Clotting system activation in patients with cancer undergoing major surgery: The role of heparin prophylaxis

Abstract

Hemostatic system activation occurs in cancer patients and the risk of postoperative venous thrombosis is increased when they undergo major surgery. Preventing this complication is of interest, since surgery is the first line therapy in many tumors. To estimate clotting activation in the presence and the absence of heparin prophylaxis (either UFH or LMW), we have measured, at different time intervals from surgery, the plasma levels of TAT complex and of both total (FVIIt) and xymo@l FVII (NIIz) in 117 patients with cancer (80% of the GI tract, 20% of lung, breast, kidney and thyroid; 75 males and 42 females, age range 40-60). Patients were on prophylaxis from day 0 (day of surgery) through day 7 and were divided in 3 8roups (G): Gl (n-39), on UFH 5000 I.U./b.i.d.; 02 (n-44), on LMW CY216 7500 I.C.U/dl and G3 (n-34), no prophylaxis. TAT complex was determined by the Enxygnost TAT kit (Istituto Behring), FVIIt by the Asserachrome VIk Ag (Diagnostica Stage) and FVIIz by an Elisa using the MoAb 23 l-7 specific to FVIIz (provided by EA. Ofosu, Hamilton). Tests were performed on day (D): -1, 0, 1,3,5 and 7; results are expressed as mean zt SD. Gn -1 the 3 parameters were not significantly different among Gl, G2 and G3 (TAT 3.4& 2.9; 3.2 * 1.7 and 4.2 i 2.7 @ml; FVIIt = 1 f 0.2; I * 0.2 and 0.9 f 0.2 U/ml; FVlIz 1 f 0.2; 1 f 0.2 and 0.9 f 0.2 U/ml; respectively). On D 0 all groups had an increase of TAT levels (G 1 30 f 46; G2 2 1 i 23; G3 15 * 23 q/ml, p ns.), followed (from day 1 on) by a decmase in G I and G2, but by a htrther increase in G3; on 3 and 7 values of G3 were significantly (p < 0.05) higher (24 f 35 and 2 1 r 35 m G2 = 1.07 f 0.3; G3 0.95 ztO.2 U/ml), in contrast FVIIz remained significantly lower in G3 (0.78 & 0.2 U/ml, p c 0.05) as compared to G 1 ( 1.1 i 0.2 U/ml) and G2 ( 1.1 f 0.4 U/ml), indicating that in 03 a higher proportion of FVIIt was activated FVII protein. The incidence of thrombosis, assessed by venography, was: 0139 in G I, l/44 in G2 (2%), 8/34 in G3 (23%). In conchision, although these results need to be conlirmed by means of appropriate prospective clinical trials, our study on 117 patients with solid tumors suggests that: 1. heparin prophylaxis can modulate the generation of TAT complex and activated FVll after major surgery; 2. evaluation of these parameters can possibly be of aid to identify those individuals at particularly high risk of post-operative thrombosis.