Post-authorization safety study of Clottafact , a triply secured fibrinogen concentrate in congenital afibrinogenemia. A prospective observational study.

Background And Objectives: A new fibrinogen concentrate Clottafact was developed according to European guidelines on plasma-derived products. A post-authorization safety study was set up in 2009 as part of the risk management plan. This was a non-interventional, prospective, non-comparative, multicenter study of the use of fibrinogen concentrate for congenital afibrinogenemia in real-life medical practice in France.

Health-related quality of life and burden of fatigue in patients with primary immune thrombocytopenia by phase of disease.

The main objective of this study was to compare health-related quality of life (HRQOL) of primary immune thrombocytopenia (pITP) patients with that of general population, overall, and by patient group (i.e., newly diagnosed, persistent, and chronic patients).

Inhibitors in Severe Hemophilia A: 25-Year Experience in Slovakia.

Unlabelled: We present 25-year experience with inhibitors in previously untreated patients (PUPs) with severe hemophilia A in Slovakia, where safe factor VIII (FVIII) concentrates have been used since 1990. A prospective study focused on inhibitor incidence in PUPs was established in 1997. Out of a total 61 PUPs born between January 1997 and October 2015, 59 were eligible for evaluation; 50 and 9 were treated with > 20 exposure days (ED) of plasma-derived FVIII (pdFVIII) and recombinant FVIII (rFVIII) products, respectively.

Clinical and prognostic significance of serum levels of von Willebrand factor and ADAMTS-13 antigens in AL amyloidosis.

Cardiac dysfunction determines prognosis in amyloid light-chain (AL) amyloidosis. The heart is the central organ of the vascular system in which endothelium function is critical for the circulatory homeostasis, but there are limited data on endothelial function in AL amyloidosis. von Willebrand factor (VWF) has been considered as a marker of endothelial activation and dysfunction, whereas a disintegrin and metalloproteinase with thrombospondin type-1 repeats 13 (ADAMTS-13) cleaves VWF multimers, but both have been associated with prognosis in cardiovascular disease.

Achievements, challenges and unmet needs for haemophilia patients with inhibitors: Report from a symposium in Paris, France on 20 November 2014.

Over the past 20 years, there have been many advances in haemophilia treatment that have allowed patients to take greater control of their disease. However, the development of factor VIII (FVIII) inhibitors is the greatest complication of the disease and a challenge in the treatment of haemophilia making management of bleeding episodes difficult and surgical procedures very challenging. A meeting to discuss the unmet needs of haemophilia patients with inhibitors was held in Paris on 20 November 2014.

Challenges of the management of severe hemophilia A with inhibitors: two case reports emphasizing the potential interest of a high-purity human Factor VIII/von Willebrand factor concentrate and individually tailored prophylaxis guided by thrombin-generation test.

Severe hemophilia A is an X-linked bleeding disorder. Immune tolerance induction (ITI) is the best strategy of treatment when patients develop inhibitors. The objective is to illustrate the benefit of a high-purity human factor VIII/von Willebrand factor (VWF) concentrate (Octanate) in the management of ITI.

Presentation and management of acute coronary syndromes among adult persons with haemophilia: results of an international, retrospective, 10-year survey.

Sparse data are available on presentation and management of acute coronary syndromes (ACS), including unstable angina and non-ST- and ST-elevation myocardial infarction, among persons with haemophilia (PWH). The aim of this study was to determine demographics, bleeding disorder characteristics, cardiovascular risk factors (CRFs), interventions, haemostatic protocol, revascularization outcomes and complications among PWH with ACS. Members of an international consortium comprising >2000 adult PWH retrospectively completed case report forms for episodes of ACS in a >10-year follow-up period (2003-2013).

Prophylaxis with FEIBA in paediatric patients with haemophilia A and inhibitors.

The benefits shown with factor VIII (FVIII) prophylaxis relating to joint health and quality of life (QoL) provide the rationale for FEIBA prophylaxis in haemophilia A patients with persistent FVIII inhibitors. FEIBA has previously shown efficacy in preventing bleeds in inhibitor patients who failed to respond to, or were ineligible for immune tolerance induction (ITI). The study examined the outcome of paediatric patients undergoing long-term FEIBA prophylaxis.

Difficult encounters with a hemophilic patient: the inner perspective of physicians.

This study aimed at exploring the hematologists' internal representation of a difficult encounter with a hemophilic patient, using a written open format. Narrations were analyzed with Interpretative Phenomenological Analysis. Three main issues were identified, each with sub-issues: (1) Inside the relationship: to tell or not to tell, the balance between a normal life and a deviant medical condition, the guilt; (2) The borders of the professional role: professional values, the "do-it-all" doctor; and (3) The existential confrontation.

Venous thromboembolism in neonates and children.

Thrombosis in children is gaining increased awareness, as advanced medical care has increased treatment intensity of hospitalized pediatric patients. Guidelines for diagnosis and treatment of children and neonates with venous thromboembolism (VTE) are mostly extrapolated from adult data, despite the uniqueness of their hemostatic system. Whereas inherited thrombophilia (IT) have been established as risk factors for VTE in adults, in children with idiopathic VTE and in pediatric populations in which thromboses were associated with medical diseases, IT have been described as additional risk factors.

Knee arthropathy: when things go wrong.

Joint bleeding, or haemarthrosis, is the most common type of bleeding episode experienced by individuals with haemophilia A and B. This leads to changes within the joints, including synovial proliferation, which results in further bleeding and chronic synovitis. Blood in the joint can also directly damage the cartilage, and with repeated bleeding, there is progressive destruction of both cartilage and bone.

Menstrual problems and contraception in women of reproductive age receiving oral anticoagulation.

Background: Oral anticoagulation is associated with increased bleeding complications. The aim of this study was to assess the changes in menstrual loss and pattern in women taking anticoagulant treatment.

Study Design: Women on oral anticoagulant (OA) treatment at the Royal Free Hospital were interviewed and completed a questionnaire about their menstrual cycle before and after commencing oral anticoagulation treatment.

Management of arthrofibrosis in haemophilic arthropathy.

Hemophilic arthropathy is one of the conditions most associated with arthrofibrosis and loss of range of motion. Progressive fibrosis of synovium leads to pain, spasm, and shortening of muscles, resulting in joint contractures and restriction of joint motion. It is common to see even young children with severe loss of motion of elbows, knees and ankles.

Consensus recommendations for the diagnosis and treatment of acquired hemophilia A.

Background: Acquired hemophilia A (AHA) is a rare bleeding disorder caused by an autoantibody to coagulation factor (F) VIII. It is characterized by soft tissue bleeding in patients without a personal or family history of bleeding. Bleeding is variable, ranging from acute, life-threatening hemorrhage, with 9-22% mortality, to mild bleeding that requires no treatment.

Rate of inhibitor development in previously untreated hemophilia A patients treated with plasma-derived or recombinant factor VIII concentrates: a systematic review.

Background: Different rates of inhibitor development after either plasma-derived (pdFVIII) or recombinant (rFVIII) FVIII have been suggested. However, conflicting results are reported in the literature.

Objectives: To systematically review the incidence rates of inhibitor development in previously untreated patients (PUPs) with hemophilia A treated with either pdFVIII or rFVIII and to explore the influence of both study and patient characteristics.

Bone mineral density in haemophilia patients. A meta-analysis.

Osteoporosis is caused by bone mineral density (BMD) reduction. Haemophilia patients are at increased risk of osteoporosis because of decreased physical activity and blood-borne virus infections. This systematic review of the literature aims at evaluating BMD reduction in severe haemophilia patients and its correlation with patients' characteristics.

Factor VIII requirement to maintain a target plasma level in the prophylactic treatment of severe hemophilia A: influences of variance in pharmacokinetics and treatment regimens.

Background: Prophylactic factor (F)VIII has been shown to reduce bleeds and arthropathy in patients with severe hemophilia A.

Objectives: Assuming that the trough FVIII level is an important determinant of the efficacy of prophylaxis, this paper addresses the effect of the inter-patient variability in pharmacokinetics and different dosing regimens on trough levels.

Methods: Simulations used FVIII half-lives and in vivo recoveries (IVR), observed during clinical trials with Advate [Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method], and commonly used prophylactic regimens to calculate their effect on FVIII levels during prophylaxis.

Hyperhomocysteinemia and C677T MTHFR genotype in patients with retinal vein thrombosis.

Introduction: Elevated homocysteine (Hcy) is associated with the risk of deep vein thrombosis, pulmonary embolism, ischemic heart disease, and stroke. Several studies have suggested that hyperhomocysteinemia (HHcy) may predispose to retinal vein thrombosis (RVT) development. The aim of this study is to investigate the relationship between Hcy, C677T methylenetetrahydrofolate reductase (MTHFR) genotype, and RVT in patients compared with controls.

Italian Registry of Haemophilia and Allied Disorders. Objectives, methodology and data analysis.

National haemophilia registries are powerful instruments to support health care and research. A national registry was established in Italy by the Ministry of Health until 1999. Since 2003 the Italian Association of Haemophilia Centres (AICE) started a new programme aiming at building up the Italian Registry of Haemophilia and Allied Disorders.

Role of hyperhomocystinemia in retinal vascular occlusive disease.

Elevated plasma homocysteine (Hcy) level is considered a risk factor for vascular diseases. In recent years, many scientific reports have suggested that hyperhomocystinemia may be associated with an increased risk of retinal vascular occlusive disease (RVOD). The prevalence of elevation of homocysteine in patients with a recent retinal vascular occlusion was compared to a health control group in this study.

Long-term evaluation of radioisotope synovectomy with Yttrium 90 for chronic synovitis in Turkish haemophiliacs: Izmir experience.

Since 2001 we have performed 105 radioisotope synovectomy (RS) in 65 children and young adults, age ranging from 3 to 25 years with a average of 15 years in Ege University Hospital, Izmir, Turkey. One fourth of cases were below 10 years of age. All patients had severe haemophilia A and B.

Treating traumatic bleeding in a combat setting: possible role of recombinant activated factor VII.

Bleeding is clearly a major cause of morbidity and death after trauma. When bleeding is attributable to transection of major vessels, surgical repair is appropriate. Posttraumatic microvascular bleeding attributable to coagulopathy secondary to metabolic derangements, hypothermia, and depletion or dysfunction of cellular and protein components requires a different approach.

Phenotypic and genetic analysis of a compound heterozygote for dys- and hypoprothrombinaemia.

We studied a 2-year-old boy with a phenotype of combined hypo- and dysprothrombinaemia. Sequencing of polymerase-chain-reaction-amplified genomic DNA revealed three different mutations in heterozygosity, a G to A transition at position 7312, resulting in the replacement of arginine 271 by histidine, an A to G transition at position 20058, resulting in the replacement of histidine 562 by arginine, and a 2-bp deletion at 20062-20063, causing a frameshift and a premature stop codon in exon 14. The first two mutations are compatible with the dysprothrombinaemia phenotype, whereas the small deletion is thought to be the cause of hypoprothrombinaemia.

Obstetric and gynaecological aspects of von Willebrand disease.

The impact of von Willebrand disease in females is pronounced in terms of menorrhagia and postpartum haemorrhage. There is a very high proportion of von Willebrand disease patients with menorrhagia and associated anaemia, impairment of quality of life, including loss of time from work or school, and a high rate of the use of hysterectomy for ultimate control of the bleeding. The 'early' detection of von Willebrand disease in females may avert these complications.