Albumin–bilirubin grade as a predictor of survival in hepatocellular carcinoma patients with thrombocytopenia

BACKGROUND The models for assessing liver function,mainly the Child–Pugh(CP),albuminbilirubin(ALBI),and platelet–ALBI(PALBI)classifications,have been validated for use in estimating the prognosis of hepatocellular carcinoma(HCC)patients.However,thrombocytopenia is a common finding and may influence the prognostic value of the three models in HCC.AIM To investigate and compare the prognostic performance of the above three models in thrombocytopenic HCC patients.METHODS A total of 135 patients with thrombocytopenic HCC who underwent radical surgery were retrospectively analyzed.Preoperative scores on the CP,ALBI and PALBI classifications were estimated accordingly.Kaplan–Meier curves with logrank tests and Cox regression models were used to explore the significant factors associated with overall survival(OS)and recurrence-free survival(RFS).RESULTS The preoperative platelet counts were significantly different among the CP,ALBI and PALBI groups.After a median follow-up of 28 mo,39.3%(53/135)of the patients experienced postoperative recurrence,and 36.3%(49/135)died.Univariate analysis suggested thatα-fetoprotein levels,tumor size,vascular invasion,and ALBI grade were significant predictors of OS and RFS.According to the multivariate Cox regression model,ALBI was identified as an independent prognostic factor.However,CP and PALBI grades were not statistically significant prognostic indicators.CONCLUSION The ALBI grade,rather than CP or PALBI grade,is a significant prognostic indicator for thrombocytopenic HCC patients.

Predictive value of thrombocytopenia for bloodstream infection in patients with sepsis and septic shock

BACKGROUND Thrombocytopenia is common in patients with sepsis and septic shock.AIM To analyse the decrease in the number of platelets for predicting bloodstream infection in patients with sepsis and septic shock in the intensive care unit.METHODS A retrospective analysis of patients admitted with sepsis and septic shock in Xingtai People Hospital was revisited.Patient population characteristics and laboratory data were collected for analysis.RESULTS The study group consisted of 85(39%)inpatients with bloodstream infection,and the control group consisted of 133(61%)with negative results or contamination.The percentage decline in platelet counts(PPCs)in patients positive for pathogens[57.1(41.3-74.6)]was distinctly higher than that in the control group[18.2(5.1–43.1)](P<0.001),whereas the PPCs were not significantly different among those with gram-positive bacteraemia,gram-negative bacteraemia,and fungal infection.Using receiver operating characteristic curves,the area under the curve of the platelet drop rate was 0.839(95%CI:0.783-0.895).CONCLUSION The percentage decline in platelet counts is sensitive in predicting bloodstream infection in patients with sepsis and septic shock.However,it cannot identify gram-positive bacteraemia,gram-negative bacteraemia,and fungal infection.

Angiotensin II administration in severe thrombocytopenia and chronic venous thrombosis:A case report

BACKGROUND The initial trials on angiotensin II(AT II)administration indicated a high incidence of thrombocytopenia and thrombosis,as well as a positive correlation between hyperreninemia and response to the medication.CASE SUMMARY We describe a case of a patient presenting with catecholamine resistant septic shock,thrombocytopenia,deep vein thrombosis,and normal renin concentration who responded immediately to AT II treatment.We observed no worsening of thrombocytopenia and no progression of thrombosis or additional thromboses during treatment.CONCLUSION Our case underscores the need for individualized assessment of patients for potential therapy with AT II.

Establishment of a Mouse Thrombocytopenia Model Induced by Cyclophosphamide

An experiment was conducted to compare the effects of two mouse thrombocytopenia models induced by cyclophosphamide at two different administration routes to determine a proper cyclophosphamide administration route that could cause stable thrombocytopenia. A suitable drug dosage that could induce thrombocytopenia in mouse efficiently with the definite administration route was then investigated. BALB/c mice were randomly divided into Normal, Model A and Model B groups. To Model A, 200 mg/kg of cyclophosphamide was given by vena caudalis injection as first dose and 30 mg/kg as maintenance dose by intraperitoneal injection at the following 6 days. To Model B, 150 mg/kg of cyclophosphamide was given by subcutaneous injection once a day for consecutive 3 days. All groups were under investigation for 15 days. The result suggested that a decrease in the number of blood platelets of Model B at the 7th day were significantly than that of Normal. Other platelet related indices like platelet distribution width, mean platelet volume and platelet-large cell ratio of Model B increased significantly in comparison with those of Normal group. The platelets count was reduced but fluctuated greatly, and more than half of the mice died in Model A. Therefore, subcutaneous injection of cyclophosphamide for 3 days was used for the cyclophosphamide dosage test. BALB/c mice were randomly divided into Normal, cyclophosphamide low dose （100 mg/kg）, medium dose （120 mg/kg） and high dose （140 mg/kg） groups. All groups were under investigation for 11 days. Though all 3 dosages successfully initiated thrombocytopenia as the platelets number dropped at the 7th day, the low dose was considered to be a suitable one that was of high efficacy and low toxicity. Thus, BALB/c mice challenged by subcutaneous injection of cyclophosphamide 100 mg/kg per day for 3 consecutive day is one simple, feasible and stable mouse thrombocytopenia model that could be used for pharmacodynamic test of the drugs which are supposed to have platelets increasing effect.

Successful Treatment of Severe Heparin-induced Thrombocytopenia with Intravenous Immunoglobulin, Platelet Transfusion and Rivaroxaban: A Case Report

Heparin-induced thrombocytopenia(HIT) is a relatively infrequent complication of heparin administration. HIT can cause devastating thrombosis, making it one of the most serious adverse drug reactions encountered in clinical practice. We successfully treated a case of severe HIT presenting with thrombosis and life-threatening bleeding complications with intravenous immunoglobulin(IVIG), platelet transfusion and oral anticoagulant Rivaroxaban. In this case, we considered that IVIG played the most important role by preventing further thrombosis, increasing the platelet count, and ensuring the efficacy of Rivaroxaban. We therefore suggest that IVIG might be the optimal treatment for patients with this urgent condition.

Management of thrombocytopenia due to liver cirrhosis:A review

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.

Acquired amegakaryocytic thrombocytopenia previously diagnosed as idiopathic thrombocytopenic purpura in a patient with hepatitis C virus infection

We report the first case of a patient with hepatitis C virus(HCV) infection and idiopathic thrombocytopenic purpura(ITP), who later developed acquired amegakaryocytic thrombocytopenia(AAMT), with autoantibodies to the thrombopoietin(TPO) receptor(c-Mpl). A 64-year-old woman, with chronic hepatitis C, developed severe thrombocytopenia and was diagnosed with ITP. She died of liver failure. Autopsy revealed cirrhosis and liver carcinoma. In the bone marrow, a marked reduction in the number of megakaryocytes was observed, while other cell lineages were preserved. Therefore, she was diagnosed with AAMT. Additionally, autoantibodies to c-Mpl were detected in her serum. Autoantibodies to c-Mpl are one of the causes of AAMT, acting through inhibition of TPO function, megakaryocytic maturation, and platelet formation. HCV infection induces several autoantibodies. HCV infection might also induce autoantibodies to c-Mpl, resulting in the development of AAMT. This mechanism may be one of the causes of thrombocytopenia in patients with HCV infection.

High frequency of thrombocytopenia in patients with acute-on-chronic liver failure treated with linezolid

BACKGROUND： Linezolid is an effective antibiotic reagent for Gram-positive bacterial infection; its most common side effect is thrombocytopenia. However, the incidence of throm- bocytopenia in patients with acute-on-chronic liver failure （ACLF） who underwent linezolid therapy was unclear. The present study was to evaluate the incidence of thrombocyto- penia in ACLF and non-ACLF patients treated with linezolid and the risk factors of thrombocytopenia in these patients.

Profound thrombocytopenia induced by clopidogrel with a prior history of long-term safe administration

Clopidogrel has shown an excellent safety,tolerability and efficacy ever since its marketing.However,here we report a rare case with profound thrombocytopenia following clopidogrel administration previously safely exposed to this same drug.This reminds us that thrombocytopenia might be induced by clopidogrel even with a prior,safe history of long-term administration.

Evaluation of the effect of partial splenic embolization on platelet values for liver cirrhosis patients with thrombocytopenia

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 × 10^3/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 paUents 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 complication rate 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.

Thrombocytopenia after liver transplantation:should we care?

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.

Close Correlation between Development of MODS during the Initial 72h of Hospitalization and Hospital Mortality in Severe Fever with Thrombocytopenia Syndrome

An emerging infectious disease was identified as severe fever with thrombocytopenia syn- drome （SFTS） in central China since late March 2009. We found the patients with SFTS had severe clinical symptoms, and progressed rapidly to multiple organ dysfunction syndrome （MODS） with high fatality rate of 25%-30%. The aim of this study was to assess the significance of risk factors predicting the development of MODS and death in SFTS patients. Consecutive SFTS admissions between May 2009 and September 2011 were analyzed for parameters of organ function during hospitalization using Marshall scoring system for MODS, and platelet counts were recorded on admission and at 24, 48, 72 h and one week after admission. We investigated the kinetics of organ failures and analyzed the associa- tion between age, platelet count and development of MODS or death. A total of 92 SFTS patients were enrolled in this study. Among them, 32 patients with dysfunction of over 4 organs were identified, 45% of them died within 72 h, 72% died within 5 days, and 76% died within 7 days after admission. We also found cumulative Marshall score was significantly higher in death patients （11.76＋2.05） than in survival patients （4.22~1.98） （P〈0.001）. In addition, SFTS patients had older age and lower platelet counts in MODS and death groups. Furthermore, we also observed that there was a close correlation between platelet count on admission and Marshall score （P〈0.001）. High Marshall score, advanced age and lower platelet counts were the main risk factors for the development of MODS, and those factors could predict mortality in SFTS patients, suggesting prompt treatment and close monitoring of severe complications, especially MODS, are of great importance in saving patients＇ lives.

Thrombocytopenia for prediction of hepatocellular carcinoma recurrence: Systematic review and meta-analysis

AIM: To investigate the association between thrombocytopenia and relapse after treatment for hepatocellular carcinoma(HCC).METHODS: We searched the Pub Med, EMBASE, and Web of Science databases to obtain eligible studies. The hazard ratios(HRs) values and 95% confidence intervals(CIs) were pooled by random effects model. Subsequently, we estimated the heterogeneity, performed a sensitivity analysis, determined the publication bias, and performed subgroup and meta-regression analyses. Study quality was assessed by using the Oxford Center for Evidence Based Medicine tool.RESULTS: We identified 18 eligible studies by retrieval(published during 2000-2014). Out of the 4163 patients with HCC who were recruited, 2746(66.0%) experienced recurrence. In general, our meta-analysis suggested that low platelet count(PLT) before therapy significantly increased the probability of postoperative recurrence(HR = 1.53, 95%CI: 1.29-1.81). PLT was also valuable in the prediction of intrahepatic distant recurrence(HR = 1.49, 95%CI: 1.25-1.77). Subgroupand meta-regression analyses identified various therapeutic modalities as the source of a high degree of heterogeneity. The pooled HR values showed no obvious change when a single study was removed, but otherwise, an opposite-effects model was used. In addition, no significant publication bias was detected.CONCLUSION: Thrombocytopenia before treatment might be an inexpensive and useful predictor of postoperative recurrence in patients with HCC.

Laparoscopic splenectomy for primary immune thrombocytopenia:Current status and challenges

Primary immune thrombocytopenia(ITP) is an immunemediated disorder affecting both adults and children, characterised by bleeding complications and low platelet counts. Corticosteroids are the first-line therapy for ITP, but only 20%-40% of cases achieve a stable response. Splenectomy is the main therapy for patients failing to respond to corticosteroids for decades, and about two-thirds of patients achieve a long-lasting response. Although some new drugs are developed to treat ITP as second-line therapies in recent years, splenectomy is still the better choice with less cost and more efficiency. Laparoscopic splenectomy(LS) for ITP proves to be a safe technique associated with lower morbidity and faster recovery and similar hematological response when compared to traditional open splenectomy. Based on the unified hematological outcome criteria by current international consensus, the response rate of splenectomy should be reassessed. So far, there are not widely accepted preoperative clinical indicators predicting favorable response to LS. Since the patients undergoing surgery take the risk of complications and poor hematological outcome, the great challenge facing the doctors is to identify a reliable biomarker for predicting longterm outcome of splenectomy which can help make the decision of operation.

Wilson disease associated with immune thrombocytopenia: A case report and review of the literature

BACKGROUND Wilson disease (WD) is a genetic disorder of hepatic copper excretion,leading to copper accumulation in various tissues.The manifestations are quite variable,and hemolytic anemia is the most common hematological presentation.WD associated with thrombocytopenia is very rare.CASE SUMMARY We report the case of an 11-year-old Chinese girl with WD that was associated with immune thrombocytopenia (ITP).Thrombocytopenia was the initial chief complaint for her to visit a hematologist,and ITP was diagnosed based on the results of a bone marrow biopsy and positive antiplatelet autoantibodies.About two weeks before the thrombocytopenia was found,the patient developed drooling.Tremors developed in her right hand about one week after being diagnosed with ITP,after which she was admitted to our hospital.Further evaluations were performed.Ceruloplasmin was decreased,with an increased level of copper in her 24-h urine excretion.Kayser Fleischer's ring (K-F ring) was positive.The ultrasound showed liver cirrhosis,and brain magnetic resonance imaging showed that the lenticular nucleus,caudate nucleus,and brainstem presented a low signal intensity in T1-weighted images and high signal intensity in T2-weighted images.WD was diagnosed and a genetic analysis was performed.A compound heterozygous mutation in ATP7B was detected;c.2333G>T (p.Arg778Leu) in exon 8 and c.3809A>G (p.Asn1270Ser) in exon 18.The former was inherited from her father and the latter from her mother.However,her parents showed normal liver function and negative K-F rings.Such a compound mutation in a case of WD associated with ITP in children has not been published previously.CONCLUSION WD can associate with thrombocytopenia but the mechanism is still unclear.We recommend that antiplatelet autoantibodies should be tested in WD patients with thrombocytopenia in future to verify the association.

Interferon-α induced severe thrombocytopenia:A case report and review of the literature

We report a case of severe thrombocytopenia following pegylated interferon-α 2a(Peg-IFN-α 2a)treatment of hepatitis C virus infection and summarize the clinical characteristics of 16 cases of IFN-α induced severe thrombocytopenia and its immune-mediated mechanism.Discontinuation of IFN-α and early administration of immunosuppressants are the effective therapy for IFN-αinduced severe thrombocytopenia.

Expert consensus on the diagnosis and treatment of thrombocytopenia in adult critical care patients in China

Thrombocytopenia is a common complication of critical care patients.The rates of bleeding events and mortality are also significantly increased in critical care patients with thrombocytopenia.Therefore,the Critical Care Medicine Committee of Chinese People’s Liberation Army(PLA)worked with Chinese Society of Laboratory Medicine,Chinese Medical Association to develop this consensus to provide guidance for clinical practice.The consensus includes five sections and 27 items:the definition of thrombocytopenia,etiology and pathophysiology,diagnosis and differential diagnosis,treatment and prevention.

Thrombocytopenia in cirrhosis:Impact of fibrinogen on bleeding risk

AIMTo investigate the relationship between baseline platelet count, clauss fibrinogen, maximum amplitude (MA) on thromboelastography, and blood loss in orthotopic liver transplantation (OLT). METHODSA 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 ( RESULTSOf 322 OLT patients, 77 were excluded due to fulminant disease; redo transplant or baseline haemoglobin (Hb) of 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 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. CONCLUSIONPlatelet 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.

Severe immune thrombocytopenia after peg-interferonalpha2a, ribavirin and telaprevir treatment completion: a case report and systematic review of literature

Mild to moderate autoimmune thrombocytopenia(AITP) is a common finding in patients receiving interferonbased antiviral treatment, due to bone marrow suppression. Here we report the case of a patient with chronic genotype 1b hepatitis C virus(HCV) infection treated with pegylated-interferon alpha-2a, ribavirin and telaprevir for 24 wk; the patient developed severe AITP three weeks after treatment withdrawal. We performed a systematic literature search in order to review all published cases of AITP related to HCV antiviral treatment. To our knowledge, this is the second case of AITP observed after antiviral treatment withdrawal. In most published cases AITP occurred during treatment; in fact, among 24 cases of AITP related to interferonbased antiviral treatment, only one occurred after discontinuation. Early diagnosis of AITP is a key factor in order to achieve an early interferon discontinuation; in the era of new direct antiviral agents those patients have to be considered for interferon-free treatment regimens. Prompt prescription of immuno-suppressant treatment(i.e., corticosteroids, immunoglobulin infusion and even rituximab for unresponsive cases) leads to favourable prognosis in most of cases. Physicians using interferonbased treatments should be aware that AITP can occur both during and after treatment, specially in the new era of interferon-free antiviral treatment. Finally, in the case of suspected AITP, presence of anti-platelet antibodies should be checked not only during treatment but alsoafter discontinuation.

Preservation of platelet function in patients with cirrhosis and thrombocytopenia undergoing esophageal variceal ligation

Background:Thrombocytopenia is a possible risk factor for bleeding after band ligation of esophageal varices.However,elevated von Willebrand factor(VWF)in cirrhosis improves platelet function and could decrease this risk.Our objective was to assess platelet function in patients with cirrhosis undergoing esophageal variceal ligation(EVL).Methods:The assessment consisted of platelet count,antigen and activity of VWF and VWF-cleaving protease ADAMTS-13 activity,and a platelet adhesion and aggregation test simulating vascular flow in vivo(Impact-RR)prior to EVL.Results:Totally 111 patients were divided into three groups according to platelet count:(1)<50×109/L(n=38,34.2%);(2)50×109/L to 100×109/L(n=47,42.3%);and(3)>100×109/L(n=26,23.4%).No statistically significant difference was found in the aggregate size of platelets[group 1:41.0(31.8–67.3)μm 2;group 2:47.0(33.8–71.3)μm 2;and group 3:47.0(34.0–66.0)μm 2;P=0.60]and no significant correlation was found between aggregate size and platelet count(Spearman r=0.07;P=0.47).Surface coverage was 4.1%(2.8%–6.7%),8.5%(4.0%–10.0%),and 9.0%(7.1%–12.0%)(P<0.001)in groups 1,2 and 3,respectively and correlated with platelet count(Spearman r=0.39;P<0.0001).There was no significant difference between groups in VWF or ADAMTS-13.Post-EVL bleeding occurred in six(5.4%)patients(n=2 in group 1,n=1 in group 2,and n=3 in group 3;P=0.32).Patients with bleeding had higher MELD scores[15.0(11.3–20.3)versus 12.0(10.0–15.0);P=0.025],but no difference was demonstrated for platelet function parameters.Conclusion:Platelet function is preserved even in the presence of thrombocytopenia,including in the patients with post-EVL bleeding.