Emergency red cell exchange for the management of acute complications in sickle cell disease: Automated versus manual.

BACKGROUND: Red blood cell exchange is the cornerstone of the management for acute complications of sickle cell disease. It improves anaemia and improvesperipheral tissue oxygen delivery while at the same time reduces the proportion of circulating sickle erythrocytes. Even though automated red cell exchange is very effective in rapidly lowering the Hb S level, 24-h availability is currently not feasible for most specialist centres including our own. OBJECTIVE: Here, we describe our experience using both automated and manual red cell exchange for the management of acute sickle cell complications. METHODS: Eighty-six such episodes have been recorded between June 2011 and June 2022 comprising of 68 episodes of automated and 18 episodes of manual red cell exchange. RESULTS: The post procedure Hb S/S + C level was 18% after automated and 36% after manual red cell exchange. The platelet count dropped by 41% and 21% after automated and manual red cell exchange respectively. The clinical outcomes including need for organ support, duration of stay in the intensive care unit and overall length of hospitalisation was comparable between the two groups. CONCLUSION: In our experience, manual red cell exchange is a safe and effective alternative to an automated procedure that can be used while specialist centres are building up their capacity to offer automated red cell exchange for all patients requiring the intervention.

Therapeutic plasma exchange in the management of acute complications of sickle cell disease: A single centre experience.

Sickle cell disease results in systemic inflammation even at steady state and this is accentuated during acute crises. The plasma of affected patients contains several proinflammatory cytokines as well as adhesion molecules and prothrombotic factors. This environment promotes further red cell sickling while many of these substances can cause direct tissue toxicity and end-organ damage. Even though red cell transfusion, whether simple or exchange, is the mainstay of treatment of severe acute complications, addition of therapeutic plasma exchange could potentially provide additional benefit by removing such harmful substances. Here, we describe two cases where therapeutic plasma exchange was used. The first involved a patient with the acute chest syndrome who despite adequate red cell exchange remained significantly hypoxic and in severe pain. We therefore proceeded to perform plasma exchange; this led to rapid clinical improvement and resolution of his symptoms. The second case involved a patient with intractable chest wall pain and impending acute chest syndrome; this patient also had a past history of hyperhaemolysis. The patient underwent therapeutic plasma exchange with very rapid resolution of the pain, avoidance of any respiratory deterioration and full recovery. We also give a brief summary of our previous experience using plasma exchange in patients with sickle cell disease. Plasma exchange was well tolerated with no adverse events in all cases we have treated, led to rapid resolution of pain irrespective of primary indication and in the majority of cases to a favourable clinical outcome.

Complete neurological recovery from fat embolism syndrome in sickle cell disease after sequential red cell exchange transfusion and therapeutic plasma exchange.

Fat embolism syndrome in sickle cell disease is associated with great mortality, while more than half of survivors suffer severe neurological sequelae. Release of fat droplets leads to obstruction of the microcirculation as well as generation of proinflammatory cytokines that can cause direct tissue injury. Red cell exchange transfusion can be life-saving but the addition of therapeutic plasma exchange may further improve outcomes by removing such inflammatory mediators. Here, we describe the case of a 27-year-old male patient with sickle cell anaemia presenting with typical features of fat embolism syndrome including neurological involvement with greatly reduced level of consciousness. MRI of his brain showed multiple widespread microhemorrhages giving the characteristic "star field" pattern but also a cytotoxic lesion of the corpus callosum, known to be the result of direct neurotoxicity by proinflammatory cytokines. The patient underwent emergency red cell exchange transfusion leading only to modest clinical improvement but fully regained consciousness after three cycles of therapeutic plasma exchange. This case highlights the deleterious effect of the hyperinflammatory state characteristic of many sickle cell complications and supports further exploring the potential benefit from plasma exchange as an adjunct to red cell exchange in order to remove proinflammatory cytokines during acute complications of sickle cell disease.

Mortality Rates and autopsy findings in fat embolism syndrome complicating sickle cell disease.

Fat embolism syndrome is a rare but underdiagnosed complication of sickle cell disease associated with high morbidity and mortality. It affects predominantly patients with a previously mild course of their illness and those of non-SS genotypes while there is possibly an association with infection with human parvovirus B19 (HPV B19). Here, we present the mortality rates and autopsy findings of all reported cases to date. A systematic review has revealed 99 published cases in the world literature with a mortality rate of 46%. Mortality varied greatly according to the time of reported cases with no survivors in the 1940s, 1950s or 1960s and no deaths since 2020. 35% of cases had previously undiagnosed sickle cell disease and the latter was only identified at autopsy after developing fat embolism with a fatal outcome. 20% of cases reported after 1986 tested positive for HPV B19 with an associated mortality of 63% whereas in cases that have not documented HPV B19 infection the mortality was 32%. The organs most often staining positive for fat were the kidneys, lungs, brain and heart whereas ectopic haematopoietic tissue was found in 45% of the examined lung specimens.

Pitfalls in Diagnosing Thrombotic Thrombocytopenic Purpura in Sickle Cell Disease.

Thrombotic thrombocytopenia purpura is characterised by microangiopathic haemolytic anaemia and red cell fragmentation on the peripheral smear, neurological involvement and thrombocytopenia. Diagnosis in the context of sickle cell disease can be challenging due to the inherent haemolytic state and the multitude of other associated complications of the latter. Specifically, fat embolism syndrome characterised by respiratory failure, neurological impairment and thrombocytopenia can be misdiagnosed this way. Confirmation of a diagnosis of thrombotic thrombocytopenic purpura requires demonstration of very low levels (<10%) of the metalloproteinase ADAMTS13 which in fat embolism syndrome is normal. Existing scoring systems used to estimate the pre-test probability for thrombotic thrombocytopenic purpura cannot be applied in patients with sickle cell disease due to the chronic underlying haemolysis. Here, we analyse the diagnostic approach in published cases of thrombotic thrombocytopenic purpura affecting patients with sickle-cell disease. The vast majority of cases were characterised by severe respiratory failure before any other manifestation, a feature of fat embolism syndrome but not of thrombotic thrombocytopenic purpura, and all received red cell transfusion prior to receiving therapeutic plasma exchange. Despite the potential overestimation of the pre-test probability using the existing scoring systems, a large number of cases still scored low. There were no cases with documented low ADAMTS13. In the majority this was not tested, while in the 3 cases that ADAMTS13 was tested, levels were normal. Our review suggests that due to many overlapping clinical and laboratory features thrombotic thrombocytopenic purpura may be erroneously diagnosed in sickle cell disease instead of other complications such as fat embolism syndrome and confirmation with ADAMTS13 testing is essential.

Rate of Dental Extractions in Patients with Sickle Cell Disease.

BACKGROUND: Sickle cell disease is an inherited disorder associated with chronic haemolysis and anaemia, recurrent episodes of pain and potentially multisystem end-organ damage. A lot less is known about the dental health of these patients. AIMS: To explore the incidence of severe dental disease leading to dental extraction in our sickle cell population. PATIENT/METHODS: We undertook an audit looking at the rate of dental extractions, as a composite marker of severe dental disease, among sickle cell patients over a 3-month period. The patients were unselected and approached during routine assessments. We analysed both clinical and laboratory data to look for possible associations between dental disease and sickle cell characteristics. RESULTS: 177 patients were interviewed between February 2022 and April 2022. Overall, 71% of the patients had at least one dental extraction with a median number of teeth extracted of three and a median age at first extraction of 26. More than half of the patients stated that they do not have regular dental check-ups. There were no significant associations with the severity of sickle cell phenotype, baseline Hb or markers of haemolysis. CONCLUSION: A large number of patients with sickle cell disease require dental extractions at a relatively young age. The lack of any correlation with disease severity suggests that poor engagement with dental services and the underestimation of the importance of dental health are the main factors behind the increased prevalence of severe dental disease. Actively enquiring about dental problems should be part of any routine consultation with these patients, both in primary and specialist care.