Transfusion therapy for anemia

Article written and reviewed by Dr Luca Moretti

Transfusion therapy is an essential resource in the treatment of anemia in all its forms when the severity of the clinical presentation, the acute nature of symptoms or refractoriness to other treatments makes rapid restoration of oxygen-carrying capacity necessary. Although the fundamental purpose of blood-component transfusion is temporary correction of the red-cell deficit, its use entails clinical, ethical and organizational implications that require thorough knowledge of the pathophysiologic mechanisms of anemia, indications, possible complications and risk-prevention strategies.

Red blood cell transfusion, now based predominantly on the use of packed red blood cells, is not an etiologic treatment for anemia but a replacement measure intended to rapidly correct inadequate red-cell function while the underlying cause is being treated or when it cannot otherwise be corrected. The modern approach to transfusion therapy is individualized, with careful assessment of the balance between benefits and risks according to clinical condition, age, comorbidities and the characteristics of the anemia itself.

Indications and principles of transfusion therapy in anemia

The use of transfusion in the treatment of anemia should always be guided by an integrated clinical assessment that considers not only laboratory parameters but especially the symptomatic presentation, the rate at which anemia developed and the risk of ischemic events related to inadequate tissue oxygen delivery. A transfusion threshold should never be regarded as an absolute value, but rather as a reference to be adjusted to individual needs. In hemodynamically stable hospitalized adults, the 2023 AABB guidelines recommend considering a restrictive strategy with transfusion when hemoglobin is <7 g/dL; approximate thresholds of 7.5 g/dL may be chosen in cardiac surgery and 8 g/dL in orthopedic surgery or in patients with preexisting cardiovascular disease. These values do not automatically apply to active major hemorrhage or other settings in which clinical assessment predominates. In hospitalized patients with acute myocardial infarction, the 2025 AABB guideline instead suggests a liberal strategy when hemoglobin is <10 g/dL (conditional recommendation, low-certainty evidence), while still integrating the decision with the clinical context.

In patients with acute anemia, for example during massive hemorrhage or in the perioperative setting, sudden loss of red-cell mass can rapidly compromise perfusion and oxygenation of vital tissues. In these circumstances, transfusion may be lifesaving because it rapidly restores oxygen-carrying capacity; prevention of hemorrhagic shock also requires control of the bleeding source and appropriate hemostatic and volume resuscitation.

In chronic anemia, assessment is often more complex: the body develops progressive adaptive mechanisms, such as increased cardiac output, reduced hemoglobin affinity for oxygen and fluid retention, which can permit tolerance of very low hemoglobin levels without obvious symptoms. However, the onset of signs of myocardial distress such as angina or worsening dyspnea, neurologic symptoms such as confusion or dizziness, or cardiopulmonary or ischemic decompensation attributable to anemia may strengthen the indication for transfusion even when hemoglobin values are not extremely low. Worsening renal failure, in isolation, is not an independent indication for transfusion.

It is also essential to consider the rate of onset of anemia: a gradual reduction in hemoglobin is generally better tolerated than rapid loss, which leaves less time for physiologic adaptation and increases the risk of acute events. The presence of cardiovascular or pulmonary disease further reduces tolerance of anemia, making transfusion more likely to be required.

In addition to the absolute hemoglobin value, the transfusion decision should integrate factors such as:

• the patient's age and overall frailty,
• the presence of signs or symptoms of inadequate tissue oxygenation,
• the dynamic trend of hematologic values,
• comorbidities and the risk of organ decompensation,
• the presence of active bleeding.

The central principle of transfusion in anemia therefore remains individualization, with continuous attention to avoiding unnecessary transfusions because every unit of blood carries biological and immunologic risk.

Selection and characteristics of blood components

Transfusion therapy for anemia is based almost exclusively on packed red blood cells, which represent the standardized and safe form of red-cell administration. Preparation, storage and selection of blood components follow strict criteria designed to maximize efficacy and minimize risk.

Packed red blood cells are obtained by separating donated whole blood or by apheresis, with removal of most plasma; leukoreduction, when applied, is a specific treatment of the blood component. This process concentrates the red-cell component, reducing the risk of volume overload and immunologic reactions related to leukocyte antigens or residual plasma proteins. Leukoreduction, currently mandatory in many countries, significantly reduces the incidence of febrile nonhemolytic reactions, immunization against leukocyte antigens and transmission of some infectious agents such as cytomegalovirus.

In situations defined by guidelines, rather than generically in all immunocompromised patients, neonates or transplant candidates, irradiated blood components are used to prevent transfusion-associated graft-versus-host disease; washed red cells are instead reserved mainly for specific allergic indications or indications related to IgA deficiency.

Administration of plasma or platelets is considered when there are specific concomitant indications, such as coagulopathy for plasma or thrombocytopenia/platelet dysfunction for platelets, and is not a treatment for correction of anemia alone.

An essential consideration is ABO and Rh compatibility between donor and recipient, which drastically reduces the risk of acute hemolytic reactions. In emergencies, uncrossmatched group O packed red blood cells may be used: O negative should be prioritized for children and people with reproductive potential, whereas O positive may be appropriate for other adults according to local transfusion protocols.

Pretransfusion management and patient safety

The pretransfusion phase plays a central role in ensuring procedural safety and preventing complications.
Before every transfusion, a careful clinical assessment is essential, including collection of the patient's transfusion history, investigation of any previous adverse reactions, the presence of irregular antibodies and analysis of comorbidities that may increase the risk of complications, such as heart failure, renal failure and immunocompromised states.

Blood-group determination (ABO and Rh) is performed according to international standards, often on two separate samples, to avoid identification errors. Irregular red-cell antibody screening is performed at the same time and is particularly important in multiply transfused patients, women of childbearing potential and patients with previous immune hemolytic events. When irregular antibodies are present, selection of a compatible blood component may require additional testing and more time.

A crucial step is the crossmatch, the compatibility test between the patient's serum and the donor's red cells. This test can identify incompatibilities not detected by serologic typing alone and reduce the risk of acute hemolytic reactions, one of the most serious transfusion complications. In absolute emergencies, crossmatching may be abbreviated, but this choice should always be supported by careful assessment of the benefit-risk balance.

Informed consent is another essential step: the patient, or legal representative when necessary, should be adequately informed about the benefits, risks, available alternatives and possible complications of transfusion. Careful documentation of consent protects both the patient and healthcare professionals.

Transfusion administration and monitoring

Performing a transfusion requires strict application of operating protocols, with every phase designed to ensure maximum safety and prompt identification of any adverse reaction.
After all pretransfusion checks have been completed, the procedure begins by verifying the patient's identity and matching the data in the clinical documentation with those on the blood-component unit. This step is crucial to prevent errors with potentially very serious consequences, such as administration of incompatible blood.

Packed red cells are transfused through appropriate venous access and a standard filter designed to retain clots and macroaggregates. The standard filter does not specifically prevent microembolism or inflammatory reactions.

The infusion rate is individualized according to the clinical condition. In patients at risk of volume overload, slower infusion, split units and close monitoring may be used; the blood component is not routinely "diluted", and transfusion must be completed within the interval specified by local procedures, generally no more than 4 hours.

Clinical monitoring must be continuous: temperature, blood pressure, heart rate and respiratory rate should be measured before starting, after the first 15 minutes, when most acute reactions manifest, and then at regular intervals until the end of the infusion and after completion. Staff must be trained to recognize early signs of adverse reactions, such as fever, chills, urticaria, back pain, dyspnea, tachycardia, hypotension or any other atypical symptom.
If any reaction is suspected, the transfusion should be stopped immediately and protocols for management of transfusion reactions activated.

Post-transfusion management and follow-up

The period after transfusion requires particular attention to early recognition of both immediate and delayed complications.
After the infusion is completed, observation and vital-sign monitoring should follow the clinical condition and local procedure; there is no universal mandatory observation interval of 30 to 60 minutes. Patients should receive instructions about symptoms that may occur after leaving.

In the following days, hematologic response should be assessed by evaluating the expected increase in hemoglobin and hematocrit: generally, one unit of packed red blood cells raises adult hemoglobin by approximately 1 g/dL, although this may vary because of hemodilution, hemolysis or ongoing bleeding.
Hemolysis markers such as bilirubin, lactate dehydrogenase and haptoglobin should be measured when there is suspicion of a hemolytic reaction, an unexpected hemoglobin response or other clinical or laboratory evidence; they are not mandatory routine monitoring for every asymptomatic multiply transfused patient.

Transfusion documentation must be accurate and complete, recording the type, quantity and number of units transfused, identification data for the units, the presence or absence of adverse reactions and the results of hematologic follow-up. This information is essential for future transfusions and for transfusion-risk management.

Complications of transfusion therapy

Despite advances in the selection and processing of blood components, transfusion still carries a risk of acute and chronic complications that clinicians must know in detail in order to prevent, recognize and manage them promptly.

Acute complications may occur during transfusion or within 24 hours; the specific time window varies according to the type of reaction and includes:

• Acute hemolytic reactions, which may be caused by ABO incompatibility or unidentified irregular antibodies and are often characterized by fever, back pain, chills, hypotension and, in the most severe cases, acute kidney injury and shock.
• Allergic reactions, ranging in severity from simple urticaria to anaphylaxis, more frequent in sensitized patients or after infusion of components containing residual plasma proteins.
• Febrile nonhemolytic reactions, related to cytokines or residual leukocytes and now much less frequent because of routine leukoreduction.
• Transfusion-associated circulatory overload (TACO), particularly in older patients or those with heart failure.
• Transfusion-related acute lung injury (TRALI), rare but potentially fatal, characterized by acute respiratory failure and noncardiogenic pulmonary infiltrates.
• Bacterial contamination of the blood component and transfusion-associated sepsis, rare but potentially rapidly progressive, with fever, chills, hypotension and shock.

Delayed complications or complications associated with repeated transfusions are particularly relevant in patients receiving chronic transfusion regimens, such as those with hereditary anemias, including thalassemia major and sickle cell disease, and myelodysplastic disorders. These patients may develop:

• Secondary hemochromatosis (iron overload), requiring pharmacologic management with chelating agents.
• Alloimmunization against minor red-cell antigens, with increasing difficulty finding compatible blood and a risk of delayed hemolytic reactions.
• Transfusion-transmitted infections, mainly viral or parasitic, with variable and generally delayed onset; residual risk is exceptional in systems with advanced donor selection and screening.

The balance between benefits and risks of transfusion therapy should therefore be assessed carefully, especially in patients who may require repeated transfusions over time.

Strategies for preventing adverse reactions

Prevention of transfusion complications is based on a combination of strict organizational protocols, technological innovations and careful clinical selection.
Universal leukoreduction has drastically reduced febrile nonhemolytic reactions, HLA alloimmunization and the risk of leukocyte-associated CMV transmission, whereas irradiated or washed blood components are reserved for patients at high risk of immune-mediated or allergic complications.
The use of latest-generation serologic and molecular testing has brought transfusion safety to very high levels in industrialized countries.

Continuous education and training of healthcare professionals, appropriate patient information and complete traceability of every procedural phase are essential to minimize adverse events and ensure prompt identification and management of any suspected reaction.

In patients with previous adverse reactions, the mechanism should be defined and prevention targeted, for example with washed blood components for selected recurrent allergic reactions. Routine premedication with corticosteroids or antihistamines does not reliably prevent all transfusion reactions.

Ethical, organizational and management aspects of transfusion in anemia

Although transfusion therapy for anemia is an established and lifesaving procedure, it raises ethical and organizational issues that must be considered carefully in everyday clinical practice. Transfusion involves management of a limited biological resource that is voluntarily donated and entails responsibility both toward the individual patient and toward the community.

One fundamental principle is appropriate prescribing: every transfusion must be justified by a genuine clinical need because unnecessary use of blood creates risks not only for the individual but also for the healthcare system by potentially reducing the availability of blood components for critically ill patients. In this context, recommendations from major scientific societies emphasize restrictive strategies based on integrated clinical and laboratory assessment and careful balancing of risks and benefits.

Patient information and informed consent are ethical and legal cornerstones. Patients should be actively involved in decision making and informed clearly and understandably about risks, benefits, available alternatives and the possible consequences of refusing transfusion. Particular attention should be given to patients who refuse transfusion for religious or cultural reasons, such as Jehovah's Witnesses: in these cases, all available alternative strategies should be implemented, including erythropoietic agents, intravenous iron, intraoperative blood-recovery techniques and multidisciplinary support, while respecting patient autonomy and professional ethics.

From an organizational perspective, management of the transfusion chain requires close collaboration among clinicians, immunohematology and transfusion-medicine services, laboratories and nursing staff. Every phase, from request to administration, must be traceable and documented. Blood-bank information systems, unit coding and computerized data recording reduce the risk of human error and improve overall procedural safety.

Continuing education for healthcare personnel is essential to maintain current knowledge of new technologies, applicable regulations and risk-prevention strategies. A nonpunitive culture of reporting adverse events and near misses contributes to continuous improvement in transfusion quality and safety.

Finally, blood-inventory management and monitoring of national self-sufficiency are critical public-health issues: awareness campaigns and promotion of voluntary, regular, responsible and nonremunerated donation, together with rigorous appropriateness in transfusion use, are indispensable for ensuring the availability of safe blood for all patients who truly need it.

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