Mazyar Javidroozi, MD
Englewood Hospital and Medical Center
Englewood, New Jersey, USA

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See Figure1

Managing Anemia in Specific Populations

Anemia management is a rapidly changing field. New data regarding the clinical effects of anemia on the quality of life, morbidity and mortality have raised awareness about the syndrome and the need to treat anemic patients. In light of concerns about allogeneic blood, including safety, thinking has shifted away from blood transfusion as the first treatment choice and toward pharmaceutical treatment options and blood conservation protocols aimed at minimizing patients’ exposure to allogeneic blood.

Anemia is defined by the World Health Organization (WHO) as a hemoglobin (Hb) level <13 g/dL in men and <12 g/dL in women. While this definition is very helpful, one should not forget that anemia is a complex physiologic entity that extends beyond a simple abnormal laboratory measurement. The body’s response to anemia is influenced by numerous pathophysiologic parameters. Hence, the etiology of anemia and other coexisting conditions are major considerations when deciding on the treatment and mode of management.

Patients Who Refuse Blood

While allogeneic blood transfusions remain one of the mainstay treatment approaches to acute severe anemia, especially in cases of trauma and acute cardiac and noncardiac surgical bleeding, certain populations (mainly those of the Jehovah’s Witness [JW] faith) refuse to receive blood based on their religious beliefs. The pattern of acceptance varies among these “bloodless” patients, and while all JW patients refuse transfusion of whole blood, red blood cells, platelets and plasma, many accept blood fractions such as albumin and factor concentrates (including recombinant factors). Although circulating blood back to the body (as in cases of cardiopulmonary extracorporeal circulation) generally is acceptable if certain conditions are followed, JW patients do not accept preoperative autologous donation, which involves storing blood outside the body for a period of time. Detailed and case-by-case discussion of acceptable products and procedures is critical with these patients and should be initiated as soon as possible to avoid potential problems.

Interestingly, numerous case reports indicate that JW patients have survived Hb levels of 5 g/dL or less. Moreover, reported morbidity and mortality rates in JW patients undergoing surgery are low and comparable to those of freely transfused patients. Extensive experience has led to the practice dubbed bloodless medicine and surgery (BMS). BMS is a strategy to improve patient outcomes without allogeneic blood transfusions. To be successful, such a strategy requires a coordinated multiprofessional team dedicated to optimizing preoperative Hb levels, maximizing hematopoiesis, minimizing blood loss during the stay in the intensive care unit (ICU), and maximizing oxygen delivery to tissues. The team can use these techniques to conserve blood in other patients as well. (see Figure 1)

Not all “bloodless” patients have religious convictions against transfusion. An increasing number of patients refuse blood because of fear of blood-borne infections, adverse reactions and other nonreligious reasons. BMS techniques, combined with detailed and careful explanation of transfusion risks and benefits and the patient’s full understanding of blood refusal, are recommended in these cases.

Although anemia poses a significant challenge in these patients, it undoubtedly has provided us with a unique opportunity to explore and develop treatment approaches other than transfusion. Given the risks and costs of transfusion, many – not only those patients who refuse blood – are likely to benefit from these developments. More prospective outcome data are needed to develop BMS as a standard of care.

Cardiac Patients

As anemia develops, the oxygen-carrying capacity of blood decreases. However, in a normovolemic setting, the net result in tissue oxygenation is offset by adaptive changes in the Hb dissociation curve, tissue oxygen extraction, hemodynamic parameters and microcirculation by recruitment of functional capillaries. In normovolemic anemia, an increase in cardiac output does not result in increased oxygen demand (due to decreased blood viscosity). This is one of the major empensatory mechanisms activated in anemic patients.

Because of this, anemia is especially troublesome in patients with heart problems, possibly increasing morbidity and mortality rates in ischemic heart disease as well as in heart failure and valve disorders. Cardiac patients have limited heartreserve, and compensatory responses to anemia (especially tachycardia) can derange an ailing heart and lead to a crisis. Uncontrolled hemodilution due to cardiopulmonary bypass can further escalate anemia in cardiac surgery patients. Controversy exists as to the optimal and/or lowest acceptable Hb level in this patient population. Published data are inconclusive and fraught with pitfalls and criticism.

Certainly, anemia with accompanying tachycardia is detrimental in this population.
Healthcare professionals should make every effort to avoid unnecessary increases in myocardial oxygen consumption in these patients. In cardiac procedures, if circulating volume is maintained and heart rate is controlled, the low viscosity of blood with its effective “unloading” (as a byproduct of anemia) actually may improve post-obstructive flow and maintain sufficient oxygenation in the diseased coronary circulation. Hence, strong feelings that Hb levels in this group generally should be kept higher than in equivalent patients without coronary artery disease are not supported by convincing evidence.

Therapy for anemia in this population has consisted of allogeneic blood, especially in the face of mild to moderate anemia and evidence of cardiac ischemia. Right or wrong, support of this practice is essentially tradition and conviction. The mounting evidence that treatment with transfusion leads to poorer outcomes is concerning and requires a fresh look at how we manage these cardiac patients. In this complex situation, the detrimental effect of anemia may not be resolved and may be compounded by the use of allogeneic transfusions.

Blood conservation techniques (as depicted in Figure1) also are useful in cardiac surgery patients. For instance, use of a smaller prime volume and smaller circuits in CPB would be an effective way to minimize further Hb drops. Until more data on safe Hb levels in these patients are available, the suggested course of action for cardiac patients involves the combined use of such strategies together with controlled heart rate and more conservative allogeneic blood transfusion.

Anemia in the Elderly

Elderly patients have many of the same issues related to anemia as cardiac patients. As many as three-quarters of all hospitalized patients older than age 65 years are reportedly anemic. Increased age often is associated with a higher prevalence of chronic diseases and, expectedly, anemia of chronic inflammation (previously known as anemia of chronic disease) is the most common cause of anemia in the elderly. An acute variant of anemia of chronic inflammation, known as anemia of critical illness, may be caused by tissue damage and acute inflammatory changes. This is indicated by reduced red blood cell production by the bone marrow due to iron deficiency secondary to iron trapping by macrophages and the inability of the normal bone marrow to increase erythropoiesis.

Anemia in the elderly is multifactorial. Many patients have anemia of chronic inflammation, anemia of nutrition and iron deficiency anemia, which may be due to acute or chronic blood loss. Chronic kidney disease is another cause of chronic anemia seen in the elderly. There is decreased production of erythropoietin as well as ongoing blood loss in patients on hemodialysis. Early studies showed that anemia in elderly patients (as induced by normovolemic hemodilution) might not be associated with increased cardiac output, and the oxygen transport transporting capacity of blood can be reduced significantly. The main compensatory mechanism was found to be increased oxygen extraction in tissues and raised arterial oxygen tension. Anemia is an independent risk factor for mortality and is associated with impaired cognitive function and reduced quality of life. It also can act as a multiplier of coexisting disorders. Evidence suggests that treatment of anemia of chronic inflammation can reduce hospital admissions, improve quality of life and even slow the activity of the underlying chronic disease.

Management of anemia in the elderly largely depends on the presence of anemia-related symptoms and cardiovascular disorders. Although transfusion may be appropriate in significant bleeding episodes, its use at a specific Hb level in the absence of anemia-related symptoms is controversial. On the other hand, many agree that epoetin or darbepoetin alfa generally are appropriate for treatment of anemia in the elderly across a broader range of Hb levels. Adequate iron supply is required for these hematopoietic treatments to be effective, and poor response might be due to the presence of iron deficiency, inflammation, occult blood loss or other conditions.

Even healthy individuals have difficulty supporting erythropoiesis at greater than three to four times the basal rate due to insufficient iron. Oral iron therapy sometimes is insufficient to maintain the increased rate of erythropoiesis; in such situations, intravenous iron therapy is preferred and should be given at one- to two-week intervals to maintain the increased rate of erythropoiesis. Finally, one must not forget to treat the underlying cause of the anemia. For instance, iron deficiency anemia might indicate a malignancy (e.g., colon) and may be the key to early treatment.

Conclusion
Left undetected or untreated, anemia can be an independent predictor for increased mortality and morbidity. However, the traditional approach of “transfusion first” is not necessarily the answer. Fuelled by the concerns patients have regarding the safety of blood, a new approach for minimizing allogeneic blood transfusions has emerged. Blood conservation strategies are sound and recommended for all patients, including the special cases reviewed here.

In addition to preoperative optimization of Hb levels in elective surgeries, avoidance of anticoagulant/antiplatelet agents perioperatively, and blood conservation techniques in the operating room, anemic postoperative and medical patients should be treated with recombinant human erythropoietin, iron, folic acid and vitamin B12. Ascorbic acid also can be administered to facilitate oral iron absorption. These modalities, along with restricted diagnostic phlebotomy, will help manage anemia without unnecessary blood transfusions.

Transfusions should be reserved for only the most critical cases, and the decision to transfuse should be based on evaluation of all relevant clinical parameters, not solely on a single arbitrary Hb level. Anemia and its management remain areas of active debate as the healthcare community continues to investigate the safety and efficacy of all approaches.