scholarly journals Proteomic Profiles in Patients with Thrombosis Due to COVID-19 Are Distinct from Non-COVID-19 Thrombosis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 777-777
Author(s):  
Daria V Madeeva ◽  
Kelly Borges ◽  
Marcus Shallow ◽  
Prerak V Juthani ◽  
Stephen Y Wang ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Complement Activation ◽  
Conflicts Of Interest ◽  
Endothelial Damage ◽  
Protein Profiling ◽  
Complement Factor ◽  
Thromboembolic Events ◽  
Lipocalin 2 ◽  
Thromboembolic Complications ◽  
Amyloid A

Abstract BACKGROUND. COVID-19 is a prothrombotic disease, characterized by endotheliopathy, hypercoagulability, and thromboembolic complications. We hypothesized that the pathogenesis of thromboembolism associated with COVID-19 might differ from thromboembolism in patients without COVID-19. In this study, we sought to evaluate the proteomic signatures of plasma from patients with venous thromboembolism with and without COVID-19. METHODS. Between December 17, 2020 and February 25, 2021 blood was collected from 48 hospitalized patients. Of these 24 had a confirmed diagnosis of COVID-19 infection (COVID+) and radiologic confirmation of arterial or venous thromboembolism (TE+); 17 had COVID-19 infection with absence of arterial thrombosis clinically and absence of venous thromboembolism on lower extremity Doppler ultrasound or chest CT angiography (COVID+/TE-), while 7 were arterial or venous thromboembolism in the absence of COVID-19 (COVID-/TE+). Blood was collected in sodium citrate tubes and centrifuged at 4000 rpm for 20 minutes, with resulting plasma supernatant used for protein profiling performed at Eve Technologies (Calgary, Alberta, Canada). Institutional Review Board approval was obtained for this study. Statistical analysis was performed using GraphPad Prism (v9.1, GraphPad Software, San Diego, CA) and R (v4, R Core Team). P values <0.05 were considered statistically significant. A heatmap was generated using Heatmapper (heatmapper.ca) to represent the concentrations of proteins. RESULTS. The median age was 63 years; overall 25 (52%) were men (13 [54%] among COVID+/TE+, 11 [65%] among COVID+/TE-, and 1 [14%] among COVID-/TE+). In COVID-19 patients who developed thromboembolic events, several proteins associated with inflammation, complement activation, and hemostasis were present at higher levels than in non-COVID-19 patients who developed thromboembolic events (Fig. 1). These included complement factors C2 and C5a, pentraxin-3 (PTX-3), lipocalin-2 (LCN2), resistin (RETN), platelet endothelial cell adhesion molecule-1 (Pecam1), serum amyloid A (SAA), and tissue factor (TF). The heatmap indicates relative protein levels detected in each subject (columns) for proteins (rows) that had statistically significant differences between groups (Fig. 2). Heatmap revealed relatively lower levels of all proteins in patients with thromboembolism without COVID-19 and relatively higher levels of proteins in patients with COVID-19, and especially in ICU patients with COVID-19 and thromboembolism. CONCLUSIONS. Thromboembolic complications in patients with COVID-19 are associated with increased levels of various proteins involved in complement activation and immunothrombotic cascades, compared to thrombotic events in the absence of COVID-19. Activation of the classical complement pathway as evidenced by a relative increase in complement factor C2 may lead to increased TF activation, reflecting more substantial endothelial damage in COVID-19 patients. Higher levels of Pecam1, SAA, LCN2, and RETN all point to increased endotheliopathy, inflammation, and tissue damage in COVID-19 compared to non-COVID-19 thrombosis. These findings may offer insights into novel therapeutic strategies to treat immunothrombotic complications of COVID-19. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Regulation of Complement Activation by Thrombomodulin.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5127-5127
Author(s):  
Mieke Delvaeye ◽  
Astrid DeVriese ◽  
Michael Moons ◽  
Naomi Esmon ◽  
Charles Esmon ◽  
...  
Keyword(s):  
Complement Activation ◽  
Conflicts Of Interest ◽  
Vascular Endothelial Cells ◽  
Leukocyte Adhesion ◽  
Alternative Pathway ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Negative Regulator ◽  
Classical Pathway ◽  
Complement Factor ◽  
Wide Range

Abstract Abstract 5127 Thrombomodulin (TM) is an integral membrane glycoprotein, ubiquitously expressed by vascular endothelial cells. Its epidermal growth factor (EGF)-like repeats amplify thrombin-mediated generation of activated protein C and activated thrombin activatable fibrinolysis inhibitor, thereby suppressing coagulation, inflammation and fibrinolysis, and inactivating the anaphylatoxins, C3a and C5a. TM also has direct anti-inflammatory properties, interfering with leukocyte adhesion, and preventing complement activation via its lectin-like domain. We recently established that TM is a physiologically important negative regulator of the alternative pathway (AP) of complement activation, defects of which increase the risk of the thrombotic microangiopathy, atypical hemolytic uremic syndrome. In this report, we assessed the role of TM in the other complement activation pathways. In serum, TM interferes with classical pathway (CP) mediated erythrocyte cell lysis, and protects against CP-induced cell death. TM co-precipitates with C4b, and enhances its inactivation and cleavage to C4c and C4d by complement factor I in the presence of the cofactor C4b binding protein. TM also interferes with the coagulation complement pathway by interfering with thrombin cleavage and activation of C5 to C5a. Overall, TM negatively regulates complement via the major recognized pathways. The findings implicate defects in TM in a wide range of diseases in which complement plays a role, and underlines the potential of TM as a therapeutic target. Disclosures No relevant conflicts of interest to declare.

scholarly journals Thromboembolism in patients with congenital afibrinogenaemia

2016 ◽  
Vol 116 (10) ◽  
pp. 722-732 ◽  
Author(s):  
Michael Nagler ◽  
Lorenzo Alberio ◽  
Kristiina Peter-Salonen ◽  
Hendrik von Tengg-Kobligk ◽  
Daniel Lottaz ◽  
...  
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Effective Treatment ◽  
Laboratory Data ◽  
Favourable Outcome ◽  
Thromboembolic Events ◽  
Thromboembolic Complications ◽  
Effective Treatment Option ◽  
Venous Thromboembolic Events

SummaryFrequent arterial and venous thromboembolism in patients with congenital afibrinogenaemia (CA) is neither understood nor is a safe and effective treatment established. It was our objective to report on the clinical observations and laboratory data contributing to the understanding of the frequency, physiopathology, prognosis and treatment of CA. We observed the long-term clinical course and laboratory data in a cohort of four patients with CA and thromboembolic complications, and conducted a systematic review retrieving all available data. Four patients with CA developed recurrent and extensive arterial and venous thromboembolism (TE) from an age of 25–51 years. In two patients, a treatment strategy targeting at maintaining constantly measurable fibrinogen (Fbg) levels (≥0.5 g/l) either by regular Fbg replacement or by orthotopic liver transplantation resulted in long-term remissions. Radiological imaging documented resolved arterial thrombi after 6–12 months. In contrast, recurrent thromboembolic events were observed in two other patients with infrequent Fbg replacement. A systematic review of the literature revealed 48 reports of TE in patients with CA (median age at first event 31 years), and a favourable outcome in most patients with frequent application of Fbg, aimed at constantly measurable trough levels. Present data suggests that patients with CA are at high risk of arterial and venous thromboembolic events, probably caused by thrombin excess owing to lack of thrombin scavenging by Fbg/fibrin. Regular low-dose Fbg replacement might be a safe and effective treatment option in patients with CA and thromboembolic complications.Note: Preliminary data of this report were presented as oral presentation at the XXV Congress of the International Society on Thrombosis and Haemostasis, June 20th to 25th, Toronto, Canada.Supplementary Material to this article is available online at www.thrombosis-online.com.

Pulmonary emboli due to venous aneurysm of extremities

VASA ◽  
2011 ◽  
Vol 40 (4) ◽  
pp. 327-332 ◽  
Author(s):  
Gabrielli ◽  
Rosati ◽  
Vitale ◽  
Millarelli ◽  
Siani ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Surgical Resection ◽  
Potential Risk ◽  
Acute Pulmonary Embolism ◽  
Prophylactic Surgery ◽  
Venous Aneurysm ◽  
Pulmonary Emboli ◽  
Thromboembolic Events ◽  
Thromboembolic Complications ◽  
Risk Patients

Venous aneurysms are uncommon but they can have devastating consequences, including pulmonary embolism, other thromboembolic events and death. We report six cases of venous aneurysm of the extremities, in which the first sign of presence was acute pulmonary embolism. Surgical resection is recommended whenever possible. Our experience suggests that prophylactic surgery is cautiously recommended for low-risk patients with venous aneurysms of the abdomen and strongly recommended for extremity deep and superficial venous aneurysms for their potential risk of developing thromboembolic complications despite adequate anticoagulation. Other venous aneurysms should be excised only if they are symptomatic or enlarging.

scholarly journals Inpatient Outcomes and Rates of Venous Thromboembolism and Gastrointestinal Bleeding in Patients with Hepatocellular Carcinoma: Results from Nationwide Inpatient Sample Database 2007-2016

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2162-2162
Author(s):  
Kamelah Abushalha ◽  
Sawsan Abulaimoun ◽  
Ryan Walters ◽  
Sara Albagoush ◽  
Hussain I Rangoonwala ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Venous Thromboembolism ◽  
Gastrointestinal Bleeding ◽  
Hospital Mortality ◽  
Hospital Cost ◽  
Clinical Decision Making ◽  
Conflicts Of Interest ◽  
Increased Risk ◽  
Increasing Trend ◽  
Increasing Trends

Background: Patients with hepatocellular carcinoma (HCC) are at an increased risk for developing venous thromboembolism (VTE)- mainly portal venous thrombosis (PVT). Malignancy and liver cirrhosis ( 80%-90% of HCC cases are related to cirrhosis) are conditions that can perturb the hemostatic balance towards a prothrombotic state. Also, these patients with HCC are at high risk for gastrointestinal bleeding (GIB), making thromboprophylaxis and anticoagulation a treatment challenge. Additional information regarding the outcomes and severity of both VTE and GIB in patients with HCC would be useful to guide clinical decision-making Aim: To determine the rates, inpatient mortality, length of stay (LOS) and hospital cost of VTE and GIB-related admissions in patients with hepatocellular carcinoma. Method: We used ICD-9-CM and ICD-10-CM codes to identify hospitalizations from 2007 to 2016 that included HCC with primary discharge diagnoses of GIB or VTE. Linear trends in the rate of GIB and VTE, as well as in-hospital mortality, LOS, and inflation-adjusted hospital cost (in 2016 US dollars), were evaluated using Daniel's test; piecewise slopes were used as needed. All analyses accounted for the NIS sampling design with updated hospital trend weights used as appropriate. SAS v. 9.4 was used for all analyses. Results: Between 2007 and 2016, we identified 6,527,871 hospitalizations with HCC and a primary discharge diagnosis of GIB (3,517,059; 53.9%) or VTE (3,010,812; 46.1%). From 2007 to 2010, a decreasing trend was observed in the rate of GIB diagnoses (55.5% to 51.6%, ptrend < .001), whereas an increasing trend was observed for VTE diagnoses (44.5% to 48.4%, ptrend < .001). By contrast, from 2010 to 2016, an increasing trend was observed in GIB (51.6% to 55.2%, ptrend < .001), whereas a decreasing trend was observed in VTE (48.4% to 44.8%, ptrend < .001). For in-hospital mortality, a decreasing trend was observed for GIB (2.3% to 1.9%, ptrend < .001), whereas a decreasing trend was observed in VTE until 2012 (1.8% to 1.5%, ptrend < .001), after which no trend was indicated (1.5% to 1.6%, ptrend = .337). Although decreasing trends in LOS were observed for GIB (3.4 days to 3.2 days, ptrend < .001) and VTE (4.3 days to 3.3 days, ptrend < .001), increasing trends were observed for inflation-adjusted hospital cost for both GIB ($6,996 to $7,707, ptrend < .001) and VTE ($7,283 to $7,584, ptrend = .048). Conclusion: In this NIS cohort of hospitalized patients with HCC, GIB was more frequently observed than VTE. Trends observed in the rates of GIB and VTE went in opposite directions. In general decreasing trends were observed in in-hospital mortality and LOS for both VTE and GIB. By contrast, increasing trends were observed in the hospital cost for both diagnoses. Clinicians should balance benefits against risks when deciding VTE prophylaxis and treatment in patients with HCC. Future studies are needed to determine the ideal agent and specific dosages to treat HCC-associated VTE. Disclosures No relevant conflicts of interest to declare.

scholarly journals Apixaban Anti-Xa Level Monitoring in Treatment of Provoked Acute Upper Extremity Deep Vein Thrombosis for Patient on Dialysis: A Case Report

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-14
Author(s):  
Guillaume Roberge ◽  
Philip S. Wells
Keyword(s):  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Upper Extremity ◽  
Conflicts Of Interest ◽  
Subcutaneous Fat ◽  
Chronic Hemodialysis ◽  
Vein Thrombosis ◽  
Acute Venous Thromboembolism ◽  
Deep Vein ◽  
Trough Levels

Background. Patients with end stage renal disease on dialysis are at higher risk of major bleeding and recurrent thrombosis and as such, treatment of acute venous thromboembolism (VTE) is challenging. Ideally, treatment would avoid inpatient admission as for most other patients with acute VTE. DOACs represent the easiest option but there are concerns over bioaccumulation increasing bleeding risk. Despite the absence of a standardized therapeutic range, anti-Xa trough level is measured to monitor potential DOACs bioaccumulation and thus, used for safety surveillance. Methods. We describe a case of a 51 yo female, 36 kg, on chronic hemodialysis with a provoked acute upper extremity deep vein thrombosis. Due to a lack of subcutaneous fat and calciphylaxis we were reluctant to use low molecular weight heparin and warfarin. She was treated with apixaban 2,5 mg twice daily for 6 weeks. Over 4 weeks, the apixaban anti-Xa trough levels were measured on dialysis days 12 hours after the morning dose. Results. The anti-Xa trough levels ranged from 58 to 84 ng/mL, similar to what is expected in patients with normal kidney function. There were no adverse events in the 3 months after anticoagulation initiation. Conclusion. We saw no evidence of bioaccumulation. This indicates a potential role for apixaban low doses in acute venous thromboembolism for patients on dialysis. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: The use of Apixaban for treatment of acute venous thromboembolism in patient on dialysis has not been approved.

scholarly journals Success of Online CME at Improving Knowledge and Confidence Around Guideline-Directed Management of Cancer-Associated Thrombosis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-13
Author(s):  
Caroline Padbury ◽  
Margaret Harris ◽  
Michael LaCouture ◽  
Jelena Spyropoulos
Keyword(s):  
Clinical Practice ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Treatment Guidelines ◽  
Conflicts Of Interest ◽  
Oral Anticoagulants ◽  
Roundtable Discussion ◽  
Patients With Cancer ◽  
Cancer Associated Thrombosis ◽  
Post Assessment

Title:Success of Online CME at Improving Knowledge and Confidence Around Guideline-Directed Management of Cancer-Associated Thrombosis Study Objectives:Recent guidance statements recommend the use of direct oral anticoagulants (DOACs) as primary thromboprophylaxis in ambulatory patients with cancer who are starting chemotherapy and in patients with cancer and acute venous thromboembolism at low risk of bleeding and no drug-drug interactions.[Farge 2019; Key 2020] Yet, many clinicians lack knowledge and confidence with integrating DOACs into management strategies for patients with cancer in accordance to guideline recommendations.[Cushman 2015; Khorana 2016] We sought to determine if online continuing medical education (CME) could improve the knowledge and confidence of hematologists/oncologists regarding guideline-directed use of DOACs in the management of cancer-associated thrombosis. Methods:This CME intervention comprised of a 30-minute online video-based roundtable discussion among experts in the field of cancer-associated thrombosis management. Responses to 3 multiple-choice, knowledge questions and 1 self-efficacy, 5-point Likert scale confidence question were analyzed using a repeated pairs pre-/post-assessment study design. A chi-square test (P &lt;.05 is considered significant) assessed pre- to post-activity change . The activity launched December 23, 2019, and data were collected through February 24, 2020. Results:In total, 71 Hematologists/Oncologists were included in this study. Overall, there were knowledge and confidence improvements seen among all groups from pre- to post-assessment: 27% of hematologists/oncologists (P&lt;.01) improved at identifying guideline-directed therapy regarding recommended thromboprophylaxis in patients with cancer per guideline recommendations.27% of hematologists/oncologists (P&lt;.01) improved at selecting guideline-appropriate treatment options for cancer-associated thrombosis.44% of hematologists/oncologists had an increase in confidence in managing thrombosis in patients with cancer. Continued educational gaps: 25% of hematologists/oncologists failed to select guideline recommended DOAC therapy for thromboprophylaxis in cancer patients.45% of hematologists/oncologists failed to select guideline recommended DOAC therapy for treatment of thrombosis in cancer patients.66% of hematologists/oncologists still remain at only a rating of 1 to 3 on a scale of 1 to 5 in their confidence managing thrombosis in patients with cancer. Conclusion:This study demonstrates the success of online, CME-accredited, video-based roundtable discussion with experts in the field on significantly improving knowledge and confidence of hematologists/oncologists related to the guideline-recommended use of DOACs in the management of cancer-associated thrombosis. Continued gaps were also identified for future educational targets. Sources of support: Developed through an independent educational grant from Janssen in partnership with the University of Chicago. References: Cushman M, Creager MA. Improving awareness and outcomes related to venous thromboembolism. JAMA. 2015;314(18):1913-4. Farge D, Frere C, Connors JM, et al. 2019 International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. The Lancet Oncology. 2019;20(10):e566-581. Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2020 Feb 10;38(5):496-520. Khorana AA, Yannicelli D, McCrae KR, et al. Evaluation of US prescription patterns: are treatment guidelines for cancer-associated venous thromboembolism being followed? Thromb Res. 2016 Sep;145:51-3. Disclosures No relevant conflicts of interest to declare.

scholarly journals P0531CONTINUOUS HEMODIAFILTRATION WITH PMMA HEMOFILTER MODULATED COMPLEMENT ACTIVATION AND RENAL DYSFUNCTION IN A SWINE MODEL OF SEPSIS-INDUCED ACUTE KIDNEY INJURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Alessandra Stasi ◽  
ROSSANA FRANZIN ◽  
Fabio Sallustio ◽  
Chiara Divella ◽  
Claudia Curci ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Kidney Injury ◽  
Complement Activation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Kidney Injury ◽  
Swine Model ◽  
Complement Factor ◽  
Factor B ◽  
Renal Biopsies

Abstract Background and Aims Sepsis-induced acute kidney injury (AKI) is a growing health care problem, refractory to conventional treatments. This disease is characterized by an overwhelmed immune response against a primary insult that become responsible for renal dysfunction and poor outcome. Therapeutic strategies based on blood purification have been developed for the treatment of this disease. The use of polymethyl methacrylate (PMMA) membrane hemofilter in continuous hemodiafiltration (CHDF) modality showed better hemodynamic stability and efficient renal support in chronic dialysis maintenance. Here we investigated the efficacy of Hemofeel PMMA membrane (TORAY, Japan) in interfering with Complement activation and renal damage in a swine model of sepsis-induced AKI. Method After 3 hours from LPS infusion, 7 hours of PMMA-CVVH treatment or 7 hours of polysulfone (PSF)-CVVH were performed. Animals were sacrificed after 24h from LPS infusion. Histologic and renal function parameters were analyzed in all pigs. Pentraxin-3 (PTX3) and C5b-9 deposits were assessed on renal biopsies. Systemic Complement activation was evaluated by Wieslab kit. Gene expression profile was obtained from isolated PBMCs by Agilent SurePrint G3 Porcine Gene Expression Microarrays. Genespring and R software were used for the analysis. Results were validated by Real-time PCR. Results Analysis of renal biopsies from septic pigs presented increased interstitial leucocyte infiltrate, extensive collagen deposition and diffuse glomerular thrombi compared to healthy pigs (p&lt;0.05). Confocal analysis showed extensive PTX-3 and C5-b9 deposits at tubulo-interstitial level associated with significant activation of systemic complement classical and alternative pathways (p&lt;0.05). Interestingly, PMMA-CVVH treatment significantly reduced local and systemic complement activation, leucocyte infiltrate and tubule-interstitial fibrosis (p&lt;0.05). On the contrary, no significant improvement was observed by PSF-CVVH treatment. Then, we compared the whole-genome gene expression profiles of swine PBMC. We identified 711 differentially expressed genes comparing PBMC before LPS infusion (LPS T0) and after 24 hours from LPS infusion (LPS T24) and 913 genes comparing gene expression profiles of LPS T24 group with that of septic pigs treated with PMMA-CVVH (PMMA T24 group) (fold change &gt;2 ; false discovery rate &lt;0.05). The most modulated genes were Granzime B, Complement Factor B, Complement Component 4 Binding Protein Alpha, IL-12, SERPINB-1 and TIMP-2 that were closely related to sepsis-induced immunological process. Finally, quantitative PCR confirmed the microarray data indicating that Granzime B and Complement Factor B upregulation in PBMC was significantly hampered by PMMA treatment. Conclusion Our data suggest that LPS induced AKI is characterized by activation of Classical and alternative Complement pathways resulting in significant renal tissue damage. By interfering with complement activation and inflammatory response, PMMA membrane might prevent dysfunctional activation of resident renal cells with prevention of sepsis-induced AKI.

scholarly journals Endothelial lesion and complement activation in patients with Scleroderma Renal Crisis

2019 ◽  
Vol 41 (4) ◽  
pp. 580-584
Author(s):  
Ney Arencibia Pérez ◽  
María Luisa Agüera Morales ◽  
Rafael Sánchez Sánchez ◽  
Rosa María Ortega Salas ◽  
Rafael Ángel Fernández de la Puebla ◽  
...  
Keyword(s):  
Complement Activation ◽  
Analytical Data ◽  
Clinical Signs ◽  
Endothelial Damage ◽  
Hypertensive Retinopathy ◽  
Scleroderma Renal Crisis ◽  
Acute Type ◽  
Vascular Endothelial ◽  
Acute Injuries ◽  
Renal Crisis

Abstract In kidney biopsies reviews, scleroderma renal crisis (SRC) is characterized by vascular endothelial injuries, C4d deposits on peritubular vessels, and acute and chronic injuries coexisting on the same biopsy. The clinical signs of thrombotic microangiopathy (TMA) are described in systemic sclerosis (SSc), nevertheless, it has not been related to acute injuries described on kidney biopsies. We report a case of SRC in a patient with scleroderma-dermatomyositis overlap syndrome, which also showed clinical and histopathological data of TMA. On fundus examination, a severe acute hypertensive retinopathy was found. The kidney biopsy showed severe endothelial damage with widening of mucoid cells at the level of the intima, focal concentric proliferation on most small arterioles, and C3, C4d, and IgM deposits along the capillary walls. The genetic study of complement only showed the presence of membrane cofactor protein (MCP) risk haplotypes, without other genetic complement disorders. We understand that in a patient with TMA and SSc, the kidney damage would be fundamentally endothelial and of an acute type; moreover, we would observe clear evidence of complement activation. Once further studies correlate clinical-analytical data with anatomopathological studies, it is likely that we will be forced to redefine the SRC concept, focusing on the relationship between acute endothelial damage and complement activation.

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