GISAP a multicentre open study was aimed to confirm the feasibility and safety of iloprost treatment in normal clinical practice and to identify subgroups of patients with severe POAD more likely to benefit from iloprost treatment than others. One hundred forty six patients were treated at the maximum tolerated dose of iloprost up to 2 ng/kg/min, 6 hours infusion per day, for a minimum of 3 weeks and a maximum of 8 weeks. Clinical efficacy was assessed by rest pain reduction, analgesic consumption, healing of trophic lesions, walking ability. A significant improvement of the efficacy parameters was recorded during and at the end of treatment: no difference between diabetics and non diabetics, stage III and IV patients was observed. After one year follow-up 10% major amputation and 6.8% death were recorded, these events were balanced between the diabetic and non diabetic patients. Overall 80% of the patients at risk of amputation at entry to the trial were alive with a viable limb after one year. Tolerability resulted quite acceptable. Even with the limitation of an open trial, it has been confirmed the therapeutic potential of iloprost in the treatment of POAD patients.

Summary This study investigated whether the pre‐surgical plasma levels of TAT and F1 + 2 of patients undergoing major surgery for localized tumours could identify patients at higher risk of thrombosis, and how heparin prophylaxis affected in vivo coagulation after cancer surgery. We measured the pre‐and post‐operative levels of TAT, F1+2, total factor VII (FVIIt) and zymogen FVII (FVIIz) in 117 cancer patients, with and without heparin prophylaxis. The end points of this study were DVT. ihitially detected by 125I‐fibrinogen uptake test and confirmed by ascending venography. Pre‐operative [TAT] and [Fl+2] of the cancer patients were significantly higher than those of age‐matched control subjects (n=50) (P<0.005 and P<0.05, respectively): pre‐operative [FVII] was not significantly different. One of the 83 patients receiving prophylaxis, and 8/34 not receiving prophylaxis developed post‐operative DVT. Of the parameters evaluated, only the pre‐operative [TAT] > 3. 5 ng/ml identified patients at higher risk for post‐operative DVT. Heparin reduced plasma TAT levels and FVII consumption following surgery, suggesting that heparin modulates coagulation associated with cancer surgery. The results of this study also suggest that the pre‐operative [TAT] may identify patients with higher risk for post‐operative DVT.

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.