Summary. Participants in an international conference on prophylactic therapy for severe haemophilia developed a consensus summary of the findings and conclusions of the conference. In the consensus, participants agreed upon revised definitions for primary and secondary prophylaxis and also made recommendations concerning the need for an international system of pharmacovigilance. Considerations on starting prophylaxis, monitoring outcomes, and individualizing treatment regimens were discussed. Several research questions were identified as needing further investigation, including when to start and when to stop prophylaxis, optimal dosing and dose interval, and methods for assessment of long-term treatment effects. Such studies should include carefully defined cohorts, validated orthopaedic and quality-of-life assessment instruments, and cost-benefit analyses.

Haemarthroses (intra-articular haemorrhages) are a frequent finding typically observed in patients with haemophilia. Diagnosis and treatment of these bleeding episodes must be delivered as early as possible. Additionally, treatment should ideally be administered intensively (enhanced on-demand treatment) until the resolution of symptoms. Joint aspiration plays an important role in acute and profuse haemarthroses as the presence of blood in the joint leads to chondrocyte apoptosis and chronic synovitis, which will eventually result in joint degeneration (haemophilic arthropathy). Ultrasonography (US) is an appropriate diagnostic technique to assess the evolution of acute haemarthrosis in haemophilia, although magnetic resonance imaging remains the gold standard as far as imaging techniques are concerned. Some patients experience subclinical haemarthroses, which eventually tend to result in some degree of arthropathy, especially in the ankles. Nowadays, the most effective way of protecting these patients is primary prophylaxis, which in practice changes severe haemophilia into moderate haemophilia, preventing or at least minimizing the occurrence of haemarthrosis. If primary prophylaxis is, for whatever reason not an option, secondary prophylaxis and enhanced on demand treatment should be considered. Two alternatives are available for inhibitor patients: (i) control of haemostasis using by-passing agents (rFVIIa or aPCCs) either as enhanced on demand treatment or secondary prophylaxis, as appropriate, following the same basic principles used for non-inhibitor patients and (ii) immune tolerance induction (ITI) to eradicate the inhibitor.

The most important clinical strategy for management of patients with hemophilia is the avoidance of recurrent hemarthroses by means of continuous, intravenous hematological prophylaxis. When only intravenous ondemand hematological treatment is available, frequent evaluations are necessary for the early diagnosis and treatment of episodes of intra-articular bleeding. The natural history of the disease in patients with poorly controlled intra-articular bleeding is the development of chronic synovitis and, later, multi-articular hemophilic arthropathy. Once arthropathy develops, the functional prognosis is poor. Treatment of these patients should be conducted through a comprehensive program by a multidisciplinary hemophilia unit. Although continuous prophylaxis can avoid the development of the orthopedic complications of hemophilia still seen in the twenty-first century, such a goal has not, so far, been achieved even in developed countries. Therefore, many different surgical procedures such as arthrocentesis, radiosynoviorthesis (radiosynovectomy) (yttrium-90, rhenium-186), tendon lengthenings, alignment osteotomies, joint arthroplasties, removal of pseudotumours, and fixation of fractures are still frequently needed in the care of these patients.

It is very likely that with the advent of widespread maintenance therapy, pseudotumours will be less common in the future. It is important that they are diagnosed early, and prevention of muscular haematomas is the key to reducing their incidence. There are a number of therapeutic alternatives for this dangerous condition: surgical removal, percutaneous management, exeresis and filling of the dead cavity, irradiation, and embolization. The management of a patient with a haemophilic pseudotumour is complex, with a high rate of potential complications. Surgical excision is the treatment of choice but should only be carried out in major haemophilia centres by a multidisciplinary surgical team. The main postoperative complications are death, infection, fistulization, and pathological fractures (even requiring amputations of affected limbs). Pelvic pseudotumours can even become complicated by fistulization to the large bowel and by obstruction of the ureters. Untreated, proximal pseudotumours will ultimately destroy soft tissues, erode bone, and may produce neurovascular complications.