Thrombopoietin induces rapid resolution of thrombocytopenia after orthotopic liver transplantation through increased platelet production.
Thrombopoietin (TPO) deficiency has been proposed as an important etiologic factor for thrombocytopenia in advanced-stage liver disease. To clarify the contributions of platelet production, platelet consumption, coagulation activation, and splenic sequestration to thrombocytopenia in liver disease, we studied TPO serum levels and markers of platelet production, platelet activation, and coagulation activation before and 14 days after orthotopic liver transplantation (OLT) in 18 patients with advanced liver cirrhosis. Thrombocytopenia before transplantation occurred with low-normal serum levels of TPO, normal levels of platelet and coagulation activation markers, and no increase in bone marrow production of platelets. TPO serum levels increased significantly on the first day after OLT, preceding the increase of reticulated platelets by 3 days and peripheral platelets by 5 days. Normalization of the peripheral platelet count occurred in most patients within 14 days of OLT, irrespective of the change in spleen size assessed by computed tomography volumetry. Normalization of platelet counts was not hampered by a certain degree of platelet activation observed during the steepest increase in the peripheral platelet count. Bone marrow production of platelets increased significantly within 2 weeks of transplantation. Low TPO serum levels with low platelet counts and without platelet consumption suggests low TPO production in end-stage liver disease. The rapid increase in TPO serum levels after transplantation induces an increase in the bone marrow production of platelets. Decreased TPO production in the cirrhotic liver is an important etiologic factor for thrombocytopenia in liver disease that is rapidly reversed by transplantation.
Peck-Radosavljevic
M
M
Department of Gastroenterology and Hepatology, University of Vienna, Austria. markus.peck@akh-wien.ac.at
Wichlas
M
M
Zacherl
J
J
Stiegler
G
G
Stohlawetz
P
P
Fuchsjäger
M
M
Kreil
A
A
Metz-Schimmerl
S
S
Panzer
S
S
Steininger
R
R
Mühlbacher
F
F
Ferenci
P
P
Pidlich
J
J
Gangl
A
A
D000328:Adult; D000368:Aged; D015415:Biomarkers; D001792:Blood Platelets / Q000473:pathology; D001798:Blood Proteins / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008533:Megakaryocytes / Q000473:pathology*; D008875:Middle Aged; D015539:Platelet Activation; D010976:Platelet Count; D013154:Spleen / Q000473:pathology; D013921:Thrombocytopenia / Q000209:etiology*; D013926:Thrombopoietin / Q000097:blood / Q000172:deficiency / Q000502:physiology*; D013997:Time Factors
D015415:Biomarkers; D001798:Blood Proteins; D013926:Thrombopoietin