11
Table 3. Hemophagocytic Lymphohistiocytosis (HLH)
Recommendations
Workup/Evaluation:
• Complete blood count with differential and coagulation studies (PT, aPTT,
fibrinogen, D-dimer).
• Liver function tests (ALT, AST, GGT, total bilirubin, albumin, and lactate
dehydrogenase).
• Serum triglycerides (fasting ) and serum ferritin.
• Soluble IL-2 receptor alpha (sCD25 or sIL-2R), and/or CXCL9.
• The following testing should be performed in all patients, based on the signs and
symptoms of specific organ involvement and/or the degree of suspicion for the
presence of HLH:
▶ Cultures of blood, bone marrow, urine, and cerebrospinal fluid (CSF); and viral
titers and quantitative polymerase chain reaction (PCR) testing for EBV, CMV,
adenovirus, and other suspected viruses. Follow levels of any identified virus during
treatment with the appropriate anti-viral therapy.
▶ Bone marrow aspirate and biopsy.
▶ Electrocardiograph, chest radiography, and echocardiogram.
▶ Lumbar puncture with CSF analysis.
▶ Brain MRI scan with and without contrast. Imaging of the central nervous system
may show parameningeal infiltrations, subdural effusions, necrosis, and other
abnormalities.
Grading Management
All Grades • Offer supportive care.
• Use corticosteroids if patient is deteriorating or
unstable.
• While data are insufficient to recommend a
transfusion threshold, replacement of fibrinogen
should be considered in patients with a
fibrinogen level below 150 mg/dL.
• Manage G ≥3 organ toxicity with IL-6
antagonist plus corticosteroids.
• If insufficient response after 48 hours, consider
adding anakinra.
• Etoposide could be considered in severe,
refractory cases, although there is a lack of
data in this setting and concern for effect on
lymphocytes. Intrathecal cytarabine, with or
without hydrocortisone, may also be considered
for patients with HLH-associated neurotoxicity.
