Clinical efficacy, safety and pharmacokinetic properties of the plasma-derived factor IX concentrate Haemonine in previously treated patients with severe haemophilia B.

Plasma-derived factor IX (FIX) concentrate remains an important choice for replacement therapy in haemophilia B patients. Haemonine is a high purity double-virus inactivated human plasma-derived coagulation FIX concentrate (pdFIX). Aim was to evaluate the clinical efficacy, safety and pharmacokinetic properties of Haemonine in three prospective, open-label uncontrolled studies and a compassionate use program in previously treated patients with severe haemophilia B. Long-term efficacy and safety were investigated in 29 patients treated prophylactically and, in addition, treatment on-demand (TOD) in the case of acute haemorrhage. Pharmacokinetic properties were assessed in 14 patients at baseline and after 3 months of regular treatment. Pharmacokinetic parameters were in accordance with published data and remained nearly unchanged over time, notably recovery and half-life. Mean terminal elimination half-life was 27.6 h and 25.0 h, mean incremental recovery (IU dL(-1) /IU kg(-1)) was 1.55 and 1.60, at baseline and 3 months, respectively. Haemonine was shown to be effective in preventing and controlling bleeds. 55.2% (16/29) of patients were free of bleeds under prophylaxis. 38 haemorrhages occurred, 42% (16/38) required treatment and 87.5% (14/16) resolved after a single infusion, 12.5% after 2 infusions. All responses reported on haemorrhages were rated as 'excellent' or 'good'. Moreover, 'excellent' haemostatic efficacy was demonstrated in 12 surgeries with no complications. Few adverse events (AEs) and no thrombogenic complication, nor induction of FIX inhibitory antibodies were observed. Haemonine is effective, safe and well tolerated in long-term prophylaxis, TOD and when applied after minor and major surgeries.

Risks and challenges of orthopaedic invasive interventions in haemophilia in a low-resource country. A single-center experience.

UNLABELLED: Haemophilic arthropathy is a defining feature and a debilitating condition of persons with haemophilia (PwH) in low resource countries. Orthopaedic surgery is unavoidable for patients with high occurrence of joint damage. AIMS: We aimed to evaluate the spectrum and outcome of invasive orthopaedic therapies in PwH and von Willebrand diseases (VWD). PATIENTS AND METHODS: Our descriptive observational retrospective study included 131 invasive surgical procedures, performed on 76 consecutive patients, most of them (93.4%) with severe disease, treated in Timisoara's Haemophilia Center over a period of 12 years; 17.1% had pre-operation anti-FVIII inhibitors. Invasive elective procedures were predominant (90.8%) as compared to emergency measures (9.2%); according to their invasiveness, 20.6% of interventions were major, 44.3% intermediate and 35.1% minor. Results were good in the majority of cases; significantly reduced joint bleed rate and pain score were the most consistent achievements. The greatest proportion of complications occurred after major (66.7%), compared to moderate (25.6%) and minor (7.7%) interventions. The main threatening complication was the development (3.8%) or increase (4.6%) of inhibitor titer. Local bacterial infections and wound dehiscence complicated the evolution in 4.6% and 0.8 % of cases, respectively; we noticed no blood-borne infections or thrombotic accidents. Low dosage (10.7%) and short duration of substitution (21.4%) led to increased post-surgical bleeding and post-haemorrhagic anaemia. CONCLUSIONS: Surgery is a highly demanding intervention in haemophilia, which cannot be ignored in a low resource country. It represents a life or limb-saving and quality of life-improving measure.

Long-term outcome of an unusual haemophilic pseudotumour.

Haemophilia, a lifelong congenital bleeding disease, is a highly demanding disorder, due to the costs of its replacement therapy. In the absence of this pivotal treatment, life expectancy and quality of life are deleteriously affected. As illustration, we present a 14 years long follow-up of a patient with severe haemophilia A, treated sporadically with fresh plasma, cryoprecipitate and factor concentrates, who developed a giant iliopsoas pseudotumor. Since he was an infant, under on demand therapy with fresh frozen plasma, cryoprecipitate and low doses of factor concentrates he presented many spontaneous bleedings, developing multiple disabling arthropathies. At the age of 14 years, an iliopsoas hematoma occurred, which relapsed several times, developing an iliopsoas pseudotumour. After 5 years, sepsis with Klebsiella was diagnosed. A CT scan revealed fistula between the pseudotumor and the gut. Under antibiotics, the evolution of sepsis improved, but over a period of 10 months 5 episodes of haematemesis and melena, followed by one episode of macroscopic haematuria occurred; two months later he developed an inguino-crural mass, which fistulized through the abdominal wall. A mixt german-romanian team solved the clinical concern. After 108 hospitalization days and consumption of 104840 IU factor VIII he left the clinic in good condition. One year later, the temporary colostomy with anus praeter was closed. The follow-up reveals now, after almost 10 years with favourable outcome, that the patient is well, active within his family and profession.