We investigated the ability of human lung cancer cells of different histological subtypes to cause platelet aggregation. Tumor-cell-induced platelet aggregation (TCIPA) was studied in vitro in 13 human lung cancer cell lines [small-cell lung cancer (SCLC), squamous-cell lung cancer, large-cell lung cancer, adenocarcinoma and alveolar-cell lung cancer]. Three tumor cell lines failed to aggregate platelets in platelet-rich plasma, whereas platelet aggregation was induced by 12 cell lines when added to washed platelets and minimal amounts of platelet-poor plasma (0.5% v/v). The thrombin antagonist hirudin inhibited TCIPA in non-small-cell lung cancer cell lines (NSCLC). In SCLC, TCIPA was fully abolished only when the ADP scavenger apyrase was added to hirudin. Thus ADP and thrombin generation by these tumor cell lines are responsible for platelet aggregation. The ability to activate platelets independently of coagulation factors VII and X was demonstrated for 8 cell lines. Electron-microscopically, direct tumor-cell/platelet contact was found to be the initiating mechanism of TCIPA in SCLC, whereas tumor-cell/platelet contacts in NSCLC could only be observed at the peak of the aggregation curve. Lung cancer cells activate platelets in vitro by generation of thrombin and/or ADP.

Pancreatic carcinoma cells are able to induce platelet aggregation via activation of thrombin. This might support metastasis in pancreatic cancer and possibly explain the incidence of thrombosis in this tumor.

The activation markers (means +/- SEM) were lower in the 33 responders (RSP; complete or partial remission) than in the 66 non-responders (NRSP): TAT 3.96 +/- 0.48 vs. 9.69 +/- 1.57 micrograms/l (P < 0.001), and F1 + 2 1.09 +/- 0.09 vs. 1.64 +/- 0.25 nmol/l (P < 0.05). TAT levels were > 6 micrograms/l in 30 of 66 (45%) NRSP, but only 4 of 33 (12%) RSP. 88% of patients with TAT < or = 6 micrograms/l achieved remission, and 45% with TAT > 6 micrograms/l (P = 0.0014). In the subgroup of 46 patients with advanced disease, the six RSP showed lower TAT than the 40 NRSP: 4.65 +/- 0.94 vs. 11.92 +/- 2.49 micrograms/l (P < 0.01); one of six (17%) RSP, but 21 of 40 (53%) NRSP showed TAT > 6 micrograms/l. These data suggest that in lung cancer the activation of coagulation is an independent prognostic factor, since TAT levels were different between RSP and NRSP, also within the homogeneously unfavourable metastatic subgroup. It should be further studied, whether TAT can identify patients, whose prognosis could be improved by anticoagulation as an adjunct to standard antineoplastic therapy.

Tumor matrix generation and tumor cell growth are supported by coagulation processes within the tumor tissue. Activators of coagulation were searched for in suspensions of 9 permanent human squamous-cell lung-cancer (EPLC 32MI, U1752), large-cell lung-cancer (LCLC 97TMI, LCLC 103H, U1810), and small-cell lung-cancer (N-592, H-526, DMS79, 86MI) cell lines. Incubation with these cells shortened the recalcification time in normal plasma (also in the presence of antibodies against tissue factor) or coagulation-factor-VII-, VIII-, IX- or X-deficient plasmas. The activators of coagulation in the 2 most active cell lines (U1752 and LCLC 103H) were further characterized in purified systems: the cleavage of chromogenic substrates, and the generation of markers of pro-thrombin activation were assessed. Three activators of coagulation were found in intact or sonicated cell suspensions and culture supernatants: (i) a tissue factor (TF)-like activity; (ii) an activity activating factor X, which in contrast to "cancer pro-coagulant" was not inhibited by iodoacetamide; and (iii) an activity-activating pro-thrombin, which was inhibited by the serine protease inhibitor PMSF and appeared to require plasmatic co-factor(s). The heterogeneous expression of coagulation activators by lung-tumor cell lines might be of significance for tumor biology and response to therapy.

The majority of acute infection-associated hemolytic diseases of infancy and childhood have been suggested to be caused by exogenic alterations of the erythrocyte surface, though laboratory methods for their further evaluation were not yet available. Investigating 96 children, the present study characterizes 72% of cases as corresponding to this type of acute acquired hemolytic anemia, which cannot be clearly related to autoantibodies against unmodified components of the host's own red cells. Using a new immunofluorescence test, the erythrocyte membrane of 80% of these children was found to be altered in vivo by nonspecific adsorption of foreign material released from the infectious micro-organisms. In 24% of cases additive binding of complement was detectable by an antiglobulin test. Thus, the adsorption of microbial antigens to the red cell surface is suggested to be one of the causes for the removal of altered erythrocytes due to phagocytosis or a complement-dependent destruction during the course of infection-associated hemolytic anemia. Especially in childhood, the immunofluorescent detection of an erythrocyte sensitization in vivo provides a further characterization of this type of mostly transient hemolytic disease, which probably can be treated without any immunosuppressive drug, merely by elimination of the underlying infection.