1. A diagnostic algorithm for the investigation and management of a patient presenting with thrombotic microangiopathy.
A diagnostic algorithm for the investigation and management of a patient presenting with thrombotic microangiopathy. Supportive treatment is essential. This comprises fluid management and, if indicated, judicious packed red blood cell transfusion, intensive care unit admission, and RRT. Platelet transfusion may worsen the TMA and so should be avoided if possible. The complete evaluation of a patient presenting with TMA comprises complement analysis and investigations for all conditions in which TMA can manifest, and usually enables the disease cause to be established. However, collating the results of the requisite investigations may take considerable time. The clinical evaluation during the acute presentation of a TMA requires some time-critical decision-making, which should focus initially on the consideration of TTP, because immediate management is imperative given the high mortality rate if untreated, and therefore in adults, PE should be instituted on the presumption that it is TTP unless other evidence is available that strongly suggests an alternative cause. In children, in whom TTP is rarer, first-line treatment with eculizumab should be considered if complement-mediated aHUS is suspected and should not be delayed while ADAMTS13 activity is determined. In the absence of a defined cause, complement-mediated aHUS is presumed and treatment with eculizumab is recommended, pending the complete evaluation. Eculizumab is not universally available; in these circumstances, treatment should comprise PE, and there may be a role for liver transplantation. *Full complement evaluation is recommended (Kidney Disease: Improving Global Outcomes consensus [6]) in individuals with pregnancy-associated aHUS and de novo transplantation-associated aHUS because of the high prevalence of rare genetic variants described in these subgroups, and in cases of STEC-HUS that result in ESRD, as rare genetic variants have been described after HUS recurrence in a subsequent kidney transplant. Additionally, it is recognized that infection can trigger manifestation of complement-mediated aHUS. In other secondary cases of aHUS, insufficient evidence exists to recommend a full genetic evaluation, although rare genetic variants have been described in many of these presentations. In cases where the role of complement is as yet unclear, the clinician should decide on the evaluation on the basis of the potential clinical consequences of a positive result (e.g., listing for renal transplantation). +ve, positive; AAV, ANCA-associated vasculitis; Ab, antibody; ACA, anticentromere antibody; ACEI, angiotensin-converting enzyme inhibitor; ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; Ag, antigen; aHUS, atypical hemolytic uremic syndrome; ANA antinuclear antibody; anti-ds DNA, antidouble-stranded DNA; anti–Scl70, anti-topoisomerase I antibody; BMT; bone marrow transplant; C3G, C3 glomerulopathy; CAPS, catastrophic antiphospholipid syndrome; DGKE, gene encoding diacylglycerol kinase ε; DIC, disseminated intravascular coagulation; FH, factor H; FI, factor I; Hb, hemoglobin; HUS, hemolytic uremic syndrome; LDH, lactate dehydrogenase; MAHA, microangiopathic hemolytic anemia; MN, membranous nephropathy; MPGN, membranoproliferative GN; PE, plasma exchange; SRC, scleroderma renal crisis; STEC, shiga toxin–producing Escherichia coli; Stx, shiga toxin; T-Ag, Thomsen–Friedenreich antigen; TMA, thrombotic microangiopathy; TTP, thrombotic thrombocytopenic purpura.
Vicky Brocklebank et al. CJASN 2018;13:
©2018 by American Society of Nephrology