vitamin-k-semiquinone-radical and Subarachnoid-Hemorrhage

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

The increased prevalence of rodents resistant to warfarin led to the development of the hydroxycoumarin anticoagulant brodifacoum. A 25-year-old man attempted suicide by consuming four boxes of d-CON Mouse-Prufe II; each box contains 42 g of bait that is 0.005% brodifacoum. He presented to a hospital nine days later with syncope, hematochezia, gross hematuria, epistaxis, anemia, and a severe coagulopathy. Radiographic studies were consistent with pleural, pericardial, and mediastinal hemorrhages. Vitamin K and fresh frozen plasma were given, and he was later discharged on oral phytonadione (vitamin K1). The patient's coagulopathy recurred, necessitating multiple plasma transfusions and prolonged treatment with oral phytonadione. Fifteen weeks after hospital discharge, he presented again with a history of additional brodifacoum ingestion. Neurologic status was initially normal, but in the emergency department he suddenly became comatose soon after emesis was induced with syrup of ipecac. Computed tomography of the brain revealed a subarachnoid hemorrhage that led to brain death less than 24 hours later. This case demonstrates the severe and prolonged coagulopathy that can result from ingestion of brodifacoum, a compound that has a toxic potency about 200-fold that of warfarin and a half-life as much as 60 times longer.

Topics: 4-Hydroxycoumarins; Adult; Blood Coagulation Disorders; Blood Transfusion; Drug Overdose; Emergency Service, Hospital; Humans; Ipecac; Male; Partial Thromboplastin Time; Patient Readmission; Phenobarbital; Plasma; Poisoning; Prothrombin Time; Rodenticides; Subarachnoid Hemorrhage; Suicide; Tomography, X-Ray Computed; Vitamin K

An increased risk of recurrent stroke is noted in patients with atrial fibrillation despite direct oral anticoagulant (DOAC) use. We investigated the efficacy and safety of treatment with each of 4 different DOACs or warfarin after DOAC failure.. We retrospectively analyzed patients with atrial fibrillation with ischemic stroke despite DOAC treatment between January 2002 and December 2016. The different outcomes of patients with DOAC failure were compared, including recurrent ischemic stroke, major cardiovascular events, intracranial hemorrhage and subarachnoid hemorrhage, mortality, and net composite outcomes according to switching to different DOACs or vitamin K antagonist after index ischemic stroke. We identified 3759 patients with DOAC failure. A total of 84 patients experienced recurrent ischemic stroke after switching to different oral anticoagulants, with a total follow-up time of 14 years. Using the vitamin K antagonist group as a reference, switching to any of the 4 DOACs was associated with a 69% to 77% reduced risk of major cardiovascular events (adjusted hazard ratio [aHR], 0.25 [95% CI, 0.16-0.39] for apixaban, 0.23 [95% CI, 0.14-0.37] for dabigatran, 0.23 [95% CI, 0.09-0.60] for edoxaban, and 0.31 [95% CI, 0.21-0.45] for rivaroxaban), and a 69% to 83% reduced risk of net composite outcomes (aHR, 0.25 [95% CI, 0.18-0.35] for apixaban, 0.17 [95% CI, 0.11-0.25] for dabigatran, 0.31 [95% CI, 0.17-0.56] for edoxaban, and 0.31 [95% CI, 0.23-0.41] for rivaroxaban).. In Asian patients with DOAC failure, continuing DOACs after index stroke was associated with fewer undesirable outcomes than switching to a vitamin K antagonist. Alternative pharmacologic and nonpharmacologic strategies warrant investigation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Ischemic Stroke; Retrospective Studies; Rivaroxaban; Stroke; Subarachnoid Hemorrhage; Vitamin K; Warfarin

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

The study objective was to investigate the relationship between use of antithrombotic drugs and subarachnoid haemorrhage (SAH). We identified patients discharged from Danish neurosurgery units with a first-ever SAH diagnosis in 2000 to 2012 (n=5,834). For each case, we selected 40 age-, sex- and period-matched population controls. Conditional logistic regression models were used to estimate odds ratios (aOR), adjusted for comorbidity, education level, and income. Low-dose aspirin (ASA) use for < 1 month was associated with an increased risk of SAH (aOR 1.75, 95 % confidence interval [CI] 1.28-2.40). This aOR decreased to 1.26 (95 %CI: 0.98-1.63) with 2-3 months of ASA use, and approached unity with use for more than three months (1.11, 95 %CI 0.97-1.27). Analyses with first-time users confirmed this pattern, which was also observed for clopidogrel. ASA treatment for three or more years was associated with an aOR of SAH of 1.13 (95 %CI: 0.86-1.49). Short-term use (< 1 month) of vitamin K-antagonists (VKA) yielded an aOR of 1.85 (95 %CI 0.97-3.51) which dropped after 3+ years to 1.24, 95 %CI: 0.86-1.77. The risk of SAH was higher in subjects in dual antithrombotic treatment (aOR 2.08, 95 %CI: 1.26-3.44), and in triple antithrombotic treatment (aOR 5.74, 95 %CI: 1.76-18.77). In conclusion, use of aspirin,clopidogrel and VKA were only associated with an increased risk of SAH in the first three months after starting treatment. Long-term aspirin use carried no reduced SAH risk. Results should be interpreted cautiously due to their observational nature.

Topics: Aged; Aspirin; Case-Control Studies; Clopidogrel; Denmark; Drug Therapy, Combination; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Neurosurgical Procedures; Postoperative Complications; Risk; Subarachnoid Hemorrhage; Thrombosis; Ticlopidine; Vitamin K

Use of platelet aggregation inhibitors and vitamin K antagonists has been associated with an increased risk of intracranial hemorrhage (ICH). Whether the use of these antithrombotic drugs is associated with an increased risk of subarachnoid hemorrhage (SAH) remains unclear, especially as confounding by indication might play a role.. The aim of the present study was to investigate whether use of platelet aggregation inhibitors or vitamin K antagonists increase the risk of SAH.. We applied population-based case-control, case-crossover and case-time-control designs to estimate the risk of SAH while addressing issues both of confounding by indication and time varying exposure within the PHARMO Record Linkage System database. This system includes drug dispensing records from community pharmacies and hospital discharge records of more than 3 million community-dwelling inhabitants in the Netherlands. Patients were considered a case if they were hospitalized for a first SAH (ICD-9-CM code 430) in the period between 1st January 1998 and 31st December 2006. Controls were selected from the source population, matched on age, gender and date of hospitalization. Conditional logistic regression was used to estimate multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of SAH during use of platelet aggregation inhibitors or vitamin K antagonists. In the case-crossover and case-time-control designs we selected 11 control periods preceding the index date in successive steps of 1 month in the past.. In all, 1004 cases of SAH were identified. In the case-control analysis the adjusted OR for the risk of SAH in current use of platelet aggregation inhibitors was 1.32 (95% CI: 1.02-1.70) and in current use of vitamin K antagonists 1.29 (95% CI: 0.89-1.87) compared with no use. In the case-crossover analysis the ORs for the risk of SAH in current use of platelet aggregation inhibitors and vitamin K antagonists were 1.04 (95% CI: 0.56-1.94) and 2.46 (95% CI: 1.04-5.82), respectively. In the case-time-control analysis the OR for platelet aggregation inhibitors was 0.50 (95% CI: 0.26-0.98) and for vitamin K antagonists 1.98 (95% CI: 0.82-4.76).. The use of platelet aggregation inhibitors was not associated with an increased SAH risk; the modest increase observed in the case-control analysis could be as a result of confounding. The use of vitamin K antagonists seemed to be associated with an increased risk of SAH. The increase was most pronounced in the case-crossover analysis and therefore cannot be explained by unmeasured confounding.

Topics: Adult; Aged; Anticoagulants; Case-Control Studies; Cross-Over Studies; Databases, Factual; Female; Humans; Male; Medical Record Linkage; Middle Aged; Netherlands; Odds Ratio; Platelet Aggregation Inhibitors; Risk Factors; Subarachnoid Hemorrhage; Vitamin K

Oral anticoagulant therapy with vitamin K antagonists is associated with an increased risk of bleeding, particularly gastrointestinal bleeding. It remains unclear, however, whether use of these medications is a risk factor for subarachnoid haemorrhage (SAH). We therefore examined the association between oral vitamin K antagonist use and risk of SAH.. We conducted this population-based case-control study using medical databases in Northern Denmark (population 1,150,000). We identified 1188 patients admitted to neurologic or neurosurgical departments with a first-time diagnosis of SAH between 1996 and 2008 and 11,880 population controls. We obtained information on use of vitamin K antagonists, other medication use, and comorbidity. We used logistic regression analysis to compute odds ratios (ORs) comparing oral anticoagulant users and non-users, controlling for potential confounding factors.. 9 cases (0.8%) and 157 controls (1.3%) were current users of vitamin K antagonists (at least one prescription filled within 90 days of the diagnosis/index date). Current use of vitamin K antagonists was not associated with increased SAH risk compared with non-use [adjusted OR=0.80 (95% CI: 0.37-1.74)]. Changing the exposure window from 90 days to 120 days or to 60 days before the diagnosis/index date did not change the estimate substantially.. We found no evidence to support an association between use of vitamin K antagonists and increased SAH risk.

Topics: Adolescent; Adult; Aged; Anticoagulants; Case-Control Studies; Confidence Intervals; Female; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Phenprocoumon; Risk Factors; Subarachnoid Hemorrhage; Thromboembolism; Vitamin K; Warfarin; Young Adult

Biliary atresia (BA) is occasionally diagnosed in infants whose first symptom is a bleeding disorder, such as intracranial bleeding, nasal bleeding or gastrointestinal bleeding. The authors describe 3 cases in which a bleeding disorder was the first symptom of BA. The presenting symptom was intracranial bleeding in a male on day 55 after birth, nasal bleeding in a female at 65 days, and gastrointestinal bleeding in a female at 25 days. Coagulation studies revealed a vitamin K deficiency in all patients. After the administration of vitamin K, the results of coagulation tests normalized and the bleeding tendency of the infants ceased. Subsequently, BA was suspected to be the cause of these bleeding disorders based on imaging findings. BA should therefore be considered in all infants with sudden onset of a tendency to bleed.

Topics: Biliary Atresia; Cholangiography; Female; Hematoma, Subdural; Humans; Infant; Liver Transplantation; Male; Subarachnoid Hemorrhage; Vitamin K; Vitamin K Deficiency

The incidence of spontaneous intracranial haemorrhage has increased markedly in line with the increased use of oral anticoagulant agents. Recent guidelines for reversal of this acquired coagulation defect in an emergency have been established, but they are not adhered to in all centres. Our unit is referred between 20 and 60 patients per year (1994-1999) who are anticoagulated and require urgent neurosurgical intervention. In order to investigate this, we performed a prospective study using prothrombin complex concentrate (PCC). PCC was given to the first six patients with intracranial haemorrhage admitted to the neurosurgical unit requiring urgent correction of anticoagulation (Group 1) and compared with patients receiving standard treatment with fresh frozen plasma and vitamin K (Group 2). Mean International Normalised Ratios of Group 1 were 4.86 pretreatment and 1.32 posttreatment, and of Group 2 were 5.32 and 2.30, respectively. Results for complete reversal and reversal time were significant for PCC with p < 0.001. We recommend PCC for rapid and effective reversal of warfarin in life-threatening neurosurgical emergencies.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation Factors; Cerebral Hemorrhage; Emergencies; Female; Hematoma, Subdural; Humans; International Normalized Ratio; Male; Middle Aged; Pilot Projects; Preoperative Care; Prospective Studies; Subarachnoid Hemorrhage; Vitamin K; Warfarin

A bleeding syndrome due to severe prothrombin complex deficiency is reported in 93 infants. Most were breast fed (98 per cent), aged 2 weeks to 1 year and there were no serious preceding or associated diseases. Hemorrhagic diathesis, pallor and mild hepatomegaly were the major manifestations. The incidence of intracr anial bleeding was strikingly high (63 per cent) particularly with subdural and subarachnoid hemorrhage. Acute onset, short course and rapid clinical and laboratory improvement after vitamin K therapy were observed. Mortality rate was 35 per cent but has been reduced to 17 per cent since 1969. The location of bleeding, prompt diagnosis and early treatment are the major factors affecting prognosis. Severe prothrombin complex deficiency due to vitamin K deficiency accounted for the pathogenesis of bleeding. Possible causes of vitamin K deficiency were discussed but definite conclusions could not be drawn.

Topics: Cerebral Hemorrhage; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Hypoprothrombinemias; Infant; Infant, Newborn; Male; Subarachnoid Hemorrhage; Syndrome; Vitamin K; Vitamin K Deficiency

Topics: Alanine Transaminase; Anemia; Aspartate Aminotransferases; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Blood Transfusion; Cerebral Hemorrhage; Ecchymosis; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Prognosis; Prothrombin; Prothrombin Time; Seizures; Spinal Puncture; Subarachnoid Hemorrhage; Thrombin; Thromboplastin; Vitamin K

Topics: Anemia; Anemia, Hypochromic; Chlorpromazine; Heparin; Humans; IgA Vasculitis; Iron; Methenamine; Nandrolone; Neurosurgery; Nitrofurantoin; Paraplegia; Phenindione; Postoperative Care; Prednisolone; Purpura; Rehabilitation; Subarachnoid Hemorrhage; Thrombophlebitis; Urinary Tract Infections; Venous Thrombosis; Vitamin K