Interferon-induced thrombocytopenia: Is it time for thrombopoietin?

Martin, Thomas G.; Shuman, Marc A.

doi:10.1002/hep.510280536

Cited by 26 publications

(8 citation statements)

References 20 publications

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“…2 In contrast, we failed to detect an inverse relationship between TPO levels and platelet counts in children with ALF, similar to the situation in adult cirrhotic patients with thrombocytopenia. 11 At first glance, the preoperative serum TPO concentration measured by us in children with ALF (median, 156 pg/mL) would not appear to be inappropriately low compared with the reference value of 90 pg/mL in healthy adults. However, it has been demonstrated that TPO levels in healthy children are 2.3 times higher than in adults.…”

Section: Discussionmentioning

confidence: 77%

“…8,9 Others measured no differences in serum TPO concentrations when the values were compared in normal persons and cirrhotic patients. 10 In a recent editorial in HEPATOLOGY, 11 the need for additional studies on TPO production in cirrhotic patients was indicated. Along these lines, the ratio of the level of TPO mRNA to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA has been reported to be slightly lower (by 26%) in cirrhotic than in normal liver.…”

mentioning

confidence: 99%

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Hepatic thrombopoietin mRNA levels in acute and chronic liver failure of childhood

Wolber¹,

Ganschow

Burdelski

et al. 1999

Hepatology

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The liver is the main production site of the hormone thrombopoietin (TPO), the major regulator of megakaryopoiesis. To investigate the role of an impaired TPO gene expression in the pathogenesis of thrombocytopenia in pediatric patients suffering from liver failure, we measured hepatic TPO mRNA in children with acute or chronic end-stage liver disease undergoing orthotopic liver transplantation. Tissue samples for RNA extraction were obtained from 12 children with compensated cirrhosis (CC), 22 children with decompensated cirrhosis (DC), and 9 children with acute liver failure (ALF). The glycoprotein hormone, thrombopoietin (TPO), is the major regulator of megakaryopoiesis and platelet production. 1,2 Northern blot analyses have demonstrated that TPO mRNA is expressed predominantly in liver, and to a minor degree, in kidney, spleen, and brain. 3,4 A recent report from this laboratory has shown that hepatic TPO mRNA accounts for 94% of the total in the perinatal period. 5 In situ hybridization studies have localized TPO mRNA in parenchymal cells of the human 6 and murine 7 liver. Hepatocytes appear to produce TPO at a constant rate. The plasma concentration of the hormone is regulated by the degree of receptor-mediated binding and degradation of TPO by platelets and, in all likelihood, megakaryocytes.

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Section: Discussionmentioning

confidence: 77%

mentioning

confidence: 99%

Hepatic thrombopoietin mRNA levels in acute and chronic liver failure of childhood

Wolber¹,

Ganschow

Burdelski

et al. 1999

Hepatology

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“…The significance was determined using an unpaired, two-tailed student's t test (*p % 0.05, **p % 0.01, ***p % 0.001, ****p % 0.0001, and non-significant: NS). (Cole et al, 1998;Kawamoto, 2003;Martin and Shuman, 1998;Rajan et al, 2005).…”

Section: Discussionmentioning

confidence: 97%

Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors

et al. 2015

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Infections are associated with extensive platelet consumption, representing a high risk for health. However, the mechanism coordinating the rapid regeneration of the platelet pool during such stress conditions remains unclear. Here, we report that the phenotypic hematopoietic stem cell (HSC) compartment contains stem-like megakaryocyte-committed progenitors (SL-MkPs), a cell population that shares many features with multipotent HSCs and serves as a lineage-restricted emergency pool for inflammatory insults. During homeostasis, SL-MkPs are maintained in a primed but quiescent state, thus contributing little to steady-state megakaryopoiesis. Even though lineage-specific megakaryocyte transcripts are expressed, protein synthesis is suppressed. In response to acute inflammation, SL-MkPs become activated, resulting in megakaryocyte protein production from pre-existing transcripts and a maturation of SL-MkPs and other megakaryocyte progenitors. This results in an efficient replenishment of platelets that are lost during inflammatory insult. Thus, our study reveals an emergency machinery that counteracts life-threatening platelet depletions during acute inflammation.

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“…Platelet counts may decrease by as much as 25% to 50% from baseline [9]. This effect is dose dependent, usually occurs within the first few weeks of IFN therapy, and leads to dose reductions or withdrawal from therapy in up to 25% of patients [10]. Because interferon treatment is the only critical treatment that eliminate hepatitis C virus, reduces fibrosis stage, and decrease the risk of hepatocellular carcinoma, medical or surgical reversal of hypersplenism is necessary.…”

Section: Interferonmentioning

confidence: 99%

Overwhelming Postsplenectomy Infection for Splenectomized HCV Patients

Hashimoto¹

2015

OALib

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Pegylated-interferon (IFN) plus ribavirin remains the most effective therapeutic regimen for patients with chronic hepatitis C interferon. Thrombocytopenia is a common side effect of this treatment, often leading to discontinuation of a potentially curative therapy. Splenectomy was a clinically effective treatment for hepatitis C virus-associated thrombocytopenia. Splenectomy in patients with hepatitis C cirrhosis is now safer prelude to antiviral treatment. Overwhelming post splenectomy infection (OPSI) syndrome is a rare condition, but is associated with high mortality. However, recognition and clinical management of OPSI is not well established. We reviewed the literature characterizing the clinicopathological features of OPSI and assessed the most effective and feasible administration of the condition. Prevention strategies such as vaccination and education are also potentially important parts of the strategy for splenectomized HCV patients.

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Interferon-induced thrombocytopenia: Is it time for thrombopoietin?

Abstract: Abbreviations: TPO, thrombopoietin; mRNA, messenger RNA; IFN, interferon alfa; PEG-rHuMGDF, pegylated recombinant human megakaryocyte growth and development factor; rHuTPO, recombinant human thrombopoietin.

Cited by 26 publications

References 20 publications

Hepatic thrombopoietin mRNA levels in acute and chronic liver failure of childhood

Hepatic thrombopoietin mRNA levels in acute and chronic liver failure of childhood

Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors

Overwhelming Postsplenectomy Infection for Splenectomized HCV Patients

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