title: Hypersplenism in liver disease and SLE revisited: current evidence supports an active rather than passive process.
abstract: BACKGROUND
  Active and passive theories have been advanced to explain splenomegaly and cytopenias in liver disease. Dameshek proposed active downregulation of hematopoiesis. Doan proposed passive trapping of blood components in a spleen enlarged by portal hypertension. Recent findings do not support a passive process.
  
  
  CONCLUSIONS
  Cytopenias and splenomegaly in both liver disease and systemic lupus erythematosus (SLE) poorly correlate with portal hypertension, and likely reflect an active process allocating stem cell resources in response to injury. Organ injury is repaired partly by bone-marrow-derived stem cells. Signaling would thus be needed to allocate resources between repair and routine marrow activities, hematologic and bone production. Granulocyte-colony stimulating factor (G-CSF) may play a central role: mobilizing stem cells, increasing spleen size and downregulating bone production. Serum G-CSF rises with liver injury, and is elevated in chronic liver disease and SLE. Signaling, not sequestration, likely accounts for splenomegaly and osteopenia in liver disease and SLE. The downregulation of a non-repair use of stem cells, bone production, suggests that repair efforts are prioritized. Other non-repair uses might be downregulated, namely hematologic production, as Dameshek proposed.
  
  
  CONCLUSIONS
  Recognition that an active process may exist to allocate stem-cell resources would provide new approaches to diagnosis and treatment of cytopenias in liver disease, SLE and potentially other illnesses.
authors: Division of Interventional Radiology, Department of Radiology, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03766 USA ; Geisel School of Medicine at Dartmouth, One Rope Ferry Road, Hanover, NH 03755 USA.
authors: John M
authors: JM
authors: Gemery
authors: Geisel School of Medicine at Dartmouth, One Rope Ferry Road, Hanover, NH 03755 USA.
authors: Andrew R
authors: AR
authors: Forauer
authors: Geisel School of Medicine at Dartmouth, One Rope Ferry Road, Hanover, NH 03755 USA.
authors: Anne M
authors: AM
authors: Silas
authors: Geisel School of Medicine at Dartmouth, One Rope Ferry Road, Hanover, NH 03755 USA.
authors: Eric K
authors: EK
authors: Hoffer
keywords: Cytopenias; Dameshek; Doan; Hematopoiesis; Hypersplenism; Liver disease; SLE; Splenomegaly; Stem cells; Systemic lupus erythematosus