Augmented procoagulant activity in cancer patients, treated with recombinant interferon-γ in addition to recombinant tumor necrosis factor-α and melphalan

André B. Mulder, Jan H. Zwaveling, W. Martin Smid, John K. Maring, Robert J. Van Ginkel, Armand R.J. Girbes, Heimen Schraffordt Koops, Jan Van Der Meer

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Several investigators have reported that interferon-gamma (IFNγ) can alter tumor necrosis factor alpha induced effects in vitro, We assessed in vivo effects of recombinant interferon-gamma (rIFNγ) on recombinant tumor necrosis factor-alpha (rTNFα) induced activation of systemic blood coagulation in a non-randomized study in 20 consecutive cancer patients. Eight patients were treated with rIFNγ prior to and during hyperthermic isolated limb perfusion with rTNFα and melphalan (IFNγ group). They were compared with twelve patients who did not additionally receive rIFNγ (non-IFNγ group). Before start of perfusion, higher levels of TNFα, F1+2 and TAT levels were found in the IFNγ group. Fibrinogen and ATIII levels tended to be lower in this group. High TNFα 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 IFNγ 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 IFNγ group. In conclusion our data confirm a strong activation of coagulation induced by rTNFα in cancer patients. They suggest that rIFNγ may lead to a slight activation of coagulation and augments TNFα induced procoagulant activity. These effects may be due to rIFNγ induced sustained monocytic TF activity.

Original languageEnglish
Pages (from-to)897-901
Number of pages5
JournalThrombosis and haemostasis
Issue number6
Publication statusPublished - 1 Dec 1996

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