Hemostasis initiates a wound healing process and stops bleeding of blood within a damaged tissue, an important process in human and animal systems. However, this process needs to revert temporarily during surgery and analyze the clotting mechanism. In the past decade, heparin has been used widely as an anticoagulant in surgery to prevent unwanted blood clotting as it is not expensive, not difficult to control, lack of suitable replacement as well as less harmful to the human. However, heparin has several disadvantages, which include thrombocytopenia and non-specific plasma binding. Moreover, using heparin it may lead dysfunction and platelet aggregation. In this overview, potential clotting factors and anticoagulants are reviewed and special focus was given to get more insights.
There are different clotting factors present in blood, carries the clotting cascade and excessive bleeding may cause a deficiency in the clotting Diagnosis of this deficiency in clotting drastically reduces the potential fatality. For enabling a sensor to detect the clotting factors, suitable probes such as antibody and aptamer have been used to capture these targets on the sensing surface. Two major clotting factors were widely studied for the diagnosis of clotting deficiency, which includes factor IX and thrombin. In addition, factor IX is considered as the substitute for heparin and the prothrombotic associated with the increased thrombin generation are taking into account their prevalence. The biosensors, surface plasmon resonance, evanescent-field-coupled waveguide-mode sensor, metal-enhanced PicoGreen fluorescence and electrochemical aptasensor were well-documented and improvements have been made for high-performance sensing. We overviewed detecting factor IX and thrombin using these biosensors, for the potential application in medical diagnosis.
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.
KEYWORDS: albumin fusion proteins; factor IX; haemophilia B; orthopaedic surgery; recombinant fusion proteins