Complement-mediated thrombotic microangiopathy or sepsis with disseminated intravascular coagulation -what is primary?

Thrombotic microangiopathies (TMAs) are induced by several underlying conditions; most are resolved by treating background disease. Eculizumab is a human monoclonal antibody that blocks the final stage of the complement system and effectively treats atypical hemolytic uremic syndrome (aHUS). In this report, we present a patient with TMA related to sepsis- induced coagulopathy, who was successfully treated with eculizumab.A 44-year-old woman, who had no special medical history or familial history of TMAs, hospitalized for acute kidney injury.Blood tests revealed a decreased platelet count, disseminated intravascular coagulation (DIC), renal dysfunction, hemolysis, and infection. Although the coagulation disorder improved with intensive care, the low platelet count, elevated lactate dehydrogenase levels, and renal dysfunction persisted. Our investigations subsequently excluded thrombotic thrombocytopenic purpura and Shiga toxin-producing Escherichia coli-induced HUS. Plasma exchange only improved lactate dehydrogenase levels. We clinically diagnosed this case as atypical HUS and started eculizumab treatment. The patient's platelet count increased, her renal dysfunction improved. We encountered a case of complement-mediated TMA accompanied by DIC, which was successfully treated with eculizumab. Further studies are necessary to support the optimal use of eculizumab for TMA with background diseases.

1. George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med 2014;371:654-666. Doi: 10.1056/NEJMra1312353

2. Scully M, Goodship T. How I treat thrombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome. Br J Haematol 2014;164:759-766. Doi: 10.1111/bjh.12718

3. Wada H, Matsumoto T, Suzuki K et al. Differences and similarities between disseminated intravascular coagulation and thrombotic microangiopathy. Thrombosis Journal 2018;16:14. Doi. org/10.1186/s12959-018-0168-2

4. Zhao X, Chen YX, Li CS. Predictive value of the complement system for sepsis-induced disseminated intravascular coagulation in septic patients in emergency department. J Crit Care 2015;30:290-299. Doi: 10.1074/jbc

5. Wada H, Matsumoto T, Katayama N. Emicizumab prophylaxis in hemophilia a with inhibitors. N Engl J Med 2017;377:2193-2194. Doi: 10.1056/NEJMoa1703068

6. De Sousa Amorim E, Blasco M, Quintana L et al. Eculizumab in pregnancy-associated atypical hemolytic uremic syndrome: insights for optimizing management. J Nephrol 2015;28:641-645. Doi: 10.1007/s40620-015-0173-5

7. Sakamaki X Konishi K, Hayashi K et al. Renal thrombotic microangiopathy in a patient with septic disseminated intravascular coagulation. BMC Nephrol 2013;14:260. Doi: 10.1186/1471-2369-14-260

8. Booth KK, Terrell DR, Vesely SK et al. Systemic infections mimicking thrombotic thrombocytopenic purpura. Am J Hematol 2011;86:743-751. Doi: 10.1002/ajh.22091

9. Abe T, Sasaki A, Ueda T, Miyakawa X Ochiai H. Complement-mediated thrombotic microangiopathy secondary to sepsis-induced disseminated intravascular coagulation successfully treated with eculizumab: A case report. Medicine (Baltimore) 2017;96(6):e6056. Doi: 10.1097/MD.0000000000006056

10. Jokiranta TS. HUS and atypical HUS. Blood 2017; 129:2847-2856. Doi: 10.1182/blood-2016-11-709865

11. Coppo R, Peruzzi L, Amore A et al. Dramatic effects of eculizumab in a child with diffuse proliferative lupus nephritis resistant to conventional therapy. Pediatr Nephrol 2015;30:167-172. Doi: 10.1186/s12882-016-0299-2

12. Thomas CP, Nester CM, Phan AC et al. Eculizumab for rescue of thrombotic microangiopathy in PM-Scl antibody-positive autoimmune overlap syndrome. Clin Kidney J 2015;8:698-701. Doi: 10.1093/ckj/sfv101