Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has ...Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has been proved that traditional Chinese medicine(TCM)has displayed definite therapeutic effects on viral hemorrhagic fever,indicating its potential to treat SFTS.In this study,SFTS-relative key targets were predicted via gene ontology(GO)analysis and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Molecular docking was then used to select stable binders.Molecules matched TCMs were identified,and a new prescription,Qingqi Guxue decoction(QQGX),was formulated to clear heat and nourish blood,with a resulting drug composition network.We explored the optimal drug proportion for QQGX.Through an in-depth study of molecular mechanisms,we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2(CCNA2)and cyclin-dependent kinase 2(CDK2),thereby inhibiting SFTSV replication.Finally,we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV.In summary,our study prepared a TCM decoction using the method of network pharmacology.This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.展开更多
BACKGROUND Patients with acute-on-chronic liver failure(ACLF)have a high mortality rate,poor prognosis,and often experience concurrent thrombocytopenia and bleeding events.AIM To evaluate the efficacy and safety of re...BACKGROUND Patients with acute-on-chronic liver failure(ACLF)have a high mortality rate,poor prognosis,and often experience concurrent thrombocytopenia and bleeding events.AIM To evaluate the efficacy and safety of recombinant human thrombopoietin(rhTPO)in patients with ACLF with concomitant severe thrombocytopenia.METHODS This was a prospective,open-label study.We assigned 70 ACLF patients with severe thrombocytopenia into the rhTPO group and control group,with 35 patients in each group.Patients in the rhTPO group received subcutaneous injections of rhTPO at a dose of 15000 IU/day for 7 consecutive days,while patients in the control group did not receive rhTPO treatment.The primary endpoint was the proportion of patients with platelet count>50×10^(9)/L on day 14.RESULTS The proportion of patients with platelet count>50×10^(9)/L on day 14 was 60.7%in the rhTPO group,which was significantly higher than that(12.0%)in the control group(P<0.001).The platelet count in the rhTPO group on day 14 was 64×10^(9)/L,exceeding the baseline of 28×10^(9)/L.Compared to the control group,the rhTPO group exhibited a significant increase in platelet count from baseline(P<0.05).Model for end-stage liver disease score,albumin level and international normalized ratio improved significantly from baseline on day 14 after rhTPO injection.The concentrations of serum thrombopoietin and hepatocyte growth factor in the rhTPO group after 7 days were 143.7 and 195.4 pg/mL,respectively,showing a significant increase from baseline(P<0.05).Eight(22.9%)patients had bleeding events in the control group compared with four(11.4%)in the rhTPO group.The incidence of 90-day mortality was also higher in the control group(6,17.1%)than that in the rhTPO group(3,8.6%).CONCLUSION rhTPO significantly increased the platelet count in ACLF patients with thrombocytopenia and reduce the occurrence of bleeding events,with a good safety profile.展开更多
Thrombocytopenia (defined as platelet count <sup>9</sup>/L) is present in 7% - 12% of pregnant women at delivery. Although there are mild etiologies of this condition that are often diagnosed incidentally,...Thrombocytopenia (defined as platelet count <sup>9</sup>/L) is present in 7% - 12% of pregnant women at delivery. Although there are mild etiologies of this condition that are often diagnosed incidentally, there are more severe causes that can be life threating. Thrombocytopenia also has a great implication in surgical risk and regional anesthesia. A structured evaluation of thrombocytopenia is necessary to allow an adequate diagnostic approach. Here we summarized the current knowledge of thrombocytopenia in pregnancy.展开更多
Gastrointestinal bleeding(GIB)presents a significant challenge for patients with hematologic malignancies,especially those with severe thrombocytopenia.Although endoscopic intervention is frequently used in managing G...Gastrointestinal bleeding(GIB)presents a significant challenge for patients with hematologic malignancies,especially those with severe thrombocytopenia.Although endoscopic intervention is frequently used in managing GIB,its safety and effectiveness in this high-risk group remain unclear.A recent study by Alhumayyd et al provided insight into this issue.However,it has notable limitations,including its retrospective nature,small sample size,and failure to adjust for important confounding factors such as disease severity,hemodynamic status,and platelet function.The study’s findings indicated that urgent endoscopy may help decrease the incidence of recurrent bleeding;however,it did not show a clear benefit in terms of mortality.Future research ought to prioritize prospective,multicenter studies that employ standardized protocols and incorporate risk stratification models to better understand the impact of endoscopic treatment for GIB in these patients.Additionally,integrating platelet function assays could improve clinical decision-making.Addressing these research gaps is essential for improving patient outcomes and developing effective guidelines for managing GIB in individuals with thrombocytopenia.展开更多
BACKGROUND Tamoxifen,a selective estrogen receptor modulator,is pivotal in managing hor-mone receptor-positive breast cancer.While its common side effects are well-do-cumented,tamoxifen-induced thrombocytopenia is a r...BACKGROUND Tamoxifen,a selective estrogen receptor modulator,is pivotal in managing hor-mone receptor-positive breast cancer.While its common side effects are well-do-cumented,tamoxifen-induced thrombocytopenia is a rare,serious adverse event requiring drug discontinuation.CASE SUMMARY We report a case of tamoxifen-induced thrombocytopenia in a 51-year-old preme-nopausal woman with breast cancer,occurring within 4 weeks of initiating adju-vant tamoxifen therapy.Platelet counts normalized after drug cessation,but th-rombocytopenia recurred upon rechallenge,leading to permanent disconti-nuation.CONCLUSION This case underscores the need for regular complete blood count monitoring in patients on tamoxifen to detect rare hematologic adverse events promptly.展开更多
Immune thrombocytopenia(ITP)is a hemorrhagic autoimmune disease characterized by antibody-mediated platelet injury.ITP has complicated immunopathological mechanisms that need further elucidation.It is well known that ...Immune thrombocytopenia(ITP)is a hemorrhagic autoimmune disease characterized by antibody-mediated platelet injury.ITP has complicated immunopathological mechanisms that need further elucidation.It is well known that the costimulatory molecules OX40 ligand(OX40L)and OX40 play essential roles in the immunological mechanisms of autoimmune diseases.Previously,we discovered that the expression of OX40L and OX40 is significantly increased in the peripheral blood mononuclear cells(PBMCs)of ITP patients.In our present study,OX40L-induced follicular helper T(Tfh)cells exhibited an activated phenotype with elevated expression of inducible T-cell costimulator(ICOS),programmed cell death protein-1(PD-1),and cluster of differentiation 40 ligand(CD40L)in vitro.Moreover,aberrant OX40L-OX40 expression might promote the Tfh1-to-Tfh2 shift in vivo,inducing the generation of autoantibodies by enhancing the helper function of Tfh cells for B lymphocytes in a mouse model,which might accelerate the progression of ITP.Additionally,signal transduction through the OX40L-OX40 axis might be related to the activation of tumor necrosis factor receptor-associated factor(TRAF)-nuclear factor-κB(NF-κB)and Janus kinase(JAK)-signal transducer and activator of transcription(STAT)signaling pathways.Overall,OX40L-OX40 signaling is proposed as a potential novel therapeutic target for ITP.展开更多
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 th...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.展开更多
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 cl...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.展开更多
Severe fever with thrombocytopenia syndrome （SFTS） is an emerging infectious disease caused by SFTS virus （SFTSV）. SFTSV is associated with a high mortality rate and has been reported in China, South Korea and Jap...Severe fever with thrombocytopenia syndrome （SFTS） is an emerging infectious disease caused by SFTS virus （SFTSV）. SFTSV is associated with a high mortality rate and has been reported in China, South Korea and Japan. SFTSV undergoes rapid changes owing to evolution, gene mutations, and reassortment between different strains of SFTSV. In this review, we summarize the recent cases and general properties of SFTS, focusing on the epidemiology, genetic diversity, clinical features, and diagnostics of SFTSV in China. From 2010 to October 2016, SFTS cases were reported in 23 provinces of China, with increased numbers yearly. Infection and death cases are mainly found in central China, where the Haemaphysalis Iongicornis ticks are spread. The national average mortality rate of SFTS infection was 5.3%, with higher risk to elder people. The main epidemic period was from May to July, with a peak in May. Thus, SFTS reminds a significant public health problem, and development of prophylactic vaccines and effective antiviral drugs will be highly needed.展开更多
Severe fever with thrombocytopenia syndrome(SFTS),caused by SFTS virus(SFTSV)infection,was first reported in 2010 in China with an initial fatality of up to 30%.The laboratory confirmation of SFTSV infection in terms ...Severe fever with thrombocytopenia syndrome(SFTS),caused by SFTS virus(SFTSV)infection,was first reported in 2010 in China with an initial fatality of up to 30%.The laboratory confirmation of SFTSV infection in terms of detection of viral RNA or antibody levels is critical for SFTS diagnosis and therapy.In this study,a new luciferase immunoprecipitation system(LIPS)assay based on p REN2 plasmid expressing SFTSV NP gene and tagged with Renilla luciferase(Rluc),was established and used to investigate the levels of antibody responses to SFTSV.Totally 464 serum samples from febrile patients were collected in the hospital of Shaoxing City in Zhejiang Province in 2019.The results showed that 82 of the 464 patients(17.7%)had antibody response to SFTSV,which were further supported by immunofluorescence assays(IFAs).Further,q RT-PCR and microneutralization tests showed that among the 82 positive cases,15 patients had viremia,10 patients had neutralizing antibody,and one had both(totally 26 patient).However,none of these patients were diagnosed as SFTS in the hospital probably because of their mild symptoms or subclinical manifestations.All the results indicated that at least the 26 patients having viremia or neutralizing antibody were the missed diagnosis of SFTS cases.The findings suggested the occurrence of SFTS and the SFTS incidence were higher than the reported level in Shaoxing in 2019,and that LIPS may provide an alternative strategy to confirm SFTSV infection in the laboratory.展开更多
Exposure to heparin is associated with a high incidence of immunization against platelet factor 4(PF4)/heparin complexes. A subgroup of immunized patients is at risk of developing heparin-induced thrombocytopenia(HIT)...Exposure to heparin is associated with a high incidence of immunization against platelet factor 4(PF4)/heparin complexes. A subgroup of immunized patients is at risk of developing heparin-induced thrombocytopenia(HIT), an immune mediated prothrombotic adverse drug effect. Transplant recipients are frequently exposed to heparin either due to the underlying end-stage disease, which leads to listing and transplantation or during the transplant procedure and the perioperative period. To review the current scientific knowledge on antiheparin/PF4 antibodies and HIT in transplant recipients a systematic Pub Med literature search on articles in English language was performed. The definition of HIT is inconsistent amongst the publications. Overall, six studies and 15 case reports have been published on HIT before or after heart, liver, kidney, and lung transplantation, respectively. The frequency of seroconversion for anti-PF4/heparin antibodies ranged between 1.9% and 57.9%. However, different methods to detect anti-PF4/heparin antibodies were applied. In none of the studies HIT-associated thromboembolic events or fatalities were observed. More importantly, in patients with a history of HIT, reexposure to heparin during transplantation was not associated with thrombotic complications. Taken together, the overall incidence of HIT after solid organ transplantation seems to be very low. However, according to the current knowledge, cardiac transplant recipients may have the highest risk to develop HIT. Different alternative suggestions for heparin-free anticoagulation have been reported for recipients with suspected HIT albeit no official recommendations on management have been published for this special collective so far.展开更多
Verifying platelet counts can prevent unwarranted diagnostic tests and transfusions. In case of thrombocytopenia, if the clinical picture and history do not suggest bleeding tendency, one should always perform periphe...Verifying platelet counts can prevent unwarranted diagnostic tests and transfusions. In case of thrombocytopenia, if the clinical picture and history do not suggest bleeding tendency, one should always perform peripheral blood smear by directly obtaining blood by finger puncture before doing any further tests. If the peripheral blood smear exhibits platelet clumps, pseudothrombocytopenia should always be remembered. In this case, we present a neonate with a diagnosis of transplacental transmission of EDTA-dependant pseudothrombocytopenia.展开更多
Immune thrombocytopenia is an autoimmune disease resulting in the destruction of platelets.It is classified as acute,thrombocytopenia occurring for < 6 mo and usually resolving spontaneously,and chronic,lasting >...Immune thrombocytopenia is an autoimmune disease resulting in the destruction of platelets.It is classified as acute,thrombocytopenia occurring for < 6 mo and usually resolving spontaneously,and chronic,lasting >6 mo and requiring therapy to improve the thrombocytopenia.The underlying defects leading to autoantibody production are unknown.Molecular mimicry appears to play a role in the development of self-reactive platelet antibodies after vaccination and certain viral infections.Platelet life span is reduced as a consequence of antibody-mediated clearance by tissue macrophages in essentially all patients.Diagnosis is based on the exclusion of the other causes of thrombocytopenia.Steroid is the first choice of the treatment,often followed by splenectomy in unresponsive cases.Intravenous immunoglobulin,anti-Rho(D) immune globulin,azathioprine,cyclosporine A,cyclophosphamide,danazol,dapsone,mycophenolate mofetil,rituximab,thrombopoietin receptor agonists and vinca alkaloids are other choices of treatment.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
Hubei Province is a major epidemic area of severe fever with thrombocytopenia syndrome bunyavirus(SFTSV) in China. However, to date, a few SFTSV strains have been isolated from Hubei Province, preventing effective stu...Hubei Province is a major epidemic area of severe fever with thrombocytopenia syndrome bunyavirus(SFTSV) in China. However, to date, a few SFTSV strains have been isolated from Hubei Province, preventing effective studies of epidemic outbreaks. Here, we report three confirmed patients(2015–2016) with typical symptoms of severe fever with thrombocytopenia syndrome disease(SFTS) who were farmers resident in different regions in Hubei Province. Three new SFTSV strains were isolated from the serum samples of each patient. Characterization of viral growth properties showed that there were no significant differences in virus production. All strains were completely sequenced, and phylogenetic analysis showed that unlike the other strains from Hubei province, which belonged to the SFTSV C3 genotype, one of the three strains belonged to the SFTSV C2 genotype. These results suggested that multiple SFTSV genotypes have been circulating in Hubei Province, providing insights into SFTSV evolution and improving our understanding of SFTSV prevalence in Hubei Province.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
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 improve...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.展开更多
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...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.展开更多
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 exp...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.展开更多
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-...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.展开更多
基金supported by the National Natural Science Foundation of China(32170144 and 32470146).
文摘Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has been proved that traditional Chinese medicine(TCM)has displayed definite therapeutic effects on viral hemorrhagic fever,indicating its potential to treat SFTS.In this study,SFTS-relative key targets were predicted via gene ontology(GO)analysis and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Molecular docking was then used to select stable binders.Molecules matched TCMs were identified,and a new prescription,Qingqi Guxue decoction(QQGX),was formulated to clear heat and nourish blood,with a resulting drug composition network.We explored the optimal drug proportion for QQGX.Through an in-depth study of molecular mechanisms,we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2(CCNA2)and cyclin-dependent kinase 2(CDK2),thereby inhibiting SFTSV replication.Finally,we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV.In summary,our study prepared a TCM decoction using the method of network pharmacology.This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-034A.
文摘BACKGROUND Patients with acute-on-chronic liver failure(ACLF)have a high mortality rate,poor prognosis,and often experience concurrent thrombocytopenia and bleeding events.AIM To evaluate the efficacy and safety of recombinant human thrombopoietin(rhTPO)in patients with ACLF with concomitant severe thrombocytopenia.METHODS This was a prospective,open-label study.We assigned 70 ACLF patients with severe thrombocytopenia into the rhTPO group and control group,with 35 patients in each group.Patients in the rhTPO group received subcutaneous injections of rhTPO at a dose of 15000 IU/day for 7 consecutive days,while patients in the control group did not receive rhTPO treatment.The primary endpoint was the proportion of patients with platelet count>50×10^(9)/L on day 14.RESULTS The proportion of patients with platelet count>50×10^(9)/L on day 14 was 60.7%in the rhTPO group,which was significantly higher than that(12.0%)in the control group(P<0.001).The platelet count in the rhTPO group on day 14 was 64×10^(9)/L,exceeding the baseline of 28×10^(9)/L.Compared to the control group,the rhTPO group exhibited a significant increase in platelet count from baseline(P<0.05).Model for end-stage liver disease score,albumin level and international normalized ratio improved significantly from baseline on day 14 after rhTPO injection.The concentrations of serum thrombopoietin and hepatocyte growth factor in the rhTPO group after 7 days were 143.7 and 195.4 pg/mL,respectively,showing a significant increase from baseline(P<0.05).Eight(22.9%)patients had bleeding events in the control group compared with four(11.4%)in the rhTPO group.The incidence of 90-day mortality was also higher in the control group(6,17.1%)than that in the rhTPO group(3,8.6%).CONCLUSION rhTPO significantly increased the platelet count in ACLF patients with thrombocytopenia and reduce the occurrence of bleeding events,with a good safety profile.
文摘Thrombocytopenia (defined as platelet count <sup>9</sup>/L) is present in 7% - 12% of pregnant women at delivery. Although there are mild etiologies of this condition that are often diagnosed incidentally, there are more severe causes that can be life threating. Thrombocytopenia also has a great implication in surgical risk and regional anesthesia. A structured evaluation of thrombocytopenia is necessary to allow an adequate diagnostic approach. Here we summarized the current knowledge of thrombocytopenia in pregnancy.
文摘Gastrointestinal bleeding(GIB)presents a significant challenge for patients with hematologic malignancies,especially those with severe thrombocytopenia.Although endoscopic intervention is frequently used in managing GIB,its safety and effectiveness in this high-risk group remain unclear.A recent study by Alhumayyd et al provided insight into this issue.However,it has notable limitations,including its retrospective nature,small sample size,and failure to adjust for important confounding factors such as disease severity,hemodynamic status,and platelet function.The study’s findings indicated that urgent endoscopy may help decrease the incidence of recurrent bleeding;however,it did not show a clear benefit in terms of mortality.Future research ought to prioritize prospective,multicenter studies that employ standardized protocols and incorporate risk stratification models to better understand the impact of endoscopic treatment for GIB in these patients.Additionally,integrating platelet function assays could improve clinical decision-making.Addressing these research gaps is essential for improving patient outcomes and developing effective guidelines for managing GIB in individuals with thrombocytopenia.
文摘BACKGROUND Tamoxifen,a selective estrogen receptor modulator,is pivotal in managing hor-mone receptor-positive breast cancer.While its common side effects are well-do-cumented,tamoxifen-induced thrombocytopenia is a rare,serious adverse event requiring drug discontinuation.CASE SUMMARY We report a case of tamoxifen-induced thrombocytopenia in a 51-year-old preme-nopausal woman with breast cancer,occurring within 4 weeks of initiating adju-vant tamoxifen therapy.Platelet counts normalized after drug cessation,but th-rombocytopenia recurred upon rechallenge,leading to permanent disconti-nuation.CONCLUSION This case underscores the need for regular complete blood count monitoring in patients on tamoxifen to detect rare hematologic adverse events promptly.
基金supported by the National Natural Science Foundation of China(Nos.82172335,81971994,91846103,and 81871709)the Zhejiang Provincial Key Research and Development Program(No.2020C03032),China.
文摘Immune thrombocytopenia(ITP)is a hemorrhagic autoimmune disease characterized by antibody-mediated platelet injury.ITP has complicated immunopathological mechanisms that need further elucidation.It is well known that the costimulatory molecules OX40 ligand(OX40L)and OX40 play essential roles in the immunological mechanisms of autoimmune diseases.Previously,we discovered that the expression of OX40L and OX40 is significantly increased in the peripheral blood mononuclear cells(PBMCs)of ITP patients.In our present study,OX40L-induced follicular helper T(Tfh)cells exhibited an activated phenotype with elevated expression of inducible T-cell costimulator(ICOS),programmed cell death protein-1(PD-1),and cluster of differentiation 40 ligand(CD40L)in vitro.Moreover,aberrant OX40L-OX40 expression might promote the Tfh1-to-Tfh2 shift in vivo,inducing the generation of autoantibodies by enhancing the helper function of Tfh cells for B lymphocytes in a mouse model,which might accelerate the progression of ITP.Additionally,signal transduction through the OX40L-OX40 axis might be related to the activation of tumor necrosis factor receptor-associated factor(TRAF)-nuclear factor-κB(NF-κB)and Janus kinase(JAK)-signal transducer and activator of transcription(STAT)signaling pathways.Overall,OX40L-OX40 signaling is proposed as a potential novel therapeutic target for ITP.
基金Supported by the 211 Project of Jinan Universitythe Team Project of Natural Science Foundation of Guangdong Province (8351063201000003)+3 种基金the Popular Science Foundation of Science & Technology Bureau of Guangzhou City (2008KP055)the Natural Science Foundation of Guangdong Province (06025198)the Jinan University Natural Science Foundation (51204017)the Science and Technology Innovation Project for Undergraduates (cx08120)
文摘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.
文摘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.
基金supported by grants from the China Mega-Project for Infectious Diseases (2012ZX10004207)the China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases (S2012Y03)+1 种基金the key project of the Health Ministry of Hubei Province (JX5A06)the Hubei Provincial Outstanding Medical Academic Leader program
文摘Severe fever with thrombocytopenia syndrome （SFTS） is an emerging infectious disease caused by SFTS virus （SFTSV）. SFTSV is associated with a high mortality rate and has been reported in China, South Korea and Japan. SFTSV undergoes rapid changes owing to evolution, gene mutations, and reassortment between different strains of SFTSV. In this review, we summarize the recent cases and general properties of SFTS, focusing on the epidemiology, genetic diversity, clinical features, and diagnostics of SFTSV in China. From 2010 to October 2016, SFTS cases were reported in 23 provinces of China, with increased numbers yearly. Infection and death cases are mainly found in central China, where the Haemaphysalis Iongicornis ticks are spread. The national average mortality rate of SFTS infection was 5.3%, with higher risk to elder people. The main epidemic period was from May to July, with a peak in May. Thus, SFTS reminds a significant public health problem, and development of prophylactic vaccines and effective antiviral drugs will be highly needed.
基金supported by the National Program on Key Research Project of China(2018YFE0200400,2019YFC1200700)the National Natural Science Foundation of China(U20A20135)+1 种基金the Strategic Biological Resources Capacity Building Project of Chinese Academy of Sciences(KFJ-BRP-017-06)the Key deployment projects of Chinese Academy of Sciences(KJZD-SW-L11)
文摘Severe fever with thrombocytopenia syndrome(SFTS),caused by SFTS virus(SFTSV)infection,was first reported in 2010 in China with an initial fatality of up to 30%.The laboratory confirmation of SFTSV infection in terms of detection of viral RNA or antibody levels is critical for SFTS diagnosis and therapy.In this study,a new luciferase immunoprecipitation system(LIPS)assay based on p REN2 plasmid expressing SFTSV NP gene and tagged with Renilla luciferase(Rluc),was established and used to investigate the levels of antibody responses to SFTSV.Totally 464 serum samples from febrile patients were collected in the hospital of Shaoxing City in Zhejiang Province in 2019.The results showed that 82 of the 464 patients(17.7%)had antibody response to SFTSV,which were further supported by immunofluorescence assays(IFAs).Further,q RT-PCR and microneutralization tests showed that among the 82 positive cases,15 patients had viremia,10 patients had neutralizing antibody,and one had both(totally 26 patient).However,none of these patients were diagnosed as SFTS in the hospital probably because of their mild symptoms or subclinical manifestations.All the results indicated that at least the 26 patients having viremia or neutralizing antibody were the missed diagnosis of SFTS cases.The findings suggested the occurrence of SFTS and the SFTS incidence were higher than the reported level in Shaoxing in 2019,and that LIPS may provide an alternative strategy to confirm SFTSV infection in the laboratory.
文摘Exposure to heparin is associated with a high incidence of immunization against platelet factor 4(PF4)/heparin complexes. A subgroup of immunized patients is at risk of developing heparin-induced thrombocytopenia(HIT), an immune mediated prothrombotic adverse drug effect. Transplant recipients are frequently exposed to heparin either due to the underlying end-stage disease, which leads to listing and transplantation or during the transplant procedure and the perioperative period. To review the current scientific knowledge on antiheparin/PF4 antibodies and HIT in transplant recipients a systematic Pub Med literature search on articles in English language was performed. The definition of HIT is inconsistent amongst the publications. Overall, six studies and 15 case reports have been published on HIT before or after heart, liver, kidney, and lung transplantation, respectively. The frequency of seroconversion for anti-PF4/heparin antibodies ranged between 1.9% and 57.9%. However, different methods to detect anti-PF4/heparin antibodies were applied. In none of the studies HIT-associated thromboembolic events or fatalities were observed. More importantly, in patients with a history of HIT, reexposure to heparin during transplantation was not associated with thrombotic complications. Taken together, the overall incidence of HIT after solid organ transplantation seems to be very low. However, according to the current knowledge, cardiac transplant recipients may have the highest risk to develop HIT. Different alternative suggestions for heparin-free anticoagulation have been reported for recipients with suspected HIT albeit no official recommendations on management have been published for this special collective so far.
文摘Verifying platelet counts can prevent unwarranted diagnostic tests and transfusions. In case of thrombocytopenia, if the clinical picture and history do not suggest bleeding tendency, one should always perform peripheral blood smear by directly obtaining blood by finger puncture before doing any further tests. If the peripheral blood smear exhibits platelet clumps, pseudothrombocytopenia should always be remembered. In this case, we present a neonate with a diagnosis of transplacental transmission of EDTA-dependant pseudothrombocytopenia.
文摘Immune thrombocytopenia is an autoimmune disease resulting in the destruction of platelets.It is classified as acute,thrombocytopenia occurring for < 6 mo and usually resolving spontaneously,and chronic,lasting >6 mo and requiring therapy to improve the thrombocytopenia.The underlying defects leading to autoantibody production are unknown.Molecular mimicry appears to play a role in the development of self-reactive platelet antibodies after vaccination and certain viral infections.Platelet life span is reduced as a consequence of antibody-mediated clearance by tissue macrophages in essentially all patients.Diagnosis is based on the exclusion of the other causes of thrombocytopenia.Steroid is the first choice of the treatment,often followed by splenectomy in unresponsive cases.Intravenous immunoglobulin,anti-Rho(D) immune globulin,azathioprine,cyclosporine A,cyclophosphamide,danazol,dapsone,mycophenolate mofetil,rituximab,thrombopoietin receptor agonists and vinca alkaloids are other choices of treatment.
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.
基金supported by the Science and Technology Basic Work Program (2013FY113500)the National Key Research and Development Program (2016YFE 0113500) from the Ministry of Science and Technology of Chinathe European Union’s Horizon 2020 EVAg project (No 653316)
文摘Hubei Province is a major epidemic area of severe fever with thrombocytopenia syndrome bunyavirus(SFTSV) in China. However, to date, a few SFTSV strains have been isolated from Hubei Province, preventing effective studies of epidemic outbreaks. Here, we report three confirmed patients(2015–2016) with typical symptoms of severe fever with thrombocytopenia syndrome disease(SFTS) who were farmers resident in different regions in Hubei Province. Three new SFTSV strains were isolated from the serum samples of each patient. Characterization of viral growth properties showed that there were no significant differences in virus production. All strains were completely sequenced, and phylogenetic analysis showed that unlike the other strains from Hubei province, which belonged to the SFTSV C3 genotype, one of the three strains belonged to the SFTSV C2 genotype. These results suggested that multiple SFTSV genotypes have been circulating in Hubei Province, providing insights into SFTSV evolution and improving our understanding of SFTSV prevalence in Hubei Province.
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.
文摘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.
文摘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.
基金supported by grants from the China National Science and Technology Major Project(2012ZX10002004 and 2013ZX10002001)Zhejiang CTM Science and Technology Project(2011ZB061)
文摘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.
