Emicizumab prophylaxis in infants: Single-centre experience.

The hallmark of haemophilia A (HA) therapy is prophylaxis, aimed at spontaneous bleeding prevention. Emicizumab provides a viable alternative to intravenous factor replacement therapy. However, data on its use in infants are limited.

BAY 81-8973 demonstrated efficacy, safety and joint status improvement in patients with severe haemophilia A in the LEOPOLD I extension for ≤2 years.

Objectives: BAY 81-8973 (Kovaltry ), a full-length, unmodified, recombinant human factor VIII, provided excellent bleeding control for patients with haemophilia A in the pivotal 1-year LEOPOLD I trial. The LEOPOLD I extension evaluated long-term efficacy and safety of BAY 81-8973 prophylaxis.

Methods: After completing LEOPOLD I, patients continued receiving 20-50 IU/kg BAY 81-8973 two- or three-times weekly in the extension.

Long-term safety and efficacy of rIX-FP prophylaxis with extended dosing intervals up to 21 days in adults/adolescents with hemophilia B.

Background: An international, multicenter extension study evaluated recombinant fusion protein linking recombinant coagulation factor IX (FIX) with recombinant human albumin (rIX-FP) in hemophilia B (FIX ≤ 2%) patients previously enrolled in a phase III study or who initiated rIX-FP prophylaxis following surgery.

Objectives: To investigate the long-term safety and efficacy of rIX-FP prophylaxis in adult previously treated patients (PTPs) with hemophilia B.

Methods: Male PTPs were treated with a 7- (35-50 IU/kg), 10- or 14-day regimen (50-75 IU/kg).

Cellular Factor XIII, a Transglutaminase in Human Corneal Keratocytes.

Cellular factor XIII (cFXIII, FXIII-A), a transglutaminase, has been demonstrated in a few cell types. Its main function is to cross-link proteins by isopeptide bonds. Here, we investigated the presence of cFXIII in cells of human cornea.

Genetic Variation in the Syntaxin-Binding Protein STXBP5 in Type 1 von Willebrand Disease Patients.

von Willebrand factor (VWF) levels in healthy individuals and in patients with type 1 von Willebrand disease (VWD) are influenced by genetic variation in several genes, for example, , and . Here, we comprehensively screen for variants and investigate their association with type 1 VWD in Swedish patients and controls. The coding region of the gene was re-sequenced in 107 type 1 VWD patients and the detected variants were genotyped in the type 1 VWD population and a Swedish control population (464 individuals).

Genetic Variation in the von Willebrand Factor Gene in Swedish von Willebrand Disease Patients.

von Willebrand factor (VWF) level and function are influenced by genetic variation in and several other genes in von Willebrand disease type 1 (VWD1) patients. This study comprehensively screened for variants and investigated the presence of genotypes and common and rare variants in Swedish VWD1 patients. The gene was resequenced using Ion Torrent and Sanger sequencing in 126 index cases historically diagnosed with VWD.

Clinical and laboratory characteristics of antithrombin deficiencies: A large cohort study from a single diagnostic center.

Introduction: Inherited antithrombin (AT) deficiency is a heterogeneous disease. Due to low prevalence, only a few studies are available concerning genotype-phenotype associations. The aim was to describe the clinical, laboratory and genetic characteristics of AT deficiency in a large cohort including children and to add further laboratory data on the different sensitivity of functional AT assays.

Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial.

A global phase 3 study evaluated the pharmacokinetics, efficacy, and safety of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 63 previously treated male patients (12-61 years) with severe hemophilia B (factor IX [FIX] activity ≤2%). The study included 2 groups: group 1 patients received routine prophylaxis once every 7 days for 26 weeks, followed by either 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively; group 2 patients received on-demand treatment of bleeding episodes for 26 weeks and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. The mean terminal half-life of rIX-FP was 102 hours, 4.

Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR) Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease.

The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12) could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype.

Resistance: what is new and on the horizon, and a time to teach old dogs new tricks?

Understanding HIV drug resistance has played a key role in the success of antiretroviral therapy. This knowledge allowed for the prediction of resistance evolution when a specific drug or combinations of drugs were administered, informing strategies implemented for initial and subsequent drug regimens. Resistance testing of individual patients detects transmitted as well as acquired drug resistance as a result of treatment failure, leading to improved treatment choices in drug naïve and drug experienced patients accordingly.

Long-standing prophylactic therapy vs. episodic treatment in young people with severe haemophilia: a comparison of age-matched Danish and Russian patients.

Two distinctly different substitution principles are commonly used in haemophilia: treatment at bleeding episodes only referred to as on-demand treatment, and prophylactic factor administration. The aim of the cross-sectional study which was undertaken in young patients suffering severe haemophilia A was to challenge our hypothesis that on-demand treatment is inferior to prophylactic substitution in prevention of chronic joint disease at young age. The method involved an investigation of 40 patients from Russia (n = 27) and Denmark (n = 13) born between 1975 and 1990 with no history of inhibitors; Russian patients had exclusively received factor VIII on demand, while Danish patients were managed with prophylactic treatment during a mean period of 16 years since median age of 5 years.

Occurrence of thrombosis in rare bleeding disorders.

Paradoxically, there are reports of thrombotic events for some rare bleeding disorders associated with significant bleeding tendency. Afibrinogenemia, factor (F) VII, or FXI deficiencies are those most commonly associated with venous or arterial thrombosis. Pathogenesis is multifactorial and the main conditions associated with this complication relate to the coexistence of inherited or acquired thrombotic risk factors linked to certain specific characteristics of the underlying defect.

Management of the elbow joint.

The elbow is a complex joint that is prone to bleeding episodes. These features as well as the close proximity of the ulnar nerve and the need to use the elbow in many activities of daily living can lead to a range of symptoms including recurrent bleeds, pain, instability or loss of range of movement and nerve compression. Conservative management includes splinting and proprioceptive retraining monitored by a physiotherapist who is a musculoskeletal expert in hemophilia care.

Thrombosis in rare bleeding disorders.

Inherited deficiencies of blood coagulation factors are usually associated with lifelong bleeding tendency. In addition to Haemophilias A and B and von Willebrand disease, congenital deficiencies of such factors as fibrinogen, prothrombin (FII)), FV, FVII, FX, FXI, FXIII, and combined deficiencies occur and can lead to a diversity of clinical conditions. Paradoxically, for some of these disorders associated with significant bleeding tendency there are reports of thrombotic events, both arterial and venous.

A highly sensitive thrombin generation assay for assessment of recombinant activated factor VII therapy in haemophilia patients with an inhibitor.

Bypass agents are the common treatment for haemophilia patients who develop inhibitory antibodies. Laboratory assessment of the efficacy of bypassing agent therapy is a challenge. In the present work we modified the conditions triggering thrombin generation (TG) assay in order to find the most sensitive assay for detection of rFVIIa and its analogue NN1731 in haemophilic plasma.

Perthes' disease and the search for genetic associations: collagen mutations, Gaucher's disease and thrombophilia.

The role of heritable thrombophilic risk factors in the pathogenesis of the Perthes' disease is controversial. The clinical and radiological findings of Perthes' disease may be indistinguishable from those of Gaucher's disease, and the most common Jewish N370S Gaucher mutation is threefold greater in patients with Perthes' disease. Familial osteonecrosis of the femoral head is associated with variant mutations of collagen type II (COL2A1 mutations).

Chemical synoviorthesis with oxytetracycline clorhydrate (Emicine) in recurrent haemarthrosis.

This is a non-controlled experimental prospective clinical study that evaluates the satisfactory results in the chemical synovectomy (synoviorthesis) with oxytetracycline clorhydrate (Emicine, Lab. Pfizer Ltda, Guarulhos, Sao Paulo, Brazil) in recurrence haemarthrosis in different joints, demonstrating that it is an effective method in the treatment of these recurrent haemarthrosis in haemophilia. 84 patients of whom 77 concluded the full course of treatment.

Haematuria in patients with haemophilia and its influence on renal function and proteinuria.

To investigate renal function in a group of patients with a history of haemophilia and haematuria. We reviewed 32 medical records of the patients with haemophilia and gross haematuria identified through a computerized haemophilia registry, from January 1993 to December 2004. In all patients but three (two refused to participate and one died) clinical and laboratory tests were performed by the nephrologist.

Percutaneous treatment of haemophilic digital pseudo tumours.

In young patients with haemophilia, blood cysts in the finger bones may grow rapidly and imitate a malignant tumour (pseudo tumour). The condition must initially be treated with administration of factor VIII-IX. If this does not control the growth, surgical treatment is indicated.

The treatment of intra-articular synovitis by the use of chemical and radioactive substances.

As the Chairperson of the session relating the intra-articular use of chemical and radioactive substances it would seem appropriate to give credit to those who contributed to the recent supplement of our Journal Haemophilia. I have extracted key sentences and concepts from the contributed articles. All the papers can be found in Haemophilia, Volume 7, Supplement 2, July 2001.

Orthopaedic outcome of total knee replacement in haemophilia A.

A consecutive series of 16 patients with classical Haemophilia underwent 21 total knee replacements between 1989 and 1997 for haemophilic arthropathy. The patients received Factor VIII replacement therapy via continuous infusion, and fibrin glue was used to facilitate haemostasis. Three different types of prostheses were used.

Safety and efficacy of continuous infusion of a combined factor VIII-von Willebrand factor (vWF) concentrate (Haemate-P) in patients with von Willebrand disease.

We studied the safety and efficacy of treatment with continuous infusion of a von Willebrand factor (vWF) concentrate Haemate-P in patients with von Willebrand disease (vWD). Three patients with mild and 5 patients with severe forms of vWD, were treated with continuous infusion of Haemate-P by minipump. The indications for treatment were: to prevent bleeding during 9 surgical procedures or 1 vaginal delivery in 6 patients and to treat 2 bleeding episodes in 2 patients.

Continuous infusion therapy in haemophilia.

The application of coagulation factor therapy by continuous infusion (CI) was first suggested by Brinkhous in the early 1950s. The recent introduction of this mode of therapy to everyday practice was made possible after the demonstration of a good stability of most factor concentrates which were also found safe regarding potential bacterial contamination. Other developments included a better understanding of the pharmacokinetics of factors concentrates as well as the availability of a new delivery system.