of 637 adult patients in our centre had at least one red blood cell (RBC) transfusion in 2158 separate transfusion episodes. Twenty-three DHTR events occurred in 17 patients (13 female) including 15 HbSS, one HbSC and one HbSb 0 thalassaemia, equating to a DHTR rate of 7Á7% of patients transfused. Mean interval from RBC transfusion to DHTR event was 10Á1 AE 5Á4 d, and typical presenting features were fever, pain and haemoglobinuria. Twenty of the 23 (87Á0%) DHTR episodes occurred following transfusion in the acute setting. Notably, 11/23 (47Á8%) of DHTRs were not diagnosed at the time of the event, most were misdiagnosed as a vaso-occlusive crisis. 16/23 DHTRs had 'relative reticulocytopenia', which was more common in older patients. Seven of 23 episodes resulted in alloantibody formation, and three caused autoantibody formation. DHTRs are a severe but uncommon complication of RBC transfusion in SCD and remain poorly recognized, possibly because they mimic an acute painful crisis. Most of the DHTRs are triggered by RBC transfusion in the acute setting when patients are in an inflammatory state.

No abstract

Sickle cell disease (SCD) has evolved into a debilitating disorder with emerging end-organ damage. One of the organs affected is the liver, causing “sickle hepatopathy,” an umbrella term for a variety of acute and chronic pathologies. Prevalence of liver dysfunction in SCD is unknown, with estimates of 10%. Dominant etiologies include gallstones, hepatic sequestration, viral hepatitis, and sickle cell intrahepatic cholestasis (SCIC). In addition, causes of liver disease outside SCD must be identified and managed. SCIC is an uncommon, severe subtype, with outcome of its acute form having vastly improved with exchange blood transfusion (EBT). In its chronic form, there is limited evidence for EBT programs as a therapeutic option. Liver transplantation may have a role in a subset of patients with minimal SCD-related other organ damage. In the transplantation setting, EBT is important to maintain a low hemoglobin S fraction peri- and posttransplantation. Liver dysfunction in SCD is likely to escalate as life span increases and patients incur incremental transfusional iron overload. Future work must concentrate on not only investigating the underlying pathogenesis, but also identifying in whom and when to intervene with the 2 treatment modalities available: EBT and liver transplantation.

SummaryTransfusion therapy is effective in the prevention and treatment of many complications of sickle cell disease (SCD). However, its benefits must be balanced against its risks, including delayed haemolytic transfusion reactions (DHTR). Not only is the relative rate of alloimmunization higher in patients with SCD than in other patient populations, but attendant risks associated with DHTR are even greater in SCD. Clinicians' awareness of DHTR events is poor because symptoms of DHTR mimic acute vaso-occlusive pain and immunohaematology findings are often negative. Transfusions delivered in the acute rather than elective setting appear to confer a higher risk of DHTR. Management of DHTR in SCD depends on the clinical severity, ranging from supportive care to immunosuppression, and optimization of erythropoiesis. DHTR must be considered in any recently transfused patient presenting with acute sickle cell pain. Meticulous documentation of transfusion and immunohaematology history is key. We anticipate an increase in DHTR events in SCD patients with the increasing use of red blood cell transfusion therapy.

Faced with the rapidly evolving COVID-19 pandemic, in March 2020 the UK Government advocated strict self-isolation ('shielding') to protect extremely vulnerable patient groups deemed at high risk of severe SARS-CoV-2 infection. 1 These included children and adults with sickle cell anemia (HbSS). On the advice of the National Hemoglobinopathy Panel (NHP), a multidisciplinary expert advisory group, shielding guidance was extended to all sickle cell disease (SCD) sub-types. Patients with transfusion dependent (TDT) and non-transfusion dependent thalassemia (NTDT), Diamond-Blackfan anemia (DBA) and other rare inherited anemias were also advised to shield if considered at high risk based on agreed clinical criteria. These included severe iron overload, splenectomy, diabetes and cardiac disease. 2 Data provided by two participating centers with the largest thalassemia cohorts indicate up to 30% of patients meet these criteria. In order to evaluate the impact of these measures and inform guidance on the clinical management of COVID-19 and public health policy, a real-time survey of confirmed and suspected cases of COVID-19 in hemoglobinopathy and rare inherited anemia patients was initiated on behalf of the NHP and National Health Service (NHS) England Clinical Reference Group for Hemoglobinopathies. Data were submitted weekly by the 14 Hemoglobinopathy Coordinating Centers (HCC) in England, providing national coverage. HCC were encouraged to follow World Health Organization (WHO) case definitions which include both confirmed and clinically suspected COVID-19. 3 Anonymised data were collected using a standardised report template (see the Online Supplementary Data) and presented weekly to the NHP. Between April 8 and May 6, 2020, a total of 195 confirmed or suspected COVID-19 cases (male: 87; female: 108) were reported. The timeline of case accrual is shown in Figure 1A. The median age was 33 years (range: 6 weeks to 92 years). The distribution according to age and sex is shown in Figure 1B. PCR for SARS-CoV-2 RNA was positive in 99 of 157 (63%) cases tested (Figure 2A). Laboratory confirmation was not available for 34 (17.4%) cases, 31 of which were managed in the community for suspected COVID-19 before widespread testing became available. SCD accounted for 166 (85.1%) of cases reported, with 129 (77.7%) severe (HbSS or HbSβ 0-thalassemia) and 37 (22.3%) mild (HbSC, HbSβ +-thalassemia or HbSE) genotypes (Figures 2A-B). There were 149 adults and 17 children (defined as ≤18 years). Ninety-five (57%) were female. One hundred and twenty-eight (77.1%) SCD patients were admitted to hospital of whom 15 (11.7%), all adults, required non-invasive and/or mechanical ventilation (Figure 2B). The proportion of patients who required critical care was higher in mild genotypes, 8 of 29 (27.6%), than severe genotypes, 7 of 99 (7.1%) (Figure 2B). Sixty of 154 (39%) patients for whom data were available received transfusion (red cell exchange 46 [29%]; simple [top-up] transfusion 15 [10%]) during the COVID-19 episode. The proportion of tr...

A dedicated NBAC clinic and more consistent approach to labour management can help improve VBAC rates. Further targeted counselling towards women with previous malpresentation and/or East Asian descent may further improve VBAC attempt rates.

A 20-year-old black African-Caribbean male (patient 1), known to have sickle cell anemia (SCA) and on hydroxyurea therapy, presented to our hospital with a one day history of chest and lower back pain. He had a history of multiple previous vaso-occlusive crises requiring simple analgesia. At the time of admission, he was afebrile and hemodynamically stable with no abnormalities detected on physical examination. Laboratory values on admission were: hemoglobin (Hb) 117 g/L (usual baseline Hb 110 g/L), hematocrit 37%, white cell count 14.0 3 10 9 /L, reticulocyte count 216 3 10 9 /L, platelets 303 3 10 9 /L, serum creatinine 49 mmol/L, and total serum bilirubin 75 mmol/L.Sickle cell disease (SCD) results from the recessive inheritance of a mutant beta globin gene in which valine is substituted for glutamic acid at position 6 of the beta-globin chain, resulting in the formation of sickle hemoglobin (HbS). Our patient had sickle cell anemia (SCA), the homozygous form (HbSS) and presented with symptoms suggestive of vaso-occlusion, a hallmark feature of SCD. Vaso-occlusion is caused by the deformed sickle shaped red cells blocking microvasculature leading to tissue infarction and acute inflammation, which results in a painful "crisis" for the patient. At this stage, it appeared that our patient was suffering from a simple unprecipitated vaso-occlusive crisis.Patient 1 was commenced on supportive therapy with simple analgesia, oral fluids, and low molecular weight heparin (LMWH) for prevention of venous thromboembolism. The next day he spiked a fever and was started on intravenous antibiotics because of consolidation on the chest X-ray, consistent with acute chest syndrome. On the same day, he reported a lump on his head over the left parietal area, which was fluctuant and initially measured 2 3 4 cm. The patient denied any headache or trauma. Over the next 24 hr, he deteriorated with ongoing fevers and worsening pain requiring escalation to an opiate based "patient controlled analgesia" pain relief. His laboratory parameters also changed significantly: Hb dropped acutely to 54 g/L with a hematocrit of 17%, and reticulocyte count of 69.9 3 10 9 /L; his platelet count dropped to 75 3 10 9 /L with normal coagulation (PT, APTT, fibrinogen). His C-reactive protein (CRP) level reached a peak of 408 mg/L. The hemolysis markers became markedly elevated: lactate dehydrogenase (LDH) reaching a peak of 3,675 IU/L and bilirubin 200 mmol/L (conjugated bilirubin 29 mmol/L). Three units of packed red blood cells were transfused improving his Hb to 84 g/L. The LMWH was stopped in view of the thrombocytopenia. Twelve hours after the acute fall in Hb, it was noted that his scalp lump had increased in size to 6 3 8 cm and the patient then complained of paraesthesia involving the left side of his chin together with a mild frontal headache.Another hallmark feature of SCD is the hemolytic anemia due to the shortened life-span of the irreversibly sickled RBCs. Patient 1's findings were consistent with an acute hemolytic episode but the mass...

Key Points The 3 established HbF genetic loci can be summarized into 1 quantitative variable, g(HbF), in SCD and influence markers of SCD severity. g(HbF) provides a quantitative marker for the genetic component of HbF% variability, potentially useful in genetic and clinical studies in SCD.