Treatment of haemophilia A in Tunisia: efficacy and inhibitor study

Summary

Cryoprecipitate is the principal type of factor VIII (FVIII) concentrate used for treating haemophilia A in Tunisia. Allergic reactions, viral transmission, and inhibitor formation remain the most serious complications of FVIII therapy. The aims of the study presented here were to evaluate the efficacy of FVIII therapy, to investigate the inhibitor prevalence, and the factors which may affect inhibitor formation in our haemophilia A patients. Plasma samples were screened for FVIII inhibitors by the Bethesda method. 30 minutes FVIII recovery was also determined for each patient. In this prospective study, 18 previously treated haemophilia A patients, four with severe (FVIII concentration <2%) and 14 with moderate haemophilia, were closely followed up during administration of 223 FVIII concentrates (cryoprecipitate and/or fresh frozen plasma). The median age of the patients involved in the study was 13.5 years (range 5 to 53).Clinical response to FVIII was consistently good to excellent. In the majority of cases, actual and predicted FVIII recovery correlated’ well. Adverse reactions were not observed. Five patients, aged less than 18 years and minimally treated (<36 FVIII exposure days), were found to have low titre FVIII inhibitors (<10 Bethesda units) at the end of the study. Inhibitor activity was detected in one patient with severe and in four patients with moderate haemophilia. In conclusion, FVIII therapy was effective, well tolerated, and low titre inhibitors identified did not preclude continued on demand FVIII therapy. Our study has also demonstrated that patients’ age and treatment regimen do not affect inhibitor formation. Further studies are necessary to confirm these findings.

Zusammenfassung

Kryopräzipitat des Faktor VIII(FVIII)-Konzentrats wird in Tunesien hauptsäuchlich zur Therapie der Hämophilie A verwendet. Allergische Reaktionen, Übertragung von Viren und Inhibitorbildung bleiben die schwerwiegendsten Komplikationen einer FVIII-Therapie. Die Ziele der hier vorgestellten Studie bestanden darin, die Wirksamkeit der FVIII-Therapie, die Prävalenz von Inhibitoren und die Faktoren, die zu Inhibitorbildung bei unseren Hämophilie-A-Patienten führen, zu untersuchen. Die Plasmaproben wurden mit Hilfe der Bethesda-Methode auf FVIII-Inhibitoren untersucht. Es wurden auch für jeden Patienten 30 min FVIII-Erholung festgelegt. Es wurden in dieser prospektiven Studie 18 zuvor behandelte Hämophilie-A-Patienten (mittleres Alter: 13,5 Jahre), vier mit schwerer (FVIII <2%) und 14 mit mäßiger Hämophilie, während der Gabe von 223 FVIII-Konzentraten (Kryopräzipitat und/oder frisches Gefrierplasma), engmaschig überwacht. Das klinische Ansprechen auf FVIII war durchgehend gut bis ausgezeichnet. In der Mehrzahl der Fälle korrelierten eigentliche und vorausgesagte FVIII-Erholung gut miteinander. Nebenwirkungen waren nicht zu beobachten. Bei fünf Patienten unter 18 Jahren, die minimal therapiert wurden (<36 FVIII-Expositionstage), zeigten sich bei Studienende niedrige Titer von FVIII-Inhibitoren (<10 Bethesda-Einheiten). Bei einem Patienten mit schwerwiegender und vier Patienten mit mäßiger Hämophilie wurde eine Inhibitoraktivität nachgewiesen. Insgesamt war die FVIII-Therapie wirksam und gut verträglich, niedrige Titer identifizierter Inhibitoren schlossen eine kontinuierliche FVIII-Therapie bei Bedarf nicht aus. In der hier vorliegenden Studie zeigte sich auch, dass Patientenalter und Therapieschema die Inhibitorbildung nicht beeinflussen. Weitere Studien werden benötigt, um diese Ergebnisse zu bestätigen.

Keywords

Haemophilia A - factor VIII - recovery - inhibitors

Schlüsselwörter

Hämophilie A - Faktor VIII - Inhibitorbildung

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