Thrombotic Thrombocytopenic Purpura in Pregnancy Presented with Stroke at 29 Weeks: A Case Report

Thrombotic thrombocytopenic purpura (TTP) is a rare but acute, life-threatening condition which may be precipitated by pregnancy. This disorder that presents with thrombocytopenia, haemolytic anemia, and clinical consequences of microvascular thrombosis such as stroke. The exact cause is not known but it is associated with a deficiency of ADAMTS13 enzymes. Immune mediated TTP is more common and can present in pregnancy. The aim of this case is to bring awareness as many clinicians are unaware of this condition in pregnancy, its diagnosis may be missed or delayed, leading to fetal loss or serious maternal implications. In this case the patient presented at 29 weeks with stroke in Emergency department, referred to delivery suit for Obstetric review, with suspicion of Pre-eclampsia/HELLP. The diagnosis of TTP was achieved by a multidisciplinary team who worked tirelessly together. The patient was transferred to a Specialist Tertiary Care Centre for further management. The pregnancy continued until 33 weeks and 5 days. She underwent an emergency caesarean section for fetal distress. Steroids and Rituximab were continued postnatally. The outcome was favourable due to fast and efficient multidisciplinary care. Awareness of this rare but important condition can lead to recognition of clinical presentation, prompt diagnosis and appropriate management.

Efficacy of Rituximab Combined with Plasma Exchange in the Treatment of Thrombotic Thrombocytopenic Purpura(TTP)

Objective:To analyze the curative effect of rituximab combined with plasma exchange in the treatment of thrombotic thrombocytopenic purpura.Methods:70 patients with thrombotic thrombocytopenic purpura that were treated in our hospital from January 2022 to January 2023 were selected for this study.They were divided into two groups according the treatment method they were about to receive.The patients in the control group received plasma exchange.The observation group was given rituximab in addition to plasma exchange.Then,the therapeutic effects of the two groups were observed,and the incidence of adverse reactions was compared.Results:The rate of effectiveness of the treatment received in observation group and the control group was 97.14%and 82.86%,respectively.The treatment received in observation group had a better therapeutic effect(P<0.05).The incidence of adverse reactions in the observation group(22.86%)was lower than that of the control group(5.71%),with P<0.05.Conclusion:Rituximab combined with plasma exchange is relatively more effective than plasma exchange alone,with less adverse reaction,making it a viable treatment option.

Identification of 8 Rare Deleterious Variants in ADAMTS13 by Next-generation Sequencing in a Chinese Population with Thrombotic Thrombocytopenic Purpura

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.

Acute pancreatitis-induced thrombotic thrombocytopenic purpura:A case report

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.

Successful treatment of plasma exchange-refractory thrombotic thrombocytopenic purpura with rituximab:A case report

BACKGROUND Thrombotic thrombocytopenic purpura(TTP),a subtype of thrombotic microangiopathy,has a very high fatality rate if there is no timely diagnosis or treatment.Here,we report a case of TTP refractory to high displacement plasma exchange,which was later successfully treated with rituximab.CASE SUMMARY Here we report a case of refractory TTP in a 63-year-old woman with a low platelet count and decreased ADAMTS13 activity.Her platelet count was 9×109/L,hemoglobin level was 81 g/L,and ADAMTS13 was<5%.She was diagnosed with thrombotic thrombocytopenic purpura.After 8 d of daily plasma exchange(PEX),her platelet levels were still low.However,after 6 d of treatment with rituximab,her platelet count increased and ADAMTS13 activity returned to normal.CONCLUSION PEX can cure most patients,but the relapse rate can be up to 50%-60%.This case suggested that rituximab can improve the curative efficiency of PEX and prevent disease relapse in TTP.

Acute myocardial infarction and extensive systemic thrombosis in thrombotic thrombocytopenic purpura: A case report and review of literature

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.

Thrombotic thrombocytopenic purpura misdiagnosed as hepatic encephalopathy:a case report

Background:thrombotic thrombocytopenic purpura(TTP)is an autoimmune disease with high mortality.An AD AMTS 13(a disintegrin and metallopro-tection with a thrombospondin type 1 motif,member 13)activity level of less than 10% supports the diagnosis of TTP in appropriate clinical contexts.Historically,nearly all patients died during the first month of illness with severe hemolytic anemia,abundant schistocytes,profound thrombocytopenia,neurological deficits,renal injury,and fever.Most such patients have severe ADAMTS13 deficiency.Currently,the first-line treatment of TTP including plasma exchange therapy and preemptive B-cell depletion with rituximab can increase the survival rate and reduce the recurrence rate.Case presentation:a 34-year-old male patient who presented with hemato-chezia and progression of disorder of consciousness was misdiagnosed with esophageal and gastric varices bleeding and hepatic encephalopathy based on his history of hepatitis B.However,he was diagnosed with TTP based on clinical and laboratory results.He received comprehensive and systemic treatments including taking methylprednisolone,rituximab,and multiple sessions of plasmapheresis.The patient recovered well after active treatment.Conclusion:in this article,we reported a patient diagnosed as TTP and reviewed the disease characteristics,pathogenesis,and treatment of TTP in order to deepen the understadning of TTP and to reduce its missed diagnosis and misdiagnosis.

Cardiac implications of thrombotic thrombocytopenic purpura

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.

Low ADAMTS-13 in plavix induced thrombotic thrombocytopenic purpura

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.

Spontaneous Tumor Lysis Syndrome and Secondary Thrombotic Thrombocytopenic Purpura in Early Stage Colorectal Cancer

Introduction Acute tumor lysis syndrome (ATLS) is a well-described oncological emergency that is usually associated with hematological malignancies complicated by treatment.It is typically related to a high tumor burden,

Lupus-associated thrombotic thrombocytopenic purpura-like microangiopathy

Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura(TTP)-like syndrome suggest a survival benefit to early treatment with plasma exchange. The following is a report of the eighth such case in the last ten years. A 44-yearold 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.

A Case of Investigation and Diagnosis of Immune Thrombocytopenic Purpura After Vaccination of COVID-19 Inactivated Vaccine

Objective:Analyze the relationship between inoculating one case of the COVID-19 inactivated vaccine(Vero cell)and immune thrombocytopenic purpura to provide a reference for the standardized handling of adverse events following immunization.Methods:According to the"National Monitoring Program for Suspected Adverse Reactions to Vaccinations,"an on-site investigation,data collection and analysis,expert group diagnosis,and medical association assessment were conducted on a case of immune thrombocytopenic purpura in District A of Chongqing after vaccination with the inactivated COVID-19 vaccine.The assessment report was delivered to the three relevant parties,the case was reviewed,and the experience was summarized.Results:The investigation and diagnosis by the district-level vaccination abnormal reaction expert group concluded that the disease that occurred after vaccination with the COVID-19 inactivated vaccine was secondary immune thrombocytopenic purpura,an abnormal reaction to the vaccination.The medical damage was classified as Level II Grade B.The vaccine production enterprise raised objections to this conclusion.After re-assessment by the municipal-level medical association,the conclusion was consistent with that of the district-level medical association.The vaccine production enterprise did not raise any further objections.Conclusion:Through active collaboration among district and municipal-level medical associations,disease control institutions,and vaccination units,the recipients have been promptly and effectively treated,providing financial support for their subsequent treatment and safeguarding their rights.The investigation and disposal procedures for adverse events following immunization in Chongqing are clear,and the mechanism is sound.It is necessary to continue strengthening the monitoring of adverse events following immunization according to the existing plan and to ensure timely and standardized handling.Simultaneously,it is crucial to strengthen vaccine management and vaccination management.

Thrombotic Thrombocytopenic Purpura in a Parturient Leading to Life-Threatening Thrombocytopenia and Neonatal Demise—A Case Report

Thrombocytopenia is common (up to 12%) in pregnancy;thrombotic thrombocytopenia is a rare cause of thrombocytopenia;however,it is immediately life-threatening to both mother and fetus and requires immediate intervention.This is compounded by the need to act on a presumptive diagnosis with high level of suspicion given the relatively long laboratory confirmation time.A 31-year-old gravida 3,para 1 parturient at 26 weeks of gestation presented to outside hospital with recent onset of easy bruising and blurry vision.A blood count was drawn and showed a platelet count of 19,000/μL.She was transferred to our institution for management where an initial diagnosis of preeclampsia with severe features was made based on thrombocytopenia and fetal growth restriction (<1%).Platelet count nadired at 14,000/μL and a blood smear showed schistocytes,suggesting microangiopathic hemolysis,prompting discussion of urgent cesarean delivery and anesthesia consult.An urgent hematology consult led to presumptively diagnosing thrombotic thrombocytopenic purpura and cesarean delivery was deferred after discussion with the patient and team.Plasma exchange and steroid therapy were started promptly,and her platelet count improved within 12 hours.Unfortunately,the patient experienced neonatal demise.Undetectable ADAMTS13 levels confirmed diagnosis of thrombotic thrombocytopenia.She was transitioned to rituximab,platelets recovered to baseline,and she continues to do well.Thrombotic thrombocytopenia is a rare,life-threatening cause of thrombocytopenia in pregnancy.Despite grim fetal prognosis,especially in early pregnancy,low threshold of suspicion,early anesthesia involvement,and multi-disciplinary approach can facilitate diagnosis and timely intervention.In our case,it was likely lifesaving.

Evaluation of von Willebrand factor-cleaving protease activity in patients with thrombotic thrombocytopenic purpura

Background Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy. In this study we investigated the von Willebrand factor-cleaving protease (vWF-cp) activity deficiency in patients with TTP.Methods The plasma or serum vWF-cp activity was measured using a sensitive enzyme-linked immunosorbent assay (ELISA) by detecting the residual collagen binding activity (R-CBA) of von Willebrand factor (vWF) before and after digestion by vWF-cp. Multimers of vWF in plasma of patients with TTP were also analyzed by SDS-agarose electrophoresis. Moreover,the serum vWF-cp activities were compared between the patients with TTP and those with tumors.Results The coefficient of variation for intra-batch and inter-batch of the assay were 3.60% and 8.35%. The plasma and serum vWF-cp activity in healthy individuals were (78.79±9.17)% (n=30) and (79.47±10.78)% (n=53),respectively,while the plasma vWF-cp activity in 5 patients with TTP was markedly decreased [(21.83±19.98)%,P <0.001]. The unusually large vWF multimers were observed in two plasma samples of the patients with TTP. Although the vWF-cp activities in patients with benign and malignant tumors were also decreased ( P <0.03 and P <0.001,respectively),they were relatively high in comparison with that of TTP patients ( P <0.001).Conclusion Measurement of the vWF-cp activity using R-CBA is a simple and rapid method for diagnosing TTP. The vWF-cp activity in patients with TTP was markedly lower than those of patients with tumors.

The Effect of Costimulatory Factors in the Pathogenesis of Chronic Idiopathic Thrombocytopenic Purpura

To investigate the effect of costimulatory factors in the pathogenesis of chronic idiopathic thrombocytopenic purpura(CITP), we examined the expression of CD80 on platelets and megakaryocytes in patients with CITP and the controls by FACS. By using CD80 monoclonal antibody (McAb) to inhibit interaction among cells which is mediated by costimulatory factors, we observed the effect of CD80 McAb on the growth and maturation of megakaryocytic progenitors of patients with CITP in vitro . The results showed the expression of CD80 on platelets and megakaryocytes in CITP group was significantly higher than that in controls ( P <0.01). There was a significantly positive correlation between the expression of CD80 on platelets and serum PAIgG in CITP (r=0.86, P <0.05). The mean of various clone numbers (CFU MK, BFU MK and mCFU MK) in CITP were all lower than those in controls ( P <0.05). In megakaryocytes co cultured with CD80 McAb, there was an increasing tendency of the number of CFU MK and big CFU MK (the number of megakaryocyte with GPⅢ a positive was more than 20) and mediate CFU MK (the number of megakaryocyte with GPⅢ a positive was 11-20). When the concentration of CD80 McAb was 10 μg/L, there was a significant difference in the number of megakaryocytic colony formation (CFU MK, BFU MK and mCFU MK) between the group with CD80 McAb and that without it ( P <0.05).These showed the abnormality of costimulatory factors had important effect in the pathogenesis of CITP.

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

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

A murine model for human immune thrombocytopenic purpura and comparative analysis of multiple gene expression in bone marrow and spleen

Homeostasis of platelet number in human and other mammals is well maintained for prevention of minor bleeding and for other im- munological functions, but the exact molecular mechanism responsible for immune thrombocytopenic purpura （ITP） has not been fully understood. In an effort to identify genetic factors involved in initiation of platelet production in response to bleeding injury or platelet destruction, we have successfully generated an animal model of human ITP via intraperitoneal injection of anti-platelet antibody into the Balb/c mouse. Platelet counts were dropped dramatically in animals that received antibody injection within 4 h, maintained at the mini- mum level for a period of 44 h, started to rebound after 48 h, and reached to the maximum at 144 h （6 days）. Final homeostasis reached at approximately 408 h （17 days）, following a minor cycle of platelet number fluctuation. Using semi-quantitative RT-PCR, we assessed and compared mRNA level of CD41, c-myb, c-mpl, caspase-3, caspase-9, GATA-1, and Bcl-xl in bone marrow and spleen. Alteration of mRNA expression was correlated with the change of platelet level, and an inverse relationship was found for expression of the genes be- tween bone marrow and spleen. No transcription was detectable for any of the seven genes in bone marrow at the time when platelet number reached the maximum （144 h）. In contrast, mRNA transcripts of the seven genes were found to be at the highest level in spleen tissue. This is the first study of simultaneous detection of multiple platelet related genes in a highly reproducible ITP animal model. Our results provided the supportive evidence that expression of the above seven genes are more related to negative regulation of platelet number in spleen tissue, at least in the model animals.

Clinical Study on the Effect of Shengxueling (生血灵) on Idiopathic Thrombocytopenic Purpura

Objective:To observe the clinical effect of Shengxueling (生血灵, SXL) on idiopathic thrombocytopenic purpura (ITP), and study the possible mechanism.Methods: Eighty-six cases of ITP were randomly divided into two groups. The SXL group, 56 patients treated with SXL, a traditinal Chinese medicine and 30 patients administered with prednisone were taken as control. Each group took drugs for 3 months and was under follow-up observation.Results: In the SXL group, the total effective rate was 85.71%, similar to prednisone 83.33%( P >0.05) for 3 months, but the total effective rate of SXL (91.07%) were obviously better than that of the control group (53.33%) ( P <0.01) for 6 months and had no obvious adverse reaction. The patients bleeding was alleviated or stopped, the general condition was improved. At the same time, blood platelet count (PLT) was increased, platelet associated immunoglobulin (PAIg) and interleukin-4 (IL-4) were markedly dropped, the level of natural killers cells activity (NKa) increased, the rate of T lymphocyte subsets gradually returned to normal level. Megakaryocyte tended to maturation on bone marrow smear after treatment. All differences above were statistically significant.Conclusion: SXL is an effective and safe medicine for ITP. Its mechanism could regulate cytoimmune, inhibit platelet antibody to reduce the destruction of platelet, increase the number of platelet, promote the division and maturation of megakaryocyte, facilitate the production and release of platelet, lower the fragility of capillary, prevent and cure hemorrhagic tendency.

Immune thrombocytopenic purpura induced by intestinal tuberculosis in a liver transplant recipient

A variety of clinical manifestations are associated directly or indirectly with tuberculosis. Among them, haematological abnormalities can be found in both the pulmonary and extrapulmonary forms of the disease. We report a case of immune thrombocytopenic purpura(ITP) associated with intestinal tuberculosis in a liver transplant recipient. The initial management of thrombocytopenia, with steroids and intravenous immunoglobulin, was not successful, and the lack oftuberculosis symptoms hampered a proper diagnostic evaluation. After the diagnosis of intestinal tuberculosis and the initiation of specific treatment, a progressive increase in the platelet count was observed. The mechanism of ITP associated with tuberculosis has not yet been well elucidated, but this condition should be considered in cases of ITP that are unresponsive to steroids and intravenous immunoglobulin, especially in immunocompromised patients and those from endemic areas.