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.
© 2011 Blackwell Publishing Ltd.
MeSH terms
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Adult
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Benzoates / administration & dosage
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Benzoates / adverse effects*
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Benzoates / therapeutic use
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Bone Marrow / metabolism
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Bone Marrow / pathology*
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Combined Modality Therapy
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Cytokines / blood
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Female
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Hepatocyte Growth Factor / blood*
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Humans
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Hydrazines / administration & dosage
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Hydrazines / adverse effects*
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Hydrazines / therapeutic use
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Intercellular Signaling Peptides and Proteins / blood
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Male
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Middle Aged
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Peptide Fragments / blood*
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Primary Myelofibrosis / blood
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Primary Myelofibrosis / chemically induced*
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Procollagen / blood*
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Purpura, Thrombocytopenic, Idiopathic / blood
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Purpura, Thrombocytopenic, Idiopathic / drug therapy*
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Purpura, Thrombocytopenic, Idiopathic / pathology
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Purpura, Thrombocytopenic, Idiopathic / surgery
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Pyrazoles / administration & dosage
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Pyrazoles / adverse effects*
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Pyrazoles / therapeutic use
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Receptors, Fc / administration & dosage
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Receptors, Fc / therapeutic use
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Receptors, Thrombopoietin / agonists*
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / adverse effects*
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Recombinant Fusion Proteins / therapeutic use
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Reticulin / analysis*
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Splenectomy
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Thrombopoietin / administration & dosage
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Thrombopoietin / adverse effects*
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Thrombopoietin / therapeutic use
Substances
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Benzoates
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Cytokines
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HGF protein, human
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Hydrazines
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Intercellular Signaling Peptides and Proteins
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Peptide Fragments
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Procollagen
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Pyrazoles
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Receptors, Fc
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Receptors, Thrombopoietin
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Recombinant Fusion Proteins
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Reticulin
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procollagen Type III-N-terminal peptide
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MPL protein, human
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Hepatocyte Growth Factor
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Thrombopoietin
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romiplostim
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eltrombopag