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Whether to resume the anticoagulant or the antiaggregant therapy after an episode of major haemorrhage is a difficult dilemma for the physician. The physician has to take into consideration two major questions: whether the benefits of restarting anticoagulation outweigh the risk, and if so, when and how should anticoagulation be restarted. Although some case reports suggest that anticoagulation can be withheld safely for short periods after ICH, even in patients with mechanical heart valves, it is still not clear if long-term anticoagulation can be safely reinstituted after haemorrhage, for example in patients with atrial fibrillation. In fact, no large and well-conducted randomised clinical trials are available, and there is lack of strong evidence on which guidelines recommendations can be based. The article summarise the available literature findings. Finally, a protocol is suggested which may represent a useful tool for assessing treatment options.

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4222 Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon acquired disorder, consequence of a clonal expansion of haematopoietic stem cells that have acquired a somatic mutation of PIGA gene and is characterized by intravascular haemolysis, susceptibility to infections and arterial and venous thromobophilia. PNH frequently arises in association with disorders of bone marrow failure, particularly aplastic anaemia. Venous thrombo-embolism (VTE) is a major cause of morbidity and mortality in accounting for about 1/3 of all death. Pathogenesis of VTE is multifactorial but may be related to the ongoing haemolysis and the increased platelets activation by release of ADP and consumption of nitric oxide. Thromboembolic risk is known to be related to the clone size being higher in patients with PNH granulocytes > 50%, and probably to the ongoing haemolysis. PNH often affects the middle aged adults, of reproductive age, but women with PNH have to be generally discouraged from becoming pregnant because of the increased risk of complication both for the mother and the foetus. Twenty-six published clinical reports describe pregnancy outcome in 43 women with PNH: in the majority of cases no prophylactic anticoagulant therapy was administrated. Major maternal complication (mainly thromboembolic events) are reported in 16,3% of cases during pregnancy and in 30.2% of cases during puerperium. Five patients died as a consequence of thromboembolic events (n=3) and infections (n=2). The pregnancy terms with a pre-term delivery in 38% of cases, usually as a consequence of maternal complication: no foetal abnormalities were reported. Anticoagulation with low molecular weight heparin (LMWH) is generally recommended during pregnancy and puerperium, however, it provide only partial protection from thrombotic complications. Eculizumab is a humanized monoclonal antibody directed against the C5 complement protein, with inhibition of complement-mediated cell lysis. This drug is effective in controlling intravascular haemolysis, stabilizes haemoglobin levels, reduces transfusion requirements and thrombotic events and improves quality of life of PNH patients. It is composed by a hybrid IgG2-IgG4 constant fraction portion without antibody effector mechanism, moreover IgG2 isotypes do not cross placenta but few and partial experiences have been reported about its effects during pregnancy. We report the case of a 35-year old woman with a diagnosis of PNH establish in 2003 evolved from aplastic anaemia (1995). She needed about one unit of packed red blood cells monthly. She started eculizumab treatment at standard dosage (900 mg every other week) in April 2005 obtaining a rapid normalization of haemoglobin and LDH levels. She hadn't further haemolytic events and she never presented vascular complications. The patient became pregnant in October 2008: flow-cytometry analysis demonstrated that 35% of neutrophils and monocytes had loss of CD55 and CD59. Although the patient had a relatively small PNH clone and she hadn't previous thrombotic event, we decided to continue eculizumab during pregnancy in order to avoid haemolysis and the consequent VTE risk. Moreover, we started a prophylactic anticoagulant therapy with LMWH and anti-platelet therapy with acetylsalicylic acid at 16 weeks of gestation. During the entire pregnancy the patient never required transfusional support and the minimal haemoglobin dosage was 9 g/dl. Anti-platelet therapy was stopped at 36 weeks of gestation. At 38th weeks of gestation the patient delivered vaginally a child male, 3430 g, with Apgar score of 9 and 10. Both the mother and the newborn didn't experience any complication in particular the mother didn't need transfusional support and haemoglobin level maintained stable in spite of a mild LDH increase. Eculizumab treatment was continued also in the puerperium. In absence of data about the possible presence of eculizumab in breast milk and its possible effect on the newborn, we decided to avoid breast-feeding. At this time, after 2 months from the childbirth, both the mother and the newborn haven't medical complication. This is the first report of a pregnancy carried out during eculizumab treatment without significant toxicity for both the mother and the baby. The role of eculizumab in pregnancy and puerperium has to be further investigate in order to reduce the disease related maternal and foetal risk. Disclosures: No relevant conflicts of interest to declare.