Table 2.

Syndromes of Thrombotic Microangiopathy (TMA)*.

Primary TMA

Hereditary

Thrombotic thrombocytopenic purpura (TTP) – biallelic mutations in ADAMTS13

Complement-mediated TMA, also called atypical hemolytic uremic syndrome (aHUS)

Mutations in proteins in the alternate pathway of complement (CAP)**

Metabolism-mediated TMA (homozygous MMACHC mutations) – rare

Coagulation-mediated TMA (homozygous DGKE mutations) – rare  Acquired

Autoantibodies against ADAMTS13

Shiga-toxin-mediated hemolytic uremic syndrome (STEC-HUS)

Autoantibodies against CAP proteins, typically Factor H

Secondary TMA***

Drug-induced TMA

Immune-mediated (e.g., quinine)

Toxic and dose related (e.g., gemcitabine)

Infection-mediated TMA (other than Shiga-toxin producing organisms)

Metastatic cancer

Pregnancy associated TMA, including preeclampsia/HELLP syndrome

Autoimmune associated TMA

Systemic lupus

Antiphospholipid syndrome

Scleroderma renal crisis

Hematopoietic stem cell transplantation associated TMA

Solid organ transplant associated TMA

Paraprotein associated TMA****

*Adapted from George and Nester (8).

**Approximately 50% of patients with a clinical picture compatible with complement-mediated TMA will not have detectable pathogenic mutations in CAP proteins. Some refer to these as idiopathic aHUS, although response to complement inhibition with eculizumab is equally efficacious.

***Many patients with secondary causes have underlying genetic mutations similar to those causing complement-mediated HUS. Such secondary causes may serve in those instances as triggers in predisposed individuals. Treatment should involve removal/treatment of the secondary cause if possible, with consideration of eculizumab on a case by case basis..

ADAMTS13, A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13; MMACHC, methylmalonic aciduria and homocystinuria type C gene; DGKE, diacylglycerol kinase epsilon gene.

****Provisional.