Increased mononuclear cell tissue factor and type-2 plasminogen activator inhibitor and reduced plasma fibrinolytic capacity in children with lymphoma.
Blood clotting activation and fibrin deposition are common findings in lymphoma patients. We evaluated the capacity of peripheral blood mononuclear cells to produce procoagulant activity (PCA) and plasminogen activator inhibitor (PAI) in 12 children with newly diagnosed lymphoma (8 non-Hodgkin's, 4 Hodgkin's) and in 12 matched healthy donors. In the same subjects we also measured plasma antigen levels of tissue-type PA (t-PA), urokinase-type PA (u-PA), PAI-1, PAI-2, and D-dimer. PCA generated by mononuclear cells after incubation for 20 h at 37 degrees C was significantly higher in patients than in controls (p = 0.027). In all samples it was identified as tissue factor by functional criteria (dependence on factor VII). Moreover, culture medium obtained from patients' mononuclear cells after incubation for 20 h at 37 degrees C contained significantly higher amounts of PAI activity and PAI-2 antigen than control samples (p < 0.001). Plasma PAI-1 and t-PA antigens were significantly augmented in patients (p < 0.005), the mean increase of PAI-I being about 5 times higher than that of t-PA. Plasma levels of D-dimer were markedly increased in the patient's group (p < 0.001), whereas u-PA and PAI-2 antigens did not differ from controls. It is suggested that monocytes from lymphoma patients are endowed with functional abnormalities leading to the simultaneous expression of tissue factor and antifibrinolytic activity. These abnormalities, coupled with a reduced plasma fibrinolytic potential, could play an important pathogenetic role in blood clotting activation and fibrin deposition associated with lymphoma.
Semeraro
N
N
Dipartimento di Scienze Biomediche e Oncologia Umana, Università di Bari, Italy.
Montemurro
P
P
Giordano
P
P
Santoro
N
N
De Mattia
D
D
Colucci
M
M
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008228:Lymphoma, Non-Hodgkin / Q000097:blood*; D008297:Male; D017396:Plasminogen Activator Inhibitor 2 / Q000097:blood*; D013925:Thromboplastin / Q000378:metabolism*
D017396:Plasminogen Activator Inhibitor 2; D013925:Thromboplastin