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.

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.

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.

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.

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.

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.

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.

Immune Thrombocytopenia Purpura (ITP) with Grave’s Disease, in a Plasmodium Vivax Positive Patient. A Case Report

Hyperthyroidism and thrombocytopenia have long been associated with each other. We present a case of 38 years old female presenting with complaints of bleeding from gums, bleeding per rectum, hematuria and easy bruising since 7 days ago. She also had a diffuse, non-tender neck swelling moving with deglutition and positive bruit on auscultation. Her laboratory results indicated thrombocytopenia (22 × 10^9/L) and her thyroid function test revealed TSH of 0.01 mIU/ml (normal: 0.17 - 4.05), free T3 of 19.19 pg/ml (normal: 1.6 - 3.7), free T4 of 4.09 ng/dl (normal: 0.89 - 1.79). Thyroid scan showed diffuse goiter with increased tracer uptake. Furthermore, her serum anti-thyroglobulin and anti-thyroid peroxide were elevated to 205 IU/ml and 713 IU/ml respectively. She was started on carbimazole and methylprednisolone immediately. On the 3rd day of admission, she was tested to be positive for Plasmodium Vivax after a fever spike and was started on Chloroquine (CQ) and later shifted to Primaquine (PQ). During 2 weeks of admission, her platelet count kept fluctuating between <10 × 10^9/L and <100 × 10^9/L with frequent transfusions of mega units of platelets. During 3rd week, her platelets improved and she was discharged with a platelet count of 370 × 10^9/L. This case, therefore, supports the association between autoimmune thyroid diseases such as Graves’ disease and idiopathic thrombocytopenic purpura (ITP) strongly suggesting the need for evaluating thyroid disease in cases of severe thrombocytopenia especially those refractory to treatment. Also, the effectiveness of treatment of thyroid disease on thrombocytopenia is also highlighted. In addition, it showed the possible added exacerbating effects of malarial infection on thrombocytopenia.

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.

Rapid progressive vaccine-induced immune thrombotic thrombocytopenia with cerebral venous thrombosis after ChAdOx1 nCoV-19(AZD1222)vaccination:A case report

BACKGROUND Vaccine-induced immune thrombotic thrombocytopenia(VITT)is a rare and potentially life-threatening condition after receiving coronavirus disease vaccines.It is characterized by symptom onset at 5 to 30 d postvaccination,thrombocytopenia,thrombosis,high D-dimer level,and antiplatelet factor 4(anti-PF4)antibody positivity.VITT can progress very fast,requiring urgent management.Only few studies have described its detailed clinical course and imaging changes.We report a typical VITT case in a patient who underwent regular repeated brain imaging examinations.CASE SUMMARY A young woman presented with headaches at 7 d after the ChAdOx1 nCoV-19vaccine(AZD1222)injection.She then showed progressive symptoms of left upper limb clumsiness.Brain computed tomography revealed venous infarction at the right parietal lobe with a hyperacute thrombus in the cortical vein.Two hours later,brain magnetic resonance imaging revealed hemorrhage at the same area.Magnetic resonance venography showed an irregular contour of the right transverse sinus.Laboratory examination revealed a high D-dimer level,thrombocytopenia,and a high titer for anti-PF4 antibodies.She was treated with anticoagulants,intravenous immunoglobulin,and steroids and analgesic agents were administered for pain control.She had a marked improvement on headaches and clumsiness after treatment along with radiological thrombus resolution.During follow-up at the outpatient department,her modified Rankin scale at 90 d was 1.CONCLUSION Clinicians should be alerted whenever patients present with persistent and progressive headaches or focal motor/sensory deficits postvaccination.

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.

Effectiveness of total therapy in immune thrombocytopenia purpura:case series

Immune Thrombocytopenic purpura(ITP)is a haematologicimmune-mediated disorder in which the amount of platelet in the blood decreases abnormally.Single-agent therapies for ITP have not proven successful in achieving long-term remission,with relapse occurring in about half of the patients(p/t).Treatment options which include Rituximab with Dexamethasone as frontline therapy,have durable response rates ranging from 58%to 76%.In this study,we have used‘Total therapy’as treatment which includes low-dose Rituximab in combination with Thrombopoietin receptor agonist(TPO-RA)(Romiplostim)and high-dose Dexamethasone.In this case series study,each patient received romiplostim(250 mcg weekly s/c,4 doses)in combination with low-dose rituximab(100 mg weekly IV,4 doses)and high-dose dexamethasone(40 mgIV on days 1-4and days 15-18).This treatment combination demonstrated rapid response rates and a low rate of side effects,making it a good alternative for individuals with ITP.

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.

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.

Clinical Case: About a Probable Case of Post-Transfusion Purpura in a Homozygous Sickle Cell

Alloimmunization to platelet antigens exposes to a serious immunological incident. We report a probable case of a post-transfusion purpura from homozygous sickle cell child alloimmunized against platelet antigen. We detail the challenges of alloantibody identification and transfusion management. These challenges are due to the lack of laboratory techniques for typing HLA and HPA system and the use of leukocyte-depleted (filtered) blood products.

Chronic Immune Thrombocytopenic Purpura in a Young Female with Rheumatoid Arthritis (Unusual Course)

We present a case of a 29-year-old female from Sudan, who was diagnosed with rheumatoid arthritis (RA) in 2005 and with immune thrombocytopenic purpura (ITP) in 2009. The ITP immediately followed using, for four weeks, a combination of medications that included rifampicin. The platelets count continued to be low thereafter. During the year following her diagnosis with ITP, she reported gradual improvement in her joints symptoms, which continued during her pregnancy in 2011. Following puerperium, her chronic ITP resolved completely;however, her joint disease flared up few months later. To our knowledge, there are no reported cases of chronic ITP, which were drug induced at first in a patient of RA except with gold therapy. Similarly, there are no reports on cases that recovered from chronic ITP after delivery. Finally, this case highlights the impact different coexisting autoimmune diseases may have on each other regarding course and prognosis.

Thrombotic microangiopathy after kidney transplantation: Expanding etiologic and pathogenetic spectra

Thrombotic microangiopathy(TMA)is an uncommon but serious complication that not only affects native kidneys but also transplanted kidneys.This review is specifically focused on post-transplant TMA(PT-TMA)involving kidney transplant recipients.Its reported prevalence in the latter population varies from 0.8%to 14%with adverse impacts on both graft and patient survival.It has many causes and associations,and the list of etiologic agents and associations is growing constantly.The pathogenesis is equally varied and a variety of pathogenetic pathways lead to the development of microvascular injury as the final common pathway.PT-TMA is categorized in many ways in order to facilitate its management.Ironically,more than one causes are contributory in PT-TMA and it is often difficult to pinpoint one particular cause in an individual case.Pathologically,the hallmark lesions are endothelial cell injury and intravascular thrombi affecting the microvasculature.Early diagnosis and classification of PT-TMA are imperative for optimal outcomes but are challenging for both clinicians and pathologists.The Banff classification has addressed this issue and has developed minimum diagnostic criteria for pathologic diagnosis of PT-TMA in the first phase.Management of the condition is also challenging and still largely empirical.It varies from simple maneuvers,such as plasmapheresis,drug withdrawal or modification,or dose reduction,to lifelong complement blockade,which is very expensive.A thorough understanding of the condition is imperative for an early diagnosis and quick treatment when the treatment is potentially effective.This review aims to increase the awareness of relevant stakeholders regarding this important,potentially treatable but under-recognized cause of kidney allograft dysfunction.