Pertinent Keys To Perioperative Management Of Patients With The Sickle Cell Trait

Although patients with sickle cell trait pose a low risk of experiencing a related pain crisis, these authors discuss careful perioperative measures that can reduce postoperative risks.  

Sickle cell trait (SCT) affects between 2.5 million and four million individuals in the United States.^1,2 The African-American population is primarily affected with a prevalence of six to nine percent and 0.01 to 0.07 percent of the general population include those of Southeast Asian, Hispanic, Arab or Mediterranean descent.^1,3-5 Sickle cell trait results from an abnormal hemoglobin called sickle hemoglobin (HbS) due to a point mutation that causes red cells to sickle when exposed to a low oxygen threshold.  

Sickle cell trait is benign relative to sickle cell disease (SCD) when patients have both recessive alleles. Those with the sickle cell trait rarely experience vaso-occlusive crises. However, there are reports of adverse conditions with sickle cell trait such as exercise collapse leading to rhabdomyolysis and death, and an implication of venous thromboembolism due to renal injury.^6-8 Thus, patients with sickle cell trait still warrant evaluation prior to foot and ankle surgery to identify and lower the risk of postoperative adverse events.

Patients with sickle cell trait could present similarly to those with sickle cell anemia if they are exposed to conditions that favor sickling such as severe hypoxia, dehydration, increased sympathetic outflow, hypothermia/hyperthermia and release of inflammatory cells.⁹ In the surgical scenario, ischemia and hypoxic environments may cause sickle hemoglobin to clog the osseous capillary vessels or other organs including the heart, lungs, and kidneys, resulting in hematuria or rhabdomyolysis.

Increased risks associated with operating on patients with sickle cell disease include vaso-occlusive crisis, acute chest syndrome, post-operative infections and congestive heart failure.^10-20 Those with sickle cell trait do not typically have the severity nor elevated risk level of these potential complications. However, a complete history and workup are necessary to assess the postoperative risks in this patient population.

Important Considerations In the Perioperative Evaluation Of Patients With Sickle Cell Pathology

In the U.S., every state mandates screening of all newborns prior to discharge due to the Sickle Cell Anemia Control Act of 1972.²¹  Unfortunately, estimates suggest only 16 percent of individuals know of their sickle cell trait status.²² Additionally, non-U.S.-born individuals may not be aware of their condition.

A good family history should be sufficient to raise concern that the patient may have sickle cell trait, especially when he or she is a member of or descends from the aforementioned populations that have a higher prevalence of the sickle cell trait. For testing, a simple blood sickling test with electrophoresis will give a percentage of each hemoglobin type.²¹

Any preexisting cardiac and pulmonary complications warrant further cardiac clearance. Depending on the amounts of fluid administered perioperatively, cardiac echography may be helpful to assess the extent of cardiac dysfunction in patients with prior history of heart failure, poor functional status or dyspnea at baseline. See the table “Cardiac And Pulmonary Complications With Sickle Cell Disease.”²³ 

Perioperative measures may mitigate common triggers of acute crisis that include anxiety, emotional stress, infection, dehydration, acidosis, hypoxia, vascular stasis and increased blood viscosity.^24,25 One should consider counseling to calm emotional stress and anxiety about the procedure. If necessary, providers may also consider anxiolytics with caution.

Since intracellular dehydration may trigger sickle hemoglobin polymerization, prolonged preoperative fasting is contraindicated and patients may consider drinking clear fluids up to two to four hours before surgery with anesthesiology consultation agreement.^24-26 In theory, hypotonic fluids decrease red blood cell sickling and are preferable.^27-29 Excessive fluid loading is associated with pulmonary edema and may also precipitate acute chest syndrome.^30,31

The most significant trigger of sickle cell crisis is hypoxia.^24-26 Perioperative oxygen monitoring is imperative in all patients as pulse oximetry does not correlate well with arterial oxygen tension in some patients with sickle cell disease.³² Arterial blood gas confirmation is necessary in hypoxic patients. Postoperatively, incentive spirometry decreases the incidence of atelectasis and acute chest syndrome in the inpatient setting.^30,33

Complications Of Sickle Cell Trait: What You Should Know

Even though sickle cell trait is widely thought of as a benign condition, these patients do have risk for medical and clinical complications. These may include hematuria secondary to renal papillary necrosis, splenic infarction, chronic kidney disease, sudden death due to exertion and asymptomatic bacteriuria.²¹

The typical presentation of a patient with renal papillary necrosis includes gross hematuria and abdominal pain. Prognosis is good in these cases because this condition only affects a single papillary and there is more viable tissue than injured tissue.²¹

Splenic infarction may occur due to low oxygen exposure such as high altitude, dehydration, increased acidity and viscosity in the blood vessels.³⁴ Sickle cell trait has an association with increased chronic kidney disease in the African-American male population.³⁵ The belief is that due to chronic reversible sickling induced by hypoxia in the renal medullae, the renal tubules are subject to constant ischemia and microinfarction, resulting in the release of vasoactive elements that contribute to sclerosis and proteinuria.³⁵

Sudden death due to exertion in these patients has led the National Collegiate Athletic Association (NCAA) to mandate a sickle cell trait screening program that has reportedly identified 2,000 NCAA Division I student-athletes with this trait.³⁶  Researchers suggest that this screening program may prevent seven fatalities, due to a lack of intervention, in this population over a 10-year period.³⁶

People with sickle cell trait have a 54 percent higher rate of exertional rhabdomyolysis.³⁷ Naik and Haywood noted that exertional rhabdomyolysis  was linked to the sudden death of a 19-year-old college athlete, resulting in the college making its sickle cell trait screening program mandatory.³⁸

When A Patient With Sickle Cell Trait Has Foot And Ankle Surgery

A 50-year-old African-American male with a medical history of sickle cell trait and hypertension had a retrocalcaneal exostectomy with partial detachment and reattachment of the Achilles tendon after failure of conservative treatment for insertional Achilles tendinitis.

The patient had no medical or family history of coagulopathies or blood clots, and no underlying cardiac or pulmonary pathology. He did have a past history of some renal insufficiency, which resolved. His hypertension was well-controlled. The patient obtained surgical clearance with a full cardiac workup including an echocardiogram that only revealed right ventricular hypertrophy. A stress test was normal and his cardiologist cleared him for the procedure with minimal risk. A complete metabolic panel and renal function markers were all within normal limits at baseline. Lastly, there was preoperative consultation with the anesthesiology team to coordinate perioperative management. The use of half-normal saline began at 100 mL/hr for one hour prior to surgery with this rate decreasing intraoperatively. The anesthesia team performed popliteal and adductor canal blocks.

We performed the procedure without a tourniquet and with the patient in a prone position. For exposure, we used a posteromedial longitudinal incision over the retrocalcaneal prominence. Due to the severity of the prominence and involvement of the Achilles tendon, we had to reflect more than 75 percent of the Achilles tendon attachment. After resecting the exostosis with osteotomes, we reattached the Achilles tendon to the posterior calcaneus using four absorbable bone anchors. Upon reattaching the Achilles tendon, we performed a gastrocnemius recession to address the remaining equinus contracture. We successfully completed the surgery in less than 60 minutes and placed the patient into a posterior splint.

Postoperatively, the patient related severe pain to the toes on the surgical side, which was not relieved by medication. Pain did not improve after removal of the splint and loosening of the bandaging. The anesthesiology team attempted a second popliteal block with a pump that only slightly improved the level of pain. 

We then admitted the patient for postoperative intravenous pain management. Continued hydration measures half-normal saline at 100 mL/hr. We employed pulse oximetry to assess oxygen perfusion intraoperatively and continued to do so through his admission. Blood work and renal function monitoring demonstrated a slightly decreased glomerular filtration rate, but no hematuria was evident. We also encouraged the use of incentive spirometry postoperatively.

Anticoagulation therapy began with heparin at admission postoperatively and transitioned to low-molecular weight heparin in preparation for the patient’s discharge. Pain levels slowly improved after admission and were well-controlled by the next morning. Clinicians reapplied a posterior splint prior to discharge the next day.

The patient was non-weightbearing postoperatively for six weeks and healed uneventfully with no further pain issues. We kept him on anticoagulation therapy for six weeks. Physical therapy began early at eight weeks postoperatively. At one year post-op, the patient noted regained strength and improved functional status in comparison to his initial presentation.

In Conclusion

While many have long considered sickle cell trait to be an asymptomatic condition, it is not free of additional risk and postoperative complications. A detailed history should include personal and family history of coagulopathies, sickling events and the triggers, and risk of pulmonary or renal disease. Preoperative blood work should also include baseline renal function and hemoglobin/hematocrit levels. Perioperative measures must include hydration measures, perfusion monitoring and anticipation of potential postoperative pain management. Prompt identification of complications associated with sickle cell trait and initiation of treatment will lead to faster recovery and improved patient care.

Dr. Mahajan is a graduate of the McLaren Oakland Hospital in Pontiac, Mich. and is currently in private practice in the southeast Michigan.

Dr. Goldstein is a member of the podiatric surgery faculty at McLaren Oakland Hospital in Pontiac, Mich.

Dr. Husain is the Podiatric Residency Program Director at McLaren Oakland Hospital in Pontiac, Mich. Dr. Husain is in private practice with Great Lakes Foot and Ankle Institute in Rochester, Mich.

1. Naik RP, Smith-Whitley K, Hassell KL, et al.  Clinical outcomes associated with sickle cell trait: a systematic review. Ann Intern Med. 2018;169(9):619-627.
2. Little I, Vinogradova Y, Orton E, Kai J, Qureshi N. Venous thromboembolism in adults screened for sickle cell trait: a population-based cohort study with nested case-control analysis. BMJ Open. 2017;7(3):e012665.
3. Grant AM, Parker CS, Jordan LB, et al. Public health implications of sickle cell trait: a report of the CDC meeting. Am J Prev Med. 2011;41(6S4): S435-439.
4. Ojodu J, Hulihan MM, Pope SN, Grant AM. Incidence of sickle cell trait- United States, 2010. MMWR Morb Mortal Wkly Rep.  2014;63(49): 1155-1158.
5. Gibson JS, Rees DC. How benign is sickle cell trait? EBioMedicine. 2016;11:21-22.
6. Jones SR, Binder RA, Donowho EM. Sudden death in sickle-cell trait. N Eng J Med. 1970;282(6):323-325.
7. Harmon KG, Drezner JA, Klossner D, Asif IM. Sickle cell trait associated with a RR of death of 37 times in national collegiate athletic association football athletes: a database with 2 million athlete-years as the denominator, Br J Sports Med. 2012;46(5):325-330.
8. Goldsmith JC, Bonham VL, Joiner CH, et al. Framing the research agenda for sickle cell trait: building on the current understanding of clinical events and their potential implications. Am J Hematol. 2012;87(3):340-346.
9. Ashorobi D, Ramsey A, Bhatt R. Sickle cell trait. StatPearls. Available at: http://ncbi.nim.nih.gov/books/NBK537130/. Published July 18, 2020. Accessed August 21, 2020.
10. Holzmann L, Finn H, Lichtman HC, Harmel MH. Anesthesia in patients with sickle cell disease: a review of 112 cases. Anesth Analg. 1969;48(4):566-572.
11. Patterson RH, Wilson H, Diggs LW. Sickle-cell anemia: a surgical problem. II. Further observation on the surgical implications of sickle-cell anemia. Ann Surg. 1950;28(2):393-403.
12. Brown RA. Anaesthesia in patients with sickle-cell anaemia. Br J Anaesth. 1965;37(3):181-188.
13. Shapiro ND, Poe MF. Sickle-cell disease: an anesthesiological problem. Anesthesiology. 1955;16(5):771-780.
14. Oduro KA. Anaesthesia and sickle cell haemoglobin. Br J Anaesth. 1973;45(1):123.
15. Oduro KA, Searle JF. Anaesthesia in sickle-cell states: a plea for simplicity. Br Med J. 1972;4(5840):596-598.
16. Searle JF, Anaesthesia in sickle cell states: a review. Anaesthesia 28:1, 48-58, 1973.
17. Firth PG, Head CA. Sickle cell disease and anesthesia. Anesthesiology. 2004;101(3):766-785.
18. Vichinsky EP, Neumayr LD, Haberkern C, et al. The perioperative complication rate of orthopedic surgery in sickle cell disease: report of the national sickle cell surgery study group. Am J Hematol. 1999;62:3, 129-138.
19. Koshy M, Weiner SJ, Miller ST, et al. Surgery and anesthesia in sickle cell disease. Cooperative study of sickle cell diseases. Blood. 1995;86(10): 3676-3684.
20. Buck J, Davies SC. Surgery in sickle cell disease. Hematol Oncol Clin North Am. 2005;19(5):897-902.
21. El Ariss AB, Younes M, Matar J, Berjaoui Z. Prevalence of sickle cell trait in the southern suburb of Beirut, Lebanon. Mediterr J Hematol Infect Dis. 2016;8(1):e2016015.
22. Creary S, Adan I, Stanek, J, et al. Sickle cell trait knowledge and health literacy in caregivers who receive in-person sickle cell trait education. Mol Genet Genomic Med. 2017;5(6):692-699.
23. Adjepong KO, Otegbeye F, Adjepong YA. Perioperative management of sickle cell disease. Mediterr J Hematol Infect Dis. 2018;10(1): e2018032.
24. Noguchi CT, Schechter AN, Rodgers GP, Sickle cell disease pathophysiology. Baillière’s Clin Haematol. 1993;6(1): 57-91.
25. Manwani D, Frenette PS. Vaso-occlusion in sickle cell disease: a pathophysiology and novel targeted therapies. Blood. 2013;122(24):3892-3898.
26. Kato GJ, Hebbel RP, Steinberg MH, Gladwin MT. Vasculopathy in sickle cell disease: biology, pathophysiology, genetics, translational medicine, and new research directions. Am J Hematol. 2009;84(9):618-625.
27. Guy RB, Gavrilis PK, Rothenberg SP. In vitro and in vivo effect of hypotonic saline on the sickling phenomenon. Am J Med Sci. 1973;266(4):267-277.
28. Carden MA, Fay M, Sakurai Y, et al. Normal saline is associated with increased sickle cell red cell stiffness and prolonged transit times in a microfluidic model of the capillary system. Microcirculation. 2017;24(5):e12353.
29. Carden MA, Fay ME, Lu X, et al. Extracellular fluid tonicity impacts sickle red blood cell deformability and adhesion. Blood. 2017;130(24): 2654-2663.
30. Vichinsky EP, Styles LA, Colangelo LH, Wright EC, Castro O, Nickerson B. Acute chest syndrome in sickle cell disease: clinical presentation and course. Cooperative study of sickle cell disease. Blood. 1997;89(5):1787-1792.
31. Haynes J, Allison RC. Pulmonary edema: complication in the management of sickle cell pain crisis. Am J Med. 1986;80(5):833-840.
32. laisdell CJ, Goodman S, Clark K, Casella JF, Loughlin GM. Pulse oximetry is a poor predictor of hypoxemia in stable children with sickle cell disease. Arch Pediatr Adolesc Med. 2000;154(9):900-903.
33. Bellet PS, Kalinyak KA, Shukla R, Gelfand MJ, Rucknagel DL. Incentive spirometry to prevent acute pulmonary complications in sickle cell diseases. N Engl J Med. 1995;333(11):699-703.
34. Yanamandra U, Das R, Malhotra P, Varma S. A case of autosplenectomy in sickle cell trait following an exposure to high altitude. Wilderness Environ Med. 2018;29(1):85-89.
35. Naik RP, Derebail VK, Grams ME, et al. Association of sickle cell trait with chronic kidney disease and albuminuria in african americans. JAMA. 2015;312(20):2115-2125.
36. Tarini BA, Brooks MA, Bundy DG. A policy impact analysis of the mandatory NCAA sickle cell trait screening program. Health Serv Res. 2012;47(1 Pt 2):446-461.
37. Nelson DA, Deuster PA, Carter R, Hill OT, Wolcott VL, Kurina LM. Sickle cell trait, rhabdomyolysis, and mortality among US army soldiers. N Engl J Med. 2016;375(5):435-442.
38. Naik RP, Haywood C. Sickle cell trait diagnosis: clinical and social implications. Hematology Am Soc Hematol Educ Program. 2015;2015(1):160-167.