British journal of haematology
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The anticoagulant effect of unfractionated heparin (UFH) is monitored using the activated partial thromboplastin time (APTT). An APTT of 1.5-2.5 times the control is usually taken as the therapeutic range and assumed to reflect an anti-activated factor X (anti-Xa) level of 0.35-0.7 u/ml. However, in some cases, despite administration of sufficient heparin to achieve a therapeutic anti-Xa assay level, the APTT remains sub-therapeutic. ⋯ The relationship between heparin level, APTT and anticoagulant effect at different FVIII concentrations was determined using thrombelastography and the thrombin generation assay. Thromboelastographic and thrombin generation parameters concurred with APTT, demonstrating a genuine heparin resistance in the presence of high FVIII levels. This suggests that APTT may be a more accurate measure of anticoagulant effect in vivo than anti-Xa.
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The widespread use of central neuraxial block (CNB) and the prevalence of anticoagulation for different indications have led to an inevitable overlap between the two. The most serious complication of CNB in anticoagulated patients is the risk of spinal/epidural haematoma. Performing CNB in these patients is a complex decision that should take into account the twin risks of bleeding and venous/arterial thrombosis if anticoagulation therapies were to be stopped. ⋯ However, the evidence base for many such recommendations is weak, relying mainly on case reports, small studies and pharmacokinetics of the drugs. Given these limitations it is crucial to fully assess individual risk factors and understand anticoagulant pharmacokinetics in order to appropriately set time intervals for catheter insertion/removal. This paper will review traditional and newer anticoagulation/antiplatelet therapies with a view to improving the management of anticoagulated patients undergoing CNB.
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Practice Guideline
Significant haemoglobinopathies: guidelines for screening and diagnosis.
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Depletion of B lymphocytes using the anti-CD20 monoclonal antibody rituximab has wide-spread use in the treatment of patients with autoimmune disorders. As haematopoietic progenitor cells and only a fraction of differentiated plasma express CD20, the effect of rituximab on immune function appears to be minimal. ⋯ Reactivation of latent JC virus, resulting in progressive multifocal leucoencephalopathy, and hepatitis B virus, resulting in hepatoxicity, have been documented in patients receiving rituximab; although confounding effects of concomitant immunosuppressive therapies and immune dysregulation due to the underlying disease make causal associations of infections problematic. This review discusses the efficacy of B cell depletion therapy in the treatment of autoimmune diseases, the effect of B cell depletion on infection and immunity including the role of the B cell in autoimmunity, and identifies areas of controversy.
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Practice Guideline
Clinical guidelines for testing for heritable thrombophilia.