Lithium and hematology: established and proposed uses

Abstract

Lithium (as lithium carbonate) is an inexpensive drug, widely used in psychiatry for over 50 years in treatment of mood instability (bipolar disorder) and as an adjunct to antidepressants. Hematological effects of neutrophilia and increased circulating CD34+ cells of marrow origin have long been known. Lithium was at the center of hematological investigations in the 1980s, but no definitive use in hematology has yet emerged. We review evidence that lithium increases G-CSF and augments G-CSF effects. We suggest possible therapeutic uses of lithium in neutropenia. In bone marrow transplantation, preharvest lithium-assisted hematopoietic stem cell mobilization may be useful as well.

Pivotal role for glycogen synthase kinase–3 in hematopoietic stem cell homeostasis in mice

“…Because lithium directly inhibits glycogen synthase kinase-3 (GSK-3; ref. 5), activating critical signaling pathways such as the Wnt and PI3K/PTEN/Akt pathways (6,7), these clinical and laboratory observations implicate GSK-3 as an important regulator of HSC homeostasis (6,8,9). Support for this hypothesis comes from pharmacological studies showing that HSCs and hematopoietic progenitor cells (HPCs) are increased, and hematopoietic repopulation is enhanced, when BM transplant recipient mice are treated with alternative GSK-3 inhibitors (10)(11)(12).…”

Therapeutic Potential of Mood Stabilizers Lithium and Valproic Acid: Beyond Bipolar Disorder

“…There have also been reports of hepatotoxicity and hematopoietic damage (thrombocytopenia, platelet dysfunction, factor XIII deficiency, hypofibrinogenemia, and vitamin K-dependent factor deficiency) after VPA treatment (Koenig et al, 2006;McFarland et al, 2008). Of interest, lithium was suggested to be used in treating hematopoietic deficits via increasing colony-stimulating factor (reviewed in Focosi et al, 2009). VPA was also reported to increase prevalence of von Wilbrant disease (Serdaroglu et al, 2002;Koenig et al, 2008), a coagulation abnormality presenting with increased bleeding tendency in the form of easy bruising, nosebleeds, and bleeding gums, and a nine-fold increase in aplastic anemia (Handoko et al, 2006), a condition in which a patient has lower red blood cells, white blood cells, and platelets because of bone marrow not producing sufficient new cells.…”

Gelatinous Marrow Transformation and Hematopoietic Atrophy in a Miniature Horse Stallion

“…The horse was also empirically treated with lithium carbonate, which is thought to increase production of granulocyte colony-stimulating factor and stimulate hematopoietic stem cell recruitment, leading to increased granulopoiesis and thrombopoiesis in humans. 8 Blood concentrations considered therapeutic in humans were not achieved in this horse; therefore, whether lithium contributed to hematopoietic recovery is questionable. Reversal of hematopoietic atrophy in anorexic humans occurs within 14 to 25 days after institution of proper nutrition.…”