highest risk of anticoagulant associated bleeding. In this review we critically examine the balance between risks and benefits of NOACs compared with vitamin K antagonists in elderly patients enrolled in phase 3 randomized controlled trials for the management of venous thrombosis and stroke prevention in atrial fibrillation. Results show that the favourable balance between risks and benefits of NOACs is preserved in the elderly population.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Drug Administration Schedule; Humans; Intracranial Hemorrhages; Morpholines; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Vitamin K; Warfarin

Treatment with vitamin K antagonists are subject to a common iatrogenic mainly characterized by hemorrhagic stroke. Their narrow therapeutic range associated with variability largely explains this phenomenon. New oral anticoagulants (NOAC) are now available. dabigatran (Pradaxa®) is a direct and specific thrombin inhibitor. It is excreted mainly by the kidney and is the only which can be dialyzed. Rivaroxaban (Xarelto®) and apixaban (Eliquis®) are factor X activated direct inhibitors. They are highly bound to plasma proteins and are metabolized mainly by the liver, via CYP3A4. All NOAC are substrates of P-glycoprotein (P-gp). Due to pharmacological changes, some populations at risk were identified: patients with hepatic impairment, renal impairment, elderly patients or low weight. Some pharmacokinetic or pharmacodynamic drug interactions alter the concentration and the expected impact of NOAC. The NOAC does not require biological monitoring. They interfere with the routine coagulation tests which should be interpreted with caution. Specific tests exist and can be used in case of emergencies. Currently, no antidote is available. The new oral anticoagulant look promising in the elderly. However, certain rules must be followed to reduce the risk of iatrogenic.

Topics: Administration, Oral; Aged; Anticoagulants; Benzimidazoles; beta-Alanine; Cerebral Infarction; Dabigatran; Dose-Response Relationship, Drug; Drug Interactions; Drugs, Investigational; Humans; Iatrogenic Disease; Intracranial Hemorrhages; Morpholines; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Vitamin K

A best evidence topic in cardiac surgery was written according to the structured protocol. The question addressed was about the best time to restart anticoagulation in patients with intracranial bleed with a prosthetic valve in situ. This difficult clinical decision has to balance the risk of thromboembolism during the period that the anticoagulation was reversed and later withheld vs the risk of haematoma expansion or rebleed if the anticoagulation was started early. Altogether, more than 80 papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. There were two prospective studies and eight retrospective studies. There were no randomized controlled trials on this topic. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Seven studies reported the strategy of reversal of anticoagulation with vitamin K, fresh frozen plasma or prothrombin concentrate. The emphasis was on prompt initial reversal of anticoagulation; however, the best agent for reversal was not defined. Four studies dealt exclusively with intracranial bleed in patients with prosthetic valve in situ. The remaining six studies on intracranial bleed had only a subset of patients with a prosthetic valve in situ. The anticoagulation was restarted with heparin and later switched to oral anticoagulant. Thromboembolic events during the period of reversal and cessation of anticoagulants were low (5%) as was the incidence of rebleed or haematoma expansion (0.5%). We conclude that anticoagulation can safely be withheld for a short period, up to 7-14 days in a patient with intracranial bleed with a very low probability of thromboembolic phenomenon. In patients with prosthetic valves, in situ anticoagulation in the form of heparin can safely be restarted as early as 3 days and switched to oral anticoagulation in the form of warfarin at 7 days without major concerns of bleeding.

Topics: Administration, Oral; Anticoagulants; Benchmarking; Blood Coagulation Factors; Drug Administration Schedule; Drug Substitution; Evidence-Based Medicine; Heart Valve Prosthesis Implantation; Heparin; Heparin Antagonists; Humans; Intracranial Hemorrhages; Plasma; Risk Assessment; Risk Factors; Thromboembolism; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Vitamin K antagonists (warfarin, syncumar, phenylin, etc.) are commonly used to treat and prevent thrombotic diseases. The risk for varying degrees of hemorrhagic syndrome (intracranial hemorrhage in particular) is the most important problem in the use of drugs from this group. The rapid neutralization of the effects of used anticoagulants, which is verified by correcting the international normalized ratio (INR), is required in these cases and when emergency surgical interventions are needed. Transfusions of prothrombin complex concentrates (PCCs) in combination of vitamin K preparations are optimal for this purpose. The reason for the rational use of PCCs to promptly correct INR is the balanced composition of this transfusion medium (a combination of blood coagulation factors and biological anticoagulants). This regimen for emergency correction of INR minimizes the risk of thrombotic events.

Topics: Anticoagulants; Blood Coagulation Factors; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Syndrome; Time Factors; Vitamin K

Atrial fibrillation (AF) is the most common cardiac arrhythmia and an important independent stroke risk factor, especially in the elderly. This article provides the reader with an overview as well as an update on primary and secondary stroke prevention strategies in patients with AF. Vitamin K antagonists remain the cornerstone therapy in AF patients at high risk of stroke. Both aspirin monotherapy and the combination of aspirin and clopidogrel are inferior to vitamin K antagonists in patients with AF. The new direct thrombin inhibitor dabigatran is at least as effective as warfarin and leads to a significant and clinically relevant decrease in hemorrhagic stroke and intracranial bleeds. Interventional therapies such as percutaneous closure of the left atrial appendage or radiofrequency catheter ablation have not yet been proven to decrease the stroke risk in patients with AF.

Topics: Aged; Animals; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Platelet Aggregation Inhibitors; Primary Prevention; Risk Factors; Secondary Prevention; Stroke; Vitamin K

Topics: Administration, Oral; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Factors; Contraindications; Humans; Intracranial Hemorrhages; Phenprocoumon; Plasma; Vitamin K

Spontaneous intracerebral haemorrhage is one of the most feared complications of long-term anticoagulation. Warfarin therapy not only increases the likelihood of suffering an intracranial haemorrhage, but also increases the mortality associated with it. This review aims to examine the incidence, pathogenesis, and outcome following a warfarin associated intracranial haemorrhage. It also evaluates the available evidence regarding optimal management of these patients, including timing and strategies for reversal of the coagulopathy, the role of neurocritical care and surgery, and indications for re-anticoagulation once the acute phase has past. The specific management of patients with prosthetic heart valves is also discussed. A summary of current societal guidelines is also included, as are some key practice points.

Topics: Anticoagulants; Blood Coagulation Factors; Factor VIIa; Humans; Incidence; Intracranial Hemorrhages; Recombinant Proteins; Vitamin K; Warfarin

Optimal timing for restarting anticoagulant therapy after intracranial bleeding is a critical issue. The purpose of this systematic review is to summarize published studies on the management of oral anticoagulant therapy after intracranial bleeding secondary to the use of vitamin K antagonists in patients with a mechanical heart valve. A computer-assisted search of the MEDLINE and EMBASE electronic databases till January 2008 was performed. Two investigators independently performed study selection and completed a predefined quality assessment and data extraction form. Main inclusion criterion was the enrolment of patients with a mechanical heart valve and intracranial haemorrhage during oral anticoagulant treatment. Any randomised controlled trial, observational cohort study, case series and reports was included. No randomised controlled trials were identified. Six observational cohort studies were included in the final analysis. All studies were of low quality. A total of 120 patients were enrolled. Anticoagulation was restarted within a broad time range (2 days to 3 months). Four ischaemic strokes and two recurrent cerebral haemorrhages occurred after anticoagulation was restarted after a mean follow-up of 7.9 months. Eighteen patients were described in the selected case reports. Anticoagulant therapy was restarted within four days to eight weeks. Two patients had a recurrent haemorrhagic event, and no ischaemic events were reported. In conclusion, restarting oral anticoagulant therapy few days and, indirectly, stopping anticoagulant therapy for a few days (even for 7-14 days) after the occurrence of cerebral haemorrhage are both safe. However, well-designed studies are strongly recommended to provide better evidence.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Child; Drug Administration Schedule; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Intracranial Hemorrhages; Male; Middle Aged; Risk Assessment; Thromboembolism; Treatment Outcome; Vitamin K

Stroke remains an increasing worldwide cause of disability and mortality, and it is the second leading cause of death in industrialized countries. Patients with atrial fibrillation form a unique group with increased risk of cardioembolic stroke. Despite the widespread application of the National Institutes of Health stroke scale and guidelines, patients with atrial fibrillation represent a clinically challenging group that deserves a special approach during the acute stroke phase. The mechanism of stroke in these patients is either cardioembolic [especially with an international normalized ratio (INR) < 2.0] or hemorrhagic (especially with INR > 5.0) (Figure 1). Atrial fibrillation with valvular heart disease significantly increases the risk for ischemic stroke. Specifically, patients with mitral stenosis who develop atrial fibrillation increase their risk of cardioembolism by 3 to 7 times. Many patients with atrial fibrillation still develop ischemic or hemorrhagic stroke despite appropriate use of anticoagulation. Prior stroke, transient ischemic attacks, congestive heart failure, hypertension, age > 75, and diabetes mellitus are all well-established risk factors for the development of stroke in patients with atrial fibrillation. The CHADS-2 score is the most widely studied and clinically used method for stratifying patients with nonrheumatic atrial fibrillation. In our review, we present the most recent clinical guidelines and trends for the approach to and management of this patient group.

Topics: Anticoagulants; Antifibrinolytic Agents; Aspirin; Atrial Fibrillation; Factor VIIa; Heparin; Humans; Intracranial Hemorrhages; Plasma; Recombinant Proteins; Stroke; Thrombolytic Therapy; Vitamin K; Warfarin

Drugs that inhibit platelet function are widely used to decrease the risk of occlusive arterial events in patients with atherosclerosis. There are three families of anti-platelet agents with proven clinical efficacy: (1) cyclo-oxygenase inhibitors, such as aspirin; (2) adenosine diphosphate receptor antagonists, such as the thienopyridine compounds ticlopidine and clopidogrel; and (3) glycoprotein IIb/IIIa antagonists. All these drugs are used during coronary interventions and in the medical management of acute coronary syndromes, while only aspirin and thienopyridine compounds are used in the long-term prevention of cardiovascular and cerebrovascular events in patients at risk. Despite the good risk-to-benefit ratio of anti-platelet agents, the risk of severe bleeding complications, including cerebral haemorrhage, is slightly increased, albeit to a much lesser extent than that associated with the use of other antithrombotic drugs, such as anticoagulants or thromobolytic agents. In addition, it must be noted that the increased incidence of haemorrhagic stroke is usually outweighed by a significant decrease in the incidence of ischaemic strokes. The combination of aspirin and vitamin K antagonists may be associated with the heightened risk of cerebral haemorrhage, compared to treatment with either drug alone.

Topics: Acute Coronary Syndrome; Aspirin; Cerebral Hemorrhage; Clinical Trials as Topic; Humans; Intracranial Hemorrhages; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Purinergic P2 Receptor Antagonists; Randomized Controlled Trials as Topic; Risk; Treatment Outcome; Vitamin K

Topics: Blood Component Transfusion; Disseminated Intravascular Coagulation; Hemostasis; Humans; Infant, Newborn; Intracranial Hemorrhages; Liver Diseases; Plasma; Vitamin K

Biliary atresia (BA) is a rare disease, characterized by progressive and obliterative cholangiopathy, and is one of the major causes of secondary vitamin K deficiency in infancy. We describe 15 infants (10 female, 5 male) with BA, presenting with intracranial hemorrhage (ICH), including 10 subdural hemorrhages, 4 subarachnoid hemorrhages, 2 intraventricular hemorrhages, and 1 intraparenchymal hemorrhage. The age at onset of ICH ranged from 26 to 79 (mean 54.2) days. Eight patients underwent successful surgical evacuation of ICH, following administration of vitamin K. All 15 patients underwent Kasai portoenterostomy for BA 8-30 days after onset. During a mean follow-up period of 86.8 (range 2-352) months, 4 patients died of liver failure despite lack of neurological sequelae. Two patients underwent living-related donor and 1 patient living-unrelated donor liver transplantation. Only 2 patients suffered neurological signs and symptoms, including mental retardation and epilepsy, whereas 3 were noted to have temporary hemiparesis which recovered completely during the follow-up period. The possibility of BA should be considered in the treatment of ICH due to vitamin K deficiency, since it is reported to be one of the major causes of secondary vitamin K deficiency. Urgent surgical intervention for ICH can be performed successfully following sufficient administration of vitamin K or fresh frozen human plasma. Moreover, early performance of Kasai portoenterostomy is possible even for patients who have undergone craniotomy.

Topics: Biliary Atresia; Epilepsy; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Intellectual Disability; Intracranial Hemorrhages; Liver Failure; Liver Transplantation; Male; Paresis; Vitamin K; Vitamin K Deficiency; Vitamins

Topics: Adult; Aged; Anticoagulants; Factor VII; Factor VIIa; Female; Hematoma, Subdural; Humans; Intracranial Hemorrhages; Israel; Male; Middle Aged; Recombinant Proteins; Stroke; Vitamin K

Anticoagulation with antivitamin K (AVK) is very effective for primary and secondary prevention of thromboembolic events. However, questions persist about the risks and management of over-anticoagulation. For reversal of excessive anticoagulation by warfarin, AVK withdrawal, oral or parenteral vitamin K administration, prothrombin complex or fresh frozen plasma may be used, depending on the excess of anticoagulation, the existence and site of active bleeding, patient characteristics and the indication for AVK. In over-anticoagulated patients, vitamin K aims at rapid lowering of the international normalized ratio (INR) into a safe range to reduce the risk of major bleeding and therefore improving patient outcome without exposing the patient to the risk of thromboembolism due to overcorrection, resistance to AVK, or an allergic reaction to the medication. The risk of bleeding increases dramatically when the INR exceeds 4.0-6.0, although the absolute risk of bleeding remains fairly low, <5.5 per 1000 per day. Patient characteristics, including advanced age, treated hypertension, history of stroke, and concomitant use of various drugs, affect the risk of bleeding. The absolute risk of thromboembolism associated with overcorrection appears to be in the same range as the risk of bleeding due to over-anticoagulation. The use of vitamin K in patients with warfarin over-anticoagulation lowers excessively elevated INR faster than withholding warfarin alone; however, it has not been clearly demonstrated that vitamin K treatment does, in fact, lower the risk of major hemorrhage. As vitamin K administration via the intravenous route may be complicated by anaphylactoid reactions, and via the subcutaneous route by cutaneous reactions, oral administration is preferred. A dose of 1-2.5mg of oral phytomenadione (vitamin K(1)), reduces the range of INR from 5.0-9.0 to 2.0-5.0 within 24-48 hours, and for an INR >10.0, a dose of 5mg may be more appropriate. Overcorrection of the INR or resistance to warfarin is unlikely if the above doses of vitamin K are used. Vitamin K is less effective for over-anticoagulation after treatment with acenocoumarol or phenprocoumon than after treatment with warfarin.

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Coagulation; Blood Coagulation Factors; Dose-Response Relationship, Drug; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Risk Factors; Vitamin K

Warfarin is the most commonly used oral anticoagulant in the UK. It is associated with few side effects apart from haemorrhage. The most appropriate way to reverse the anticoagulant effect of warfarin depends on the clinical circumstances. In serious bleeding, rapid reversal is required, whereas in minor bleeding or asymptomatic over anticoagulation, a more leisurely approach is usually appropriate. This review discusses the current approaches to warfarin reversal in clinical practice. The development of a uniform approach to warfarin reversal in the Northern Region is described.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Child; Coagulants; Drug Administration Schedule; Factor VII; Factor VIIa; Hemorrhage; Humans; Intracranial Hemorrhages; Plasma; Practice Guidelines as Topic; Recombinant Proteins; Vitamin K; Warfarin

There is currently little evidence for the optimal dosing strategy of four-factor prothrombin complex concentrates (PCC) in vitamin K antagonist (VKA)-related bleeds. The generally accepted dosing strategy is the use of a variable dose calculated using patient-specific characteristics as per manufacturer's instruction. However, evidence exists that the use of a fixed low dose of 1000 international units of factor IX (IU fIX) might also suffice. Recent studies indicate that in terms of haemostatic effectiveness, the fixed dosing strategy might be even superior to the variable dosing strategy. The PROPER3 (PROthrombin complex concentrate: Prospective Evaluation and Rationalisation, number 3) study aims to confirm the non-inferiority, and explore superiority, in haemostatic effectiveness of the fixed PCC dosing strategy compared with the variable dosing strategy in VKA-related extracranial bleeding emergencies.. The study is designed as a randomised controlled multicentre non-inferiority trial. Eligibility criteria are an indication for PCC due to VKA-related extracranial bleeding in subjects 18 years of age or older. The control group will receive a variable dose, determined by patient-specific bodyweight and international normalised ratio. The intervention group is dosed a fixed 1000 IU fIX PCC. Primary outcome is the haemostatic effectiveness of both treatments, as defined by the 2016 International Society on Thrombosis and Haemostasis (ISTH) criteria. The sample size is set at 155 patients per treatment arm, requiring 310 patients in total. Non-inferiority on the proportion (risk) difference of the primary outcome will be evaluated using the asymptotic Wald test for non-inferiority. The non-inferiority margin is set at 6%. The primary analysis will be based on the per-protocol population.. Study results will be published in an international journal, communicated to discipline-specific associations and presented at (inter)national meetings and congresses.. EUCTR2014-000392-33; Pre-results.

Topics: Anticoagulants; Blood Coagulation Factors; Dose-Response Relationship, Drug; Humans; Intention to Treat Analysis; Intracranial Hemorrhages; Treatment Outcome; Vitamin K

Haematoma expansion is a major cause of mortality in intracranial haemorrhage related to vitamin K antagonists (VKA-ICH). Normalisation of the international normalised ratio (INR) is recommended, but optimum haemostatic management is controversial. We assessed the safety and efficacy of fresh frozen plasma (FFP) versus prothrombin complex concentrate (PCC) in patients with VKA-ICH.. We did an investigator-initiated, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Patients aged at least 18 years with VKA-ICH who presented within 12 h after symptom onset with an INR of at least 2·0 were randomly assigned (1:1) by numbered sealed envelopes to 20 mL/kg of intravenous FFP or 30 IU/kg of intravenous four-factor PCC within 1 h after initial cerebral CT scan. The primary endpoint was the proportion of patients with INR 1·2 or lower within 3 h of treatment initiation. Masking of treatment was not possible, but the primary analysis was observer masked. Analyses were done using a treated-as-randomised approach. This trial is registered with EudraCT, number 2008-005653-37, and ClinicalTrials.gov, number NCT00928915.. Between Aug 7, 2009, and Jan 9, 2015, 54 patients were randomly assigned (26 to FFP and 28 to PCC) and 50 received study drug (23 FFP and 27 PCC). The trial was terminated on Feb 6, 2015, after inclusion of 50 patients after a safety analysis because of safety concerns. Two (9%) of 23 patients in the FFP group versus 18 (67%) of 27 in the PCC group reached the primary endpoint (adjusted odds ratio 30·6, 95% CI 4·7-197·9; p=0·0003). 13 patients died: eight (35%) of 23 in the FFP group (five from haematoma expansion, all occurring within 48 h after symptom onset) and five (19%) of 27 in the PCC group (none from haematoma expansion), the first of which occurred on day 5 after start of treatment. Three thromboembolic events occurred within 3 days (one in the FFP group and two in the PCC group), and six after day 12 (one and five). 43 serious adverse events (20 in the FFP group and 23 in the PCC group) occurred in 26 patients. Six serious adverse events were judged to be FFP related (four cases of haematoma expansion, one anaphylactic reaction, and one ischaemic stroke) and two PCC related (ischaemic stroke and pulmonary embolism).. In patients with VKA-related intracranial hemorrhage, four-factor PCC might be superior to FFP with respect to normalising the INR, and faster INR normalisation seemed to be associated with smaller haematoma expansion. Although an effect of PCC on clinical outcomes remains to be shown, our data favour the use of PCC over FFP in intracranial haemorrhage related to VKA.. Octapharma.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Blood Component Transfusion; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Outcome Assessment, Health Care; Plasma; Single-Blind Method; Vitamin K

We conducted a multicenter retrospective cohort study to elucidate the characteristics of intracranial hemorrhage (ICH) in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants (NOACs).. We sent a questionnaire to the directors of 241 stroke centers in Japan to establish the clinical characteristics of NOAC-associated cerebral hemorrhage (CH), including hematoma size, hematoma enlargement (HE) and in-hospital mortality of patients treated in their institutions. We undertook a literature review to establish the clinical characteristics of warfarin-associated CH and compared these with our data. We received 174 responses (72.2%), of which 67 (38.5%) gave anonymous details of 130 eligible patients (male, 67.7%; mean age, 77.3±8.3 years, in-hospital mortality rate, 11.5%). We judged that 87 of the 130 patients had presented with CH: one-fifth had taken antiplatelet drugs. We found that the incidences of HE and mortality in the 87 patients presenting with NOAC-associated CH were lower than would have been expected in those with warfarin-associated CH (17% vs. 26%, and 16% vs. 35%, respectively).. More than half the stroke center directors who responded to our questionnaire had not experienced cases of NOAC-associated ICH. Compared with warfarin, NOACs appear to present a lower risk of HE and death in patients with atrial fibrillation who develop CH.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hospital Mortality; Humans; Intracranial Hemorrhages; Japan; Male; Retrospective Studies; Vitamin K; Warfarin

Intracranial hemorrhage (ICH) is a life-threatening complication of anticoagulation.. We investigated the rate, outcomes, and predictors of ICH in 14 264 patients with atrial fibrillation from Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Cox proportional hazards modeling was used.. During 1.94 years (median) of follow-up, 172 patients (1.2%) experienced 175 ICH events at a rate of 0.67% per year. The significant, independent predictors of ICH were race (Asian: hazard ratio, 2.02; 95% CI, 1.39-2.94; black: hazard ratio, 3.25; 95% CI, 1.43-7.41), age (1.35; 1.13-1.63 per 10-year increase), reduced serum albumin (1.39; 1.12-1.73 per 0.5 g/dL decrease), reduced platelet count below 210×10(9)/L (1.08; 1.02-1.13 per 10×10(9)/L decrease), previous stroke or transient ischemic attack (1.42; 1.02-1.96), and increased diastolic blood pressure (1.17; 1.01-1.36 per 10 mm Hg increase). Predictors of a reduced risk of ICH were randomization to rivaroxaban (0.60; 0.44-0.82) and history of congestive heart failure (0.65; 0.47-0.89). The ability of the model to discriminate individuals with and without ICH was good (C-index, 0.69; 95% CI, 0.64-0.73).. Among patients with atrial fibrillation treated with anticoagulation, the risk of ICH was higher among Asians, blacks, the elderly, and in those with previous stroke or transient ischemic attack, increased diastolic blood pressure, and reduced platelet count or serum albumin at baseline. The risk of ICH was significantly lower in patients with heart failure and in those who were randomized to rivaroxaban instead of warfarin. The external validity of these findings requires testing in other atrial fibrillation populations.

Topics: Aged; Anticoagulants; Asian People; Atrial Fibrillation; Black People; Double-Blind Method; Embolism; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Morpholines; Prospective Studies; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Vitamin K; Warfarin

Intracerebral haemorrhage is the most feared complication in patients who are on treatment with vitamin K antagonists. Vitamin K antagonist related intracerebral haemorrhage occurs in about 10% of patients. Intracerebral haemorrhage has the worst prognosis of all subtypes of stroke including spontaneous intracerebral haemorrhage, and a mortality rate of up to about 65%. The higher rate of haematoma expansion due to rebleeding is thought to be responsible for the higher mortality. Current international treatment recommendations include fresh frozen plasma and prothrombin complex concentrate. It is known that these substances lower the international normalised ratio, and thus it is assumed that normalisation of coagulopathy may lead to haemostasis and reduction of rebleeding. However, the issue of whether to use fresh frozen plasma or prothrombin complex concentrate for urgent reversal of vitamin K antagonists is unresolved: safety and efficacy of these treatments have never been studied in a randomised controlled trial. Our questions are: how effective are the two substances in normalisation of the international normalized ratio? How feasible is it to apply either of these treatments in an acute situation? What is the safety profile of each of these substances? Is there a difference in haematoma growth and clinical outcome?. We designed a prospective, randomised, controlled multicentre trial to compare biological efficacy and safety of fresh frozen plasma and prothrombin complex concentrate in vitamin K antagonist related intracerebral haemorrhage. The study is observer-blinded for laboratory, neuroradiological, and clinical outcomes. Patients will be included if a computed tomography scan shows an intraparenchymal or subdural haematoma within 12 h after onset of symptoms, if the patient is on treatment with vitamin K antagonists, and the international normalized ratio is ≥2. Primary endpoint is the normalisation of the international normalized ratio (≤1·2) within three-hours after the start of antagonising therapy. Main exclusion criteria are secondary intracerebral haemorrhage, other known coagulopathies, and known acute ischaemic events.. We discuss the rationale of our trial on the basis of the current recommendations and specific aspects of trial design as, time window, choice of endpoints, dosing of fresh frozen plasma and prothrombin complex concentrate, monitoring and analysis of safety parameters, and rescue treatment.. This will be the first prospective trial comparing fresh frozen plasma and prothrombin complex concentrate in the indication of vitamin K antagonist related intracerebral hemorrhage. Recruitment of subjects started in August 2009. Until now, 19 patients have been included.

Topics: Acute Disease; Adolescent; Adult; Aged; Anticoagulants; Coumarins; Endpoint Determination; Female; Hematoma, Subdural; Hemostasis; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Plasma; Prospective Studies; Prothrombin; Research Design; Risk Assessment; Tomography, X-Ray Computed; Vitamin K; Young Adult

The comparison of anticoagulants dabigatran and warfarin might be most equitable in vitamin K antagonist (VKA)-naive patients.. Warfarin and 2 doses of dabigatran-110 mg BID (D110) and 150 mg BID (D150)-were compared in a balanced population of VKA-naive (≤62 days of lifetime VKA exposure, with 33% never prescribed a VKA) and VKA-experienced patients with atrial fibrillation (n=18 113). For VKA-naive and -experienced patients assigned warfarin, the time in therapeutic range (international normalized ratio 2.0 to 3.0) was 62% and 67%, respectively, and 61% and 66% for those never and ever prescribed a VKA. In VKA-naive patients, stroke and systemic embolism rates were 1.57%, 1.07%, and 1.69% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.65); D150 was superior (P=0.005). Major bleeding rates were 3.11%, 3.34%, and 3.57% per year, respectively. D110 and D150 were similar to warfarin (P=0.19 and P=0.55). Intracranial bleeding rates were 0.19%, 0.33%, and 0.73% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 and P=0.005). In VKA-experienced patients, stroke and systemic embolism rates were 1.51%, 1.15%, and 1.74% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.32); D150 was superior (P=0.007). Major bleeding rates were 2.66%, 3.30%, and 3.57% per year, respectively. D110 was lower than warfarin (P=0.003); D150 was similar (P=0.41). Intracranial bleeding rates were 0.26%, 0.32%, and 0.79% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 for both). Results were similar for patients never on a VKA.. Previous VKA exposure does not influence the benefits of dabigatran at either dose compared with warfarin.. http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Dose-Response Relationship, Drug; Embolism; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Pyridines; Risk Factors; Stroke; Treatment Outcome; Vitamin K; Warfarin

Use of oral vitamin K antagonists (VKAs) may place patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke caused by large vessel occlusion at increased risk of complications.. To determine the association between recent use of a VKA and outcomes among patients selected to undergo EVT in clinical practice.. Retrospective, observational cohort study based on the American Heart Association's Get With the Guidelines-Stroke Program between October 2015 and March 2020. From 594 participating hospitals in the US, 32 715 patients with acute ischemic stroke selected to undergo EVT within 6 hours of time last known to be well were included.. VKA use within the 7 days prior to hospital arrival.. The primary end point was symptomatic intracranial hemorrhage (sICH). Secondary end points included life-threatening systemic hemorrhage, another serious complication, any complications of reperfusion therapy, in-hospital mortality, and in-hospital mortality or discharge to hospice.. Of 32 715 patients (median age, 72 years; 50.7% female), 3087 (9.4%) had used a VKA (median international normalized ratio [INR], 1.5 [IQR, 1.2-1.9]) and 29 628 had not used a VKA prior to hospital presentation. Overall, prior VKA use was not significantly associated with an increased risk of sICH (211/3087 patients [6.8%] taking a VKA compared with 1904/29 628 patients [6.4%] not taking a VKA; adjusted odds ratio [OR], 1.12 [95% CI, 0.94-1.35]; adjusted risk difference, 0.69% [95% CI, -0.39% to 1.77%]). Among 830 patients taking a VKA with an INR greater than 1.7, sICH risk was significantly higher than in those not taking a VKA (8.3% vs 6.4%; adjusted OR, 1.88 [95% CI, 1.33-2.65]; adjusted risk difference, 4.03% [95% CI, 1.53%-6.53%]), while those with an INR of 1.7 or lower (n = 1585) had no significant difference in the risk of sICH (6.7% vs 6.4%; adjusted OR, 1.24 [95% CI, 0.87-1.76]; adjusted risk difference, 1.13% [95% CI, -0.79% to 3.04%]). Of 5 prespecified secondary end points, none showed a significant difference across VKA-exposed vs VKA-unexposed groups.. Among patients with acute ischemic stroke selected to receive EVT, VKA use within the preceding 7 days was not associated with a significantly increased risk of sICH overall. However, recent VKA use with a presenting INR greater than 1.7 was associated with a significantly increased risk of sICH compared with no use of anticoagulants.

Topics: Administration, Oral; Aged; Anticoagulants; Brain Ischemia; Endovascular Procedures; Female; Fibrinolytic Agents; Hemorrhage; Hospital Mortality; Humans; International Normalized Ratio; Intracranial Hemorrhages; Ischemic Stroke; Male; Retrospective Studies; Thrombectomy; Treatment Outcome; Vitamin K

An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs).. An externally validated model improves ICH risk stratification.. Independent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register.. In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 0.28-0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non-VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 0.65-0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets.. Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Registries; Renal Insufficiency, Chronic; Risk Factors; Stroke; Vitamin K

Although oral anticoagulant use has been implicated in worse outcomes for patients with a traumatic brain injury (TBI), prior studies have mostly examined the use of vitamin K antagonists (VKAs). In an era of increasing use of direct oral anticoagulants (DOACs) in lieu of VKAs, the authors compared the survival outcomes of TBI patients on different types of premorbid anticoagulation medications with those of patients not on anticoagulation.. The authors retrospectively reviewed the records of 1186 adult patients who presented at a level I trauma center with an intracranial hemorrhage after blunt trauma between 2016 and 2022. Patient demographics; comorbidities; and pre-, peri-, and postinjury characteristics were compared based on premorbid anticoagulation use. Multivariable Cox proportional hazards regression modeling of mortality was performed to adjust for risk factors that met a significance threshold of p < 0.1 on bivariate analysis.. Of 1186 patients with a traumatic intracranial hemorrhage, 49 (4.1%) were taking DOACs and 53 (4.5%) used VKAs at the time of injury. Patients using oral anticoagulants were more likely to be older (p < 0.001), to have a higher Charlson Comorbidity Index (p < 0.001), and to present with a higher Glasgow Coma Scale (GCS) score (p < 0.001) and lower Injury Severity Score (ISS; p < 0.001) than those on no anticoagulation. Patients using VKAs were more likely to undergo reversal than patients using DOACs (53% vs 31%, p < 0.001). Cox proportional hazards regression demonstrated significantly increased hazard ratios (HRs) for VKA use (HR 2.204, p = 0.003) and DOAC use (HR 1.973, p = 0.007). Increasing age (HR 1.040, p < 0.001), ISS (HR 1.017, p = 0.01), and Marshall score (HR 1.186, p < 0.001) were associated with an increased risk of death. A higher GCS score on admission was associated with a decreased risk of death (HR 0.912, p < 0.001).. Patients with a traumatic intracranial injury who were on oral anticoagulant therapy before injury demonstrated higher mortality rates than patients who were not on oral anticoagulation after adjusting for age, comorbid conditions, and injury presentation.

Topics: Adult; Anticoagulants; Brain Injuries, Traumatic; Humans; Intracranial Hemorrhage, Traumatic; Intracranial Hemorrhages; Retrospective Studies; Risk Factors; Vitamin K

Topics: Brain Ischemia; Endovascular Procedures; Humans; Intracranial Hemorrhages; Retrospective Studies; Stroke; Thrombectomy; Treatment Outcome; Vitamin K

Topics: Brain Ischemia; Endovascular Procedures; Humans; Intracranial Hemorrhages; Retrospective Studies; Stroke; Thrombectomy; Treatment Outcome; Vitamin K

Mild traumatic brain injury (TBI) in anticoagulated patients is a common challenge for emergency departments because of lack of appropriate epidemiological data and huge management variability for those under oral anticoagulation therapy. Given the discrepancies between guidelines, the aim of the present study was to quantify the association between oral anticoagulant therapy (either vitamin K antagonist (VKA) or direct oral anticoagulant (DOAC)) and the post-traumatic intracranial hemorrhage worsening compared to admission CT scan.. We included all consecutive records of patients admitted to our emergency department for mild TBI as chief complaint and with a positive admission CT scan. After statistical univariate comparison, cause-specific hazard ratio (HR) and 95% confidence interval (CI) were determined with the use of Cox proportional hazard model.. In the study period, 4667 patients had a CT scan for mild TBI; 439 (9.4%) were found to have intracranial hemorrhage. Among these patients, 299 (68.1%) were prescribed observation and control CT: 46 (15.38%) were on anticoagulant therapy, 23 (50%) on VKA, and 23 (50%) on DOAC. In multivariate analysis, only oral anticoagulation therapy was significantly associated to an increased risk of intracranial hemorrhage progression (HR 2.58; 95% CI 1.411-4.703; p = .002 and HR 1.9; 95% CI 1.004-3.735; p = .0048 for VKA and DOAC, respectively). Surgery was due to isolated subdural hematoma in 87.5% of cases, to subdural hematoma associated with intraparenchymal hemorrhage in 9.38% and to intraparenchymal hemorrhage only in 3.12%; 13 cases (4.35%) deceased in intensive care unit.. In our series, anticoagulation was associated to a significant increase in intracranial progression, leaving the question open as to what this implies in current clinical practice; subdural hematoma was the major finding associated to evolution and surgery. Against this background, further studies are needed to clarify patients' management and DOAC safety profile compared to VKA in mild TBI.

Topics: Administration, Oral; Anticoagulants; Brain Concussion; Humans; Intracranial Hemorrhages; Risk Factors; Vitamin K

Background Clinical evidence on the safety and effectiveness of using direct oral anticoagulants (DOACs) in patients with atrial fibrillation after transcatheter aortic valve replacement (TAVR) remains limited. The aim of this study was to investigate the trends and outcomes of using DOACs in patients with TAVR and atrial fibrillation. Methods and Results Data from the STS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) Registry was used to identify patients who underwent successful TAVR with preexisting or incident atrial fibrillation who were discharged on oral anticoagulation between January 2013 and May 2018. Patients with a mechanical valve, valve-in-valve procedure, or prior stroke within a year were excluded. The adjusted primary outcome was 1-year stroke events. The adjusted secondary outcomes included bleeding, intracranial hemorrhage, and death. A total of 21 131 patients were included in the study (13 004 TAVR patients were discharged on a vitamin K antagonist and 8127 were discharged on DOACs.) The use of DOACs increased 5.5-fold from 2013 to 2018. The 1-year incidence of stroke was comparable between DOAC-treated patients and vitamin K antagonist-treated patients (2.51% versus 2.37%; hazard ratio [HR], 1.00; 95% CI, 0.81-1.23) whereas DOAC-treated patients had lower 1-year incidence of any bleeding (11.9% versus 15.0%; HR, 0.81; 95% CI, 0.75-0.89), intracranial hemorrhage (0.33% versus 0.59%; HR, 0.54; 95% CI, 0.33-0.87), and death (15.8% versus 18.2%; HR, 0.92; 95% CI, 0.85-1.00). Conclusions In patients with TAVR and atrial fibrillation, DOAC use, when compared with vitamin K antagonists, was associated with comparable stroke risk and significantly lower risks of bleeding, intracranial hemorrhage, and death at 1 year.

Topics: Anticoagulants; Aortic Valve; Aortic Valve Stenosis; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Intracranial Hemorrhages; Registries; Risk Factors; Stroke; Transcatheter Aortic Valve Replacement; Treatment Outcome; United States; Vitamin K

Fetal brain hemorrhage is rare. It is caused mainly by maternal trauma or fetal coagulation disorder, but in some cases, vitamin K deficiency may be the cause.. We describe the case of a pregnant woman with bowel obstruction who was susceptible to vitamin K deficiency due to oral diet restriction, decreased intestinal absorption, and limited intravenous vitamin K supplementation.. After 18 days of intermittent total parenteral nutrition, acute onset of severe fetal brain hemorrhage developed.. After acute onset of fetal brain hemorrhage, the patient underwent an emergency cesarean section at 25 + 3 weeks of gestation due to fetal non-reassuring fetal monitoring.. The Apgar score at birth was 0/0, and despite cardiopulmonary resuscitation, neonatal death was confirmed. After the baby was delivered, we checked the maternal upper abdominal cavity and found a massive adhesion in the small bowel to the abdominal wall near the liver and stomach with an adhesion band. The adhesion band, presumably a complication of previous hepatobiliary surgery, appeared to have caused small bowel obstruction. Adhesiolysis between the small bowel and abdominal wall was performed.. This case demonstrates that even relatively short-term total parenteral nutrition can cause severe fetal brain hemorrhage. Vitamin K supplementation is required for mothers who are expected to be vitamin K deficient, especially if they are on total parenteral nutrition for more than 3 weeks.

Topics: Adult; Cesarean Section; Female; Fetal Diseases; Humans; Infant, Newborn; Intestinal Obstruction; Intracranial Hemorrhages; Parenteral Nutrition, Total; Pregnancy; Vitamin K; Vitamin K Deficiency

The objective of this study was to evaluate clinical outcomes associated with time to administration and dose of four-factor prothrombin complex concentrate (4F-PCC) in patients with ICH on warfarin.. This was a single-center retrospective analysis of patients with ICH on warfarin who received 4F-PCC.. The site of the study was a large, Level I trauma, academic medical center with a dedicated neurologic intensive care unit and an emergency department (ED) that has approximately 72,000 visits annually.. Patients were included if they were ≥18 years of age, diagnosed with ICH, had an INR >1 due to warfarin use, and received both 4F-PCC and IV vitamin K for anticoagulation reversal. Exclusion criteria included patients who were less than 18 years of age, were not currently taking warfarin, had a bleeding site other than ICH, were pregnant or incarcerated, had an inadequate medical record, had a left ventricular assist device, had known liver disease with Child-Pugh Class C, received anticoagulation with heparin therapy within 24 h of anticoagulation reversal, or did not receive vitamin K within 24 h of hospital admission.. Our primary outcome was a composite of hematoma expansion or death due to neurologic injury. Treatment groups were defined as receipt of 4F-PCC within 0-30, 31-60, 61-90, 91-120 min, or greater than 120 min. Hematoma expansion was defined as any increase in hematoma size as assessed by a radiologist via standard 6-h CT. Death due to neurologic injury was defined as death prior to a repeat CT being performed or documentation of a neurologic cause of death. Adequate INR reversal (INR ≤1.3 on repeat INR) vs. inadequate INR reversal and weight-based vs. fixed-dose 4F-PCC were also assessed.. A total of 94 patients met the inclusion criteria. Forty-one patients (43.6%) met the composite endpoint, including 60% of the 31-60 min group, 47.6% of the 61-90 min group, 71.4% of the 91-120 min group, and 30.6% of the >120-min group. A significant difference in primary outcome occurred between the 91-120 min and >120-min groups (71.4% vs. 30.6%; p= 0.005), but this difference was not observed when accounting for disparities in Glasgow Coma Scale (GCS). Patients with adequate INR reversal were less likely to meet the primary endpoint than those with inadequate INR reversal (28.1% vs. 58.6%; p= 0.0059). There was less failure of anticoagulation reversal with weight-based dosing compared with fixed dosing (24.2% vs. 65.0%; p< 0.001).. No difference in clinical outcomes among 4F-PCC dosing strategies or time windows to administration was observed in patients with GCS <15. Rates of repeat INR ≤1.3 were higher with weight-based dosing, suggesting investigation of populations in which fixed dosing may be inappropriate is warranted.

Topics: Anticoagulants; Blood Coagulation Factors; Factor IX; Hematoma; Humans; International Normalized Ratio; Intracranial Hemorrhages; Retrospective Studies; Vitamin K; Warfarin

We present a case of a 6-week-old infant who presented with seizure-like activity. Workup revealed abnormal coagulation and imaging confirmed intracranial hemorrhage. Parental refusal of vitamin K treatment at birth suggested vitamin K deficiency bleeding (VKDB) in this newborn. Though VKDB is rare in developed countries, rates have been rising which coincides with an increasing trend of parental refusal of vitamin K prophylaxis at birth.

Topics: Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Ischemic Stroke; Stroke; Tissue Plasminogen Activator; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Ischemic Stroke; Stroke; Tissue Plasminogen Activator; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Ischemic Stroke; Stroke; Tissue Plasminogen Activator; Treatment Outcome; Vitamin K

Although the preliminary evidence seems to confirm a lower incidence of post-traumatic bleeding in patients treated with direct oral anticoagulants (DOACs) compared to those on vitamin K antagonists (VKAs), the recommended management of mild traumatic brain injury (MTBI) in patients on DOACs is the same as those on the older VKAs, risking excessive use of CT in the emergency department (ED).. To determine which easily identifiable clinical risk factors at the first medical evaluation in the ED may indicate an increased risk of post-traumatic intracranial haemorrhage (ICH) in patients on DOACs with MTBI.. Patients on DOACs who were evaluated in the ED for an MTBI from 2016 to 2020 at four centres in Northern Italy were considered. A decision tree analysis using the chi-square automatic interaction detection (CHAID) method was conducted to assess the risk of post-traumatic ICH after an MTBI. Known pre- and post-traumatic clinical risk factors that are easily identifiable at the first medical evaluation in the ED were used as input predictor variables.. Among the 1146 patients on DOACs in this study, post-traumatic ICH was present in 6.5% (75/1146). Decision tree analysis using the CHAID method found post-traumatic TLOC, post-traumatic amnesia, major trauma dynamic, previous neurosurgery and evidence of trauma above the clavicles to be the strongest predictors associated with the presence of post-traumatic ICH in patients on DOACs. The absence of a concussion seems to indicate subgroups at very low risk of requiring neurosurgery.. The machine-based CHAID model identified distinct prognostic groups of patients with distinct outcomes based on clinical factors. Decision trees can be useful as guides for patient selection and risk stratification.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Brain Concussion; Decision Trees; Female; Glasgow Coma Scale; Humans; Intracranial Hemorrhages; Italy; Male; Predictive Value of Tests; Prognosis; Retrospective Studies; Risk Assessment; Vitamin K

We present a family who suffered recurrent sibling losses due to vitamin K deficiency bleed. The index child was asymptomatic at presentation, had normal clinical examination, and was investigated for coagulation disorders in view of previous 3 sibling losses as a result of intracranial hemorrhage. His investigations showed deranged coagulogram and clotting factors' assay. The baby was given vitamin K1 1 mg intramuscularly following which his coagulogram and clotting factors' assay returned to normal. The genetic analysis did not identify any inherited cause of bleeding tendency. The significant family history, exclusive breastfeeding, no diarrhea, failure to thrive or drug use, no prophylaxis with vitamin K at birth, recovery of clotting factors on vitamin K administration, and a corroborative molecular analysis confirmed diagnosis of vitamin K deficiency in the index child. This case gives a strong reminder not to miss birth dose of vitamin K in any neonate.

Topics: Antifibrinolytic Agents; Blood Coagulation; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Male; Siblings; Vitamin K; Vitamin K Deficiency

Although mild traumatic brain injury (MTBI) in people on oral anticoagulant treatment (OAT) is a frequent challenge for Emergency Department (ED), strong guidelines recommendations are lacking. In the attempt to assess the safety profile of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs), we have recruited 473 patients with a MTBI on OAT (43.6% males; age 81.8 ± 8.7 years), admitted to the Pisa's University Hospital ED (Jan 2016-Oct 2018). All patients underwent a head CT scan with those with no sign of acute bleedings remaining under clinical observation for the ensuing 24 h. Fifty patients (10.6%, 95% CI: 8.1-13.7%) had immediate intracranial hemorrhage (ICH), with a prevalence of patient-important outcomes due to immediate ICH of 1.1% (95% CI 0.4-2.4%); 3 patients died (0.6%, 95% CI 0.2-1.8) and 2 required neurosurgical intervention. Immediate ICHs were more frequent in VKA-treated than in DOAC-treated patients (15.9 vs. 6.4%. RR 2.5. 95%CI 1.4-4.4. p < 0.05). Multivariate analysis identified that post-traumatic amnesia, evidence of trauma above clavicles, high blood glucose, high blood pressure (BP) at arrival, and low prothrombin activity were predictors of immediate ICH. The prevalence of delayed ICH was 1.0% (95%CI 0.4-2.5%) without differences between DOACs and VKAs. Despite ICH being a frequent complication of MTBI in patients on OAT, immediate and delayed patient-important outcomes are rare. DOACs have a better safety profile than VKAs. Simple clinical parameters such as blood pressure at arrival or blood glucose might provide useful predictors of immediate ICH.Trial registration number: 11924_CIPRIANO. Local ethics committee approval number 33096.

Topics: Administration, Oral; Aged, 80 and over; Anticoagulants; Brain Concussion; Emergency Service, Hospital; Female; Glasgow Coma Scale; Humans; Intracranial Hemorrhages; Italy; Male; Prospective Studies; Vitamin K

Direct oral anticoagulants (DOACs) were developed to avoid the limitations of vitamin K antagonists (VKAs). DOACs are associated with a greater incidence of gastrointestinal bleeding and a smaller number of intracranial haemorrhages than VKAs. Therefore, it is important to deepen our knowledge of their safety profiles. The aim of this study was thus to analyse adverse drug reaction (ADR) reports on DOACs and VKAs using the Sicilian Spontaneous Reporting System (SRS) database.. All ADR reports with DOACs and VKAs as suspected drugs that were entered into the Sicilian SRS database during the period 2001-2019 were selected. In detail, all reports with the following single active substances were included: dabigatran etexilate, rivaroxaban, apixaban and edoxaban; acenocoumarol and warfarin were included as a comparator group. Descriptive statistical methodology was used to evaluate characteristics of the reported cases with a case-by-case assessment.. Out of 521 reports related to anticoagulants, 444 (85.2%) and 77 (14.8%) involved DOACs and VKAs, respectively. DOAC-related reports were mainly of gastrointestinal disorders. In contrast, VKAs were mostly associated with blood and lymphatic system disorders, injury, investigations and vascular disorders. Many more cases of ADRs in the form of gastrointestinal disorders concerned dabigatran etexilate (n = 179, 73.7%) than the other DOACs, while ADRs in the form of blood disorders were mainly associated with acenocoumarol (n = 27, 57.4%). The most commonly reported Preferred Terms for DOACs were dyspepsia (n = 89, 17.1%), upper abdominal pain (n = 41, 9.2%) and pruritus (n = 26, 5.8%), whereas for VKAs, they were anaemia (n = 21, 27.3%) and hypocoagulable state (n = 18, 3.5%). Potentially interacting concomitant medications particularly included antithrombotic agents (n = 19, 4.3%) for DOACs and proton-pump inhibitors (PPIs) (n = 37, 48.1%) and antithrombotic agents (n = 13, 16.9%) for VKAs.. The ADRs most commonly associated with DOACs, especially dabigatran, were gastrointestinal disorders, particularly gastrointestinal bleeding. Our study also highlights the potential role of drug-drug interactions in the ADRs. The cases of gastrointestinal bleeding highlight the need for careful prescribing of DOACs and use of potentially interacting concomitant drugs.

Topics: Adverse Drug Reaction Reporting Systems; Anticoagulants; Drug Interactions; Factor Xa Inhibitors; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Italy; Vitamin K

The objective of the study was to assess the effectiveness of individual direct oral anticoagulants versus vitamin K antagonists for primary prevention of stroke (ischemic and hemorrhagic) in routine clinical practice in patients with various clinical risk factors depending on their atrial fibrillation (AF) patterns.. A nested case-referent study was conducted using data from 2 national registries of patients with stroke and AF. Stroke cases with previous history of AF were matched to up to 2 randomly selected referent patients with AF and no stroke. The association of individual anticoagulant use with ischemic or hemorrhagic stroke was studied in patients with or without permanent AF using multivariable conditional logistic models, controlled for clinically significant risk factors and multiple other cardiovascular risk factors.. In total, 2586 stroke cases with previous AF and 4810 nonstroke referent patients with AF were retained for the study. Direct oral anticoagulant users had lower odds of stroke of any type than vitamin K antagonist users: the adjusted-matched OR for ischemic stroke were 0.70 (95% CI, 0.50–0.98) for dabigatran, 0.68 (95% CI, 0.53–0.86) for rivaroxaban, and 0.73 (95% CI, 0.52–1.02) for apixaban while for hemorrhagic stroke they were 0.31 (95% CI, 0.14–0.68), 0.64 (95% CI, 0.39–1.06), and 0.70 (95% CI, 0.33–1.49), respectively. The effects of individual direct oral anticoagulants relative to vitamin K antagonists were similar in permanent AF and nonpermanent AF patients.. Similar results were observed for each direct oral anticoagulant in real life as those observed in the pivotal clinical trials. The pattern of AF did not affect the outcome.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Dabigatran; Female; Heart Disease Risk Factors; Humans; Intracranial Hemorrhages; Ischemic Stroke; Male; Middle Aged; Risk Factors; Stroke; Treatment Outcome; Vitamin K

Infants who are born in The Netherlands receive oral vitamin K to prevent bleeding due to a vitamin K deficiency. However the incidence of such bleedings are higher compared to other European countries. Therefore, the Dutch Health Council advised in 2017 to change this guideline from oral to intramuscular administration.. A 2 months old girl presented with a fatal intracranial hemorrhage. A day before she developed a hematoma on her foot and orbit. Despite daily oral vitamin K, blood results revealed a severe vitamin K deficiency-related bleeding. Postmortem liver biopsy and genetic studies showed cholestasis as the most likely cause of malabsorption of fat soluble vitamins due to a heterozygous pathogenic variant in the ABCB11 gene, which could possibly be transient.. Our case illustrates the importance of revising the national guideline for vitamin K prophylaxis to intramuscular administration, according to the recommendation of the Dutch Health Council.

Topics: Cholestasis; Female; Hemorrhage; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Vitamin K; Vitamin K Deficiency Bleeding

Patients with mechanical heart valves are at high thrombotic risk and require warfarin. Among those developing intracranial hemorrhage, limited data are available to guide clinicians with antithrombotic reinitiation. This 13-patient case series of warfarin-associated intracranial hemorrhages found the time to reinitiate antithrombotic therapy (17 days, interquartile range 21.5 days), and changes to international normalized ratio targets were variable and neither correlated with the type, location, or etiology of bleed, nor the valve and associated thromboembolic risk. The initial presentation significantly impacted prognosis, and diligent assessment and follow-up may support positive long-term outcomes.

Topics: Aged; Anticoagulants; Antifibrinolytic Agents; Aortic Valve; Aspirin; Blood Coagulation Factors; Cerebral Hemorrhage; Female; Heart Valve Prosthesis; Hematoma, Subdural; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Mitral Valve; Plasma; Platelet Aggregation Inhibitors; Pregnancy; Retrospective Studies; Subarachnoid Hemorrhage; Subarachnoid Hemorrhage, Traumatic; Thromboembolism; Vitamin K; Warfarin

Despite the utility of neuroimaging in the diagnostic and therapeutic management of patients with acute ischemic stroke (AIS), imaging characteristics in patients with preceding direct oral anticoagulants (DOAC) compared to vitamin K antagonists (VKA) have hardly been described. We aimed to determine presence of large vessel occlusion (LVO), thrombus length, infarction diameter, and occurrence of hemorrhagic transformation in AIS patients with preceding DOAC as compared to VKA therapy.. Using a prospectively collected cohort of AIS patients, we performed univariate and multivariable regression analyses regarding imaging outcomes. Additionally, we provide a sensitivity analysis for the subgroup of patients with confirmed therapeutic anticoagulation.. We included AIS in patients with preceding DOAC (N = 75) and VKA (N = 61) therapy, median age 79 (IQR 70-83), 39% female. Presence of any LVO between DOAC and VKA patients (29.3% versus 37.7%, P = 0.361), and target LVO for endovascular therapy (26.7% versus 27.9%, P = 1.0) was equal with a similar occlusion pattern. DOAC as compared to VKA were associated with a similar rate of target LVO for EVT (aOR 0.835, 95% CI 0.368-1.898). The presence of multiple lesions and characteristics of the thrombus were similar in DOAC and VKA patients. Acute ischemic lesion diameter in real world patients was equal in patients taking DOAC as compared to VKA. Lesion diameter in VKA patients (median 13 mm, IQR 6-26 versus median 20 mm, IQR 7-36, P = 0.001), but not DOAC patients was smaller in the setting of confirmed therapeutic VKA. The frequency of radiological hemorrhagic transformation and symptomatic intracranial hemorrhage in OAC patients was low. Sensitivity analysis considering only patients with confirmed therapeutic anticoagulation did not change any of the results.. Preceding DOAC treatment showed equal rates of LVO and infarct size as compared to VKA in AIS patients. This study adds to the knowledge of imaging findings in AIS patients with preceding anticoagulation.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Brain Ischemia; Cohort Studies; Female; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Prospective Studies; Stroke; Vitamin K

To compare mortality between anticoagulated atrial fibrillation patients and general population and among anticoagulation specific categories [direct oral anticoagulants (DOACs) vs. vitamin K antagonists(VKA)].. This was a population-based study including all residents in the Veneto Region aged 18 years or older. Administrative claims from July 2013 to September 2017 were used to identify anticoagulation-naïve atrial fibrillation patients. Propensity score matching was employed to compare patients on new and old anticoagulants.. Overall, 17 225 patients on direct anticoagulants were 1 : 1 matched to patients on VKA (49% males, median age 77 years). Mortality was higher with respect to the general population by 22 and 39% among patients on direct anticoagulants and VKA, respectively. Mortality from intracranial hemorrhage in the direct anticoagulant group was similar to that in the general population [standardized mortality ratio: 1.06, 95% confidence intervals (CI) 0.76-1.48], whereas it almost doubled in VKA group (1.92, 95% CI 1.49-2.46). When directly compared with the VKA cohort, the risk of death from intracranial hemorrhage halved with DOACs (hazard ratio 0.56, 95% CI 0.37-0.84).. The mortality rate of anticoagulated atrial fibrillation patients is increased with respect to the general population, particularly among patients treated with VKAs. The mortality rate for intracranial bleeding with DOACs is similar to that observed in the general population.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cause of Death; Databases, Factual; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Italy; Male; Middle Aged; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vitamin K

Intracranial hemorrhage (ICH) is associated with severe prognosis and recurrent risk. This impacts on the decision to resume anticoagulation in atrial fibrillation (AF) or venous thromboembolism (VTE) patients. Purpose of our study is to evaluate the incidence rate of recurrent ICH in patients with AF or VTE resuming anticoagulation after a first ICH episode.. We report data of two cohorts of AF or VTE after a first ICH. The Vitamin K antagonist (VKA) cohort (166 patients) derives from CHIRONE Study, the direct oral anticoagulant (DOAC) cohort (178 patients) derives from START2-Register RESULTS: The clinical characteristics of the two cohort are similar with the exception of more prevalence of history of previous stroke/TIA in DOAC patients with respect to VKA (p = 0.02) and serum creatinine levels>1.5 mg/dL in VKA patients with respect to DOAC(p = 0.0001). The index ICH was spontaneous in 66.4% and in 33.7% among DOAC and VKAs cohort respectively (p = 0.0001). During follow-up, 14 recurrent ICH were recorded; 9 (rate 2.5 × 100 patient-years) in VKA and 5 (rate 1.3 × 100 patient-years) in DOAC (Relative Risk 1.9; 95% CI 0.6-7.4; p = 0.2). The univariate logistic regression analysis showed that patients with recurrent ICH were more frequently males, hypertensive, with a history of previous Stroke/TIA and older than patients without recurrence. VKA patients showed a higher risk of recurrence with respect to DOAC patients (OR 1.9;95% CI 0.7-6.7).. A trend toward fewer ICH recurrences was detected among DOACs patients in comparison to the previously reported rate of patients on warfarin.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Male; Venous Thromboembolism; Vitamin K

Topics: Aged; Aged, 80 and over; Craniocerebral Trauma; Emergency Service, Hospital; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Male; Retrospective Studies; Tomography, X-Ray Computed; Vitamin K

The evidence of effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) among elderly East Asians is limited.. We aimed to describe the effectiveness and safety outcomes associated with NOACs and warfarin among elderly Koreans aged ≥80 years.. Using the Korean Health Insurance Review and Assessment service database, patients with atrial fibrillation (AF) who were naïve to index oral anticoagulant between 2015 and 2017 were included in this study (20,573 for NOACs and 4086 for warfarin). Two treatment groups were balanced using the inverse probability of treatment weighting (IPTW) method. The clinical outcomes including ischemic stroke, major bleeding including intracranial hemorrhage (ICH) and gastrointestinal bleeding (GIB), and a composite of these outcomes were evaluated.. Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio 0.74 [95% confidence interval 0.62-0.89]), and composite outcome (0.78 [0.69-0.90]). NOACs showed nonsignificant trends towards to lower risks of GIB and major bleeding than warfarin. The risk of ICH of NOAC group was comparable with the warfarin group. Among NOACs, apixaban and edoxaban showed better composite outcomes than warfarin. Among the clinical outcomes, only ischemic stroke and the composite outcome had a significant interaction with age subgroups (80-89 years and ≥90 years, P-for-interaction = .097 and .040, respectively).. NOACs were associated with lower risks of ischemic stroke and the composite outcome (ischemic stroke and major bleeding) compared to warfarin in elderly East Asians. Physicians should be more confident in prescribing NOACs to elderly East Asians with AF.

Topics: Aged, 80 and over; Atrial Fibrillation; Brain Ischemia; Databases, Factual; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Pyrazoles; Pyridines; Pyridones; Republic of Korea; Stroke; Thiazoles; Vitamin K; Warfarin

Intracranial hemorrhage (ICH) is the most feared complication of anticoagulation with a high mortality and morbidity. Before registration of a specific reversal agent for factor Xa inhibitors (FXa-I), international guidelines recommended prothrombin complex concentrate (PCC), which also is the specific reversal agent for vitamin K antagonists (VKA). In two contemporary cohorts, we compared clinical outcomes between patients with FXa-I and VKA related ICH treated with PCC between 2014 and 2018. Primary outcome was effective hemostasis after 24 h, according to the International Society of Thrombosis and Hemostasis definition. Safety outcomes were defined as venous and arterial thromboembolic complications and death within 30 days. Thirty-six patients with FXa-I-ICH and 39 patients with VKA-ICH were available for analysis. Baseline characteristics were comparable between both groups, except for time from start of symptoms to presentation at the hospital. In the FXa-I-ICH cohort, 24 (73%) patients achieved effective hemostasis compared to 23 (62%) patients in the VKA-ICH cohort (crude odds ratio [OR] 1.62 [95%CI 0.59-4.48], adjusted OR 1.45 [95%CI 0.44-4.83]). Eight (24%) patients with FXa-I-ICH deceased compared to 17 (45%) patients with VKA-ICH (crude OR 0.38 [95%CI 0.14-1.24], adjusted OR 0.41 [95%CI 0.12-1.24]). In this observational cohort study, the outcome of ICH managed with PCC was similar in patients with FXa-I-ICH and in patients with VKA-ICH.

Topics: Anticoagulants; Blood Coagulation Factors; Factor Xa Inhibitors; Humans; Intracranial Hemorrhages; Vitamin K

Vitamin K is a fat-soluble vitamin essential for the formation of factors in the clotting cascade. Newborns are born with insufficient levels of vitamin K, resulting in high risk for vitamin K deficiency bleeding (VKDB). Vitamin K deficiency bleeding can occur in the first week of life ("classic" VKDB) and also between 2 weeks and 3 months of age ("late" VKDB). Vitamin K deficiency bleeding can present as bleeding in the skin or gastrointestinal tract, with as many as half of affected neonates experiencing intracranial bleeding. A single intramuscular injection of vitamin K effectively prevents both classic and late VKDB. Although intramuscular vitamin K is safe and effective, VKDB has reemerged because of decreased utilization. Parents refuse intramuscular vitamin K for a variety of reasons, including a disproven association with childhood cancer, the desire to avoid exposure to additives, and valid concerns about early neonatal pain. Many parents request oral vitamin K, an inferior alternative strategy that requires multiple doses utilizing products not designed for neonatal oral administration. In this setting, health care professionals must understand the epidemiology of VKDB and compassionately counsel parents to assuage concerns. Delivery of intramuscular vitamin K to all newborns remains a public health imperative, benefitting thousands of infants annually.

Topics: Child; Hemorrhage; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Parents; Vitamin K; Vitamin K Deficiency Bleeding

The risk of intracranial hemorrhage (ICH) in patients taking direct oral anticoagulants (DOACs) after mild traumatic brain injury (MTBI) is unclear.. To assess the differences in the risk of developing early, delayed, and comprehensive bleeding after MTBI among patients treated with DOACs as compared with those treated with vitamin K antagonists (VKAs).. All MTBI patients taking oral anticoagulants in our emergency department between June 2017 and August 2018 were included. All patients on oral anticoagulants underwent immediate cerebral computed tomography (CT) and a second CT scan after 24 h of clinical observation.. There were 451 patients enrolled: 268 were on VKAs and 183 on DOACs. Of the DOAC-treated patients, 7.7% (14/183) presented overall intracranial bleeding, compared with 14.9% (40/268) of VKA-treated patients (p = 0.026). Early bleeding was present in 5.5% (10/183) of DOAC-treated patients and in 11.6% (31/268) of VKA-treated patients (p = 0.030). Multivariable analysis showed that VKA therapy (odds ratio [OR] 2.327), high-energy impact (OR 11.229), amnesia (OR 2.814), loss of consciousness (OR 5.286), Glasgow Coma Scale score < 15 (OR 4.719), and the presence of lesion above the clavicles (OR 2.742) were associated with significantly higher risk of global ICH. A nomogram was constructed to predict ICH using these six variables. Discrimination of the nomogram revealed good predictive abilities (area under the receiver operating characteristic curve: 0.817).. DOAC-treated patients seem to have lower risk of posttraumatic intracranial bleeding compared with VKA-treated patients.

Topics: Aged; Aged, 80 and over; Brain Concussion; Emergency Service, Hospital; Factor Xa Inhibitors; Female; Humans; Intracranial Hemorrhages; Italy; Male; Retrospective Studies; Severity of Illness Index; Time Factors; Vitamin K

The correlation between direct oral anticoagulants (DOACs) or Vitamin K Antagonist (VKAs) intake and the incidence of intracranial complications after minor head injury (MHI) is still object of debate: preliminary observation seems to demonstrate lower incidence in intracranial bleeding complications (ICH) in patients taking DOACs than VKA. METHODS. This prospective and observational study was performed to clarify the incidence of ICH in patients in DOACs compared to VKAs. Between January 2016 and April 2018 we have recorded in our ED patients with MHI taking oral anticoagulants. Their hemorragic risk score was calculated and recorded for each patient (Has Bled, Atria and Orbit). RESULTS A total of 402 patients with MHI taking anticoagulant were collected: 226 were receiving one of the four DOACs (dabigatran, rivaroxaban, apixaban or edoxaban) while 176 patients were in therapy with VKA. The rate of intracranial complications was significantly lower in patients receiving DOACs than in patients treated with VKA (p < 0.01). In the VKA group two patients died because of intracranial bleeding. No deaths were recorded in the DOACs group. DISCUSSION patients with MHI who take DOACs have a significant lower incidence of intracranial bleeding complications than those treated with vitamin k antagonists. This statement is supported by the observation that the hemorrhagic risk, measured according to the chosen scores, was similar between the two groups.

Topics: Aged; Aged, 80 and over; Anticoagulants; Craniocerebral Trauma; Dabigatran; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pyrazoles; Pyridines; Pyridones; Risk; Rivaroxaban; Thiazoles; Vitamin K; Warfarin

Recent studies indicated that functional outcome after intracranial hemorrhage (ICH) related to direct oral anticoagulation (DOAC-ICH) is similar, if not better, than vitamin K antagonist (VKA)-related ICH (VKA-ICH) due to a smaller initial hematoma volume (HV). However, the association with hematoma expansion (HE) and location is not well understood.. We retrospectively analyzed 102 consecutive patients with acute non-traumatic ICH on oral anticoagulation therapy to determine HV and HE stratified by hematoma location, and the relation to the 90-day outcome.. DOAC-ICH (n = 25) and VKA-ICH (n = 77) had a similar admission HV and HE (unadjusted p > 0.05, each). Targeted reversal strategies were used in 93.5% of VKA-ICH versus 8% of DOAC-ICH. After adjustment, an unfavorable 90-day functional outcome (modified Rankin scale score 4-6) was independently associated with a lower admission Glasgow Coma Scale score (OR 1.63; 95% CI 1.26-2.10; p < 0.001) and greater HV (OR 1.03; 95% confidence interval (CI) 1.00-1.05; p = 0.046). After exclusion of patients without follow-up head computed tomography to allow for adjustment by occurrence of HE, VKA-ICH was associated with an approximately 3.5 times greater odds for a poor 90-day outcome (OR 3.64; 95% CI 1.01-13.09; p = 0.048). However, there was no significant association of the oral anticoagulant strategy with 90-day outcome in the entire cohort (OR 2.85; 95% CI 0.69-11.86; p = 0.15).. DOAC use did not relate to worse HE, HV, and functional outcome after ICH, adding to the notion that DOAC is a safe alternative to VKA even in the absence of access to targeted reversal strategies (which are still not universally available).

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Female; Hematoma; Humans; Intracranial Hemorrhages; Male; Radiography; Retrospective Studies; Stroke; Vitamin K

Nonvitamin K antagonist oral anticoagulants (NOACs) are considered superior, or at least noninferior, to warfarin in preventing stroke or systemic embolism in patients with nonvalvular atrial fibrillation. Here, we recruited acute ischemic stroke patients with nonvalvular atrial fibrillation and at least one cerebral microbleed (CMB), and evaluated the proportion of patients who had an increased number of CMBs (%) after receiving anticoagulant therapy with NOACs or with warfarin for 12 months.. This was a multicenter, prospective, observational cohort study at 20 centers, conducted between 2015 and 2017, in which we recruited 85 patients with at least one CMB detected by 1.5T magnetic resonance imaging (T2*WI) at baseline, who received NOACs or warfarin for at least 12 months. We compared the proportions of patients with increased numbers of CMBs in the NOACs and warfarin treatment groups.. The proportions of patients with increased numbers of CMBs at month 12 of treatment were 28.6% and 66.7% in the NOACs and warfarin groups, respectively. The new CMBs showed no specific regional localization in either group. In the NOACs and warfarin groups, physicians prescribed lower-than-standard dosing in 13.3% and 50% of the cases, respectively. The administration of reduced doses at physicians' discretion did not appear to alter the incidence of new CMBs.. This is the first evidence to suggest efficacy of NOACs for preventing further CMBs in patients with at least one CMB, although no statistical evaluation was carried out.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Humans; Incidence; Intracranial Hemorrhages; Japan; Magnetic Resonance Imaging; Male; Middle Aged; Pilot Projects; Prospective Studies; Recurrence; Risk Factors; Stroke; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Vitamin K prophylaxis in infancy aims to prevent life-threatening vitamin K deficiency bleeding (VKDB). The Dutch prophylactic oral daily regimen was increased sixfold from 25 to 150 μg because of a high failure rate. To evaluate the efficacy of this new regimen, incidences of intracranial VKDB under both regimens were compared using both general and targeted surveillance. Late VKDB in the general pediatric population was identified by the Netherlands Pediatric Surveillance Unit, between 1 October 2014 and 31 December 2016. Additionally, infants with intracranial vitamin K deficiency bleeding were identified using the Dutch Pediatric Intensive Care Evaluation registry. The incidence of intracranial VKDB as assessed by general and targeted surveillance decreased from 1.6 per 100,000 (95% CI, 0.4-5.1) to 1.3 per 100,000 (95% CI, 0.5-3.2) and from 3.1 per 100,000 live births (95% CI, 1.9-5.0) to 1.2 per 100,000 live births (95% CI, 0.6-2.3), respectively. Median time between consecutive cases in the latter increased from 24 to 154 days (p < 0.001).Conclusion: A sixfold increase in oral vitamin K prophylaxis was associated with a surprisingly modest reduction in the incidence of intracranial VKDB, indicating that factors other than the dose need addressing to improve efficacy. What is Known: • The efficacy of intramuscular vitamin K prophylaxis is threatened by an increasing number of parents opting out. • Oral prophylaxis represents an attractive and less invasive alternative but is inferior, especially in infants with malabsorption of vitamin K due to cholestasis. What is New: • Increasing the daily oral dose of vitamin K sixfold had a surprisingly modest effect on the incidence of late vitamin K deficiency bleeding. • This finding indicates that factors other than the dose must play an important role.

Topics: Administration, Oral; Antifibrinolytic Agents; Cross-Sectional Studies; Dose-Response Relationship, Drug; Female; Humans; Incidence; Infant; Infant, Newborn; Intracranial Hemorrhages; Male; Netherlands; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Asian People; Atrial Fibrillation; Brain Ischemia; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Kidney Function Tests; Male; Republic of Korea; Retrospective Studies; Risk Factors; Stroke; Vitamin K

Cerebral amyloid angiopathy is a common hemorrhagic small vessel disease of the brain, often associated with high risk of spontaneous lobar intracerebral hemorrhage. When the suspicion of cerebral amyloid angiopathy is raised, clinicians are hesitant in prescribing oral anticoagulation in patients in whom it is otherwise indicated, including the case of non-valvular atrial fibrillation. This is one of the thorniest clinical dilemmas in the field currently. In this short Leading Opinion piece by an international panel of clinicians-researchers active in the field, we present our consistent approach and future outlook on oral anticoagulation post intracerebral hemorrhage and in the setting of clinical-radiologic evidence of cerebral amyloid angiopathy. We discuss recent advances and support a more balanced approach with implications for the wider neurological clinical community in regards to successful recruiting this patient population in ongoing and future randomized trials.

Topics: American Heart Association; Amyloid; Anticoagulants; Cerebral Small Vessel Diseases; Clinical Decision-Making; Expert Testimony; Humans; Intracranial Hemorrhages; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Risk Assessment; Stroke; United States; Vitamin K; Warfarin

Topics: Administration, Intravenous; Aged; Anticoagulants; Atrial Fibrillation; Brain; Emergency Service, Hospital; Factor V; Factor Xa; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Paresis; Plasma; Tomography, X-Ray Computed; Vitamin K; Warfarin

Prognosis after mild traumatic brain injury (MTBI) on oral anticoagulant therapy (OAT) is uncertain. We evaluated the rate of immediate and delayed traumatic intracranial hemorrhage (ICH) comparing vitamin K antagonists (VKAs) to direct oral anticoagulants (DOACs) and the safety of a clinical management protocol. In this single-center prospective observational study, we enrolled 220 patients on OAT with MTBI. After a first negative CT scan, asymptomatic patients underwent a close neurological observation; if neurologically stable, they were discharged without a second CT scan and followed up for 1 month. Out of the 220 patients, 206 met the inclusion criteria. 23 of them (11.2%) had a positive first CT scan for ICH. Only 1 (0.5%, 95% CI 0.0-1.4%) died because of ICH; no one required neurosurgical intervention. The observed prevalence rate of immediate ICH resulted statistically higher in VKAs-treated patients compared to those treated with DOACs (15.7 vs. 4.7%, RR 3.34, 95% CI 1.18-9.46, P < 0.05). In the 1-month follow-up, 5 out of the 183 patients with a negative CT scan were lost. Out of the remaining 178 patients, only 3 showed a delayed ICH (1.7%, 95% CI 0.0-3.6%), 1 of them died (0.6%, 95% CI 0.5-1.7%) and the others did not require neurosurgical intervention. DOACs resulted safer than VKAs also in the setting of MTBI. In our observation, the rate of delayed hemorrhage was relatively low. Patients presenting with a negative first CT scan and without neurological deterioration could be safely discharged after a short period of in-ward observation with a low rate of complications and without a second CT scan.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Brain Concussion; Female; Humans; Intracranial Hemorrhages; Male; Prospective Studies; Retrospective Studies; Thrombolytic Therapy; Vitamin K

To determine the preventability of serious adverse drug reactions (ADRs) related to the use of direct oral anticoagulants (DOACs), and to explore contributing factors to preventable ADRs. Results were compared with vitamin K antagonists (VKAs).. We conducted a prospective observational study in the emergency departments of two teaching hospitals from July 2015 to January 2016. Patients admitted with a thrombotic or bleeding event while under DOAC or VKA were included. Four independent reviewers assessed causality, seriousness and preventability of ADRs using pilot-tested scales. For cases of serious and potentially preventable ADRs, we performed semi-structured interviews with general practitioners to identify contributing factors to ADRs. The primary outcome was the proportion of serious ADRs that were potentially preventable.. The analysis included 46 DOAC and 43 VKA patients (median age 79 years). Gastrointestinal (n = 34) and intracranial (n = 16) bleedings were the most frequent ADRs. Results were that 53% of DOAC- and 61% of VKA-related serious ADRs were deemed potentially preventable. Prescribing issues and inadequate monitoring were frequent for DOAC and VKA respectively. We identified many causes of preventable ADRs that applied to all oral anticoagulants, such as pharmacodynamic drug interactions and lack of communication.. More than half of serious ADRs were potentially preventable for both DOACs and VKAs. Interventions focusing on prescribing, patient education and continuity of care should help improve the use of DOACs in practice.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Continuity of Patient Care; Emergency Service, Hospital; Female; Gastrointestinal Hemorrhage; Hospitalization; Humans; Intracranial Hemorrhages; Male; Patient Education as Topic; Prospective Studies; Stroke; Thromboembolism; Vitamin K

We present here a late preterm infant with extensive brain lesions resulting from vitamin K deficiency. A female infant was born after 35 weeks of gestation by emergent cesarean section because of non-reassuring fetal status. Her mother had severe eating disorder and recurrent vomiting since early pregnancy. She was immediately intubated and ventilated because she was extremely pale, hypotonic, and non-reactive. Cerebral magnetic resonance imaging immediately after birth showed intraparenchymal hemorrhage in the left frontal lobe and cerebellum, marked cerebral edema, and cerebellar hypoplasia. Coagulation studies of the infant showed hepaplastin test <5%, prolonged PT and APTT, and a marked elevation of protein induced by vitamin K absence or antagonist-II. This case highlighted a potential risk of intracranial bleeding due to maternal vitamin K deficiency and difficulty in its prediction before delivery. Vitamin K supplementation to high risk mothers might be indispensable for preventing severe fetal vitamin K deficiency. Even when coagulation studies in mothers is normal, it is imperative to provide vitamin K supplementation for total protection.

Topics: Adult; Feeding and Eating Disorders; Female; Humans; Infant, Newborn; Intracranial Hemorrhages; Maternal Nutritional Physiological Phenomena; Mothers; Pregnancy; Pregnancy Complications, Hematologic; Prenatal Exposure Delayed Effects; Treatment Outcome; Vitamin K; Vitamin K Deficiency; Vomiting

Intracranial hemorrhage (ICH) is the most fearful side effect of oral anticoagulant therapy. It is still unclear which risk factor is involved in ICH during vitamin K antagonists (VKAs) treatment and if commonly used bleeding risk scores are able to predict ICH.. Search for individual risk factors and bleeding risk scores (HAS-BLED, ATRIA and ORBIT) associated with ICHs in patients with atrial fibrillation treated with VKAs.. This is a retrospective case-control study in a single Thrombosis Center. During a 7-year period, patients with nonvalvular atrial fibrillation (NVAF) who developed ICH during VKAs were identified as cases. Four control patients matched for gender, age and length of VKAs were assigned to each case. The association between considered risk factors and ICHs was evaluated using a linear logistic regression method and expressed as odds ratio. Receiver operator characteristic (ROC) curves to assess the predictive ability of bleeding risk scores HAS-BLED, ATRIA and ORBIT were also evaluated.. Fifty-one cases of ICH, most of whom were 80 years of age or older (72.5%), were retrieved from the Thrombosis Center's database. Compared to 204 controls, no individual risk factors were associated with ICH. Poor ability to predict ICH was also found using ROC curves (C-statistic for HAS-BLED, ATRIA, and ORBIT were 0.55, 0.53 and 0.54, respectively).. ICHs during VKA therapy preferentially occur in very elderly patients. The risk of ICH is not predicted by the commonly used risk scores.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Humans; Intracranial Hemorrhages; Italy; Male; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome; Vitamin K

Intracranial hemorrhage (ICH) is a complication of warfarin-associated anticoagulation resulting in significant morbidity and mortality. The purpose of this study was to assess whether interhospital transfer delays the administration of 4-factor prothrombin complex concentrate to patients with warfarin-associated ICH.. This was a retrospective cohort study of all patients presenting to a 60,000 visit academic ED between August 2013 and July 2017 requiring emergent anticoagulation reversal for warfarin-associated ICH. Patients were divided into 2 cohorts: (1) transfer patients who arrived at the academic center after receiving care in a local community hospital and (2) control patients who presented directly to the academic center ED. The primary outcome was time to administration of 4-factor prothrombin complex concentrate. Secondary outcomes included hematoma expansion, guideline-adherent vitamin K administration (10mg IV), intensive care unit and hospital length of stay, disposition at discharge, and in-hospital mortality.. This study included 203 patients (177 transfer patients, 26 control). The median time to arrival in transfer patients was 186 minutes (IQR 145-242). The median time to administration of guideline-adherent therapy in transfer patients was 296 minutes, compared to 119 minutes in patients who were not transferred (median difference= -176, 95% confidence interval -143 to -208, P ≤ .001). Delay in anticoagulation reversal did not result in hematoma expansion, intensive care unit and hospital length of stay, discharge disposition, or in-hospital mortality.. Patients requiring interhospital transfer experienced significant delays in guideline-adherent anticoagulation reversal for warfarin-associated ICH, but this delay was not associated with worse outcomes.

Topics: Academic Medical Centers; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Coagulants; Drug Administration Schedule; Female; Guideline Adherence; Hospital Mortality; Hospitals, Community; Humans; Intracranial Hemorrhages; Length of Stay; Male; Patient Discharge; Patient Transfer; Practice Guidelines as Topic; Retrospective Studies; Risk Factors; Time Factors; Time-to-Treatment; Treatment Outcome; Vitamin K; Warfarin

Background and Purpose- Acute ischemic strokes under vitamin K antagonist (VKA) treatment are not uncommon, but intravenous thrombolysis (IVT) is not recommended for international normalized ratio (INR) >1.7 because of the excess bleeding risk. However, VKA-induced anticoagulation can be easily reversed by IV infusions of 4-factor prothrombin complex concentrate bolus and vitamin K. Our pilot study aimed to determine whether IVT immediately after anticoagulation reversal could be feasible and safe in acute ischemic stroke patients under VKA with INR >1.7. Methods- Consecutive acute ischemic stroke patients, otherwise eligible for IVT except for VKA intake and INR >1.7, were given IVT after infusing 4-factor prothrombin complex concentrate and vitamin K. Safety and efficacy were assessed clinically and by cerebral imaging at 24 hours. Results- Twenty-six patients (age, 77.8±12.8 years; atrial fibrillation, 84.6%; initial National Institutes of Health Stroke Scale, 11.6±5.6) were prospectively included. INR values were 2.3±0.6 initially and 1.3±0.2, 5 minutes postreversal. No symptomatic intracranial hemorrhage or thrombotic events occurred during the first 3 days. One patient developed major systemic hemorrhoidal bleeding that required blood transfusion; 61.5% of the patients were independent (modified Rankin Scale score of ≤2) at 3 months. Conclusions- A reversal strategy of 4-factor prothrombin complex concentrate bolus and vitamin K before IVT could be feasible and safe in acute ischemic stroke patients under VKA with INR >1.7. Well-designed, randomized controlled trials are warranted to confirm these preliminary findings.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Pilot Projects; Stroke; Thrombolytic Therapy; Vitamin K

Topics: Aged, 80 and over; Anticoagulants; Dabigatran; Dementia; Drug Overdose; Fatal Outcome; Humans; Intracranial Hemorrhages; Male; Multiple Organ Failure; Skull Fractures; Vitamin K

This article presents the case of a 6-week-old infant who, despite oral vitamin K prophylaxis and otherwise normal developmental progress, suffered a severe intracerebral and subdural hemorrhage, which required surgical evacuation. The interdisciplinary approach is described with emphasis on the management of hemostasis. Furthermore, the clinical picture of intracranial bleeding due to vitamin K deficiency, which is nowadays rare in the Western World, is described in the anesthesiology literature for the first time. The usual recommendations regarding prophylaxis as well as certain risk factors are presented.

Topics: Anesthesiologists; Blood Coagulation Disorders; Hemostasis; Hemostatics; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Male; Risk Factors; Thrombelastography; Vitamin K; Vitamin K Deficiency

Topics: Administration, Oral; Anticoagulants; Aspirin; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Dabigatran; Humans; Intracranial Hemorrhages; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Vitamin K; Warfarin

Patients with in-hospital strokes (IHS) may be eligible for recanalization therapies. The objective of this study is to compare outcomes in patients with IHS and community-onset strokes (COS) treated by recanalization therapy. We analysed data prospectively collected in consecutive patients treated by thrombolysis, thrombectomy, or both for cerebral ischemia at the Lille University Hospital. We compared four outcomes measures at 3 months in patients with IHS and COS: (1) modified Rankin scale (mRS) 0-1, (2) mRS 0-2, (3) death, and (4) symptomatic intracranial haemorrhage (ECASS 2 definition). Of 1209 patients, 64 (5.3%) had IHS, with an increasing proportion over time (p = 0.001). Their median onset-to-needle time was 128 min vs. 145 in COS (p < 0.001). They were more likely to have had a recent TIA [odds ratio (OR) 30.1; 95% confidence interval (CI) 11.5-78.7], to have been treated by vitamin K antagonist before (OR 4.2; 95% CI 1.4-12.0) and to undergo mechanical thrombectomy (45 vs. 10%, p < 0.001). They were less likely to have a pre-stroke mRS 0-1 (OR 0.22; 95% CI 0.09-0.50). After adjustment, IHS was not associated with any of the four outcome measures. Patients with IHS are treated 17 min earlier than patients with COS, but, taking into account that they were already in the hospital, delays are still too long. Their outcome does not differ from that of patients with COS, suggesting room for improvement if delays can be reduced. IHS being frequent, pre-specified pathways should be organised.

Topics: Administration, Intravenous; Aged; Aged, 80 and over; Brain Ischemia; Female; Fibrinolytic Agents; Follow-Up Studies; Hospitalization; Humans; Intracranial Hemorrhages; Male; Mechanical Thrombolysis; Middle Aged; Prospective Studies; Stroke; Thrombolytic Therapy; Time-to-Treatment; Treatment Outcome; Vitamin K

Factor Xa (fXa)-inhibitors are as effective and safer than vitamin-K-antagonists (VKA) in the treatment of venous thromboembolism (VTE). We previously classified the severity of clinical presentation and course of all major bleeding events from the EINSTEIN, AMPLIFY and HOKUSAI-VTE trials separately. The current aim was to combine these findings in order to increase precision, assess a class effect and analyse presentation and course for different types of bleeding, i. e. intracranial, gastro-intestinal, and other. We classified the clinical presentation and course of all major bleeding events using pre-defined criteria. Both classifications comprised four categories; one being the mildest, and four the most severe. Odds ratios (OR) were calculated for all events classified as category three or four between fXa-inhibitors and VKA recipients. Also, ORs were computed for different types of bleeding. Major bleeding occurred in 111 fXa-inhibitor recipients and in 187 LMWH/VKA recipients. The clinical presentation was classified as category three or four in 35% and 48% of the major bleeds in fXa inhibitor and VKA recipients, respectively (OR 0.59, 95% CI 0.36-0.97). For intracranial, gastro-intestinal and other bleeding a trend towards a less severe presentation was observed for patients treated with fXa inhibitors. Clinical course was classified as severe in 22% of the fXa inhibitor and 25% of the VKA associated bleeds (OR 0.83, 95% CI 0.47-1.46). In conclusion, FXa inhibitor associated major bleeding events had a significantly less severe presentation and a similar course compared to VKA. This finding was consistent for different types of bleeding.

Topics: Aged; Aged, 80 and over; Anticoagulants; Disease Progression; Factor Xa Inhibitors; Female; Gastrointestinal Diseases; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Odds Ratio; Venous Thromboembolism; Vitamin K

Millions of patients receive vitamin K antagonist (VKA) therapy worldwide. Annually 0.2-1 % of all VKA users develops an intracranial hemorrhage (ICH). Prothrombin complex concentrate (PCC) is administered to restore the INR ≤ 1.5 in an attempt to limit hematoma growth. In order to facilitate PCC dosing, our hospital recently changed from a variable dose based on bodyweight, baseline- and target-INR, to a fixed 1000 IU fIX PCC dosing protocol for ICH.. In a before and after design, we compared successful achievement of an INR ≤ 1.5 with a fixed dosing strategy versus the variable dosing strategy of PCC in patients presenting with intracranial bleeding complications of VKA. Data of the two cohorts of patients were retrospectively collected from medical records.. A median dosage of 1750 IU was given per patient in the variable dose group (n = 25) versus 1000 IU in the fixed dose group (n = 28). In the intention-to-treat analysis, 96 % achieved an INR ≤ 1.5 after an initial dose in the variable dose cohort compared to 68 % in the fixed dose cohort (p = 0.01). An additional dose was given in 2 (8 %) versus 9 (32 %) patients, respectively (p = 0.04). The median door-to-PCC-order time was 42 versus 32 min (p = 0.37) and the door-to-needle time was 81, respectively 60 min (p = 0.42).. The fixed dose protocol necessitates additional PCC infusions more frequently to achieve a target INR ≤ 1.5. Door-to-order and door-to-needle time were shorter but, in this small cohort, not significantly so. The effect on clinical outcome remains unknown.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Outcome Assessment, Health Care; Retrospective Studies; Vitamin K

Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are widely used as stroke prophylaxis in non-valvular atrial fibrillation (AF), but comparative data are sparse.. To compare dabigatran, rivaroxaban, and apixaban vs. VKA and the risk of stroke/thromboembolism (TE) and intracranial bleeding in AF.. Using Danish nationwide registries (2011-15), anticoagulant-naïve AF patients were identified when initiating VKA or an NOAC. Outcomes were stroke/TE and intracranial bleeding. Multiple outcome-specific Cox regression was performed to calculate average treatment effects as standardized differences in 1-year absolute risks.. Overall, 43 299 AF patients initiated VKA (42%), dabigatran (29%), rivaroxaban (13%), and apixaban (16%). Mean CHA2DS2-VASc (SD) score was: VKA 2.9 (1.6), dabigatran 2.7 (1.6), rivaroxaban 3.0 (1.6), and apixaban 3.1 (1.6). Within patient-specific follow-up limited to the first 2 years, 1054 stroke/TE occurred and 261 intracranial bleedings. Standardized absolute risk (95% CI) of stroke/TE at 1 year after initiation of VKA was 2.01% (1.80% to 2.21%). In relation to VKA, the absolute risk differences were for dabigatran 0.11% (-0.16% to 0.42%), rivaroxaban 0.05% (-0.33% to 0.48%), and apixaban 0.45% (-0.001% to 0.93%). For the intracranial bleeding outcome, the standardized absolute risk at 1 year was for VKA 0.60% (0.49% to 0.72%); the corresponding absolute risk differences were for dabigatran -0.34% (-0.47% to - 0.21%), rivaroxaban -0.13% (-0.33% to 0.08%), and apixaban -0.20% (-0.38% to - 0.01%).. Among anticoagulant-naïve AF patients, treatment with NOACs was not associated with significantly lower risk of stroke/TE compared with VKA, but intracranial bleeding risk was significantly lower with dabigatran and apixaban.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Dabigatran; Denmark; Female; Hospitalization; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Vitamin K; Warfarin

Background There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. Aims To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. Methods We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals. Clinical and demographic data were obtained from individual medical records. Intracranial hemorrhage was classified as intracerebral, extra-axial, or multifocal using brain computed tomography. Three-month functional outcome was assessed using the modified Rankin Scale. Results Among 246 patients included, 24 (9.8%) were anticoagulated with a non-vitamin K antagonist oral anticoagulants and 222 (90.2%) with a vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants patients were older (81.5 vs. 76 years, p = 0.048) and had intracerebral hemorrhage more often (83.3% vs. 63.1%, p = 0.048). We detected a non-significant trend for larger intracerebral hemorrhage volumes in vitamin K antagonists patients ( p = 0.368). Survival analysis adjusted for age, CHA

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Female; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Male; Stroke; Treatment Outcome; Vitamin K

The most feared complication of vitamin K antagonists (VKAs) treatment is intracranial hemorrhage (ICH). The previously published CHIRONE Study fails to identify risk factors associated with ICH recurrence after VKAs resumption. The aim of this secondary analysis of the study is to evaluate if patients who need surgery or with severe neurological sequelae after the first episode show a higher risk of ICH recurrence. The HASBLED score was used to stratify bleeding risk and to evaluate the distribution of recurrence in relation to each class of risk. The study included 267 patients from 27 Italian centers. The treatment of the index ICH, surgical or medical was recorded; modified Rankin Scale score of 3 or more was used to define patients with severe neurological impairment; HASBLED score of 3 or more was used to identify high bleeding risk patients. During follow-up, 20 patients (7.5%) had ICH recurrence (rate of 2.56 × 100 patient-years). No difference in the type of treatment [hazard ratio = 1.5; 95% confidence interval (CI): 0.49-4.74] and neurological impairment with modified Rankin Scale 3 or more (hazard ratio = 0.9; 95% CI: 0.31-2.83) were found in relation to ICH recurrence. The mean HASBLED score was similar between the two groups (P = 0.54). In conclusion, the results of our study suggest that neither the severity of the index ICH at presentation nor the HASBLED clinical prediction rule should be used to assess the risk of recurrence in patients who need VKAs resumption after a previous ICH.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Child; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Recurrence; Risk Factors; Treatment Outcome; Vitamin K; Young Adult

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Time Factors; Vitamin K

The optimal management of major bleeding associated with vitamin K antagonists remains unclear.. The aim of the study was to assess the determinants of outcome of vitamin K antagonists-associated major bleeding and the outcome of bleeding in relation with the therapeutic management.. Patients hospitalized for major bleeding while on vitamin K antagonists were included in a prospective, cohort study. Major bleeding was defined according to the criteria of the International Society of Thrombosis Haemostasis. The primary study outcome was death at 30days from major bleeding.. 544 patients were included in this study, of which 282 with intracranial hemorrhage. Prothrombin complex concentrates were used in 51% and in 23% of patients with intracranial hemorrhage or non-intracranial major bleeding, respectively (p<0.001); fresh frozen plasma was used in 7% and in 17% of patients with intracranial hemorrhage or non-intracranial major bleeding (p<0.001). Death at 30days occurred in 100 patients (18%), 72 patients with intracranial hemorrhage and 28 patients with non-intracranial major bleeding. Age over 85years, low Glasgow Coma Scale score and shock were independent predictors of death at 30days. Invasive procedures were associated with decreased risk of death.. Among the patients hospitalized for major bleeding while on vitamin K antagonists, the risk for death is substantial. The risk for death is associated with the clinical severity of major bleeding as assessed by the GCS score and by the presence of shock more than with the initial localization of major bleeding (ICH vs other sites).

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Disease Management; Female; Fibrinolytic Agents; Glasgow Coma Scale; Humans; International Normalized Ratio; Intracranial Hemorrhages; Italy; Length of Stay; Male; Middle Aged; Plasma; Prognosis; Proportional Hazards Models; Prospective Studies; Vitamin K; Warfarin

Previous trials investigating usage of four-factor prothrombin complex concentrate (4F-PCC) excluded patients with various thrombotic risk factors. The objective of this study was to evaluate the safety and effectiveness of 4F-PCC in a real-world setting based on an institutional protocol that does not have strict exclusion criteria.. This was a retrospective study of adult patients who received 4F-PCC. The primary outcome was a confirmed thromboembolism within 14 days after 4F-PCC administration. Secondary outcomes included international normalized ratio (INR) correction to <1.5 at first draw and incidence of INR rebound for patients undergoing reversal of warfarin and hemostatic effectiveness for patients experiencing a bleed.. Ninety-three patients received 4F-PCC. Sixty-three (67.7%) were reversed for bleeding and 30 (32.3%) for surgery. Eleven patients (11.8%) developed a thromboembolism within 14 days. The median (interquartile range) time to event was 5 (2-7) days. Significant risk factors were heparin-induced thrombocytopenia (P= .01) and major surgery within 14 days (P= .02), as well as the presence of >6 thrombotic risk factors (P= .01). For patients post-warfarin reversal, 45/63 (71.4%) achieved INR correction at first draw, 55/63 (87.3%) achieved INR correction within 24 hours, and 14/55 (25.5%) experienced INR rebound. Of these 14 patients, 8 (57.1%) did not receive concomitant vitamin K.. 4F-PCC was associated with a notable thromboembolic risk. All patient-specific risk factors should be considered prior to administration. 4F-PCC remains a useful agent for warfarin reversal. Lack of concomitant vitamin K may contribute to INR rebound.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Factors; Cardiac Surgical Procedures; Dabigatran; Emergencies; Female; Gastrointestinal Hemorrhage; Heart Transplantation; Hemorrhage; Hemostatics; Heparin; Humans; Incidence; International Normalized Ratio; Intracranial Hemorrhages; Laparotomy; Male; Middle Aged; Preoperative Care; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Surgical Procedures, Operative; Thrombocytopenia; Thromboembolism; Vitamin K; Warfarin

Vitamin K antagonists (VKA) are widely used for the prevention and curative treatment of thromboembolic events. This study aims to describe the epidemiological, clinical and evolutionary aspects of overdose in Vitamin K antagonists administration and determine its hemorrhagic factors. We conducted a monocentric cross-sectional descriptive study at the Principal Hospital in Dakar. All patients with an INR greater than 5 were included. We studied patients' gender and age, VKA used, drug use period, indications, INR value, associated drugs, presence of hemorrhage, immediate management and evolution. We enrolled 154 patients. Acenocoumarol was the most prescribed VKA. Sex ratio favoured women. The average age was 63 years. Overdose was asymptomatic in 43% of patients. Hemorrhagic symptoms were mainly represented by gingival bleeding, epistaxis. Major bleeding episodes were found in 8.6% of patients and they were represented by melena in 6 patients (3.9%), deep muscle hematoma in 2 patients (1.3%) and intracerebral parenchymal hematoma in 2 patients. Two patients had cardiovascular collapse associated with deglobulisation. Nonsteroidal anti-inflammatory drugs (NSAIDs) assumption was noted in 21% of patients. VKA assumption was suspended transiently in all patients. Mortality was 2%, due to intracranial hemorrhage. The reduction in VKA overdose requires caregivers to manage overdose factors and provide proper patient education.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Cross-Sectional Studies; Drug Overdose; Female; Hematoma; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Senegal; Vitamin K; Young Adult

During the last few decades, the survival of preterm infants has increased dramatically. Nevertheless, with the increasing number of very young and extremely low birth weight infants, morbidity is still a major problem. Intraventricular Haemorrhage (IVH) is a major complication of preterm birth, and large haemorrhages or haemorrhages associated with parenchymal brain lesions may yield a high rate of future disability. IVH is a complex, multi-factorial disorder. Prematurity and low birth weight remain as its most important risk factors, affecting vulnerability of the germinal matrix as well as the coagulation system. Approximately 80% of IVHs occur by 72 h after birth, but a considerable proportion of IVH is already visible on the first cranial ultrasound scan within a few hours of birth. The hypothesis that a severe coagulation deficiency in the premature newborn could be a major contributing factor to IVH has been suggested, and small open label interventional studies targeting the premature coagulation system have been conducted with ethamsylate, vitamin K, fresh frozen plasma, recombinant activated factor VII and prothrombin complex concentrate. The outcome of these studies will be reviewed.

Topics: Blood Coagulation; Blood Coagulation Factors; Brain; Cerebral Ventricles; Ethamsylate; Factor VIIa; Gestational Age; Hemostatics; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Intracranial Hemorrhages; Plasma; Recombinant Proteins; Risk Factors; Treatment Outcome; Vitamin K

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Pressure; Comorbidity; Diet; Dose-Response Relationship, Drug; Endoscopy, Digestive System; Gastrointestinal Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Medical History Taking; Polypharmacy; Referral and Consultation; Vitamin K; Warfarin

Very premature infants are at high risk of bleeding complications; however, few data exist on ranges for standard coagulation tests.. The primary objective of this study was to measure standard plasma coagulation tests and thrombin generation in very premature infants compared with term infants. The secondary objective was to evaluate whether an association existed between coagulation indices and intraventricular hemorrhage (IVH).. Cord and peripheral blood of neonates < 30 weeks gestational age (GA) was drawn at birth, on days 1 and 3 and fortnightly until 30 weeks corrected gestational age. Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and coagulation factor levels were measured and tissue factor-stimulated thrombin generation was characterized. Control plasma was obtained from cord blood of term neonates.. One hundred and sixteen infants were recruited. Median (range) GA was 27.7 (23.7-29.9) weeks and mean (SD) birth weight was 1020 (255) g. Median (5th-95th percentile) day 1 PT, APTT and fibrinogen were 17.5 (12.7-26.6) s, 78.7 (48.7-134.3) s and 1.4 (0.72-3.8) g L(-1) , respectively. No difference in endogenous thrombin potential between preterm and term plasma was observed, where samples were available. Levels of coagulation factors II, VII, IX and X, protein C, protein S and antithrombin were reduced in preterm compared with term plasma. Day 1 APTT and PT were not associated with IVH.. In the largest cross-sectional study to date of very preterm infants, typical ranges for standard coagulation tests were determined. Despite long clotting times, thrombin generation was observed to be similar in very preterm and term infants.

Topics: Blood Coagulation Factors; Blood Coagulation Tests; Blood Component Transfusion; Cerebral Ventricles; Cross-Sectional Studies; Female; Fetal Blood; Fibrinogen; Gestational Age; Hemorrhagic Disorders; Humans; Infant, Newborn; Infant, Premature; Infant, Small for Gestational Age; Intensive Care, Neonatal; Intracranial Hemorrhages; Male; Partial Thromboplastin Time; Prospective Studies; Prothrombin Time; Recombinant Proteins; Reference Standards; Thrombin; Thromboplastin; Vitamin K

Topics: Administration, Oral; Antibodies, Monoclonal, Humanized; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation; Coagulants; Humans; Intracranial Hemorrhages; Vitamin K

Topics: Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Stroke; Vitamin K

Intracerebral hemorrhage (ICH) is the most feared complication associated with vitamin K antagonists (VKAs). We performed a retrospective study on the clinicoradiologic characteristics that influence its outcome.. We reviewed the clinical histories and neuroimaging studies of all patients attended at the Hospital Universitario Central de Asturias in 2010-2011 who had an ICH while being on VKA and analyzed the differential characteristics between patients with acceptable versus poor outcomes attending to 3 end points: death, poor outcome (modified Rankin Scale [mRS] score ≥ 4) at discharge, and poor outcome 3 months later. Additionally, CHA2DS2-VASc and HAS-BLED scores (validated tools for prediction of the risk of stroke and major hemorrhage, respectively, in patients with atrial fibrillation) were calculated to assess a priori risk-benefit balance for anticoagulant therapy.. Eighty patients entered the sample (median age of 79 years). A priori annual risk of major bleeding surpassed ischemic stroke risk-without anticoagulation-only in 4. Fifty percent of the patients had an initial Glasgow Coma Scale (GCS) score lower than 13; in 51.3%, initial international normalized ratio was above their therapeutic range. Median hematoma size was 24.75 cc(3); relevant growth (≥33%) occurred in 29.4% of patients with a second computed tomography scan. On multivariable analysis, overall in-hospital mortality (47.5%) was related to prior antiplatelet therapy (P = .008), GCS (P = .001), and perilesional edema size (P = .036). Baseline mRS (P = .058) and National Institutes of Health Stroke Scale (NIHSS) scores (P = .008) were associated with poor outcome at discharge (77.5%). Initial NIHSS (P = .005) and glycemia (P = .038) predicted 3-month poor outcome (68.3%). VKA reversal was performed in almost all patients, which prevented assessment of its therapeutic value.. VKA-associated ICH presents in a particularly vulnerable population and has a poor prognosis that may be reliably predicted by several clinicoradiologic features.

Topics: Aged; Aged, 80 and over; Anticoagulants; Brain; Female; Glasgow Coma Scale; Hospital Mortality; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Retrospective Studies; Risk Factors; Treatment Outcome; Vitamin K

Late vitamin K deficiency bleeding (VKDB) can be serious and manifest as early onset intracranial haemorrhage (ICH). This study aimed to determine the frequency of ICH in relation to vitamin K deficiency and the outcome in infants aged two to 24 weeks.. A hospital-based study was conducted in two main tertiary hospitals in Cairo, Egypt, from May 2011 to May 2012 with 40 patients with ICH and 50 age-matched controls without ICH.. Forty patients with ICH were recruited, 19 were excluded for clinical reasons and the remaining 21 had a significantly low vitamin K level. Exclusive breast feeding (81% of patients), diarrhoea lasting more than 1 week (38.1%) and antibiotic consumption within a week before the development of ICH (57.1%) were more common in the patients than in the control group (p value>0.05, <0.01 and <0.01, respectively).. A high frequency of ICH due to late VKDB was reported in Egyptian infants aged two to 24 weeks, with poorer outcomes than international studies. A national survey is required to evaluate the timing and protective value of a second booster vitamin K dose to reduce ICH, especially in high-risk patients in this age group.

Topics: Case-Control Studies; Egypt; Female; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Male; Sex Distribution; Tertiary Care Centers; Vitamin K; Vitamin K Deficiency Bleeding

To evaluate the risk of recurrent intracranial hemorrhage (ICH) in patients on vitamin K antagonists (VKAs) after a first episode of ICH.. The Cerebral Haemorrhage in patients Restarting Oral Anticoagulant Therapy (CHIRONE) Study collected data of patients eligible for the study from the database of 27 centers affiliated with the Italian Federation of Anticoagulation Clinics.. We enrolled 267 patients (163 male, median age 73.9 years) who had received VKA anticoagulation after an ICH event. During the total period of follow-up (778 patient-years), ICH recurred in 20 patients (7.5%; rate 2.56 × 100 patient-years) at a median time of 16.5 months, and was fatal in 5 patients (25%; rate 0.4 × 100 patient-years). Male sex, hypertension, prosthetic valves, previous ischemic stroke, renal failure, cancer, and spontaneous events were associated with the risk of recurrence, though none of them in isolation reached statistical significance. More than one-third of spontaneous recurrences occurred in patients with a posttraumatic index event.. Our results show that patients with a history of ICH carry a significant risk of recurrent ICH when treated with VKA anticoagulation. The risk is also present, though to a lower degree, in patients with previous posttraumatic events. All patients with a history of ICH require a careful evaluation of their thromboembolic risk to estimate the net clinical benefit of (re)starting anticoagulation with VKAs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Child; Female; Follow-Up Studies; Health Surveys; Humans; Intracranial Hemorrhages; Male; Middle Aged; Recurrence; Risk Factors; Time Factors; Vitamin K; Young Adult

Topics: Administration, Oral; Animals; Anticoagulants; Heparin; Humans; Intracranial Hemorrhages; Pyridines; Rats; Thiazoles; Vitamin K

There are no studies demonstrating that prothrombin complex concentrates (PCC) improves outcome compared FFP in patients with warfarin-associated intracranial hemorrhage.. A prospective, observational study was conducted of patients who received PCC (Bebulin VH), FFP, or PCC + FFP. All groups received vitamin K 10 mg IV. INR reversal (<1.4), adverse events (venous thromboembolism, myocardial infraction, pulmonary edema), major hemorrhage (new or worsened intracranial hemorrhage, anemia requiring transfusion or GI bleed), and 3-month functional outcome were compared between the groups using Chi squared and logistic regression analysis.. Of 64 patients, PCC alone was used in 16 (mean dose 48 IU/kg), FFP alone in 25 (mean dose 12.5 ml/kg), and PCC + FFP in 23 (median doses 47.4 IU/kg and 11.4 ml/kg, respectively). INR correction occurred in 88, 84, and 70 %, respectively. There were no differences in time to INR correction or adverse events between the groups, but FFP alone was associated with more major hemorrhage after administration (52 %, OR 5.0, 95 % CI 1.6-15.4, P = 0.006) and PCC with less (6 %, OR 0.1, 95 % CI 0.01-0.8, P = 0.033). After adjusting for age, admission GCS, initial INR, and bleed type, the use of PCC was associated with a lower risk of death or severe disability at 3-months (adjusted OR 0.02, 95 % CI 0.001-0.8, P = 0.039), while FFP alone was associated with a higher risk (adjusted OR 51.6, 95 % CI 1.2-2163.1, P = 0.039).. PCC adequately corrected INR without any increase in adverse events compared to FFP and was associated with less major hemorrhage and improved 3-month outcomes in patients with warfarin-associated intracranial hemorrhage.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Component Transfusion; Female; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Logistic Models; Male; Middle Aged; Plasma; Prospective Studies; Treatment Outcome; Vitamin K; Warfarin; Young Adult

Vitamin K deficiency bleeding is one of the most common causes of acquired hemostatic disorder in early infancy. Although vitamin K is practiced routinely after every birth in Turkey, children with type of vitamin K deficiency bleedings (L-VKDB) can be encountered. We aimed to evaluate the clinical features of the children with L-VKDB reported from Turkey.. Between 1995 and 2013, 48 studies reporting 534 children with L-VKDB were evaluated in this study.. Of the 534 reported children (178 girls, 356 boys), 486 (91 %) were extremely breastfed. The most common bleeding sites were intracranial hemorrhage, gastrointestinal, and umbilical in 414 (77.4 %), 33 (6.2 %), and 33 (6.2 %) children, respectively, and 35 (6.6 %) children had been diagnosed incidentally without any bleeding. The etiology of 399 (74.7 %) children were classified as idiopathic, whereas 135 (25.3 %) were secondary. Intramuscular vitamin K was administered in 248 (46.4 %), not administered in 228 (42.7 %), and the administration of vitamin K were not determined in 58 (10.9 %) children. The outcomes of Turkish cohort showed that 111 (20.8) children died, 257 (48.1 %) cases developed neurologic deficit (mainly epilepsy and psychomotor retardation), and only 166 (31.1 %) patients recovered without squeal.. The compliance of prophylactic measures in Turkey does not seem to be satisfactory. As a further measure of tomorrow, we vigorously emphasize that a national surveillance program may be initiated. An additional intramuscular dose or oral supplementation of vitamin K especially for exclusively breast-fed infants may reduce this catastrophic problem in our country.

Topics: Databases, Factual; Female; Humans; Infant; Intracranial Hemorrhages; Male; Retrospective Studies; Turkey; Vitamin K; Vitamin K Deficiency Bleeding

Newborns are at risk for vitamin K deficiency and subsequent bleeding unless supplemented at birth. Vitamin K deficiency bleeding is an acquired coagulopathy in newborn infants because of accumulation of inactive vitamin K-dependent coagulation factors, which leads to an increased bleeding tendency. Supplementation of vitamin K at birth has been recommended in the United States since 1961 and successfully reduced the risk of major bleeding. Refusal or omission of vitamin K prophylaxis is increasing and puts newborn infants at risk for life-threatening bleeding.. Over an eight month period, we encountered seven infants with confirmed vitamin K deficiency; five of these patients developed vitamin K deficiency bleeding.. The mean age of the seven infants with vitamin K deficiency was 10.3 weeks (range, 7-20 weeks); manifestations ranged from overt bleeding to vomiting, poor feeding, and lethargy. None of the infants had received vitamin K at birth, and all were found to have profound derangement of coagulation parameters, which corrected rapidly with administration of vitamin K in IV or intramuscular form. Four of the seven infants had intracranial hemorrhage; two of these infants required urgent neurosurgical intervention.. Supplementation of vitamin K at birth for all newborns prevents major hemorrhagic complications, such as intracranial bleeding, due to vitamin K deficiency. Parental refusal of vitamin K is increasingly common. It is critical that health care providers and the public be made aware of the varied presentation of this preventable acquired coagulopathy.

Topics: Age of Onset; Brain; Female; Follow-Up Studies; Humans; Infant; Intracranial Hemorrhages; Male; Treatment Refusal; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

Dabigatran etexilate (DE), rivaroxaban, and apixaban are nonvitamin K antagonist oral anticoagulants (NOACs) that have been compared in clinical trials with existing anticoagulants (warfarin and enoxaparin) in several indications for the prevention and treatment of thrombotic events. All NOACs presented bleeding events despite a careful selection and control of patients. Compared with warfarin, NOACs had a decreased risk of intracranial hemorrhage, and apixaban and DE (110 mg BID) had a decreased risk of major bleeding from any site. Rivaroxaban and DE showed an increased risk of major gastrointestinal bleeding compared with warfarin. Developing strategies to minimize the risk of bleeding is essential, as major bleedings are reported in clinical practice and specific antidotes are currently not available. In this paper, the following preventive approaches are reviewed: improvement of appropriate prescription, identification of modifiable bleeding risk factors, tailoring NOAC's dose, dealing with a missed dose as well as adhesion to switching, bridging and anesthetic procedures.

Topics: Administration, Oral; Anticoagulants; Clinical Trials as Topic; Humans; Intracranial Hemorrhages; Risk Factors; Vitamin K

Topics: Brain; Female; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Male; Parents; Treatment Refusal; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

To compare the safety and effectiveness of three methods of reversing coagulopathic effects of warfarin in patients with potentially life-threatening intracranial hemorrhage.. A retrospective electronic medical record review of 63 patients with warfarin-related intracranial hemorrhage between 2007 and 2010 in an integrated health care delivery system was conducted. The three methods of rapid warfarin reversal were fresh-frozen plasma (FFP), activated factor VII (FVIIa; NovoSevenRT [Novo Nordisk, Bagsværd, Denmark]), and prothrombin complex concentrate (PCC; BebulinVH [Baxter, Westlake Village, California, USA], ProfilnineSD [Grifols, North Carolina, USA]), each used adjunctively with vitamin K (Vit K, phytonadione). We determined times from reversal agent order to laboratory evidence of warfarin reversal (international normalized ratio [INR]) in the first 48 hours and compared INR rebound rates and complications in the first 48 hours.. Reversal with FFP took more than twice as long compared with FVIIa or PCC. To reach an INR of 1.3, mean (±SD) reversal times were 1933 ± 905 minutes for FFP, 784 ± 926 minutes for FVIIa, and 980 ± 1021 minutes for PCC (P < 0.001; P < 0.01 between FFP and FVIIa, P < 0.05 between FFP and PCC). INR rebound occurred in 0 of 31 patients for FFP, 4 of 8 for FVIIa, and 0 of 7 for PCC (P = 0.001). Complications were uncommon. FVIIa was 15 and 3.5 times as expensive as FFP and PCC, respectively.. As an adjunct to Vit K for rapid warfarin reversal, FVIIa and PCC appear more effective than FFP. Either FVIIa or PCC are reasonable options for reversal, but FVIIa is considerably more expensive and may have greater risk of INR rebound.

Topics: Aged; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Electronic Health Records; Emergency Medical Services; Factor VII; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Neurosurgical Procedures; Plasma; Recombinant Proteins; Retrospective Studies; Vitamin K; Warfarin

Dabigatran, rivaroxaban, and apixaban are the new oral anticoagulants (NOAC) which have been investigated in patients with atrial fibrillation (AF) for primary and secondary prevention of stroke and thromboembolism. In these trials NOAC had a similar efficacy and safety profile compared to traditional vitamin-K-antagonists such as warfarin. We advise caution in the use of NOAC in patients with stroke or cerebral hemorrhage because of the following reasons: 1) Patients with cerebral bleeding were excluded from the trials. 2) Stroke within 14 days and severe stroke within 6 months before screening were exclusion criteria in the trials investigating dabigatran and rivaroxaban. 3) There is no antidote for reversal and no reliable laboratory monitoring of the anticoagulant effect for emergency situations. 4) NOAC are either substrates of the P-glycoprotein (P-gp) or are metabolized by the cytochrome P450 (CYP) system, or both. Drug-drug interactions between NOAC and P-gp and CYP-affecting drugs are largely unknown. 5) Long-term effects of thrombin generation inhibition on the occurrence of infections, malignancies, dementia, and other diseases are unknown. Based on these considerations it is our opinion that studies of NOAC in patients with stroke compared with other prevention strategies, as well as more post marketing surveillance data, are required.

Topics: Animals; Anticoagulants; Humans; International Normalized Ratio; Intracranial Hemorrhages; Platelet Aggregation Inhibitors; Stroke; Thrombin; Vitamin K

The objective of the present study was to investigate the efficacy of a four-factor prothrombin complex concentrate (Prothromplex, PTX) in shortening prolonged international normalized ratio or controlling life-threatening bleeding. The study was a retrospective single-centre study that included 142 patients treated with PTX and allocated in three groups: patients on vitamin K antagonists (VKA) (acenocumarol) and undergoing invasive procedure or presenting with severe bleeding (n = 76), patients treated with VKA presenting with intracranial haemorrhage (n = 22), and patients not on VKA and presenting with uncontrolled bleeding (n = 44). The primary outcome variable was international normalized ratio (INR) return to the norm after PTX infusion. Secondary outcome variables included bleeding control and reduction of transfusion rate. Overall, patients received a median of 1200 IU (≈15 IU/kg) of PTX, and INR decreased from 4 ± 3 to 1.7 ± 1.2 (P < 0.01) in all groups, although it remained at least 1.4 in 38% of patients (29.3% among patients receiving 25 IU/kg vs. 42.6% among those receiving 15 IU/kg; P < 0.05). Patients with initial INR at least 4 benefited the most from treatment. After PTX administration, there was a significant reduction in both transfused blood components units (P < 0.01) and estimated blood loss volume (from 1500 ± 1500 to 200 ± 100 ml; P < 0.01), and only one episode of deep venous thrombosis was observed. Administration of fixed doses of PTX shortened prolonged international normalized ratio and improved life-threatening bleeding in patients with or without VKA therapy. Higher dose attained a more adequate post-infusion INR.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Factors; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Adolescent; Anticoagulants; Female; Humans; Intracranial Hemorrhages; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Intracranial Hemorrhages; Meta-Analysis as Topic; Stroke; Vitamin K

Deficiency of vitamin K predisposes to early, classic or late hemorrhagic disease of the newborn (HDN); of which late HDN may be associated with serious and life-threatening intracranial hemorrhage. Late HDN is characterized intracranial bleeding in infants aged 1 week to 6 months due to severe vitamin K deficiency. Late HDN is still an important cause of mortality and morbidity in developing countries where vitamin K prophylaxis is not routinely practiced. Children with cholestatic liver disease are at risk for developing secondary vitamin K deficiency because of fat malabsorbtion and inadequate dietary intake. In this study, we described 11 infants with cholestatic liver disease with different etiologies exhibiting intracranial hemorrhage (ICH). Six patients underwent surgical evacuation of ICH, following the administration of vitamin K and/or fresh frozen plasma. The possibility of cholestatic liver disease should be considered in the treatment of ICH due to vitamin K deficiency.

Topics: Brain; Cholestasis, Intrahepatic; Fatal Outcome; Female; Giant Cells; Hepatitis; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Neurosurgical Procedures; Plasma; Tomography, X-Ray Computed; Vitamin K; Vitamin K Deficiency Bleeding; Vitamins

Prothrombin complex concentrates (PCCs) offer a means for the rapid reversal of warfarin, particularly in the setting of life-threatening bleeding. We evaluated the effectiveness and safety of a PCC-based protocol in patients with warfarin-associated intracerebral hemorrhage (ICH), subdural hematoma (SDH), or subarachnoid hemorrhage (SAH). This was a retrospective case-series review of patients treated with an institution-approved warfarin reversal protocol. Patients with intracranial hemorrhage and known warfarin use with an international normalized ratio (INR)>1.4 received fresh frozen plasma (FFP), vitamin K (phytonadione), and weight-based, 3-factor PCC (Profilnine(®) SD) dose based on the initial INR. Demographic and clinical information, the degree of and time to INR normalization, and adverse events were recorded. The thirty study patients included 19 with primary ICH, 7 with SDH, and 4 with SAH. The mean age was 72.8 (±11) years, including 11 (37%) patients ≥80years old. The median presenting INR was 2.3 (IQR 2-3.3) and post-treatment INR was 1.4 (IQR 1.3-1.5, Z score 6.4, p<0.001). Median time from PCC administration to the first follow up INR was 95 (IQR 50-140) min. No patient's INR increased by more than 0.3 over 72h. Nine patients (30%) underwent neurosurgical procedures after PCC administration and no procedure-related bleeding complication was noted. Adverse events included 3 instances of early hematoma expansion, one ischemic stroke in a patient with endocarditis on post-PCC day 1, one pulmonary embolism 5weeks after PCC treatment, and one coronary in-stent thrombosis 60days after PCC treatment. 6 patients died prior to hospital discharge of anticipated complications of their initial event, and none from identifiable thrombotic complications of PCC. A 3-factor PCC preparation (Profilnine(®) SD), administered with FFP and vitamin K to patients with acute warfarin-associated intracranial bleeding is a reasonable approach to urgent warfarin reversal. However, randomized, prospective trials are needed to verify the safety and clinical effectiveness of PCC administration in this population.

Topics: Aged; Aged, 80 and over; Algorithms; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Hemostatics; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Neurosurgical Procedures; Plasma; Treatment Outcome; Vitamin K; Warfarin

Topics: Anticoagulants; Humans; Intracranial Hemorrhages; Risk Factors; Secondary Prevention; Stroke; Vitamin K

The prophylactic oral administration of vitamin K to newborns has markedly reduced the incidence of vitamin K deficiency (VKD); however, intracranial hemorrhage (ICH) is still one of the complications found in biliary atresia (BA) patients and is associated with VKD bleeding. Therefore, we aimed to investigate the incidence and long-term outcome of ICH in patients with BA who previously received prophylactic vitamin K during the neonatal period.. Eighty-eight consecutive infants with BA were treated and followed up at Kyushu University Hospital from 1979 to 2009. The clinical records and imaging study results were retrospectively reviewed in the infants with BA who presented with ICH.. ICH occurred in 7.95% of patients with BA. The onset of ICH occurred at 47 to 76 days after birth, before the patients underwent surgery for BA (9-37 days after the onset of ICH). Coagulopathy was found upon admission in all of the cases with available data and improved after intravenous administration of vitamin K. A craniotomy was required in 2 cases before the surgery for BA. During the 22 to 278 months of follow-up, some neurologic sequelae persisted in 5 of 7 cases. Follow-up head computed tomography scans showed a low-density area in the left hemisphere in 5 cases.. Although vitamin K prophylaxis had been given during the neonatal period, ICH-associated VKD bleeding was still found in 7.95% of patients with BA. Persistent neurologic sequelae were found in 5 of 7 cases, with low-density area in the left hemisphere.

Topics: Administration, Oral; Biliary Atresia; Female; Follow-Up Studies; Humans; Incidence; Infant, Newborn; Intracranial Hemorrhages; Male; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome; Vitamin K; Vitamin K Deficiency Bleeding

This retrospective study presents clinical, demographical features and radiological findings as well as outcomes of 31 infants with intracranial hemorrhage (ICH) due to vitamin K deficiency and hence evaluates the risk factors involved.. Thirty-one cases (17 males and 14 females) having a mean age of 52.52 ± 20.80 days with intracranial hemorrhage due to late hemorrhagic disease of the newborn (LHDN), hospitalized in our clinics were included in the study. Cranial computerized tomography (CT) was performed in all patients for the diagnosis and evaluation of ICH.. It was found that the most frequent presenting symptoms were pallor (77.4%), seizures (58%), altered consciousness (58%), vomiting (44%) and poor feeding (35%). Pulsatile fontanel was found in 61% and bulging in 26%. Seven (22.5%) patients had prior history of antibiotic usage. All patients (93.5%) except two were breast fed. Sixteen (51.6%) were delivered at home. Eighteen (58%) had a history of single-dose vitamin K prophylaxis on the first day of delivery. Parenchymal (44%), subdural (39%) or subarachnoidal (22.5%) bleeding was observed. Seven (22.6%) were exitus. During the follow-up period (ranging from 3 months to 18 months) neurological examination findings were recorded.. Our results indicate that it may be questionable whether single-dose vitamin K prophylaxis at birth is adequate for the prevention of LHDN and if a different timing of this prophylaxis should be made for the exclusively breast fed infants.

Topics: Female; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Male; Retrospective Studies; Risk Factors; Tomography, X-Ray Computed; Turkey; Vitamin K; Vitamin K Deficiency Bleeding; Vitamins

Topics: Administration, Oral; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Factors; Contraindications; Humans; Intracranial Hemorrhages; Phenprocoumon; Plasma; Vitamin K

Although the incidence of vitamin K deficiency bleeding (VKDB) in neonates has dramatically decreased in the developed world since the adoption of routine vitamin K prophylaxis, in developing countries the incidence is still high. Intracranial hemorrhage (ICH) is the most dangerous complication. Early recognition and management are important to decrease the mortality rate and neurological sequelae. The authors conducted a prospective study between January 2008 and June 2010. They included all full-term neonates referred to the Department of Neurosurgery at Mansoura University Children's Hospital with ICH complicating VKDB and necessitating surgical evacuation. The objective was to evaluate the clinical presentation, diagnosis, hospital course, and outcome of ICH in full-term neonates with VKDB after surgical evacuation.. Thirty-two neonates with ICH due to VKDB were included. Diagnosis and classification of ICH were based on detailed history, physical examination, and the interpretation of CT or MR imaging studies. The diagnosis of VKDB was based on pretreatment coagulation studies (prothrombin time [PT] and partial thromboplastin time [PTT]), which are grossly abnormal, together with a normal platelet count and correction of coagulation results to normal after vitamin K administration.. The mean age (± SD) at onset of symptoms was 20.4 ± 4.9 days. Two neonates (6.25%) had early VKDB, 7 (21.9%) had classic VKDB, and 23 (71.9%) had late VKDB. The most common neurological manifestations included focal seizures, disturbed consciousness level, and tense anterior fontanel. The most common general manifestations included pallor, respiratory distress, and bleeding from other sites. Radiological findings varied from acute subdural hemorrhage (SDH) in 18 cases (56.3%), intracerebral hemorrhage in 10 (31.3%), and acute SDH with underlying intracerebral hemorrhage, intraventricular hemorrhage, and/or subarachnoid hemorrhage in 4 (12.5%). Before administration of vitamin K, the PT was 72.1 ± 45.0 seconds and the PTT was 112.4 ± 57.6 seconds. Six to 12 hours after administration of vitamin K, the PT was 14.6 ± 1.6 seconds and the PTT was 34.4 ± 1.0 seconds. All patients underwent surgery for evacuation of the ICH after correction of PT, prothrombin activity, and international normalized ratio. Evacuation of the ICH was done by either free or osteoblastic bone flap. Six patients (18.8%) died, and the other 26 patients had variable degrees of morbidity during the follow-up period (3-24 months).. Vitamin K deficiency bleeding, especially the late-onset form, is an important cause of neonatal ICH. In the present study, the most frequent form of ICH in neonates was SDH. Focal seizures, disturbed consciousness level, tense anterior fontanel, unexplained anemia, and respiratory distress were the major presenting signs. Despite early surgical evacuation, these cases are associated with high mortality rate and neurological disabilities. Vitamin K prophylaxis at birth may reduce these severe complications.

Topics: Female; Hematoma, Subdural; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intracranial Hemorrhages; Male; Prospective Studies; Tomography, X-Ray Computed; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Antiparkinson Agents; Female; Humans; Indoles; Intracranial Hemorrhages; Middle Aged; Parkinson Disease; Vitamin K

Patients with prosthetic heart valves require lifelong anticoagulation to prevent thromboembolism. When they have intracranial haemorrhage, anticoagulation has to be withheld. This study was aimed to identify safety duration and complications of anticoagulation withholding in patients with prosthetic heart valves and intracranial haemorrhage. This was a retrospective descriptive study in 26 prosthetic heart valve patients hospitalised in Srinagarind Hospital, Khon Kaen University because of intracranial haemorrhage from 2003 to 2008. Range of anticoagulation withholding was 1 to 26 days with mean 8.5 ± 7.7 days. Most patients (84.6%) were withheld anticoagulation for less than 14 days. There were five in-hospital deaths mostly within 3 days of admission from severe intracranial haemorrhage. No data of reintroduction of anticoagulation was found in three patients because they were lost to follow up. One patient had right basal ganglia infarction after 7 days of anticoagulation withholding. Prosthetic heart valve dysfunction was suspected in one patient who withheld anticoagulant for 76 days. Discontinuation of anticoagulation in patients with prosthetic heart valves and intracranial haemorrhage for less than 7 days was associated with low thromboembolic risk and there was no clinical evidence of prosthetic heart valve dysfunction when anticoagulation was withheld for less than 14 days.

Topics: Adult; Anticoagulants; Aspirin; Atrial Fibrillation; Combined Modality Therapy; Comorbidity; Contraindications; Craniotomy; Female; Heart Valve Prosthesis; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Thailand; Thromboembolism; Time Factors; Vitamin K; Warfarin

To describe the characteristics, management and outcomes of patients with major trauma who were taking warfarin; explore the use of rapid anticoagulation reversal; and assess the effect of reversal on outcomes.. Retrospective cohort analysis of prospective data extracted from the trauma registries and patient charts of the two adult trauma referral hospitals with neurosurgical units in Western Australia, 2000 to 2005. Inclusion criteria were: major trauma (injury severity score > 15); first international normalised ratio (INR) after injury > 1.4; and documented (in registry or chart) warfarin use.. Eighty patients were identified. Their mean age was 76.8 years. Forty-six were men; 34 were transferred from another hospital; 28 died; and the functional outcomes of 58 were worse at discharge from hospital than before injury. Intracranial haemorrhage (ICH) occurred in 62, of whom 25 died; the difference in mortality between those with ICH and those without ICH was insignificant. Warfarin reversal started 17.4 hours (mean) after injury and the documented period between injury and completion of reversal was 54.2 hours (mean). Multiple logistic regression models, controlling for age, sex, on-scene Glasgow Coma Scale (GCS), initial INR and progressive ICH, showed no independent survival benefit for rapid reversal. Factors associated with mortality were age (22% increase per year [95% CI, 17%-34%]) and progressive ICH on computed tomography scan (24 of the 36 patients with progressive ICH died v one of the 26 patients with stable ICH died). Every point increase in on-scene GCS > 8 increased survival likelihood by 215% (95% CI, 119%-388%).. Patients with major trauma taking warfarin at the time of injury have high mortality rates, poor functional outcomes and long delays to initiation and completion of anticoagulation reversal. Rapid, appropriate warfarin reversal was rarely performed and was not independently associated with survival. Age, low on-scene GCS and progressive ICH were strongly associated with mortality, but presenting INR, ICH v no ICH, and sex were not.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Causality; Cohort Studies; Factor VIII; Female; Fibrinogen; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Plasma; Registries; Treatment Outcome; Vitamin K; Warfarin; Western Australia; Wounds and Injuries

We report the case of a 6-week-old female who presented an intracranial hemorrhage due to late vitamin K deficiency bleeding (VKDB). No other evident bleeding sites were present at the moment of diagnosis. Intramuscular vitamin K (1 mg) was administered at birth. She was exclusively breast-fed. No other risk factors for VKDB were detected. Low levels of vitamin K-dependent coagulation factors and their normalization after vitamin K administration confirmed the diagnosis of late VKDB. The present case suggests potential risks related to a single dose of intramuscular vitamin K at birth.

Topics: Age of Onset; Antifibrinolytic Agents; Female; Humans; Infant, Newborn; Injections, Intramuscular; Intracranial Hemorrhages; Treatment Outcome; Vitamin K; Vitamin K Deficiency

In Texas, apprentice midwives do not have prescriptive authority to administer parenteral vitamin K. This case report underscores the importance of parenteral vitamin K administration in preventing vitamin K deficiency bleeding and the potential danger in prohibiting apprentice midwives from providing this standard of care to the newborn.

Topics: Antifibrinolytic Agents; Brain Death; Humans; Infant; Injections, Intramuscular; Intracranial Hemorrhages; Male; Midwifery; Texas; Vitamin K; Vitamin K Deficiency

In rare cases, severe fetal vitamin K deficiency bleeding may occur in utero as a result of insufficient vitamin K placental transfer. We present a case of a 32-week-preterm infant born with severe intracranial hemorrhage to a pregnant woman who suffered from hyperemesis gravidarum. Neonatal hematologic status was compatible with vitamin K deficiency whereas the maternal coagulation function was normal. This case emphasizes the potential risk of fetal bleeding owing to vitamin K deficiency in pregnancies complicated with hyperemesis gravidarum. These women should be closely monitored and vitamin K prophylaxis might be considered.

Topics: Adult; Antifibrinolytic Agents; Female; Fetal Diseases; Gestational Age; Humans; Hyperemesis Gravidarum; Infant, Newborn; Intracranial Hemorrhages; Male; Pregnancy; Pregnancy Trimester, Third; Vitamin K; Vitamin K Deficiency

Intracranial haemorrhage in typhoid fever is very rare. We report another case of non-traumatic intracranial hemorrhage in a 6-year-old boy suffering from typhoid fever, unconsciousness, seizure and non-coherent speech. Investigations revealed severe thrombocytopenia and prolonged prothrombin time. CT scan of brain showed intraparenchymal haemorrhage in frontal regions bilaterally with perilesional oedema, subarachnoid bleed and extension into the lateral ventricles. No aneurysm or arterio-venous malformation was seen on MR angiography. The patient recovered without any neurological deficit.

Topics: Anti-Bacterial Agents; Antifibrinolytic Agents; Blood Transfusion; Ceftriaxone; Child, Preschool; Humans; Intracranial Hemorrhages; Male; Risk Factors; Typhoid Fever; Vitamin K

Topics: Adult; Female; Fetal Diseases; Gestational Age; Humans; Hydrocephalus; Hyperemesis Gravidarum; Intracranial Hemorrhages; Parenteral Nutrition, Total; Pregnancy; Ultrasonography, Prenatal; Vitamin K; Vitamin K Deficiency

Since vitamin K2 (VitK2) syrup prophylaxis has become a routine measure for neonates and young infants, the incidence of vitamin K deficiency (VitK-D) in infancy has markedly decreased. However, we recently experienced 2 infantile cases of VitK deficiency, in whom intracranial hemorrhage (ICH) was the first clinical sign of CMV hepatitis. Case 1 is a breast-fed boy who received VitK2 syrup orally at birth and at the age of 1 month. He did not suckle well and developed a generalized tonic convulsion twice at the age of 8 weeks. Case 2 is a mixed-fed boy who also received VitK2 syrup twice but developed vomiting and drowsiness at the age of 4 months. In both cases, laboratory tests showed anemia, leukocytosis, liver dysfunction with cholestasis, and coagulopathy, consistent with VitK-D abnormality. Their serological analyses showed that cytomegalovirus (CMV) IgG and IgM were both positive. In case 1, CMV DNA was positive, as judged by the PCR method. In case 2, CMV antigenemia was positive. Hence we diagnosed these two patients as having VitK-D ICH caused by CMV hepatitis with cholestasis. CMV hepatitis is a risk factor of VitK-D ICH.

Topics: Cholestasis, Intrahepatic; Cytomegalovirus; Cytomegalovirus Infections; Hepatitis, Viral, Human; Humans; Infant; Intracranial Hemorrhages; Male; Radionuclide Imaging; Vitamin K; Vitamin K Deficiency

Late haemorrhagic disease of the newborn (HDN) can occur owing to a lack of vitamin K prophylaxis, as a manifestation of an underlying disorder or idiopatically from the 8th day to 12 weeks after birth.. Eight infants admitted to Kocaeli University Hospital with nine episodes of late HDN between January 2002 and April 2005 were evaluated retrospectively from hospital records.. The median age at presentation was 46 (26-111) days. All the infants were born at full-term to healthy mothers and were exclusively breast-fed. All had an uneventful perinatal history, except one who had meconium aspiration. Four patients had received no vitamin K prophylaxis and another three had uncertain histories. At presentation, six had intracranial bleeding and the remainder had bleeding either from the venepuncture site or the gastro-intestinal tract. The presenting signs and symptoms were irritability, vomiting, bulging or full fontanelle, convulsions and diminished or absent neonatal reflexes. Galactosaemia was detected in a 2-month-old infant with prolonged jaundice. There was no surgery-related mortality or complications but one survived for only 2 days on ventilatory support following surgery. Only one of the six survivors had severe neurological sequelae.. Late HDN frequently presents with intracranial haemorrhage, leading to high morbidity and mortality. HDN can be the manifestation of an underlying metabolic disorder. Vitamin K prophylaxis of the newborn should be routine in developing countries.

Topics: Age Factors; Female; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Male; Prognosis; Retrospective Studies; Treatment Outcome; Vitamin K; Vitamin K Deficiency Bleeding

Topics: Antifibrinolytic Agents; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Vitamin K; Vitamin K Deficiency Bleeding

Warfarin-associated intracranial hemorrhage (ICH) requires rapid normalization of clotting function. Current therapies are associated with significant complications and/or prolonged time to correction of coagulopathy. Recombinant factor VIIa (FVIIa) might allow faster and safer correction of coagulopathy.. This article presents a retrospective chart review of all patients with warfarin-associated ICH treated in a neurology/neurosurgery intensive care unit over an 11-month period.. All patients were treated to rapidly reverse the warfarin effect. Fifteen patients received vitamin K and fresh frozen plasma (FFP) alone (FFP group). Twelve patients also received FVIIa (FVIIa group). The median times from presentation to an international normalization ratio (INR) of less than 1.3 were 32.2 and 8.8 hours in the FFP the FVIIa groups, respectively (p = 0.016). INR normalized slowly (at 110 and 130 hours, respectively) in two patients with end-stage renal failure who were given FVIIa, one of whom developed disseminated intravascular coagulation after three doses of FVIIa. No other complications occurred from FVIIa administration. One patient in the FFP group developed severe pulmonary edema.. FVIIa may be an effective adjunct to FFP in warfarin-related ICH, facilitating faster correction of INR and decreasing FFP requirements. A prospective, randomized trial is needed to confirm these preliminary findings and to determine whether there is a clinical benefit.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Drug Therapy, Combination; Factor VII; Factor VIIa; Female; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Plasma; Recombinant Proteins; Retrospective Studies; Treatment Outcome; Vitamin K; Warfarin

Vitamin K deficiency in infants can cause life-threatening haemorrhages. To prevent this, neonates in the Netherlands receive an oral dose of 1 mg vitamin K directly after birth. In addition, because breast milk contains little vitamin K, breast-fed infants receive a daily dose of 25 micrograms the first three months. Of three female infants aged 4 weeks, 5 months and 3 months, respectively, two developed an intracranial haemorrhage, which caused death in one. In two cases there were signs of a bleeding tendency, but no tests were done because the patients appeared healthy otherwise. The underlying resorptive disorders, cholestasis and fat malabsorption, caused few symptoms and were discovered only after a vitamin K deficiency bleeding had occurred. In an infant with a bleeding tendency, one should consider the possibility of vitamin K deficiency, even if adequate prophylaxis has been given.

Topics: Antifibrinolytic Agents; Breast Feeding; Cholestasis; Fatal Outcome; Female; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Lipid Metabolism, Inborn Errors; Vitamin K; Vitamin K Deficiency; Vitamin K Deficiency Bleeding

The use of replacement FVII is critical to the successful treatment of life-threatening bleeds in newborns and infants with severe FVII deficiency (<1%). However, the clinical efficacy, optimum dosage and pharmacologic recovery of rFVIIa in such children has not been studied systematically. This report is a case of an infant with severe FVII deficiency (FVII:C at 0%) and massive intracranial haemorrhage in which successful use of rFVIIa (NovoSeven) was carefully monitored. The drug was administered by intravenous bolus through a central line every 4 h at each of three dose levels: 15 microg kg-1, 22 microg kg-1 and 30 microg kg-1. FVII:C was >100% between 30 and 180 min after each infusion with mean trough levels above 25% for all three dose levels. There was no evidence of hyper-coagulation as indicated by measurements of the platelet count, D-dimer, plasma protamine paracoagulant and fibrinogen levels in spite of high FVII:C concentration. In this infant, rFVIIa was well-tolerated, maintained effective haemostasis with good clinical outcome, and produced consistent therapeutic mean trough levels above 25% FVII:C even at 15 microg kg-1 every 4 h.

Topics: Antigens; Blood Coagulation Tests; Factor VII; Factor VII Deficiency; Factor VIIa; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hematoma; Hemostasis; Hispanic or Latino; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intracranial Hemorrhages; Male; Platelet Count; Protamines; Prothrombin; Recombinant Proteins; Vitamin K

Topics: Breast Feeding; Female; Follow-Up Studies; Humans; Infant; Injections, Intramuscular; Intracranial Hemorrhages; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Vitamin K; Vitamin K Deficiency

A retrospective study is presented of the clinical features and outcome of late onset haemorrhagic disease due to vitamin K deficiency in 11 babies who were admitted to the emergency or child neurology unit during a 4-year period (January 1994-December 1997). The disease occurred in infants between 30 and 119 days of age (mean: 56+/-24 days). None of them received vitamin K after birth and all were breastfed. The presenting complaints were seizures (91%), drowsiness (82%), poor sucking (64%), vomiting (46%), fever (46%), pallor (46%), acute diarrhoea (27%), irritability and high-pitched cry (18%). On examination, tense or bulging fontanelle (73%), anisocoria (36%), weak neonatal reflexes (18%), cyanoses (18%) were the most frequent findings. The localizations of the intracranial haemorrhage were as follows: intracerebral (91%), subarachnoid (46%), subdural (27%), and intraventricular (27%). No fatality was observed. However, after a follow-up period ranging from 6 to 48 months (mean: 21+/-13 months), only three (27%) infants remained neurologically normal. Seizure disorders (73%), severe psychomotor retardation (46%), cerebral palsy (46%) and microcephaly (46%) were observed in the remainder. Hydrocephalus developed in three (27%) babies but none of them required shunt replacement. The value is emphasized of vitamin K prophylaxis in the newborn to reduce the incidence of late onset intracranial haemorrhage and handicap in children.

Topics: Follow-Up Studies; Humans; Infant; Intracranial Hemorrhages; Retrospective Studies; Tomography, X-Ray Computed; Vitamin K; Vitamin K Deficiency

Topics: Adrenal Cortex Hormones; Cerebral Hemorrhage; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intracranial Hemorrhages; Pathology; Prednisone; Vitamin K

Topics: Antifibrinolytic Agents; Cerebral Hemorrhage; Child; Hemostatics; Humans; Infant; Infant, Newborn; Intracranial Hemorrhages; Prothrombin Time; Vitamin K