Case Description
19-year-old female with SCD (S/β0thalassemia-type),
chronic pain syndrome, history of leg ulcers and hepatic crisis, on
monthly transfusions with iron overload (average ferritin 3465 ng/mL
over prior year) requiring deferasirox (DFX) chelation, was hospitalized
for VOC when COVID-19 was diagnosed by positive SARS-CoV-2 PCR. Her pain
improved, she started hydroxychloroquine, and was discharged three days
later. She returned after two days with nausea, emesis, dehydration, and
transient AST/ALT elevation, presumed due to hydroxychloroquine,
(thereafter discontinued). She developed acute chest syndrome with
fever, decreased hemoglobin, but no hypoxemia, managed with simple red
cell transfusion and antibiotics, and was discharged a few days later.
Four weeks later she was re-hospitalized with persistent anorexia and
fatigue, dyspnea, and diffuse worsening pain, but with headache and
abdominal pain not typical for her usual VOC. She received morphine and
ketorolac and continued home medications including DFX. Repeat SARS-CoV2
nasal PCR was negative twice this hospitalization. On hospital day
three, she developed fever 38.9ºC for which blood culture was
obtained and ceftriaxone administered. Five hours later she became
acutely disoriented and agitated, without any focal neurologic deficit,
and was transferred to the ICU. Laboratory evaluation revealed elevated
ammonia of 350 mmol/L, lactate 7.9 mmol/L, AST 55 unit/L, ALT 29 unit/L,
ALP 92 unit/L, TB 4.2 mg/dL, Cr 1.3 mg/dL (baseline 0.7), normal
albumin, mildly increased PT (17.8 sec), and elevated CRP (6.7 mg/dL)
(Figures 1, 2). CT Head and non-contrast MRI brain were normal;
abdominal ultrasound showed isolated cholelithiasis and normal
hepatoportal blood flow. She started lactulose and neomycin for
hyperammonemia, and DFX was held due to possible toxicity. Her clinical
encephalopathy progressed, with EEG consistent with severe diffuse
cerebral dysfunction; she was then intubated for declining neurologic
status. She underwent hemodialysis for progressive encephalopathy with
persistent hyperammonemia, with improved ammonia from 369 mmol/L to 153
mmol/L (Figure 1). She developed elevated transaminases (Figure 1) and
worsened synthetic liver function (PT 23.1 sec, bilirubin 10.7 mg/dL),
shock requiring vasoactive support, increased creatinine to 1.49 mg/dL,
and thrombocytopenia (platelet 95,000) with coagulopathy (normal
fibrinogen 249 mg/dL but elevated D-dimer 4.4 mcg/mL – Figure 2),
consistent with multiorgan failure syndrome (MOFS). Because of this,
erythrocytapheresis (red blood cell exchange transfusion, RBCX) was
performed (hemoglobin S pre-/post-RBCX 29% and 11% respectively).
Despite RBCX, CRP increased further to 15.1 mg/dL, with persistent
thrombocytopenia and fever, so therapeutic plasma exchange (TPE) was
performed for cytokine clearance and thrombocytopenia-associated
MOFS6,7. Following TPE, AST, ALT, PT, and ammonia all
normalized (Figure 1). CRP decreased to 2.1 mg/dL, with resolved fever,
and neurologic exam revealing purposeful movements. However, repeat
brain MRI noted interval bilateral thalamic T2 hyperintensity,
concerning for ischemia or localized cytotoxic edema from hepatic
encephalopathy. She also developed a nonocclusive catheter-related left
common femoral vein thrombus, so enoxaparin anticoagulation was started
(prophylactic anticoagulation not started earlier due to coagulopathy).
Five days after TPE, she returned to neurologic baseline without any
deficits. She was discharged on hospital day 15 with residual but
improved pain, improved D-dimer and CRP (Figure 2), and normal liver
function tests. On outpatient follow-up one week later, her CRP
normalized.