Abstract
Circulating blood plasma contains proteinase‐degraded forms of thrombomodulin that are soluble. We quantitatively assayed the plasma levels of thrombomodulin in 15 patients with chronic myelogenous leukemia (CML) in chronic phase by method of an enzymelinked immunosorbent assay using a monoclonal antibody to protease‐degraded products of thrombomodulin. Plasma levels of thrombomodulin in patients with CML at diagnosis were significantly increased (19.5 ± 6.2 ng/ml: means ± SD) compared with the levels in normal controls (8.0 ± 1.9 ng/ml, n = 20) (P < 0.001). Fibrin degradation products (D‐dimer), thrombin‐antithrombin III complex, and plasmin α~2~‐antiplasmin complex were almost normal, suggesting that intravascular coagulation or plasmin‐mediated fibrinolysis little occurred in these patients. On the other hand, the plasma levels of elastase‐α~1~‐proteinase inhibitor (E‐α~1~PI) complex, which was the indicator of released leukocyte elastase, were significantly increased in CML (P < 0.0001). The plasma levels of thrombomodulin and E‐α~1~ PI complex were decreased in parallel with decline of leukocyte counts in 10 patients with CML following anti‐leukemic therapy. Furthermore, a statistically significant correlation was observed between the plasma levels of thrombomodulin and E‐α~1~PI complex obtained at 39 time points in 15 patients with CML (r = 0.81, P < 0.001).
These results suggest that the increased plasma levels of thrombomodulin in CML may be partly caused by leukocyte elastase, which may split the surface thrombomodulin and release protease‐degraded fragments of it into the circulation.