Surgery in haemophilic patients with inhibitor against factor (F)VIII or FIX is high risk. Surgery may be performed with the administration of sufficiently high dose of FVIII in patients with low-response inhibitor or who, despite having a high response, present a low inhibitor titre at the time of surgery. The use of high doses of FX is more complicated in patients with a low-titre FIX inhibitor, as there is a high risk of anaphylactic reactions. In the case of patients with high-titre inhibitors, several treatments have been proposed, such as porcine FVIII, recombinant FVIIa (rFVIIa), and activated prothrombin complex concentrate (APCC). We present our 20 years' experience in the treatment and subsequent management of haemophilic patients with inhibitor in surgery and evaluate the results obtained with the products available for haemostatic control in 64 surgical procedures. The efficacy we obtained with FVIII is good in 100% of the cases described; we had no haemorrhagic complication (HC) in the 18 procedures in which it was used (three major and 15 minor surgery). With APCC we obtained excellent results with only one HC in a synoviorthesis in the form of bleeding and haematomas out of 32 procedures. Good results were obtained with rFVIIa with few haemorrhagic episodes. Thus, in major surgery there was one HC out of three cases. In minor surgery, greater efficacy was observed using extremely large doses of rFVIIa (> or =120 mg kg(-1) 2 h(-1)) because of the shorter half-life of this factor in this type of patients.

Summary Multifactorial mechanisms leading to diminished platelet counts in immune thrombocytopaenia (ITP) might condition the ability of patients with ITP to respond to treatments. Examining their platelet and immune features, we aimed to detect singular characteristics of patients with ITP who do not respond to any treatment. We studied patients with chronic primary ITP who had been without treatment, or untreated (UT‐ITP), for at least six months; included were responders to agonists of thrombopoietin receptors (TPO‐RA), patients who showed no response to first‐ and second‐line treatments (NR‐ITP), and healthy controls. Platelets from NR‐ITP patients exposed a reduced amount of sialic acid residues. Increased loss of platelet surface sialic acid residues was associated with increased platelet apoptosis. NR‐ITP patients had an increased fraction of naive lymphocyte (L) B cells and a reduced LTreg (Lymphocyte T‐regulator) subset. They also presented an anomalous monocyte and NK (Natural Killer) cells distribution. TPO‐RA‐treated patients seemed to recover an immune homeostasis similar to healthy controls. In conclusion, our results indicate a severe deregulation of the immune system of NR‐ITP. The inverse correlation between loss of sialic acid and LTreg count suggests a potential relationship between glycan composition on the platelet surface and immune response, positing terminal sugar moieties of the glycan chains as aetiopathogenic agents in ITP.

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Despite their low platelet count some immune thrombocytopenia (ITP) patients seldom bleed, indicating the presence of factors to compensate thrombocytopenia. Moreover, ITP patients may have an increased risk for thrombosis. These facts suggest the presence of procoagulant mechanisms that have not been clarified yet. The aim of this study was to identify these possible factors. Moreover, the utility of rotational thromboelastometry (ROTEM ) to test haemostasis in these patients was also evaluated. Patients with ITP presented a procoagulant profile due to an increased amount of platelet- and red cell-microparticles, an increased resistance to protein C and the formation of a clot more resistant to fibrinolysis due to augmented levels of plasminogen activator inhibitor-1, which might reflect an endothelial damage/activation in ITP patients. Despite increased maximum clot firmness and reduced lysis, ROTEM profiles showed a prolonged clotting time that might rely on the presence of anti-platelet antibodies as suggested by the increased lagtime in thrombin generation test caused by plasma from ITP patients on platelets from healthy controls. These results indicate the need to individualize therapeutic treatment for ITP patients, considering their procoagulant profile and the presence of concomitant risk factors. Moreover, ROTEM appeared to be useful for evaluating haemostasis in ITP patients.

Fanhdi is an effective and safe plasma-derived FVIII/VWF concentrate that can be used as an alternative to the current replacement therapy in patients with VWD to provide an adequate haemostasis during surgical procedures and treatment of bleeding episodes.