Thrombotic microangiopathy

• Syndrome of microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis leading to organ dysfunction

Disease	Clinical Clues
Primary
Thrombotic thrombocytopenia purpura	PT/INR and PTT are normal
Hemolytic-uremic syndrome	PT/INR and PTT are normal, severe AKI
Atypical hemolytic-uremic syndrome	PT/INR and PTT are normal, severe AKI
HELLP syndrome	pregnancy
Secondary
Autoimmune disease, including systemic lupus erythematosus or antiphospholid antibody syndrome
Drug-induced thrombotic microangiopathy	including quinine, ticlopidine, and chemotherapy (mitomycin, gemcitabine, cyclosporine, and tacrolimus, though it may also be caused by the underlying condition
Sepsis
Secondary hemolytic-uremic syndrome	most commonly from Streptococcus pneumoniae or influenza
DIC	PT/INR and PTT are prolonged
Malignancy
HIV

Investigations

• Confirm presence of TMA: CBC, reticulocyte count, LDH, peripheral blood film, and haptoglobin
• Assess for end-organ damage: electrolytes, troponin, lactate, liver enzymes, bilirubin, urinalysis, urea, creatinine, lipase
• Assess for TTP: plasma ADAMTS-13 activity ± inhibitor
• Assess for infectious causes: stool for culture (for STEC), stool for Shiga toxin (PCR or ELISA, as available), and-LPS antibodies, chest x-ray, blood cultures ± urine ± CSF cultures, multiplex NP swab, HIV serology, hepatitis B and C serology
• Assess for other coexisting diseases:
  • Lipase, complement C3/C4, ANA, anti-dsDNA, anti-centromere, anti-Scl-70, calcium, INR/PTT, fibrinogen, FDP, D-dimer, lupus anticoagulant, anti-cardiolipin, β2 glycoprotein, DAT/Coombs test
  • ANCA, anti-GBM, beta-hCG
• Assess for atypical HUS: tests of complement activation (CFB/Ba/Bb, C5b-9 level, CH50),, anti-CFH antibodies, MCP surface expression, screening for mutations in complement pathway genes

Further Reading

• Making the Correct Diagnosis in Thrombotic Microangiopathy: A Narrative Review. Can J Kidney Health Dis. 2021;8. doi: 10.1177/205435812110087