Skip to content

Member Log In

Sickle Cell Disease and Related Hemoglobinopathies

Sickle cell disease and related hemoglobinopathies
Objectives
  1. Describe different combinations of normal and abnormal hemoglobins and their phenotypic expression
  2. Describe the pathophysiology of vasooclusion secondary to hemoglobinopathies
  3. Define and describe hand-foot syndrome
  4. Describe features of osteomyelitis secondary to sickle cell disease and its differentiation from bone infarct
  5. Describe features of avascular necrosis of bone associated with sickle cell disease
  6. Discuss the complication rate of orthopaedic surgery for problems secondary to sickle cell disease
  7. Describe the major non-orthopaedic problems associated with sickle cell disease

Discussion
Sickle cell disorders are prevalent and a frequent cause of orthopaedic admissions. Hemoglobin S results from an abnormality of the beta-globulin gene on chromosome 11. The gene for hemoglobin S is common in the African and African-American race; estimated as being present in 8% of the African-American population. Hemoglobin C results from a different amino acid substitution on the same gene. Patients homozygous for hemoglobin S have sickle cell disease; patients with hemoglobin S and C have SC disease. The severity of disease in S-thalassemia is variable, depending on the ability to synthesize hemoglobin A. Patients who synthesize no hemoglobin A have a course similar to SS disease, this category is referred to as S-beta( 0) thalassemia. Those who synthesize some hemoglogbin A S-beta(+) thalassemia, have a course similar to SC disease, which is not as severe.

Low oxygen tension polymerizes the hemoglobin S molecule, distorting the erythrocyte and making it more fragile. At the same time, sickle cells are more viscous, predisposing to an ability to occlude small vessels. This is the basis for virtually all the problems related to sickle cell disease. Obviously, there is considerable variation in severity of this phenomenon in the family of hemoglobinopathies related to sickle cell disease, as indeed there is variation in those with homozygous sickle cell disease.

Non-orthopaedic conditions include cardiomegaly, anemia, hepato and splenomegaly, leg ulcers, priapism, and gallstones. Pubertal growth and skeletal maturation are delayed. The major orthopaedic complications of the sickle hemoglobinopathies are bone infarct, osteomyelitis, and avascular necrosis of the femoral and humeral heads. Bone infarct of the hand and/ or foot is common in the first two years of life, presenting as swelling and pain and fever below 38 degrees. Radiography demonstrates initial soft tissue swelling, followed by periosteal reaction and bone lysis. Salmonella osteomyelitis has been reported concomitantly with hand-foot syndrome, also known as dactylitis.

The most frequent cause for admission in children with sickle cell disease is extremity pain, with a differential diagnosis of infarct versus osteomyelitis. A great deal of effort can be expended trying to differentiate between the two. Recent reports favor gadolinium enhanced MRI and ultrasound as diagnostic aids, as differentiation can be difficult. Subperiosteal fluid of greater than 10mm was almost always associated with osteomyelitis. Children with frequent bone infarcts are not surprisingly more predisposed to osteomyelitis. Nevertheless, a study of admissions to a large children's hospital revealed that only 1.6% of admissions for musculoskeletal pain were identified as being secondary to osteomyelitis. Staphylococcus and salmonella have predominated as the major offending organism in larger series, both are common.

Avascular necrosis is also common, with an overall prevalence of 9.8% in the hip in a study of 2890 patients. Those with Ss disease and alpha-thalassemia were at greatest risk. Children with onset during the middle years tend to have a better outcome than those affected shortly before skeletal maturity, presumably because of greater time to remodel. Results of total hip and shoulder arthroplasties have not been good, with a high complication rate. A study of complications following orthopaedic procedures on patients with sickle cell disease revealed a serious complication rate of 67%, the most two common complications were excessive blood loss and acute chest syndrome.

References
  1. Acurio MT, Friedman RJ. Hip arthroplasty in patients with sickle-cell haemoglobinopathy. Journal of Bone & Joint Surgery -British Volume 1992; 74( 3): 367-71.
  2. Bayoumi RA, Abu Zeid YA, Abdul Sadig A, Awad Elkarim O. Sickle cell disease in Sudan. Transactions of the Royal Society of Tropical Medicine & Hygiene 1988; 82( 1): 164-8.
  3. Bennett OM. Salmonella osteomyelitis and the hand-foot syndrome in sickle cell disease. Journal of Pediatric Orthopedics 1992; 12( 4): 534-8.
  4. Booz MM, Hariharan V, Aradi AJ, Malki AA. The value of ultrasound and aspiration in differentiating vaso-occlusive crisis and osteomyelitis in sickle cell disease patients. Clinical Radiology 1999; 54( 10): 636-9.
  5. Dalton GP, Drummond DS, Davidson RS, Robertson WW, Jr. Bone infarction versus infection in sickle cell disease in children. Journal of Pediatric Orthopedics 1996; 16( 4): 540-4.
  6. David HG, Bridgman SA, Davies SC, Hine AL, Emery RJ. The shoulder in sickle-cell disease. Journal of Bone & Joint Surgery -British Volume 1993; 75( 4): 538-45.
  7. Epps CH, Jr., Bryant DDd, Coles MJ, Castro O. Osteomyelitis in patients who have sickle-cell disease. Diagnosis and management. Journal of Bone & Joint Surgery - American Volume 1991; 73( 9): 1281-94.
  8. Greene WB. Diseases related to the hematopoietic system. In: Morrissy RT, Weinstein SL, editors. Pediatric Orthopaedics. Philadelphia: Lippincott-Raven; 1996. p. 345-91.
  9. Karayalcin G, Rosner F, Kim KY, Chandra P, Aballi AJ. Sickle cell anemia-clinical manifestations in 100 patients and review of the literature. American Journal of the Medical Sciences 1975; 269( 1): 51-68.
  10. Milner PF, Kraus AP, Sebes JI, Sleeper LA, Dukes KA, Embury SH, et al. Sickle cell disease as a cause of osteonecrosis of the femoral head. New England Journal of Medicine 1991; 325( 21): 1476-81.
  11. Milner PF, Kraus AP, Sebes JI, Sleeper LA, Dukes KA, Embury SH, et al. Osteonecrosis of the humeral head in sickle cell disease. Clinical Orthopaedics & Related Research 1993( 289): 136-43.
  12. Moran MC, Huo MH, Garvin KL, Pellicci PM, Salvati EA. Total hip arthroplasty in sickle cell hemoglobinopathy. Clinical Orthopaedics & Related Research 1993( 294): 140-8.
  13. Sadat-Ali M. Avascular necrosis of the femoral head in sickle cell disease. An integrated classification. Clinical Orthopaedics & Related Research 1993( 290): 200-5.
  14. Sadat-Ali M, Ammar A, Corea JR, Ibrahim AW. The spine in sickle cell disease. International Orthopaedics 1994; 18( 3): 154-6.
  15. Stevens MC, Maude GH, Cupidore L, Jackson H, Hayes RJ, Serjeant GR. Prepubertal growth and skeletal maturation in children with sickle cell disease. Pediatrics 1986; 78( 1): 124-32.
  16. Styles LA, Vichinsky EP. Core decompression in avascular necrosis of the hip in sickle-cell disease. American Journal of Hematology 1996; 52( 2): 103-7.
  17. Umans H, Haramati N, Flusser G. The diagnostic role of gadolinium enhanced MRI in distinguishing between acute medullary bone infarct and osteomyelitis. Magnetic Resonance Imaging 2000; 18( 3): 255-62.
  18. Vichinsky EP, Neumayr LD, Haberkern C, Earles AN, Eckman J, Koshy M, et al. The perioperative complication rate of orthopedic surgery in sickle cell disease: report of the National Sickle Cell Surgery Study Group. American Journal of Hematology 1999; 62( 3): 129-38.
  19. Wright J, Thomas P, Serjeant GR. Septicemia caused by Salmonella infection: an overlooked complication of sickle cell disease [see comments]. Journal of Pediatrics 1997; 130( 3): 394-9.

See Also

Physician Education

Annual Meeting

Annual Meeting Location May 16-19, 2012 in Denver, CO

Meeting Archives

Past Annual Meeting Location

Parents & Patients

Patient photos

Find a doctor