Perioperative PAI-1 values in surgically treated colorectal carcinoma patients under low molecular weight heparin...

We have monitored the perioperative changes of plasmatic values of plasminogen activator inhibitor -1 (PAI-1) in colorectal carcinoma patients depending on the stage of disease and the use of prophylactic low molecular weight heparin (LMWH).

One hundred 100 colorectal carcinoma patients (64 men and 36 women) with average age of 60, in two randomized groups. All patients were surgically treated using the same technique and in all cases adenocarcinoma was confirmed. Two hours before the surgery, the first group (48 patients) received LMWH-nadroparin calcium in doses of 0.3 or 0.4 mL sc, while the second group (52 patients) received it eight hours after the surgery. Following the surgery, Nadroparin calcium was administered daily using the same dose as before. Blood samples were collected: before the surgery, 10 minutes after the first surgical incision, 8 hours after the surgery, and on the 3rd, 5th and 10 th postoperative days. The staging of the disease (according to the Dukes classification) was compared with the patients' blood plasma concentration of PAI-1. Statistical analysis using the c2 test, the LSD test, Wilcoxon and Mann-Whitney test was performed.

Adenocarcinoma was patohistologicaly confirmed in all 100 subjects. According to the Dukes classification, 6 patients had stage A, 51 had stage B, and 43 had stage C. PAI-1 measurements showed that baseline measurements were within normal boundaries for both groups. Ten minutes after the first incision a sharp decline of PAI-1 values in the plasma of both patient groups was observed, which could be explained by the use due to the effect on t-PA secreted from the damaged endothelium. PAI-1 values in both groups of subjects have returned to starting (baseline) values, and remained within these values through the third, fourth and fifth measurement in both groups of patients. There was no difference between the two randomized groups which leads to the conclusion that the application of LMWH does not affect PAI-1 values. A statistically significant difference of the tested parameters according to the Dukes classification was obtained only for parameter PAI-1 for pairs Dukes A:B as well as Dukes A:C. A statistically significant correlation was found for plasma values of fibrinolysis inhibitor PAI-1 according to the Dukes classification, but it does not correlate to the tumor invasion through intestinal wall structures. The reason for the statistically significant increase of PAI-1 values in the Dukes A stage remains unclear.

By activating t-PA and blocking PAI-1, Nadroparin calcium perioperatively makes the haemostasis system stable and balanced.