Effect of thrombocytopenia and platelet transfusion on outcomes of acute variceal bleeding in patients with chronic liver disease

BACKGROUND Platelet transfusion in acute variceal bleeding(AVB)is recommended by few guidelines and is common in routine clinical practice,even though the effect of thrombocytopenia and platelet transfusion on the outcomes of AVB is unclear.AIM To determine how platelet counts,platelets transfusions,and fresh frozen plasma transfusions affect the outcomes of AVB in cirrhosis patients in terms of bleeding control,rebleeding,and mortality.METHODS Prospectively maintained database was used to analyze the outcomes of cirrhosis patients who presented with AVB.The outcomes were assessed as the risk of rebleeding at days 5 and 42,and risk of death at day 42,considering the platelet counts and platelet transfusion.Propensity score matching(PSM)was used to compare the outcomes in those who received platelet transfusion.Statistical comparisons were done using Kaplan-Meier curves with log-rank tests and Coxproportional hazard model for rebleeding and for 42-d mortality.RESULTS The study included 913 patients,with 83.5%men,median age 45 years,and Model for End-stage Liver Disease score 14.7.Platelet count<20×10^(9)/L,20-50×10^(9)/L,and>50×10^(9)/L were found in 23(2.5%),168(18.4%),and 722(79.1%)patients,respectively.Rebleeding rates were similar between the three platelet groups on days 5 and 42(13%,6.5%,and 4.7%,respectively,on days 5,P=0.150;and 21.7%,17.3%,and 14.4%,respectively,on days 42,P=0.433).At day 42,the mortality rates for the three platelet groups were also similar(13.0%,23.2%,and 17.2%,respectively,P=0.153).On PSM analysis patients receiving platelets transfusions(n=89)had significantly higher rebleeding rates on day 5(14.6%vs 4.5%;P=0.039)and day 42(32.6%vs 15.7%;P=0.014),compared to those who didn't.The mortality rates were also higher among patients receiving platelets(25.8%vs 23.6%;P=0.862),although the difference was not significant.On multivariate analysis,platelet transfusion and not platelet count,was independently associated with 42-d rebleeding.Hepatic encephalopathy was independently associated with 42-d mortality.CONCLUSION Thrombocytopenia had no effect on rebleeding rates or mortality in cirrhosis patients with AVB;however,platelet transfusion increased rebleeding on days 5 and 42,with a higher but nonsignificant effect on mortality.

First platelet transfusion refractoriness in a patient with acute myelocytic leukemia: A case report

BACKGROUND Platelet transfusion is of great significance in the treatment of thrombocytopenia caused by myelosuppression during intensive chemotherapy in patients with acute leukemia.In recent years,with platelet transfusion increasing,ineffective platelet transfusion has become increasingly prominent.Generally speaking,platelet antibodies can be produced after repeated transfusion,thus rendering subsequent platelet transfusion ineffective.We report a case of first platelet transfusion refractoriness(PTR)in a patient with acute myelocytic leukemia(AML).Due to the rarity of such cases in clinical practice,there have been no relevant case reports so far.CASE SUMMARY A 51-year-old female patient attended the hospital due to throat pain and abnormal blood cells for 4 d.Her diagnosis was acute myelocytic leukemia[M2 type Fms related receptor tyrosine kinase 3,Isocitrate Dehydrogenase 1,Nucleophosmin 1,Neuroblastoma RAS viral oncogene homolog(+)high-risk group].She was treated with"IA"(IDA 10 mg day 1-3 and Ara-C 0.2 g day 1-5)chemotherapy.When her condition improved,the patient was discharged from the hospital,instructed to take medicine as prescribed by the doctor after discharge,and returned to the hospital for further chemotherapy on time.CONCLUSION We report a rare case of first platelet transfusion failure in a patient with AML during induction chemotherapy,which may be related to the production of platelet antibodies induced by antibiotics and excessive tumor load.This also suggests that we should consider the influence of antibiotics when the rare situation of first platelet transfusion failure occurs in patients with AML.When platelet antibodies are produced,immunoglobulins can be used to block antibodies,thereby reducing platelet destruction.For patients with PTR,both immune and non-immune factors need to be considered and combined in clinical practice along with individualized treatment to effectively solve the problem.

Platelet transfusion refractoriness after T-cell-replete haploidentical transplantation is associated with inferior clinical outcomes

Haploidentical stem cell transplantation (haplo-SCT) has been an alternative source of bone marrow for patients without human leukocyte antigen (HLA)-matched donors. The aim of this study was to investigate the relationships between platelet transfusion refractoriness (PTR) and clinical outcomes in the setting of haplo-SCT. Between May 2012 and March 2014, 345 patients who underwent unmanipulated haplo-SCT were retrospectively enrolled. PTR occurred in 20.6% of all patients. Patients in the PTR group experienced higher transplant-related mortality (TRM, 43.7% vs. 13.5%, P<0.001), lower overall survival (OS, 47.9%vs. 76.3%, P<0.001) and lower leukemia-free survival (LFS, 47.9% vs. 72.3%, P<0.001) compared to patients in the non-PTR group. The multivariate analysis showed that PTR was associated with TRM (P=0.002), LFS (P<0.001), and OS (P<0.001).The cumulative incidences of PTR in patients receiving >12 platelet (PLT) transfusions (third quartile of PLT transfusions) were higher than in patients receiving either >6 (second quartile) or >3 (first quartile) PLT transfusions (56.1% vs. 41.6% vs. 28.2%,respectively; P<0.001). The multivariate analysis also showed that PTR was associated with the number of PLT transfusions(P<0.001). PTR could predict poor transplant outcomes in patients who underwent haploidentical SCT.

Thrombocytopenia in chronic liver disease:Physiopathology and new therapeutic strategies before invasive procedures

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.

Recombinant human thrombopoietin treatment in patients with chronic liver disease-related thrombocytopenia undergoing invasive procedures:A retrospective study

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.

肿瘤患者的血小板输注效果观察

目的:观察肿瘤患者在接受不同类型的血小板输注后的输注效果,探讨有助于解决血小板输注无效的方法。方法:对223例曾经反复输注血小板的肿瘤患者按照输注的血小板类型分为单采辐照、单采非辐照、手工辐照、手工非辐照4组,通过CCI值及临床症状改善情况对输注后疗效进行监测和评价。结果:在单采和手工血小板中,辐照组的有效输注率均略高于非辐照组,在辐照和非辐照血小板中,手工血小板的输注有效率高于单采血小板;临床疗效观察,患者输后有明显症状改善者单采血小板优于手工血小板。但均未达到统计学的显著差异。结论:总体上手工血小板的输注疗效不亚于单采血小板,辐照血小板有助于提高输注效果,可在临床上推广应用辐照手工血小板。

Vancomycin-induced thrombocytopenia in endocarditis:A case report and review of literature

BACKGROUND Thrombocytopenia is a serious complication in the medical practice of numerous drugs.Vancomycin is frequently used for the prophylaxis and treatment of suspected or identified methicillin-resistant positive infections.Several cases with vancomycin-induced thrombocytopenia(VIT)have been reported.However,these have rarely been extensively reviewed.The present report describes a case of VIT in endocarditis,and reviews all VIT cases reported in the literature.CASE SUMMARY A 26-year-old male diagnosed with infective endocarditis was admitted.The patient was treated with multiple drugs,including vancomycin,which was initially intravenously given at 1000 mg every 12 h and subsequently at 500 mg every 8 h on day 3.On day 11,the platelet count decreased to 51×10^(9)/L,vancomycin was switched to 500 mg every 12 h,and platelet transfusion was given.On day 17,the platelet count dropped to 27×10^(9)/L,and platelet transfusion was administered again.On day 23,vancomycin was adjusted to 500 mg every 8 h as the trough concentration dropped to the minimum effective concentration.On day 33,the platelet count declined to approximately 40×10^(9)/L.After platelet transfusion,the platelet count rebounded to 90×10^(9)/L on day 35 but dropped again to 42×10^(9)/L on day 43.Based on the time-to-platelet count curve and Naranjo’s Adverse Drug Reaction Probability Scale score,VIT was suspected.After vancomycin discontinuation and platelet transfusion,the platelet count gradually normalized.CONCLUSION The diagnosis of VIT can be achieved through the time-to-platelet count curve and Naranjo’s Adverse Drug Reaction Probability Scale score.The platelet count cannot be normalized simply by platelet transfusion alone,and vancomycin discontinuation is essential.

Glucocorticoid-induced thrombotic microangiopathy in paroxysmal nocturnal hemoglobinuria:A case report and review of literature

BACKGROUND Thrombotic microangiopathy(TMA)is a group of disorders that converge on excessive platelet aggregation in the microvasculature,leading to consumptive thrombocytopenia,microangiopathic hemolysis and ischemic end-organ dysfunction.In predisposed patients,TMA can be triggered by many environmental factors.Glucocorticoids(GCs)can compromise the vascular endothelium.However,GC-associated TMA has rarely been reported,which may be due to the lack of awareness of clinicians.Given the high frequency of thrombocytopenia during GC treatment,particular attention should be given to this potentially fatal complication.CASE SUMMARY An elderly Chinese man had a 12-year history of aplastic anemia(AA)and a 3-year history of paroxysmal nocturnal hemoglobinuria(PNH).Three months earlier,methylprednisolone treatment was initiated at 8 mg/d and increased to 20 mg/d to alleviate complement-mediated hemolysis.Following GC treatment,his platelet counts and hemoglobin levels rapidly decreased.After admission to our hospital,the dose of methylprednisolone was increased to 60 mg/d in an attempt to enhance the suppressive effect.However,increasing the GC dose did not alleviate hemolysis,and his cytopenia worsened.Morphological evaluation of the marrow smears revealed increased cellularity with an increased percentage of erythroid progenitors without evident dysplasia.Cluster of differentiation(CD)55 and CD59 expression was significantly decreased on erythrocytes and granulocytes.In the following days,platelet transfusion was required due to severe thrombocytopenia.Observation of platelet transfusion refractoriness indicated that the exacerbated cytopenia may have been caused by the development of TMA due to GC treatment because the transfused platelet concentrates had no defects in glycosylphosphatidylinositol-anchored proteins.We examined blood smears and found a small number of schistocytes,dacryocytes,acanthocytes and target cells.Discontinuation of GC treatment resulted in rapidly increased platelet counts and steady increases in hemoglobin levels.The patient’s platelet counts and hemoglobin levels returned to the levels prior to GC treatment 4 weeks after GC discontinuation.CONCLUSION GCs can drive TMA episodes.When thrombocytopenia occurs during GC treatment,TMA should be considered,and GCs should be discontinued.