ABSTRACT
Autoimmune hemolytic anemia (AIHA) is a very rare presentation of COVID-19, and AIHA due to COVID-19 alone (i.e., in the absence of an associated underlying disorder) is extremely rare. Warm agglutinin disease accounts for the majority of AIHA in general. Here, we report a case of a 23-year-old male with bronchial asthma who was referred to our hospital with SARS-COV-2 infection and severe anemia presenting as acute immune-mediated hemolytic crisis due to warm autoimmune hemolytic anemia (AIHA). Extensive laboratory testing was performed, including polyspecific direct antiglobulin test, complete autoimmune workup and common infections leading to AIHA were ruled out by serology and molecular methods. The patient required multiple blood transfusions and other therapeutic interventions before clinical stabilization. Treatment of new-onset AIHA is always challenging in the presence of an active viral replication; combining immunosuppression with active COVID-19 infection creates extremely difficult diagnostic and management settings, as this case illustrates.
ABSTRACT
This work attempts to resolve one of the key issues related to the design and development of sustained-release spherule of aspirin for oral formulations, tailored to treat COVID-19. For that, in the Design of Experiments (DOE) an arbitrary interface, "coating efficiency" (CE) is introduced and scaled the cumulative percentage coating (CPC) to get predictable control over drug release (DR). Subsequently, the granules containing ASP are converted to spherules and then to Ethyl cellulose (EC) Coated spherules (CS) by a novel bed coating during the rolling (BCDR) process. Among spherules, one with 0.35 mm than 0.71 mm shows required properties. The CS has a low 1200 angle by Optical Microscopy (OM), smooth surface without cracks by scanning electron microscopy (SEM), and better flow properties (Angle of repose 29.69 ± 0.780, Carr's index 6.73 ± 2.24%, Hausner's Ratio 1.07 ± 0.03) than granules and spherules. Once certain structure-dependent control over release is attained (EC coated spherules shows 10% reduction in burst release (BR) than uncoated spherules showing a release of 80-91%) the predictability is achieved and Design of space (DOS) by DOE (CE-70.14%and CPC-200% and DR-61.54%) is established. The results of DOE to experimentally validated results were within 20% deviation. The aspirin is changing its crystal structure by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) from Form-I to Form-II showing polymorphism inside the drug reservoir with respect to the process. This CE and CPC approach in DOE can be used for delivery system design of other labile drugs similar to aspirin in emergency situations.