ABSTRACT
Autoimmune haemolytic anaemia (AIHA) is rare but described after the SARS-CoV- 2 Pfizer-BioNTech vaccine. We present a case of severe refractory warm AIHA after this vaccine, managed with emergency splenectomy and complement inhibition with eculizumab. A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and AIHA (aged 6 years) presented to his district general hospital with jaundice, dark urine, fatigue and chest discomfort 48 h after the first dose of SARS-CoV- 2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed haemoglobin (Hb) of 70 g/L and bilirubin of 98 mumol/L, which was treated as AIHA. The patient initially responded to prednisolone (1 mg/kg, 60 mg) but subsequently deteriorated and failed to respond to second-line rituximab (375 mg/m2) and two units of packed red blood cells (PRBC). By day 29 the patient had developed life-threatening anaemia culminating in a Hb of 35 g/L (after transfusion), lactate dehydrogenase (LD) of 1293 units/L and bilirubin of 228 mumol/L. This necessitated an immediate transfer to our tertiary centre for specialist support. Further investigations revealed a haptoglobin <0.1 g/L and direct antiglobulin test (DAT) strongly positive for IgG (4+) and negative for C3d. The peripheral blood film showed severe anaemia, nucleated red cells, anisocytosis and spherocytes with no autoagglutination, schistocytes or platelet clumps. Thrombocytopaenia (platelets 49 +/- 109/L) was present. Differentials were ruled out, such as paroxysmal nocturnal haemoglobinuria and heparin-induced thrombocytopaenia. HIV and hepatitis serology were negative, as were adenovirus, cytomegalovirus and Epstein-Barr virus PCR assays. A CT showed splenomegaly of 15.5 cm. Urinalysis found urobilinogen and bilirubin at high concentrations and negative urinary haemosiderin. Together, the investigations were consistent with warm AIHA. On day 29, four units of PRBC were transfused alongside 100 mg methylprednisolone and 1 g/kg IVIG. On day 30 the patient deteriorated despite the escalated treatment: Hb had only increased to 54 g/L, bilirubin was 200 mumol/L and LD was rising. Considering this life-threatening fulminant haemolysis, an emergency splenectomy was performed. This slowed haemolysis but did not completely ameliorate it: by day 33 the patient had received 15 units of PRBC. Thus, eculizumab, a terminal complement pathway inhibitor, was trialled to arrest intravascular haemolysis, alongside rituximab, repeat IVIG 1 g/kg, prednisolone 40 mg and tacrolimus 2 mg. This showed a favourable response, requiring less frequent transfusions and settling haemolysis. This case highlights the rare complication of warm AIHA with the SARS-CoV- 2 Pfizer-BioNTech vaccine, the use of emergency splenectomy for disease control, and the potential of eculizumab for refractory cases.
ABSTRACT
Background and Aims Sarcopenia can be defined as loss of muscle mass, strength and function and has been shown to be associated with increased morbidity and mortality in the adult population. Sarcopenia has been assessed by decreased psoas muscle surface area (PMSA) on Computer tomography (CT) and has been validated in paediatric studies. The impact of Sarcopenia in children with end stage liver disease and oncological conditions is now being recognised. There is scarce literature on the effect of sarcopenia on motor function. CT imaging exposes children to radiation and hence is done in a select group of children at the time of transplant assessment. The aim of this audit was to assess the prevalence of Sarcopenia in children undergoing liver transplant assessment and its relationship on laboratory variables, functional activity and clinical outcomes. Methods Retrospective single centre case review of patients with liver disease undergoing transplant assessment and CT imaging between 2018-2020. Psoas muscle was analysed at the level of L4/L5. The z-Scores were calculated using ageand gender-specific reference values. Sarcopenia was defined as tPMA z score less than -2. We assessed the relationship of Sarcopenia to the biochemical parameters, nutritional status, effect on motor delay/physical abilities (assessed by a range of age appropriate standardised developmental and physical assessments due to COVID pandemic isolation restrictions) and post-transplant complications. Results Thirty one children that met the inclusion criteria were included. Sarcopenia was prevalent in 17 children (6 males: 11 females), with a median age of 3.5 years (SD = 4.9). The common conditions were biliary atresia (n= 11, 35%), hepatoblastoma (n=6, 19%), Autoimmune hepatitis (n=3) etc. Twenty- four patients required additional nutritional support (77% nasogastric feeding, 13% PN and 6% oral supplementation). Mean tPMA z-score was -2.27. Data for the assessment of physical abilities/functional activity was available in 21 children. Impairment of motor skills/physical abilities was overall noted in 14/21 children (67%);9/13 (69%) in the sarcopenic group (6 significant impairment) vs 5/8 (63%) in non sarcopenic group (4 significant impairment). Sarcopenia was associated with increased complications (27 vs 7, p = 0.005) and hypoalbuminaemia (p=0.01), but was not statistically significant (p> 0.05) for the overall length of stay (total and intensive care). Discussion Sarcopenia was commonly identified in children with liver diseases undergoing transplant assessment. Reduction in physical abilities/functional activity was observed in both groups which may be a consequence of loss of muscle mass in children secondary to liver diseases or underlying oncological conditions leading to delay in gross motor skills. Although there was no statistical difference in the duration of stay or impairment of motor skills, complications were higher in the sarcopenic group. Conclusion In this pilot study, sarcopenia is prevalent in children being assessed for liver transplantation and was associated with increased complications. Better non-invasive methods (aside from CT scan) of assessing sarcopenia needs to be developed and validated for the paediatric age group, which would help to better characterise the true incidence and prevalence of sarcopenia in children with chronic liver disease. There is a need to offer nutritional support and assess physical function early in the pre transplant period in order to initiate appropriate physiotherapy interventions to halt and even reverse the progression of sarcopenia.
ABSTRACT
Purpose: The COVID pandemic presents a unique set of challenges during pregnancy including thromboembolic complications, direct placental infection, transplacental transmission, and systemic hyperinflammatory state. The liver is the second most commonly affected organ in COVID infection after the lungs. Mechanisms of liver injury in COVID-19 patients include: direct viral cytopathic effect, drug-induced hepatotoxicity, worsening of underlying liver disease, cytokine storm, hypoxic ischemic injury, and cholangiopathy. Post-COVID cholangiopathy leads to marked cholestasis with ongoing jaundice that persists long after other organs have recovered from infection. Method(s): We describe three infants at Texas Children's Hospital with intrauterine or perinatal COVID exposure with persistent cholestasis and extrahepatic biliary obstruction (mimicking biliary atresia), suggesting cholangiopathy. Result(s): All three patients described in this case series developed liver failure in the setting of low GGT cholestasis with histologic evidence of extrahepatic biliary obstruction, and all three required liver transplantation within the first year of life. Conclusion(s): Though post-COVID cholangiopathy is described in adults in the literature, our series is unique in that it is the first to describe this phenomenon in infancy. Additionally none of our infants had moderate or severe COVID infection but still progressed to advanced liver disease. Though further studies are needed to determine if additional factors are at play, our case series certainly raises the question of if the timing of exposure/infection might play a role in overall prognosis.