Correspondence  |   April 2003
Use of Recombinant Activated Factor VII in Patients with Severe Coagulopathy and Bleeding
Author Affiliations & Notes
  • Anthony M.-H. Ho, M.Sc., M.D., F.R.C.P.C., F.C.C.P.
  • *Prince of Wales Hospital, Shatin, NT, Hong Kong.
Article Information
Correspondence   |   April 2003
Use of Recombinant Activated Factor VII in Patients with Severe Coagulopathy and Bleeding
Anesthesiology 4 2003, Vol.98, 1025-1026. doi:
Anesthesiology 4 2003, Vol.98, 1025-1026. doi:
To the Editor:—
The emergence of recombinant activated factor VII (rFVIIa) as potentially a panhemostatic agent that will “save the day” for patients with severe hemorrhage is truly exciting. The positive experiences reported by Tobias, 1 Slappendel et al.  , 2 and Svartholm et al.  3 add valuable data to help define the role of this agent in clinical practice. With time, however, it is likely that we will find out that, in addition to cost advantages, there are problems and limitations associated with the use of rFVIIa. Just as antibiotics have not eliminated the need for infection control and for expert management of infections in patients, rFVIIa will not replace the need for aggressive prevention and reversal of coagulopathy in patients.
By definition, dilutional coagulopathy suggests that insufficient coagulation factors have been given during the course of severe hemorrhage and blood product replacement. It is therefore theoretically preventable and reversible, mainly with the use of adequate amounts of fresh frozen plasma (FFP). In the first case presented by Tobias, 1 the patient was clearly having significant ongoing bleeding, as indicated by chest tube drainage, deterioration of the coagulation indices and hematocrit, and other evidence. When the international normalized ratio reached 2.0, plasma factor concentrations had probably decreased to just slightly above 30% of normal. 4 At that point, the inadequate use of FFP continued with the transfusion of only 1 unit of FFP in the face of ongoing bleeding.
In Tobias’1 second case, the patient's coagulation indices at 12 h postoperatively indicated severe dilutional coagulopathy, suggesting that in the ensuing hours little or no coagulation factors were given in spite of continuing hemorrhage. From our experience and on the basis of calculations, the prevention of severe dilutional coagulopathy involves the use of FFP by the time the coagulation factors reach 40–50% of normal, and FFP must be given henceforth if significant bleeding continues, at a ratio of at least 1 unit of FFP for every unit of packed erythrocytes transfused.
In regard to the case presented by Slappendel et al.  , 2 we are surprised that the patient's hemostatic parameters were not at least partially corrected before the elective surgery, especially in light of the type of surgery being performed and the use of spinal anesthesia. Intraoperatively, the use of cell saver does not prevent further dilution of coagulation factors, as is clearly reflected in the abnormal laboratory results. The appropriate action should have been the transfusion of FFP before surgery or, at the very least, as soon as bleeding started.
In the case presented by Svartholm et al.  , 3 the patient had received 19 l (equivalent by our calculation to 63 units) of packed erythrocytes and 4.5 l (18 units) of FFP. If we assume that some crystalloid or colloid solution had also been given (such that the patient's hematocrit was not excessively high due to the large amount of packed erythrocytes and the relatively small volume of FFP), then using this amount of FFP equaled transfusing whole blood with a plasma coagulation factor concentration of 30% or less. In the face of severe hemorrhage, such a low level of FFP dosing is inadequate. Prothrombin complex concentrate does not contain all of the factors. Exacerbating the situation was that another 8 l of packed erythrocytes was given over the next 11 h, with no apparent supplementation with FFP. With coagulation factor concentrations low and continuing to dwindle, the reliance on pharmacologic supplements rather than on coagulation factor replenishment seemed inappropriate.
We respectfully suggest that in all of the aforementioned cases 1–3 the patients might have suffered from an underdosing of FFP. This likely resulted in the transfusion of increased amounts of blood products. While we are excited by the impressive evidence accumulating on the use of rFVIIa in “refractory” bleeding, we wish to caution against an excessive and premature reliance on the use of this (or any new) technology to bail us out of difficult situations that we could have avoided getting into in the first place.
Tobias JD: Synthetic factor VIIa to treat dilutional coagulopathy during posterior spinal fusion in two children. A nesthesiology 2002; 96: 1522–5Tobias, JD
Slappendel R, Huvers FC, Benraad B, Novakova I, van Hellemondt GG: Use of recombinant factor VIIa (NovoSeven) to reduce postoperative bleeding after total hip arthroplasty in a patient with cirrhosis and thrombocytopenia. A nesthesiology 2002; 96: 1525–7Slappendel, R Huvers, FC Benraad, B Novakova, I van Hellemondt, GG
Svartholm E, Annerhagen V, Lanne T: Treatment of bleeding in severe necrotizing pancreatitis with recombinant factor VIIa. A nesthesiology 2002; 96: 1528Svartholm, E Annerhagen, V Lanne, T
Reiss RF: Hemostatic defects in massive transfusion: rapid diagnosis and management. Am J Crit Care 2000; 9: 158–67Reiss, RF