Objective:To investigate the pathological changes of reactive thrombocytosis induced by recombinant human thrombopoietin（rhTPO）in mice. Methods:Forty-eight 4-week-old SPF BALB/c mice were randomly divided into rhTPO group and control group

24 in each group. Mice in rhTPO group has been intraperitoneally injected rhTPO 500 μg/（kg·d）

0.3 ml daily for 10 days

while those in control group received saline 0.3 m L. Six mice in each group were executed on day 3

5

7

10 respectively;peripheral blood cell count was measured;PLT aggregation test（PAgT）

PLT ATP release test

plasma D-dimer concentration detection were conducted;manifestations of thrombosis in mice were observed;bone marrow biopsy as well as coefficient of spleen and liver and pathological examination of spleen and liver were all performed. Results:PLT was significantly higher in rhTPO group than in control group on day 3（P<0.05）and was significantly higher in rhTPO group than in control group on day 5

7 and 10（P<0.01）. There was no difference in five-min maximum aggregation rates and PLT ATP released quantities on day 3

5

7

10 between rhTPO group and control group（P>0.05）. Plasma D-dimer in rhTPO group were significantly higher than that in control group on day 3（P<0.05）and was significantly higher in rhTPO group than in control group on day 5

7

10（P<0.01）. Manifestations of thrombosis were not observed in both groups. Bone marrow biopsy for rhTPO group on day 3

5

7

10 showed megakaryocytic hyperplasia

increased volume

which became increasingly obvious as time went by. Spleen coefficients in rhTPO group were significantly higher than those in control group on day 5

7

and was significantly higher in rhTPO group than in control group on day 10（P<0.01）. Hepatic coefficients in rhTPO group were significantly higher than those in control group on day 10（P<0.05）. Megakaryocytes in spleen and spleen volume in rhTPO group were unchanged within 3 days

but megakaryocytes in spleen gradually proliferated on day 5

7

10. Erythroid proliferation was found on day 10. At the same time

spleen volume gradually increased on day 5

7

10. Erythroid

myeloid

megakaryocytic hyperplasia and increased volume were found in liver on day 10. Conclusion:Pathological changes of reactive thrombocytosis induced by high dose rhTPO in BALB/c mice include bone marrow megakaryocytes proliferation

a sharp increase in the number of peripheral blood PLT with normal PLT production function

no pathological change in spleen and liver at initial stage

extramedullary hematopoiesis and increased volume in spleen and liver at middle and late stage

megakaryocytic proliferation in spleen at middle and late stage

erythroid hyperplasia in spleen at late stage as well as increased spleen volume

erythroid

myeloid

megakaryocytic hyperplasia and increased volume in liver at late stage.