Thrombopoietin induces rapid resolution of thrombocytopenia after orthotopic liver transplantation through increased platelet production

Blood ◽  
2000 ◽  
Vol 95 (3) ◽  
pp. 795-801 ◽  
Author(s):  
Markus Peck-Radosavljevic ◽  
Martina Wichlas ◽  
Johannes Zacherl ◽  
Gabriele Stiegler ◽  
Petra Stohlawetz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Liver Transplantation ◽  
Platelet Count ◽  
Liver Disease ◽  
Orthotopic Liver Transplantation ◽  
Platelet Activation ◽  
Serum Levels ◽  
Etiologic Factor ◽  
Coagulation Activation ◽  
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.

scholarly journals TESTOSTERONE CHANGES IN PATIENTS WITH LIVER CIRRHOSIS BEFORE AND AFTER ORTHOTOPIC LIVER TRANSPLANTATION AND ITS CORRELATION WITH MELD

2014 ◽  
Vol 51 (1) ◽  
pp. 59-63 ◽  
Author(s):  
Rodrigo NITSCHE ◽  
Júlio Cezar Uili COELHO ◽  
Alexandre Coutinho Teixeira de FREITAS ◽  
Clementino ZENI NETO ◽  
Eduardo MARTINS
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Orthotopic Liver Transplantation ◽  
Free Testosterone ◽  
Serum Levels ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
End Stage Liver Disease ◽  
End Stage

Context Hypogonadism is a common clinical situation in male patients with liver cirrhosis. Objectives The aim of the present study was to evaluate the effects of orthotopic liver transplantation on testosterone, free testosterone and sex hormone-binding globulin in male with advanced liver disease and also to determine the relationship of these changes with Model for End-stage Liver Disease (MELD) score. Methods In a prospective study, serum levels of testosterone, free testosterone and sex hormone-binding globulin of 30 male adult patients with end-stage liver disease were measured 2 to 4 hours before and 6 months after orthotopic liver transplantation. Results Total testosterone levels increased after orthotopic liver transplantation and the number of patients with normal testosterone levels increased from 18 to 24. Free testosterone mean level in the pre-transplant group was 7.8 pg/mL and increased to 11.5 pg/mL (P = 0.10) and sex hormone-binding globulin level decreased after orthotopic liver transplantation returning to normal levels in MELD ≤18 - group (A) (P<0.05). Conclusions Serum level changes of testosterone, free testosterone and sex hormone-binding globulin are more pronounced in cirrhotic males with MELD ≤18. Serum levels of testosterone and free testosterone increase and serum levels of sex hormone-binding globulin decrease after orthotopic liver transplantation.

scholarly journals Implication for Bone Marrow Derived Stem Cells in Hepatocyte Regeneration after Orthotopic Liver Transplantation

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
N. Pilat ◽  
L. Unger ◽  
G. A. Berlakovich
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Liver Transplantation ◽  
Liver Regeneration ◽  
Orthotopic Liver Transplantation ◽  
Liver Tissue ◽  
Hepatic Regeneration ◽  
Liver Growth ◽  
Cell Source ◽  
The Impact

The liver has the outstanding ability to regenerate itself and restore parenchymal tissue after injury. The most common cell source in liver growth/regeneration is replication of preexisting hepatocytes although liver progenitor cells have been postulated to participate in liver regeneration in cases of massive injury. Bone marrow derived hematopoietic stem cells (BM-HSC) have the formal capacity to act as a source for hepatic regeneration under special circumstances; however, the impact of this process in liver tissue maintenance and regeneration remains controversial. Whether BM-HSC are involved in liver regeneration or not would be of particular interest as the cells have been suggested to be an alternative donor source for the treatment of liver failure. Data from murine models of liver disease show that BM-HSC can repopulate liver tissue and restore liver function; however, data obtained from human liver transplantation show only little evidence for liver regeneration by this mechanism. The cell source for liver regeneration seems to depend on the nature of regeneration process and the extent of injury; however, the precise mechanisms still need to be resolved. Current data suggest, that in human orthotopic liver transplantation, liver regeneration by BM-HSC is a rather rare event and therefore not of clinical relevance.

scholarly journals The Y14-p53 Regulatory Circuit in Megakaryocyte Differentiation and Thrombocytopenia

2020 ◽  
Author(s):  
Chun-Hao Su ◽  
Wei-Ju Liao ◽  
Wei-Chi Ke ◽  
Ruey-Bing Yang ◽  
Woan-Yuh Tarn
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Ex Vivo ◽  
Critical Role ◽  
Platelet Production ◽  
Noncoding Regions ◽  
Regulatory Circuit ◽  
Hel Cells ◽  
Absent Radius ◽  
Megakaryocyte Differentiation

SUMMARYThrombocytopenia-absent radius syndrome is caused by a deletion in chromosome 1q21.1 in trans with RBM8A mutations in the noncoding regions. We generated megakaryocyte-specific Rbm8a knockout (Rbm8aKOMK) mice that exhibited marked thrombocytopenia, internal hemorrhage, and splenomegaly, indicating a disorder of platelet production. Rbm8aKOMK mice accumulated immature megakaryocytes in the bone marrow and spleen. Depletion of Y14/RBM8A in human erythroleukemia (HEL) cells inhibited phorbol ester-induced polyploidy and downregulated the signaling pathways associated with megakaryocyte maturation. Accordingly, Rbm8aKOMK mice had reduced expression of surface glycoproteins on platelets and impaired coagulation. Moreover, p53 level was increased in Y14-depleted HEL cells and Rbm8aKOMK megakaryocytes. Treatment with a p53 inhibitor restored ex vivo differentiation of Rbm8aKOMK megakaryocytes and unexpectedly activated Y14 expression in HEL cells. Knockout of Trp53 in part restored the platelet count of Rbm8aKOMK mice. These results indicate that the Y14-p53 circuit plays a critical role in megakaryocyte differentiation and platelet production.

scholarly journals Progression of Neurovisceral Storage Disease With Supranuclear Ophthalmoplegia Following Orthotopic Liver Transplantation

PEDIATRICS ◽  
1986 ◽  
Vol 77 (1) ◽  
pp. 104-106
Author(s):  
J. Carlton Gartner ◽  
Ira Bergman ◽  
J. Jeffrey Malatack ◽  
Basil J. Zitelli ◽  
Ronald Jaffe ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bone Marrow ◽  
Liver Transplantation ◽  
Orthotopic Liver Transplantation ◽  
Storage Disease ◽  
Initial Period ◽  
Storage Material ◽  
Neurologic Symptoms ◽  
Progressive Ataxia

A 7-year-old girl with progressive ataxia, spasticity, supranuclear ophthalmoplegia, and sea-blue histiocytes in her bone marrow underwent orthotopic liver transplantation for hepatocellular carcinoma. After an initial period of stabilization, she has shown progression of neurologic symptoms with recurrence of storage material in the transplanted liver.

Tranexamic Acid Reduces Blood Loss, Transfusion Requirements, and Coagulation Factor Use in Primary Orthotopic Liver Transplantation

1996 ◽  
Vol 85 (5) ◽  
pp. 1043-1048 ◽  
Author(s):  
John F. Boylan ◽  
John R. Klinck ◽  
Alan N. Sandler ◽  
Ramiro Arellano ◽  
Paul D. Greig ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Blood Loss ◽  
Tranexamic Acid ◽  
Orthotopic Liver Transplantation ◽  
Interquartile Range ◽  
High Dose ◽  
Intraoperative Blood Loss ◽  
End Stage ◽  
Donor Exposure

Background Patients with end-stage liver disease frequently incur large-volume blood loss during liver transplantation associated with mechanical factors, preexisting coagulopathy, and intraoperative fibrinolysis. Methods Between April 1992 and May 1994, the authors of this double-blind, randomized, placebo-controlled study examined the effect of high-dose tranexamic acid (maximum of 20 g) on blood loss and blood product requirements in patients undergoing primary isolated orthotopic liver transplantation. Primary outcome measures were volume of blood loss (intraoperative blood loss and postoperative drainage) and erythrocyte, plasma, platelet, and cryoprecipitate use during surgery and the first 24 h of intensive care unit stay. Results Patients receiving tranexamic acid (n = 25) had less intraoperative blood loss (median, 4.3 l; interquartile range, 2.5 to 7.9; P = 0.006) compared with the placebo group (n = 20; median, 8 l; interquartile range, 5 to 15.8), and reduced intraoperative plasma, platelet, and cryoprecipitate requirements. Median perioperative erythrocyte use was 9 units (interquantile range, 4 to 14 units) in patients receiving tranexamic acid and 13 units (interquantile range, 7.5 to 31 units) in controls (P = 0.03). Total perioperative donor exposure was 20.5 units (interquantile range, 16 to 41 units) in patients receiving tranexamic acid and 43.5 units (interquantile range, 29.5 to 79 units) in controls (P = 0.003). Results for postoperative wound drainage were similar. Hospital stay and need for retransplantation were comparable in both groups. No patient in either group showed clinical evidence of hepatic artery or portal venous thrombosis within 1 month of transplantation. Conclusions High-dose tranexamic acid significantly reduces intraoperative blood loss and perioperative donor exposure in patients with end-stage parenchymal liver disease who are undergoing orthotopic liver transplantation, with marked reductions in platelet and cryoprecipitate requirements.

scholarly journals Aortic Balloon Valvuloplasty Prior to Orthotopic Liver Transplantation: A Novel Approach to Aortic Stenosis and End-Stage Liver Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Edward Coverstone ◽  
Kevin Korenblat ◽  
Jeffrey S. Crippin ◽  
William C. Chapman ◽  
Andrew M. Kates ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Orthotopic Liver Transplantation ◽  
Severe Aortic Stenosis ◽  
Balloon Aortic Valvuloplasty ◽  
End Stage Liver Disease ◽  
Aortic Valvuloplasty ◽  
End Stage

The combination of severe aortic stenosis and end-stage liver disease increases the morbidity and mortality of surgical aortic valve replacement or orthotopic liver transplantation resulting in a prohibitive operative risk. We propose a staged approach of balloon aortic valvuloplasty prior to orthotopic liver transplantation as a bridge to definitive aortic valve replacement. Between 2010 and 2012, four patients with severe aortic stenosis and end-stage liver disease underwent staged balloon aortic valvuloplasty followed by orthotopic liver transplantation. All patients had been deemed to be inappropriate candidates for liver transplantation or aortic valve surgery due to their comorbidity. One patient died of complications from a perivalvular abscess. Three patients went on to successful graft implantation and function and surgical recovery. Two of the three patients proceeded to definitive surgical aortic valve replacement with the remainder currently undergoing evaluation. In this case series, we present a novel approach of balloon aortic valvuloplasty prior to liver transplantation as a potential bridge to definitive treatment of severe aortic stenosis in the end-stage liver patient.

scholarly journals Determinants of hyperhomocysteinemia in patients with chronic liver disease and after orthotopic liver transplantation

2003 ◽  
Vol 77 (5) ◽  
pp. 1269-1277 ◽  
Author(s):  
Anja Bosy-Westphal ◽  
Martina Ruschmeyer ◽  
Norbert Czech ◽  
Gerd Oehler ◽  
Holger Hinrichsen ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Orthotopic Liver Transplantation ◽  
Chronic Liver
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