title: 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: Department of Pediatric Hematology/Oncology, Weill Cornell Medical College, New York, NY 10065, USA. wghanima@c2i.net
authors: Waleed
authors: W
authors: Ghanima
authors: Peter
authors: P
authors: Junker
authors: Hans Carl
authors: HC
authors: Hasselbalch
authors: Leonardo
authors: L
authors: Boiocchi
authors: Julia T
authors: JT
authors: Geyer
authors: Xingmin
authors: X
authors: Feng
authors: Sif
authors: S
authors: Gudbrandsdottir
authors: Attilio
authors: A
authors: Orazi
authors: James B
authors: JB
authors: Bussel
mesh_terms: D000328:Adult; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D055728:Primary Myelofibrosis / Q000097:blood / Q000139:chemically induced*; D011347:Procollagen / Q000097:blood*; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011961:Receptors, Fc / Q000008:administration & dosage / Q000627:therapeutic use; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012155:Reticulin / Q000032:analysis*; D013156:Splenectomy; D013926:Thrombopoietin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D001565:Benzoates; D016207:Cytokines; C066855:HGF protein, human; D006834:Hydrazines; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D011347:Procollagen; D011720:Pyrazoles; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; D012155:Reticulin; C041876:procollagen Type III-N-terminal peptide; C082218:MPL protein, human; D017228:Hepatocyte Growth Factor; D013926:Thrombopoietin; C488777:romiplostim; C520809:eltrombopag