Target plasma factor levels for personalized treatment in haemophilia: a Delphi consensus statement.

BACKGROUND: Prophylactic replacement with factor concentrate is the optimal treatment for persons with severe haemophilia to avoid or minimize bleeding. This ultimately prevents or reduces joint disease and improves life expectancy and quality of life towards values matching those in the normal population. However, uncertainty still exists around the optimal regimens to be prescribed for prophylaxis. An increasing number of treating physicians and patients are showing interest in patient-tailored approaches to prophylaxis, which aim to harmonize the prophylaxis regimen with the patients' bleeding phenotype, levels of physical activity and a variety of other variables. METHODS: A modified Delphi technique was adopted to generate consensus. The expert panel met in person to set the objectives, be trained on the Delphi technique and agree on the desired level of consensus. Three iterations were used to identify the targets, the scenarios and their combinations. RESULTS: Twenty-eight scenarios and eight target levels were identified and used to issue recommendations. The panel reached the desired level of consensus on positive or negative recommendations. Areas where consensus was not reached were identified and proposed as areas for future research. Prospective assessment of the validity of most of the proposed targets is recommended. CONCLUSIONS: We have generated, by expert consensus, target plasma levels of factor concentrate to be used to tailor treatment for persons with haemophilia.

Prophylaxis in 10 patients with severe haemophilia A and inhibitor: different approaches for different clinical situations.

The effect of bypassing agents is not as predictable as replacement therapy with the deficient factor in inhibitor patients. Consequently, these patients have more levels of arthropathy than patients without inhibitors. Prophylaxis for inhibitor patients has gained attention over the last decade and some papers have reported that bypassing agents could work in the prevention of arthropathy. However, there is a lack data to support any specific agent or regimen or even to recommend their use in different clinical conditions. We report ten patients with haemophilia A and inhibitors treated prophylacticaly with bypassing agents (5 with FEIBA and 5 with NovoSeven). The variable conditioning the choice of one agent or the other was the intention to initiate of immune tolerance induction therapy (ITI) in the future. In 8/10 patients (4 in FEIBA group and 4 in rFVIIa group) there was a decrease of bleeding episodes while 9/10 maintained or increased their joint range of motion (ROM). In the rFVIIa prophylaxis group, prophylaxis can be considered primary since all of them had had less than one joint bleed before prophylaxis. Economic analysis showed that prophylaxis is an expensive treatment. In our experience both agents seem to be safe and effective in reducing the number of bleeds in patients with inhibitors. The anamnestic response provoked by FEIBA could be an issue while awaiting a decline in titres before ITI can be initiated and so rFVIIa may be the best option for prophylaxis in patients with inhibitors who have not yet begun ITI.

Fractures of the coracoid process: presentation of seven cases and review of the literature.

Coracoid process fracture is a rare and uncommon clinical entity. Seven cases of the base of the coracoid process are presented. This fracture was isolated in one case, being in the other six cases combined with injuries, either to acromioclavicular dislocation or to fracture of the superior glenoid cavity disorder. One of these patients had associated fractures of the clavicle and the coracoid process. The treatment was conservative in all cases. Results were satisfactory and therefore nonoperative management is advocated.

[Unusual bone tumor in a hemophiliac patient. Diagnosis using aspiration biopsy of the lesion]. / Tumor óseo inusual en paciente hemofílico. Diagnóstico mediante punción aspirado de la lesión.

Bone tumors due to repeated haemorrhages in haemophiliacs (haemophilic pseudotumours) usually are no diagnostic trouble. However, when x-ray findings are not conclusive, the differential diagnosis with malignant tumours may be difficult as bleeding complications hinder invasive diagnostic procedures. A fifteen year-old patient with severe haemophilia A is presented, who had a tumor in his left fibula with no previous traumatism. X-ray and CT scan images showed a broken cortical substance with reactive sclerosis and no alteration of the soft tissues. In order to establish the diagnosis and choose the adequate surgical management, aspiration with thin needle was performed through the cortical hole, under visual control with CT scan. A benign lesion was found upon study of the aspirate. No haemorrhagic or infectious complications developed after tumor dissection and filling with heterologous lyophilized bone. The final diagnosis was "giant cell reparative granuloma", an uncommon lesion in the fibula not previously reported in haemophiliacs. It was concluded that aspiration, when appropriately applied, may be a useful diagnostic procedure which should be borne in mind for the diagnosis of bone tumors in haemophiliacs.

Tarsometatarsal fractures and dislocations.

A total of 32 cases of tarsometatarsal fracture dislocations, treated during a 15-year period, have been retrospectively reviewed. Results were assessed in 29 patients with a mean age of 33.8 years and a mean follow-up of 6.3 years. On the basis of Quénu and Küss' classification, five patients had homolateral dislocations, three had divergent dislocations, and 21 had partial dislocations (seven medial partial and 14 lateral partial). Treatment included closed manipulative reduction, occasionally followed by Kirschner (K)-wire fixation. If closed reduction was not achieved, open reduction was performed. Results were assessed according to Hardcastle's scoring system. On that basis, 20 good, 5 fair, and 3 poor results were obtained and there was one early amputation. Good results were associated with an accurate reduction. Open treatment is advocated if minor displacement persists. Routine K-wire fixation is advised for all cases.