Prophylactic unfractionated heparin and hemorrhage in neurocritically ill underweight patients: A case series and review of the literature.

PURPOSE: Three cases of major bleeding associated with thromboprophylactic unfractionated heparin (UFH) therapy in underweight neurocritically ill patients are reported. SUMMARY: Three underweight patients (body mass index of <18.5 kg/m2) were treated in the intensive care unit with major bleeds associated with UFH thromboprophylaxis. Two of the patients, a 76-year-old female and a 56-year-old female, had hemorrhages on presentation; the third patient, a 29-year-old male, developed bleeding during his admission. All 3 patients had past medical histories consisting of acute neurologic conditions within 6 weeks of presentation, including subdural hematoma, subarachnoid hemorrhage, and obstructive hydrocephalus secondary to a brain mass. All hemorrhages developed following the receipt of prophylactic UFH at doses of 5,000 units every 8 to 12 hours, which translated to high weight-based dosages (>300 units/kg/d). Additionally, hemorrhages were associated with prolonged activated partial thromboplastin time, which declined following heparin discontinuation. The major bleeds following UFH administration included an acute on chronic subdural hematoma, acute rectus sheath hematoma, and cerebellar hematoma. Stabilization of the subdural hematoma was achieved without the use of protamine and the patient was discharged in stable condition. The other 2 patients expired secondary to their hemorrhagic events. Naranjo nomogram scores for the patients indicated that heparin was the probable cause of bleed in 2 cases and a possible cause in 1 case. CONCLUSION: Three major hemorrhages developed following the administration of UFH. Underweight patients with neurologic injury may require increased clinical vigilance, reduced doses, and pharmacodynamic monitoring to improve safety outcomes associated with thromboprophylaxis.

Anticoagulation Bridge Therapy in Patients with Atrial Fibrillation: Recent Updates Providing a Rebalance of Risk and Benefit.

In 2011 we reviewed clinical updates and controversies surrounding anticoagulation bridge therapy in patients with atrial fibrillation (AF). Since then, options for oral anticoagulation have expanded with the addition of four direct oral anticoagulant (DOAC) agents available in the United States. Nonetheless, vitamin K antagonist (VKA) therapy continues to be the treatment of choice for patients who are poor candidates for a DOAC and for whom bridge therapy remains a therapeutic dilemma. This literature review identifies evidence and guideline and consensus statements from the last 5 years to provide updated recommendations and insight into bridge therapy for patients using a VKA for AF. Since our last review, at least four major international guidelines have been updated plus a new consensus document addressing bridge therapy was released. Prospective trials and one randomized controlled trial have provided guidance for perioperative bridge therapy. The clinical trial data showed that bridging with heparin is associated with a significant bleeding risk compared with not bridging; furthermore, data suggested that actual perioperative thromboembolic risk may be lower than previously estimated. Notably, patients at high risk for stroke have not been adequately represented. These findings highlight the importance of assessing thrombosis and bleeding risk before making bridging decisions. Thrombosis and bleeding risk tools have emerged to facilitate this assessment and have been incorporated into guideline recommendations. Results from ongoing trials are expected to provide more guidance on safe and effective perioperative management approaches for patients at high risk for stroke.

Increased transcription and activity of glutathione synthase in response to deficiencies in folate, vitamin E, and apolipoprotein E.

Oxidative stress is a major contributing factor in neurodegeneration and can arise from dietary, environmental, and genetic sources. Here we examine the separate and combined impact of deprivation of folate and vitamin E, coupled with dietary iron as a prooxidant, on normal mice and transgenic mice lacking apolipoprotein E (ApoE-/- mice). Both mouse strains exhibited increased levels of glutathione when deprived of folate and vitamin E, but a substantial further increase was observed in ApoE-/- mice. To determine the mechanism(s) underlying this increase, we quantified transcription and activity of glutathione synthase (GS). Both normal and ApoE-/- mice demonstrated increased GS activity when deprived of folate and vitamin E. However, transcription was increased only in ApoE-/- mice deprived of folate and vitamin E. These findings demonstrate that deficiency in one gene can result in compensatory up-regulation in a second relevant gene and, furthermore, indicate that compensation for oxidative stress can occur in brain tissue at epigenetic and genetic levels depending on the nature and/or extent of oxidative stress.