Mode of action of recombinant factor VIIa and the use in severe haemorrhage states
Abstract
Background: Diffuse non-surgical life threatening haemorrhages are common cause of death in surgical patients. They are usually caused by a disorder of haemostasis of different aetiologies. When the haemorrhage can not be stopped with standard measures, we can resort to the rFVIIa preparation. Numerous studies have proven the effectiveness of rFVII in treating of untractable haemorrhages as well as in preventing the haemorrhages in patients with known blood coagulation disorders. When high dosages of rFVIIa, which binds to tissue factor (TF), are administered, huge quantity of thrombin forms. Thrombin affects fibrinogen and at the same time activates huge quantity of factor XIII and of Thrombin Activatable Fibrinolysis Inhibitor (TAFI). The created fibrin clot is more resistant to fibrinolysis than a normal one. It is also important to know that rFVIIa in high concentrations can activate factors IX and X on the surface of thrombocytes, independently of TF. The effect of rFVIia is limited to the location of injury but despite this there is a possibility of thrombosis. Because rFVIIa binds not only to the TF containing cells, but also to injured cells containing phospatidyl serine, caution is needed where septic patients, patients with extensive tissue necrosis or with atherosclerotic changes are concerned. The following facts must hold true in order for rFVIIa to be administered: the haemorrhage is non-surgical and does not stop after application of standard measures; the patient does not suffer from hypothermia; the platelets value is higher than 50 × 109/l (except when thrombocytopenia is the indication for use); the fibrinogen value is higher than 50 mg/l; blood pH is higher than 7.2. The initial intravenous dosage of rFVIIa should be 90–120 μg/kg; if the haemorrhage does not stop, we administer the second dosage, 90–100 μg/kg, in the interval of up to 2 hours. There is no specific laboratory test; however it is known that, when using rFVIIa, the value of prothrombin time (PT/INR) normalizes or reaches even supraphysiological values.
Conclusions: rFVIIa was successfully used in many surgical patients with diffuse bleeding. Despite this several additional studies have to be carried out in order to find out other, for now still not known adverse events and to determine conditions for the optimal efficacy of the preparation.
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