American journal of hematology
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Comment Letter
Use of prothrombin complex concentrates in anticoagulation.
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We genotyped single nucleotide polymorphisms (SNPs) in: (1) the beta-globin gene-like cluster, (2) quantitative trait loci (QTL) previously associated with fetal hemoglobin (HbF) concentration on chromosomes 6q, 8q, and Xp, and (3) candidate genes that could effect HbF levels, in sickle cell anemia subjects. HbF concentration was modeled as a continuous variable with values in a finite interval using a novel Bayesian approach. We first tested the associations of SNPs with HbF in a group of 1,518 adults and children (CSSCD study), and validated the results in a second independent group of 211 adults (MSH study). ⋯ These studies confirm prior analyses using traditional analytical approaches showing associations of SNPs in TOX, GPM6B, and the beta-globin gene-like cluster with HbF levels. We also identified an additional candidate regulatory region in chromosome 15q22 that is associated with HbF level. By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia.
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Argatroban is a direct thrombin inhibitor approved for the treatment of heparin-induced thrombocytopenia (HIT) type II. Argatroban is predominantly metabolized in the liver. It is widely believed that no dosage adjustment is required in patients with renal insufficiency, making it a preferred agent in patients on renal replacement therapy (Reddy and Grossman, Ann Pharm 2005;39:1601-1605). ⋯ A chromogenic antifactor IIa assay could be useful for monitoring argatroban in the presence of a lupus anticoagulant, but it is not widely available at present. We report a patient with end-stage renal disease, maintained on peritoneal dialysis with HIT, who demonstrated a markedly prolonged half-life when treated with argatroban despite the discontinuation of therapy. This case also demonstrates the lack of guidelines for the monitoring of argatroban therapy in the presence of an underlying lupus anticoagulant.
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A common side effect of opioids is nausea and vomiting; however, the incidence in hospitalized patients receiving opioids for acute pain is unknown. We performed a retrospective study in adult patients with sickle cell disease admitted for an acute pain crisis during a six-month period to evaluate the incidence of nausea and vomiting and characterize the prescribing of antiemetics. Eligibility included normal hepatic and renal function. ⋯ The clinical benefit of these medications is limited due to uneven documentation. In conclusion, many of our patients experienced nausea or vomiting with antiemetics infrequently prescribed on an as needed basis. This suggests a need for better approaches to manage nausea and vomiting in patients receiving opioids.
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Over-anticoagulation is a common problem with warfarin therapy and can lead to major or life-threatening bleeding. The goal of urgent warfarin reversal is to elevate or replace vitamin K-dependent clotting factors. In the United States, fresh frozen plasma (FFP) is considered the standard of care for warfarin reversal. ⋯ A review of the published literature over the last 30 years found that PCCs offer a rapid and specific method for replacing vitamin K-dependent clotting factors and restoring normal hemostasis in the context of over-coagulation. In those studies in which PCCs were compared with FFP, PCCs were found more effective in shortening the time to INR correction and were associated with a low risk of thrombotic adverse events. Evidence-based treatment guidelines are needed to optimize the use of PCCs for warfarin reversal.