Thrombin Generation after Abrupt Cessation versus Weaning over 8 hours of Continuous Infusion of Unfractionated Heparin in ICU-patients after Discontinuation of Continuous Venovenous Hemofiltration (CVVH).

The F1K-MC-EVBR-trial (Xigris and Prophylactic hEparin in Severe Sepsis:
XPRESS) study demonstrated that adult patients with severe sepsis receiving
drotrecogin alfa (activated) with concomitant heparin treatment had an absolute
28 day mortality reduction of 3.6% compared to treatment with drotrecogin alfa
(activated) combined with placebo. Evaluation of subgroups showed that patients
receiving heparin at baseline who are assigned to treatment with placebo have a
higher 28-day mortality (35.6%) and a higher incidence of venous
thromboembolism (VTE) and other serious (thrombotic) adverse events than
patients receiving heparin at baseline assigned to study treatment with heparin
(26.9%). Patients who did not receive heparin previous to study enrollment
performed similar to the latter group (placebo 28.9%, study-heparin 29.5%)
[unpublished data]. A possible explanation for this difference in mortality and
(thrombotic) adverse events could be that thrombin generation is increased as a
result of discontinuing heparin treatment.

Our hypothesis is that rebound thrombin generation occurs in ICU-patients after
abrupt cessation of heparin treatment in terms of elevation of
coagulation-markers and reduction fibrinolysis-markers. IV weaning of heparin
reduces this rebound thrombin generation.

The objective op this study is to answer the following questions:
-Is thrombin generation increased after abrupt cessation of intravenous
unfractionated heparin after discontinuation of CVVH?
-Is there a difference in increase in thrombin generation after abrupt
cessation of heparin versus intravenous weaning over a period of 8 hours?

Prospective, randomized study.

In one group of patients Heparin infusion will be stopped simultaneous to
stopping of CVVH.
In the other group of patients UFH infusion will be reduced to 50% from the
previous infusion rate. After 4 hours the infusion rate will be reduced again
by 50% (25% of original infusion rate) and discontinued 4 hours later. Blood
samples will be taken at specific intervals to evaluate thrombin generation.

The risks associated with participation are minimal. Bloodsamples (7 x 10 ml)
will be taken from an already present arterial catheter and IV administration
of heparine will be either stopped or continued for 8 hours in a
medical-surgical ICU setting in an academic hospital. This prolonged
administration of heparin increases bleeding risk.
No direct benefit for the individual patient is to be expected from
participation however extending the knowledge of the effects of heparin on ICU
patients could benefit the entire patient group.