Differential diagnosis, investigations and treatment:
Our patient presented with fever and altered level of consciousness
raising suspicion of meningoencephalitis. Patient on examination was
obtunded, had pinpoint pupils and lost consciousness acutely, hence
organophosphorus poisoning was another differential. Malaria and Dengue
were ruled out. Urine toxicology screening did not reveal any toxic
substances in urine. During the hospital stay when patient developed
anemia, severe thrombocytopenia and acute kidney injury, Thrombotic
thrombocytopenic purpura (TTP) was our top differential considering the
hematological, renal and liver derangements and immediate hematological
consultation was sought and prompt management was started on lines of
TTP once diagnosis was confirmed.
Routine laboratory workup on first day of admission including complete
blood count, renal and liver functions test and inflammatory markers are
given in Table 1. Chest X-Ray was unremarkable. Considering the ongoing
pandemic, nasopharyngeal swab for SARS-CoV-2 (polymerase chain reaction)
was done which was positive. Malarial parasite was not seen on
peripheral blood film and Dengue antigen was negative. CAT (computerized
axial tomography) scan brain ruled out intracranial bleed or infarct.
Patient was managed on lines of COVID pneumonia (mild) and presumed
meningoencephalitis. Upon presentation to emergency room, patient was
intubated for airway protection and was kept on mechanical ventilator.
He was started on high dose of intravenous ceftriaxone and vancomycin to
treat presumed meningoencephalitis. Cerebrospinal fluid analysis was
normal hence doses of antibiotics were reduced. During ICU stay patient
was on minimal ventilatory settings (Fraction of inspired Oxygen
[FiO2] of 40% and Positive End Expiratory Pressure [PEEP of
5]). Mild acute kidney injury on presentation got resolved with
intravenous hydration.
On sixth day of hospital stay patient developed anemia, severe
thrombocytopenia and acute kidney injury. Laboratory workup including
reticulocytes, Direct Coombs, renal and liver function tests are shown
in Table 1. Peripheral film on sixth day of hospital stay showed
schistocytes as shown in Figure 1. Due to unavailability of ADAMTS13
levels at our center, Plasmic score was calculated to estimate ADAMTS13
deficiency. A score of 5 showed patient to be in intermediate risk group
with 6% chance of severe ADAMTS13 deficiency (severe ADAMTS13
deficiency is defined as activity of less than 15%). Lactate
dehydrogenase (LDH), total and indirect bilirubin and reticulocyte
counts were raised. Direct Coombs test came out to be weakly positive
while peripheral blood smear showed presence of schistocytes (5.8%) and
thrombocytopenia (as mentioned in Table 1). Immediate hematological
consultation was sought and prompt management was started on lines of
TTP. Intravenous methylprednisolone pulse (1 gram) and plasma exchange
(PLEX) was instituted. Steroid therapy was continued for three days and
seven sessions of PLEX were done. Patient also received one dose of IV
rituximab at a dose of 375mg/m2. Patient’s hemoglobin
and platelet count started to increase after first session of PLEX.
Renal function along with urine output also started to improve. Since
target platelet count was not achieved after five sessions of PLEX, two
additional sessions were done. Patient was extubated after third session
of PLEX. However hospital stay got complicated with development of
ventilator associated pneumonia (tracheal secretions showed growth ofEscherichia coli and Pseudomonas aeruginosa ) and
candidemia (blood culture showed growth of Candida glabrata )
which was treated with intravenous meropenem and IV Amphotericin B.