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.