Thrombocytopenia in association with splenomegaly during granulocyte-colony-stimulating factor treatment in mice is not caused by hypersplenism and is resolved spontaneously.

Abstract

BACKGROUND:

Granulocyte-colony-stimulating factor (G-CSF) is used for hematopoietic progenitor cell (HPC) mobilization. Platelet (PLT) counts decrease during G-CSF administration. The mechanisms have not been determined, however. Because splenic pooling of PLTs caused thrombocytopenia in patients with splenomegaly and splenic enlargement was observed in G-CSF-treated donors, it was hypothesized that hypersplenism might cause G-CSF-induced thrombocytopenia.

STUDY DESIGN AND METHODS:

Mice were treated with several concentrations of G-CSF, and PLT count was measured. Because transfused PLTs should be cleared rapidly from the blood stream under hypersplenic state, PLT life span was studied. To determine direct role of spleen on thrombocytopenia, G-CSF was given to splenectomized mice. Because PLT count did not decrease in G-CSF-expressing transgenic mice, G-CSF was given to mice for a longer period of time and PLT count was investigated.

RESULTS:

PLT counts decreased while spleen weight increased in a dose-dependent manner by G-CSF treatment. No significant difference in PLT life span was found between G-CSF-treated and control mice. Histologic analysis showed no significant increase in PLT numbers trapped in either spleen or other tissue after PLT transfusion in G-CSF-treated mice. In splenectomized mice as well as in normal mice, G-CSF caused thrombocytopenia. When G-CSF was given to mice for a longer period of time, PLT counts decreased during the first 7 days and thereafter began to increase followed by returning to baseline on Day 15.

CONCLUSION:

Thrombocytopenia coincided with splenomegaly during G-CSF treatment, but hypersplenism was not responsible for thrombocytopenia. G-CSF-induced thrombocytopenia was a transient event and improved spontaneously despite continual G-CSF treatment.

• Authors: Yasushi Takamatsu, Shiro Jimi, Tomohito Sato, Shuuji Hara, Junji Suzumiya, Kazuo Tamura
• Journal: Transfusion (Transfusion) Vol. 47 Issue 1 Pg. 41-9 (Jan 2007) ISSN: 0041-1132 [Print] United States
• PMID: 17207228 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Granulocyte Colony-Stimulating Factor

Topics

• Animals
• Bone Marrow (pathology)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Granulocyte Colony-Stimulating Factor (administration & dosage, pharmacology)
• Hypersplenism (chemically induced, complications)
• Megakaryocytes (pathology)
• Mice
• Mice, Inbred C57BL
• Platelet Count
• Remission, Spontaneous
• Spleen (pathology)
• Splenectomy
• Splenomegaly (chemically induced, etiology)
• Thrombocytopenia (blood, chemically induced, etiology, physiopathology)