Perioperative dilutional coagulopathy treated with fresh frozen plasma and fibrinogen concentrate: a prospective randomized intervention trial.
OBJECTIVE
Treatment of dilutional coagulopathy by transfusing fresh frozen plasma (FFP) remains sub-optimal. We hypothesized that partial replacement of transfused FFP by fibrinogen concentrate results in improved coagulant activity and haemostasis. This was tested in a controlled clinical intervention trial with patients experiencing massive bleeding during major surgery.


METHODS
Patients undergoing major elective surgery were treated according to current protocols. When transfusion with FFP was required, patients were randomized as follows: group A received 4 units FFP and group B received 2 units FFP plus 2 g fibrinogen concentrate. Blood samples were taken before and after the intervention. Analysts were blinded to the treatment type.


RESULTS
Group A (B) consisted of 21 (22) patients, in 16 (17) of whom bleeding stopped after intervention. Plasma fibrinogen increased significantly more in group B (0·57 g/l) than in group A (0·05 g/l). However, levels of prothrombin and factors VIII, IX and X increased more in group A than in group B. Rotational thromboelastometry (ROTEM) of whole blood and plasma revealed improved fibrin clot formation in group B but not in group A. Thrombin generation [calibrated automated thrombogram (CAT)] in plasma increased more in group A. Principal parameters determining whole-blood thromboelastometry were the fibrinogen level and platelet count. In vitro addition of fibrinogen and prothrombin complex concentrate to pre-intervention samples restored both ROTEM and CAT parameters.


CONCLUSIONS
Partial replacement of transfused FFP by fibrinogen increases fibrin clot formation at the expense of less improved thrombin generation. Coagulation factors other than fibrinogen alone are required for full restoration of haemostasis.
Department of Anesthesiology, CARIM, Maastricht University Medical Center, Maastricht, The Netherlands.
M D
MD
Lancé
M
M
Ninivaggi
S E M
SE
Schols
M A H
MA
Feijge
S K
SK
Oehrl
G J A J M
GJ
Kuiper
M
M
Nikiforou
M A E
MA
Marcus
K
K
Hamulyak
E C M
EC
van Pampus
H
H
ten Cate
J W M
JW
Heemskerk
D000368:Aged; D001778:Blood Coagulation Disorders / Q000097:blood / Q000209:etiology / Q000628:therapy*; D001779:Blood Coagulation Factors / Q000378:metabolism; D016913:Blood Component Transfusion; D016063:Blood Loss, Surgical / Q000517:prevention & control; D005260:Female; D005337:Fibrin / Q000187:drug effects / Q000378:metabolism; D005340:Fibrinogen / Q000627:therapeutic use*; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000378:metabolism; D010976:Platelet Count; D019106:Postoperative Hemorrhage / Q000517:prevention & control / Q000628:therapy; D011446:Prospective Studies; D013514:Surgical Procedures, Operative / Q000009:adverse effects* / Q000379:methods*; D013916:Thrombelastography
D001779:Blood Coagulation Factors; D005337:Fibrin; D005340:Fibrinogen