Hepatitis C virus(HCV)infection,traditionally regarded as a hepatotropic disease,is increasingly recognized as a systemic condition with significant thrombotic implications.Chronic HCV induces a persistent proinflamma...Hepatitis C virus(HCV)infection,traditionally regarded as a hepatotropic disease,is increasingly recognized as a systemic condition with significant thrombotic implications.Chronic HCV induces a persistent proinflammatory and prothrombotic state that substantially elevates the risk of both venous and arterial events.Mechanistically,HCV drives endothelial dysfunction,enhances platelet activation,disrupts coagulation and fibrinolytic balance,and promotes immunemediated vascular injury through cryoglobulinemia and chronic systemic inflammation.Clinical manifestations range from portal vein thrombosis and venous thromboembolism to coronary artery disease and ischemic stroke,highlighting the far-reaching consequences of virus-driven coagulopathy.Emerging evidence challenges the historical view of cirrhosis as a“naturally anticoagulated”state,instead describing a fragile hemostatic balance prone to both bleeding and thrombosis.Directacting antiviral therapy has transformed outcomes,not only achieving sustained virological response but also reversing systemic inflammation,improving endothelial function,and reducing thrombotic complications.However,patients with advanced fibrosis and comorbidities remain at elevated risk despite viral clearance,underscoring the need for ongoing surveillance.This minireview highlights the interplay between hepatic dysfunction,viral-induced inflammation,and cardiovascular sequelae in chronic HCV,emphasizing the importance of integrating thrombotic risk assessment into clinical care and research frameworks.展开更多
BACKGROUND Thrombotic microangiopathy(TMA)is an acute syndrome characterized by microangiopathic hemolytic anemia,thrombocytopenia,and multi-organ dysfunction due to the microcirculation of platelet thrombi.Cancer-ass...BACKGROUND Thrombotic microangiopathy(TMA)is an acute syndrome characterized by microangiopathic hemolytic anemia,thrombocytopenia,and multi-organ dysfunction due to the microcirculation of platelet thrombi.Cancer-associated TMA is a rare and fatal complication,which often occurs during cancer remission.It is frequently misdiagnosed because of limited clinical awareness.CASE SUMMARY A middle-aged female patient presented to our clinic with a 15-days history of back pain,15 months post-gastrectomy.Cancer-associated TMA was confirmed through bone marrow aspiration,biopsy,and imaging.The patient received intermittent transfusions,fluids,nutrition,and microcirculation therapy with partial coagulation improvement.The family refused intensive care unit admission and plasma exchange,preferring palliative care.The patient died of cerebral hemorrhage and herniation due to disease progression.This case indicates that TMA may serve as an early manifestation of various malignancies,particularly gastric cancer.However,it is often misdiagnosed.Its pathogenesis is not well understood and needs to be further investigated.Currently,no standardized treatment have been developed.Plasma exchange is the only intervention available,though other therapies may also be effective.CONCLUSION In this case of gastric signet-ring cell carcinoma complicated by TMA,the patient achieved transient remission with supportive care but died following treatment discontinuation.Further studies are needed to elucidate the pathological mechanisms and therapeutic strategies for cancer-associated TMA.展开更多
Pulmonary tumour thrombotic microangiopathy(PTTM)is a rare but under-recognised cause of rapidly progressive pulmonary hypertension(PH)and cor pulmonale,characterised by diffuse obstruction of small pulmonary arteries...Pulmonary tumour thrombotic microangiopathy(PTTM)is a rare but under-recognised cause of rapidly progressive pulmonary hypertension(PH)and cor pulmonale,characterised by diffuse obstruction of small pulmonary arteries by metastatic tumour cells.These tumour emboli lead to obstructive intimal proliferation and in situ thrombosis within the pulmonary vasculature,further compromising the overall permeability of the pulmonary vascular bed and exacerbating PH.[1]The clinical and imaging manifestations of PTTM often overlap with those of other causes of PH,including chronic thromboembolic PH,pulmonary veno-occlusive disease and pulmonary capillary haemangiomatosis,often leading to diagnostic delays.展开更多
Thrombotic thrombocytopenic purpura(TTP)is a rare and life-threatening form of thrombotic microangiopathy,primarily caused by a deficiency of ADAMTS-13 activity.Immune-related adverse events(irAEs)are autoimmune toxic...Thrombotic thrombocytopenic purpura(TTP)is a rare and life-threatening form of thrombotic microangiopathy,primarily caused by a deficiency of ADAMTS-13 activity.Immune-related adverse events(irAEs)are autoimmune toxicities mediated by the use of immune checkpoint inhibitors(ICIs).Here,the study reports a case of thrombotic thrombocytopenic purpura that developed in a patient with renal cell carcinoma and vertebral metastasis following combined treatment with Toripalimab and Pazopanib.The patient received Toripalimab in combination with Pazopanib after undergoing radical nephrectomy for right renal cell carcinoma.Five days later,a generalized erythematous rash appeared,partly confluent,accompanied by congestion and swelling of both palpebral and bulbar conjunctiva.Based on the clinical presentation and laboratory results showing thrombocytopenia and hemolytic anemia,the diagnosis of TTP was established.The condition was considered an adverse effect associated with the combination therapy of Toripalimab and Pazopanib.Plasma exchange and high-dose intravenous immunoglobulin therapy were promptly initiated.The treatment regimen was subsequently modified to Axitinib combined with radiotherapy,leading to a gradual recovery of platelet counts.This report highlights the potential risk of TTP associated with combined ICI and TKI therapy,and underscores the importance of early recognition and timely management of this potentially fatal complication.展开更多
This editorial article is intended to perform a discussion on the manuscript entitled“Simultaneous portal vein thrombosis and splenic vein thrombosis in a COVID-19 patient:A case report and review of literature”writ...This editorial article is intended to perform a discussion on the manuscript entitled“Simultaneous portal vein thrombosis and splenic vein thrombosis in a COVID-19 patient:A case report and review of literature”written by Abramowitz et al.The article focuses on the diagnostic processes in a 77-year-old-male patient with a simultaneous portal vein and splenic artery thrombosis accompanying coronavirus disease 2019(COVID-19).The authors postulated that splanchnic thrombosis should be on the list of differential diagnoses in a patient presenting with abdominal pain in presence of a COVID-19 infection.The tendency for venous and arterial thrombosis in COVID-19 patients is encountered,largely attributed to hypercoagulopathy.In general,venous thromboembolism mostly manifest as deep vein thrombosis(DVT),pulmonary embolism(PE)or catheterrelated thromboembolic events.Acute PE,DVT,cerebrovascular events and myocardial infarction are seen as the most common thromboembolic complications in COVID-19 patients.COVID-19-associated hemostatic abnormalities include mild thrombocytopenia and increased D-dimer level.Similar to other coagulopathies,the treatment of the underlying condition is the mainstay.Addition of antiplatelet agents can be considered in critically ill patients at low bleeding risk,not on therapeutic anticoagulation,and receiving gastric acid suppression Early administration of antithrombotic drugs will have a beneficial effect in both the prevention and treatment of thrombotic events,especially in non-ambulatory patients.Low molecular weight heparin(LMWH)should be started if there is no contraindication,including in non-critical patients who are at risk of hospitalization LMWH(enoxaparin)is preferred to standard heparin.展开更多
Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura （TTP）-like syndrome suggest a survival beneft to early treatment with plasma exchange. The following is a report of the eighth su...Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura （TTP）-like syndrome suggest a survival beneft to early treatment with plasma exchange. The following is a report of the eighth such case in the last ten years. A 44-year-old lady known for lupus presented with the nephrotic syndrome and a renal biopsy was consistent with class 4G lupus nephritis. She was given high-dose steroids and cytotoxic therapy, but her induction therapy was complicated by the classic pentad of TTP. She was subsequently treated with another course of high-dose steroids, a different cytotoxic agent, and plasma exchange, with clinical resolution shortly thereafter. Similar to seven recently reported cases of microangiopathy in lupus, this lady’s TTP-like syndrome improved dramatically after initiation of plasma exchange, despite not having a severely deficient ADAMTS13. This has implications on both current clinical practice and on the pathogenesis of TTP-like syndromes in lupus.展开更多
Ischemic stroke seriously threatens human health and quality of life.Xiao-Xu-Ming(XXM)decoction has been a classical prescription for stroke therapy.In our previous studies,we have found that XXM exerts neuroprotectiv...Ischemic stroke seriously threatens human health and quality of life.Xiao-Xu-Ming(XXM)decoction has been a classical prescription for stroke therapy.In our previous studies,we have found that XXM exerts neuroprotective effects,improves brain injury,and attenuates neuroinflammation in cerebral ischemia rats.In this study,we investigated the effects and possible mechanism of XXM on thrombotic focal cerebral ischemia.After treatment with XXM,the neurological function and motor abilities were improved,and cerebral infarction volume was significantly decreased compared with rats of thrombotic focal cerebral ischemia.Besides,the results of BBB integrity detected by EB leakage and tight junction(TJ)protein expression showed that XXM could maintain BBB integrity and improve the expressions of TJ proteins,including claudin-1,occluding,and ZO-1,in the ischemic ipsilateral cortex disrupted by thrombotic cerebral ischemia.Furthermore,proteomic techniques were used to identify the differentially expressed proteins(DEPs)in the ischemic cerebral cortex,and the results showed that 132 DEPs regulated by XXM were detected in the ischemic cerebral cortex.Bioinformatic analysis showed that these regulated proteins by XXM were mainly involved in complement and coagulation cascade,and lysosome,etc.Furthermore,there was an interaction among DEPs,including Lgals3,Ctsz,Capg,C1qa,S100a4,Grn,Hspb1,Aif1,and Anxa1,etc.In conclusion,XXM ameliorated brain injury of thrombotic focal ischemic stroke,and Lgals3,Ctsz,Capg,C1qa,S100a4,Grn,Hspb1,Aif1,and Anxa1 could help provide possible therapeutic targets of XXM for ischemic stroke and offer research direction for further research.展开更多
BACKGROUND Pulmonary tumor thrombotic microangiopathy(PTTM)is a rare condition in patients with hepatocellular carcinoma(HCC);to date,few cases have been reported.While hepatic dysfunction has been focused on the late...BACKGROUND Pulmonary tumor thrombotic microangiopathy(PTTM)is a rare condition in patients with hepatocellular carcinoma(HCC);to date,few cases have been reported.While hepatic dysfunction has been focused on the later stages of HCC,the management of symptoms in PTTM is important for supportive care of the cases.For the better understanding of PTTM in HCC,the information of our recent case and reported cases have been summarized.CASE SUMMARY A patient with HCC exhibited acute and severe respiratory failure.Radiography and computed tomography of the chest revealed the multiple metastatic tumors and a frosted glass–like shadow with no evidence of infectious pneumonia.We diagnosed his condition as acute respiratory distress syndrome caused by the lung metastases and involvement of the pulmonary vessels by tumor thrombus.Administration of prednisolone to alleviate the diffuse alveolar damages including edematous changes of alveolar wall caused by the tumor cell infiltration and ischemia showed mild improvement in his symptoms and imaging findings.An autopsy showed the typical pattern of PTTM in the lung with multiple metastases.CONCLUSION PTTM is caused by tumor thrombi in the arteries and thickening of the pulmonary arterial endothelium leading to the symptoms of dyspnea in terminal staged patients.Therefore,supportive management of symptoms is necessary in the cases with PTTM and hence we believe that the information presented here is of great significance for the diagnosis and management of symptoms of PTTM with HCC.展开更多
AIM: To evaluate the prevalence of genetic and acquired prothrombotic risk factors and their association with the extent of fibrosis and fatty infiltration in patients with non-alcoholic fatty liver disease (NAFLD).ME...AIM: To evaluate the prevalence of genetic and acquired prothrombotic risk factors and their association with the extent of fibrosis and fatty infiltration in patients with non-alcoholic fatty liver disease (NAFLD).METHODS: Forty-four patients with chronic hepatitis (28 men and 16 women, with mean age of 45±11 and 49±12 years, respectively) constituted the patient population of this study. The groups were divided as follows: 15 patients with fatty liver (FL); 15 with non-alcoholic steatohepatitis (NASH); 14 with chronic viral hepatitis (CH) diagnosed by histology and liver technetium scan or ultrasound; and 10 healthy individuals. Thrombophilic, coagulation factors and genetic mutations were diagnosed by standard hemostatic and molecular coagulation assays.RESULTS: Activated protein C (APC) resistance and protein S were the most prevalent thrombotic risk factors (6% and 10% in NAFLD vs 21% and 14% in CH; P＜0.01 and P＜0.05, respectively). One thrombotic risk factor was identified in 41% of patients (23% mild fibrosis, 18% severe fibrosis) and two thrombotic risk factors in 6% of patients with NAFLD and severe fibrosis. While no differences in APC ratio, lupus anticoagulant, fibrinogen, factor V Leiden,prothrombin, and MTHFR mutation were found. Protein S levels were significantly lower in NASH patients than in patients with FL alone (92±19 vs106±2, P＜0.01). Protein C levels were markedly higher in patients with NAFLD and mild or severe fibrosis as compared to the patients with CH, respectively (128±40 vs96±14, P＜0.001 or 129±36 vs 88±13, P＜0.01).CONCLUSION: Up to 46% of patients with NAFLD may have thrombotic risk factors, and the presence of thrombotic risk factors is correlated with the extent of hepatic fibrosis,suggesting a crucial role of the coagulation system in the pathogenesis of hepatic fibrosis.展开更多
Thrombotic thrombocytopenic purpura(TTP) is a multisystem disorder that essentially can affect any organ in the human body. The hallmark of the pathogenesis in TTP is the large von Willebrand factor multimers on plate...Thrombotic thrombocytopenic purpura(TTP) is a multisystem disorder that essentially can affect any organ in the human body. The hallmark of the pathogenesis in TTP is the large von Willebrand factor multimers on plateletmediated micro-thrombi formation, leading to microvascular thrombosis.Autopsy studies showed that cardiac arrest and myocardial infarction are the most common immediate causes of death in these patients. Clinical manifestations of cardiac involvement in TTP vary dramatically, from asymptomatic elevation of cardiac biomarkers, to heart failure, MI and sudden cardiac death. There is limited knowledge about optimal cardiac evaluation and management in patients with TTP. The absence of typical cardiac symptoms,combined with complicated multi-organ involvement in TTP, may contribute to the under-utilization of cardiac evaluation and treatment. Prompt diagnosis and timely initiation of effective therapy could be critically important in selected cases. Based on our experience and this review of the literature, we developed several recommendations for focused cardiac evaluation for patients with acute TTP:(1) patients with suspected or confirmed TTP should be screened for the potential presence of cardiac involvement with detailed history and physical,electrocardiogram and cardiac enzymes;(2) clinical deterioration of TTP patients warrants immediate cardiac reevaluation;(3) TTP patients with clinical evidence of cardiac involvement should be monitored for telemetry, cardiac biomarkers and evaluated with transthoracic echocardiography. These patients require urgent targeted TTP treatment as well as cardiac-specific treatment. Aspirin therapy is indicated for all TTP patients. Since epicardial coronary artery involvement is rare, cardiac catheterization is usually not required, given the high risk for hemorrhage and kidney injury;(4) we recommend evidence-based medical therapy for ischemic symptoms and heart failure. TTP patients with evidence of cardiac involvement would also benefit from routine cardiology follow up during remission.展开更多
Thrombotic microangiopathy(TMA) is one of the most devastating sequalae of kidney transplantation. A number of published articles have covered either de novo or recurrent TMA in an isolated manner. We have, hereby, in...Thrombotic microangiopathy(TMA) is one of the most devastating sequalae of kidney transplantation. A number of published articles have covered either de novo or recurrent TMA in an isolated manner. We have, hereby, in this article endeavored to address both types of TMA in a comparative mode. We appreciate that de novo TMA is more common and its prognosis is poorer than recurrent TMA; the latter has a genetic background, with mutations that impact disease behavior and, consequently, allograft and patient survival. Post-transplant TMA can occur as a recurrence of the disease involving the native kidney or as de novo disease with no evidence of previous involvement before transplant. While atypical hemolytic uremic syndrome is a rare disease that results from complement dysregulation with alternative pathway overactivity, de novo TMA is a heterogenous set of various etiologies and constitutes the vast majority of post-transplant TMA cases. Management of both diseases varies from simple maneuvers, e.g., plasmapheresis, drug withdrawal or dose modification, to lifelong complement blockade, which is rather costly. Careful donor selection and proper recipient preparation, including complete genetic screening, would be a pragmatic approach. Novel therapies, e.g., purified products of the deficient genes, though promising in theory, are not yet of proven value.展开更多
BACKGROUND Sodium valproate is widely used in the treatment of epilepsy in clinical practice.Most adverse reactions to sodium valproate are mild and reversible,while serious idiosyncratic side effects are becoming app...BACKGROUND Sodium valproate is widely used in the treatment of epilepsy in clinical practice.Most adverse reactions to sodium valproate are mild and reversible,while serious idiosyncratic side effects are becoming apparent,particularly hepatotoxicity.Herein,we report a case of fatal acute liver failure(ALF)with thrombotic microangiopathy(TMA)caused by treatment with sodium valproate in a patient following surgery for meningioma.CASE SUMMARY A 42-year-old man who received antiepileptic treatment with sodium valproate after surgery for meningioma exhibited extreme fatigue,severe jaundice accompanied by oliguria,soy sauce-colored urine,and ecchymosis.His postoperative laboratory values indicated a rapid decreased platelet count and hemoglobin level,severe liver and kidney dysfunction,and disturbance of the coagulation system.He was diagnosed with drug-induced liver failure combined with TMA.After plasma exchange combined with hemoperfusion,pulse therapy with high-dose methylprednisolone,and blood transfusion,his liver function deteriorated,and finally,he died.CONCLUSION ALF with TMA is a rare and fatal adverse reaction of sodium valproate which needs to be highly valued.展开更多
Thrombotic thrombocytopenia purpura(TTP) was fi rst described in 1924 as a "pathologic alteration of the microvasculature, with detachment or swelling of the endothelium, amorphous material in the sub-endothelial...Thrombotic thrombocytopenia purpura(TTP) was fi rst described in 1924 as a "pathologic alteration of the microvasculature, with detachment or swelling of the endothelium, amorphous material in the sub-endothelial space, and luminal platelet aggregation leading to compromise of the microcirculation". Ticlopidine induced TTP has been highly associated with autoimmune induced reduction in ADAMTS-13 activity. These findings, to a lesser extent, have also been found in clopidogrel induced TTP. We report a case of clopidogrel associated TTP in a patient that presented with acute stroke, renal failure, and non-ST elevation myocardial infarction.展开更多
BACKGROUND Interferons(IFNs)are characterized by a wide range of biological effects,which justifies their potential therapeutic use in several pathologies,but also elicit a wide array of adverse effects in almost ever...BACKGROUND Interferons(IFNs)are characterized by a wide range of biological effects,which justifies their potential therapeutic use in several pathologies,but also elicit a wide array of adverse effects in almost every organ system.Among them,renal involvement is probably one of the most complex to identify.CASE SUMMARY We describe four cases of kidney damage caused by different IFN formulations:IFN-β-related thrombotic microangiopathy,IFN-β-induced systemic lupus erythematosus,and two cases of membranous nephropathy secondary to pegylated-IFN-α2B.In each case,we carefully excluded any other possible cause of renal involvement.Once suspected as the casual relationship between drug and kidney damage,IFN treatment was immediately discontinued.In three cases,we observed a complete and persistent remission of clinical and laboratory abnormalities after IFN withdrawal,while the patient who developed thrombotic microangiopathy,despite IFN withdrawal and complement-inhibitor therapy with eculizumab,showed persistent severe renal failure requiring dialysis.CONCLUSION This case series highlights the causal relationship between IFN treatment and different types of renal involvement and enables us to delineate several peculiarities of this association.展开更多
AIM:To investigate thrombotic microangiopathy (TMA)in liver transplantion,because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS:A total of 206 patients who underwent livi...AIM:To investigate thrombotic microangiopathy (TMA)in liver transplantion,because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS:A total of 206 patients who underwent living-donor liver transplantation (LDLT) were evaluated,and the TMA-like disorder (TMALD) occurred in seven recipients. RESULTS:These TMALD recipients showed poor outcomes in comparison with other 199 recipients. Although two TMALD recipients successfully recovered,the other five recipients finally died despite intensive treatments including repeated plasma exchange (PE) and re-transplantation. Histopathological analysis of liver biopsies after LDLT revealed obvious differences according to the outcomes. Qualitative analysis of antibodies against a disintegrin-like domain and metalloproteinase with thrombospondin type 1 motifs (ADAMTS-13) were negative in all patients. The fragmentation of red cells,the microhemorrhagic macules and the platelet counts were early markers for the suspicion of TMALD after LDLT. Although the absolute values of von Willebrand factor (vWF) and ADAMTS-13 did not necessarily reflect TMALD,the vWF/ADAMTS-13 ratio had a clear diagnostic value in all cases. The establishment of adequate treatments for TMALD,such as PE for ADAMTS-13 replenishment or treatments against inhibitory antibodies,must be decided according to each case. CONCLUSION:The optimal induction of adequate therapies based on early recognition of TMALD by the reliable markers may confer a large advantage for TMALD after LDLT.展开更多
BACKGROUND Thrombotic thrombocytopenic purpura(TTP)is a life-threatening but treatable disorder.Acute pancreatitis is a well-described consequence of TTP,but TTP as a consequence of acute pancreatitis is rare.CASE SUM...BACKGROUND Thrombotic thrombocytopenic purpura(TTP)is a life-threatening but treatable disorder.Acute pancreatitis is a well-described consequence of TTP,but TTP as a consequence of acute pancreatitis is rare.CASE SUMMARY A 32-year-old male developed acute pancreatitis due to a fatty diet and suffered splenectomy 3 years ago due to trauma.From day 4 of his onset of pain the blood examination showed the platelet extremely reduced,bilirubin elevated and creatinine increased.High clinical suspicion of TTP was made and prompt initiation of plasma exchange was given followed intravenous drip methylprednisolone.After 7 sessions of plasm exchange and the laboratory parameters were back to normal and the patient was discharged from the hospital on the 13th day of admission.CONCLUSION Patients develop acute pancreatitis with no apparent causes for hemolytic anemia and thrombocytopenia,the possibility of TTP should be considered.Treatments for TTP including plasm exchange should be evaluated as soon as a diagnosis is made.展开更多
BACKGROUND Thrombotic thrombocytopenic purpura(TTP)is a thrombotic microangiopathy characterized by the pentad of hemolytic anemia,fever,thrombocytopenia,renal failure,and neurological dysfunction.The formation of mic...BACKGROUND Thrombotic thrombocytopenic purpura(TTP)is a thrombotic microangiopathy characterized by the pentad of hemolytic anemia,fever,thrombocytopenia,renal failure,and neurological dysfunction.The formation of microthrombi in the arterioles and capillaries of various organs is one of the main pathophysiological mechanisms.Clinical manifestations of cardiac involvement in TTP patients are variable.Acute myocardial infarction has been reported as a complication with TTP as the secondary thrombotic event.Its emergence as the initial thrombotic event is extremely rare.CASE SUMMARY A 49-year-old previously healthy man was admitted for fever,typical angina chest pain 3 d prior to presentation,and newly onset left lower limb pain.The electrocardiogram illustrated ST-elevation acute myocardial infarction of the anterolateral wall of the left ventricle.Transthoracic echocardiography depicted two large thrombi at the apex of the left ventricle and moderately reduced ejection fraction(40%).Venous Doppler ultrasound showed occlusion of the left popliteal artery.Laboratory tests showed severe thrombocytopenia,mild hemolytic anemia,elevated D-dimers,and high troponin and creatine kinase-MB.Abdominal computed tomography revealed other thrombotic sites(superior mesenteric artery,posterior aortic wall,spleen and renal infarction,and ileum necrosis).He was immediately started on steroids and addressed to surgery for acute abdominal pain.After an initial stabilization of the hematological deficit,he went into general surgery for resection of the necrotic ileum but died soon after the intervention due to multiple organ failure.CONCLUSION Cardiac involvement in TTP patients is common,challenging and more often fatal,especially when other thrombotic complications coexist.展开更多
Objective Thrombotic thrombocytopenic purpura(TTP)is a rare and fatal disease caused by a severe deficiency in the metalloprotease ADAMTS13 and is characterized by thrombotic microangiopathy.The present study aimed to...Objective Thrombotic thrombocytopenic purpura(TTP)is a rare and fatal disease caused by a severe deficiency in the metalloprotease ADAMTS13 and is characterized by thrombotic microangiopathy.The present study aimed to investigate the genes and variants associated with TTP in a Chinese population.Methods Target sequencing was performed on 220 genes related to complements,coagulation factors,platelets,fibrinolytic,endothelial,inflammatory,and anticoagulation systems in 207 TTP patients and 574 controls.Subsequently,logistic regression analysis was carried out to identify the TTP-associated genes based on the counts of rare deleterious variants in the region of a certain gene.Moreover,the associations between common variants and TTP were also investigated.Results ADAMTS13 was the only TTP-associated gene(OR=3.77;95%CI:1.82–7.81;P=3.6×10^(-4))containing rare deleterious variants in TTP patients.Among these 8 variants,5 novel rare variants that might contribute to TTP were identified,including rs200594025,rs782492477,c.T1928G(p.I643S),c.3336_3361del(p.Q1114Afs*20),and c.3469_3470del(p.A1158Sfs*17).No common variants associated with TTP were identified under the stringent criteria of correction for multiple testing.Conclusion ADAMTS13 is the primary gene related to TTP.The genetic variants associated with the occurrence of TTP were slightly different between the Chinese and European populations.展开更多
Liver transplantation(LT)is the life saving therapeutic option for patients with acute and chronic end stage liver disease.This is a routine procedure with excellent outcomes in terms of patient survival and quality o...Liver transplantation(LT)is the life saving therapeutic option for patients with acute and chronic end stage liver disease.This is a routine procedure with excellent outcomes in terms of patient survival and quality of life post LT.Orthotopic LT(OLT)patients require a critical care as they are prone to variety of post-operative vascular,cardiovascular,biliary,pulmonary and abdominal complications.Thrombotic complications(both arterial and venous)are not uncommon post liver transplant surgery.Such vascular problems lead to increased morbidity and mortality in both donor and graft recipient.Although thromboprophylaxis is recommended in general surgery patients,no such standards exist for liver transplant patients.Drastic advancements of surgical and anesthetic procedures have improvised survival rates of patients post OLT.Despite these,haemostatic imbalance leading to thrombotic events post OLT cause significant graft loss and morbidity and even lead to patient’s death.Thus it is extremely important to understand pathophysiology of thrombosis in LT patients and shorten the timing of its diagnosis to avoid morbidity and mortality in both donor and graft recipient.Present review summarizes the current knowledge of vascular complications associated with LT to highlight their impact on short and long-term morbidity and mortality post LT.Also,present report discusses the lacunae existing in the literature regarding the risk factors leading to arterial and venous thrombosis in LT patients.展开更多
Thrombotic microangiopathy(TMA)is potentially life-threatening condition caused by small-vessel microthrombi and is associated with schistocyte formation,low platelets and end-organ damage that may not be reversible.[...Thrombotic microangiopathy(TMA)is potentially life-threatening condition caused by small-vessel microthrombi and is associated with schistocyte formation,low platelets and end-organ damage that may not be reversible.[1,2]As a life-threatening condition,TMA recognition in hospitalized patients after organ transplantation is key to improving survival.Transplant-associated TMA(TATMA)can occur after both solid organ or hematopoietic stem cell transplantation and often mimics other disease processes such as thrombotic throm-bocytopenic purpura(TTP)with similar constellation of symptoms during presentation.We present a rare case of a patient with TATMA after orthotopic heart transplantation.展开更多
文摘Hepatitis C virus(HCV)infection,traditionally regarded as a hepatotropic disease,is increasingly recognized as a systemic condition with significant thrombotic implications.Chronic HCV induces a persistent proinflammatory and prothrombotic state that substantially elevates the risk of both venous and arterial events.Mechanistically,HCV drives endothelial dysfunction,enhances platelet activation,disrupts coagulation and fibrinolytic balance,and promotes immunemediated vascular injury through cryoglobulinemia and chronic systemic inflammation.Clinical manifestations range from portal vein thrombosis and venous thromboembolism to coronary artery disease and ischemic stroke,highlighting the far-reaching consequences of virus-driven coagulopathy.Emerging evidence challenges the historical view of cirrhosis as a“naturally anticoagulated”state,instead describing a fragile hemostatic balance prone to both bleeding and thrombosis.Directacting antiviral therapy has transformed outcomes,not only achieving sustained virological response but also reversing systemic inflammation,improving endothelial function,and reducing thrombotic complications.However,patients with advanced fibrosis and comorbidities remain at elevated risk despite viral clearance,underscoring the need for ongoing surveillance.This minireview highlights the interplay between hepatic dysfunction,viral-induced inflammation,and cardiovascular sequelae in chronic HCV,emphasizing the importance of integrating thrombotic risk assessment into clinical care and research frameworks.
基金Supported by the Research Project for Clinical Research on Precision Diagnosis and Innovative Treatment of Bone Marrow Failure,No.2024YFC2510500Jiangsu Provincial Traditional Chinese Medicine Science and Technology Development Plan,No.YB2020102Nantong Municipal Health Commission Research Project,No.QN2023007.
文摘BACKGROUND Thrombotic microangiopathy(TMA)is an acute syndrome characterized by microangiopathic hemolytic anemia,thrombocytopenia,and multi-organ dysfunction due to the microcirculation of platelet thrombi.Cancer-associated TMA is a rare and fatal complication,which often occurs during cancer remission.It is frequently misdiagnosed because of limited clinical awareness.CASE SUMMARY A middle-aged female patient presented to our clinic with a 15-days history of back pain,15 months post-gastrectomy.Cancer-associated TMA was confirmed through bone marrow aspiration,biopsy,and imaging.The patient received intermittent transfusions,fluids,nutrition,and microcirculation therapy with partial coagulation improvement.The family refused intensive care unit admission and plasma exchange,preferring palliative care.The patient died of cerebral hemorrhage and herniation due to disease progression.This case indicates that TMA may serve as an early manifestation of various malignancies,particularly gastric cancer.However,it is often misdiagnosed.Its pathogenesis is not well understood and needs to be further investigated.Currently,no standardized treatment have been developed.Plasma exchange is the only intervention available,though other therapies may also be effective.CONCLUSION In this case of gastric signet-ring cell carcinoma complicated by TMA,the patient achieved transient remission with supportive care but died following treatment discontinuation.Further studies are needed to elucidate the pathological mechanisms and therapeutic strategies for cancer-associated TMA.
文摘Pulmonary tumour thrombotic microangiopathy(PTTM)is a rare but under-recognised cause of rapidly progressive pulmonary hypertension(PH)and cor pulmonale,characterised by diffuse obstruction of small pulmonary arteries by metastatic tumour cells.These tumour emboli lead to obstructive intimal proliferation and in situ thrombosis within the pulmonary vasculature,further compromising the overall permeability of the pulmonary vascular bed and exacerbating PH.[1]The clinical and imaging manifestations of PTTM often overlap with those of other causes of PH,including chronic thromboembolic PH,pulmonary veno-occlusive disease and pulmonary capillary haemangiomatosis,often leading to diagnostic delays.
基金Natural Science Foundation of Gansu Province(Project No.:24JRRA615)Outstanding Talent Recruitment Program and the Doctoral Start-up Fund of Gansu Provincial Central Hospital(Project No.:GMCCH2024-2-6)。
文摘Thrombotic thrombocytopenic purpura(TTP)is a rare and life-threatening form of thrombotic microangiopathy,primarily caused by a deficiency of ADAMTS-13 activity.Immune-related adverse events(irAEs)are autoimmune toxicities mediated by the use of immune checkpoint inhibitors(ICIs).Here,the study reports a case of thrombotic thrombocytopenic purpura that developed in a patient with renal cell carcinoma and vertebral metastasis following combined treatment with Toripalimab and Pazopanib.The patient received Toripalimab in combination with Pazopanib after undergoing radical nephrectomy for right renal cell carcinoma.Five days later,a generalized erythematous rash appeared,partly confluent,accompanied by congestion and swelling of both palpebral and bulbar conjunctiva.Based on the clinical presentation and laboratory results showing thrombocytopenia and hemolytic anemia,the diagnosis of TTP was established.The condition was considered an adverse effect associated with the combination therapy of Toripalimab and Pazopanib.Plasma exchange and high-dose intravenous immunoglobulin therapy were promptly initiated.The treatment regimen was subsequently modified to Axitinib combined with radiotherapy,leading to a gradual recovery of platelet counts.This report highlights the potential risk of TTP associated with combined ICI and TKI therapy,and underscores the importance of early recognition and timely management of this potentially fatal complication.
文摘This editorial article is intended to perform a discussion on the manuscript entitled“Simultaneous portal vein thrombosis and splenic vein thrombosis in a COVID-19 patient:A case report and review of literature”written by Abramowitz et al.The article focuses on the diagnostic processes in a 77-year-old-male patient with a simultaneous portal vein and splenic artery thrombosis accompanying coronavirus disease 2019(COVID-19).The authors postulated that splanchnic thrombosis should be on the list of differential diagnoses in a patient presenting with abdominal pain in presence of a COVID-19 infection.The tendency for venous and arterial thrombosis in COVID-19 patients is encountered,largely attributed to hypercoagulopathy.In general,venous thromboembolism mostly manifest as deep vein thrombosis(DVT),pulmonary embolism(PE)or catheterrelated thromboembolic events.Acute PE,DVT,cerebrovascular events and myocardial infarction are seen as the most common thromboembolic complications in COVID-19 patients.COVID-19-associated hemostatic abnormalities include mild thrombocytopenia and increased D-dimer level.Similar to other coagulopathies,the treatment of the underlying condition is the mainstay.Addition of antiplatelet agents can be considered in critically ill patients at low bleeding risk,not on therapeutic anticoagulation,and receiving gastric acid suppression Early administration of antithrombotic drugs will have a beneficial effect in both the prevention and treatment of thrombotic events,especially in non-ambulatory patients.Low molecular weight heparin(LMWH)should be started if there is no contraindication,including in non-critical patients who are at risk of hospitalization LMWH(enoxaparin)is preferred to standard heparin.
文摘Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura （TTP）-like syndrome suggest a survival beneft to early treatment with plasma exchange. The following is a report of the eighth such case in the last ten years. A 44-year-old lady known for lupus presented with the nephrotic syndrome and a renal biopsy was consistent with class 4G lupus nephritis. She was given high-dose steroids and cytotoxic therapy, but her induction therapy was complicated by the classic pentad of TTP. She was subsequently treated with another course of high-dose steroids, a different cytotoxic agent, and plasma exchange, with clinical resolution shortly thereafter. Similar to seven recently reported cases of microangiopathy in lupus, this lady’s TTP-like syndrome improved dramatically after initiation of plasma exchange, despite not having a severely deficient ADAMTS13. This has implications on both current clinical practice and on the pathogenesis of TTP-like syndromes in lupus.
基金The National Natural Science Foundation of China (Grant No. 81473383)the Significant New-Drugs Creation of Science and Technology Major Projects (Grant No. 2018ZX09711001-003-019)+1 种基金the Medical and Health Innovation Project of Chinese Academy of Medical Sciences (Grant No. 2016-I2M-3-007)Innovation Fund for Graduate of Beijing Union Medical College (Grant No. 2018-1007-04)。
文摘Ischemic stroke seriously threatens human health and quality of life.Xiao-Xu-Ming(XXM)decoction has been a classical prescription for stroke therapy.In our previous studies,we have found that XXM exerts neuroprotective effects,improves brain injury,and attenuates neuroinflammation in cerebral ischemia rats.In this study,we investigated the effects and possible mechanism of XXM on thrombotic focal cerebral ischemia.After treatment with XXM,the neurological function and motor abilities were improved,and cerebral infarction volume was significantly decreased compared with rats of thrombotic focal cerebral ischemia.Besides,the results of BBB integrity detected by EB leakage and tight junction(TJ)protein expression showed that XXM could maintain BBB integrity and improve the expressions of TJ proteins,including claudin-1,occluding,and ZO-1,in the ischemic ipsilateral cortex disrupted by thrombotic cerebral ischemia.Furthermore,proteomic techniques were used to identify the differentially expressed proteins(DEPs)in the ischemic cerebral cortex,and the results showed that 132 DEPs regulated by XXM were detected in the ischemic cerebral cortex.Bioinformatic analysis showed that these regulated proteins by XXM were mainly involved in complement and coagulation cascade,and lysosome,etc.Furthermore,there was an interaction among DEPs,including Lgals3,Ctsz,Capg,C1qa,S100a4,Grn,Hspb1,Aif1,and Anxa1,etc.In conclusion,XXM ameliorated brain injury of thrombotic focal ischemic stroke,and Lgals3,Ctsz,Capg,C1qa,S100a4,Grn,Hspb1,Aif1,and Anxa1 could help provide possible therapeutic targets of XXM for ischemic stroke and offer research direction for further research.
文摘BACKGROUND Pulmonary tumor thrombotic microangiopathy(PTTM)is a rare condition in patients with hepatocellular carcinoma(HCC);to date,few cases have been reported.While hepatic dysfunction has been focused on the later stages of HCC,the management of symptoms in PTTM is important for supportive care of the cases.For the better understanding of PTTM in HCC,the information of our recent case and reported cases have been summarized.CASE SUMMARY A patient with HCC exhibited acute and severe respiratory failure.Radiography and computed tomography of the chest revealed the multiple metastatic tumors and a frosted glass–like shadow with no evidence of infectious pneumonia.We diagnosed his condition as acute respiratory distress syndrome caused by the lung metastases and involvement of the pulmonary vessels by tumor thrombus.Administration of prednisolone to alleviate the diffuse alveolar damages including edematous changes of alveolar wall caused by the tumor cell infiltration and ischemia showed mild improvement in his symptoms and imaging findings.An autopsy showed the typical pattern of PTTM in the lung with multiple metastases.CONCLUSION PTTM is caused by tumor thrombi in the arteries and thickening of the pulmonary arterial endothelium leading to the symptoms of dyspnea in terminal staged patients.Therefore,supportive management of symptoms is necessary in the cases with PTTM and hence we believe that the information presented here is of great significance for the diagnosis and management of symptoms of PTTM with HCC.
文摘AIM: To evaluate the prevalence of genetic and acquired prothrombotic risk factors and their association with the extent of fibrosis and fatty infiltration in patients with non-alcoholic fatty liver disease (NAFLD).METHODS: Forty-four patients with chronic hepatitis (28 men and 16 women, with mean age of 45±11 and 49±12 years, respectively) constituted the patient population of this study. The groups were divided as follows: 15 patients with fatty liver (FL); 15 with non-alcoholic steatohepatitis (NASH); 14 with chronic viral hepatitis (CH) diagnosed by histology and liver technetium scan or ultrasound; and 10 healthy individuals. Thrombophilic, coagulation factors and genetic mutations were diagnosed by standard hemostatic and molecular coagulation assays.RESULTS: Activated protein C (APC) resistance and protein S were the most prevalent thrombotic risk factors (6% and 10% in NAFLD vs 21% and 14% in CH; P＜0.01 and P＜0.05, respectively). One thrombotic risk factor was identified in 41% of patients (23% mild fibrosis, 18% severe fibrosis) and two thrombotic risk factors in 6% of patients with NAFLD and severe fibrosis. While no differences in APC ratio, lupus anticoagulant, fibrinogen, factor V Leiden,prothrombin, and MTHFR mutation were found. Protein S levels were significantly lower in NASH patients than in patients with FL alone (92±19 vs106±2, P＜0.01). Protein C levels were markedly higher in patients with NAFLD and mild or severe fibrosis as compared to the patients with CH, respectively (128±40 vs96±14, P＜0.001 or 129±36 vs 88±13, P＜0.01).CONCLUSION: Up to 46% of patients with NAFLD may have thrombotic risk factors, and the presence of thrombotic risk factors is correlated with the extent of hepatic fibrosis,suggesting a crucial role of the coagulation system in the pathogenesis of hepatic fibrosis.
文摘Thrombotic thrombocytopenic purpura(TTP) is a multisystem disorder that essentially can affect any organ in the human body. The hallmark of the pathogenesis in TTP is the large von Willebrand factor multimers on plateletmediated micro-thrombi formation, leading to microvascular thrombosis.Autopsy studies showed that cardiac arrest and myocardial infarction are the most common immediate causes of death in these patients. Clinical manifestations of cardiac involvement in TTP vary dramatically, from asymptomatic elevation of cardiac biomarkers, to heart failure, MI and sudden cardiac death. There is limited knowledge about optimal cardiac evaluation and management in patients with TTP. The absence of typical cardiac symptoms,combined with complicated multi-organ involvement in TTP, may contribute to the under-utilization of cardiac evaluation and treatment. Prompt diagnosis and timely initiation of effective therapy could be critically important in selected cases. Based on our experience and this review of the literature, we developed several recommendations for focused cardiac evaluation for patients with acute TTP:(1) patients with suspected or confirmed TTP should be screened for the potential presence of cardiac involvement with detailed history and physical,electrocardiogram and cardiac enzymes;(2) clinical deterioration of TTP patients warrants immediate cardiac reevaluation;(3) TTP patients with clinical evidence of cardiac involvement should be monitored for telemetry, cardiac biomarkers and evaluated with transthoracic echocardiography. These patients require urgent targeted TTP treatment as well as cardiac-specific treatment. Aspirin therapy is indicated for all TTP patients. Since epicardial coronary artery involvement is rare, cardiac catheterization is usually not required, given the high risk for hemorrhage and kidney injury;(4) we recommend evidence-based medical therapy for ischemic symptoms and heart failure. TTP patients with evidence of cardiac involvement would also benefit from routine cardiology follow up during remission.
文摘Thrombotic microangiopathy(TMA) is one of the most devastating sequalae of kidney transplantation. A number of published articles have covered either de novo or recurrent TMA in an isolated manner. We have, hereby, in this article endeavored to address both types of TMA in a comparative mode. We appreciate that de novo TMA is more common and its prognosis is poorer than recurrent TMA; the latter has a genetic background, with mutations that impact disease behavior and, consequently, allograft and patient survival. Post-transplant TMA can occur as a recurrence of the disease involving the native kidney or as de novo disease with no evidence of previous involvement before transplant. While atypical hemolytic uremic syndrome is a rare disease that results from complement dysregulation with alternative pathway overactivity, de novo TMA is a heterogenous set of various etiologies and constitutes the vast majority of post-transplant TMA cases. Management of both diseases varies from simple maneuvers, e.g., plasmapheresis, drug withdrawal or dose modification, to lifelong complement blockade, which is rather costly. Careful donor selection and proper recipient preparation, including complete genetic screening, would be a pragmatic approach. Novel therapies, e.g., purified products of the deficient genes, though promising in theory, are not yet of proven value.
文摘BACKGROUND Sodium valproate is widely used in the treatment of epilepsy in clinical practice.Most adverse reactions to sodium valproate are mild and reversible,while serious idiosyncratic side effects are becoming apparent,particularly hepatotoxicity.Herein,we report a case of fatal acute liver failure(ALF)with thrombotic microangiopathy(TMA)caused by treatment with sodium valproate in a patient following surgery for meningioma.CASE SUMMARY A 42-year-old man who received antiepileptic treatment with sodium valproate after surgery for meningioma exhibited extreme fatigue,severe jaundice accompanied by oliguria,soy sauce-colored urine,and ecchymosis.His postoperative laboratory values indicated a rapid decreased platelet count and hemoglobin level,severe liver and kidney dysfunction,and disturbance of the coagulation system.He was diagnosed with drug-induced liver failure combined with TMA.After plasma exchange combined with hemoperfusion,pulse therapy with high-dose methylprednisolone,and blood transfusion,his liver function deteriorated,and finally,he died.CONCLUSION ALF with TMA is a rare and fatal adverse reaction of sodium valproate which needs to be highly valued.
基金Supported by The "East Carolina Heart Institute"
文摘Thrombotic thrombocytopenia purpura(TTP) was fi rst described in 1924 as a "pathologic alteration of the microvasculature, with detachment or swelling of the endothelium, amorphous material in the sub-endothelial space, and luminal platelet aggregation leading to compromise of the microcirculation". Ticlopidine induced TTP has been highly associated with autoimmune induced reduction in ADAMTS-13 activity. These findings, to a lesser extent, have also been found in clopidogrel induced TTP. We report a case of clopidogrel associated TTP in a patient that presented with acute stroke, renal failure, and non-ST elevation myocardial infarction.
文摘BACKGROUND Interferons(IFNs)are characterized by a wide range of biological effects,which justifies their potential therapeutic use in several pathologies,but also elicit a wide array of adverse effects in almost every organ system.Among them,renal involvement is probably one of the most complex to identify.CASE SUMMARY We describe four cases of kidney damage caused by different IFN formulations:IFN-β-related thrombotic microangiopathy,IFN-β-induced systemic lupus erythematosus,and two cases of membranous nephropathy secondary to pegylated-IFN-α2B.In each case,we carefully excluded any other possible cause of renal involvement.Once suspected as the casual relationship between drug and kidney damage,IFN treatment was immediately discontinued.In three cases,we observed a complete and persistent remission of clinical and laboratory abnormalities after IFN withdrawal,while the patient who developed thrombotic microangiopathy,despite IFN withdrawal and complement-inhibitor therapy with eculizumab,showed persistent severe renal failure requiring dialysis.CONCLUSION This case series highlights the causal relationship between IFN treatment and different types of renal involvement and enables us to delineate several peculiarities of this association.
基金Supported by the Grant from Uehara Memorial Foundation, No. 200940051, Tokyo, 171-0033, Japan
文摘AIM:To investigate thrombotic microangiopathy (TMA)in liver transplantion,because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS:A total of 206 patients who underwent living-donor liver transplantation (LDLT) were evaluated,and the TMA-like disorder (TMALD) occurred in seven recipients. RESULTS:These TMALD recipients showed poor outcomes in comparison with other 199 recipients. Although two TMALD recipients successfully recovered,the other five recipients finally died despite intensive treatments including repeated plasma exchange (PE) and re-transplantation. Histopathological analysis of liver biopsies after LDLT revealed obvious differences according to the outcomes. Qualitative analysis of antibodies against a disintegrin-like domain and metalloproteinase with thrombospondin type 1 motifs (ADAMTS-13) were negative in all patients. The fragmentation of red cells,the microhemorrhagic macules and the platelet counts were early markers for the suspicion of TMALD after LDLT. Although the absolute values of von Willebrand factor (vWF) and ADAMTS-13 did not necessarily reflect TMALD,the vWF/ADAMTS-13 ratio had a clear diagnostic value in all cases. The establishment of adequate treatments for TMALD,such as PE for ADAMTS-13 replenishment or treatments against inhibitory antibodies,must be decided according to each case. CONCLUSION:The optimal induction of adequate therapies based on early recognition of TMALD by the reliable markers may confer a large advantage for TMALD after LDLT.
文摘BACKGROUND Thrombotic thrombocytopenic purpura(TTP)is a life-threatening but treatable disorder.Acute pancreatitis is a well-described consequence of TTP,but TTP as a consequence of acute pancreatitis is rare.CASE SUMMARY A 32-year-old male developed acute pancreatitis due to a fatty diet and suffered splenectomy 3 years ago due to trauma.From day 4 of his onset of pain the blood examination showed the platelet extremely reduced,bilirubin elevated and creatinine increased.High clinical suspicion of TTP was made and prompt initiation of plasma exchange was given followed intravenous drip methylprednisolone.After 7 sessions of plasm exchange and the laboratory parameters were back to normal and the patient was discharged from the hospital on the 13th day of admission.CONCLUSION Patients develop acute pancreatitis with no apparent causes for hemolytic anemia and thrombocytopenia,the possibility of TTP should be considered.Treatments for TTP including plasm exchange should be evaluated as soon as a diagnosis is made.
文摘BACKGROUND Thrombotic thrombocytopenic purpura(TTP)is a thrombotic microangiopathy characterized by the pentad of hemolytic anemia,fever,thrombocytopenia,renal failure,and neurological dysfunction.The formation of microthrombi in the arterioles and capillaries of various organs is one of the main pathophysiological mechanisms.Clinical manifestations of cardiac involvement in TTP patients are variable.Acute myocardial infarction has been reported as a complication with TTP as the secondary thrombotic event.Its emergence as the initial thrombotic event is extremely rare.CASE SUMMARY A 49-year-old previously healthy man was admitted for fever,typical angina chest pain 3 d prior to presentation,and newly onset left lower limb pain.The electrocardiogram illustrated ST-elevation acute myocardial infarction of the anterolateral wall of the left ventricle.Transthoracic echocardiography depicted two large thrombi at the apex of the left ventricle and moderately reduced ejection fraction(40%).Venous Doppler ultrasound showed occlusion of the left popliteal artery.Laboratory tests showed severe thrombocytopenia,mild hemolytic anemia,elevated D-dimers,and high troponin and creatine kinase-MB.Abdominal computed tomography revealed other thrombotic sites(superior mesenteric artery,posterior aortic wall,spleen and renal infarction,and ileum necrosis).He was immediately started on steroids and addressed to surgery for acute abdominal pain.After an initial stabilization of the hematological deficit,he went into general surgery for resection of the necrotic ileum but died soon after the intervention due to multiple organ failure.CONCLUSION Cardiac involvement in TTP patients is common,challenging and more often fatal,especially when other thrombotic complications coexist.
基金supported by the National Natural Science Foundation of China(No.82003561).
文摘Objective Thrombotic thrombocytopenic purpura(TTP)is a rare and fatal disease caused by a severe deficiency in the metalloprotease ADAMTS13 and is characterized by thrombotic microangiopathy.The present study aimed to investigate the genes and variants associated with TTP in a Chinese population.Methods Target sequencing was performed on 220 genes related to complements,coagulation factors,platelets,fibrinolytic,endothelial,inflammatory,and anticoagulation systems in 207 TTP patients and 574 controls.Subsequently,logistic regression analysis was carried out to identify the TTP-associated genes based on the counts of rare deleterious variants in the region of a certain gene.Moreover,the associations between common variants and TTP were also investigated.Results ADAMTS13 was the only TTP-associated gene(OR=3.77;95%CI:1.82–7.81;P=3.6×10^(-4))containing rare deleterious variants in TTP patients.Among these 8 variants,5 novel rare variants that might contribute to TTP were identified,including rs200594025,rs782492477,c.T1928G(p.I643S),c.3336_3361del(p.Q1114Afs*20),and c.3469_3470del(p.A1158Sfs*17).No common variants associated with TTP were identified under the stringent criteria of correction for multiple testing.Conclusion ADAMTS13 is the primary gene related to TTP.The genetic variants associated with the occurrence of TTP were slightly different between the Chinese and European populations.
文摘Liver transplantation(LT)is the life saving therapeutic option for patients with acute and chronic end stage liver disease.This is a routine procedure with excellent outcomes in terms of patient survival and quality of life post LT.Orthotopic LT(OLT)patients require a critical care as they are prone to variety of post-operative vascular,cardiovascular,biliary,pulmonary and abdominal complications.Thrombotic complications(both arterial and venous)are not uncommon post liver transplant surgery.Such vascular problems lead to increased morbidity and mortality in both donor and graft recipient.Although thromboprophylaxis is recommended in general surgery patients,no such standards exist for liver transplant patients.Drastic advancements of surgical and anesthetic procedures have improvised survival rates of patients post OLT.Despite these,haemostatic imbalance leading to thrombotic events post OLT cause significant graft loss and morbidity and even lead to patient’s death.Thus it is extremely important to understand pathophysiology of thrombosis in LT patients and shorten the timing of its diagnosis to avoid morbidity and mortality in both donor and graft recipient.Present review summarizes the current knowledge of vascular complications associated with LT to highlight their impact on short and long-term morbidity and mortality post LT.Also,present report discusses the lacunae existing in the literature regarding the risk factors leading to arterial and venous thrombosis in LT patients.
文摘Thrombotic microangiopathy(TMA)is potentially life-threatening condition caused by small-vessel microthrombi and is associated with schistocyte formation,low platelets and end-organ damage that may not be reversible.[1,2]As a life-threatening condition,TMA recognition in hospitalized patients after organ transplantation is key to improving survival.Transplant-associated TMA(TATMA)can occur after both solid organ or hematopoietic stem cell transplantation and often mimics other disease processes such as thrombotic throm-bocytopenic purpura(TTP)with similar constellation of symptoms during presentation.We present a rare case of a patient with TATMA after orthotopic heart transplantation.
