Browsing by Author "Makris, Mike"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Inhibitor development according to concentrate after 50 exposure days in severe hemophilia: data from the European HAemophilia Safety Surveillance (EUHASS)
    (Elsevier, 2024-05-27) Fischer, Kathelijn; Lassila, Riitta; Peyvandi, Flora; Gatt, Alexander; Gouw, Samantha C.; Hollingsworth, Rob; Lambert, Thierry; Kaczmarek, Radek; Carbonero, Diana; Makris, Mike; European HAemophilia Safety Surveillance (EUHASS) participants; Pediatrics, School of Medicine
    Background: Patients with hemophilia have a life-long risk of developing neutralizing antibodies (inhibitors) against clotting factor concentrates. After the first 50 exposure days (EDs), ie, in previously treated patients (PTPs), data on inhibitor development are limited. Objectives: To report inhibitor development according to factor (F)VIII or FIX concentrate use in PTPs with severe hemophilia A and B. Methods: Inhibitor development in PTPs was collected since 2008 from 97 centers participating in European HAemophilia Safety Surveillance. Per concentrate, inhibitors were reported quarterly and the number of PTPs treated annually. Incidence rates (IRs)/1000 treatment years with 95% CIs were compared between concentrate types (plasma derived FVIII/FIX, standard half-life recombinant FVIII/FIX, and extended half-life recombinant (EHL-rFVIII/IX) concentrates using IR ratios with CI. Medians and IQRs were calculated for inhibitor characteristics. Results: For severe haemophilia A, inhibitor rate was 66/65,200 treatment years, IR 1.00/1000 years (CI 0.80-1.30), occurring at median 13.5 years (2.7-31.5) and 150 EDs (80-773). IR on plasma-derived pdFVIII (IR, 1.13) and standard half-life recombinant FVIII (IR, 1.12) were similar, whereas IR on EHL-rFVIII was lower at 0.13 (incidence rate ratio, 0.12; 95% CI, <0.01-0.70; P < .01).For severe hemophilia B, inhibitor rate was 5/11,160 treatment years and IR was 0.45/1000 years (95% CI, 0.15-1.04), at median 3.7 years (95% CI, 2.1-42.4) and 260 EDs (95% CI, 130 to >1000). Data were insufficient to compare by type of FIX concentrates. Conclusion: Low inhibitor rates were observed for PTPs with severe hemophilia A and B. Data suggested reduced inhibitor development on EHL-rFVIII, but no significant difference between plasma-derived FVIII and standard half-life recombinant FVIII. FIX inhibitor rates were too low for robust statistical analysis.
  • Thumbnail Image
    Item
    Inhibitor development according to concentrate in severe hemophilia: reporting on 1392 Previously Untreated Patients from Europe and Canada
    (Elsevier, 2023-11-20) Fischer, Kathelijn; Lassila, Riitta; Peyvandi, Flora; Gatt, Alexander; Hollingsworth, Rob; Lambert, Thierry; Kaczmarek, Radek; Bettle, Amanda; Samji, Nasrin; Rivard, Georges-Étienne; Carcao, Manuel; Iorio, Alfonso; Makris, Mike; Pediatrics, School of Medicine
    Background: Clotting factor concentrates have been the mainstay of severe hemophilia treatment over the last 50 years. Differences in risk of neutralizing antibody (inhibitor) formation according to concentrate used remain clinically relevant. Objectives: To assess inhibitor development according to type of clotting factor concentrate in previously untreated patients (PUPs) with severe hemophilia A and B. Methods: The European Haemophilia Safety Surveillance (EUHASS) and Canadian Bleeding Disorders Registry (CBDR) have been monitoring adverse events overall and according to concentrate for 11 and 8 years, respectively. Inhibitors were reported quarterly, and PUPs completed 50 exposure days without inhibitor development annually. Cumulative inhibitor incidences and 95% confidence intervals (CIs) were compared without adjustment for other risk factors. Results: Fifty-six European and 23 Canadian centers reported inhibitor development in 312 of 1219 (26%; CI, 23%-28%) PUPs with severe hemophilia A and 14 of 173 (8%; CI, 5%-13%) PUPs with severe hemophilia B. Inhibitor development was lower on plasma-derived factor (F)VIII (pdFVIII, 20%; CI, 14%-26%) than on standard half-life recombinant FVIII (SHL-rFVIII, 27%; CI, 24%-30% and odds ratio, 0.67; CI, 0.45%-0.98%; P = .04). Extended half-life recombinant FVIII (EHL-rFVIII, 22%; CI, 12%-36%) showed an intermediate inhibitor rate, while inhibitor rates for Advate (26%; CI, 22%-31%) and Kogenate/Helixate (30%; CI, 24%-36%) overlapped. For other SHL-rFVIII concentrates, inhibitor rates varied from 3% to 43%. Inhibitor development was similar for pdFIX (11%; CI, 3%-25%), SHL-rFIX (8%; CI, 3%-15%), and EHL-rFIX (7%; CI, 1%-22%). Conclusion: While confirming expected rates of inhibitors in PUPs, inhibitor development was lower in pdFVIII than in SHL-rFVIII. Preliminary data suggest variation in inhibitor development among different SHL-rFVIII and EHL-rFVIII concentrates.
  • Thumbnail Image
    Item
    Management of COVID-19-associated coagulopathy in persons with haemophilia
    (Wiley, 2021) Pipe, Steven W.; Kaczmarek, Radoslaw; Srivastava, Alok; Pierce, Glenn F.; Makris, Mike; Hermans, Cedric; Pediatrics, School of Medicine
    Introduction: The SARS-CoV-2 coronavirus-induced infection (COVID-19) can be associated with a coagulopathy mainly responsible for pulmonary microvasculature thrombosis and systemic thromboembolic manifestations. The pathophysiology and management of the COVID-19 coagulopathy are likely more complex in patients with inherited bleeding diseases such as haemophilia. These individuals might indeed present with both bleeding and thrombotic complications and require simultaneous antithrombotic and haemostatic treatments. Objective: We propose practical guidance for the diagnosis and management of COVID-19 coagulopathy in persons with haemophilia. Results: Continuation of regular haemostatic treatment is recommended for ambulatory patients. For patients requiring hospital admission and on replacement therapy with factors VIII or IX concentrates, prophylaxis with concentrates should be intensified according to the risk of bleeding complications and associated with prophylactic doses of LMWH. For patients on nonreplacement therapy, emicizumab should be continued and possibly combined with factor VIII and prophylactic doses of LMWH depending on the risk of bleeding and thrombosis. Dose escalation of LMWH tailored to the risk of thrombosis can be employed but not supported by evidence. Conclusions: These practical recommendations are based on the current literature on COVID-19 with its impact on haemostasis, indications and modalities for thromboprophylaxis mainly in nonhaemophilic patients and how that is likely to affect persons with haemophilia in different circumstances. They will need to be tailored to each patient's clinical status and validated in future studies.