Efficacy and safety of long-acting recombinant fusion protein linking factor IX with albumin in haemophilia B patients undergoing surgery.

INTRODUCTION: Recombinant factor IX fusion protein (rIX-FP) has been developed to improve the pharmacokinetic (PK) profile of factor IX (FIX), allowing maintenance of desired FIX activity between injections at extended intervals, ultimately optimizing haemophilia B treatment. AIM: To determine the efficacy and safety of rIX-FP in the perioperative setting. METHODS: Subjects were adult and paediatric patients with severe to moderately severe haemophilia B (FIX ≤ 2%) participating in three Phase III clinical trials and undergoing a surgical procedure. PK profiles were established prior to surgery for each patient. Haemostatic efficacy was assessed by the investigator for up to 72 h after surgery. Safety measurements during the study included adverse events and inhibitors to FIX. FIX activity was monitored during and after surgery to determine if repeat dosing was required. RESULTS: Twenty-one, both major and minor, surgeries were performed in 19 patients. Haemostatic efficacy was rated as excellent (n = 17) or good (n = 4) in all surgeries. A single preoperative dose maintained intraoperative haemostasis in 20 of 21 surgeries. Nine major orthopaedic surgeries were conducted in eight patients with a mean of 7 (range: 6-12) rIX-FP injections during surgery and the 14-day postoperative period. Median rIX-FP consumption for orthopaedic surgeries was 87 IU kg(-1) preoperatively and 375 IU kg(-1) overall. No subject developed inhibitors to FIX or antibodies to rIX-FP. CONCLUSION: Recombinant factor IX fusion protein was well tolerated and effectively maintained haemostasis during and after surgery. Stable FIX activity was achieved with a prolonged dosing interval and reduced consumption compared to conventional or currently available long-acting recombinant FIX.

Cryoprecipitate-removed plasma 'cryo-removed plasma' as a source of factor IX in the treatment of haemophilia B.

Fresh frozen plasma (FFP) is the main source of factor IX (FIX) in the treatment of bleeding episodes of haemophilia B in the Philippines. Cryoprecipitate-removed plasma otherwise known in the Philippines as cryosupernate, is a by-product of cryoprecipitate preparation. These blood products expire in storage or are just thrown- away because of less demand for clinical use. By theory, this product should have almost the same amount of FIX as in FFP, therefore can be used in the treatment of haemophilia B. There is no local data on the actual FIX content of the cryoprecipitate-removed plasma. Hence, the authors established these data to support the use of this product. Eighty-three bags of cryoprecipitate-removed plasma received from three different blood banks in Manila, Philippines were tested for FIX activity using an activated partial thromboplastin time (APTT)-based one-stage FIX assay. The FIX content in each bag of cryoprecipitate-removed plasma was calculated by multiplying its volume in mL with that of FIX activity per mL of plasma measured in vitro. The total mean FIX content per bag was 212.20 U (+/-88.98) exceeding the contents set by the American Association of Blood Banks (AABB, 70-90 U). The mean FIX activity per bag was 127.62% (+/-38.23) with the mean volume of 164.28 mL (+/-52.23). Statistically significant difference on volume (P = 0.000) was found across the three sources resulting to a significant variation of the actual FIX content (P = 0.000).

Thawed cryoprecipitate stored for 6 h at room temperature: a potential alternative to factor VIII concentrate for continuous infusion.

Continuous infusion (CI) of factor VIII concentrates has been demonstrated to be cost-effective method in maintaining stable levels of FVIII activity in haemophilia A patients with major bleeding or undergoing major surgery. Cryoprecipitates remain the major source of FVIII in developing countries-like the Philippines because of limited availability and high cost of concentrates. To support the use of cryoprecipitate as alternative to FVIII concentrate for CI in centres with no factor concentrates, FVIII levels in 37 bags of random cryoprecipitate were measured at 0, 2, 4 and 6 h after thawing, kept at room temperature with bacteriological culture studies performed on the sixth hour. The mean FVIII content at hour 0 was 108.10 U per bag. Type ORh+ blood had lower FVIII content (+/-78.91 U per bag) compared with blood types ARh+ (+/-121.64 U per bag) and BRh+ (+/-117.04 U per bag). The units stored <6 months had higher FVIII content (+/-117.74 U per bag) compared with those stored for over 6- but <12-months (+/-66.77 U per bag). The mean rate of decline of FVIII activity at 2, 4 and 6 h was statistically significant at 10.35% (P = 0.000), 21.49% (P = 0.000) and 29.41% (P = 0.000) from baseline, respectively, using the paired t-test. Similar finding was found across different blood types and storage duration. Only one of 37 bags grew Staphylococcus aureus on day 10 of incubation.