Microangiopathy Disease Research Articles

Therapeutical plasma exchange for thrombotic thrombocytopenic purpura in the emergency department: A single center experience

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening and easily misdiagnosed thrombotic microangiopathy disease. Few studies have reported the use of therapeutic plasma exchange (TPE) for TTP in emergency departments in China. The present study was a retrospective analysis of patients with TTP who were treated with TPE in our emergency intensive care unit (EICU). This study retrospectively analyzed patients with TTP who received TPE management from July 1, 2014 to February 1, 2020. The following clinical data of these patients were collected: laboratory results, first symptoms, ADAMTS13 levels, glucocorticoid levels, TPE times and outcomes. The study included 19 patients (9 male and 10 female) with 20 clinical episodes, and 1 female patient had two episodes. TPE was used in 17 patients, and TPE was performed once every 2-3days in patients. The volume for each TPE treatment was 2000ml. In total, 4 male patients died, and 15 patients survived. One female experienced a relapse. No significant differences in age, RBC, HGB, PLT, ALT, AST, BUN, Cr, LDH, or bilirubin were noted between the survival and death groups. The mortality rate of male patients was significantly higher than that of female patients(p=0.0325, p<0.05), and the mean age of deceased patients was 64.25±4.78years, which was older than the mean age of survivors (47.38±4.30). However, no significant difference was noted (p=0.0787). TPE had satisfactory results for TTP patients although it was not performed every day. Older male TTP patients exhibited a relatively increased risk of death.

Acute Coronary Syndrome in Patients with Thrombotic Thrombocytopenic Purpura

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening clinical syndrome characterized by microangiopathy and a variable degree of end-organ ischemic damage. Cardiac involvement has been recognized as a major cause of mortality in these patients (Patschan et al, Nephrol Dial Transplant, 2006; Benhamou et al, J Thromb. Haemost, 2015). In this study, we aim to investigate clinical predictors and outcomes of acute coronary syndrome in the setting of TTP admissions. Methods: The National Inpatient Sample (NIS) was queried for all hospitalizations with a primary diagnosis of thrombotic microangiopathy (ICD- 9-CM code 4466 and ICD-10-CM code M3.11) from 2002 to 2017. Using ICD-9-CM procedure codes (9972), (9971), and (9979), as well as ICD-10-CM procedure codes (6A551Z3) and (6A550Z3) we identified patients who received plasma exchange (PLEX) during the same admission. Due to the wide spectrum of thrombotic microangiopathy diseases, we decided to include only those who received PLEX to get a more specific subpopulation who were presumed to have TTP. We stratified patients based on whether or not they had acute coronary syndrome (ACS) during the admission, defined as presence of any ICD code for either ST-segment elevation myocardial infarction (STEMI), Non-STEMI, or unstable angina. Baseline characteristics and inpatient outcomes were compared between groups. Statistical analysis was performed using SPSS v26 (IBM Corp, Armonk, NY, USA). The odds ratio (OR) and 95% confidence interval (CI) were calculated using the Cochran-Mantel-Haenszel test. A multivariate regression model was deployed to assess predictors of inpatient mortality. Complex weights were used throughout all calculations, enabling appropriate national projections. Results: A total of 15,640 patients with the diagnosis of thrombotic microangiopathy were identified during the studied period. Of those, 6,214 patients had received PLEX treatment during their admission (39.7%). The annual admission rate for TTP was ranging between 5-7/100,000 admissions. Patients had a mean age of 47.8 years; 67% were females, and 46.5% were Caucasian. Stratifying by geographic region, 24% were from the Northeast, 21% from the Midwest, 42% from the South, and 13% from the West. The most common primary payer was private insurance (42.7%). Overall inpatient mortality was 9.1%. The most common complications reported included acute kidney injury (42.5%), followed by acute respiratory failure (14.9%), incident dialysis (14.3%), acute encephalopathy (7.7%), acute heart failure (7.3%), acute cerebrovascular accident (7.2%), and acute coronary syndrome (6.3%). ACS was documented in 6.7% of patients. Compared with patients without ACS, those with ACS were relatively older and had a relatively higher prevalence of coronary artery disease, dyslipidemia, diabetes mellitus, essential hypertension, chronic kidney disease, and heart failure. Patients with ACS had a 3-fold higher in-hospital mortality and a longer mean hospital stay (19 days vs. 15 days, P&amp;lt;0.001). Using stepwise logistic regression, we identified age (aOR 1.03; 95% CI, 1.02 - 1.03; P &amp;lt;0.001), history of heart failure (aOR 2.02; 95% CI, 1.53-2.67; P &amp;lt;0.001), and history of coronary artery disease (aOR 2.69; 95% CI, 2.03 - 3.57; P &amp;lt;0.001) as independent predictors of ACS among patients hospitalized with TTP. On another regression analysis, certain complications were more prevalent in the ACS group including acute cerebrovascular accidents, acute heart failure, acute kidney injury, cardiogenic shock, and respiratory failure. Conclusion: Despite wider utilization of therapeutic plasmapheresis and improved supportive treatments for patients with TTP, associated morbidity and mortality remain significant. We demonstrate from this large retrospective cohort that ACS is an independent predictor of higher morbidity and mortality in TTP patients. We identified older age, history of heart failure, and history of coronary artery disease as independent predictors of ACS among patients admitted with TTP. Further studies are warranted to develop risk stratification models for patients with TTP. Figure Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Overall Neutralization of Complement Factor H by Autoantibodies in the Acute Phase of the Autoimmune Form of Atypical Hemolytic Uremic Syndrome

Complement is a major innate immune surveillance system. One of its most important regulators is the plasma protein factor H (FH). FH inactivation by mutations or by autoantibodies is associated with a thrombotic microangiopathy disease, atypical hemolytic uremic syndrome. In this study, we report the characterization of blood samples from 19 anti-FH Ab-positive atypical hemolytic uremic syndrome patients collected at the acute phase of the disease. Analyses of the functional consequences and epitope mapping, using both fluid phase and solid phase approaches, were performed. The anti-FH Abs perturbed FH-mediated cell protection (100%), inhibited FH interaction with C3 (46%), and caused C3 consumption (47%). The Abs were directed against multiple FH epitopes located at the N and C termini. In all tested patients, high titers of FH-containing circulating immune complexes were detected. The circulating immune complex titers correlated with the disease stage better than did the Ab titers. Our results show that anti-FH autoantibodies induce neutralization of FH at acute phase of the disease, leading to an overall impairment of several functions of FH, extending the role of autoantibodies beyond the impairment of the direct cell surface protection.

Clinical Application Study of Plasma Thrombmodulin.

Objective: To investigate the clinical value of plasma thrombmoclulin (PTM).Methold: PTM was determined in 979 patients and 60 healthy controls with ELISA method.Result: The PTM of the control group was 20.40±7.72 μg/L, there was no difference in genders and ages. The PTM of the patients with microangiopathy were higher than that of the patients with macroangiopathy (P <0.01). We defined PTM level higher than its normal upper limit (35.54μg/L) as PTM positive, in microangiopathy diseases, the sensitivity of PTM was 77.7%, the specificity was 71.2% and the positive predictive value was 75.6%. In chronic primary glomerular disease, the PTM of chronic renal failure (CRF) group was higher than that of non-CRF group (P <0.01), the sensitivity was 85.7%, the specificity was 82.4%, the positive predictive value was 77.8%. The PTM level in septemia group was higher than that of non-septemia group(P <0.01),the sensitivity of PTM was 86.6%, the specificity was 89.5% and the positive predictive value was 76.5%. In multiple trauma, the PTM of multiple organ failare (MOF) group was higher than that of non-MOF group (P <0.01), the sensitivity of PTM was 77.8%, the specificity was 77.3% and the positive predictive value was 73.7%. In systemic lupus erythematosus (SLE), the PTM of the patients with albuminuria was higher than that of the patients without albuminuria(P <0.01), the sensitivity was 77.8%, the specificity 92.3% and the positive predictive value was 93.3%. In diabetes, the PTM of complication group was higher than that of no complication group, the sensitivity was 53.4%, the specificity was 97.1% and the positive predictive value was 98.6%, the PTM of microangiopathy group was higher than that of macroangiopathy group (P <0.01), the sensitivity was 71.2%, the specificity was 97.1%, and the positive predictive value was 97.9%. Compared the acute stage with restoration stage in stroke, pre-chemotherapeutics with post-operation in AL and MM, and pre-operation with post-operation in cancer, the PTM was connected with clinical development.Conclusion: PTM was a good criterion in evaluating the microangiopathy in clinical application. PTM was also a valuable index in prediction or assessment of the severity of diseases or in the observation of therapeutic effectiveness.