Pharmacokinetics and safety of plasma‐derived factor XIII concentrate (human) in patients with congenital factor XIII deficiency

Abstract

Summary. Congenital factor XIII (FXIII) deficiency is a rare condition with substantial risk for lifethreatening bleeding. Replacement of deficient FXIII with plasma-derived FXIII concentrate is a treatment option. The current 12-week study evaluated the steady-state pharmacokinetic (PK) and safety profile of prophylactic infusions of FXIII concentrate (human) in patients with congenital FXIII deficiency. Patients received FXIII concentrate (human) 40 IU kg À1 on Days 0, 28, and 56. FXIII levels were assessed before and after each infusion; steady-state PK parameters were assessed up to 28 days after the infusion on Day 56. Treatment effectiveness in maintaining trough FXIII activity levels ≥5% over 28 days and safety parameters were also assessed. Fourteen patients received FXIII concentrate (human) and 13 completed the study. Post-infusion, FXIII activity levels increased to within the range found in patients without congenital FXIII deficiency without reaching supratherapeutic levels. Non-baseline-adjusted trough FXIII activity levels were maintained at or above 10% at all post-baseline visits in all patients. Steady-state PK parameters were baseline-adjusted; maximum FXIII activity was 87.7% at 1.72 h post-infusion, subsequently declining to a minimum of 5.0%. The half-life was 6.6 days. FXIII concentrate (human) was generally well tolerated. Two patients had possibly treatment-related adverse events. There were no reports of thromboembolism, viral transmission, bleeding events or treatment-related hypersensitivity. These findings support use of FXIII concentrate (human) 40 IU kg À1 every 28 days as an appropriate regimen for routine, long-term prophylaxis in children and adults with congenital FXIII deficiency. Clinical trial registration: www.clinicaltrials.gov/ct2/show/ NCT00883090.

Efficacy and safety of prophylactic treatment with plasma‐derived factor XIII concentrate (human) in patients with congenital factor XIII deficiency

“…There were no severe bleeding episodes in a number of studies of prophylactic treatment with FXIII concentrate (human) [8,16,22] or rFXIII [23]. This is in contrast to the 2.5/PY rate observed in untreated patients with congenital FXIII deficiency [8].…”

Rare coagulation disorders: fibrinogen, factor VII and factor XIII

“…Treatment or prophylaxis with plasma-derived FXIII concentrate is appropriate for patients with either A or B subunit deficiency. Clearly, recombinant FXIII-A 2 factor is only indicated for patients with FXIII-A subunit deficiency and is contraindicated for patients where FXIII levels are decreased due to FXIII-B subunit absence or mutations [14,15]. The FXIII and Fibrinogen SSC Subcommittee of the ISTH proposed an algorithm for diagnosing FXIII deficiency, starting with the quantitative functional FXIII activity assay as the primary screening tool.…”

Minimal factor XIII activity level to prevent major spontaneous bleeds: comment

“…To prevent these bleeds, primary prophylaxis is mandatory for all patients with severe congenital FXIII deficiency from the time of diagnosis. Different prophylaxis programs, ranging from 10 IU kg −1 every 4–6 weeks to 40 IU kg −1 every 4 weeks with FXIII concentrate, have been used for the management of patients with congenital FXIII deficiency . In our 4‐year experience, Iranian patients ( n = 380) have received 10 IU kg –1 Fibrogammin P (Dade Behring, Marburg, Germany) every 4 weeks, and preprophylaxis FXIII:C assay on day 28 in ~ 10% of these patients revealed FXIII:C of < 5%, but none of these 380 patients experienced spontaneous major bleeding during this time.…”