Open synovectomy of the ankle joint in young haemophiliacs: mid-term to long- term results of a single-centre series of 32 procedures.

INTRODUCTION: In haemophiliacs, recurrent hemarthrosis and chronic synovitis lead to chronic arthropathy. Synovectomy is indicated when medical treatment fails. Few studies report the results of open synovectomy of the ankle in haemophiliacs with a small number of procedures and also a limited follow-up. AIM: The aim of this paper is to report the long-term results of open surgical synovectomy of the tibio-talar joint. METHODS: Thirty-two open synovectomies were performed in 21 young haemophiliacs in the same haemophilia center using an antero-lateral and postero-medial approaches. The median follow-up was 15.4 years. Clinical (Petrini scores) and radiological evaluations (Pettersson scores) were made preoperatively and at each multidisciplinary follow-up visit. Wilcoxon and Spearman's tests were used for the statistical analysis. RESULTS: Preoperative median Petrini score was 6 (range 3-12), and improved at 2 and 5 years follow-up (P = 0.0003 and P = 0.0001 respectively). At 10 and 15 years follow-ups, median score remained below preoperative score (median 3.5, range 0-11). Ten ankles had a follow-up of more than 20 years. Preoperative median Petterson score presented a slight but continuous worsening in the first 2 and 5 years of follow-ups (P = 0.02, P = 0.003), but not correlation between clinical and radiological results was observed. CONCLUSION: Our long-term results support that clinical scores are improved even if radiological scores progress. Open synovectomy retards the progression of the arthropathy, but not stops it. Bleeding and pain are controlled and even if recurrence of bleedings is frequent, it is less severe, less painful and requiring less factors replacement.

Batch recall of French plasma-derived products due to variant Creutzfeldt-Jakob disease risk: the psychological impact on haemophilic patients, changes in their therapeutic demands and behaviour and ethical considerations.

The choice of plasma-derived products (PdP) vs. recombinant products (RP) for treating haemophilia is influenced by the infectious and perceived safety of the products. Batch recall of PdP due to the risk of variant Creutzfeldt-Jakob disease (vCJD) may have unfavourable psychological impacts on haemophilia patients and influence their product preferences. This study aimed to assess the psychological impact of batch recalls of PdP in six haemophilia patients and their therapeutic demands, and to discuss the ethical problems in physicians' management of this event. A survey was conducted using a new interview form and an existing anxiety and depression questionnaire. Batch recalls produce recurrent negative emotional outcomes in haemophiliacs and their families. The quality, understanding and efficiency of the batch recall announcements were unsatisfactory in some respects. Only one patient still had some of the vials in question, and only three patients understood the real reason for the batch recall. Four patients asked to change their PdP for RP; a fifth patient was considering doing so. Here, topics for discussion include the delivery of an unclear message to patients about a very uncertain risk of a frightening disease, the reasons to maintain PdP when RP are largely available, except in specific cases, and the related discomfort for caregivers. The ethical questions revealed by batch recalls and the high psychological impact of vCJD risk on patients can no longer be ignored, and require surveys assessing the rationales and choices of the healthcare authorities, manufacturers, prescribers and users.

Long-term follow-up of children with haemophilia - low incidence of infections with central venous access devices.

This study reports on 15 years of experience, in a single haemophilia care centre in France, with central venous access devices (VADs) in children with haemophilia. Following the insertion of a central VAD, patients were requested to return to the hospital on a quarterly basis for a multidisciplinary appointment which included clinical examination, chest X-ray, cardiac and major vessels ultrasound and preventive fibrinolysis. The family was urged to return to the Haemophilia Care Centre if complications or problems occurred. The follow-up comprised 50 patients. Data were collected prospectively. The total number of days with a VAD was 86 461 days and the total number of times the VAD was used was 41 192 (approximately every other day). Mean duration of VAD placement was 1269 days (range 113-2794 days). There were 25 complications, of which 9 haematomas and 5 systemic infections. Two VADs, infected with Staphylococcus aureus, had to be replaced. The infection rate was calculated as 0.0578 infections/1000 catheter days. There were no cases of thrombosis. This study concluded that most VAD infections in children can be avoided, even in patients requiring intense, prolonged treatment. The very low infection rate was achieved through the efforts of a multidisciplinary team, combined with extensive training for all individuals involved, adherence to written protocols and specific monitoring measures.

Spontaneous obturator internus muscle haematoma: a new unpublished cause of ilioipelvic pain in haemophilia.

Obturator muscles haematoma are rarely reported. The most often reported cases are primary pyomyositis or posttraumatic haematomas occurring during pelvic fractures. We firstly report herein two cases of spontaneous obturator internus haematoma (OIH) in two haemophiliacs with inhibitor. Clinical data and imaging of two patients treated in our clinic are reported here according to previously defined criteria of OIH in posttraumatic situation. Both patients were children suffering from severe and moderate haemophilia A, respectively, with an inhibitor at the time of the event. The clinical feature was marked by an iliopelvic pain letting discussing hip haemarthrosis, appendicitis or iliopsoas haematoma. For both patients ultrasonography (US) failed to provide the diagnosis. Careful and repeated clinical examinations eventually lead to suspect obturator haematoma which was confirmed by abdominopelvic computed tomography (CT) and magnetic resonance imaging (MRI). Respectively, high dose of FVIII or rFVIIa regimen allowed a rapid control of the muscular bleeding in the low and high responder inhibitor patients. Spontaneous OIH may be added to the differential diagnosis of iliopelvic pain in severe forms of haemophilia. US still often performed at first in such case remains unhelpful; abdominopelvic CT or MRI should be performed to discriminate among different diagnoses, including OIH which stays probably undiagnosed.

Screening for von Willebrand disease: contribution of an automated assay for von Willebrand factor activity.

Measuring von Willebrand factor (VWF) activity is essential to the diagnosis of von Willebrand disease (VWD). The VWF activity is usually assessed based on measurement of the ristocetin cofactor (VWF:RCo). However, that test is technically challenging and has high intra- and inter-assay variabilities. The HemosIL VWF activity (VWF:AC) is a fully automated assay, recently proposed as a good alternative to VWF:RCo for VWD diagnosis. This study was undertaken to assess this new method. First, the analytical performance of VWF:AC on an automated coagulo-meter (ACLTop) was determined, and then this new method was compared with VWF:RCo and the platelet function analyzer (PFA100) for 160 patients referred for VWD screening. The VWF:AC achieved acceptable precision with within-run and between-run coefficients of variation ranging from 2.3% to 14.1%, and linearity from 10% to 100%. Despite some marked differences between VWF:AC and VWF:RCo for 10 plasmas tested, their agreement for VWD diagnosis was good. The VWF:AC had sensitivity similar to that of PFA100 (close to 100%), but better specificity (97.7% vs. 66% or 60%, depending on the cartridge used). The good analytical performance, and the sensitivity and specificity of VWF:AC to detect VWF deficiency renders it a suitable method for VWD screening. Our findings support VWF:AC use for the diagnostic work-up of VWD, paying close attention to concomitant clinical signs and bleeding score, as recommended for VWD.

Deaths associated with acquired haemophilia in France from 2000 to 2009: multiple cause analysis for best care strategies.

Deaths occurring in the context of acquired haemophilia (AH) may be related to inter-connected causes and mechanisms including bleeding, specific or older patient co-morbidities or iatrogenic complications. However, their magnitude remains unknown. This study aimed to determine the respective weight and frequency of the various causes of death in AH. Multiple-cause analysis based on death certificates data is used in this purpose. Over a 10-year period (2000-2009), 121 deaths with AH as a cause were registered in France. All the deaths were of adults (extremes: 47 and 99 years; mean age: 80.7 years). The average number of causes per death certificate was 4.7. AH was the underlying cause of death (UCD) in 69.4% of the cases, and was more frequent in the older subjects. In contrast, before age of 75 years, AH was more often a contributing cause of death. No postpartum or obvious thromboembolism-related deaths were registered. Haemorrhagic shock was the most frequent direct cause of death (DCD), followed by infectious events, cardiac dysfunction, metabolic and nutritional disorders with muscle wasting and decubitus complications, and cancers (52.9%, 26.4%, 7.5%, 5.8% and 4.1%, respectively). However, when AH was not reported as an UCD, infections become the first DCD (32.4%) followed by bleeding events (16.2%). Best prophylactic and curative strategies for infections are particularly required to improve the prognosis in AH. Moreover, as several of its DCD correspond also to steroids side effects, best tolerated immunosuppressant regimen with steroid-sparing agents adjoining are particularly awaited in AH population.

Uncomplicated neurosurgical resection of a malignant glioneuronal tumour under haemostatic cover of rFVIIa in a severe haemophilia patient with a high-titre inhibitor: a case report and literature review of rFVIIa use in major surgeries.

The development of inhibitors following factor VIII replacement therapy is a serious complication in severe inherited haemophilia. Whereas significant experience, notably in orthopaedic surgery, is now obtained with the use of bypassing agents in haemophilia with high-titre inhibitor, new surgical challenges might occur due to patients' increasing life expectancy. A 56-year-old severe haemophilia A patient with a high-titre inhibitor was diagnosed for probable right temporoparietal malignant glioneuronal tumour on cerebral magnetic resonance imaging (MRI) (4 cm x 3 cm cerebromeningeal tumour with perilesional oedema and transfalcial herniation) requiring total resection. Then recombinant activated FVII (rFVIIa) was chosen as the haemostatic agent: bolus of 270 microg kg(-1) every 2 h during the first 24 h, 180 microg kg(-1) every 3, 4 and 6 h, respectively, at days 2-3, from days 4-10 and finally from days 11-15. Tranexamic acid was associated. Pre- and postoperative courses were uneventful, the surgical procedure being assessed at optimal haemostatic condition without any unusual haemorrhage on MRI controls, diffuse intravascular coagulation criteria or thromboembolic event. Intensive rFVIIa therapy has shown to be safe and effective in this first reported neurosurgery about a malignant tumour exhibiting to a high-bleeding risk notably in haemophilia with high-titre inhibitor. The use of lower doses of rFVIIa might have been possible; however, in the absence of accurate test for monitoring rFVIIa therapy, the potentially life-threatening complications of this procedure required maximum haemostasis with high rFVIIa doses.

Single-dose (270 microg kg(-1)) recombinant activated factor VII for the treatment and prevention of bleeds in haemophilia A patients with inhibitors: experience from seven European haemophilia centres.

Several studies have suggested that recombinant factor VIIa (rFVIIa) is effective and safe at doses >90 microg kg(-1). In March 2007, the European Medicines Agency approved the use of single-dose rFVIIa 270 microg kg(-1) for the treatment of mild-to-moderate bleeds in haemophilia patients with inhibitors. The aim of this study was to describe the use of single-dose rFVIIa in a real-life setting. In November 2007, seven haemophilia specialists from five European countries convened to share and discuss their experiences with the single-dose rFVIIa regimen within haemophilia A. Case histories of eight patients were discussed in this retrospective study. Six adult and two paediatric patients (age range, 19 months-40 years) were treated with single-dose rFVIIa for a variety of target-joint bleeding, other bleeds and bleeding prevention. Treatment was successful in all the eight cases, with most patients requiring one dose to achieve bleeding resolution. No thrombotic or other safety concerns were raised by single-dose rFVIIa treatment. All patients and physicians preferred single-dose rFVIIa treatment to multiple injections; key benefits of single-dose rFVIIa treatment reported by patients and physicians included improved quality of life, greater convenience and ease of administration, improved compliance, faster control of bleeding, less injection-related pain and faster pain relief. In the patients reported here, single-dose rFVIIa 270 microg kg(-1) appears to be an effective and safe haemostatic treatment that improves the quality of life and convenience of treatment for patients. Such treatment might be of particular benefit for patients with difficult venous access or needle phobia.

Use of recombinant factor VIIa (NovoSeven) in patients with Glanzmann thrombasthenia.

Recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) appears effective and relatively safe for the treatment of bleeding and for surgical prophylaxis in patients with Glanzmann thrombasthenia as reported to the International Registry on rFVIIa and Congenital Platelet Disorders. One of the shortcomings of the Registry data is the heterogeneity of treatment protocol, including dosage, number of doses used, duration of treatment before declaration of failure, and mode of rFVIIa administration (bolus v continuous infusion). The data are not yet sufficient to define optimal regimens for various indications such as the type of bleeding or the type of procedures. The place of this drug compared to platelet transfusion in the overall management of patients with Glanzmann thrombasthenia will need to be determined in relationship to a number of challenges and unresolved issues in the clinical care of these patients. These issues include: how to improve local measures for patients with mucosal bleeds, optimal management of young women during menarche, optimal platelet transfusion regimens for various indications, the relationship between antiplatelet antibodies detected by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) and effectiveness of platelet transfusion, whether there are other biological tests that may correlate with effectiveness of platelet transfusion, and management of pregnancy and delivery regarding antiplatelet immunization.

Analysis of biological phenotypes from 42 patients with inherited factor VII deficiency: can biological tests predict the bleeding risk?

BACKGROUND AND OBJECTIVES: Inherited factor VII (FVII) deficiency is a rare bleeding disorder characterized by a poor relationship between reported FVII clotting activity (FVII:C) and bleeding tendency. Our study was aimed at defining biological parameters that are possibly predictive for bleeding risk in this condition. DESIGN AND METHODS: Forty-two FVII-deficient patients (FVII:C <30%) were classified into two opposite clinical groups defined as severe and non-or-mild bleeders. For each patient, plasma samples were collected and then investigated for FVII:C (using a sensitive method and human recombinant thromboplastin as the reagent), FVII antigen, activated FVII coagulant activity (FVIIa:C) and the free-form of tissue factor pathway inhibitor. RESULTS: None of these tests could be used as highly accurate predictors of bleeding. Nevertheless, both FVII:C and FVIIa:C differed significantly between the two clinical groups. Using ROC-curve analysis, two critical values of 8% and 3mIU/mL for FVII:C and FVIIa:C, respectively, could be proposed to discriminate between severe bleeders and non-or-mild bleeders. INTERPRETATION AND CONCLUSIONS: A highly accurate diagnostic test for predicting bleeding tendency in inherited FVII deficiency still eludes definition, highlighting the fact that factors other than FVII itself interfere with the expression of bleeding phenotypes in this condition. Nevertheless, potential critical values using sensitive FVII:C and FVIIa:C methods may be useful in clinical laboratories for FVII-deficient patients. Those patients with FVII:C levels higher than 8% FVII:C or FVIIa:C higher than 3 mIU/mL, with no other hemostatic defect, seem to have a minimal risk of severe bleeding. Extended clinical studies are needed to support these findings.

[Papular filariasis]. / Gale filarienne.

UNLABELLED: 'River blindness' is the main problem of onchocerciasis. Despite a high prevalence of onchocerciasis in endemic countries, cases of imported cutaneous or ocular onchocerciasis in France are rare. CASE REPORT: We report the case of a chronic papular onchodermatitis with voluminous lymphadenopathy in a Cameroonian child, resolving with a treatment of ivermectin. CONCLUSION: The main symptom of cutaneous onchocerciasis is pruritus, which symptom may alert physicians when dealing with patients who come from endemic countries for onchocerciasis. Cutaneous aspects may vary depending on length of exposure to antigens and immune responses by the host against microfilariae. Nowadays, onchocerciasis is treated with a single dose of ivermectin, which is sufficient for eye and cutaneous symptoms. However, this therapy is efficient only against microfilariae, and treatments have to be repeated many times to avoid relapses linked to persistence of adult worms.

[Epidural hematoma in a child with hemophilia: diagnostic difficulties]. / Hématome épidural chez l'enfant hémophile: difficultés diagnostiques.

UNLABELLED: Spinal epidural hematoma is an uncommon complication in hemophilia. CASE REPORTS: The cases of an extensive epidural hematoma in two boys with severe hemophilia are reported. CONCLUSION: Acute onset of severe neck pain or backache leads to the diagnosis of epidural hematoma in children with hemophilia, even in the absence of neurologic symptoms. Early diagnosis is important and relies on magnetic resonance imaging. Replacement therapy is mandatory and must be prescribed before neuroradiologic imaging. Generally, children have a good neurologic outcome.

[Adenoidectomy and tonsillectomy in children with hemophilia and von Willebrand disease]. / Adénoïdectomies et amygdalectomies chez les enfants atteints d'hémophilie et de la maladie de Willebrand.

Hemophilia type A or B is due to deficiency in factor VIII C or IX C, but whatever the type and whether the affection is severe or attenuated the risk of hemorrhage after surgery is identical. Willebrand's disease is due to either a qualitative or quantitative anomaly of willebrand's factor. Between 1979 and 1984, 15 children with these diseases were operated upon for removal of tonsils and adenoids. Surgery was performed under cover of substituted therapy with frozen cryoprecipitate for Willebrand's disease, either frozen or dried cryoprecipitate together with F VIII concentrates for hemophilia A, and PPSB for hemophilia B. This treatment was continued pastoperatively for 7 days after adenoidectomy and 10 days after tonsillectomy. Follow up examinations enabling possible adjustment of transfusional needs included determination of CKT and assay of factors VIII C or IX C in the hemophiliac children, and assay of factors F VIII R, AG, F VIII RCF and F VIII C in those will willebrand's disease.

Surgical synovectomy of the knee in young haemophiliacs: long-term results of a monocentric series of 23 patients.

BACKGROUND: In haemophiliacs, synovectomy is indicated for recurrent joint bleedings, despite medical treatment. METHOD: We report a series of 23 surgical synovectomies of the knee with a median follow-up of 8.8 years. The median age of patients at surgery was 13.5 years. Clinical and radiological evaluations were made according to the Petrini and the Pettersson scores, at 1 and 5 years after surgery, and at the last follow-up. Wilcoxon and Spearman's tests were used for the statistical analysis. RESULT: The Petrini score improved at 1 and 5 years (P < 0.001). Nine patients have 20 years of follow-up and a stable result. In more than half of the knees, no episode of recurrent bleeding occurred. The effect of surgery on the range of motion (ROM) was moderate and mobilisation under anaesthesia did not improve it significantly. There was a progressive worsening of the radiological score, but no correlation between clinical and radiological score was noticed (ρ = 0.08, P = 0.77). CONCLUSION: Complete synovectomy gives good long-term results in term of bleeding recurrence and overall function.

Intracranial haemorrhages in French haemophilia patients (1991-2001): clinical presentation, management and prognosis factors for death.

Intracranial haemorrhage (ICH) is known to be a severe although uncommon complication of haemophilia. A national survey has been conducted in France in order to collect information about ICHs which occurred in haemophiliacs between 1991 and 2001 and to propose recommendations for the diagnostic and treatment of ICH. Within this period, 123 episodes of ICH were recorded from 106 patients. Two-thirds of ICH concerned patients with severe haemophilia. Half of the cases occurred in patients under 15 years of age, 67.2% of which were post-traumatic. Ten cases occurred in neonates with three fatal outcomes. Overall mortality was high (21.9%) suggesting that availability of clotting factor concentrates has not improved the prognosis of this event. Morbidity was also high with 60% of long-term sequelae. The following parameters have been identified as prognostic factors for death: thrombocytopenia, HCV infection, intraventricular or intraparenchymatous haemorrhage. A delay in diagnosis was mentioned in 43.3% of cases, often related to the lack of recognition of the initial symptoms, which may be very common (apathy, tearfulness in young children and headache in elder patients). Delayed replacement therapy was recorded in 37.2% of cases. Emergency units initially dealt with half of these patients. Information concerning recognition and management of these episodes, not only in severe haemophilia, but also in moderate and mild forms, should be regularly supplied to paediatricians in maternity and physicians from emergency units, as well as to patients and their relatives.

[A case of AIDS in a hemophilia B patient in France]. / Un cas de SIDA chez un hémophile B en France.

AIDS is reported in a 14 year old hemophiliac B. This patient was treated on demand and used 800 F IX IU per kg B.W. and per year. He presented with severe opportunistic infection (Toxoplasmosis) and profound impairment of cellular immunity. He suffered of chronic active hepatitis and he was chronic HBs Ag carrier. A retrovirus (LAV) was isolated from his cultured T lymphocytes. He had no other identified risk factor than severe hemophilia B. The occurrence of AIDS in hemophiliacs suggests a relationship between the transfusion of blood products and the disease. The cause of AIDS is unknown. A possible relationship between LAV and AIDS is discussed.

Treatment of type III von Willebrand's disease with solvent/detergent-treated factor VIII concentrates.

An intermediate purity concentrate of factor VIII, treated with solvent and detergent (SD), was successfully used for treatment of intracerebral hematoma in a newborn with type III von Willebrand's disease. At the present time, the SD process used for the preparation of this factor VIII concentrate seems to be one of the most effective methods for viral inactivation. In this product, the biological properties of factor VIII and von Willebrand factor are preserved. Thus, the intermediate purity factor VIII SD concentrate could be used instead of frozen cryoprecipitate, as a safer therapy in the treatment of von Willebrand's disease.