Martin Besser

Background/Objective Sickle cell disease (SCD) is a group of inherited health conditions affecting 7.74 million people worldwide. Regular automated red blood cell exchange (aRBCX) transfusions have been shown to improve control and management of SCD compared with manual RBCX (mRBCX). The aim of this study was to estimate the lifetime clinical and economic impact of aRBCX versus mRBCX in two United Kingdom-based populations with SCD (paediatrics initiated aged 5 years and adults initiated aged 38 years) that were clinically indicated for chronic disease-modifying transfusions (DMTs). Methods An individual patient-level simulation model was developed to estimate lifetime quality-adjusted life years (QALYs) and healthcare costs. DMT administration programmes aligned with recommended treatment schedules. Monte Carlo methods determined baseline characteristics and clinical event occurrence. Pragmatic review findings and expert opinion informed model parameters and assumptions. Second-order probabilistic sensitivity analysis (PSA) was performed for 1000 individuals’ lifetimes over 500 iterations. Results Per individual, aRBCX reduced acute clinical events by 19% in both populations versus mRBCX. The time spent receiving chelation therapy reduced by 63 and 32 months for paediatric-initiated and adult-initiated individuals, respectively. Total lifetime DMT costs were reduced by £71,217 and £30,740 for paediatric-initiated and adult-initiated individuals, respectively. Overall, aRBCX increased QALYs and reduced costs by 0.29 and £112,811 in paediatric-initiated individuals and 0.24 and £61,895 in adult-initiated individuals. aRBCX was cost-effective in 100% of PSA iterations for both populations. Conclusion aRBCX shows potential to improve health outcomes and reduce healthcare costs for individuals with SCD initiating a chronic DMT programme.

Iron deficiency (ID) is a major contributor to global disease burden and the leading cause of anaemia. Early detection is important for proactive management, but conventional complete blood count (CBC) screening often fails to identify non-anaemic iron deficiency (NAID) as many individuals maintain haemoglobin and red cell indices within reference ranges. Analysing 153,565 subjects from the INTERVAL, COMPARE and STRIDES studies, we show that CBC screening has only 40.5 % sensitivity for ID detection, falling to 21.9 % for NAID, highlighting a detection gap. CBC analysers generate a wealth of data beyond Electronic Health Record CBC parameters. We demonstrate that artificial intelligence applied to single-cell flow cytometry data from the CBC analyser achieves 83.7 % sensitivity for ID and 79.3 % for NAID. Our findings show that AI can greatly improve detection of a high-prevalence, important condition without changing infrastructure or diagnostic pathways, providing a valuable tool for proactive anaemia management.

COVID-19 has resulted in an exponential increase in patients with severe respiratory failure requiring extracorporeal membrane oxygenation (ECMO). Patients on ECMO regularly require high volumes of blood and blood products but, so far, there has been no comparison of transfusion requirements between COVID-19 and non-COVID-19. Using electronic patient records at two major UK ECMO centres, Royal Papworth Hospital and University Hospital South Manchester, we reviewed the transfusion requirements of patients requiring ECMO between January 2019 to December 2021. A total of 271 patients, including 168 COVID-19 patients were available for analysis. Since COVID-19 patients spent almost twice as long on ECMO (27.1 vs. 14.16 days, p ≤ 0.0001) we indexed transfusion in both groups to days on ECMO to allow comparison. COVID-19 patients required less red blood cells (RBC) per day (0.408 vs. 0.996, p = 0.0005) but more cryoprecipitate transfusions (0.117 vs. 0.106, p = 0.022) compared to non-COVID-19 patients. COVID-19 patients had more than double the mortality of non-COVID-19 patients (47% vs. 20.4%, p = 0.0001) and those who died during the study period had higher platelet transfusion requirements (p = 0.007) than their non-COVID-19 counterparts. Transfusion requirements and coagulopathy differ between COVID-19 and non-COVID-19 patients. The distinctly different transfusion patterns between the two groups remain difficult to interpret, but further investigations may help explain the haematological aspects of severe COVID-19 infection.

Many hematological diseases are characterized by altered abundance and morphology of blood cells and their progenitors. Myelodysplastic syndromes (MDS), for example, are a type of blood cancer manifesting via a range of cytopenias and dysplastic changes of blood and bone marrow cells. While experts analyze cytomorphology to diagnose MDS, similar alterations can be observed in other conditions such as haematinic deficiency anemias, and definitive diagnosis requires complementary information such as blood counts, karyotype and molecular testing. However, recent works demonstrated that computational analysis of bone marrow slides predicts not only MDS or AML but also the presence of specific mutations. Here, we present and make available Haemorasis, a computational method that detects and characterizes white and red blood cells (WBC and RBC, respectively) in peripheral blood slides, and apply it to over 300 individuals with different conditions ( SF3B1 -mutant and SF3B1 -wildtype MDS, megaloblastic anemia and iron deficiency anemia), where Haemorasis detects over half a million WBC and millions of RBC. We then show how these large sets of cell images can be used in diagnosis and prognosis, whilst identifying novel associations between computational morphotypes and disease. We find that hypolobulated neutrophils and large RBC are characteristic of SF3B1 -mutant MDS, and, while prevalent in both iron deficiency and megaloblastic anemia, hyperlobulated neutrophils are larger in the latter. Finally, we externally validate these methods, showing they generalize to other centers and scanners.

Introduction: Patients with COVID‐19 are known to have a coagulopathy with a thrombosis risk. It is unknown whether this is due to a generalized humoral prothrombotic state or endothelial factors such as inflammation and dysfunction. The aim was to further characterize thrombin generation using a novel analyser (ST Genesia, Diagnostica Stago, Asnières, France) and a panel of haematological analytes in patients with COVID‐19.Methods: Platelet poor plasma of 34 patients with noncritical COVID‐19 was compared with 75 patients with critical COVID‐19 (as defined by WHO criteria) in a retrospective study by calibrated automated thrombography and ELISA. Patients were matched for baseline characteristics of age and gender.Results: Critical patients had significantly increased fibrinogen, CRP, interleukin‐6 and D‐dimer compared to noncritical patients. Thrombin generation, in critical patients, was right shifted without significant differences in peak, velocity index or endogenous thrombin potential. Tissue plasminogen activator (tPA), tissue factor pathway inhibitor (TFPI) and vascular endothelial growth factor (VEGF) were significantly increased in the critical versus noncritical patients. Critically ill patients were on haemodiafiltration (31%; heparin used in the circuit) or often received escalated prophylactic low‐molecular weight heparin.Conclusion: These results confirm increased fibrinogen and D‐dimer in critical COVID‐19‐infected patients. Importantly, disease severity did not increase thrombin generation (including thrombin‐antithrombin complexes and prothrombin fragment 1 + 2) when comparing both cohorts; counter‐intuitively critical patients were hypocoaguable. tPA, TFPI and VEGF were increased in critical patients, which are hypothesized to reflect endothelial dysfunction and/or contribution of heparin (which may cause endothelial TFPI/tPA release).

There are unique complications arising from mechanical support devices but some of the long-term systemic haematological complications are indistinguishable from management problems affecting the care of other patients receiving intermediate to long term care in the cardiac ICU. The field of mechanical cardiac assist device (MCAD) is evolving. Despite major changes in design of these devices the most feared haematological complications have remained unchanged, namely haemolysis, pump thrombosis or thromboembolism. This review article gives an overview over the pathophysiology of MCAD related haematological complications, their management and where possible an outlook on future strategies to prevent such complications. The impact of MCAD on blood is discussed, starting with rheology, common pump mechanisms, current and future pump surface coating materials, anatomical considerations of the connection of the circuit and design of the circuit itself. Moreover, the duration of the cardiovascular support, impact of bleeding complications and other patient factors. This article also covers the impact of long term mechanical cardiac support on the properties of platelets, the anticoagulation strategies and a basic guide to the differential diagnosis of haemolysis is reviewed. The section on anaemia considers anaemia in the wider perioperative setting for patients in critical care having undergone cardiac surgery and also discusses transfusion alternatives.

Patients with COVID-19 have a coagulopathy and high thrombotic risk. In a cohort of 69 intensive care unit (ICU) patients we investigated for evidence of heparin resistance in those that have received therapeutic anticoagulation. 15 of the patients have received therapeutic anticoagulation with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH), of which full information was available on 14 patients. Heparin resistance to UFH was documented in 8/10 (80%) patients and sub-optimal peak anti-Xa following therapeutic LMWH in 5/5 (100%) patients where this was measured (some patients received both anticoagulants sequentially). Spiking plasma from 12 COVID-19 ICU patient samples demonstrated decreased in-vitro recovery of anti-Xa compared to normal pooled plasma. In conclusion, we have found evidence of heparin resistance in critically unwell COVID-19 patients. Further studies investigating this are required to determine the optimal thromboprophylaxis in COVID-19 and management of thrombotic episodes.

CSF (Cerebrospinal Fluid) xanthochromia by spectroscopy should not be dismissed in the context of hyperbilirubinemia in a patient with sickle cell anemia. Xanthochromia detected by spectrophotometry offers a vital clue that further invasive diagnosis is required.