Movement Is Life—Optimizing Patient Access to Total Joint Arthroplasty: Anemia and Sickle Cell Disease Disparities

Abstract

Anemia and sickle cell anemia before surgery are often unrecognized medical comorbidities that can and should be addressed. Nearly 6% of the American population meets the criteria for anemia. The elderly, along with patients with renal disease, cancer, heart failure, or diabetes mellitus are more likely to be anemic. The most common form of anemia is due to iron deficiency, which can be easily treated before surgery. Sickle cell anemia occurs in 1 in 365 Black births and 1 in 16,300 Hispanic births, with 100,000 Americans currently living with sickle cell anemia. Patients who have anemia or sickle cell anemia are at increased risk for postoperative complications, including the need for blood transfusions and delayed healing. For those with sickle cell disease, surgeries can precipitate a sickle cell crisis. Patients with sickle cell anemia face barriers in accessing appropriate care; however, these patients can be optimized using preoperative red blood cell transfusions to dilute sickle cells and elevate the hemoglobin level. There should also be careful consideration and monitoring of the pain level of patients with sickle cell anemia in the perioperative period.

Anemia, defined as a hemoglobin (Hgb) level less than 13.5 g/dL in men or less than 12.0 g/dL in women, affects 5.6% of the American population.¹ Anemia is most frequently caused by iron deficiency¹ and has a wide range of clinical implications because of the resultant decreased oxygen-carrying capacity of blood. Common causes of anemia are listed in Table 1.

Table 1 - Common Causes of Anemia

Anemia due to blood loss

Gastrointestinal bleeding

Trauma

Surgery

Heavy menses

Anemia due to deficient red blood cell production

Iron deficiency

Vitamin deficiency (folate, B12)

Sickle cell disease (also classified as extravascular hemolytic anemia)

Bone marrow disorder

Chronic diseases (inflammatory, kidney)

Advanced age

Anemia due to destruction of red blood cells

Hemolytic anemia

Enlarged spleen

Immune system disorder

Prosthetic implant (heart valve, vascular graft)

Sickle cell disease (SCD) is an inherited disorder of red blood cells (RBCs) caused by a mutation in the beta globin gene resulting in an abnormal hemoglobin (HbS) that causes RBCs to sickle under certain conditions² and impairs the delivery of oxygen to tissues. Individuals with SCD often have anemia (sickle cell anemia). The sickle cell gene is most commonly found in individuals from areas where malaria is endemic, given that the trait (one sickle gene and one normal gene) can be protective against the disease. The disorder also affects individuals of Mediterranean, Caribbean, Middle-Eastern, and Asian origin.³ Currently, 100,000 Americans live with sickle cell anemia.⁴

An additional 2.5 million to 3 million Americans live with sickle cell trait (SCT). With SCT, only one allele of the Hgb gene is abnormal in contrast to sickle cell anemia in which both alleles are affected. SCT has not been found to cause statistically significant differences in surgical outcomes in comparison with the unaffected population. However, these individuals are more prone to venous thromboembolism, pulmonary embolism, proteinuria, and chronic kidney disease than the general population.⁵

Importantly, neither anemia nor sickle cell anemia is equally distributed throughout the American population. Anemia is highly associated with other comorbid conditions, such as chronic kidney disease, hypertension, and diabetes, more commonly found in vulnerable communities and in the elderly.⁶ Risk factors are often compounded in at risk groups. For example, 35.6% of 80 to 85-year-old Black women are anemic, which is 6.4 times higher than the population at large.¹ Sickle cell anemia is more common in people of African ancestry (1 in 365 live Black births in the United States) and Hispanic population (1 in 16,300 live Hispanic births in the United States).³ Importantly, preoperative anemia and sickle cell anemia are often overlooked leading to avoidable complications.

Clinical Implications of Anemia and Sickle Cell Anemia Related to TKA and Total Hip Arthroplasty

Preoperative anemia is associated with worse postoperative outcomes and has been found to be a strong predictor of the need for postoperative red cell transfusions.⁷ Specifically, anemia has been found to be associated with an increase in postoperative transfusions, morbidity, and mortality.⁸ Anemia prevalence varies but has been found in up to 46% of the elderly patients undergoing hip fracture surgery.^6,9 The elderly and patients with renal disease, cancer, heart failure, or diabetes are at an increased risk of being anemic,⁶ creating an intersection of multiple risk factors for postoperative complications. These risk factors are also more highly represented in vulnerable communities,^10–15 and comorbidities such as diabetes and heart failure are additionally associated with other comorbidities, including obesity and hypertension, that are independently associated with postoperative complications. This creates an ever-growing cycle of comorbidities that cluster together, creating a constellation of risk factors that do not exist in a vacuum. Currently, many patients proceed with surgery without evaluation and optimization of their Hgb level.⁸

An especially vulnerable group are patients with sickle cell anemia, most of whom are Black. Importantly, sickle cell patients who develop osteonecrosis of the femoral head often require total hip arthroplasty, positioning them as an important population that requires notable preoperative attention. Osteonecrosis of the femoral head is seen in 10 to 40% of the patients with sickle cell anemia.¹⁶ This unfortunately typically represents young, active patients, as opposed to those who suffer from primary osteoarthritis requiring total hip arthroplasty,¹⁷ thus predisposing them to implant failure. Patients with sickle cell disease may have fatty infiltration in the bone marrow of the femur leading to sclerosis and narrowing of the femoral canal. The canal may need to be widened to accommodate even a small femoral implant. An increased likelihood of encountering bony defects is also observed in the acetabulum requiring the use of a multihole cup with screw fixation. These challenges play a role in the increased risk of implant malposition and prosthetic dislocation in patients with SCD.¹⁸ Osteonecrosis caused by sickle cell disease predisposes patients to postoperative complications, such as aseptic cup loosening, delayed wound healing, revision arthroplasty, osteomyelitis, sepsis, longer length of stay, and increased likelihood of readmission,^19–22 as summarized in Table 2.

Table 2 - Postoperative Complications/Risks for Patients With Sickle Cell Anemia

Intraoperative	Acute Postoperative	Subacute/Chronic
Increased blood loss	Longer length of stay	Increased risk of infection
Implant malposition	Venous thromboembolic events	Heterotopic ossification
	Delayed wound healing	Increased risk of dislocation
	Increased risk of readmission	Aseptic cup loosening

Surgery can also predispose to sickle cell formation, possibly acting as a trigger for pain crises, as well as deep vein thrombosis (DVT), pulmonary emboli, acute chest syndrome, and other respiratory complications.^23,24 Importantly, after TJA, these patients have notable improvements in function, mobility, and pain,^17,25 making this a vital surgery for this population.

Identifying effective strategies to optimize the patient with anemia or sickle cell anemia is critical to reduce risk in this population. Various preoperative optimization strategies are currently being conducted by experts in the field of arthroplasty in anemic patients. A multicenter qualitative survey study was conducted to collect evidenced-based strategies and individualized optimization protocols for vulnerable populations (New York University, OrthoVirginia, Hospital for Special Surgery, Yale New Haven Health, Louisiana State University, Brigham and Women's Hospital, and the Hospital of the University of Pennsylvania—Penn Presbyterian). Importantly, there was wide variability in optimization protocols among institutions and members of the surgical care team, both within and across institutions. The following highlights approaches followed by some of these institutions.

Guidelines have been developed for patient blood management which prioritize preoperative detection, evaluation, and management of preoperative anemia. These are patient-centered and evidence-based approaches.^26,27 The goals of these guidelines are to reduce RBC transfusion. This begins with the measurement of Hgb and transferrin levels 28 days before surgery. If levels are abnormal, the underlying cause must be determined. Patients are typically referred to their primary care physician for additional evaluation and treatment. If the cause is iron-deficiency anemia, supplementation over 3 weeks with ferrous sulfate is an effective, inexpensive option to correct anemia. If the cause is B12 deficiency or folate, which is highly associated with primary bariatric surgery (of great relevance to this preoperative population, due to the association of obesity with osteoarthritis), treatment can be with either folic acid for 1 to 4 months or intramuscular B12 shots for 7 days, followed by weekly intramuscular B12 shots for 4 weeks.²⁶ Additional but less common options include erythropoiesis-stimulating agents and short-acting erythropoietin. In this vulnerable population who likely have greater food insecurity and possible malnutrition, it is important to also screen and address malnutrition. Surgeons should work with the patient and their primary care physician to ensure that the patient receives the treatment they need and to identify any barriers that could preclude the patient from addressing this risk factor. For elective orthopaedic procedures, it is recommended that the preoperative Hgb be in the normal range based on sex (for men, 13.5—17.5 g/dL; for women, 12.0—15.5 g/dL)²⁶ at least to a Hgb level of 10 to 11 g/dl.¹⁸

Optimization for patients with sickle cell anemia begins early with ongoing consultation with the patient's hematologist. Early consultations should also include anesthesia, infectious disease, and cardiology because intraoperative hypoxia, hypothermia, acidosis, dehydration, and anemia all contribute to sickle cell formation and ultimately postoperative complications.²⁸ Patients with sickle cell anemia should be admitted to the hospital 1 day before surgery to begin the optimization process early. Patients should receive preoperative RBC transfusions to dilute sickle cells, aiming for a preoperative Hgb level >10 g/dL.²⁹ It is recommended that patients be placed on 1.25× maintenance fluids the night before surgery²⁸ to ensure adequate hydration. Adequate perioperative fluid and blood loss management can also help to mitigate pain crises and acute chest syndrome. Owing to their increased likelihood of DVT/pulmonary emboli events, DVT prophylaxis should be more aggressive than standard patients.²¹ Of utmost relevance is pain control in the postoperative period. Patients with sickle cell disease are frequently denied necessary pain medication because of bias from healthcare providers and undue suspicion of drug-seeking behavior,³⁰ despite their notable pain. Therefore, in the postoperative period, NSAIDs should be combined with analgesics to potentiate their effects and be regularly scheduled to provide adequate pain control.³¹ It is helpful to have a well-outlined, documented analgesic plan before surgery to avoid conflict. There should also be very low threshold to consult infectious disease if there is even low suspicion for infection in the postoperative period.

Summary

Patients with anemia and sickle cell anemia require early optimization. For patients with anemia, the underlying cause must be ascertained and addressed with appropriate supplementation. This requires early measurement of Hgb levels. For patients with sickle cell anemia, early consultation with hematology, anesthesia, infectious disease, and cardiology is of vital importance to ensure the best possible outcome of surgery. Patients should all receive 1.25× maintenance fluids and RBC transfusions to Hgb > 10 g/dL the night before surgery. DVT prophylaxis should be more aggressive and pain control should be an explicit focus.