Fibroproliferative activity in patients with immune thrombocytopenia (ITP) treated with thrombopoietic agents.

Abstract

This study assessed the grade of bone marrow (BM) fibrosis and its association with a seromarker for collagen-III formation and fibrosis-related cytokines in 25 immune thrombocytopenia (ITP) patients treated with thrombopoietin receptor agonists (Tpo-RA) who had at least one BM biopsy. Assessment of 8 pre- and on-treatment BM biopsies revealed statistically significant increases in reticulin. Reticulin in biopsies performed after a median of 1·4 years of treatment was graded: MF-0 in 3 (12%), MF-1 in 19 (76%), MF-2 in 2 (8%) and MF-3 in 1 (4%). No cytogenetic or flow-cytometric abnormalities were detected. Median pretreatment Procollagen III N-propeptide (PIIINP) (6·6 μg/l) was significantly higher than on-treatment levels (5·6 μg/l); both were higher than controls (3·4 μg/l; P < 0·001). PIIINP was negatively correlated with treatment duration (r = -0·49) suggesting a decelerated reticulin production over time. There was a trend towards an association between grade of reticulin and PIIINP. Transforming growth factor (GF)-beta and basic-Fibroblast GF were not different between patients and controls but Hepatocyte GF (HGF), an anti-fibrotic cytokine, was significantly elevated in patients. In conclusion, low-grade BM reticulin fibrosis is seen in most ITP patients on Tpo-RA. The novel findings of decreasing PIIINP and elevated HGF need further investigation to explore their significance in BM fibrogenesis.

• Authors: Waleed Ghanima, Peter Junker, Hans Carl Hasselbalch, Leonardo Boiocchi, Julia T Geyer, Xingmin Feng, Sif Gudbrandsdottir, Attilio Orazi, James B Bussel
• Journal: British journal of haematology (Br J Haematol) Vol. 155 Issue 2 Pg. 248-55 (Oct 2011) ISSN: 1365-2141 [Electronic] England
• PMID: 21902682 (Publication Type: Journal Article)
• Copyright: © 2011 Blackwell Publishing Ltd.

Chemical References

• Benzoates
• Cytokines
• HGF protein, human
• Hydrazines
• Intercellular Signaling Peptides and Proteins
• Peptide Fragments
• Procollagen
• Pyrazoles
• Receptors, Fc
• Receptors, Thrombopoietin
• Recombinant Fusion Proteins
• Reticulin
• procollagen Type III-N-terminal peptide
• MPL protein, human
• Hepatocyte Growth Factor
• Thrombopoietin
• romiplostim
• eltrombopag

Topics

• Adult
• Benzoates (administration & dosage, adverse effects, therapeutic use)
• Bone Marrow (metabolism, pathology)
• Combined Modality Therapy
• Cytokines (blood)
• Female
• Hepatocyte Growth Factor (blood)
• Humans
• Hydrazines (administration & dosage, adverse effects, therapeutic use)
• Intercellular Signaling Peptides and Proteins (blood)
• Male
• Middle Aged
• Peptide Fragments (blood)
• Primary Myelofibrosis (blood, chemically induced)
• Procollagen (blood)
• Purpura, Thrombocytopenic, Idiopathic (blood, drug therapy, pathology, surgery)
• Pyrazoles (administration & dosage, adverse effects, therapeutic use)
• Receptors, Fc (administration & dosage, therapeutic use)
• Receptors, Thrombopoietin (agonists)
• Recombinant Fusion Proteins (administration & dosage, adverse effects, therapeutic use)
• Reticulin (analysis)
• Splenectomy
• Thrombopoietin (administration & dosage, adverse effects, therapeutic use)