Fibrinolytic and coagulant responses to regional limb perfusions of tumor necrosis factor, interferon-gamma, and/or melphalan.
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-gamma (IFN-gamma), 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 [F1 + 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.
Merryman
P
P
Clinical Pathology Department, Warren G. Magnuson Clinical Center, Bethesda, MD, USA.
Tannenbaum
S H
SH
Gralnick
H R
HR
Yu
K
K
Arnold
W S
WS
Alexander
H R
HR
Fraker
D
D
Horne
M K
MK
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects*; D005121:Extremities; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy*; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D010477:Perfusion; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D008558:Melphalan