- Safety of a pasteurized plasma-derived Factor VIII and von Willebrand factor concentrate: analysis of 33 years of pharmacovigilance data. [Journal Article]
- TTransfusion 2017; 57(10):2390-2403
- CONCLUSIONS: More than 33 years of pharmacovigilance data continue to support the safety of Humate-P.
- Cross-reacting Material-positive Hemophilia A Diagnosed in a Patient with a Spontaneous Thigh Hemorrhage. [Case Reports]
- IMIntern Med 2017; 56(13):1719-1723
- A 53-year-old man, who had been diagnosed with mild hemophilia A (HA) at 35 years of age, was hospitalized with a thigh hematoma. His bleeding continued despite the administration of recombinant fact...
A 53-year-old man, who had been diagnosed with mild hemophilia A (HA) at 35 years of age, was hospitalized with a thigh hematoma. His bleeding continued despite the administration of recombinant factor VIII (FVIII). The results of an FVIII/von Willebrand factor binding assay were normal. The patient's FVIII coagulant activity (FVIII:C) was low, but his FVIII antigen levels were within the normal limits, suggesting FVIII protein dysfunction. The FVIII:C measurements obtained by one-stage clotting and chromogenic assays were different. An FVIII gene analysis revealed a missense mutation p.Ser308Leu, which is rare in Japan. This case highlights that gene analyses and chromogenic assays are necessary to interpret the discrepancies between FVIII:C and the bleeding phenotype of patients with mild HA.
- Advances in the treatment of bleeding disorders. [Review]
- JTJ Thromb Haemost 2016; 14(11):2095-2106
- Historically, the bleeding episodes in subjects with coagulation disorders were treated with substitution therapy, initially with whole blood and fresh frozen plasma, and more recently with specific ...
Historically, the bleeding episodes in subjects with coagulation disorders were treated with substitution therapy, initially with whole blood and fresh frozen plasma, and more recently with specific factor concentrate. Currently, patients with hemophilia have the possibility of choosing different effective and safe treatments, including novel extended half-life and alternative hemostatic drugs. The availability of novel extended half-life products could probably overcome current prophylaxis limitations, particularly in hemophilia B patients, by reducing the frequency of injections, achieving a higher trough level, and improving the quality of life of the patients. In addition, subcutaneous administration of alternative therapeutics would simplify prophylaxis in patients with hemophilia A and B with and without inhibitors. Regarding von Willebrand disease, a recombinant von Willebrand factor was recently developed to control bleeding episodes in patients with this disease, in addition to available von Willebrand factor/factor VIII concentrates. The management of patients affected by rare bleeding disorders (RBDs) is still a challenge, owing to the limited number of specific products, which are mainly available only in countries with high resources. Some improvements have recently been achieved by the production of new recombinant factor (F) XIII A subunit-derived and FX plasma-derived products for the treatment of patients affected by FXIII and FX deficiency. In addition, the development of novel alternative therapeutics, such as anti-tissue factor pathway inhibitor, ALN-AT3, and ACE910, for patients with hemophilia might also have a role in the treatment of patients affected by RBDs.
- Monitoring Therapy during Treatment of von Willebrand Disease. [Review]
- STSemin Thromb Hemost 2017; 43(3):338-354
- von Willebrand factor (VWF) is an adhesive plasma protein that primarily acts to bridge platelets to sites of vascular injury and thus prevent bleeding. von Willebrand disease (VWD) is the most commo...
von Willebrand factor (VWF) is an adhesive plasma protein that primarily acts to bridge platelets to sites of vascular injury and thus prevent bleeding. von Willebrand disease (VWD) is the most common inherited bleeding disorder and is caused by deficiency and/or defects of VWF, leading to low levels of plasma VWF or dysfunctional VWF. Factor VIII (FVIII) is also reduced in many patients with VWD, since VWF stabilizes and protects FVIII from degradation. Treatment of VWD primarily entails replacement of VWF, and sometimes FVIII, to protect against bleeding. This may entail use of VWF/FVIII concentrates, and/or desmopressin (1-deamino-8-d-arginine vasopressin) to release endogenous VWF in some patients. Adjunct therapies include antifibrinolytics and hormonal therapies in women. Optimal treatment of VWD entails measuring the effects of treatment, either as a trial before surgery or during therapeutic management. This is usually accomplished by performance of the same tests that are used to help diagnose VWD, although additional monitoring (clinically and/or by laboratory testing) may also be performed. The current review provides an overview of the treatment of VWD but is primarily focused on the monitoring of such therapy.
- High-affinity von Willebrand factor binding does not affect the anatomical or hepatocellular distribution of factor VIII in rats. [Journal Article]
- JTJ Thromb Haemost 2016; 14(9):1803-13
- Essentials Von Willebrand factor (VWF) stabilizes factor VIII (FVIII) and prevents its premature clearance. Rat anatomical and hepatocellular distribution studies assessed the VWF effect on FVIII cle...
Essentials Von Willebrand factor (VWF) stabilizes factor VIII (FVIII) and prevents its premature clearance. Rat anatomical and hepatocellular distribution studies assessed the VWF effect on FVIII clearance. Hepatocytes and liver sinusoidal endothelial cells play a key role in FVIII clearance. Anatomical and hepatocellular distribution of FVIII is independent of high-affinity VWF binding.
- Neutralizing capacity of inhibitors on FVIII is lower for natural FVIII/VWF complex than for isolated FVIII: in vitro comparative study in eleven different therapeutic FVIII concentrates. [Letter]
- HHaemophilia 2016; 22(4):e341-4
- Von Willebrand factor activity assay errors. [Letter]
- HHaemophilia 2016; 22(1):e74-6
- Clinical overview of Fanhdi/Alphanate (plasma-derived, VWF-containing FVIII concentrate) in immune tolerance induction in haemophilia A patients with inhibitors. [Letter]
- HHaemophilia 2016; 22(1):e71-4
- 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. [Case Reports]
- BCBlood Coagul Fibrinolysis 2015; 26(8):940-5
- 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 o...
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. We also wanted to raise the potential interest of laboratory assays such as thrombin-generation test (TGT) and epitope mapping. Two patients were treated during ITI, first with a recombinant FVIII and then with plasma-derived factor VIII without success, and, finally, with Octanate. Bypassing agents were used based on the results of TGT. Epitope mapping was performed during ITI therapy. These observations suggest the potential contribution of Octanate in the management of ITI in difficult cases. The use of bypassing agents can be necessary in prophylaxis or to treat bleedings, and may be guided by TGT results. Epitope mapping is used to describe the inhibitor. This article shows a decrease of the inhibitor directed against the C2 domain after initiation of Octanate. A high-purity human factor VIII/von Willebrand factor concentrate (Octanate) may be a valuable therapeutical option for ITI therapy. TGT and epitope mapping could be of help in the management of ITI.
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- First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/von Willebrand factor concentrate in an observational immune tolerance induction study. [Journal Article]
- HHaemophilia 2016; 22(1):87-95
- CONCLUSIONS: Treatment with a single pdFVIII/VWF concentrate, mainly according to the Bonn protocol, resulted in a high ITI success rate in haemophilia A patients with inhibitors and poor prognosis for ITI success.