Influence of high-dose aprotinin treatment on blood loss and coagulation patterns in open-heart surgery

Intraoperative administration of the proteinase Inhibitor aprotinin
causes reduction in blood loss and homologous blood requirement in
patients undergoing cardiac surgery. To ascertain the blood-saving
effect of aprotinin and to obtain further information about the
mode of action, 40 patients undergoing primary myocardial
revascularization were randomly assigned to receive either
aprotinin or placebo treatment. Aprotinin was given as a bolus of 2
X 105 kallikrein inactivator units (KIU) before surgery followed by
a continuous infusion of 5 X 105 KIU/h during surgery.
Additionally, 2 X 105 KIU were added to the pump prime. Strict
criteria were used to obtain a homogeneous patient selection. Total
blood loss was reduced from 1,431 +/- 760 ml in the control group
to 738 +/- 411 ml in the aprotinin group (P < 0.05) and the
homologous blood requirement from 838 +/- 963 ml to 163 +/- 308 ml
(P < 0.05). In the control group, 2.3 +/- 2.2 U of homologous
blood or blood products were given, and in the aprotinin group,
0.63 +/- 0.96 U were given (P < 0.05). Twenty-five percent of
patients in the control group and 63% in the aprotinin group did
not receive banked blood or homologous blood products. The
activated clotting time as an indicator of inhibition of the
contact phase of coagulation was significantly Increased before
heparinization in the aprotinin group (141 +/- 13 s vs. 122 +/- 25
s) and remained significantly Increased until heparin was
neutralized after cardiopulmonary bypass (CPB). The concentration
of the thrombin-antithrombin III complex was significantly
decreased at the end of CPB in the aprotinin group, indicating less
thrombin generation in the aprotinin-treated group. The total
concentration of the fibrinogen-fibrin split products (FSP) and the
split products of the cross-linked fibrin (D-dimers) were also
significantly reduced due to attenuated proteolytic activities of
thrombin and plasmin. The results of the fibrin plate assay
revealed higher fibrinolytic activity during CPB in the control
group. The results demonstrate the beneficial effect of high-dose
aprotinin treatment on blood loss and homologous blood requirement.
This effect can be attributed to the inhibition of the contact
phase of coagulation and the consequently reduced thrombotic and
fibrionolytic activity during and after CPB.