Intervention pilot study with FFP or the combination of fibrinogen concentrate and FFP to patients with massive (post) operative bloodloss.

Treatment of patients with massive bleeding upon surgery cosists of infusion of
cristalloids, colloids, thrombocyte-concentrates and erythrocyte-concentrates.
Additionally fresh frozen plasma (FFP) will be transfused, this FFP is diluted
with anticoagulans and therefore FFP has a lower concentration of coagulation
factors in comparison with undiluted plasma.
Because of the fact that these patients are treated with a combination of the
above mentioned infusion fluids, an important dilution of coagulation factors
will occur together with the coagulation ability of plasma of these patients.
The dilution is only partly compensated by FFP transfusion, and as a
consequence part of the patients will continue bleeding due to insufficient
coagulation capacity. There is an increased interest for treatment of these
acquired coagulation disorders with coagulation factor concentrates.
Fibrinogen, which is involved in the clot formation, is the first coagulation
factor that will be deficit in case of massive bleeding and dilution.

In this study we will try to obtain the rise in value of fibrinogen concentrate
infusion in combination with FFP vs FFP transfusion in surgery patients with
massive peri-operative bleeding problems and cardiothoracic surgery patients
after heart valve replacement with massive post-operative bleeding problems.
The administration of fibrinogen concentrate (besides the FFP) can cause stop
of bleeding in an earlier phase, so that the total amount of bloodtransfusion
will be reduced. The recovery after surgery will be influenced positively.
Furhtermore the advantages of new laboratory tests to determine coagulation
ability and fibrin clot formation, will be studied and compared with
conventional coagulation times (insensitive for measurements of current
hemostasis) in favour of future transfusion policy.

Potential patients will be asked for informed consent before surgery, general
surgery patients with massive bloodloss during surgery will be randomised
between FFP and a lower dosage of FFP with fibrinogen concentrate.
Cardiothoracic surgery patients after heart valve surgery with massive
post-operative bleeding problems will be randomised between DDAVP and
fibrinogen concentrate. During the study 5 cc citrate blood will be taken twice
from each patient extra, however patients do not need to undergo an extra
invasive procedure.

DDAVP injection (standard therapy of cardiothoracic patients with massive
post-operative bleeding problems) vs. an combination of DDAVP with fibrinogen
concentrate.
FFP transfusion (standard therapy of general surgery patients with massive
peri-operative bleeding problems) vs. an combination of a lower dosage of FFP
with fibrinogen concentrate.

To obtain the extra tube of blood before and after the intervention, a patient
does not need to undergo an extra invase procedure, because at these time
points blood is taken anyway. The additonal amount of blood is needed to
determine additional coagulation factor concentrations, thrombin generation and
thromboelastography. The injection of fibrinogen occurs in small volumes after
which the treatment effect will appear immediately. In this way no time is lost
for the standard therapy to be given when there is no effect of the fibrinogen
concentrate.