Linking Complement Activation, Coagulation, and Neutrophils in Transplant-Associated Thrombotic Microangiopathy

2019 ◽  
Vol 119 (09) ◽  
pp. 1433-1440 ◽  
Author(s):  
Eleni Gavriilaki ◽  
Akrivi Chrysanthopoulou ◽  
Ioanna Sakellari ◽  
Ioannis Batsis ◽  
Despina Mallouri ◽  
...  
Keyword(s):  
Complement System ◽  
Complement Activation ◽  
Thrombotic Microangiopathy ◽  
Endothelial Damage ◽  
Neutrophil Extracellular Trap ◽  
Coagulation Cascade ◽  
Control Group ◽  
Common Denominator ◽  
Significant Difference ◽  
Net Release

AbstractTransplant-associated thrombotic microangiopathy (TA-TMA) is a severe and life-threatening complication of hematopoietic cell transplantation (HCT) that often coincides with graft-versus-host-disease (GVHD). Although endothelial damage seems to be the common denominator for both disorders, the role of complement system, neutrophils, and coagulation has not been clarified. In an effort to distinguish the pathogenesis of TA-TMA from GVHD, we evaluated markers of complement activation, neutrophil extracellular trap (NET) release, endothelial damage, and activation of coagulation cascade in the circulation of patients with these two disorders, as well as control HCT recipients without TA-TMA or GVHD. We observed that the terminal complement product C5b-9 levels, the levels of markers of NET formation, and thrombin–antithrombin complex levels were significantly increased in the TA-TMA group compared with patients without complications, whereas there was no significant difference between the GVHD and the control group. On the other hand, the levels of circulating thrombomodulin, an endothelial damage marker, were significantly increased in both TA-TMA and GVHD patients. These findings propose a role for the interplay between complement system, neutrophil activation through NET release, and activation of the coagulation cascade in TA-TMA.

scholarly journals Cytomegalovirus Infection as Risk of Atherogenic Lipid Profile in Iraqi Aborted Women

2020 ◽  
Vol 31 (2) ◽  
pp. 47-51
Author(s):  
Dalya Basil Hanna ◽  
Huda Jaber Waheed ◽  
Zahraa Qasim Ali ◽  
Maysaa Ali Abdul Khaleq
Keyword(s):  
Lipid Profile ◽  
Cytomegalovirus Infection ◽  
Density Lipoprotein ◽  
Predictive Marker ◽  
Endothelial Damage ◽  
Control Group ◽  
Cmv Infection ◽  
Significant Elevation ◽  
Monocyte Chemoattractant Protein 1 ◽  
Significant Difference

Introducion: Atherosclerosis is a form of the cardiovascular diseases which may occur due to a chronic inflammatory reaction to endothelial damage caused by multiple causes which include infection by microorganisms like Cytomegalovirus (CMV). Methods: The present study aims to evaluate the effect of cytomegalovirus infection in patients and its relation to atherosclerosis and to measure the monocyte chemoattractant protein-1 (MCP-1) as a predictive marker for inflammatory process. A total of 30 women who were attending the Gynecology outpatient clinics and were suffering from abortion for first time or with recurrent abortion due to CMV infection were enrolled in the current study. For comparison, twenty blood samples were collected from healthy apparent women as a control group in this study. Serum MCP-1, IL-6 and CMV-IgM were measured by using ELISA technique. Lipid profile which includes total cholesterol, triglycerides, high density lipoprotein (HDL), and low density lipoprotein (LDL) was measured by spectrophotometer. Results: The results of this study showed a significant difference in mean of IL-6 in patients was (570.67 ± 199.27) when compared to control group (pÃ0.0001). While there is no significant difference of MCP-1 level between patients and control group (P=0.134). And the results showed a significant elevation of cholesterol (P<0.05) and a highly significant elevation of triglyceride and LDL in CMV infected patients (P<0.01), while no elevation occurred in HDL values (P=0.977). Conclusion: According to the present data there is a correlation between CMV infection and atherosclerosis. Bangladesh J Medicine July 2020; 31(2) : 47-51

scholarly journals Extended High Frequency Audiometry in Polycystic Ovary Syndrome

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Cuneyt Kucur ◽  
Suna Kabil Kucur ◽  
Ilay Gozukara ◽  
Ali Seven ◽  
Kadriye Beril Yuksel ◽  
...  
Keyword(s):  
Hearing Impairment ◽  
High Frequency ◽  
Polycystic Ovary ◽  
Endothelial Damage ◽  
Reproductive Age ◽  
Control Group ◽  
Fasting Insulin ◽  
High Frequencies ◽  
High Frequency Audiometry ◽  
Significant Difference

Objective. Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder affecting 5–10% of women in reproductive age. Insulin resistance, dyslipidemia, glucose intolerance, hypertension, and obesity are metabolic disorders accompanying the syndrome. PCOS is a chronic proinflammatory state and the disease is associated with endothelial dysfunction. In diseases with endothelial damage, hearing in high frequencies are mostly effected in early stages. We evaluated extended high frequency hearing loss in PCOS patients.Material Methods. Forty women diagnosed as PCOS and 25 healthy controls were included in this study. Age and BMI of PCOS and control groups were comparable. Each subject was tested with low (250–2000 Hz), high (4000–8000 Hz), and extended high frequency audiometry (8000–20000). Hormonal and biochemical values including LH, LH/FSH, testosterone, fasting glucose, fasting insulin, HOMA-I, and CRP were calculated.Results. PCOS patients showed high levels of LH, LH/FSH, testosterone, fasting insulin, glucose, HOMA-I, and CRP levels. The hearing thresholds of the groups were similar at frequencies of 250, 500, 1000, 2000, and 4000 Hz; statistically significant difference was observed in 8000–14000 Hz in PCOS group compared to control group.Conclusion. PCOS patients have hearing impairment especially in extended high frequencies. Further studies are needed to help elucidate the mechanism behind hearing impairment in association with PCOS.

scholarly journals JUMLAH PLATELET PADA PENDERITA PRE-EKLAMPSIA

2016 ◽  
Vol 20 (1) ◽  
pp. 43
Author(s):  
M. Arif Muchlis ◽  
Suci Aprianti ◽  
Hj. Darmawati ER
Keyword(s):  
Platelet Count ◽  
Pregnant Women ◽  
Secondary Data ◽  
Large Cell ◽  
Endothelial Damage ◽  
Control Group ◽  
P Value ◽  
Distribution Width ◽  
Significant Difference ◽  
The Mean

In pregnant women who previously did not have hypertension pre-eclampsia is a pregnancy complication, which characterized by the increased of blood pressure, proteinuria and/or oedema. One of theory about aetiology of pre-eclampsia suggests that this is caused by endothelial damage that can lead to adhesion and platelet aggregation. The aim of this study was to know the platelet count and indices by analyzing, such as mean platelet volume (MPV), its distribution width (PDW) and the large cell ratio (P-LCR) for diagnostic confirmation in pre-eclampsia patients. This research was a retrospective study using secondary data of routine blood test from medical records of pre eclampsia patients who were treated at Dr. Wahidin Sudirohusodo Hospital during the period of January to December 2011 and the normal pregnant women data that were taken as control. The data obtained were platelet count, MPV, PDW, P-LCR and analyzed using independent T test. The results showed that the mean platelet count in pre-eclampsia patients was lower than the control but had no statistically significant difference (p=0.325) whereas the mean of MPV, PDW and P-LCR in pre-eclampsia patients increased compared to the control group and was statistically significant with p value of MPV (p=0.003), PDW (p=0.002) and P-LCR (p=0.010). In conclusion, platelet indices can be used as diagnostic confirmation markers in pre-eclampsia patients.

scholarly journals Assessment of the SFlt-1 and sFlt-1/25(OH)D Ratio as a Diagnostic Tool in Gestational Hypertension (GH), Preeclampsia (PE), and Gestational Diabetes Mellitus (GDM)

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Malgorzata Walentowicz-Sadlecka ◽  
Piotr Domaracki ◽  
Pawel Sadlecki ◽  
Joanna Siodmiak ◽  
Marek Grabiec ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Gestational Hypertension ◽  
Endothelial Damage ◽  
Maternal Serum ◽  
Control Group ◽  
Elevated Concentration ◽  
Significant Difference ◽  
Endothelial Integrity

Background. Placental soluble fms-like tyrosine kinase-1 (sFlt-1), an antagonist of vascular endothelial growth factor, is considered an etiological factor of endothelial damage in pregnancy pathologies. An increase in the sFlt-1 level is associated with alterations of endothelial integrity. In contrast, vitamin D exerts a protective effect and low concentrations of 25(OH)D may have an adverse effect on common complications of pregnancy, such as gestational hypertension (GH), preeclampsia (PE), and gestational diabetes mellitus (GDM). The aim of this study was to analyze the levels of sFlt-1 in Polish women with physiological pregnancies and pregnancies complicated by GH, PE, and GDM. Moreover, we analyzed relationships between the maternal serum sFlt-1 level and the sFlt-1 to 25(OH)D ratio and the risk of GH and PE. Material and Methods. The study included 171 women with complicated pregnancies; among them are 45 with GH, 23 with PE, and 103 with GDM. The control group was comprised of 36 women with physiological pregnancies. Concentrations of sFl-1 and 25(OH)D were measured before delivery, with commercially available immunoassays. Results. Women with GH differed significantly from the controls in terms of their serum sFlt-1 levels (5797 pg/ml vs. 3531 pg/ml, p=0.0014). Moreover, a significant difference in sFlt-1 concentrations was found between women with PE and those with physiological pregnancies (6074 pg/ml vs. 3531 pg/ml, p<0.0001). GDM did not exert a statistically significant effect on serum sFlt-1 levels. Both logistic regression and ROC analysis demonstrated that elevated concentration of sFlt-1 was associated with greater risk of GH (AUC=0.70, p=0.0001) and PE (AUC=0.82, p<0.0001). Also, the sFlt-1 to 25(OH)D ratio, with the cutoff values of 652 (AUC=0.74, p<0.0001) and 653 (AUC=0.88, p<0.0001), respectively, was identified as a significant predictor of GH and PE. Conclusions. Determination of the sFlt-1/25(OH)D ratio might provide additional important information and, thus, be helpful in the identification of patients with PE and GH, facilitating their qualification for intensive treatment and improving the neonatal outcomes.

scholarly journals Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations

2020 ◽  
Vol 4 (23) ◽  
pp. 6051-6063 ◽  
Author(s):  
Caroline Diorio ◽  
Kevin O. McNerney ◽  
Michele Lambert ◽  
Michele Paessler ◽  
Elizabeth M. Anderson ◽  
...  
Keyword(s):  
Complement Activation ◽  
Thrombotic Microangiopathy ◽  
Pediatric Population ◽  
Severe Disease ◽  
Endothelial Damage ◽  
Clinical Criteria ◽  
Clinical Presentations ◽  
Clinical Consequences ◽  
Healthy Control ◽  
Minimal Disease

Abstract Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory syndrome in children (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. We hypothesized that complement activation plays an important role in SARS-CoV-2 infection in children and sought to understand if TMA was present in these patients. We enrolled 50 hospitalized pediatric patients with acute SARS-CoV-2 infection (n = 21, minimal coronavirus disease 2019 [COVID-19]; n = 11, severe COVID-19) or MIS-C (n = 18). As a biomarker of complement activation and TMA, soluble C5b9 (sC5b9, normal 247 ng/mL) was measured in plasma, and elevations were found in patients with minimal disease (median, 392 ng/mL; interquartile range [IQR], 244-622 ng/mL), severe disease (median, 646 ng/mL; IQR, 203-728 ng/mL), and MIS-C (median, 630 ng/mL; IQR, 359-932 ng/mL) compared with 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL; P &lt; .001). Higher sC5b9 levels were associated with higher serum creatinine (P = .01) but not age. Of the 19 patients for whom complete clinical criteria were available, 17 (89%) met criteria for TMA. A high proportion of tested children with SARS-CoV-2 infection had evidence of complement activation and met clinical and diagnostic criteria for TMA. Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C.

scholarly journals De-escalation Antibiotic Therapy Alleviates Organ Injury through Modulation of NET Formation during Sepsis

2020 ◽  
Author(s):  
Tian Xie ◽  
Chengnan Chu ◽  
Shilong Sun ◽  
Xinyu Wang ◽  
Zehua Duan ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Late Stage ◽  
Early Stage ◽  
Neutrophil Extracellular Trap ◽  
Organ Injury ◽  
Control Group ◽  
Histopathological Analysis ◽  
Escalation Therapy ◽  
Significant Difference

Empiric broad-spectrum antimicrobials therapy is suggested to be started immediately for sepsis patients. Empiric antimicrobial therapy should be narrowed once pathogen identification and sensitivities are established. However, the detail mechanisms of de-escalation strategy are still unclear. Here we hypothesized neutrophil extracellular trap (NETs) played an essential role and de-escalation strategy might alleviate organs injury through regulation of NETs formation in sepsis. We evaluated the effect of imipenem and ceftriaxone on NETs formation in vitro and examined the role of reactive oxygen species (ROS). Next, we designed de-escalation and escalation strategy based on their effects on NETs formation in CLP model. Organ injury, inflammatory cytokines, NETs levels were compared and evaluated. The in vitro study showed that imipenem and ceftriaxone had opposite effects on NETs formation in activated neutrophils. De-escalation therapy resulted in an evaluated MPO-DNA during early stage and decreased MPO-DNA during late stage, which exerted the reverse effects in escalation therapy sepsis animal model. Inflammatory response and organ injury exacerbated when eliminated NETs with DNAseI during early stage of sepsis (p<0.01). Histopathological analysis showed decreased injury in lung, liver and intestine in de-escalation therapy compared with escalation therapy (p<0.01). De-escalation therapy results in the highest 6-day survival rate compared with the control group (p<0.01), however, no significant difference was found between de-escalation and escalation group (p=0.051). We demonstrate that de-escalation, not escalation, therapy reduces organ injury, decreases inflammatory response by promoting NETs formation in the early stage and inhibiting NETs formation in the late stage of sepsis.

scholarly journals Platelet Changes in Pregnancies with Severe Early Fetal Intrauterine Growth Restriction

Medicina ◽  
2021 ◽  
Vol 57 (12) ◽  
pp. 1355
Author(s):  
Anca Marina Ciobanu ◽  
Anca Maria Panaitescu ◽  
Nicolae Gica ◽  
Ana Maria Scutelnicu ◽  
Alexandra Bouariu ◽  
...  
Keyword(s):  
Platelet Count ◽  
Complete Blood Count ◽  
Perinatal Outcomes ◽  
Endothelial Damage ◽  
Growth Restriction ◽  
Control Group ◽  
Significant Difference ◽  
Intrauterine Fetal Growth Restriction ◽  
Adverse Perinatal Outcomes ◽  
And Control

Background and Objectives: In this study, we investigated the changes of platelet count and other platelet indices, such as mean platelet volume (MPV), in cases with severe early intrauterine fetal growth restriction (IUGR). Materials and Methods: We retrospectively analyzed all pregnancies diagnosed with severe early onset IUGR, that were followed up in our hospital between 2010 and 2015 (before implementation of screening and prophylaxis with aspirin). Pregnancies which resulted in birth of a newborn with a birthweight less than 5th percentile for gestational age, that required delivery for fetal or maternal indication before 32 weeks, were selected for the IUGR group. The IUGR cases were divided into two groups according to preeclampsia (PE) association. All cases with a complete blood count (CBC) performed within 7 days prior to delivery were included in the study, as the IUGR group. The control group included normal singleton pregnancies, delivered at term, with birthweight above 10th centile and a CBC taken at 30–32 weeks. Results: There was a significant difference in platelet count and MPV values between the IUGR group and control. Cases with IUGR presented lower platelet count and higher MPV values; there was no significant difference of these parameters when PE was associated with IUGR. Conclusions: Our results suggest that in cases of severe early IUGR, even in the absence of clinically diagnosed PE, there may be maternal endothelial damage and platelet consumption in the systemic and uteroplacental circulation. Platelet count and MPV values are simple and widely available laboratory tests that might be used as indicator of placental insufficiency; however, prospective data are required to establish the mechanistic link and to which extent these parameters are good predictors of severity or adverse perinatal outcomes.

scholarly journals Estimation of Complement Components (C3 and C4) and hs-CRP Level in Kidney Failure Patients

2019 ◽  
Vol 9 (2) ◽  
pp. 70-75
Author(s):  
Zaid N. Elia ◽  
Nisreen W. Mustafa
Keyword(s):  
Blood Pressure ◽  
Renal Failure ◽  
High Blood Pressure ◽  
Complement System ◽  
Complement Activation ◽  
Kidney Failure ◽  
Kidney Injury ◽  
Control Group ◽  
Significant Change ◽  
Hs Crp

Several kidney diseases associated with complement activation. Complement activation occurs in progressive chronic kidney disease and may contribute to the chronic inflammation that is characteristically found in the kidney. This study was aimed to detect the level of complement system in kidney failure patients. This study was included (30) patients with renal failure and (15) healthy donors as control group. Serum samples separated from the whole blood of patients and healthy individuals. C3, C4, and high sensitive C- reactive protein (hsCRP) levels were estimated for all samples. The results were analyzed according to patients who were dialysis, non-dialysis, with diabetes, without diabetes, with high blood pressure, and without high blood pressure. The results showed that there was a significant increase (P < 0.05) in C3 level for patients with renal failure (154.12 mg/dl) compared to control group (126.08 mg/dl) while C4 level for renal failure patients (35.38 mg/dl) showed no significant change compared to control group (36.26 mg/dl). However, C3 level of patients under dialysis (152.15 mg/dl), not dialysis (162.01 mg/dl), with diabetic (155.80 mg/dl), and without diabetic (153 mg/dl) recorded significant elevation compared with control group (126.08 mg/dl) but C4 level did not show any significant change for all groups. C3 and C4 concentrations did not record significant alteration (P < 0.05) in patient with hypertension, nonhypertension, and control group. Moreover, seropositivity of CRP for patients with renal failure was ranged from 33.33% to 60% in all patients groups included in this study. hsCRP concentration significantly elevated (P < 0.05) in under dialysis (1.787 mg/L), nondialysis (1.583 mg/L), with diabetic (2.766 mg/L), nondiabetic (1.066 mg/L), with hypertension (1.84 mg/L), and nonhypertension (1.26 mg/L) when compared with control group (0.667 mg/L). The present findings suggest that the increased serum levels of C3, C4, and hs-CRP reflect the of kidney injury. Hence, this reflects the complement system as an important mediator of kidney injury and the role of anti-complement therapy in nephropathy will expand in the future.

scholarly journals Hypoxia-Induced Endothelial Damage and Microthrombosis in Myocardial Vessels of Newborn Landrace/Large White Piglets

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Armando Faa ◽  
Theodoros Xanthos ◽  
Vassilios Fanos ◽  
Daniela Fanni ◽  
Clara Gerosa ◽  
...  
Keyword(s):  
Endothelial Damage ◽  
Control Group ◽  
Pathological Feature ◽  
Large White ◽  
Neonatal Piglets ◽  
Severe Hypotension ◽  
Significant Difference ◽  
Group A ◽  
Group B ◽  
Experimental Group

Objective.Evaluating the presence of endothelial changes in myocardial vessels in an experimental model of hypoxia and resuscitation in newborn piglets.Methods.Fifty male Landrace/Large White neonatal piglets were studied: ten of them were allocated in group A (control group, SHAM-operated). In group B (forty animals, experimental group) normocapnic hypoxia was induced by decreasing inspired concentration of O2to 6%–8%. When the animals developed bradycardia or severe hypotension, reoxygenation was initiated. The animals of group B were allocated in 4 subgroups of 10, according to the concentration of O2they were resuscitated with (groups 1, 2, 3, and 4 received 18%, 21%, 40%, and 100% O2, resp.).Results.Control group animals did not show any significant endothelial lesions. Contrarily, endothelial lesions were detected in all experimental group cases. When these lesions were analyzed in the different heart zones, no significant difference in their incidence was observed; analyzing the frequency in the animals of the 4 subgroups, only microthrombosis showed a higher frequency in animals in groups 4 and 3.Conclusions.Endothelial damage represents a diffuse pathological feature in the myocardial vessels of piglets subjected to normocapnic hypoxia and resuscitation suggesting a possible role of hyperoxygenation in aggravating endothelial damage.

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