POSTER ABSTRACTS

Abstract

H. Brouk1,*; A. Amireche1; A. Kessira1 1Hemobiology and blood transfusion center, faculty of medicine, University Badji Mokhtar of Annaba, Annaba, Algeria Introduction: Combined deficiency of coagulation factors V and VIII (F5F8D) is a constitutional bleeding disorder, described since 1954 by Oeri. It is rare, autosomal recessive, with an estimated prevalence of 1/100,000 to 1/1,000,000, representing the most frequent form of constitutional abnormality, associating more than one coagulation factor, and not related to the accidental coincidence of several genetically distinct inherited deficiencies, but related to a single genetic abnormality. Methods: A 56-year-old woman consulted an outpatient clinic with a complaint of continuous bleeding after tooth extraction. The patient's medical history revealed that she had been experiencing long-term bleeding episodes following a minor trauma, as well as easy bruising, ecchymoses, and menorrhagia following menstruation. Melena, hematochezia, hemoptysis, and hemarthrosis were not present in her case. Her parents were unrelated, and her vital signs and physical examination results were normal. Results: The coagulation profile revealed prolonged activated partial thromboplastin time and prothrombin time (17–20 sec and 45–66 sec, respectively). aPTT and PT values were normal after mixing the patient's plasma with a healthy plasma in a 1:1 ratio. Fibrinogen, factor VII, factor IX, factor X, and factor XI and von Willebrand factor levels were all normal. Factor V and VIII levels were measured twice, and both measured levels were low (respectively 10% and 15%). According to these findings, the patient was diagnosed as having a combined factor V and VIII deficiency. Discussion/Conclusion: Regular prophylaxisis not required during bleeding episodes in patients with combined factor V and VIII insufficiency, and the patient is often treated only as necessary. The treatment of the bleeding is replacement of factor V and VIII. Disclosure of Interest: None declared S. Christidi1,*; A. Kourampa2; G. Thivaios1; D. Katrisiotis2; P. Christoforou2; A. Chanos2; T. Tryfou3; M.-C. Kyrtsoni3; O. Katsarou2 1Trauma & Orthopaedics; 2Blood unit and National Reference Center for Congenital Bleeding Disorders, “Laiko” General Hospital; 3First Department of Propaedeutic Internal Medicine, “Laiko” General Hospital, National and Kapodistrian University of Athens, Athens, Greece Introduction: In PWH, intrarticular bleedings cause severe hemophilic arthropathy(ΗΑ). Replacement of the missing clotting factor is effective to prevent bleeding events and the ΗΑ progression. There are studies suggesting that FVIII can regulate the OPG/RANKL system, which seems to play a role in ΗΑ. The purpose of this study is to measure the OPG levels in PWH A/B and their correlation with the FVIII/FIX levels. Methods: From 11/2021 to 7/2022. 124 samples were collected for OPG and FVIII/FIX measurement in 65 PWH, mean age 38 years (IQR18–83): 55 (84.6%) with Hemophilia A and 10 with Hemophilia B(15.4%).Severe Hemophilia had 87.7%, moderate 10.8%, and mild 1.5%, of patients 8 out of them (12.3%) had anti-FVIII/FIX inhibitor and 8 (12.3%) were HIV(+). 36 samples from healthy supplies, mean age 43 years (IQR22–73) were used as controls. OPG and FVIII/FIX activity were measured by ELISA method and one stage clotting assay (Stago) respectively. Comparisons of OPG levels were made between PWH and controls, and were correlated with hemophilia type, disease severity, FVIII/FIX levels, presence of inhibitor & HIV infection. Results: The data reveals a statistically significant difference mean in OPG levels between controls and PWH (p<0.001): 1712.13 pg/ml(IQR 248.54–8828.58)vs.1015.92 pg /ml(IQR66.21–8302.30) respectively. OPG levels were not statistically associated to haemophilia type, the presence of FVIII/FIX inhibitor and HIV infection. Statistically significant differences were noted in OPG levels in relation to hemophilia severity with mean values 935.49 pg/ml(113.02-8302.30) for severe vs 1771.19 pg/ml (66.21-5728,48) for moderate and mild hemophilia (p<0.001). A statistically significant positive correlation of OPG levels with FVIII activity was found (p<0.05): Specifically, for FVIII:C<1% mean OPG value were: 938.78pg/ml(IQR 538.57–1202.15),for FVIII:C1-5% 982.93pg/ml(IQR163.04–7980.60), for FVIII:C 5-15% 1056.36pg/ml (IQR66.20–5570.78) and for FVIII:C>15% 1163.81pg/ml (IQR113.02–8302.30). Discussion/Conclusion: Based in our preliminary results, it seems that PWH have lower OPG levels than the general population. Higher levels of FVIII activity increase OPG expression which confirms the hypothesis that OPG plays a role in the progression of ΗΑ. Our study cintinues by searching for a correlation of OPG levels with the severity of arthropathy, the degree of osteoporosis and RANKL levels in the serum of PWH. Disclosure of Interest: None declared N. Vilalta1,*; N. Butta2; F. J. Rodríguez-Martorell3; A. Bernardo4; S. Mojal1; V. Cortina5 1Hemostasis Unit, Hospital de la Santa Creu i Sant Pau, Barcelona; 2Hematology, La Paz University Hospital-IdiPaz, Madrid; 3Unidad de Gestión Clínica Intercentros de Hematología, Hospital Universitario Virgen Macarena y Hospital Universitario Virgen del Rocío, Sevilla; 4 Laboratorio de Diagnóstico Clínico Hematología, Hospital Universitario Central de Asturias, Oviedo; 5Hemostasis Laboratory, Vall d'Hebron University Hospital, Barcelona, Spain Introduction: Emicizumab has emerged as a novel non-factor therapy to treat hemophilia A patients (HA). It does not exist a standardized monitoring protocol. Our aim was to test the utility of thromboplastin time (aPTT), and global tests: Rotational Thromboelastography (ROTEM -NATEM) and Thrombin generation time (TGT) to evaluate emicizumab concentration and hemostatic effect Methods: Ninety one samples from emicizumab patients obtained from 4 Spanish Hemophilia Centers have been analyzed to obtain the following parameters: aPTT, emicizumab concentration, ROTEM-NATEM parameters [Clotting time (CT), clotting formation time (CFT), Maximum clot Firmness (MCF)and alfa-angle] and TGT parameters [Lag time (LT), Thrombin peak (ThP), Time to Peak (TTP), endogenous thrombin potential (ETP) and velocity Index (VI)]. Correlation has been measured using Spearman correlation coefficient. Results: We found a positive correlation between aPTT and CT (R=0.51, p<0.001), CFT (R=0.49, p<0.001) and velocity index (R=0.53, p<0.005 ) and a negative correlation with alfa-angle (R=-0.47, p<0.001). A negative correlation was also found between Emicizumab concentration and MCF (R=-0.563, p<0.001). Discussion/Conclusion: aPTT and global tests are a good alternative to monitor HA patients under emicizumab treatment. According our results, CT, CFT and alfa angle are the ROTEM -NATEM parameters which better correlate with aPTT and emicizumab concentration. We need to report a limitation, TGT was not tested in all samples and it could be a reason because we don't find correlation with all parameters. More studies are needed. Disclosure of Interest: None declared A. Dos Santos Ortas1,*; J. M. Martín de Bustamante González-Iglesias1; M. I. Pérez Vaquero1; M. T. Álvarez-Román1,2,3; M. I. Rivas Pollmar1,2; E. G Arias-Salgado1,2; P. Acuña1,2; E. Monzón Manzano1,2; E. García Pérez1; M. D. M. Gutiérrez Alvariño1; M. Martín Salcés1,2; N. Butta1,2; V. Jiménez-Yuste1,2,3 1Hematology department, Hospital Universitario La Paz; 2IdiPAZ; 3Medical School, Universidad autónoma de Madrid, Madrid, Spain Introduction: Administration of FVIII concentrates to manage breakthrough bleeding or invasive procedures in patients with severe Hemophilia A (sHA) without inhibitor under Emicizumab (EMI) prophylaxis remains necessary nowadays. Current guidelines recommend using chromogenic FVIII (FVIII:C) levels to monitor the hemostatic response to the combination of both drugs. Here we describe the hemostatic management and monitoring with global coagulation assays (GCA) of two patients with sHA on EMI treatment undergoing orthopedic surgery. Methods: Perioperative FVIII:C levels were performed for both patients during surgery and postoperative period. Samples for GCA were collected in tubes with CTI to prevent contact pathway activation. Clotting time (CT) was evaluated by ROTEM®, using whole blood activated by tissue factor solution plus recalcification, and Thrombin peak (TP) was assessed by TGT in plasma, using tissue factor and phospholipids. Both techniques were performed in samples collected before and after FVIII administration. Samples obtained before FVIII dosing were also spiked in vitro with therapeutic amounts of FVIII products. Results: Patient 1 is a 55-year-old male who underwent an ankle arthrodesis with osteosynthesis due to hemophilic arthropathy. He received 50 U/kg of plasma-derived (pd) FVIII/FVW every day until day +7 after surgery. Patient 2 is a 52-year-old male with a cubital tunnel syndrome that required surgery. In this case, we used a single dose of 50 U/Kg of extended half-life rFVIII concentrate (rFVIII EHL) before procedure. In both cases, the postoperative course was uneventful. GCA showed that treatment with EMI was insufficient for complete normalization of hemostatic parameters. We observed an improvement in CT and TP values after every administration of both FVIII products. We noted that this improvement was similar to that obtained with in vitro spiking of equivalent doses of FVIII, and a correlation between FVIII:C levels and CT or TP values was also observed. Discussion/Conclusion: The hemostatic profile obtained with both GCA could be an important complement to FVIII:C levels for the follow-up of complex cases of bleeding or surgery in patients with severe HA without inhibitor undergoing EMI prophylaxis. Funding: ISCIII-FEDER PI19/00631; Catedra UAM-Roche. Disclosure of Interest: None declared H. Elmahmoudi1,*; R. Ghorbel1; A. Zaier1; C. Jbali1; S. Besbes1; O. Ghali1; K. Zahra1; E. gouider1 1Aziza Othmana Hospital, tunis, Tunisia Introduction: Genetic factors have been shown to be a risk factor for the development of inhibitors. Several types of mutations including small and large deletions, insertions or point mutations associated with deleterious changes such as missense mutation, nonsense mutations and splicing alterations were reported in PWH. The most common mutations in 45% of severe hemophilia A cases are the inversion of introns 22 and 1. Our goal is to identify the genetic profile in severe hemophilia A with inhibitor in our center. Methods: PWHA carrying inhibitors were included in our study. The search for the inversion of intron 22 and intron 1 is done by IS-PCR. The search for point mutations is done with PCR/sequencing. Results: Sixteen PWHA and inhibitors were identified. The most frequent mutation was the intron 22 inversion (30%, n = 5), followed by two large deletions of exon 14 and exons 1-13 respectively (12.5%, n=2). A missense mutation at exon 1 (6.25%, n=1) was also identified. For the remaining 8 patients, the inversion of intron 22 is absent and the search for the molecular defect is in progress. Discussion/Conclusion: The most common mutations reported in 45% of severe hemophilia A cases are the inversion of introns 22 and 1. Mutations inducing an absent or truncated FVIII protein are associated with a 20 to 80% risk of developing inhibitors. Reversal of introns 1 and 22, large deletions, nonsense mutations and splice site mutations are considered high risk mutations for developing an inhibitor. Missense mutations are considered low risk mutations.In our study, the inversion of intron 22 is present with a frequency of 30% (5/16). This frequency seems to be lower compared to data in the literature, where it varies between 40% and 50%. The p-value of PWHA with inhibitors carrying inversion 22 and PWHA without inhibitors carrying the same mutation is not significant (p between 0.9 and 0.1), as reported in some cohort. An increase in the number of patients is advised to better define the association between the presence of the inversion of intron 22 and the appearance of inhibitors in our Tunisian population. Knowing the type of mutation and its association as a risk factor for generating an inhibitor would make it possible to propose individualized therapeutic strategies. Disclosure of Interest: None declared F. J. López-Jaime1; A. Montaño1,2; A. Marco3; P. Marco3,4; I. Fernadez-Bello1,*; Á. Palomo-Bravo1 1Haematology and Haemotherapy, Regional University Hospital of Málaga, Málaga; 2University of Salamanca, Salamanca; 3Haematology and Haemotherapy, General University Hospital of Alicante; 4Department of Clinical Medicine, Universidad Miguel Hernández, Alicante, Spain Introduction: Emicizumab is a bispecific antibody mimicking the activity of coagulation factor VIII (FVIII). Plasma level of emicizumab might be variable, therefore, it has been proposed to measure its plasma concentration in order to adjust the dose if it were necessary. Thrombin generation test (TGT) and thromboelastometry (ROTEM) might be useful to individualize therapy with emicizumab, thus, evaluation of correlation between emicizumab plasma levels and global assays could useful in the individualization of emicizumab dosing. We aimed to determine the plasma levels of emicizumab in a group of patients on prophylaxis with this agent and to evaluate the correlation between their levels and the TGT and ROTEM tests. Methods: TGT was determined in platelet poor plasma using Genesia®. ROTEM was evaluated by naTEM test (only recalcification). Levels of emicizumab was evaluated by an aPTT modified test (Stago). Statistical analysis was performed using SPSS software taking into account the distribution of data. Results: Six patients were included. Median age (25th-75th percentiles) and plasma levels of emicizumab was 11.4 (6.5-15.5) years old and 47.5 (40.8-58.7) μg/mL respectively. No correlation between TGT, ROTEM and emicizumab plasma levels were found. No modification of emicizumab doses were needed. Discussion/Conclusion: Emicizumab is a bispecific antibody which switch-on mechanism depends on presence of activated factor IX (FIXa). Both TGT and ROTEM are affected by contact pathway activation which may produce important amount of FIXa. This could affect the TGT and ROTEM assay, thus, the use of contact activation pathway inhibitors such as corn trypsin inhibitor (CTI) could be needed. A comparative wider study using samples with and without CTI should be performed in order to evaluate this hypothesis. Disclosure of Interest: None declared J. Obregón1; J. M. Calvo Villas1; A. Marco Rico2; S. Herrero Martin3; L. E. Ureña4; F. J. Lopez Jaime5; B. Díaz Jordán6; C. García Díaz7; S. Jurado Herrera8; N. F. Perez Gonzalez9; F. Garcia Candel10; P. Marco Vera2; I. Fernández Bello5,*; A. Montaño Brioso11; on behalf of Mediterranean Hemophilia Group 1Hospital Universitario Miguel Servet, Zaragoza; 2Hospital General Universitario de Alicante Doctor Balmis, Alicante; 3Hospital Universitario de Guadalajara, Guadalajara; 4Hospital Universitario Virgen de las Nieves, Granada; 5Hospital Universitario Regional de Malaga, Malaga; 6Hospital General de Valdepeñas, Ciudad Real; 7Hospital Universitario de Burgos, Burgos; 8Hospital Universitario Torrcardenas; 9Hospital Universitario Torrecardenas, Almeria; 10Hospital Clínico Universitario Virgen de la Arrixaca, Murcia; 11Hospital Universitario Regional de Malaga. Universidad de Salamanca, Malaga, Spain Introduction: Thirty percent of patients with mild haemophilia A showed discrepancy in FVIII levels between one-stage clotting assay (FVIII:C1) and two-stage chromogenic assay (FVIII:CR). This phenomenon has been associated with genetic alterations in the FVIII gene. Methods: In an observational, ambispective and multicenter study, 52 non-severe haemophilia A (nSHA) patients from 9 Spanish hospitals were studied. FVIII:C1 and FVIII:CR were determined. TGT was evaluated in platelet poor plasma by Genesia®. Mutation analysis was performed by direct sequencing on individuals with discrepancy between FVIII:C1 and FVIII:CR assays. We defined discrepancy as FVIII:C1/FVIII:CR ≥ 2 (standard discrepancy) or FVIII:C1/FVIII:CR ≤ 0.5 (reverse discrepancy). Results: Median (IQR) of FVIII:CR= 20.3% (15.4-25.2) was higher than FVIII:C1= 17.5% (14.2-20.8) (p<0.001), with a significant correlation between FVIII:C1 and FVIII:CR (r= 0.68, p<0.001). 7 cases (63.6%) showed a reverse discrepancy and 4 (36.4%) showed a standard discrepancy. A significant correlation was observed between FVIII:CR and all TGT parameters (lag time: r= 0.57 [p 0.001], thrombin generation peak: r= 0.30 [p= 0.03] and endogenous thrombin potential (ETP): r= 0.27 [p=0.05]. Taking into account that TGT uses the own patient levels of FIX, FX and thrombin generation capacity, it might be possible to think that activation of FVIII in TGT is produced in a more physiologic condition compared with those used in the clotting or chromogenic assays. Nonetheless, the absence of correlation between FVIII:C1 and TGT might indicate that FVIII:CR might have a closer correspondence with the bleeding phenotype of the patients. Eight out 47 patients (17%) changed the diagnosis severity taking in consideration the FVIII:CR. Nine missense mutations were found in the 11 cases with discrepant FVIII results, of which 7 were within the A2 and A3 domains. It was previously reported that the p.Ser1810Pro variant, presented in 4 of our patients, were associated with FVIII assay discrepancies. Discussion/Conclusion: Discrepancy was found in 23.4% of nSHA patients. A significant correlation between FVIII:CR and TGT parameters might indicate that FVIII:CR might have more correspondence with the bleeding phenotype of the patients though this hypothesis should be evaluated in a wider study. Disclosure of Interest: None declared S. Guy1,*; E. Oliver-Newman1; A. Bowyer1; S. Kitchen1 1Sheffield Haemophilia and Thrombosis Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom Introduction: Rurioctocog alfa pegol (Adynovi, Takeda) is a PEGylated recombinant extended half-life FVIII:C replacement product, it has a half-life of 1.4 to 1.5-fold longer than Advate. According to the summary of product characteristics, the potency is assigned by chromogenic assay (CSA); it also references a field study which previously suggested that both OSA (one stage assay) and CSA methods are suitable for monitoring treatment. In this study we will look at the suitability of different APTT reagents and CSA methods using FVIII deficient plasma spiked with Adynovi to a range of concentrations. Methods: Adynovi was spiked into congenital FVIII deficient plasma (HRF Inc) producing final concentrations of 2.5,5,10,25,50,75,100 and 125 IU/dL based on labelled potency. OSA and CSA were performed on the spiked samples on three separate days. The OSA used Actin, Actin FS, Actin FSL, Pathromtin SL (all Siemens) APTT reagents performed on CS5100 (Sysmex); SynthASil, SynthAFax, and APTT-SP APTT reagents were performed on ACL TOP (all Werfen). CSA methods performed on the CS5100 were Biophen FVIII:C (Hyphen Biomed) and Siemens FVIII Chromogenic Assay (Siemens), whilst Coamatic Factor VIII (Chromogenix) and CRYOcheck Factor VIII (Precision BioLogic) were performed on ACL TOP. Results: The mean for each reagent was calculated for all spiked concentrations. Mean OSA ranged from 40.7 IU/dL (SynthASil) to 49.2 IU/dL (Pathromtin SL). Mean CSA ranged from 53.5 IU/dL (Siemens) to 69.1 IU/dL (Coamatic). For samples with >25 IU/dL Adynovi, all the OSA and Siemens and CRYOcheck CSA recovered levels within 25% of expected FVIII:C level based on potency, however the Biophen FVIII:C recovered 25% only at 125 IU/d L. At lower levels Actin demonstrated most overestimation at 2.5, 5.0 and 10 IU/dL with results of 5, 8.2 and 14 IU/dL respectively; Pathromtin SL and APTT-SP produced little variation at the lower concentrations. The CSA methods produced similar results for 2.5 and 5.0 IU/dL; however, at 10 IU/dL Adynovi: Siemens and CRYOCheck 8.9 and 8.8 IU/dL respectively but this was within expected variability. Discussion/Conclusion: Some variation was seen between the methods. Overall, APTT-SP, Pathromtin SL, Siemens and CRYOCheck gave consistent results for all the range of spiked samples, more data is required in patient samples to confirm these results. Disclosure of Interest: None declared Y. Jourdy1,*; A. Dericquebourg1; M. Frétigny1; C. Vinciguerra1 1Hospices Civils de Lyon, LYON, France Introduction: The disease-causative variant remains unidentified in about 2-4% of non-severe hemophilia A (HA) patients using conventional genetic investigations, and F8 deep intronic variations could be responsible in these cases. In this study, we performed Whole F8 gene sequencing in genetically unsolved non-severe HA patients in order to identify the causal variation. Methods: We performed whole F8 sequencing using Next Generation Sequencing (NGS) in 49 genetically unsolved non-severe HA patients. The putative splicing impact of the candidate deep intronic variations was studied using both in silico (SpliceAI and MaxEntScan) and splicing functional analysis (either F8 mRNA analysis or minigene analysis). Results: The mean (range) number of variations per patient revealed by NGS was 30 (10-63). Among them, only those with a Minor allele frequency < 0.01% were further analyzed. After filtering, 33 deep intronic variants remained (31 single nucleotide variations (SNPs), one 173-bp deletion and an 869-bp tandem triplication) from 43 propositi. No F8 candidate variant was found in 6 propositi.Four variations have been previously described in the literature as HA-causing: c.1537+325A>G (n=2), c.2113+601G>A (n=2), c.2113+1152delA (n=2), c.5587-93C>T (n=3) and no further analysis were performed for them. The most frequent variants found were c.2114-6529C>G and the association of 2113+1154G>C and c.5374-304C>T identified in 9 and 5 unrelated individuals, respectively. In silico analysis predicted splicing impact for 2/27 SNPs only (c.788-312A>G and c.6901-2992A>G). RNA sample was available for 5 cases. F8 mRNA analyzing showed a deleterious splicing impact for 3 deep intronic variations (c.6900+4104A>C, c.2114-6529C>G and c.2113+1154G>C). The minigene assay showed a splicing impact for 8/18 of the studied variants (c.671-94G>A, c.788-312A>G, c.6901-2992A>G, c.5999-820A>T, c.5999-786C>A, c.5999-669G>T, c.5999-669G>C and c.5999-669G>A). Finally, the HA causing variant was identify in 33/49 (67%) cases. Discussion/Conclusion: In this study, we described 11 new deep intronic variations as HA-causing. About the two thirds of the non-severe HA patients included in this study were elucidated. This study highlights the usefulness of the association of whole F8 gene sequencing and functional assays for the progressive reduction of unexplained HA. Disclosure of Interest: None declared M. Kjalke1,*; C. Augustsson2; K. Strandberg2 1Department of Rare Blood Disorders, Novo Nordisk A/S, Måløv, Denmark; 2Department of Clinical Chemistry and Pharmacology, Coagulation Laboratory Malmö, Division of Laboratory Medicine, Region Skåne, Sweden Introduction: Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody in phase 3 clinical development as a once-daily subcutaneous prophylactic treatment for haemophilia A or B (HA/B) with or without inhibitors. To inform potential future clinical analysis of plasma samples from patients on concizumab prophylaxis, this study assessed the impact of concizumab on coagulation assays validated for use in clinical monitoring, i.e., prothrombin time (PT) using Quick and Owren assays, activated partial thromboplastin time (aPTT), factor (F) VIII and IX one-stage clot assays (OSA) and chromogenic substrate assays (CSA). Methods: Concizumab at concentrations of 0, 250, 1000, 4000 and 16000 ng/mL (covering clinically relevant exposures) were added to normal human plasma (NHP); or pooled plasma samples from patients with HA or HB separately or with recombinant FVIII or FIX (0.1 and 1 IU/mL). Plasma samples ± concizumab were analysed on an Atellica COAG 360 analyser (Siemens) using commercially available diagnostic kits and calibrators. Differences between measurements were considered relevant for clinical practice if the measurement with concizumab was outside ±25% of the corresponding measurement without concizumab. Results: Concizumab had no influence on PT clot time. The aPTT clot time of NHP was shortened up to 0.4 s (250–16000 ng/mL concizumab), however, measurements remained within the NHP reference range (21–30 s). For haemophilia plasma, aPTT clot times were shortened by 2.6–3.4 s (HA; 250–16000 ng/mL concizumab), or 3.3–5.2 s (HB; 250–16000 ng/mL concizumab) but were within 25% of measurements without concizumab. Concizumab (4000 and 16000 ng/mL) resulted in <20% increased recovery of FVIII and FIX activity when measured in the respective OSAs. No influence of concizumab on FIX activity was detected in CSAs, however, a small decrease in recovery of FVIII activity (<5%) was observed. Discussion/Conclusion: Concizumab had no, or only a minor, effect on standard PT and aPTT assays, and FVIII or FIX activity measurements. Therefore, these assays can be used in clinical practice for monitoring patients on concizumab prophylaxis. Disclosure of Interest: M. Kjalke Shareholder of: Novo Nordisk, Employee of: Novo Nordisk, C. Augustsson Grant/Research support from: Access to insight (Novo Nordisk Health Care A.G.), K. Strandberg Consultant for: Sobi, Novo Nordisk, BioMarin, Speaker Bureau of: Octapharma, Sobi, Shire, Novo Nordisk R. Korir1,*; C. Njuguna1; C. Kilach1; A. Greist2; F. Njuguna3 1Hematology and Oncology, AMPATH/Moi Teaching and Referral Hospital, Eldoret, Kenya; 2Hematology, Indiana Hemophilia and Thrombosis Center Thrombosis, Indianapolis, United States; 3Pediatrics, Moi University, Eldoret, Kenya Introduction: The development of inhibitors is one of the most serious complications in the management of persons with hemophilia (PWH). It renders factor replacement therapy ineffective, requiring the use of by-passing products. Inhibitor testing is critical in order to offer effective treatment; this has not been fully implemented in resource-limited settings. Barriers including, limited knowledge, lack of laboratory expertise, and inadequate supply of reagents have led to a lack of adequate testing. We did inhibitor testing on our patient cohort and evaluated how the availability of inhibitor results impacted the management of PWH. Methods: PWH who presented at the Moi Teaching and Referral Hospital (MTRH) between September 2021 and October 2022 were tested for inhibitors. We used the classical Bethesda method for testing. We then assessed how the availability of inhibitor results affected patient care. Results: In total, 94 PWH were tested for inhibitors. Of these, 81 have hemophilia A (HA) and 13 hemophilia B (HB). Those who have inhibitors are 14(14.9%) of whom 12 have severe HA, 1 mild HA, and 1 severe HB. The inhibitor titer values ranged from 0.98 to 61 Bethesda Unit (B.U), (5(36%) low responders and 9(64%) high responders). The availability of these results informed clinical decisions in the management of patients who had inhibitors. Of those tested, 11 underwent circumcision 10 of whom did not have inhibitors. They underwent the procedure using factor replacement. One of them with severe HB has an inhibitor level of 6BU and underwent the procedure using by-passing products (Activated Factor 7, Activated Prothrombin Complex Concentrates). The testing has also enabled us to start those with HA and inhibitors (10) on Emicizumab prophylaxis. Following these, there was an increased awareness among the clinical team on the importance of inhibitor testing for PWH. Discussion/Conclusion: The adoption of inhibitor testing at MTRH has greatly improved clinical decisions and management of PWH, demonstrating the need to increase routine inhibitor monitoring in hemophilia treatment centers throughout the country. Disclosure of Interest: None declared R. Maxhuni1,*; V. G. Uka1; B. Abrashi1 1Hemathology, University Clinical Centre of Kosovo, Pristina, Kosovo Introduction: Hemophilia is a rare disease characterized by an inherited bleeding disorder in which the blood does not clot properly.This can lead to spontaneous bleeding, and bleeding after injuries or surgery.Expected prevalence of hemophilia an inherited recessive disease that is linked to X chromosome which there is a gene that codes the synthesis of F VIII. Population of Kosovo: 1.831 million. Number of hemophilia patients diagnosed in my country from 0-18 years old is 39. The disease is diagnosed by bleeding history, family history, Laboratory analysis: blood count, peripheral smear, PT, PTT, Biochemistry analysis and clotting factor tests (except Factor XIII) and genetics. Methods: The purpose of the work: to present the cases of hemophilia A and B in our country with a population of 1.831 milion residents and their hemophilia treatment. Material and methods: children aged 0-18 were included in a total of 39 cases. With hemophilia A, we have 24 and with hemophilia B, there are 15 cases. Results: The result: all cases with severe hemophilia were treated prophylactically, but the cases that could not be treated in time and prophylactically developed various complications such as hamartrosis. The treatment was done with human plasma factors and recombinant factors. Discussion/Conclusion: To create the Hemophylia centre of treatment.Patient registration Prophylactic treatment for all patients, laboratory testing for factor VIII and IX inhibitors, genetic testing. As a rare disease, it needs continuous and multidiciplined treatment. More work in education. The treatment of this category needs t