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.

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.

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.

Lupus-associated thrombotic thrombocytopenic purpura-like microangiopathy

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.

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.

Helicobacter pylori infection in patients with autoimmune thrombocytopenic purpura

AIM:To compare the prevalence of Helicobacter pylori (Hpylon)infection in autoimmune thrombocytopenic purpura (AITP)patients with that of nonthrombocytopenic controls, and to evaluate the efficacy of the treatment in H pylori(+) and H pylor(-)AITP patients. METHODS:The prevalence of gastric H pylori infection in 38 adult AITP patients(29 female and 9 male;median age 27 years;range 18-39 years)who consecutively admitted to our clinic was investagated. RESULTS:H pylori infection was found in 26 of 38 AITP patients(68.5%).H pylori infection was found in 15 of 23 control subjects(65.2%).The difference in H pylori infection between the 2 groups was not significant.Thrombocyte count of H pylori-positive AITP patients was significantly lower than that of H pylori-negative AITP patients(P<0.05). Thrombocyte recovery of H pylori-positive group was less than that of H pylori-negative group(P<0.05). CONCLUSION:H pylori infection should be considerecd in the treatment of AITP patients with H pylori infection.

Helicobacter pylori eradication in patients with chronic immune thrombocytopenic purpura

AIM: To assess the effect of Helicobacter pylori (H. pylori) eradication on platelet counts in patients with chronic immune thrombocytopenic purpura (cITP).

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.

Association of primary biliary cirrhosis with idiopathic thrombocytopenic purpura

Although both primary biliary cirrhosis (PBC) and idiopathic thrombocytopenic purpura (ITP) are autoimmune diseases, the association of the 2 diseases is rare. Here, we report a case of ITP that developed during the follow-up of PBC in a 74-year- old man. The patient had been diagnosed with PBC 12 years previously, and had received treatment with ursodeoxycholic acid. The platelet count decreased from approximately 60 × 109/L to 8 × 109/L, and the association of decompensated liver cirrhosis (PBC) with ITP was diagnosed. Steroid and immune gamma globulin therapy were successful in increasing the platelet count. Interestingly, human leukocyte antigen genotyping detected the alleles DQB10601 and DRB10803, which are related to both PBC and ITP in Japanese patients. This case suggests common immunogenetic factors might be involved in the development of PBC and ITP.

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.

Refractory case of ulcerative colitis with idiopathic thrombocytopenic purpura successfully treated by Janus kinase inhibitor tofacitinib:A case report

BACKGROUND Concomitant ulcerative colitis (UC) and idiopathic thrombocytopenic purpura(ITP) is a rare phenomenon. The management of UC with ITP can be challenging,since a decreased platelet count augments UC.CASE SUMMARY A 24-year-old man with UC and steroid-resistant ITP experienced UC flare.Although continuous infusion of cyclosporine was initiated, UC did not improve.The administration of tofacitinib subsequently led to the induction of remission.The patient has maintained remission of UC and ITP for over one year ontofacitinib treatment. Whole transcriptomic sequencing was performed forinflamed rectal mucosae obtained before and after the initiation of Janus kinase(JAK) inhibitor, suggesting that distinct molecular signatures seemed to beregulated by JAK inhibitors and other conventional therapies including tumornecrosis factor lockers.CONCLUSION Tofacitinib should be considered in refractory cases of UC with ITP.

Study of establishing disease-syndrome combined with animal model for immune thrombocytopenic purpura without additional conditions

Objective:To explore the feasibility of establishing the disease-syndrome combined animal model for immune thrombocytopenic purpura(ITP)without additional conditions.Methods:Three batches of data related to the ITP model mice obtained by replication at different time were analyzed,and whether the APS-injected model mice replicated through the passive immune modeling method could simulate the pathogenesis and clinical characteristics of human ITP was evaluated according to the differentiation criteria for diseasesyndrome combined model.Results:The APS-injected replicated ITP model mice possessed the following traits:(1)Compared with the normal group,the platelet count was significantly decreased,and coagulation time was significantly increased in the model group(P<.01).(2)Compared with the normal group,the medullary thrombocytogenous megakaryocytes were significantly decreased(P<.05,.01,.001).(3)The APS-injected sites and other parts of the model mice had spontaneous hemorrhage.(4)Behavioral changing signs were observed 1 week after the modeling(i.e.low activity,delayed activity,poor appetite,skin petechia/hemorrhage and spontaneous hemorrhage at the injected sites or other parts),and were getting more and more severe.Conclusion:According to the syndrome differentiation criteria for disease-syndrome combined model of ITP,the APS-injected animal model of ITP replicated through the passive immune modeling method without additional conditions possesses the characteristics of disease-syndrome combined model.It provides an ideal tool for the development of traditional Chinese medicine pharmacology experiment.

Direct Infection of Colony Forming Unit-Megakaryocyte by Human Cytomegalovirus Contributes the Pathogenesis of Idiopathic Thrombocytopenic Purpura

Human cytomegalovirus （HCMV） late mRNA expression in megakaryoblast and in turn the pathogenesis of idiopathic thrombocytopenic purpura （ITP） patients with HCMV infection, and effectiveness of ganciclovir were investigated. Colony forming unit-megakaryocytes （CFU-MK） of 46 ITP patients with HCMV infection were incubated from patients＇ bone marrow mononuclear cells （MNC）. Reverse transcriptase-polymerase chain reaction （RT-PCR） was subsequently used for CFU-MK for HCMV-late mRNA detection, Ganciclovir therapy was given to both HCMV-late mRNA positive and negative groups for comparison of therapeutic effectiveness, The results in 19 of 46 CFU-MK culture cells specimens with positive HCMV-DNA by PCR or positive CMV-IgM by enzyme linked immunosorbent assay （ELISA） in the correspondent serum of peripheral blood were positive for HCMV-late mRNA, Sixteen out of 19 patients with positive HCMV-late mRNA CFU-MK had a positive response to ganciclovir. Amongst 27 patients with negative HCMV-late mRNA CFU-MK, only 4 positive responders to ganciclovir therapy were observed. Curative effectiveness of ganciclovir in HCMV-late mRNA positive group was significantly higher than that in HCMV-late mRNA negative group （P〈0.01）, It was suggested that HCMV could directly infect CFU-MK, which might be one of the mechanisms responsible for HCMV related ITE The ganci- clovir is an effective therapy in resulting in the increases in thrombocyte in the ITP patients whose HCMV- late mRNA was positive in their CFU-MK.

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.

Therapeutic Uses of Lycium barbarum Polysaccharides on Idiopathic Thrombocytopenic Purpura Mice via Inhibition of Oxidative Stress

The aim of the present study was to investigate the effect of Lycium barbarum polysaccharides (LBP) on the treatment of ITP mice and to explore its mechanism. Forty idiopathic thrombocytopenic purpura (ITP) mice were divided randomly into a model control group and LBP groups I, II, III and IV. ITP mice in LBP groups I, II, III, and IV were administered LBP at four different doses (50, 100, 200 and 400 mg·kg-1·d-1, respectively) for 7 days by gavage. Blood samples were collected from the tail veins of the mice after treatment. Platelet counts were determined, and the total antioxidant status (TAS), total oxidant status (TOS) were measured with ELISA kits. The platelet count was (30.28 ± 13.42) × 109/L in the model control group, and the number of platelets in all LBP groups was higher than that in the model control group. The platelet count increased, and it reached (67.09 ± 10.81) × 109/L in LBP group I;the platelet counts in the other three groups increased significantly compared to LBP group I, and they did not differ significantly. TAS concentrations in the LBP groups were significantly increased compared to the model control group, whereas TOS concentrations were significantly decreased. Taken together, these results indicate that LBP is effective at increasing the number of platelet (PLT), and LBP may treat ITP mice via suppressing oxidative stress.

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, rapidly growing and chemosensitive malignancies. ATLS is characterized by the presence of hyperphosphatemia, hyperuricemia, hyperkalemia, hypocalcemia and acute renal failure. The administration of cytotoxic chemotherapy causes tumor death and tissue necrosis which leads to release of inflammatory mediators precipitating this syndrome. However, it has been rarely reported in hematological malignancies without administration of chemotherapy, and has been referred to as spontaneous tumor lysis syndrome （STLS）. STLS is even more infrequent in solid tumors.