- Pharmacokinetic and safety considerations when switching from standard to extended half-life clotting factor concentrates in hemophilia. [Journal Article]
- ERExpert Rev Hematol 2019 Jul 17
- Introduction: Plenty of new FVIII/IX concentrates have been developed and entered the market of hemophilia treatment. Others are going to end the long/demanding procedures for approval. Changes of th…
Introduction: Plenty of new FVIII/IX concentrates have been developed and entered the market of hemophilia treatment. Others are going to end the long/demanding procedures for approval. Changes of the FVIII molecule (single chain), pegylation of B-domain deleted FVIII, and fusion with Fc succeeded to improve the FVIII half-life, about 4 hours. Pegylation and fusion with albumin or Fc of rFIX caused a substantial increase of half-life, approximately 3-4 times that of FIX standard concentrates. Area covered: Extended Half-life concentrates may allow a longer time interval between the prophylaxis bolus, a feature very well accepted by young patients. Also, adherence of adolescents can be improved by these new, less demanding, concentrates. The immunogenicity of these new molecules is so far under post-marketing evaluation. The incidence of neutralizing antibodies is very low in previously treated patients, but the data on previously untreated patients are not yet assessed. The cost of some Extended Half-Life concentrates is higher than that of standard ones, and some concerns have been raised about the cost for public or private health care institutions. Expert opinion: An accurate evaluation of patients' needs, individual pharmacokinetics, and cost/effectiveness might allow a more appropriate usage of these new and expensive concentrates.
- Exploring the Impact of Infusion Frequency in Hemophilia A: Exit Interviews with Patients Participating in BAY 94-9027 Extension Studies (PROTECT VIII). [Journal Article]
- PPatient 2019 Jul 16
- CONCLUSIONS: This study provides rich insights into the experiences of patients with EHL products and the value of reduced infusion frequency. Such data could be of value to a range of stakeholders (e.g. regulators, payers) and facilitate patient-clinician discussions to promote tailored treatment decisions.
- Impact of Arterial Procedures on Coagulation and Fibrinolysis - A Pilot Study. [Journal Article]
- BJBraz J Cardiovasc Surg 2019 Jun 01; 34(3):327-334
- CONCLUSIONS: Vascular surgery leads to significant alterations in hemostatic and fibrinolytic systems. However, the direction of these changes in both pathways remains unclear and seems to be different depending on the type of surgery. A study utilizing dynamic methods of coagulation and fibrinolysis assessment performed on a larger population is warranted.
- Effects of long-term exposure to an extremely low frequency magnetic field (15 µT) on selected blood coagulation variables in OF1 mice. [Journal Article]
- EBElectromagn Biol Med 2019 Jul 13; :1-8
- The long-term exposure of OF1 mice to an extremely low frequency magnetic field (ELF-MF; 50 Hz, 15 µT [rms]) has been associated with the appearance of leukaemia. Neoplasms are usually accompanied by…
The long-term exposure of OF1 mice to an extremely low frequency magnetic field (ELF-MF; 50 Hz, 15 µT [rms]) has been associated with the appearance of leukaemia. Neoplasms are usually accompanied by changes in haemostatic processes but reports on changes in blood coagulation following exposure to an ELF-MF are scarce and rather fragmentary. The aim of the present work was to determine whether any global or partial coagulation variables are modified after such long-term exposure. A parental generation of six week-old OF1 mice was exposed to an artificial ELF-MF for 14 weeks. Mating was then allowed, and the resulting filial generation raised until the age of 31-35 weeks within the same ELF-MF. Control animals were subjected only to the magnetic field of the Earth. Whole blood samples were extracted from the anesthetised filial generation of mice by cardiac puncture. White blood cells (WBC) were counted, the activated partial thromboplastin time (APTT) and prothrombin time (PT) determined, and plasma fibrinogen, reptilase time (RT), and factor VIII activity examined. The similarity between the results for the present control animals and those recorded in the literature for human blood render OF1 mice a suitable study model. The differences in the studied coagulation variables were largely owed simply to sex. However, the females showed a very significant shortening of the PT time associated with ELF-MF exposure. Exposure also caused significant increases in the female APTT and RT values, and in general reduced the differences between the sexes.
- Mechanisms of Vascular Permeability and Remodeling Associated with Hemarthrosis in Factor VIII-Deficient Mice. [Journal Article]
- JTJ Thromb Haemost 2019 Jul 13
- CONCLUSIONS: Intact hemostasis at the time of hemarthrosis and during healing are both critical to prevent vascular remodeling, which appears worse with severe and prolonged FVIII deficiency. Unbiased RNA sequencing revealed potential targets for intervention and biomarker development to improve management of HA. This article is protected by copyright. All rights reserved.
- A comparative study on the possible protective effect of esomeprazole, spirulina, wheatgrass on indomethacin-induced gastric ulcer in male albino rats. [Journal Article]
- MBMol Biol Rep 2019 Jul 11
- Gastric ulcer is a common problem affecting the gastrointestinal tract. Spirulina and wheatgrass are natural substances that have anti-inflammatory and antioxidant effects. The aim of the Work was to…
Gastric ulcer is a common problem affecting the gastrointestinal tract. Spirulina and wheatgrass are natural substances that have anti-inflammatory and antioxidant effects. The aim of the Work was to elucidate the possible protective role of spirulina and wheatgrass versus standard treatment esomeprazole on indomethacin-induced gastric ulcer in adult male albino rats. Eighty adult male albino rats were divided into eight groups: group I (the control group), group II that received indomethacin (100 mg/kg orally), group III that received esomeprazole (20 mg/kg orally), group IV that received spirulina (1000 mg/kg orally), group V that received wheatgrass (1000 mg/kg orally), group VI that received indomethacin (100 mg/kg) + esomeprazole (20 mg/kg), group VII that received indomethacin (100 mg/kg) + spirulina (1000 mg/kg) and group VIII that received indomethacin (100 mg/kg) + wheatgrass (1000 mg/kg). Six hours after indomethacin treatment, all rats were anesthetized and their stomachs obtained for measures of gastric acidity, pepsin activity, mucin content, gastrin, ulcer index, total antioxidant capacity (TAC), tumor necrosis factor -α (TNF-α), interleukin-8 (IL8), proapoptotic protein (Bax). Histological (using H&E stain, PAS reaction) and immunohistochemical (using anti Ki67 immunostain) techniques were performed. Western immunoblot analysis for heat shock protein 70 (HSP70) was also done. Moreover, a morphometric study was done for area% of positive immunoreactive cells for Ki67 and optical density and area% of PAS reaction. All performed measurements were followed by statistical analysis. Indomethacin induced loss of normal architecture of gastric mucosa with sloughing of surface epithelium and inflammatory cellular infiltration. It also led to a significant increase in gastric acidity, inflammatory mediators (TNF-α, IL-8), pro-apoptotic protein Bax and a significant decrease in TAC levels and HSP-70 expression. There was also a significant decrease in area% of Ki67 immunoreactivity and area% and optical density of PAS reaction as compared with the control group and other pre-treated rats. These disturbed parameters were associated with increased ulcer index. In pre-treatment groups, the structure of the mucosa was similar to control with marked improvement in the biochemical assay. In conclusion, Spirulina and wheatgrass can partly protect the gastric mucosa against indomethacin-induced damage to a degree similar to that of the classical treatment esomeprazole.
- A field study evaluating the activity of N8-GP in spiked plasma samples at clinical haemostasis laboratories. [Journal Article]
- HHaemophilia 2019 Jul 11
- CONCLUSIONS: Most clinical laboratories accurately measured N8-GP and rAHF when using their in-house one-stage or chromogenic FVIII:C assays. However, three silica-based aPTT reagents underestimated N8-GP recovery.
- Fixed doses of N8-GP prophylaxis maintain moderate-to-mild factor VIII levels in the majority of patients with severe hemophilia A. [Journal Article]
- RPRes Pract Thromb Haemost 2019; 3(3):542-554
- CONCLUSIONS: Prophylaxis with fixed intervals (Q4D/twice weekly) and fixed weight-based dosing (50/60 IU/kg) ensured >1 IU/dL FVIII trough levels in both adults and children.
- Using pharmacokinetics for tailoring prophylaxis in people with hemophilia switching between clotting factor products: A scoping review. [Review]
- RPRes Pract Thromb Haemost 2019; 3(3):528-541
- The objective of this scoping review is to summarize the current use of pharmacokinetics for tailoring prophylaxis in hemophilia patients switching between clotting factor products. Patients with hem…
The objective of this scoping review is to summarize the current use of pharmacokinetics for tailoring prophylaxis in hemophilia patients switching between clotting factor products. Patients with hemophilia may require switching of clotting factor concentrates due to a variety of factors, but there have been perceived risks associated with switching, such as inhibitor development or suboptimal protection due to inadequate dosing while titrating treatment. Studies that look at patients switching from one clotting factor concentrate to another are categorized in terms of their primary and/or secondary objectives, notably biosimilarity and comparative pharmacokinetic studies and inhibitor development studies. Research on how best to switch concentrates with respect to dosing regimen are lacking, and currently a trial-and-error approach is used for dosing the new factor concentrate. In the future, studies looking at the predictability of pharmacokinetics (PK) of a new factor concentrate based on individual PK knowledge of the original factor concentrate may offer clinical benefit by providing a safer switching approach and protocol.
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- Successful use of emicizumab in a patient with refractory acquired hemophilia A and acute coronary syndrome requiring percutaneous coronary intervention. [Case Reports]
- RPRes Pract Thromb Haemost 2019; 3(3):420-423
- We report a patient with a high-titer factor VIII inhibitor refractory to immunosuppression. He initially presented with myocardial infarction requiring percutaneous coronary intervention (PCI) with …
We report a patient with a high-titer factor VIII inhibitor refractory to immunosuppression. He initially presented with myocardial infarction requiring percutaneous coronary intervention (PCI) with bare metal stent placement. Despite Feiba prophylaxis, inadequate hemostasis prompted premature discontinuation of dual antiplatelet therapy (DAPT). Fifteen weeks later, the patient presented with a left anterior descending artery in-stent restenosis. This case report examines the Key Clinical Question of how to manage in-stent restenosis in a patient with acquired hemophilia A (AHA). After multidisciplinary discussions including hematology, cardiology, cardiac surgery, laboratory medicine, and pharmacy, emicizumab was initiated to facilitate PCI. Four weeks after emicizumab initiation, the patient underwent successful PCI with drug-eluting stent placement. Five months after discharge, he remains without signs or symptoms of cardiac disease or bleeding on DAPT and emicizumab. This case provides evidence of the potential of emicizumab for bleeding prophylaxis in AHA.