BACKGROUND During cirrhosis,the liver is impaired and unable to synthesize and clear thrombopoietin properly.At the same time,the spleen assumes the function of hemofiltration and storage due to liver dysfunction,resu...BACKGROUND During cirrhosis,the liver is impaired and unable to synthesize and clear thrombopoietin properly.At the same time,the spleen assumes the function of hemofiltration and storage due to liver dysfunction,resulting in hypersplenism and excessive removal of platelets in the spleen,further reducing platelet count.When liver function is decompensated in cirrhotic patients,the decrease of thrombopoietin(TPO)synthesis is the main reason for the decrease of new platelet production.This change of TPO leads to thrombocytopenia and bleeding tendency in cirrhotic patients with hypersplenism.AIM To investigate the clinical efficacy of recombinant human TPO(rhTPO)in the treatment of perioperative thrombocytopenia during liver transplantation in cirrhotic mice with hypersplenism.METHODS C57BL/6J mice and TPO receptor-deficient mice were used to establish models of cirrhosis with hypersplenism.Subsequently,these mice underwent orthotopic liver transplantation(OLT).The mice in the experimental group were given rhTPO treatment for 3 consecutive days before surgery and 5 consecutive days after surgery,while the mice in the control group received the same dose of saline at the same frequency.Differences in liver function and platelet counts were determined between the experimental and control groups.Enzyme-linked immunosorbent assay was used to assess the expression of TPO and TPO receptor(c-Mpl)in the blood.RESULTS Preoperative administration of rhTPO significantly improved peri-OLT thrombocytopenia in mice with cirrhosis and hypersplenism.Blocking the expression of TPO receptors exacerbated peri-OLT thrombocytopenia.The concentration of TPO decreased while the concentration of c-Mpl increased in compensation in the mouse model of cirrhosis with hypersplenism.TPO pre-treatment significantly increased the postoperative TPO concentration in mice,which in turn led to a decrease in the c-Mpl concentration.TPO pre-treatment also significantly enhanced the Janus kinase(Jak)/signal transducers and activators of transcription pathway protein expressions in bone marrow stem cells of the C57BL/6J mice.Moreover,the administration of TPO,both before and after surgery,regulated the levels of biochemical indicators,such as alanine aminotransferase,alkaline phosphatase,and aspartate aminotransferase in the C57BL/6J mice.CONCLUSION Pre-treatment with TPO not only exhibited therapeutic effects on perioperative thrombocytopenia in the mice with cirrhosis and hypersplenism,who underwent liver transplantation but also significantly enhanced the perioperative liver function.展开更多
Thrombocytopenia is a common complication in liver disease and can adversely affect the treatment of liver cirrhosis,limiting the ability to administer therapy and delaying planned surgical/diagnostic procedures becau...Thrombocytopenia is a common complication in liver disease and can adversely affect the treatment of liver cirrhosis,limiting the ability to administer therapy and delaying planned surgical/diagnostic procedures because of an increased risk of bleeding.Multiple factors,including splenic sequestration,reduced activity of the hematopoietic growth factor thrombopoietin,bone marrow suppression by chronic hepatitis C virus infection and anti-cancer agents,and antiviral treatment with interferon-based therapy,can contribute to the development of thrombocytopenia in cirrhotic patients.Of these factors,the major mechanisms for thrombocytopenia in liver cirrhosis are(1)platelet sequestration in the spleen;and(2)decreased production of thrombopoietin in the liver.Several treatment options,including platelet transfusion,interventional partial splenic embolization,and surgical splenectomy,are now available for severe thrombocytopenia in cirrhotic patients.Although thrombopoietin agonists and targeted agents are alternative tools for noninvasively treating thrombocytopenia due to liver cirrhosis,their ability to improve thrombocytopenia in cirrhotic patients is under investigation in clinical trials.In this review,we propose a treatment approach to thrombocytopenia according to our novel concept of splenic volume,and we describe the current management of thrombocytopenia due to liver cirrhosis.展开更多
AIM: To investigate the effect of partial splenic embolization (PSE) on platelet values in liver cirrhosis patients with thrombocytopenia and to determine the effective embolization area for platelet values improvemen...AIM: To investigate the effect of partial splenic embolization (PSE) on platelet values in liver cirrhosis patients with thrombocytopenia and to determine the effective embolization area for platelet values improvement. METHODS: Blood parameters and liver function indicators were measured on 10 liver cirrhosis patients (6 in Child-Pugh grade A and 4 in grade B) with thrombocytopenia (platelet values < 80 × 103/μL) before embolization. Computed tomography scan was also needed in advance to acquire the splenic baseline. After 2 to 3 d, angiography and splenic embolization were performed. A second computed tomography scan was made to confirm the embolization area after 2 to 3 wk of embolization. The blood parameters of patients were also examined biweekly during the 1 year follow-up period. RESULTS: According to the computed tomography images after partial splenic embolization, we divided all patients into two groups: low (< 30%), and high (≥ 30%) embolization area groups. The platelet values were increased by 3 times compared to baseline levels after 2 wk of embolization in high embolization area group. In addition, there were significant differences in platelet values between low and high embolization area groups. GPT values decreased significantly in all patients after 2 wk of embolization. The improvement in platelet and GPT values still persisted until 1 year after PSE. In addition, 3 of 4 (75%) Child-Pugh grade B patients progressed to grade A after 2 mo of PSE. The complicationrate in < 30% and ≥ 30% embolization area groups was 50% and 100%, respectively. CONCLUSION: Partial splenic embolization is an effective method to improve platelet values and GPT values in liver cirrhosis patients with thrombocytopenia and the ≥ 30% embolization area is meaningful for platelet values improvement. The relationship between the complication rate and embolization area needs further studies.展开更多
BACKGROUND Chronic liver disease(CLD)related thrombocytopenia increases the risk of bleeding and poor prognosis.Many liver disease patients require invasive procedures or surgeries,such as liver biopsy or endoscopic v...BACKGROUND Chronic liver disease(CLD)related thrombocytopenia increases the risk of bleeding and poor prognosis.Many liver disease patients require invasive procedures or surgeries,such as liver biopsy or endoscopic variceal ligation,and most of them have lower platelet counts,which could aggravate the risk of bleeding due to liver dysfunction and coagulation disorders.Unfortunately,there is no defined treatment modality for CLD-induced thrombocytopenia.Recombinant human thrombopoietin(rhTPO)is commonly used to treat primary immune thrombocytopenic purpura and thrombocytopenia caused by solid tumor chemotherapy;however,there are few reports on the use of rhTPO in the treatment of CLD-related thrombocytopenia.AIM To evaluate the efficacy of rhTPO in the treatment of patients with CLDassociated thrombocytopenia undergoing invasive procedures.METHODS All analyses were based on the retrospective collection of clinical data of patients with CLD who were treated in the Department of Infectious Diseases at The First Affiliated Hospital of Soochow University between June 2020 and December 2021.Fifty-nine male and 41 female patients with liver disease were enrolled in this study to assess the changes in platelet counts and parameters before and after the use of rhTPO for thrombocytopenia.Adverse events related to treatment,such as bleeding,thrombosis,and disseminated intravascular coagulation,were also investigated.RESULTS Among the enrolled patients,78(78%)showed a platelet count increase after rhTPO use,while 22(22%)showed no significant change in platelet count.The mean platelet count after rhTPO treatment in all patients was 101.53±81.81×10^(9)/L,which was significantly improved compared to that at baseline(42.88±16.72×10^(9)/L),and this difference was statistically significant(P<0.001).In addition,patients were further divided into three subgroups according to their baseline platelet counts(<30×10^(9)/L,30-50×10^(9)/L,>50×10^(9)/L).Subgroup analyses showed that the median platelet counts after treatment were significantly higher(P<0.001,all).Ninety(90%)patients did not require platelet transfusion partially due to an increase in platelet count after treatment with rhTPO.No serious adverse events related to rhTPO treatment were observed.Overall,rhTPO demonstrated good clinical efficacy for treating CLD-associated thrombocytopenia.CONCLUSION rhTPO can improve platelet count,reduce the risk of bleeding,and decrease the platelet transfusion rate,which may promote the safety of invasive procedures and improve overall survival of patients with CLD.展开更多
Transient thrombocytopenia is a common phenomenon after liver transplantation. After liver transplantation(LT), platelet count decreases and reaches a nadir on postoperative days 3-5, with an average reduction in plat...Transient thrombocytopenia is a common phenomenon after liver transplantation. After liver transplantation(LT), platelet count decreases and reaches a nadir on postoperative days 3-5, with an average reduction in platelet counts of 60%; platelet count recovers to preoperative levels approximately two weeks after LT. The putative mechanisms include haemodilution, decreased platelet production, increased sequestration, medications, infections, thrombosis, or combination of these processes. However, the precise mechanisms remain unclear. The role of platelets in liver transplantation has been highlighted in recent years, and particular attention has been given to their effects beyond hemostasis and thrombosis. Previous studies have demonstrated that perioperative thrombocytopenia causes poor graft regeneration, increases the incidence of postoperative morbidity, and deteriorates the graft and decreases patient survival in both the short and long term after liver transplantation. Platelet therapies to increase perioperative platelet counts, such as thrombopoietin, thrombopoietin receptor agonist, platelet transfusion, splenectomy, and intravenous immunoglobulin treatment might have a potential for improving graft survival, however clinical trials are lacking. Further studies are warranted to detect direct evidence on whether thrombocytopenia is the cause or result of poor-graft function and postoperative complications, and to determine who needs platelet therapies in order to prevent postoperative complications and thus improve post-transplant outcomes.展开更多
Chronic liver disease is characterized by several hematological derangements resulting in a complex and barely rebalanced haemostatic environment.Thrombocytopenia is the most common abnormality observed in these patie...Chronic liver disease is characterized by several hematological derangements resulting in a complex and barely rebalanced haemostatic environment.Thrombocytopenia is the most common abnormality observed in these patients and recent advances have led to researchers focus the attention on the multifactorial origin of thrombocytopenia and on the key role of thrombopoietin(TPO)in its physiopathology.Severe thrombocytopenia(platelet count<50000/μL)complicates the management of patients with chronic liver disease by increasing the potential risk of bleeding for invasive procedures,which may be therefore delayed or canceled even if lifesaving.In the very last years,the development of new drugs which exceed the limits of the current standard of care(platelet transfusions,either immediately before or during the procedure)paves the way to a new scenario in the management of this population of patients.Novel agents,such as the TPOreceptor agonists avatrombopag and lusutrombopag,have been developed in order to increase platelet production as an alternative to platelet transfusions.These agents have demonstrated a good profile in terms of efficacy and safety and will hopefully allow reducing limitations and risks associated with platelet transfusion,without any delay in scheduled interventions.Altogether,it is expected that patients with chronic liver disease will be able to face invasive procedures with one more string in their bow.展开更多
AIM To investigate the relationship between baseline platelet count,clauss fibrinogen,maximum amplitude(MA) on thromboelastography,and blood loss in orthotopic liver transplantation(OLT).METHODS A retrospective analys...AIM To investigate the relationship between baseline platelet count,clauss fibrinogen,maximum amplitude(MA) on thromboelastography,and blood loss in orthotopic liver transplantation(OLT).METHODS A retrospective analysis of our OLT Database(2006-2015) was performed.Baseline haematological indices and intraoperative blood transfusion requirements,as a combination of cell salvage return and estimation of 300 mls/unit of allogenic blood,was noted as a surrogate for intraoperative bleeding.Two groups:Excessive transfusion(>1200 mL returned) and No excessive transfusion(<1200 m L returned) were analysed.All data analyses were conducted using IBM SPSS Statistics version 23.RESULTS Of 322 OLT patients,77 were excluded due to fulminant disease;redo transplant or baseline haemoglobin(Hb) of<80 g/L.One hundred and fourteen(46.3%) were classified into the excessive transfusion group,132(53.7%) in the no excessive transfusion group.Mean age and gender distribution were similar in both groups.Baseline Hb(P≤0.001),platelet count(P=0.005),clauss fibrinogen(P=0.004) and heparinase MA(P=0.001) were all statistically significantly different.Univariate logistic regression with a cut-off of platelets<50×10~9/L as the predictor and Haemorrhage as the outcome showed an odds ratio of 1.393(95%CI:0.758-2.563;P=0.286).Review of receiver operating characteristic curves showed an area under the curve(AUC) for platelet count of 0.604(95%CI:0.534-0.675;P=0.005) as compared with AUC for fibrinogen level,0.678(95%CI:0.612-0.744;P≤0.001).A multivariate logistic regression shows United Kingdom model for End Stage Liver Disease(P=0.006),Hb(P=0.022) and Fibrinogen(P=0.026) to be statistically significant,whereas Platelet count was not statistically significant.CONCLUSION Platelet count alone does not predict excessive transfusion.Additional investigations,e.g.,clauss fibrinogen and viscoelastic tests,provide more robust assessment of bleeding-risk in thrombocytopenia and cirrhosis.展开更多
Thrombocytopenia is a multifactorial disorder that is common in patients with chronic liver disease(CLD),leading to challenging perioperative planning.As thrombocytopenia in CLD is associated with thrombopoietin(TPO)d...Thrombocytopenia is a multifactorial disorder that is common in patients with chronic liver disease(CLD),leading to challenging perioperative planning.As thrombocytopenia in CLD is associated with thrombopoietin(TPO)deficiency,the use of TPO-receptor agonists(TPO-RAs)to increase platelet counts is a promising approach.This has led to the development of various TPO-RAs,including romiplostim,eltrombopag,avatrombopag,and lusutrombopag.Of these,only avatrombopag and lusutrombopag are approved by the United States Food and Drug Administration for the perioperative treatment of thrombocytopenia in patients with CLD.Platelet transfusion is commonly used for the clinical management of thrombocytopenia in patients with CLD undergoing invasive procedures.However,the limitations and possible risks of transfusion,including short duration of efficacy,development of antiplatelet antibodies,risk of infections and such complications as transfusion-related acute lung injury or circulatory overload,and possibility of refractoriness,limit its use.Moreover,there is no consensus among guidelines as to the platelet count at which transfusions are indicated.Results from studies using TPO-RAs perioperatively in patients with thrombocytopenia and CLD are promising and provide an alternative to platelet transfusions in the pre-and post-operative setting.These TPO-RAs are the subject of this review,with focus on their use in the perioperative setting in patients with thrombocytopenia,associated supporting clinical trials,efficacy and safety data,and their use with respect to platelet transfusions.展开更多
Second generation thrombopoietin agonists including eltrombopag and romiplostim act on the thrombopoietin receptor to increase the megakaryocyte production. These agents were needed as use of first generation recombin...Second generation thrombopoietin agonists including eltrombopag and romiplostim act on the thrombopoietin receptor to increase the megakaryocyte production. These agents were needed as use of first generation recombinant products was associated with formation of autoantibodies. Eltrombopag is an oral thrombopoietin agonist found effective in raising platelet counts in patients with immune thrombocytopenia. The drug has now been found to be useful in raising platelet counts in thrombocytopenia related to liver disease including cirrhosis and chronic viral hepatitis. Although the drug may help enable adequate interferon therapy in patients with HCV infection and help carry out invasive procedures in patients with cirrhosis, concerns have been raised of possible thrombotic complications including portal vein thrombosis. Randomized trials have shown that use of eltrombopag concomitant with pegylated interferon and ribavirin increased the chances of sustained virologic response while decreasing the dose reductions of interferon. The data on use of romiplostim in these clinical indications is also emerging. However, in the future, availability of interferon free regimens is likely to decrease the use of eltrombopag for enabling antiviral therapy. The review discusses the role of eltrombopag in management of liver disease related thrombocytopenia in wake of recent data as also the dosage, precautions and adverse effects associated with its use.展开更多
Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors require...Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors required for organ development, tissue regeneration and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease(CLD) and cirrhosis, can manifest from decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis, as well as the role of platelets in CLD, is poorly understood. In this paper, experimental evidence of platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. In addition, we describe our current perspective based on the results of these studies. Platelets improve liver fibrosis by inactivating hepatic stellate cells, which decreases collagen production. The regenerative effect of platelets in the liver involves a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these observations, we ascertained the direct effect of platelet transfusion on improving several indicators of liver function in patients with CLD and liver cirrhosis. However, unlike the results of our previous clinical study, the smaller incremental changes in liver function in patients with CLD who received eltrombopag for 6 mo were due to patient selection from a heterogeneous population. We highlight the current knowledge concerning the role of platelets in CLD and cancer and anticipate a novel application of platelet-based clinical therapies to treat liver disease.展开更多
Background/Aims: Cirrhosis represents a late stage of progressive hepatic fibrosis and is generally considered to be irreversible in its advanced stages. Esophageal varix is a complication of liver cirrhosis and is th...Background/Aims: Cirrhosis represents a late stage of progressive hepatic fibrosis and is generally considered to be irreversible in its advanced stages. Esophageal varix is a complication of liver cirrhosis and is the consequence of portal hypertension. The aim of this study was to determine the correlation between the severity of thrombocytopenia and the presenting of esophageal varices (EVs) in cirrhotic patient. Patients and Methods: This study was a retrospective, descriptive, analytic and monocentric study, which was carried out at Gastroenterology Department, Khmer Soviet Friendship Hospital, Phnom Penh, Cambodia. It was conducted from 1st September 2020 to 31<sup>st</sup> January 2021. All patients were diagnosed as liver cirrhosis by clinic, biology and ultrasound. Patients’ data were noted in standardized questionnaire with information such as age, sex, address, laboratory result, and the result of endoscopic finding. All data were registered into a data set and then analyzed by SPSS program version 23. Results: 1445 patients were enrolled for gastroscopy. Only 303 patients (21%) were suggested for variceal screening after the exclusions. Male was predominant with sex ratio F/M (1/2.03). Patients’ age varied between 21 and 80 years old, with the mean age of 55 ± 11 years old. 199 patients (66%) were found with EVs, while EVs grade 1 and 2 without red signs were predominated, accounting to 22.8% and 19.5% respectively. The majority of the patients with platelet count between 50 - 99 giga/l had EVs vs platelet count > 150 giga/l had no EVs (p Conclusion: Thrombocytopenia is a non-invasive parameter with high accuracy for the prediction of EVs in cirrhosis. The severity of thrombocytopenia increased as the grading of EVs increased. Thus, it can assist in triaging cirrhotic patients for endoscopy to identify EVs.展开更多
基金All procedures involving animals were reviewed and approved by the Tianjin Tiancheng New Drug Evaluation Co.,Ltd(Approval No.2023041701).
文摘BACKGROUND During cirrhosis,the liver is impaired and unable to synthesize and clear thrombopoietin properly.At the same time,the spleen assumes the function of hemofiltration and storage due to liver dysfunction,resulting in hypersplenism and excessive removal of platelets in the spleen,further reducing platelet count.When liver function is decompensated in cirrhotic patients,the decrease of thrombopoietin(TPO)synthesis is the main reason for the decrease of new platelet production.This change of TPO leads to thrombocytopenia and bleeding tendency in cirrhotic patients with hypersplenism.AIM To investigate the clinical efficacy of recombinant human TPO(rhTPO)in the treatment of perioperative thrombocytopenia during liver transplantation in cirrhotic mice with hypersplenism.METHODS C57BL/6J mice and TPO receptor-deficient mice were used to establish models of cirrhosis with hypersplenism.Subsequently,these mice underwent orthotopic liver transplantation(OLT).The mice in the experimental group were given rhTPO treatment for 3 consecutive days before surgery and 5 consecutive days after surgery,while the mice in the control group received the same dose of saline at the same frequency.Differences in liver function and platelet counts were determined between the experimental and control groups.Enzyme-linked immunosorbent assay was used to assess the expression of TPO and TPO receptor(c-Mpl)in the blood.RESULTS Preoperative administration of rhTPO significantly improved peri-OLT thrombocytopenia in mice with cirrhosis and hypersplenism.Blocking the expression of TPO receptors exacerbated peri-OLT thrombocytopenia.The concentration of TPO decreased while the concentration of c-Mpl increased in compensation in the mouse model of cirrhosis with hypersplenism.TPO pre-treatment significantly increased the postoperative TPO concentration in mice,which in turn led to a decrease in the c-Mpl concentration.TPO pre-treatment also significantly enhanced the Janus kinase(Jak)/signal transducers and activators of transcription pathway protein expressions in bone marrow stem cells of the C57BL/6J mice.Moreover,the administration of TPO,both before and after surgery,regulated the levels of biochemical indicators,such as alanine aminotransferase,alkaline phosphatase,and aspartate aminotransferase in the C57BL/6J mice.CONCLUSION Pre-treatment with TPO not only exhibited therapeutic effects on perioperative thrombocytopenia in the mice with cirrhosis and hypersplenism,who underwent liver transplantation but also significantly enhanced the perioperative liver function.
基金Supported by Grant-in-Aid for Young Scientists,Ministry of Education,Culture,Sports,Science and Technology of Japan,No.24791434(to Hayashi H)and Takeda Science Foundation,Japan(to Hayashi H)
文摘Thrombocytopenia is a common complication in liver disease and can adversely affect the treatment of liver cirrhosis,limiting the ability to administer therapy and delaying planned surgical/diagnostic procedures because of an increased risk of bleeding.Multiple factors,including splenic sequestration,reduced activity of the hematopoietic growth factor thrombopoietin,bone marrow suppression by chronic hepatitis C virus infection and anti-cancer agents,and antiviral treatment with interferon-based therapy,can contribute to the development of thrombocytopenia in cirrhotic patients.Of these factors,the major mechanisms for thrombocytopenia in liver cirrhosis are(1)platelet sequestration in the spleen;and(2)decreased production of thrombopoietin in the liver.Several treatment options,including platelet transfusion,interventional partial splenic embolization,and surgical splenectomy,are now available for severe thrombocytopenia in cirrhotic patients.Although thrombopoietin agonists and targeted agents are alternative tools for noninvasively treating thrombocytopenia due to liver cirrhosis,their ability to improve thrombocytopenia in cirrhotic patients is under investigation in clinical trials.In this review,we propose a treatment approach to thrombocytopenia according to our novel concept of splenic volume,and we describe the current management of thrombocytopenia due to liver cirrhosis.
文摘AIM: To investigate the effect of partial splenic embolization (PSE) on platelet values in liver cirrhosis patients with thrombocytopenia and to determine the effective embolization area for platelet values improvement. METHODS: Blood parameters and liver function indicators were measured on 10 liver cirrhosis patients (6 in Child-Pugh grade A and 4 in grade B) with thrombocytopenia (platelet values < 80 × 103/μL) before embolization. Computed tomography scan was also needed in advance to acquire the splenic baseline. After 2 to 3 d, angiography and splenic embolization were performed. A second computed tomography scan was made to confirm the embolization area after 2 to 3 wk of embolization. The blood parameters of patients were also examined biweekly during the 1 year follow-up period. RESULTS: According to the computed tomography images after partial splenic embolization, we divided all patients into two groups: low (< 30%), and high (≥ 30%) embolization area groups. The platelet values were increased by 3 times compared to baseline levels after 2 wk of embolization in high embolization area group. In addition, there were significant differences in platelet values between low and high embolization area groups. GPT values decreased significantly in all patients after 2 wk of embolization. The improvement in platelet and GPT values still persisted until 1 year after PSE. In addition, 3 of 4 (75%) Child-Pugh grade B patients progressed to grade A after 2 mo of PSE. The complicationrate in < 30% and ≥ 30% embolization area groups was 50% and 100%, respectively. CONCLUSION: Partial splenic embolization is an effective method to improve platelet values and GPT values in liver cirrhosis patients with thrombocytopenia and the ≥ 30% embolization area is meaningful for platelet values improvement. The relationship between the complication rate and embolization area needs further studies.
基金Supported by the Science and Technology Development Plan of Suzhou,Jiangsu Province,China,No.SYS2020009.
文摘BACKGROUND Chronic liver disease(CLD)related thrombocytopenia increases the risk of bleeding and poor prognosis.Many liver disease patients require invasive procedures or surgeries,such as liver biopsy or endoscopic variceal ligation,and most of them have lower platelet counts,which could aggravate the risk of bleeding due to liver dysfunction and coagulation disorders.Unfortunately,there is no defined treatment modality for CLD-induced thrombocytopenia.Recombinant human thrombopoietin(rhTPO)is commonly used to treat primary immune thrombocytopenic purpura and thrombocytopenia caused by solid tumor chemotherapy;however,there are few reports on the use of rhTPO in the treatment of CLD-related thrombocytopenia.AIM To evaluate the efficacy of rhTPO in the treatment of patients with CLDassociated thrombocytopenia undergoing invasive procedures.METHODS All analyses were based on the retrospective collection of clinical data of patients with CLD who were treated in the Department of Infectious Diseases at The First Affiliated Hospital of Soochow University between June 2020 and December 2021.Fifty-nine male and 41 female patients with liver disease were enrolled in this study to assess the changes in platelet counts and parameters before and after the use of rhTPO for thrombocytopenia.Adverse events related to treatment,such as bleeding,thrombosis,and disseminated intravascular coagulation,were also investigated.RESULTS Among the enrolled patients,78(78%)showed a platelet count increase after rhTPO use,while 22(22%)showed no significant change in platelet count.The mean platelet count after rhTPO treatment in all patients was 101.53±81.81×10^(9)/L,which was significantly improved compared to that at baseline(42.88±16.72×10^(9)/L),and this difference was statistically significant(P<0.001).In addition,patients were further divided into three subgroups according to their baseline platelet counts(<30×10^(9)/L,30-50×10^(9)/L,>50×10^(9)/L).Subgroup analyses showed that the median platelet counts after treatment were significantly higher(P<0.001,all).Ninety(90%)patients did not require platelet transfusion partially due to an increase in platelet count after treatment with rhTPO.No serious adverse events related to rhTPO treatment were observed.Overall,rhTPO demonstrated good clinical efficacy for treating CLD-associated thrombocytopenia.CONCLUSION rhTPO can improve platelet count,reduce the risk of bleeding,and decrease the platelet transfusion rate,which may promote the safety of invasive procedures and improve overall survival of patients with CLD.
文摘Transient thrombocytopenia is a common phenomenon after liver transplantation. After liver transplantation(LT), platelet count decreases and reaches a nadir on postoperative days 3-5, with an average reduction in platelet counts of 60%; platelet count recovers to preoperative levels approximately two weeks after LT. The putative mechanisms include haemodilution, decreased platelet production, increased sequestration, medications, infections, thrombosis, or combination of these processes. However, the precise mechanisms remain unclear. The role of platelets in liver transplantation has been highlighted in recent years, and particular attention has been given to their effects beyond hemostasis and thrombosis. Previous studies have demonstrated that perioperative thrombocytopenia causes poor graft regeneration, increases the incidence of postoperative morbidity, and deteriorates the graft and decreases patient survival in both the short and long term after liver transplantation. Platelet therapies to increase perioperative platelet counts, such as thrombopoietin, thrombopoietin receptor agonist, platelet transfusion, splenectomy, and intravenous immunoglobulin treatment might have a potential for improving graft survival, however clinical trials are lacking. Further studies are warranted to detect direct evidence on whether thrombocytopenia is the cause or result of poor-graft function and postoperative complications, and to determine who needs platelet therapies in order to prevent postoperative complications and thus improve post-transplant outcomes.
文摘Chronic liver disease is characterized by several hematological derangements resulting in a complex and barely rebalanced haemostatic environment.Thrombocytopenia is the most common abnormality observed in these patients and recent advances have led to researchers focus the attention on the multifactorial origin of thrombocytopenia and on the key role of thrombopoietin(TPO)in its physiopathology.Severe thrombocytopenia(platelet count<50000/μL)complicates the management of patients with chronic liver disease by increasing the potential risk of bleeding for invasive procedures,which may be therefore delayed or canceled even if lifesaving.In the very last years,the development of new drugs which exceed the limits of the current standard of care(platelet transfusions,either immediately before or during the procedure)paves the way to a new scenario in the management of this population of patients.Novel agents,such as the TPOreceptor agonists avatrombopag and lusutrombopag,have been developed in order to increase platelet production as an alternative to platelet transfusions.These agents have demonstrated a good profile in terms of efficacy and safety and will hopefully allow reducing limitations and risks associated with platelet transfusion,without any delay in scheduled interventions.Altogether,it is expected that patients with chronic liver disease will be able to face invasive procedures with one more string in their bow.
文摘AIM To investigate the relationship between baseline platelet count,clauss fibrinogen,maximum amplitude(MA) on thromboelastography,and blood loss in orthotopic liver transplantation(OLT).METHODS A retrospective analysis of our OLT Database(2006-2015) was performed.Baseline haematological indices and intraoperative blood transfusion requirements,as a combination of cell salvage return and estimation of 300 mls/unit of allogenic blood,was noted as a surrogate for intraoperative bleeding.Two groups:Excessive transfusion(>1200 mL returned) and No excessive transfusion(<1200 m L returned) were analysed.All data analyses were conducted using IBM SPSS Statistics version 23.RESULTS Of 322 OLT patients,77 were excluded due to fulminant disease;redo transplant or baseline haemoglobin(Hb) of<80 g/L.One hundred and fourteen(46.3%) were classified into the excessive transfusion group,132(53.7%) in the no excessive transfusion group.Mean age and gender distribution were similar in both groups.Baseline Hb(P≤0.001),platelet count(P=0.005),clauss fibrinogen(P=0.004) and heparinase MA(P=0.001) were all statistically significantly different.Univariate logistic regression with a cut-off of platelets<50×10~9/L as the predictor and Haemorrhage as the outcome showed an odds ratio of 1.393(95%CI:0.758-2.563;P=0.286).Review of receiver operating characteristic curves showed an area under the curve(AUC) for platelet count of 0.604(95%CI:0.534-0.675;P=0.005) as compared with AUC for fibrinogen level,0.678(95%CI:0.612-0.744;P≤0.001).A multivariate logistic regression shows United Kingdom model for End Stage Liver Disease(P=0.006),Hb(P=0.022) and Fibrinogen(P=0.026) to be statistically significant,whereas Platelet count was not statistically significant.CONCLUSION Platelet count alone does not predict excessive transfusion.Additional investigations,e.g.,clauss fibrinogen and viscoelastic tests,provide more robust assessment of bleeding-risk in thrombocytopenia and cirrhosis.
文摘Thrombocytopenia is a multifactorial disorder that is common in patients with chronic liver disease(CLD),leading to challenging perioperative planning.As thrombocytopenia in CLD is associated with thrombopoietin(TPO)deficiency,the use of TPO-receptor agonists(TPO-RAs)to increase platelet counts is a promising approach.This has led to the development of various TPO-RAs,including romiplostim,eltrombopag,avatrombopag,and lusutrombopag.Of these,only avatrombopag and lusutrombopag are approved by the United States Food and Drug Administration for the perioperative treatment of thrombocytopenia in patients with CLD.Platelet transfusion is commonly used for the clinical management of thrombocytopenia in patients with CLD undergoing invasive procedures.However,the limitations and possible risks of transfusion,including short duration of efficacy,development of antiplatelet antibodies,risk of infections and such complications as transfusion-related acute lung injury or circulatory overload,and possibility of refractoriness,limit its use.Moreover,there is no consensus among guidelines as to the platelet count at which transfusions are indicated.Results from studies using TPO-RAs perioperatively in patients with thrombocytopenia and CLD are promising and provide an alternative to platelet transfusions in the pre-and post-operative setting.These TPO-RAs are the subject of this review,with focus on their use in the perioperative setting in patients with thrombocytopenia,associated supporting clinical trials,efficacy and safety data,and their use with respect to platelet transfusions.
文摘Second generation thrombopoietin agonists including eltrombopag and romiplostim act on the thrombopoietin receptor to increase the megakaryocyte production. These agents were needed as use of first generation recombinant products was associated with formation of autoantibodies. Eltrombopag is an oral thrombopoietin agonist found effective in raising platelet counts in patients with immune thrombocytopenia. The drug has now been found to be useful in raising platelet counts in thrombocytopenia related to liver disease including cirrhosis and chronic viral hepatitis. Although the drug may help enable adequate interferon therapy in patients with HCV infection and help carry out invasive procedures in patients with cirrhosis, concerns have been raised of possible thrombotic complications including portal vein thrombosis. Randomized trials have shown that use of eltrombopag concomitant with pegylated interferon and ribavirin increased the chances of sustained virologic response while decreasing the dose reductions of interferon. The data on use of romiplostim in these clinical indications is also emerging. However, in the future, availability of interferon free regimens is likely to decrease the use of eltrombopag for enabling antiviral therapy. The review discusses the role of eltrombopag in management of liver disease related thrombocytopenia in wake of recent data as also the dosage, precautions and adverse effects associated with its use.
文摘Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors required for organ development, tissue regeneration and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease(CLD) and cirrhosis, can manifest from decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis, as well as the role of platelets in CLD, is poorly understood. In this paper, experimental evidence of platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. In addition, we describe our current perspective based on the results of these studies. Platelets improve liver fibrosis by inactivating hepatic stellate cells, which decreases collagen production. The regenerative effect of platelets in the liver involves a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these observations, we ascertained the direct effect of platelet transfusion on improving several indicators of liver function in patients with CLD and liver cirrhosis. However, unlike the results of our previous clinical study, the smaller incremental changes in liver function in patients with CLD who received eltrombopag for 6 mo were due to patient selection from a heterogeneous population. We highlight the current knowledge concerning the role of platelets in CLD and cancer and anticipate a novel application of platelet-based clinical therapies to treat liver disease.
文摘Background/Aims: Cirrhosis represents a late stage of progressive hepatic fibrosis and is generally considered to be irreversible in its advanced stages. Esophageal varix is a complication of liver cirrhosis and is the consequence of portal hypertension. The aim of this study was to determine the correlation between the severity of thrombocytopenia and the presenting of esophageal varices (EVs) in cirrhotic patient. Patients and Methods: This study was a retrospective, descriptive, analytic and monocentric study, which was carried out at Gastroenterology Department, Khmer Soviet Friendship Hospital, Phnom Penh, Cambodia. It was conducted from 1st September 2020 to 31<sup>st</sup> January 2021. All patients were diagnosed as liver cirrhosis by clinic, biology and ultrasound. Patients’ data were noted in standardized questionnaire with information such as age, sex, address, laboratory result, and the result of endoscopic finding. All data were registered into a data set and then analyzed by SPSS program version 23. Results: 1445 patients were enrolled for gastroscopy. Only 303 patients (21%) were suggested for variceal screening after the exclusions. Male was predominant with sex ratio F/M (1/2.03). Patients’ age varied between 21 and 80 years old, with the mean age of 55 ± 11 years old. 199 patients (66%) were found with EVs, while EVs grade 1 and 2 without red signs were predominated, accounting to 22.8% and 19.5% respectively. The majority of the patients with platelet count between 50 - 99 giga/l had EVs vs platelet count > 150 giga/l had no EVs (p Conclusion: Thrombocytopenia is a non-invasive parameter with high accuracy for the prediction of EVs in cirrhosis. The severity of thrombocytopenia increased as the grading of EVs increased. Thus, it can assist in triaging cirrhotic patients for endoscopy to identify EVs.
