Antiphospholipid autoantibody detection is important in all patients with systemic autoimmune diseases.

Antiphospholipid (aPL) autoantibodies are uncommon in systemic autoimmune diseases (SADs). However, the European PRECISESADS study provides the opportunity to better characterize this rare association. The study was composed of 1818 patients with SADs including 453 with systemic lupus erythematosus (SLE), 359 with rheumatoid arthritis (RA), 385 with systemic sclerosis (SSc), 367 with Sjögren's syndrome (SjS), 94 with mixed connective tissue disease (MCTD), and 160 with undifferentiated connective tissue disease (UCTD). Assays used for aPL determination include the lupus anticoagulant (LAC) analysis using the dilute Russell's viper venom time (dRVVT) assay plus anti-cardiolipin (aCL) and anti-aß2GPI autoantibodies of IgG and IgM isotype. Information regarding clinical and biological characteristics of SAD patients was available. Among SAD patients, the prevalence of aPL differs significantly between two groups: SLE (57.6%) and non-SLE SADs (13.7%, p < 10-4). Next, association between aPL plus thrombosis and miscarriage were observed in both SLE and non-SLE patients. Thrombosis was best predicted in SLE patients by dRVVT (OR = 6.1; IC95:3.5-10.3) and miscarriage by aCL±ß2GPI IgG (OR = 2.5; IC95:1.2-5.2); while in non-SLE SADs the best predictors were aCL±ß2GPI IgG for thrombosis (OR = 6.6; IC95:2.4-18.4) and aCL±ß2GPI IgM for miscarriage (OR = 2.9; IC95:1.2-6.8). In the case of multiple positivity of aPL, the risk for thrombosis and miscarriage was increased. Central nervous system involvement characterized the SLE patients, in contrast to pulmonary and skin fibrosis, valve lesions, hypertension, elevated creatinemia, C4 fraction reduction, platelet reduction and inflammation that characterized the non-SLE SAD patients. Anti-PL determination remains important in SADs patients and should not be restricted to only SLE patients.

Multicentre pharmacokinetic evaluation of rFVIII-Fc (efmoroctocog alfa) in a real life and comparison with non-extended half-life FVIII concentrates.

The use of enhanced half-life (EHL) FVIII has improved the quality of prophylaxis in haemophilia A, but with a benefit that may vary from one patient to another. We analysed the pharmacokinetic data obtained with efmoroctocog alfa (rFVIII-Fc) in 114 patients and, in 47 cases, compared them to those previously measured with non-EHL FVIII. The in vivo recovery (IVR) of rFVIII-Fc measured with one stage clotting assay (OSA) and chromogenic assay (CSA) was 2.2 and 2.8 IU/mL per IU/kg, respectively. The median half-life (T1/2 ) of rFVIII-Fc was 14.5 hours whatever the FVIII:C assay used, but variable and correlated with preinfusion VWF:Ag levels (r = .76). Both IVR and T1/2 were lower in patients under 12 years old (2.4 IU/mL per IU/kg and 11.1 hours, respectively; CSA). PK study of rFVIII-Fc vs non-EHL FVIII showed a T1/2 ratio of 1.4 in favour of rFVIII-Fc, regardless of the patient's age. However the relative increase in T1/2 with rFVIII-Fc was lower than 30% in one-third of patients evaluated, particularly when the previous FVIII administered was a BHK-derived product. This study therefore suggests that analysis of individual PK profile in response to a specific FVIII concentrate is potentially useful before a switch in haemophilia A patients.

Factor VIII and IX assays for post-infusion monitoring in hemophilia patients: Guidelines from the French BIMHO group (GFHT).

Replacement therapy with plasma-derived or recombinant FVIII and FIX (pdFVIII/pdFIX or rFVIII/rFIX) concentrates is the standard of treatment in patients with haemophilia A and B, respectively. Measurement of factor VIII (FVIII:C) or factor IX (FIX:C) levels can be done by one-stage clotting assay (OSA) or chromogenic substrate assay (CSA). The French study group on the Biology of Hemorrhagic Diseases (a collaborative group of the GFHT and MHEMO network) presents a literature review and proposals for the monitoring of FVIII:C and FIX:C levels in treated haemophilia A and B patients, respectively. The use of CSA is recommended for the monitoring of patients treated with pdFVIII or rFVIII including extended half-life (EHL) rFVIII. Except for rFVIII-Fc, great caution is required when measuring FVIII:C levels by OSA in patients substituted by EHL-rFVIII. The OSA is recommended for the monitoring of patients treated with pdFIX or rFIX. Large discordances in the FIX:C levels measured for extended half-life rFIX (EHL-rFIX), depending on the method and reagents used, must lead to great attention when OSA is used for measuring FIX:C levels in patients substituted by EHL-rFIX. Data of most of recent studies, obtained with spiked plasmas, deserve to be confirmed in plasma samples of treated patients.

A very potent factor V inhibitor interferes with the levels of all coagulation factors and causes a fatal hemorrhagic syndrome.

We report a very high factor V inhibitor affecting the measurement of all coagulation factors besides fibrinogen, all these factors being dramatically decreased. This inhibitor could be linked to antibiotic use. The patient died of massive hemorrhage before a plasma exchange could be initiated.

Decreased turnover aspirin resistance by bidaily aspirin intake and efficient cytoreduction in myeloproliferative neoplasms.

Essential thrombocythemia (ET) and polycythemia vera (PV) are myeloproliferative neoplasms (MPN) with an increased risk of arterial and venous thrombosis. Aspirin is recommended to reduce this risk, but resistance to antiplatelet therapy seems to hamper its efficacy in some patients. We have previously shown that multiple electrode aggregometry (MEA) was a valuable tool to assess aspirin resistance in MPN. In this study, MEA was used to assess the reduction in aspirin resistance after bi-daily (BID) aspirin intake or cytoreduction. Fifty one MPN patients (31 ET and 20 PV) receiving 75 mg aspirin once daily (OD) or BID, with or without cytoreductive treatment, were analyzed. Aspirin resistance was assessed using whole blood MEA (Multiplate®, Roche Diagnostics, Meylan, France). In all patients, global aspirin resistance consisted mainly of turnover resistance (TOR). 94% of patients with OD aspirin intake and without cytoreduction displayed biological aspirin resistance. By switching to a BID aspirin regimen, the proportion of resistant patients reduced to 47%. Cytoreduction also contributed to reduce aspirin resistance in a similar way (50% of aspirin resistant patients). Combining cytoreduction and BID aspirin regimen was the most efficient way to reduce aspirin resistance yielding to 12% resistant patients. Moreover, a nonlinear correlation was observed between TOR and naive platelet counts regardless of aspirin regimen. Last, mutational status did not seem to affect TOR. This study confirmed that BID aspirin is biologically more effective than OD aspirin in reduction of aspirin resistance. The latter was achieved through a reduction in TOR which was also decreased by cytoreductive therapy.

Comparison of four methods to assess high-on platelet reactivity under P2Y12 receptor inhibitor.

P2Y12 receptor inhibitors are antiplatelet agents commonly prescribed in the treatment of coronary artery disease. Their efficacy can be limited by high on-treatment platelet reactivity (HPR), which can be evaluated by different biological assays. Most commonly, HPR is evaluated by flow cytometric vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay, which can be time consuming. To evaluate the potential interest of novel technologies, we compared four different assays. Ninety patients receiving P2Y12 inhibitors were included. Four technologies were evaluated: the current standard test measuring VASP-P by flow cytometry, the historical reference test based on light transmittance aggregation (LTA), and two relatively novel techniques: whole blood multiple electrode aggregometry (MEA) and platelet function analyzer (PFA), which are less time consuming. The three latter tests were compared with the VASP-P assay as a reference using receiver operating characteristics (ROC) analysis: LTA has an excellent comparability with the VASP test (ROC AUC > 0.9); the other two tests (multiplate and PFA) have only satisfactory comparability (ROC AUC around 0.7) and therefore may not replace the VASP "gold standard" test, if importance is attached to a quantitative assessment of the substitution parameter of VASP. Nevertheless, if a binary approach of the anti-aggregation result is sought, then one can conclude that the three tests are equivalent since Cohen's kappa coefficients are very close for the three tests (k = 0.548 for LTA; k = 0.554 for MEA; k = 0.570 for PFA/P2Y), and a similar proportion of patients are misclassified (15% for LTA, 14% for MEA, and 13.6% for PFA). Discriminant factor analysis using all the parameters provided by each test did not improve the diagnostic performance of MEA or PFA. In conclusion, only LTA shows a good comparability to the VASP assay using ROC curve analysis, probably because misclassified patients have results close to the cutoff values. All three tests have moderate agreement regarding the classification of patients as responders to P2Y12 inhibition.

Venous gas emboli are involved in post-dive macro, but not microvascular dysfunction.

PURPOSE: Previous studies have shown vascular dysfunction of main conductance arteries and microvessels after diving. We aim to evaluate the impact of bubble formation on vascular function and haemostasis. To achieve this, we used a vibration preconditioning to influence bubble levels without changing any other parameters linked to the dive. METHODS: Twentty-six divers were randomly assigned to one of three groups: (1) the "vibrations-dive" group (VD; n = 9) was exposed to a whole-body vibration session 30 min prior the dive; (2) the "diving" group (D; n = 9) served as a control for the effect of the diving protocol; (3) The "vibration" protocol (V; n = 8) allowed us to assess the effect of vibrations without diving. Macro- and microvascular function was assessed for each subject before and after the dive, subsequently. Bubble grades were monitored with Doppler according to the Spencer grading system. Blood was taken before and after the protocol to assess any change of platelets or endothelial function. RESULTS: Bubble formation was lower in the VD than the diving group. The other measured parameters remained unchanged after the "vibration" protocol alone. Diving alone induced macrovascular dysfunction, and increased PMP and thrombin generation. Those parameters were no longer changed in the VD group. Conversely, a microvascular dysfunction persists despite a significant decrease of circulating bubbles. CONCLUSIONS: Finally, the results of this study suggest that macro- but not microvascular impairment results at least partly from bubbles, possibly related to platelet activation and generation of pro-coagulant microparticles.

The use of 1E12, a monoclonal anti-platelet factor 4 antibody, to improve the diagnosis of vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a complication of adenoviral-based vaccine against SARS-CoV-2 due to prothrombotic immunoglobulin (Ig) G antibodies to platelet factor 4 (PF4) and may be difficult to distinguish from heparin-induced thrombocytopenia (HIT) in patients treated with heparin. OBJECTIVES: We assessed the usefulness of competitive anti-PF4 enzyme immunoassays (EIAs) in this context. METHODS: The ability of F(ab')2 fragments of 1E12, 1C12, and 2E1, 3 monoclonal anti-PF4 antibodies, to inhibit the binding of human VITT or HIT antibodies to PF4 was evaluated using EIAs. Alanine-scanning mutagenesis was performed to define the amino acids involved in the interactions between the monoclonal antibodies and PF4. RESULTS: A strong inhibition of VITT IgG binding to PF4 was measured with 1E12 (median inhibition, 93%; n = 8), whereas it had no effect on the binding of HIT antibodies (median, 6%; n = 8). In contrast, 1C12 and 2E1 inhibited VITT (median, 74% and 76%, respectively) and HIT antibodies (median, 68% and 53%, respectively) binding to PF4. When a competitive anti-PF4 EIA was performed with 1E12 for 19 additional VITT samples, it strongly inhibited IgG binding to PF4, except for 1 patient, who had actually developed HIT according to the clinical history. Epitope mapping showed that 1E12 interacts with 5 key amino acids on PF4, of which 4 are also required for the binding of human VITT antibodies, thus explaining the competitive inhibition. CONCLUSION: A simple competitive anti-PF4 EIA with 1E12 could help confirm VITT diagnosis and distinguish it from HIT in patients when both diagnoses are possible.

Using an age and fibrinogen levels adjusted D-dimer cutoff significantly improves the specificity of two equivalent D-dimer assays for excluding pulmonary embolism.

OBJECTIVES: Our single-center prospective study compared two methods of D-dimer determination used in the exclusion of pulmonary embolism: bioMérieux method, VIDAS® D-Dimer Exclusion™ II, and Diagnostica Stago method, STA®-Liatest® D-Di Plus. For each of these two methods, we calculated optimized variable cutoffs based on fibrinogen and/or age to improve the specificity of the methods. PATIENTS - METHODS: 2530 patients admitted to the Emergency Department of the Brest University Hospital for suspected pulmonary embolism were included in this study. The comparison of the two methods was performed by calculating their different characteristics: sensitivity, specificity and negative predictive value for different cutoffs systems: fixed or age-adjusted according to Douma et al. An optimization of the variable cutoff according to age and fibrinogen was then performed. RESULTS: The two methods VIDAS and STAGO are approximately equivalent in terms of performance even if the STAGO method presents a better specificity (57.1 %) at the fixed cutoff of 0.5 µg/mL. The adoption of age-adjusted, fibrinogen-adjusted or doubly-adjusted (age and fibrinogen) cutoffs, significantly improves the specificity of the tests without affecting their excellent sensitivity. These specificities peak respectively at 75.8 % and 76 % for the VIDAS and STAGO tests when using a doubly-adjusted, age and fibrinogen, cutoff, i.e. a gain in specificity of approximately 10 % compared with the age-adjusted cutoff of Douma et al. and of approximately 20 % compared with the fixed cutoff of 0.5 µg/mL. CONCLUSION: Adopting an optimized variable cutoff based on fibrinogen and/or age significantly improves specificity of D-dimer methods for pulmonary embolism exclusion.

Microrheology and structural quantification of hypercoagulable clots.

Hypercoagulability is a pathology that remains difficult to explain today in most cases. It is likely due to a modification of the conditions of polymerization of the fibrin, the main clot component. Using passive microrheology, we measured the mechanical properties of clots and correlated them under the same conditions with structural information obtained with confocal microscopy. We tested our approach with known alterations: an excess of fibrinogen and of coagulation Factor VIII. We observed simultaneously a rigidification and densification of the fibrin network, showing the potential of microrheology for hypercoagulability diagnosis.

[Point-of-care testing for D-dimer in the exclusion of venous thromboembolism: a critical analysis]. / Les dispositifs délocalisés de dosage des D-dimères dans l'exclusion de la maladie thromboembolique veineuse : une analyse critique.

Point-of-care testing (POCT) for D-dimer is an alternative to -laboratory testing for the exclusion of venous thromboembolism (VTE). This critical review by the "CEC et biologie délocalisée" working group of the "Société Française de Thrombose et d'Hémostase" (French Society of -Thrombosis and Haemostasis) aims to present the characteristics of six POCT D-dimer assays available in France in 2023. The article highlights the need to define VTE -exclusion thresholds specific to each technique and validated by clinical studies. There is insufficient data to validate the use of cut off suggested by manufacturers, and age-adjusted thresholds. The article discusses the role of laboratories in justifying and prescribing POCT D-dimer, according to objective criteria, such as the availability and turnaround time of classical laboratory tests. They should also encourage rational prescribing, limited to patients with low risk of venous thromboembolism, following an assessment of clinical probability according to national and international guidelines.

Does Decreased Diffusing Capacity of the Lungs for Carbon Monoxide Constitute a Risk of Decompression Sickness in Occupational Divers?

Long-term alterations of pulmonary function (mainly decreased airway conductance and capacity of the lungs to diffuse carbon monoxide (DLCO)) have been described after hyperbaric exposures. However, whether these alterations convey a higher risk for divers' safety has never been investigated before. The purpose of the present pilot study was to assess whether decreased DLCO is associated with modifications of the physiological response to diving. In this case-control observational study, 15 "fit-to-dive" occupational divers were split into two groups according to their DLCO measurements compared to references values, either normal (control) or reduced (DLCO group). After a standardized 20 m/40 min dive in a sea water pool, the peak-flow, vascular gas emboli (VGE) grade, micro-circulatory reactivity, inflammatory biomarkers, thrombotic factors, and plasmatic aldosterone concentration were assessed at different times post-dive. Although VGE were recorded in all divers, no cases of decompression sickness (DCS) occurred. Compared to the control, the latency to VGE peak was increased in the DLCO group (60 vs. 30 min) along with a higher maximal VGE grade (p < 0.0001). P-selectin was higher in the DLCO group, both pre- and post-dive. The plasmatic aldosterone concentration was significantly decreased in the control group (-30.4 ± 24.6%) but not in the DLCO group. Apart from a state of hypocoagulability in all divers, other measured parameters remained unchanged. Our results suggest that divers with decreased DLCO might have a higher risk of DCS. Further studies are required to confirm these preliminary results.

Biological determinants of bleeding in patients with heterozygous factor XI deficiency.

Bleeding risk is not predictable in patients with factor XI (FXI; F11) deficiency. In this prospective study, our objectives were to determine the biological determinants for bleeding risk in patients with heterozygous FXI deficiency. Patients were classified as either bleeding patients or non-bleeding patients by calculating the bleeding score (BS) described for von Willebrand disease. Primary haemostasis, thrombin generation, thromboelastometry, procoagulant proteins, inhibitors, fibrinolysis, and F11 gene mutations were compared between bleeding and non-bleeding patients. Thirty-nine patients were included. BS significantly correlated with clinical assessment (P=0·001), and a score over 3 discriminated between bleeding (n=15) and non-bleeding (n=24) patients (P=0·034). Despite normal values, von Willebrand factor (VWF) and thrombomodulin (TM) plasma levels were significantly lower in bleeding patients than non-bleeding patients [ristocetin cofactor activity (VWF:RCo)=80·6±29·7 iu/dl and 101·8±29·5iu/dl respectively, P=0·043; and VWF antigen (VWF:Ag)=84·0±28·0 iu/dl and 106·3±36·1 iu/dl respectively, P=0·035; and TM=17·7±11·7ng/ml and 23·6±9·7ng/ml respectively, P=0·043]. When considering BS as a continuous variable, only VWF:RCo remained significant (P=0·042), which accounted for 11% of the variability in BS.

Apport du dosage des monomères de fibrine en situations obstétricales aiguës.

Depuis 2013, nous utilisons le dosage des monomères de fibrine au laboratoire d'hématologie du CHU de Brest. Ce marqueur précoce de l'activation de la coagulation nous permet de détecter très tôt une coagulation intravasculaire disséminée (CIVD) et de suivre son évolution grâce à l'utilisation du rapport monomères de fibrine/D-dimères. Le dosage des monomères de fibrine est utile dans plusieurs contextes cliniques et il est complémentaire de celui des D-dimères. Au travers de deux cas clinico-biologiques, nous allons montrer l'intérêt de ces paramètres dans deux situations obstétricales aigues. Le premier cas clinique traite d'une hémorragie du post-partum compliquée d'une coagulation intravasculaire disséminée. Dans ce cas, les monomères de fibrine ont permis de détecter rapidement l'activation de la coagulation. Le deuxième cas clinique traite d'une prise en charge d'un placenta percreta compliqué d'une coagulation intravasculaire disséminée, pour lequel les monomères ont aidé à la prise en charge chirurgicale.

Apixaban and rivaroxaban in obese patients treated for venous thromboembolism: Drug levels and clinical outcomes.

BACKGROUND: Direct oral anticoagulants (DOAC) use remains challenging in obese patients treated for Venous-Thrombo-Embolism (VTE) due to the paucity of prospective and dedicated studies. OBJECTIVE: To assess rivaroxaban and apixaban concentrations at different time-points after intake, in obese patients followed at a thrombosis center and treated for VTE; to define factors associated with DOAC levels outside the on-therapy ranges; and to evaluate bleeding and thrombosis rates during follow-up. METHODS: Observational prospective study in two French University hospitals. Apixaban or rivaroxaban concentrations were measured after the first visit, regardless of last intake in obese patients receiving DOAC for VTE. Concentrations were compared to published reference values for non-obese patients. Demographic, clinical, biological and therapeutic data were collected. Univariate and multivariate analyses were performed to identify factors associated to DOAC concentrations outside the on-therapy ranges. RESULTS: Out of the 146 patients included, 22 (15%) had DOAC concentrations outside the on-therapy ranges, mainly in the rivaroxaban group (n = 17). Age ≤ 63 years, use of rivaroxaban and time since last intake ≤8 h were associated with DOAC concentrations outside the on-therapy ranges, in multivariable analysis. During the median follow-up of 16 months, two (1%) patients receiving apixaban had recurrent VTE. No patient had major bleeding, 11 (8%) patients had minor bleeding. CONCLUSION: In this specific prospective bi-centric study dedicated to VTE obese patients, use of DOACs at fixed doses led to concentrations similar to those of non-obese patients in a high proportion of patients, without any effect of the BMI, and with risk-benefit profile comparable to non-obese patients.

Vitamin K antagonist has a higher impact than heparin in preventing circuit clotting in chronic haemodialysis patients.

BACKGROUND: In dialysis sessions, some data suggest that decreasing or even avoiding additional anticoagulation by heparin is possible among patients already treated with oral anticoagulation. However, the required dose of heparin may actually depend on the pre-dialysis international normalized ratio (INR), which varies from one session to another. The aim of our study was to determine the respective role of INR and heparin dosing in the risk of circuit clotting during chronic haemodialysis. METHODS: From early 2012 to July 2016, we analysed the totality of dialysis sessions performed at Brest University Hospital among haemodialysis patients treated by vitamin K antagonists (VKA). We established a prediction of circuit clotting on the basis of a simplified score obtained by combining INR and heparin dosing. RESULTS: In total, 7184 dialysis sessions among chronic haemodialysis patients under VKA were identified, including 233 with clotting events. The mean INR without clotting events was 2.5 versus 1.8 with clotting events (P < 0.001). Frequencies of circuit clotting were different according to INR group (INR <2.0, INR 2.0-3.0, INR >3.0; P < 0.0001). The protective role of VKA was higher than heparin, as shown by discriminant factor analysis (P < 0.0001). Conclusion. Our study established a predictive model of thrombosis risk of dialysis circuits in patients treated by VKA for a given heparin dose and a given INR. This model shows a marginal contribution of heparin to protect against the risk of thrombosis compared with VKA. Moreover, heparin would not appear to be necessary for patients with an INR >2.2.

Physiological characteristics associated with increased resistance to decompression sickness in male and female rats.

Decompression sickness (DCS) is a complex and poorly understood systemic disease with wide interindividual resistance variability. We selectively bred rats with a threefold greater resistance to DCS than standard ones. To investigate possible physiological mechanisms underlying the resistance to DCS, including sex-related differences in these mechanisms, 15 males and 15 females resistant to DCS were compared with aged-matched standard Wistar males (n = 15) and females (n = 15). None of these individuals had been previously exposed to hyperbaric treatment. Comparison of the allelic frequencies of single nucleotide polymorphisms (SNPs) showed a difference of one SNP located on the X chromosome. Compared with nonresistant rats, the neutrophil-to-lymphocyte ratio and the plasmatic activity of coagulation factor X were significantly higher in DCS-resistant individuals regardless of their sex. The maximal relaxation elicited by sodium nitroprusside was lower in DCS-resistant individuals regardless of their sex. Males but not females resistant to DCS exhibited higher neutrophil and lymphocyte counts and higher prothrombin time but lower mitochondrial basal O2 consumption and citrate synthase activity. Principal components analysis showed that two principal components discriminate the DCS-resistant males but not females from the nonresistant ones. These components were loaded with activated partial thromboplastin time, monocyte-to-lymphocyte ratio, prothrombin time, factor X, and fibrinogen for PC1 and red blood cells count and neutrophils count for PC2. In conclusion, the mechanisms that drive the resistance to DCS appear different between males and females; lower coagulation tendency and enhanced inflammatory response to decompression stress might be key for resistance in males. The involvement of these physiological adaptations in resistance to DCS must now be confirmed.NEW & NOTEWORTHY By selective breeding of individuals resistant to decompression sickness (DCS) we previously obtained a rat model of inherited resistance to this pathology. Comparison of these individuals with nonresistant animals revealed differences in leukocyte counts, coagulation, and mitochondrial and vascular functions, but not resistance to oxidative stress. This study also reveals sex-related differences in the physiological changes associated with DCS resistance. A principal components analysis of our data allowed us to discriminate DCS-resistant males from standard ones, but not females. These differences represent possible mechanisms driving resistance to DCS. Although still far from the diver, this opens a pathway to future adaptation of personalized decompression procedures for "DCS-prone" individuals.

Real Life Population Pharmacokinetics Modelling of Eight Factors VIII in Patients with Severe Haemophilia A: Is It Always Relevant to Switch to an Extended Half-Life?

We retrospectively analysed the data files of 171 adults and 87 children/adolescents with severe haemophilia, except for 14 patients (moderate; minor) (1), to develop a global population pharmacokinetic (PK) model for eight factors VIII (FVIII) that could estimate individual PK parameters for targeting the desired level of FVIII activity (FVIII:C); and (2) to compare half-life (HL) in patients switching from a standard half-life (SHL) to an extended half-life (EHL) and evaluate the relevance of the switch. One-stage clotting assay for the measurement of FVIII activity (FVIII:C, IU/mL) was used for population PK modelling. The software, Monolix version 2019R1, was used for non-linear mixed-effects modelling. A linear two-compartment model best described FVIII:C. The estimated PK parameters (between-subject variability) were: 2640 mL (23.2%) for volume of central compartment (V1), 339 mL (46.8%) for volume of peripheral compartment (V2), 135 mL/h for Q (fixed random effect), and 204 mL/h (34.9%) for clearance (Cl). Weight, age, and categorical covariate EHL were found to influence Cl and only weight for V1. This model can be used for all of the FVIII cited in the study. Moreover, we demonstrated, in accordance with previous studies, that Elocta had longer half-life (EHL) than SHL (mean ratio: 1.48) as compared to Advate, Factane, Kogenate, Novoeight, and Refacto.