TY - JOUR
T1 - Thrombocytopenia and complement activation under recombinant TNFα/IFNγ therapy in man
AU - Michelmann, I.
AU - Böckmann, D.
AU - Nürnberger, W.
AU - Eckhof-Donovan, S.
AU - Burdach, S.
AU - Göbel, U.
PY - 1997/4
Y1 - 1997/4
N2 - Infusions of recombinant human tumor necrosis-alpha plus recombinant human interferon-gamma (rhTNFα/rhIFNγ) were assessed in two patients with Ewing's sarcoma. We analyzed platelet count, coagulation and the terminal complement complex (TCC). During cycles with continuous rhTNFα-infusions we found a rapid, marked decrease of platelet count (minus 90% of initial values) and a simultaneous increase of TCC (plus 84% of initial values) at day 4. At days 5-7 a spontaneous increase of platelet count and decrease of TCC were visible. Short-term infusion led to a milder, continuous decrease of platelet counts and to a moderate, progressive increase of TCC at days 5-7. Bleeding occurred only as petechia and mild hemoglobinuria. There was no effect related to the dosage of rhTNFα or rhIFNγ. Relevant differences were seen only in the variable time courses of rhTNFα application. Ex vivo analysis of one patient's platelets showed no cytokine related effect on induced aggregation according to Born. Additionally, we analyzed in vitro effects of the cytokines on platelet count, platelet aggregation, and the assembly of TCC in platelet membranes. No effects were found after incubation of platelet-rich plasma (PRP) with 1000pg/ml rhTNFα and/or 50 pg/ml rhIFNγ. Fluid-phase and membrane-bound TCC did not change after incubation of PRP with cytokines. A slightly time-dependent increase of TCC without alteration of platelet count and platelet function did not agree with the assumption of a direct injury to platelets. We assume a cytokine-mediated role of the endothelium in platelet loss.
AB - Infusions of recombinant human tumor necrosis-alpha plus recombinant human interferon-gamma (rhTNFα/rhIFNγ) were assessed in two patients with Ewing's sarcoma. We analyzed platelet count, coagulation and the terminal complement complex (TCC). During cycles with continuous rhTNFα-infusions we found a rapid, marked decrease of platelet count (minus 90% of initial values) and a simultaneous increase of TCC (plus 84% of initial values) at day 4. At days 5-7 a spontaneous increase of platelet count and decrease of TCC were visible. Short-term infusion led to a milder, continuous decrease of platelet counts and to a moderate, progressive increase of TCC at days 5-7. Bleeding occurred only as petechia and mild hemoglobinuria. There was no effect related to the dosage of rhTNFα or rhIFNγ. Relevant differences were seen only in the variable time courses of rhTNFα application. Ex vivo analysis of one patient's platelets showed no cytokine related effect on induced aggregation according to Born. Additionally, we analyzed in vitro effects of the cytokines on platelet count, platelet aggregation, and the assembly of TCC in platelet membranes. No effects were found after incubation of platelet-rich plasma (PRP) with 1000pg/ml rhTNFα and/or 50 pg/ml rhIFNγ. Fluid-phase and membrane-bound TCC did not change after incubation of PRP with cytokines. A slightly time-dependent increase of TCC without alteration of platelet count and platelet function did not agree with the assumption of a direct injury to platelets. We assume a cytokine-mediated role of the endothelium in platelet loss.
KW - Complement activation
KW - Ewing tumor
KW - Interferon-gamma
KW - Platelet biology
KW - Tumor necrosis factor-alpha
UR - http://www.scopus.com/inward/record.url?scp=1842336908&partnerID=8YFLogxK
U2 - 10.1007/s002770050279
DO - 10.1007/s002770050279
M3 - Article
C2 - 9174546
AN - SCOPUS:1842336908
SN - 0939-5555
VL - 74
SP - 179
EP - 184
JO - Annals of Hematology
JF - Annals of Hematology
IS - 4
ER -