https://orcid.org/0000-0001-7527-2340
Transfusion provides vital supportive care for patients across many clinical settings, but high-quality evidence is not always available to guide our transfusion-related decision-making. In this case-based How I Treat series, experts offer updates on available evidence and new tools and how they use them in often-challenging clinical scenarios in daily practice. These articles provide practical guidance to help hematologists deliver better and more personalized transfusion support for our patients now and identify important evidence gaps and priorities so that we can improve in the future.
The series includes the following articles:
Jeannie L. Callum, Ronald B. George, and Keyvan Karkouti, “How I manage major hemorrhage”
Stella T. Chou and Jeanne E. Hendrickson, “How I treat challenging transfusion cases in sickle cell disease”
Renske M. van 't Oever, E. Joanne T. Verweij, and Masja de Haas, “How I use noninvasive prenatal testing for red blood cell and platelet antigens”
Helen Frances Savoia, Anna Parakh, and Stefan Charles Kane, “How I manage pregnant patients who are alloimmunized to RBC antigens”
A. P. J. Vlaar, J. J. Zwaginga, and J. C. Wiersum-Osselton, “How I diagnose and treat cardiorespiratory complications of transfusion”
Susan Nahirniak, Veera Nadarajan, and Simon J. Stanworth, “How I treat patients who are refractory to platelet transfusions”
Major hemorrhage occurs in a wide range of contexts, from trauma to gastrointestinal bleeding, surgery, and obstetrics.1 Critical bleeding is one of the commonest causes of early death in these settings, so managing the bleeding is a top priority.2 Timely access to blood components and hemostatic adjuncts such as tranexamic acid, along with surgical, anesthetic, and interventional radiological measures to prevent or stop the bleeding and to conserve the patient’s own blood, can help save lives, reduce risks, and make best use of available blood resources. However, how best we should do this is not always clear. Callum et al outline how major hemorrhage is now typically managed by multidisciplinary teams, using protocols to coordinate delivery of diagnostic (including laboratory and point-of-care testing) and therapeutic elements, and importantly, communication and documentation of interventions and outcomes. Recent trials have informed these protocols, although many aspects of transfusion management in this setting remain to be optimized.3 The authors include tables summarizing key contributors to the hemostatic disturbances in different clinical scenarios and offer practical strategies for optimizing hemostatic management and transfusion support, including vital questions to ask when consulted about a patient with life-threatening hemorrhage.
Transfusion support is also a lifeline for many patients with hemoglobin disorders, such as thalassemia and sickle cell disease; however, it is not without challenges for clinicians, blood services and, of course, patients themselves. Red blood cell top-up or exchange transfusion can be required in a wide range of acute and chronic clinical scenarios and to support allogeneic hematopoietic stem cell transplantation and other cellular or gene therapies. However, a range of transfusion-related complications can and frequently does occur. One of the most problematic in this setting is alloimmunization to red cell antigens, which can lead to hemolytic reactions and hemolytic disease of the fetus and newborn (HDFN).4 Specialized diagnostic support and matched red cells for transfusion, which can be difficult to source, may be required. Antibody evanescence and lack of information on a patient’s prior results and transfusion history can contribute to delayed hemolytic reactions, some with bystander hemolysis.5 Sometimes patients become “untransfusible.” Chou and Hendrickson share their approach to the challenging issues of prevention and management of red cell alloimmunization in a series of cases in patients with sickle cell disease. In the context of enormous red cell antigen diversity, the authors describe how the increasing availability of genotyping can build on conventional crossmatching and extended antigen-matching to provide better-matched blood. They also note the value of national antibody registries to facilitate secure access to accurate, up-to-date information on a patient’s prior transfusion history and improve the safety of transfusion practice.
Alloimmunization in pregnancy to red cell and platelet antigens can result in HDFN and fetal and neonatal alloimmune thrombocytopenia; these can cause major consequences for the baby, such as severe anemia leading to hydrops fetalis and profound thrombocytopenia leading to serious or fatal bleeding, respectively.6,7 These conditions can also affect the health of the mother and limit the possibility of future successful pregnancies. Historically, diagnosis was often delayed and/or required invasive procedures, with their own risks of complications. van 't Oever et al outline how noninvasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma can now provide safe, low-cost testing options with high diagnostic accuracy, early in pregnancy. Starting with fetal RHD and HPA genotyping and now expanded to a wide range of red cell and platelet antigens, NIPT results can be used to identify pregnancies at risk, and guide decision-making for patients and the teams treating them. Like all diagnostic tools, technical and quality considerations are integral to their use, and some challenges remain, which are discussed. Management of pregnancies affected by red cell alloimmunization is further explored by Savoia et al, through cases demonstrating the impact of availability of noninvasive monitoring, considerations for fetal and neonatal transfusion support, and approach to possible future pregnancies.
Cardiorespiratory complications of transfusion are not uncommon, and can be serious and even fatal.8 However, distinguishing between transfusion-associated circulatory overload, transfusion-related acute lung injury, allergic or anaphylactic reactions to transfusion, and other (including non-transfusion–associated) causes of dyspnea and hypoxia can be very difficult. The clinical features overlap, the pathophysiology of these conditions remain incompletely understood, no specific diagnostic tests are routinely available, and so the diagnosis remains clinical—and often uncertain.9,10 There are implications for hospital staff in recognition, documentation, prevention, and management of these events; for blood services in donor selection and product manufacturing; and for hemovigilance and public health reporting and analysis. Vlaar et al explore the limitations of current working definitions of these events, provide a practical approach to the patient at the bedside, and identify priorities for future research.
Refractoriness to platelet transfusion is quite common. In the hematology-oncology setting, patients may be profoundly thrombocytopenic due to disease or therapy (or both), and either actively bleeding or at risk of it, so lack of response to platelet transfusion can be worrying. Accurate diagnosis is key to appropriate management, and the main goal of therapy is to prevent bleeding, with or without an increment following platelet transfusion, although that makes the treating team feel a lot better! There is a lot to learn about this difficult condition to improve practice and outcomes.11 While HLA- or HPA-matched, or “selected,” platelets are commonly used along with other measures, for many patients few matched donors are available.12 Nahirniak et al offer a pragmatic approach. They address the range of immune and nonimmune causes, and patient and blood product factors, which may contribute to platelet refractoriness, also reminding us that HLA-alloimmunization does not always equal lack of clinical response to platelet transfusion. This article thoughtfully considers whether what we do improves outcomes for our patients and the measures we could take to do so, while also optimizing the availability and use of precious platelet supplies.
We hope you will find these articles useful. They richly demonstrate the need to better understand the biologic diversity underpinning these challenging clinical situations, and the importance of collaborations between different clinical and laboratory specialties in supporting patients through them. Of course, transfusion support also depends upon access to a range of (and often highly personalized) blood products, and therefore ultimately depends upon all of us—without community volunteer blood donors, none of this life-saving care would be possible.
