Augmented Procoagulant Activity in Cancer Patients, Treated with Recombinant Interferon-γ in Addition to Recombinant Tumor Necrosis Factor-α and Melphalan

Summary

Several investigators have reported that interferon-gamma (IFN³) can alter tumor necrosis factor alpha induced effects in vitro. We assessed in vivo effects of recombinant interferon-gamma (rIFN³) on recombinant tumor necrosis factor-alpha (rTNF±) induced activation of systemic blood coagulation in a non-randomized study in 20 consecutive cancer patients. Eight patients were treated with rIFN³ prior to and during hyperthermic isolated limb perfusion with rTNF± and melphalan (IFN³ group). They were compared with twelve patients who did not additionally receive rIFN³ (non-IFN³ group)

Before start of perfusion, higher levels of TNFa, F₁₊₂ and TAT levels were found in the IFN³ group. Fibrinogen and ATIII levels tended to be lower in this group. High TNF± levels, due to leakage during perfusion, were associated with activation of coagulation in all patients, that became obvious after the end of perfusion, when heparin treatment had been antagonized. Activation, measured by increased F₁₊₂ and TAT levels, was significantly stronger in the IFN³y group. Monocytic TF remained low, possibly due to shedding of TF positive vesicles and/or sequestration of TF positive activated monocytes against the vessel wall. In both groups F₁₊₂ and TAT levels declined 24 h after the perfusion, whereas monocytic TF increased to levels that were higher in the IFN³ group.

In conclusion, our data confirm a strong activation of coagulation induced by rTNF± in cancer patients. They suggest that rIFN³ may lead to a slight activation of coagulation and augments TNFa induced procoagulant activity. These effects may be due to rIFN³ induced sustained monocytic TF activity.

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