Predicting inhibitor development using a random peptide phage-display library approach in the SIPPET Cohort.

Inhibitor development is the most severe complication of hemophilia A care, and is associated with increased morbidity and mortality. The aim of this study was to use a novel IgG epitope mapping method to explore the factor VIII (FVIII)-specific epitope profile in the SIPPET cohort population and to develop an epitope-mapping based inhibitor prediction model. The population consisted of 122 previously untreated patients with severe hemophilia A that were followed-up for 50 days of exposure to FVIII or 3 years, whichever occurred first. Sampling was performed before FVIII treatment and at the end of the follow-up. The outcome was inhibitor development. The FVIII epitope repertoire was assessed by means of a novel random peptide phage-display assay. A LASSO regression model and a random forest model were fitted on post-treatment sample data and validated in pre-treatment sample data. The predictive performance of these models was assessed by the C-statistic and a calibration plot. We identified 27,775 peptides putatively directed against FVIII, which were used as input for the statistical models. The C-statistic of the LASSO and random forest models were good at 0.78 (95%CI: 0.69-0.86) and 0.80 (95%CI: 0.72-0.89). Model calibration of both models was moderately good. Two statistical models, developed on data from a novel random peptide phage display assay, were used to predict inhibitor development before exposure to exogenous FVIII. These models can be used to set up diagnostic tests that predict the risk of inhibitor development before starting treatment with FVIII.

Congenital Skin Rashes in an IVF Baby Progressed to Multisystem Langerhans Cell Histiocytosis with Lung and Bone Involvement: A Case Report and Literature Review.

Langerhans cell histiocytosis is an uncommon proliferative disorder that may influence many organs; so, the clinical presentations vary. Here we describe an 85-day-old female who was born with In vitro fertilization after 10 years of infertility. She referred to us due to severe pulmonary insufficiency and congenital progressive maculopapular rash with desquamation. There were significant cystic changes in chest imaging studies. Further evaluation demonstrated lytic lesions in cranial, femoral, and humorous bones. The skin biopsy verified the diagnosis of LCH. A combination of Vinblastine, VP16, and Dexamethasone regimen was applied for the patient. In the course of the disease, she encountered multiple bilateral pneumothoraxes but didn't respond to tube thoracostomy and chemotherapy management. The patient died due to respiratory failure raised from complications of lung involvement as a multisystem LCH, 29 days later. Pediatricians should pay much more attention to the cutaneous lesions in the neonatal period especially if there is any risk factor for presenting LCH such as IVF. The lesions should be monitored closely owing to a high correlation between skin lesions and MS LCH.

Assessment of Standard Operating Procedures (SOPs) Preparing Hygienic Condition in the Blood Donation Centers during the Outbreak of COVID-19.

Background: The coronavirus disease 2019 (COVID-19) outbreak has led to an alteration in hygienic conditions. In this situation, improving standard operating procedures (SOPs) in blood donation centers is critical. The purpose of this study was the assessment of SOPs in the blood donation centers during the outbreak of COVID-19 by regular blood donors as external audits. Materials and Methods: Regular donors were selected as external inspectors in 31 provinces of Iran. The questionnaire containing 10 closed questions was provided to assess the hygienic SOPs of blood transfusion centers in the prevention of COVID-19 transmission. Comparison and evaluation of questionnaires were conducted by assigning an importance coefficient (IC) score to each question. Results: Assessment of SOPs in blood donation departments by regular donors in 31 provinces of Iran showed that 18 centers (58.1%) received IC scores >10(Strong performance), seven centers (22.6%) received the range of IC scores between7-10(acceptable performance), and six centers (19.4%) received IC scores <7(poor performance). The difference in IC scores between provinces was not statistically significant. Conclusion: This study confirms that the assessment of blood donation centers through regular blood donor inspection is a reliable method to identify the strengths and weaknesses of blood transfusion center services and ultimately leads to corrective intervention and improvement of hygienic SOPs to prevent COVID-19 transmission.

von Willebrand factor neutralizing and non-neutralizing alloantibodies in 213 subjects with type 3 von Willebrand disease enrolled in 3WINTERS-IPS.

BACKGROUND: Type 3 von Willebrand disease (VWD) is the most severe form of this disease owing to the almost complete deficiency of von Willebrand factor (VWF). Replacement therapy with plasma-derived products containing VWF or recombinant VWF rarely cause the development of alloantibodies against VWF that may be accompanied by anaphylactic reactions. OBJECTIVE: The objective of this study was to assess the prevalence of anti-VWF alloantibodies in subjects with type 3 VWD enrolled in the 3WINTERS-IPS. METHODS: An indirect in-house enzyme-linked immunosorbent assay has been used to test all the alloantibodies against VWF. Neutralizing antibodies (inhibitors) have been tested with a Bethesda-based method by using a VWF collagen binding (VWF:CB) assay. Samples positive for anti-VWF antibodies were further tested with Bethesda-based methods by using the semiautomated gain-of-function glycoprotein-Ib binding (VWF:GPIbM) and a VWF antigen (VWF:Ag) enzyme-linked immunosorbent assay. RESULTS: In total, 18 of the 213 (8.4%) subjects tested positive for anti-VWF antibodies and 13 of 213 (6%) had VWF:CB inhibitors. These 13 were among the 18 with anti-VWF antibodies. Of the 5 without VWF:CB inhibitors, 3 had non-neutralizing antibodies, 1 only inhibitor against VWF:GPIbM, and one could not be tested further. Ten of the 13 subjects with VWF:CB inhibitors also had VWF:GPIbM inhibitors, 6 of whom also had VWF:Ag inhibitors. Subjects with inhibitors were homozygous for VWF null alleles (11/14), homozygous for a missense variant (1/14), or partially characterized (2/14). CONCLUSIONS: Anti-VWF antibodies were found in 8.4% of subjects with type 3 VWD, whereas neutralizing VWF inhibitors were found in 6%, mainly in subjects homozygous for VWF null alleles. Because inhibitors may be directed toward different VWF epitopes, their detection is dependent on the assay used.

Allogenic Hematopoietic Stem Cell Transplant in Iranian Patients With Congenital Sideroblastic Anemia: A Single-Center Experience.

Congenital sideroblastic anemia is characterized by anemia and intramitochondrial iron accumulation in erythroid precursors that form ring sideroblasts. The most common recessive forms are caused by sequence variations in the ALAS2 and SLC25A38 genes. In patients with transfusion-dependent and pyridoxine- resistant severe congenital sideroblastic anemia, hematopoietic stem celltransplantis the only curative option. Herein, we described successful implementations of allogeneic hematopoietic stem cell transplant in 4 Iranian children with congenital sideroblastic anemia. The patients had presented with clinical manifestations of anemia early in life, and the diagnoses of congenital sideroblastic anemia were established through blood tests and bone marrow aspiration. Congenital sideroblastic anemia was further confirmed by the identification of pathogenic variants in SLC25A38 in 2 patients. All 4 patients received allogeneic hematopoietic stem cell transplant with myeloablative conditioning regimen that included busulfan, cyclophosphamide, andrabbit antithymocyte globulin. A combination of cyclosporine A and methotrexate or mycophenolate mofetil was used for graft-versus-host disease prophylaxis. Bone marrow and peripheral blood from sibling or related donors with fully matched human leukocyte antigen profiles were applied. The outcomes of hematopoietic stem celltransplantin patients with congenital sideroblastic anemia were favorable. Three patients achieved full donor chimerism (>95%, 98%, and 100%), and the other patient showed mixed chimerism (75%). All patients remained transfusion independent. Hemato- poietic stem celltransplantis a curative treatmentthat can provide long-term survival for patients with congenital sideroblastic anemia, particularly when used in a timely manner. There remain ongoing challenges in various aspects of hematopoietic stem celltransplantin patients with congenital sideroblastic anemia, which remain to be elucidated.

Patient and Physician Perspectives in the Management of Immune Thrombocytopenia in Iran: Responses from the ITP World Impact Survey (I-WISh).

Data describing physicians' and patients' perspectives towards immune thrombocytopenia (ITP) management and impact of disease in Iran are limited. This ITP World Impact Survey was conducted between October 2019 and October 2020. Of the 114 patients included in the survey, 17 were aged ≤18 years. Forty-seven physicians, including 22 pediatric hematologists, participated in the survey. Fatigue and anxiety around stable platelet counts were frequent patient-reported symptoms at diagnosis and at survey completion. According to physicians, "watch-and-wait" was the preferred treatment option for mean (standard deviation) proportion of 50.1 (24.1) and 48.6 (21.8) of their adult and pediatric patients, respectively, following first diagnosis. Per adult and pediatric hematologists, the most prescribed treatments for newly diagnosed patients based on available answers were steroids (100%, n = 20/20; 89%, n = 16/18), respectively. Forty percent of adult (n = 10/25) and 38% of pediatric hematologists (n = 8/21) reported that ITP reduced patients' quality of life. Energy levels (46%, n = 52/112) and ability to concentrate on everyday activities (42%, n = 47/113) were the most affected aspects of patients' lives. This I-WISh study in Iran underlined the negative impact of ITP on patients.

Estimate of anti-SARS-CoV-2 spike IgG antibodies prevalence among Iranian population based on blood donations: A serial cross-sectional study during the third wave of the pandemic.

OBJECTIVES: Iran is one of the countries that have been confronted with the SARS-CoV-2 epidemic since February 2020. This study aimed to determine the levels of specific IgG antibodies against SARS-CoV-2 among healthy blood donors to estimate the burden of the epidemic. MATERIAL AND METHODS: A serial cross-sectional study was conducted on blood donors who referred to 31 main blood donation centers in different provinces during the third weeks of September, October, and November 2020. A questionnaire was filled out to collect socio-demographic characteristics, history of contact with COVID-19 patients, and history of COVID-19. A blood sample was collected from each participant to assess the antibodies against SARS-CoV-2 using the ELISA method. The crude prevalence of anti-SARS-CoV-2 IgG was calculated. Then it was weighted based on the gender and age groups of the general population in each province and adjusted for test sensitivity and specificity. RESULTS: During three time points of the study, 3840, 3697, and 3152 participants enrolled. The seroprevalence of SARS-CoV-2 IgG antibodies was 19.59% (17.18-22.00), 22.67% (20.70-24.65), and 32.63% (29.93-35.33) over the three rounds of the study. We found an association between the seropositivity and the highest educational level; AOR 0.76 (0.63-0.93), history of close contact with COVID-19 patients; AOR 1.69 (1.35-2.11), and history of confirmed SARS-CoV-2 infection; AOR 8.86 (5.38-14.60). CONCLUSION: This study showed that about one-third of the population had been infected with COVID-19. Furthermore, a significant upward trend in seroprevalence was observed. The predisposing factors indicate the importance of public health.

The impact of COVID-19 on blood safety and availability in the Islamic Republic of Iran.

Background: The COVID-19 pandemic has affected blood inventory and donation worldwide. The Islamic Republic of Iran was among the first countries to report the COVID-19 pandemic and it faced a significant blood shortage during the first weeks of the pandemic. Aims: We aimed to evaluate the impact of COVID-19 pandemic on the number, type, and safety of blood donations, comparing the periods before and during the pandemic. Methods: This retrospective study evaluated data from all volunteers who attended the blood transfusion centres in the Islamic Republic of Iran from March to December 2020 (during the COVID-19 pandemic) and during the same period in 2019, i.e. pre-pandemic. Data on the number of blood collections, confirmed transfusion transmissible infection marker test results, and donor demographic information were collected from the Iranian Blood Transfusion Organization integrated donor database. Results: Total blood donations decreased by 8.38%. The number of first-time, lapsed, and female blood donors increased by 4.41%, 0.17%, and 0.90% respectively. Regular blood donation decreased by 4.58%. The distribution of the 3 main blood products, red cell concentrate, frozen fresh plasma and platelets, decreased by 7.86%. All changes were statistically significant. The prevalence rates of hepatitis C virus and hepatitis B surface antigen increased significantly during the pandemic. Conclusion: COVID-19 had a negative effect on blood safety and availability in the Islamic Republic of Iran. To improve blood supply and enhance regular blood donation, the Iranian Blood Transfusion Organization needs to reassure blood donors of the safety and hygiene measures being observed at blood collection sites.

Re-positive PCR of SARS-CoV-2 in health care persons during COVID-19 pandemic.

Reinfection rate with SARS-CoV-2 and degree of protection by the induced antibody after the first episode of the infection is not well known, so it makes a big dilemma for health care personnel (HCP) who work in the front line of combating SARS-CoV-2. In this study, we investigated the frequency of SARS-CoV-2 redetection among HCP after the initial onset of the infection in a children's hospital during one year. Out of 131 seropositive HCP, 13.7% of them were symptomatic and PCR positive during 74-360 days after first sampling. Analysis of demographic data of seropositive HCP showed a correlation between a higher number of family members, higher body mass index, and the existence of underlying diseases with SARS-CoV-2 redetection. In conclusion, reinfection is one of the important problems in the SARS-CoV-2 pandemic. Research on this topic can help us to find answers to questions for estimating the duration of human protection with produced immunity after the infection or vaccination.

Von Willebrand factor propeptide and pathophysiological mechanisms in European and Iranian patients with type 3 von Willebrand disease enrolled in the 3WINTERS-IPS study.

BACKGROUND: Type 3 von Willebrand disease (VWD) is a severe bleeding disorder caused by the virtually complete absence of von Willebrand factor (VWF). Pathophysiological mechanisms of VWD like defective synthesis, secretion, and clearance of VWF have previously been evaluated using ratios of VWF propeptide (VWFpp) over VWF antigen (VWF:Ag) and factor (F)VIII coagulant activity (FVIII:C) over VWF:Ag. OBJECTIVE: To investigate whether the VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios may also be applied to understand the pathophysiological mechanism underlying type 3 VWD and whether VWFpp is associated with bleeding severity. METHODS: European and Iranian type 3 patients were enrolled in the 3WINTERS-IPS study. Plasma samples and buffy coats were collected and a bleeding assessment tool was administered at enrolment. VWF:Ag, VWFpp, FVIII:C, and genetic analyses were performed centrally, to confirm patients' diagnoses. VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios were compared among different variant classes using the Mann-Whitney test. Median differences with 95% confidence intervals (CI) were estimated using the Hodges-Lehmann method. VWFpp association with bleeding symptoms was assessed using Spearman's rank correlation. RESULTS: Homozygosity/compound heterozygosity for missense variants showed higher VWFpp level and VWFpp/VWF:Ag ratio than homozygosity/compound heterozygosity for null variants ([VWFpp median difference, 1.4 IU/dl; 95% CI, 0.2-2.7; P = .016]; [VWFpp/VWF:Ag median difference, 1.4; 95% CI, 0-4.2; P = .054]). FVIII: C/VWF:Ag ratio was similarly increased in both. VWFpp level did not correlate with the bleeding symptoms (r = .024; P = .778). CONCLUSIONS: An increased VWFpp/VWF:Ag ratio is indicative of missense variants, whereas FVIII:C/VWF:Ag ratio does not discriminate missense from null alleles. The VWFpp level was not associated with the severity of bleeding phenotype.

Positive anti-SARS-CoV-2 rapid serological test results among asymptomatic blood donors.

OBJECTIVES: The world is fighting with a COVID-19 pandemic, some of the uncertainties have been revealed. To figure out an estimation of asymptomatic patients and seropositive SARS-COV-2 blood donors in Iran, a national survey was conducted to find the prevalence of asymptomatic blood donors with positive SARS-COV-2 IgM/IgG test results at the end of May 2020. MATERIAL AND METHODS: From all 31 provinces, 1339 blood donors were included. At first, data was collected with an interview containing demographic data, risk factors and possible signs and symptoms held for each donor by a trained medical expert. Then, SARS-COV-2 serologic rapid tests were conducted. Subsequently, the test results were observed and recorded; all of their photos were checked by one single expert. We corrected the prevalence rates for sensitivity and weighted them by the last year rate of blood donation of each province. RESULTS: The corrected prevalence rates of positive serological test results for sensitivity in provinces were between zero and 38.24%. The national prevalence was calculated 14.45% after weighting. Out of 161 positive donors, only 43 cases reported related signs or symptoms during the defined period of time, while 118 (73.29%) seropositive cases had not reported any related signs or symptoms. Some signs or symptoms were reported more frequent in the SARS-COV-2 serologic rapid test positives. The highest OR (10.19) was linked to ageusia. CONCLUSIONS: This study has shown the prevalence of seropositive results to be around 14% in target population in which around ¾ had not reported any signs or symptoms.

The demographic and serological characteristics of COVID-19 convalescent plasma donors: Identification of basic criteria for optimal donor selection.

BACKGROUND AND OBJECTIVES: Convalescent plasma has attracted significant attention as a therapeutic option against infectious agents for more than a century. In March 2020, the use of Convalescent COVID-19 plasma (CCP) as a new research drug for COVID-19 treatment was approved by the FDA. The development of SARS-CoV-2 IgG antibodies following infection or vaccination is likely to be essential to provide adequate immunity for the population to halt the COVID19 pandemic. This study aimed to identify the criteria that would be used to determine the most appropriate CCP donors with the highest effective antiviral antibody titers. MATERIALS AND METHODS: In this prospective cohort, univariate analyses and multivariate regression analyses were performed to evaluate the relationship between characteristics of 11949 CCP donors and COVID-19 disease severity prior to donation with antibody titers estimated using ELISA technique and rapid tests. RESULTS: The antibody titer was measured among 8206 (68.7 %) donors. Elderly male and nulliparous female CCP donors who resided in the areas with high load of virus had positive ELISA and rapid test results as well as high levels of SARS-CoV-2 IgG antibodies titer. Moreover, the long hospital stay and elderly donors were the variables associated with high levels of SARS-CoV-2 IgG antibodies. CONCLUSION: This study suggests that nulliparous female and male donors with positive rapid tests who resided in areas with a higher prevalence of SARS-CoV-2, with more than 40 years of age and long hospitalization time can be the preferred donors for CCP donation.

Clinical and genetic characteristics of hemoglobin H disease in Iran.

Hemoglobin H (Hb H) disease is a subtype of α-thalassemia caused by deletional and/or non-deletional mutations in three alpha-globin genes in which the various genotypes determine the disease severity. This study was aimed to investigate the frequency of alpha gene mutations and genotypes and their correlation with hematological and clinical characteristics in Iran. Among 202 patients diagnosed with Hb H disease through a national study in Iran according to standard methods, we had access to the hematologic and clinical findings and genetic data of 101 patients in whom genetic study was performed. Genomic DNA from peripheral blood was extracted and analyzed for identification of α-globin gene mutations using Multiplex Gap Polymerase Chain Reaction, Reverse Hybridization Assay, and finally Direct DNA Sequencing method. Twenty-one different mutations and thirty genotypes were detected in 101 patients with Hb H disease. In total, 39 patients (38.6%) were deletional and 62 patients (61.4%) were non-deletional type of the disease. The --MED mutation was highly prevalent in almost half of the patients (56.4%). Among various genotypes, -MED/-a3.7 (29.7%) and -α20.5/-α5NT (6.9%) were the most prevalent genotypes found in the studied group. Patients with non-deletional type presented with more severe hematological and clinical findings. Hb H percentage and serum ferritin levels were significantly higher in non-deletional patients in comparison to the deletional group (p < 0.05). 12 (11.9%) and 40 (39.6%) out of 101 patients were on regular and occasional transfusions, respectively. 83% of those with regular transfusion belonged to the non-deletional group. Among transfusion-dependent patients, -MED/αCSα and α20.5/-α5NT were the most common genotypes. In this study, two patients with -α20.5/αCSα and -MED/α-5NT genotypes experienced thrombotic events. This study indicated that although non-deletional genotypes of Hb H disease were responsible for more clinical severity of the disease, due to the presence of severe phenotypes even in deletional types, no definite correlation was found between genotype and phenotype.

Early high-titer convalescent plasma therapy in patients with moderate and severe COVID-19.

BACKGROUND AND OBJECTIVES: The use of COVID-19 convalescent plasma (CCP) has been approved by the FDA. We assessed the outcome of patients with moderate and severe COVID-19 following convalescent plasma therapy and the association with variables such as antibody titer in CCP units and transfusion time. MATERIALS AND METHODS: In this prospective cohort study, 3097 patients with moderate and severe COVID-19 (according to WHO Progression Scale) had heterogeneous demographic and clinical characteristics received plasma with an unknown titer at the transfusion time. Firstly, information about age, sex, blood group, the time interval from hospitalization to CCP transfusion, underlying disease, and antibody titer with the outcome were investigated. Then, multivariate logistic regression and area under the curve (AUC) were performed for the association between disease severity and intubation variables with transfusion time and outcome. RESULTS: Patients with younger age receiving CCP in the first five days of hospitalization had lower mortality (P < 0.0001). Moreover, patients without the underlying disease had lower mortality (P < 0.001). The mortality rate also decreased in severe patients who were intubated receiving CCP for less than five days (P < 0.001). In patients with moderate severity (score less than 5) who received IgG antibody levels above 1:320 in less than five days had lower mortality (P < 0.0001). CONCLUSION: Our findings suggested that COVID-19 patients with the moderate type of disease receiving CCP units with high antibody titers in the early stages of the disease experienced greater effectiveness of CCP therapy.

Source Plasma Donation: The Experience of the Iranian Blood Transfusion Organization.

Background: A declining need for red blood cells coupled with strengthening demand for plasma-derived medicines has led to a strong focus on moving whole blood donors to plasmapheresis. The purpose of this study was to evaluate the four-year policies of the Iranian Blood Transfusion Organization (IBTO) in terms of plasmapheresis recruitment of first-time donors and its effect on plasmapheresis outcome.   Materials and Methods: Plasmapheresis data related to 16 centers from 2016 to 2019 was obtained from IBTO software. This information includes; (1) blood donation number, (2) plasmapheresis donation number, (3) number of plasmapheresis donors, (4) plasmapheresis donor demographic data, (5) plasmapheresis donor status, (6) frequency of plasma donation for each donor, (7) volume of plasma and (8) the prevalence of transfusion-transmissible infections (TTIs) in plasmapheresis donors. Results: The result of this study demonstrated that plasmapheresis collection centers have recruited 85,515 (91%) first-time and 8,595(9%) regular and repeated donors from 2016 to 2019 years. Plasmapheresis to blood donation index was increased from 0.2% in 2016 to 4.9% in 2019. The mean donation number was 2 times per year. The trend of the yearly Whole Blood Donation (WBD) Index decreased from 26.69 to 24.11/1000 for the general population. The total volume of collected source plasma was 49,203 liters during this period. However, 46,000 liters of recovered plasma were decreased due to less WBD. Furthermore, the results indicated that the prevalence of HCV was significantly higher in first-time donors compared to repeated and regular donors (P = 0.000). Conclusion: It is concluded that during four years, the net volume of plasma did not increase and plasmapheresis led to reducing WBD in our country. Moreover, first-time plasmapheresis donors can be associated with challenges such as increasing screening costs and compromising the safety of plasma resources. Therefore IBTO decided to stop the project and focus on its main role to prepare safe and sufficient blood components through WB collection and also single donor platelet and concurrent plasma by plateletpheresis.

Effects and treatment applications of polymeric nanoparticles on improving platelets' storage time: a review of the literature from 2010 to 2020.

Maintaining the quality of platelet products and increasing their storage time are priorities for treatment applications. The formation of platelet storage lesions that limit the storage period and preservation temperature, which can prepare a decent environment for bacterial growth, are the most important challenges that researchers are dealing with in platelet preservation. Nanotechnology is an emerging field of science that has introduced novel solutions to resolve these problems. Here, we reviewed the reported effects of polymeric nanoparticles-including chitosan, dendrimers, polyethylene glycol (PEG), and liposome-on platelets in articles from 2010 to 2020. As a result, we concluded that the presence of dendrimer nanoparticles with a smaller size, negative charge, low molecular weight, and low concentration along with PEGylation can increase the stability and survival of platelets during storage. In addition, PEGylation of platelets can also be a promising approach to improve the quality of platelet bags during storage.

An efficient and effective ambulatory service model for severe hemophilia-A patients; an introduction to a novel home care model.

INTRODUCTION: Hemophilia A (HA) is an inherited deficiency in blood coagulation factors. Starting the treatment based merely on patients' hemorrhage feelings results in more than 63.6% mistakes in joint bleeding diagnosis. This study aimed to design a useful ambulatory service model for Patients With Severe Hemophilia A (PWSHA). METHODS: This study was done in 3 steps. In step-I, the current service model to PWSHA in Tehran was evaluated. In step II, an ambulatory service model was proposed according to the existed gaps and their requirement. In step III, the model's acceptability was assessed from the perspective of clinicians, PWSHA, and healthcare policymakers. RESULTS: There were 1660 PWSHA in Tehran in 2018. The average use of Factor VIII (FVIII) was 44814 IU in Iran. The yearly budget of FVIII in Tehran was 10,627,320 US$ in 2018. We proposed a home care model with five care centers in Tehran. Ten caregivers and three hematologists for each care center were suggested to cover all services per day. The extracted data indicated that the total service demand would be 39 for each center per day. The results of the questionnaires in all groups were supportive and cooperative. CONCLUSION: The current service delivery model to PWSHA has significant economic and clinical defects. Implementing our model can significantly improve the efficiency of bleeding management in PWSHA. Most of the PWSHA, healthcare managers, and clinicians were satisfied with the proposed model.

A comparison between on-demand usage of rFVIIa vs prophylaxis use of emicizumab in high titer inhibitory hemophilia A patients in Iran: A cost-utility analysis.

BACKGROUND: Hemophilia A (HA) is an inherited X-linked bleeding disease with costly treatment, especially for high titer inhibitory patients. Emicizumab, a new humanized bispecific antibody, has been approved for use to prevent or reduce the frequency of bleeding episodes in HA patients with inhibitors. This study evaluated the cost-utility of emicizumab prophylaxis (EP) in comparison with recombinant factor VII activated on-demand treatment in HA patients with inhibitors. METHODS: A life-time Markov model with payer and societal perspectives was developed in different age groups with different annual bleeding rates (ABR). Efficacy of treatments were extracted from HAVEN trials. Utilities were retrieved from published evidence. Costs were calculated based on Iran food and drug administration official website, national tariff book for medical services and hospital data. One-way deterministic sensitivity analysis was performed. RESULTS: EP was dominant choice in comparison with on-demand administration of recombinant factor VII activated in all age groups with ABR 20 and 25, and it remained dominant in patients with age 2 and age 12 at start point with ABR 16 and 17. The reported incremental cost-effectiveness ratio for the group with ABR 18 at the age 20, was 12,936 United States Dollars which is lower than the acceptable threshold of cost-effectiveness in Iran (1-3 gross domestic product per capita) and EP can be considered as cost-effective choice in this scenario. CONCLUSION: EP was found to be a dominant and cost-effective choice for Iranian HA patients with factor VIII inhibitors with ABR 18 and above with considerable cost saving.