Histopathological evidence for macrophage activation driving post-transfusion hyperhaemolysis syndrome.

Post-transfusion hyperhaemolysis syndrome (PTHS) is a rare life-threatening transfusion complication reported mainly in sickle cell patients. Its pathogenesis is poorly understood. Antibody-mediated haemolysis and bystander effect have been proposed as putative mechanisms, but in half of cases, red cell antibodies are undetectable, and PTHS develops despite transfusion of cross-matched compatible RBC. An alternate hypothesis proposes activated macrophages as the main drivers of red cell destruction through direct phagocytosis. We report the histopathological findings of two patients with PTHS showing extensive macrophage expansion and erythrophagocytosis, supportive of macrophage activation driving PTHS. This supports a possible role for novel therapies that target macrophage activation.

Severe antithrombin deficiency in pregnancy: Achieving adequate anticoagulation.

Antithrombin deficiency is identified as one of the most potent risk factors for venous thromboembolism during pregnancy. Therapeutic low molecular weight heparin is recommended, but it can be difficult to attain sufficient anticoagulation since low molecular weight heparin requires antithrombin to exert its anticoagulant effect. We carried out a multicentre case-series assessing the dose of low molecular weight heparin required to achieve therapeutic anti-activated factor X levels in pregnant women with antithrombin deficiency. We assessed 27 pregnancies in 18 women with severe antithrombin deficiency, which we defined as an antithrombin level of <0.55 IU/ml (with or without prior venous thromboembolism) or an antithrombin level < 0.8 IU/ml and a personal history of venous thromboembolism. Our data illustrate the need for high doses of low molecular weight heparin to achieve therapeutic anti-activated factor X levels (average 20,220 IU/day). All pregnancies ended in live birth (excluding one elective termination), although intrauterine growth restriction occurred in five (18%).