Efficacy and tolerability of a pasteurised human fibrinogen concentrate in patients with congenital fibrinogen deficiency.

The efficacy and tolerability of a pasteurised human fibrinogen concentrate were assessed in an open, multi-centre, non-controlled retrospective study in patients with congenital fibrinogen deficiency. Haemostatic efficacy was assessed by laboratory investigation and clinical observation. The study included 12 patients (afibrinogenaemia, n = 8; hypofibrinogenaemia, n = 3; dysfibrinogenaemia combined with hypofibrinogenaemia, n = 1). Fibrinogen substitution was indicated: to stop an ongoing bleed; as prophylaxis before surgery; or for routine prophylaxis to prevent spontaneous bleeding. In total, 151 fibrinogen infusions were recorded. The median single dosage was 63.5mg/kg body weight for bleeding events or surgery and 76.9 mg/kg for prophylaxis. The median total dose per event for bleeding events or surgery was 105.6 mg/kg. Fibrinogen was administered in 26 bleeding episodes; 11 surgical operations; and 89 prophylactic infusions, of which 86 were received by one patient. The median response (n = 8) was 1.5 mg/dl per substituted mg of fibrinogen per kg body weight (0.8-2.3). The median in vivo recovery (n = 8) was 59.8% (32.5-93.9). Clinical efficacy was very good in all events with the exception of one surgical procedure, where it was moderate. No intercurrent bleeding occurred during prophylaxis. All but one infusion was well tolerated; the patient, who was administered 86 prophylactic infusions, experienced an anaphylactic reaction after the 56th infusion. In addition, one patient developed deep vein thrombosis and non-fatal pulmonary embolism with treatment for osteosynthesis after collum femoris fracture. Fibrinogen substitution could not be excluded as a contributing factor in this high-risk patient. Substitution with pasteurised human fibrinogen concentrate in patients with congenital fibrinogen deficiencies is efficient and generally well tolerated.

Pharmacokinetic properties of a pasteurised fibrinogen concentrate.

The main pharmacokinetic characteristics of a plasma-derived, pasteurised fibrinogen concentrate were assessed in an open, multicentre, non-controlled study in five patients with congenital afibrinogenaemia or severe congenital hypofibrinogenaemia. Plasma samples were assayed for fibrinogen content in laboratories of the participating clinical centres (CCs) and additionally in a central laboratory at Aventis Behring (ABL). The values of the pharmacokinetic variables, using the fibrinogen determination at ABL, yielded a somewhat shorter terminal half-life compared with that determined at the CCs, with median (range) values of 2.7 days (2.5-3.7 days) versus 3.6 days (3.0-5.3 days), respectively. Fibrinogen clearance rate was clearly lower at the ABL with values of 0.91 ml/h/kg (0.84-1.22 ml/h/kg) compared with 1.65 ml/h/kg (0.82-2.55 ml/h/kg) at the CCs. The distribution volume at steady state (V-ss) of 89 ml/kg (81-116 ml/kg) was also smaller at the ABL than at the CCs (101 ml/kg [84-139 ml/kg]). Response, in vivo recovery and area under the curve did not differ noticeably between the laboratories. The normalisation or near normalisation of pre-infusion pathological coagulation tests indicated a good haemostatic efficacy of the tested fibrinogen concentrate, which was also generally well tolerated and not associated with any serious adverse reactions.