Thrombotic Microangiopathy Care Pathway: A Consensus Statement for the Mayo Clinic Complement Alternative Pathway-Thrombotic Microangiopathy (CAP-TMA) Disease- Oriented Group  Ronald S. Go, MD, Jeffrey L. Winters, MD, Nelson Leung, MD, David L. Murray, MD, PhD, Maria A. Willrich, PhD, Roshini S. Abraham, PhD, Hatem Amer, MD, William J. Hogan, MBBCh, Ariela L. Marshall, MD, Sanjeev Sethi, MD, PhD, Cheryl L. Tran, MD, Dong Chen, MD, PhD, Rajiv K. Pruthi, MBBS, Aneel A. Ashrani, MD, MS, Fernando C. Fervenza, MD, PhD, Carl H. Cramer, MD, Vilmarie Rodriguez, MD, Alexandra P. Wolanskyj, MD, Stephan D. Thomé, MD, C. Christopher Hook, MD Ronald S. Go, MD, Jeffrey L. Winters, MD, Nelson Leung, MD, David L. Murray, MD, PhD, Maria A. Willrich, PhD, Roshini S. Abraham, PhD, Hatem Amer, MD, William J. Hogan, MBBCh, Ariela L. Marshall, MD, Sanjeev Sethi, MD, PhD, Cheryl L. Tran, MD, Dong Chen, MD, PhD, Rajiv K. Pruthi, MBBS, Aneel A. Ashrani, MD, MS, Fernando C. Fervenza, MD, PhD, Carl H. Cramer, MD, C. Christopher Hook, MD, Vesna D. Garovic, MD, Jennifer C. Yui, MD, Juliana Perez Botero, MD Ronald S. Go, MD, Jeffrey L. Winters, MD, Nelson Leung, MD, David L. Murray, MD, PhD, Maria A. Willrich, PhD, Roshini S. Abraham, PhD, Hatem Amer, MD, William J. Hogan, MBBCh, Ariela L. Marshall, MD, Sanjeev Sethi, MD, PhD, Cheryl L. Tran, MD, Dong Chen, MD, PhD, Rajiv K. Pruthi, MBBS, Aneel A. Ashrani, MD, MS, Fernando C. Fervenza, MD, PhD, Carl H. Cramer, MD, Vilmarie Rodriguez, MD, Alexandra P. Wolanskyj, MD, Stephan D. Thomé, MD, C. Christopher Hook, MD Ronald S. Go, MD, Jeffrey L. Winters, MD, Nelson Leung, MD, David L. Murray, MD, PhD, Maria A. Willrich, PhD, Roshini S. Abraham, PhD, Hatem Amer, MD, William J. Hogan, MBBCh, Ariela L. Marshall, MD, Sanjeev Sethi, MD, PhD, Cheryl L. Tran, MD, Dong Chen, MD, PhD, Rajiv K. Pruthi, MBBS, Aneel A. Ashrani, MD, MS, Fernando C. Fervenza, MD, PhD, Carl H. Cramer, MD, C. Christopher Hook, MD, Vesna D. Garovic, MD, Jennifer C. Yui, MD, Juliana Perez Botero, MD  Mayo Clinic Proceedings  Volume 91, Issue 9, Pages 1189-1211 (September 2016) DOI: 10.1016/j.mayocp.2016.05.015 Copyright © 2016 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 1 Clinicopathologic overview of thrombotic microangiopathy. Mayo Clinic Proceedings 2016 91, 1189-1211DOI: (10.1016/j.mayocp.2016.05.015) Copyright © 2016 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 2 Clinical suspicion of thrombotic microangiopathy. ADAMTS13 = a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13; APLS = antiphospholipid syndrome; DGKE = diacylglycerol kinase-ε; DIC = disseminated intravascular coagulation; HIV = human immunodeficiency virus; HTN = hypertension; PLG = plasminogen; SLE = systemic lupus erythematosus; THBD = thrombomodulin; TTP = thrombotic thrombocytopenic purpura. Associated drugs data from Blood.9 Mayo Clinic Proceedings 2016 91, 1189-1211DOI: (10.1016/j.mayocp.2016.05.015) Copyright © 2016 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 3 Care pathway 1: general considerations and Shiga toxin–induced TMA. CFH = complement factor H; CP = care pathway; DGKE = diacylglycerol kinase-ε; TMA = thrombotic microangiopathy; TPE = total plasma exchange; TTP = thrombotic thrombocytopenic purpura. Mayo Clinic Proceedings 2016 91, 1189-1211DOI: (10.1016/j.mayocp.2016.05.015) Copyright © 2016 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 4 Care pathway 2: TTP. Hgb = hemoglobin; LDH = lactate dehydrogenase; Plt = platelet count; TPE = therapeutic plasma exchange; TTP = thrombotic thrombocytopenic purpura. Mayo Clinic Proceedings 2016 91, 1189-1211DOI: (10.1016/j.mayocp.2016.05.015) Copyright © 2016 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 5 Care pathway 3: hyperhomocysteinemia. CP = care pathway; ULN = upper limit of normal. Mayo Clinic Proceedings 2016 91, 1189-1211DOI: (10.1016/j.mayocp.2016.05.015) Copyright © 2016 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 6 Care pathway 4: precipitating factors. CP = care pathway; DIC = disseminated intravascular coagulation. Mayo Clinic Proceedings 2016 91, 1189-1211DOI: (10.1016/j.mayocp.2016.05.015) Copyright © 2016 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 7 Care pathway 5: probable complement dysregulation. CFH = complement factor H; CP = care pathway; TPE = therapeutic plasma exchange. Mayo Clinic Proceedings 2016 91, 1189-1211DOI: (10.1016/j.mayocp.2016.05.015) Copyright © 2016 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 8 Care pathway 6: renal transplantation. CP = care pathway; TPE = therapeutic plasma exchange. Mayo Clinic Proceedings 2016 91, 1189-1211DOI: (10.1016/j.mayocp.2016.05.015) Copyright © 2016 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 9 Care pathway 7: stem-cell transplantation. CP = care pathway. Mayo Clinic Proceedings 2016 91, 1189-1211DOI: (10.1016/j.mayocp.2016.05.015) Copyright © 2016 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 10 Care pathway 8: complement mutations. CFB = complement factor B; CFH = complement factor H; CFI = complement factor I; THBD = thrombomodulin; TPE = therapeutic plasma exchange. Mayo Clinic Proceedings 2016 91, 1189-1211DOI: (10.1016/j.mayocp.2016.05.015) Copyright © 2016 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 11 Care pathway 9: coagulation protein mutations. DGKE = diacylglycerol kinase-ε; PLG = plasminogen; TPE = therapeutic plasma exchange. Mayo Clinic Proceedings 2016 91, 1189-1211DOI: (10.1016/j.mayocp.2016.05.015) Copyright © 2016 Mayo Foundation for Medical Education and Research Terms and Conditions