News Update on Hemophilia Research: April – 2019

Safety of recombinant coagulation factors in treating hemophilia

Introduction: throughout the last decade, new FVIII/IX concentrates are developed for the treatment of patients tormented by blood disease A/B. vital progress has been achieved relating to their half-life, however the recent issue of immunogenicity and new considerations concerning safety have to be addressed .

Areas covered: once the implementation of agent ways, each plasma-derived and recombinant coagulation factor concentrates achieved a awfully safe profile. the event of anti-FVIII antibodies is that the major adverse event of replacement medical care with each FVIII concentrates. what is more, the new extended half-life concentrates, supermolecule consolidated or pegylated, raised some considerations concerning their facet effects.

Expert Opinion: The treatment of hemophilia A with inhibitors by induction of immunotolerance and mistreatment by-passing concentrates, improved the standard of lifetime of patients however failed to permit them to possess a anticipation like that of patients while not inhibitors. The new humanized antibody (MAb) ACE910, mimicking FVIII operate, looks to be able to scale back the bleedings of hemophilia A patients with inhibitors. The post-marketing police work can clarify if the adverse events discovered throughout the clinical test clinical trials and compassionate use were because of the association with a clotting factor activated complicated concentrate or to the prothrombotic result of the drug itself. [1]

Advances in the Treatment of Hemophilia: Implications for Laboratory Testing

BACKGROUND: till recently, clinical laboratories have monitored blood disorder treatment by measure clotting factors before/after infusion of human-derived or recombinant factors. Substantial changes are expected within the close to future supported new therapeutic approaches that are or are being developed.

CONTENT: blood disorder treatment includes replacement medical aid with human-derived/recombinant factors or treatment with bypassing agents for patients while not or with inhibitors, severally. consequently, laboratory strategies for observance embrace one-stage activity or chromogenic assays meant to live either issue VIII/IX or international coagulation tests to measure the impact of bypassing agents. Recently, changed long clotting factors are introduced that discrepant results could also be expected once measuring is performed with one-stage clotting or chromogenic assays. Currently, novel medication not supported clotting factors are below development and are being tested in clinical studies. These medication do need new strategies and so laboratory analysis of blood disorder can endure dramatic changes within the close to future.

SUMMARY: From the analysis of this observe and literature, we tend to draw the subsequent conclusions: (a) coagulase generation or thromboelastometry are the logical candidate assays to observe bypassing agents. (b) goodish variations are expected once measure changed long clotting factors, reckoning on whether or not one-stage or chromogenic assays are used. though no definitive conclusions will presently be drawn, chromogenic assays are most likely additional appropriate than one-stage activity. (c) Novel medication not supported clotting factors like emicizumab, fitusiran, or concizumab that are coming into the market do need different strategies that aren’t nonetheless well established. [2]

Strategies for Individualized Dosing of Clotting Factor Concentrates and Desmopressin in Hemophilia A and B

haemophilia and Christmas disease are hereditary haemorrhage disorders, caused by a deficiency of plasma protein VIII or clotting factor IX, severally. To treat and stop bleedings, patients will administer plasma protein concentrates (hemophilia A and B) or desmopressin (hemophilia A). each plasma protein concentrates and desmopressin are presently treated in line with the patients’ weight. However, plasma protein concentrates exhibit hefty pharmacokinetic (PK) variability. Therefore, many various dosing methods to individualize dosing of plasma protein concentrates and desmopressin in haemophilia and B are planned. during this study, a review of the prevailing literature on the individuation of dosing supported PK steering was performed. In total, seventy nine articles were enclosed. The ways to individualize dosing were divided into three categories: (1) methods victimization clinical parameters, (2) empirical individual PK-guided ways, and (3) most a posteriori (MAP) Bayesian estimation ways. The clinical parameter in the main wont to individualize dosing is haemorrhage constitution. Dosing supported haemorrhage constitution could decrease plasma protein consumption. However, with this methodology, it’s uphill to individualize on-demand dosing throughout haemorrhage events or within the perioperative setting. Empirical individual PK-guided ways may be used each for hindrance and treatment of bleedings. These ways embody dose individuation employing a nomograph and personalised in vivo recovery. within the perioperative setting, adjustment of the speed of continuous infusion may be applied to get a selected target level. the ultimate class, MAP Bayesian estimation ways, depends on the supply of a population PK model. In total, twenty two population PK models describing plasma protein concentrate or desmopressin dosing are presently obtainable in literature. MAP Bayesian estimates may be wont to calculate the personalised doses needed to attain or maintain a target level in each setting. the appliance of PK-guided and pharmacodynamic-guided dosing of plasma protein concentrates and desmopressin looks promising, though any investigation is secure. Prospective studies analyzing its potential profit are on the means. [3]

Restoration of FVIII expression by targeted gene insertion in the FVIII locus in hemophilia A patient-derived iPSCs

Target-specific order piece of writing, mistreatment designed enzymes Zn finger nuclease (ZFN), transcription activator-like effector enzyme (TALEN), and kind II clustered frequently interspaced short palindromic repeats (CRISPR)/CRISPR-associated macromolecule nine (Cas9), is taken into account a promising approach to correct disease-causing mutations in numerous human diseases. specifically, bleeder’s disease may be thought-about a perfect target for cistron modification via designed nucleases as a result of it’s a genetic disease caused by a mutation in plasma protein VIII (FVIII), and a gentle restoration of FVIII levels in plasma will forestall unwellness symptoms in patients with severe bleeder’s disease. during this study, we have a tendency to describe a universal order correction strategy to revive FVIII expression in elicited pluripotent stem cells (iPSCs) derived from a patient with bleeder’s disease by the human elongation issue one alpha (EF1α)-mediated traditional FVIII organic phenomenon within the FVIII locus of the patient. we have a tendency to used the CRISPR/Cas9-mediated homology-directed repair (HDR) system to insert the B-domain deleted from the FVIII cistron with the human EF1α promoter. when cistron targeting, the FVIII cistron was properly inserted into iPSC lines at a high frequency (81.81%), and these cell lines maintained pluripotency when knock-in and antiseptic resistance container removal. additional significantly, we have a tendency to confirmed that epithelial tissue cells from the cistron-corrected iPSCs might generate functionally active FVIII macromolecule from the inserted FVIII gene. this can be the primary demonstration that the FVIII locus could be a appropriate website for integration of the conventional FVIII cistron and may restore FVIII expression by the EF1α promoter in epithelial tissue cells differentiated from the bleeder’s disease patient-derived gene-corrected iPSCs. [4]

Correlation between the Prevalence of Hepatitis B and C Viruses against Tumor Necrosis Factor- α among Patients in Babylon Province

Background: liver disease could be a disease caused by infectious and non-infectious agents. serum hepatitis and C are major public health issues worldwide. serum hepatitis (HBV) and C virus (HCV) infections are legendary to occur within the general population thanks to their multiple mode of transmission primarily through blood.

Aim: This study aimed to estimate the prevalence of serum hepatitis and C virus among population in city province and analysis of the degree of the TNF-alpha in infected patients with hepatitis B and C

Methods: The study was conduced on people spoken the Central Public Health Laboratory to analyze the prevalence of HBV and HCV infections in city province. a complete of 6061 samples was enclosed during this study, they screened by VIDAS take a look at for detection of each viruses, then confirmed by real- time PCR. Concentration of TNF- α was measured in patients with serum hepatitis and C and management cluster (Control group consisted of the healthy subjects with no history of nephritic or liver diseases and negative results for HBV and HCV take a look at) by victimization ELISA test.

Results: a complete of 6061 individual were screened, amongst them, 18 (0.29%) were positive for HBV and sixteen (0.26%) were positive for HCV by each VIDS take a look at and period of time PCR.

Most of HBV infections seen among dialysis patients followed by haemophila, whereas most HCV infections seen among thalasemia and haemophila patients than others teams.

The prevalence of each viruses was higher among male than feminine, and in urban than rural rejoin. Most of HBV infections were high in individual with age go between 20-29 and 30-39 years, whereas most HCV infections in individual with age go between 20-29 years, though it’s statistically insignificant.

The mean bodily fluid level of TNF- α was considerably higher in individual with HBV and HCV infection (68.7±12.84 pg/mL) and (89.1±22.017) as compared with management cluster (43.1±5.87 pg/mL).

Conclusion: The prevalence of HBV and HCV was comparatively low. There are increasing level of TNF-α within the bodily fluid of patients with hepatitis B and C. [5]


[1] Morfini, M. and Rapisarda, C.A.P., 2019. Safety of recombinant coagulation factors in treating hemophilia. Expert opinion on drug safety, 18(2), pp.75-85. (Web Link)

[2] Tripodi, A., Chantarangkul, V., Novembrino, C. and Peyvandi, F., 2019. Advances in the Treatment of Hemophilia: Implications for Laboratory Testing. Clinical chemistry, 65(2), pp.254-262. (Web Link)

[3] Preijers, T., Schütte, L.M., Kruip, M.J., Cnossen, M.H., Leebeek, F.W., van Hest, R.M. and Mathôt, R.A., 2019. Strategies for individualized dosing of clotting factor concentrates and desmopressin in hemophilia A and B. Therapeutic drug monitoring, 41(2), pp.192-212. (Web Link)

[4] Restoration of FVIII expression by targeted gene insertion in the FVIII locus in hemophilia A patient-derived iPSCs

Jin Jea Sung, Chul-Yong Park, Joong Woo Leem, Myung Soo Cho & Dong-Wook Kim

Experimental & Molecular Medicinevolume 51, Article number: 45 (2019) (Web Link)

[5] Saleh, R. and Hadi, B. (2016) “Correlation between the Prevalence of Hepatitis B and C Viruses against Tumor Necrosis Factor- α among Patients in Babylon Province”, Microbiology Research Journal International, 12(3), pp. 1-10. doi: 10.9734/BMRJ/2016/22185. (Web Link)

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