58
Treatment
Table 8. Hematologic Toxicities
8.3 Hemolytic Uremic Syndrome (HUS)
Workup/Evaluation
• History and physical examination (special consideration for new history of high-risk
drugs, hypertension or cardiac causes)
• CBC with indices
• Blood smear morpholog y. Note that the presence of schistocytes on smear is critical
for diagnosis
• Serum creatinine
• ADAMTS13 (to rule out TTP)
• Homocysteine/MMA
• Complement testing C3, C4, CH50 (complement inhibitory antibodies for
suspected familial)
• Evaluate reticulocyte count and MCV
• Evaluation of infectious cause including screening for viral Epstein-Barr virus (EBV),
CMV, human herpesvirus 6 (HHV6)
• Evaluation for nutritional causes of macrocytosis (B12 and folate)
• Pancreatic enzymes
• Evaluation for diarrheal causes, shiga toxin, Escherichia coli 0157, etc.
• Direct antibody test (Coombs test), haptoglobin, LDH, and other etiologies of
anemia
• Evaluation for common drugs causing hemolysis (tacrolimus, cyclosporine, sirolimus,
etc.)
• Evaluation for neurologic changes (alteration in consciousness, concurrent confusion,
seizures, pyramidal syndrome, and extrapyramidal syndrome with hypertonia)
Grading Management
G1–2: Evidence of RBC
destruction (schistocytosis)
without clinical
consequences of anemia,
thrombocytopenia grade II
• Continue ICPi with close clinical follow-up and
laboratory evaluation.
• Supportive care.
G3: Laboratory findings
with clinical consequences
(e.g., renal
insufficiency, petechiae)
• Permanently discontinue ICPi.
• Hematolog y consult
• Begin therapy with eculizumab (anti-C5 antibody)*
900 mg weekly × 4 doses, 1,200 mg week 5, then
1,200 mg every two weeks.
• Red blood transfusion according to existing
guidelines.
G4: Life-threatening
consequences, (e.g., CNS
thrombosis/embolism or
renal failure)
* Patients should be immunized with a meningococcal vaccine at least 2 weeks prior to administering
the first dose of eculizumab, unless the risks of delaying eculizumab therapy outweigh the risks of
developing a meningococcal infection.
(cont'd)
