Table 1:

Differential diagnoses of thrombotic microangiopathies and diagnostic investigations

Differential diagnosesDiagnostic tests
Primary thrombotic microangiopathy
TTP
 Congenital TTP

  • Mutations of ADAMTS13 gene7–9

 Acquired TTP

  • ADAMTS13 activity and inhibitor7,10,11

HUS
 STEC-HUS

  • PCR for the Shiga toxin, or stool culture for STEC or Shigella3,12

 Atypical HUS

  • Genetic mutations in complement regulatory proteins (e.g., CFH, CFI, MCP, C3, CFB, THBD);13–15 anti-CFH autoantibodies16

Secondary thrombotic microangiopathy
Malignant hypertension

  • Blood pressure and renal function

  • Investigation for other causes of thrombotic microangiopathy associated with hypertension17

Pregnancy-associated thrombotic microangiopathy, preeclampsia/eclampsia, HELLP

  • Pregnancy testing18

  • Elevated liver transaminase levels

Drugs and toxins (e.g., calcineurin inhibitors, quinine, ticlopidine)

  • Drug discontinuation19,20

Infections (e.g., influenza, HIV, Epstein–Barr virus, parvovirus)

  • Infection-specific testing12,21,22

Cancer

  • Imaging and other investigations including paraneoplastic syndromes1

Autoimmune disease (e.g., systemic lupus erythematosus)

  • Autoimmune serologic markers, clinical symptoms or signs as per diagnostic criteria7

Transplantation (e.g., solid organ, bone marrow)

  • Consider graft versus host disease, graft rejection, conditioning regimen, antirejection therapy23

Disseminated intravascular coagulation

  • Abnormal coagulation testing, reduced fibrinogen

  • Assess for underlying causes (e.g., sepsis, malignancy)24

Metabolic (e.g., cobalamin C deficiency)

  • Elevated serum homocysteine and serum or urine methylmalonic acid25,26

  • Note: C3 = complement component 3, CFB = complement factor B, CFH = complement factor H, CFI = complement factor I, HELLP = hemolysis, elevated liver enzymes and low platelet count, HSCT = hematopoietic stem cell transplant, HUS = hemolytic uremic syndrome, MCP = membrane cofactor protein (CD46), PCR = polymerase chain reaction, STEC = Shiga toxin–producing Escherichia coli, THBD = thrombomodulin, TTP = thrombotic thrombocytopenic purpura.