Factor 4 Research Articles

International Council for Standardization in Haematology recommendations for laboratory measurement of factor VIII and FIX type I inhibitors.

This guidance document has been prepared on behalf of the International Council for Standardisation in Hematology. The aim of the document is to provide guidance and recommendations on the measurement of factor VIII (FVIII) and factor IX (FIX) inhibitors. After an introduction on the clinical background and relevance of factor VIII and factor IX inhibitor testing, the following aspects of laboratory testing are included: screening for inhibitors, assay principle, sample requirements, testing requirements and interpretation, quality assurance, interferences and recent developments. This guidance document focusses on recommendations for a standardised procedure for the laboratory measurement of FVIII and FIX type I inhibitors. The recommendations are based on published data in peer-reviewed literature and expert opinion.

EE555 Cost-Effectiveness of Etranacogene Dezaparvovec for the Treatment of Hemophilia B

Etranacogene dezaparvovec (Etranadez) is a new gene therapy for hemophilia B. This study assessed the cost-effectiveness of Etranadez compared with Factor IX (FIX), in hemophilia B patients without inhibitors eligible for prophylaxis. A special consideration in this assessment was employing a cost savings cap for the new therapy as the existing treatments come at exceptionally high costs.

Assessment of joint bleeding and target joints in patients with severe or moderately severe hemophilia B (factor IX ≤2%) receiving prophylaxis with rIX-FP in the PROLONG-9FP clinical trial program.

To assess the impact of prophylaxis with rIX-FP, a fusion protein linking recombinant factor IX (FIX) with human albumin, on joint outcomes. Joint outcomes were assessed in pediatric (<12 years) and adult/adolescent (≥12 years) patients receiving rIX-FP prophylaxis every 7, 10, or 14 days; patients (>18 years) well-controlled on a 14-day regimen could switch to a 21-day regimen. Target joints were defined as ≥3 spontaneous bleeds into a single joint within a 6-month period. For adult/adolescent (n = 63) and pediatric (n = 27) patients, median (Q1, Q3) annualized joint bleeding rate was 0.39 (0.00, 2.31), 0.80 (0.00, 2.85), 0.20 (0.00, 2.58), and 0.00 (0.00, 1.78) when treated with 7-, 10-, 14-, or 21-day prophylaxis. 50.0%, 38.9%, 45.5%, and 63.6% of adult/adolescent patients had no joint bleeds when treated with 7-, 10-, 14-, or 21-day prophylaxis, respectively, and 40.7%, 37.5%, and 37.5% of pediatric patients had no joint bleeds when treated with 7-, 10-, or 14-day prophylaxis. Ten adult and two pediatric patients developed target joints; all resolved by the end of the study. Prophylaxis with rIX-FP produced low joint bleeding rates and provided excellent hemostatic efficacy in the treatment of joint bleeds. All target joints reported resolved with rIX-FP prophylaxis.

CRISPR-Mediated In Situ Introduction or Integration of F9-Padua in Human iPSCs for Gene Therapy of Hemophilia B.

Hemophilia B (HB) is an X-linked recessive disease caused by F9 gene mutation and functional coagulation factor IX (FIX) deficiency. Patients suffer from chronic arthritis and death threats owing to excessive bleeding. Compared with traditional treatments, gene therapy for HB has obvious advantages, especially when the hyperactive FIX mutant (FIX-Padua) is used. However, the mechanism by which FIX-Padua works remains ambiguous due to a lack of research models. Here, in situ introduction of F9-Padua mutation was performed in human induced pluripotent stem cells (hiPSCs) via CRISPR/Cas9 and single-stranded oligodeoxynucleotides (ssODNs). The hyperactivity of FIX-Padua was confirmed to be 364% of the normal level in edited hiPSCs-derived hepatocytes, providing a reliable model for exploring the mechanism of the hyperactivity of FIX-Padua. Moreover, the F9 cDNA containing F9-Padua was integrated before the F9 initiation codon by CRISPR/Cas9 in iPSCs from an HB patient (HB-hiPSCs). Integrated HB-hiPSCs after off-target screening were differentiated into hepatocytes. The FIX activity in the supernatant of integrated hepatocytes showed a 4.2-fold increase and reached 63.64% of the normal level, suggesting a universal treatment for HB patients with various mutations in F9 exons. Overall, our study provides new approaches for the exploration and development of cell-based gene therapy for HB.

The Interaction of Factor Xa and IXa with Non-Activated Antithrombin in Michaelis Complex: Insights from Enhanced-Sampling Molecular Dynamics Simulations.

The interaction between coagulation factors Xa and IXa and the activated state of their inhibitor, antithrombin (AT),have been investigated using X-ray diffraction studies. However, only mutagenesis data are available for non-activated AT. Our aim was to propose a model based on docking and advanced-sampling molecular dynamics simulations that can reveal the conformational behavior of the systems when AT is not binding a pentasaccharide. We built the initial structure for non-activated AT-FXa and AT-FIXa complexes using HADDOCK 2.4. The conformational behavior was studied using Gaussian accelerated molecular dynamics simulations. In addition to the docked complexes, two systems based on the X-ray structures were also simulated, with and without the ligand. The simulations revealed large variability in conformation for both factors. In the docking-based complex of AT-FIXa, conformations with stable Arg150-AT interactions can exist for longer time periods but the system also has a higher tendency for reaching states with very limited interaction with the "exosite" of AT. By comparing simulations with or without the pentasaccharide, we were able to gain insights into the effects of conformational activation on the Michaelis complexes. RMSF analysis and correlation calculations for the alpha-carbon atoms revealed important details of the allosteric mechanisms. Our simulations provide atomistic models for better understanding the conformational activation mechanism of AT against its target factors.

Investigation of the anticoagulant activity of cyclic sulfated glycosaminoglycan mimetics

Thrombotic disorders are among the leading causes of deaths worldwide. Anticoagulants are frequently prescribed for their prevention and/or treatment. Current anticoagulants, which target either thrombin or factor Xa, are plagued with a number of drawbacks, the most important of which is the increased risk of internal bleeding. To develop better antithrombotic agents, the anticoagulant activity of cyclic glycosaminoglycan mimetics was evaluated. Human plasma clotting assays and enzyme inhibition assays were exploited to evaluate the anticoagulant activity of sulfated β-cyclodextrin (SBCD) and its three analogs: sulfated α-cyclodextrin, β-cyclodextrin, and methylated β-cyclodextrin. In normal human plasma, SBCD selectively doubled the activated partial thromboplastin time (APTT) at ∼9 μg/mL, with no effect on prothrombin time (PT) at the same concentration. Likewise, SBCD doubled APTT at ∼9 μg/mL and at ∼8 μg/mL in antithrombin-deficient plasma and heparin cofactor II-deficient plasma, respectively. Interestingly, the three SBCD derivatives were inactive at the highest concentrations tested which highlighted the importance of the sulfate groups and the size of the molecule. Enzyme assays revealed that SBCD inhibits factor XIa (FXIa) with an IC50 value of ∼20 μg/mL and efficacy of near 100%. SBCD did not inhibit other related proteins including thrombin, factor IXa, factor Xa, factor XIIa, factor XIIIa, plasmin, chymotrypsin, or trypsin at the highest concentrations tested demonstrating a significant selectivity. In Michaelis-Menten kinetics, SBCD decreased the VMAX and increased the KM of FXIa hydrolysis of a tripeptide chromogenic substrate indicating a mixed inhibition mechanism. Together, it appears that SBCD is a potent and selective inhibitor of human FXIa with substantial anticoagulant activity in human plasma. Overall, this study introduces SBCD as a promising lead for further development as a safer anticoagulant.

Extended half-life factor IX prophylaxis up to every 21 days in hemophilia B: a longitudinal analysis of the efficacy and safety in selected adult patients

BackgroundExtended half-life factor IX (FIX) products have revolutionized prophylactic treatment for patients with hemophilia B as patients maintain protective FIX levels with minimal occurrence of spontaneous bleeding. rIX-FP is an extended half-life FIX product that allows prolonged dosing intervals. ObjectivesTo assess individualized and prolonged prophylactic dosing interval up to 21 days in adult patients (≥18 years) with hemophilia B in the rIX-FP clinical trial program. MethodsPatients who were included in the PROLONG-9FP phase III study or who received rIX-FP during surgery could continue into an extension study for long-term assessment. Patients began 7-day prophylaxis with rIX-FP, and after 6 months, they could extend dosing intervals to every 14 days. In the extension study, adult patients could switch to a 21-day regimen if well-controlled on a 14-day regimen. ResultsEleven patients transitioned from a 7-day prophylaxis regimen to a 14-day regimen and finally to a 21-day regimen, 5 of whom were treated on demand at enrollment. Patients who switched to the 21-day regimen had a median annualized spontaneous bleeding rate of 0.0 across all regimens. The median observed FIX activity remained >5 IU/dL until day 21 after a single 100-IU/kg dose of rIX-FP. After 6 months on the 21-day regimen, 2 patients switched back to a 14-day regimen. No inhibitors, anaphylactic reactions, or thromboembolic events occurred. ConclusionPatients who are well controlled on a once-weekly regimen might extend their treatment interval to 14 days, and in adult patients, further extension to up to 21 days (100 IU/kg) may be considered.

Hereditary hyperactivity of coagulation factor ix caused by a large fragment gene duplication as a rare etiology of cerebral venous sinus thrombosis

Background: Cerebral venous sinus thrombosis (CVST) is a rare cerebrovascular disease with a relatively high mortality and disability, which mainly affects young adults and children. Anticoagulation is currently the mainstay of treatment. Rapid diagnosis and prompt identification of the etiology of CVST are of great significance for the prognosis of this potentially life-threatening condition.&#x0D; Case presentation: We presented a case of recurrent cerebral venous sinus thrombosis complicated with deep venous thrombosis (DVT) due to a large fragment duplication of the factor IX gene region on the X chromosome in a young adult. Long-term rivaroxaban anticoagulant treatment was suggested, and no thrombosis events occurred under regular follow-up.&#x0D; Conclusion: Hereditary hyperactivity of coagulation factor IX is one of the relatively rare causes of hereditary hypercoagulability, which often causes venous thrombosis of lower limbs and rarely involves intracranial venous sinus, expanding the spectrum of etiology of this disorder and deserves attention.

Treatment switch to nonacog beta pegol factor IX in hemophilia B: A Canadian cost-consequence analysis based on real-world factor IX consumption and clinical outcomes

BackgroundThe Canadian Bleeding Disorders Registry (CBDR) is a source of real-world data for Canadian patients with hemophilia B. Nonacog beta pegol (N9-GP), an extended half-life (EHL) recombinant factor IX (FIX) concentrate, was awarded a Canadian Blood Services contract in 2018 and subsequently made available across Canada (except Québec) to adult patients. For most patients already on another EHL FIX treatment, a switch to N9-GP occurred. ObjectivesThis study estimates the impact on treatment costs of a switch from a prior FIX to N9-GP based on annualized bleed rates and FIX consumption volumes before and after N9-GP switch from the CBDR. MethodsReal-world data from the CBDR for total FIX consumption and annualized bleed rates were used to inform a deterministic 1-year cost-consequence model. The model considered that the EHL to N9-GP switches were from eftrenonacog alfa and the standard half-life switches were from nonacog alfa. Because FIX prices are confidential in Canada, the model assumed cost parity for annual prophylaxis with each FIX based on the product monograph recommended dosing regimen to calculate an estimated price per international unit for each product. ResultsThe switch to N9-GP resulted in improvements in real-world annualized bleed rates and therefore reductions in annual breakthrough bleed treatment costs. Switching to N9-GP also resulted in reduced real-world annual FIX consumption for prophylaxis. Overall, annual treatment costs were 9.4% and 10.5% lower after the switch to N9-GP from nonacog alfa and eftrenonacog alfa, respectively. ConclusionN9-GP improves clinical outcomes and may be cost-saving vs nonacog alfa and eftrenonacog alfa.

Abstract MP57: Coagulation Factor IX and Incident Diabetes Risk: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Introduction: A prothrombotic state is implicated in the vascular complications of type 2 diabetes (DM), and such complications disproportionately affect Black compared to White adults. However, it is not known if this is due to DM or whether coagulation factor levels are related to DM incidence. Higher coagulation factor IX (FIX) was related to increased risk of CHD and stroke among Black but not White participants in the REGARDS cohort. We hypothesized higher FIX antigen would be associated with incident DM risk, with stronger relationships in Black versus White adults. Methods: REGARDS enrolled 30,239 Black and White adults from across the contiguous US from 2003-2006 with a second in-home visit from 2013-2016. The Biomarkers as MEDiators of Racial Disparities in Risk Factors (BioMedioR) nested cohort study included 4,400 participants who completed both visits, balanced on race and sex. Modified Poisson regression models estimated the RR of incident DM per 1-SD increment log FIX. We tested for a FIX-by-race interaction a priori due to differential associations of FIX with CHD and stroke by race in REGARDS. Results: Among 3,381 participants without baseline DM (mean age 63 years, 44% Black race, 51% women), 456 (13.5%) developed incident DM over 9.5-years. Adjusting for age, sex, and race, there was a significant difference in the association of FIX with DM by race (p-interaction&lt;0.01). As shown in the Figure, adjusted for age and sex (Model 1), the RR (95% CI) for incident DM was 1.19 (1.05, 1.34) for Black adults and 1.49 (1.23, 1.81) for White adults. Adjusting for clinical risk factors (Model 2) fully attenuated this association for Black adults, and further adjusting for behavioral factors (Model 3) fully attenuated this association for Black and White adults. Conclusions: Higher FIX levels were associated with incident DM risk. Relationships between FIX and incident DM were stronger for White than Black adults. The FIX-DM association may be due to adverse clinical and behavioral risk factors.

Growing weapons to fight hemophilia

Very few rare diseases have witnessed the gigantic progress in patient care that took place for the hemophilias in the last 20 years. The first landmark was in the 1990s, when recombinant DNA technology afforded the industrial production, regulatory approval and commercialization of an array of factor VIII (FVIII) and factor IX (FIX) products, potentially available in unlimited quantity, efficacious and free from the risk of transmission of such bloodborne infections as HIV and the hepatitis virus B and C [...].

Etranacogene Dezaparvovec: First Approval.

Etranacogene dezaparvovec (etranacogene dezaparvovec-drlb; Hemgenix®) is an adeno-associated virus vector-based gene therapy being developed by uniQure and CSL Behring for the treatment of haemophilia B. In November 2022, etranacogene dezaparvovec was approved in the USA for the treatment of haemophilia B [congenital factor IX (FIX) deficiency] in adults who are currently using FIX prophylaxis therapy, have current or historical life-threatening haemorrhage or have repeated, serious spontaneous bleeding episodes. In December 2022, etranacogene dezaparvovec also received positive opinion in the EU for the treatment of haemophilia B. This article summarizes the milestones in the development of etranacogene dezaparvovec leading to this first approval.

Molecular pathogenesis of a novel Met394Thr variant causing hemophilia B.

Hemophilia B (HB), a rare bleeding disorder, shows X-linked recessive inheritance and is caused by heterogeneous variants in the FIX gene (F9) encoding coagulation factor IX (FIX). This study aimed to investigate the molecular pathogenesis of a novel Met394Thr variant causing HB. We used Sanger sequencing to analyze F9 sequence variants in members of a Chinese family with moderate HB. Subsequently, we performed in vitro experiments on the identified novel FIX-Met394Thr variant. In addition, we performed bioinformatics analysis of the novel variant. We identified a novel missense variant (c.1181T>C, p.Met394Thr) in a Chinese family with moderate HB in the proband. The proband's mother and grandmother were carriers for the variant. The identified FIX-Met394Thr variant did not affect the transcription of F9 and the synthesis and secretion of FIX protein. The variant may, therefore, affect the physiological function of FIX protein by disrupting its spatial conformation. In addition, another variant (c.88+75A>G) in intron 1 of F9 was identified in the grandmother, which may also affect FIX protein function. We identified FIX-Met394Thr as a novel causative variant of HB. Further understanding of the molecular pathogenesis underlying FIX deficiency may guide novel strategies for precision HB therapy.

An updated interactive database for 1692 genetic variants in coagulation factor IX provides detailed insights into hemophilia B

BackgroundGenetic variants in coagulation factor IX (FIX) are associated with hemophilia B, a rare bleeding disease. F9 variants are widespread across the gene and were summarized in our FIX variant database introduced in 2013. ObjectivesWe aimed to rationalize the molecular basis for 598 new F9 variants and 1645 new clinical cases, totaling 1692 F9 variants and 5358 related patient cases. MethodsNew F9 variants were identified from publications and online resources, and compiled into a MySQL database for comparison with the human FIXa protein structure. ResultsThe new total of 1692 F9 variants correspond to 406 (88%) of the 461 FIX residues and now include 70 additional residues. They comprise 945 unique point variants, 281 deletions, 352 polymorphisms, 63 insertions, and 51 others. Most FIX variants were point variants, although their proportion (56%) has reduced compared to 2013 (73%); at the same time, the proportion of polymorphisms has increased from 5% to 21%. The 764 unique mild severity variants in the mature protein with known phenotypes include 74 (9.7%) quantitative type I variants and 116 (15.2%) predominantly qualitative type II variants. The remaining 574 variants types are unspecified. Inhibitors are associated with 152 hemophilia B cases out of 5358 patients (2.8%), an increase of 93 from the previous database. ConclusionThe even distribution of the F9 variants revealed few mutational hotspots, and most variants were associated with small perturbations in the FIX protein structure. The updated database will assist clinicians and researchers in assessing treatments for patients with hemophilia B.

Impact of formaldehyde, acetaldehyde, and N-(3-(Dimethylamino)propyl)methacrylamide on the efficacy of the human derived coagulation factor IX

Polymer-borne leachables such as formaldehyde, acetaldehyde, and N-3-(Dimethylamino)propyl)methacrylamide (DMAPMA) may interact with therapeutic proteins. In this study, the leachables were spiked into human derived coagulation factor IX (FIX) at concentrations of 1, 10, 50, 100, and 500 µg/mL, corresponding to a leachable – FIX ratio of 0.5, 5, 25, 50 and 250 %, respectively. The spiked samples were visually inspected, and pH was measured. No visual effects were observed, and pH was within the drug product's specified range. Recovery experiments were performed and no loss of leachables was identified. Protein structure analysis revealed that formaldehyde reacted with lysine contained in two different positions of FIX, in a concentration-dependent manner starting at 10 µg/mL (5 %). The clotting activity of FIX was measured. The activity of the samples spiked with 500 µg/mL (250 %) of formaldehyde dropped by more than half. The activity of the samples spiked with acetaldehyde began to drop at 50 µg/mL (25 %) and continued to decline in concentration-dependent manner. DMAPMA did not impair the activity of FIX. The findings conclude that depending on the concentration, some leachables may react with or modify therapeutic proteins, potentially causing an undesired pharmacological effect however, this is specific to each protein.

Big stride in gene therapy for hemophilia B in China.

Big stride in gene therapy for hemophilia B in China.

Sodium dehydroacetate-induced disorder of coagulation function in broiler chickens and the protective effect afforded by vitamin K

Sodium dehydroacetate (S-DHA) is used widely as a preservative in several products, including poultry feed. The anticoagulation effect of 200 mg/kg S-DHA in rats has been reported to accompany a reduction in hepatic expression of vitamin K epoxide reductase complex 1 (VKORC1). Poultry and mammals have different physiology and coagulation systems, and species differences in VKORC1 expression have been found. The effect of S-DHA on blood clotting of poultry has not been studies deeply. S-DHA was given to yellow-plumage broilers (YBs) as single and multiple administrations. Vitamin K3 (VK3) was injected into YBs 2 wk after S-DHA administration. Then, the prothrombin time (PT), partial activated prothrombin time (APTT), plasma levels of vitamin K (VK), factor IX (FIX), and S-DHA, and hepatic expression of VKORC1 were obtained. Chicken hepatocellular carcinoma (LMH) cells were also exposed to S-DHA, and the cell activity, VK level, and FIX level were measured. S-DHA prolonged the PT or APTT significantly, decreased levels of VK and FIX in blood, and inhibited hepatic expression of VKORC1. The maximum changes were 1.15-fold in the PT, 1.42-fold in the APTT, 0.8-fold in the VK level, 0.7-fold in the FIX level, and 0.35-fold in VKORC1 expression compared with controls. The cell activity, VK level, FIX level, and VKORC1/VKORC1L1 expression of LMH cells were reduced significantly at S-DHA doses of 2.0 to 10.0 mM. Prolongation of the PT/APTT and lower levels of VK/FIX in YBs or the lower cell activity and VK/FIX levels in LMH cells induced by S-DHA therapy were resisted significantly by VK3 treatment. We demonstrated that S-DHA could induce a disorder in coagulation function in YBs or in LMH cells via reduction of VKORC1/VKORC1L1 expression, and that VK could resist this anticoagulation effect.

How to translate and implement the current science of gene therapy into haemophilia care?

Gene-based therapy opens an entirely new paradigm in managing people with haemophilia (PWH), offering them the possibility of a functional cure by enabling continuous expression of factor VIII (FVIII) or factor IX (FIX) after transfer of a functional gene designed to replace the PWH's own defective gene. In recent years, significant advances in gene therapy have been made, resulting in clotting factor activity attaining near-normal levels, as reflected by 'zero bleeding rates' in previously severely inflicted patients following a single administration of adeno-associated viral (AAV) vectors. While this new approach represents a major advancement, there are still several issues that must be resolved before applying this technology in clinical practice. First, awareness, communication, and education about the therapeutic potential and modalities of gene therapy must be further strengthened. To this end, objective, unbiased, transparent, and regularly updated information must be shared, in an appropriate way and understandable language with the support of patients' organizations. Second, healthcare providers should adopt a patient-centred approach, as the 'one size fits all' approach is inappropriate when considering gene therapy. Instead, a holistic patient view taking into account their physical and mental dimensions, along with unexpressed expectations and preferences, is mandatory. Third, the consent procedure must be improved, ensuring that patients' interests are maximally protected. Finally, gene therapy is likely to be first delivered in a few centres, with the highest expertise and experience in this domain. Thus, patients should be managed based on a hub-and-spoke model, taking into account that the key to gene therapy's success lies in an optimal communication and collaboration both within and between haemophilia centres sharing their experiences in the frame of international registries. This review describes recent progress and explains outstanding hurdles that must be tackled to ease the implementation of this paradigm-changing new therapy.

UpToDate®

UpToDate| January 2023 UpToDate® ASA Monitor January 2023, Vol. 87, 19. https://doi.org/10.1097/01.ASM.0000911752.19079.af Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Search Site Citation UpToDate®. ASA Monitor 2023; 87:19 doi: https://doi.org/10.1097/01.ASM.0000911752.19079.af Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll PublicationsASA Monitor Search Advanced Search Topics: blood coagulation disorders, blood pressure, cardiopulmonary bypass, factor ix concentrates, hemorrhage, mortality, older adult, oxygen, plasma, sudden cardiac death UpToDate® and ASA Monitor are collaborating to present select content abstracts on “What's New in Anesthesiology.” UpToDate is an evidence-based, clinical support resource used worldwide by health care practitioners to make decisions at the point of care. For complete, current “What's New” content, or to become a subscriber for full content access, go to www.uptodate.com. “What's New” abstract information is free for all medical professionals. Unactivated prothrombin complex concentrate (PCC) is used to rapidly correct warfarin anticoagulation. Observational studies have described off-label use of PCC to treat surgical coagulopathic bleeding, but supporting data are limited. One randomized trial compared administration of PCC 15 IU/kg with fresh frozen plasma (FFP) 10 to 15 mL/kg in 100 patients who had excessive microvascular bleeding with prothrombin time (PT) >16.6 seconds and international normalized ratio (INR) >1.6 after cardiac surgery with cardiopulmonary bypass.1 Overall efficacy and safety were comparable between... You do not currently have access to this content.

Perioperative continuous infusions of factor VIII versus factor IX for patients with hemophilia A or B undergoing major surgery.

Continuous factor VIII (FVIII) or factor IX (FIX) infusions are commonly used for patients with hemophilia A (HA) or B (HB) undergoing surgery to secure perioperative hemostasis. To describe differences between the initial recovery and subsequent FIX and FVIII levels, and describe clinical outcomes among HB and HA patients receiving perioperative continuous infusion (CI) of recombinant FVIII and FIX concentrates. Retrospective chart review was conducted on 8 consecutive patients with HB and 7 consecutive patients with HA who underwent major surgery between 2014 and 2018 and received continuous infusions of standard half-life factor concentrate. Median initial bolus dose per kilogram was higher for HB compared to HA patients [90.8 (IQR 78.0-98.7) vs. 52.1 (IQR 48.6-55.6) IU/kg], while initial CI dose-rates were similar [4.3 (IQR 3.8-4.6) vs. 4.2 (IQR 3.8-4.4) IU/kg/h]. Median post-bolus recovery was higher for FVIII compared to FIX [1.70 (IQR 1.23-1.75) vs. 0.88 (IQR 0.75-1.00) IU/mL]. Median factor levels also were higher for FVIII on post-operative days 1 to 3. HB patients had greater mean intraoperative estimated blood loss [285.7 (range 0-1000) vs. 142.8 (range 0-400) mL] and longer median length of hospital stay [9 (IQR 8-12) vs. 5 (IQR 4-6.5) days]. Our initial evidence suggests greater in vivo yield of rFVIII compared to rFIX in the perioperative setting. We identified poorer clinical outcomes in this small cohort of perioperative HB patients indicating that they may benefit from a higher CI rate for adequate surgical hemostatic coverage.