Hematology
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Recombinant human factor VIIa (rFVIIa) is approved by the US Food and Drug Administration for use in the setting of hemorrhage associated with factor VIII or factor IX inhibitors in patients with congenital or acquired hemophilia. This indication represents only a small number of bleeding conditions. Since it became available, rFVIIa has been increasingly used in the management of off-label indications, ranging from emergent hemostasis in traumatic hemorrhage to prophylactic hemostasis in patients undergoing major surgery. ⋯ Other occasions for use occur in patients with intact coagulation systems, with nontraumatic intracranial hemorrhage being the most common in this group. Uncertainties regarding the efficacy and safety associated with use of rFVIIa in these off-label scenarios have led to evidence-based assessments of patient outcomes, including mortality, the rate of thromboembolic adverse events, and posttreatment functional status. We review the evidence regarding the efficacy and safety of this important, but controversial, hemostatic agent in the off-label setting.
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Injury is the leading cause of life years lost in the United States, and uncontrolled hemorrhage is the leading cause of potentially preventable death. Traditionally, these patients have been serially resuscitated with large volumes of crystalloid and/or colloids and red blood cells, followed by smaller amounts of plasma and platelets. Transfusion data coming first from the ongoing war in Iraq and Afghanistan and followed by multiple civilian studies have brought into question this tradition-based practice. ⋯ Although there are strongly held opinions and long-standing traditions in their use, there are little quality data within which to logically guide resuscitation therapy. A multicenter prospective observational study is ongoing, and randomized trials are planned. This review will address the issues raised previously and describe recent trauma patient outcome data utilizing predetermined plasma:platelet:red blood cell transfusion ratios, and possibilities for future transfusion products and research.
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The main reason for the increased risk of thromboembolism in pregnancy is hypercoagulability, which has likely evolved to protect women from the bleeding challenges of miscarriage and childbirth. Women are at a 4- to 5-fold increased risk of thromboembolism during pregnancy and the postpartum period compared with when they are not pregnant. Eighty percent of the thromboembolic events in pregnancy are venous, with an incidence of 0.49 to 1.72 per 1000 pregnancies. ⋯ At the time of delivery, anticoagulation should be manipulated to reduce the risk of bleeding complications while minimizing the risk of thrombosis. There are no large trials of anticoagulants in pregnancy, and recommendations are based on case series, extrapolations from nonpregnant patients and the opinion of experts. Nonetheless, anticoagulants are believed to improve the outcome of pregnancy for women who have, or have had, VTE.
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Review
Heparin-induced thrombocytopenia: when a low platelet count is a mandate for anticoagulation.
Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of approximately 50 to 60 x 10(9) platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). ⋯ Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT.
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Telomeres, repeat sequences at the ends of chromosomes, are protective chromosomal structures highly conserved from primitive organisms to humans. Telomeres inevitably shorten with every cell cycle, and telomere attrition has been hypothesized to be fundamental to normal senescence of cells, tissues, and organisms. Molecular mechanisms have evolved to maintain their length and protective function; telomerase (TERT) is a reverse transcriptase enzyme that uses an RNA molecule (TERC) as the template to elongate the 3' ends of telomeres. ⋯ Additionally, telomere defects associate with predisposition to hematologic malignancy and epithelial tumors. Telomere erosion is abnormally rapid in patients with mutations in telomerase genes but also after hematopoietic stem cell transplant, and telomeres are naturally shorter in older individuals-all conditions associated with higher rates of malignant diseases. In human tissue culture, short telomeres produce end-to-end chromosome fusion, nonreciprocal translocations, and aneuploidy.