Thromb Haemost 1997; 77(01): 053-056
DOI: 10.1055/s-0038-1655906
Clinical Studies
Schattauer GmbH Stuttgart

Fibrinolytic and Coagulant Responses to Regional Limb Perfusions of Tumor Necrosis Factor, Interferon-γ, and/or Melphalan

Paula Merryman
The Hematology Section, Clinical Pathology Department, Warren G. Magnuson Clinical Center, Bethesda, MD, USA
,
Susan H Tannenbaum
The Hematology Section, Clinical Pathology Department, Warren G. Magnuson Clinical Center, Bethesda, MD, USA
,
Harvey R Gralnick
The Hematology Section, Clinical Pathology Department, Warren G. Magnuson Clinical Center, Bethesda, MD, USA
,
Kelvin Yu
1   The Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
,
W Scott Arnold
1   The Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
,
H Richard Alexander
1   The Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
,
Douglas Fraker
1   The Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
,
McDonald K Horne III
The Hematology Section, Clinical Pathology Department, Warren G. Magnuson Clinical Center, Bethesda, MD, USA
› Author Affiliations
Further Information

Publication History

Received 11 June 1996

Accepted after resubmisssion 01 October 1996

Publication Date:
11 July 2018 (online)

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Summary

Regional limb perfusion with antineoplastic agents stresses the local vasculature in a variety of ways. However, by monitoring the perfusates from limbs treated with melphalan alone or with melphalan plus tumor necrosis factor (TNF) and interferon-γ (IFN-γ), we were able to distinguish the effect of the cytokines on the observed coagulant and fibrinolytic responses. We collected samples of effluent from a series of lower extremities that were perfused with the cytokines and/or melphalan as treatment for localized melanoma. Both regimens produced statistically significant evidence of coagulant and fibrinolytic activation. However, limbs receiving cytokines in addition to the melphalan responded with a sharper rise in tissue plasminogen activator (tPA) and plasmin (plasmin-antiplasmin complexes [PAP]) than limbs treated with melphalan alone. Evidence of thrombin formation (prothrombin fragment 1+2 [FI+2], thrombin-antithrombin complexes [TAT]) was also greater when the cytokines were included, although the response was delayed and less consistent than the fibrinolytic activation.