Enhanced generation of monocyte tissue factor and increased plasma prothrombin fragment1+2 levels in patients with polycythemia vera: mechanism of activation of blood coagulation.
Polycythemia vera (PV) is associated with a high incidence of thrombosis. The association of apparent and secondary polycythemia with thrombosis is not clear. It was suggested that activation of the coagulation system contributes to thrombus formation in PV. However, the mechanism of activation is unknown. Monocytes generate a potent tissue factor (TF) upon stimulation with various substances, which is involved in thrombus formation in various disorders. Therefore, we studied the possibility that the factor is involved in the activation of coagulation and thrombus formation also in PV. Unstimulated peripheral blood mononuclear cells (PBMC) from each of the different types of polycythemia expressed weak TF activity (2 U) and antigen (41.4 to 52.9 pg/ml), which were similar to normal controls. Following stimulation with endotoxin, PBMC from normal controls and from apparent and secondary polycythemia showed a 3.9- to 4.5-fold increase in TF, while cells from PV showed a 21-fold increase (P<0.001). Similar levels were generated by PBMC after treatment of PV and at the spent phase. TF was generated by monocytes but not by lymphocytes. Plasma prothrombin fragment1+2 (F1+2) levels, assayed at the same time, were significantly higher in PV (2.46 nm) compared to normals and apparent and secondary polycythemia (0.22 to 0.32 nm), and were in a significant correlation with monocyte TF activity and antigen levels (r = 0.77, 0.87). The high levels of F1+2 confirm that the coagulation system is activated in PV. The increased capacity of monocytes to generate TF may be responsible for the activation of the coagulation system and thrombus formation. The hypercoagulability state that is induced by this mechanism suggests that long-life oral anticoagulation should be considered once thrombosis has been developed in PV.
Kornberg
A
A
Institute of Hematology and Blood Bank, Assof Harofeh Medical Center, Zerifin, Israel.
Rahimi-Levene
N
N
Yona
R
R
Mor
A
A
Rachmilewitz
E A
EA
D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D006801:Humans; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011087:Polycythemia Vera / Q000097:blood*; D011516:Prothrombin / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*
D010446:Peptide Fragments; D011516:Prothrombin; D013925:Thromboplastin