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.