Complications

• chronic sickle pain
  • is defined as an episode of pain of greater than 3-6 months
  • often caused by orthopaedic conditions such as avascular necrosis, vertebral collapse, or chronic arthritis (1)
    
    
• bones and joints
  • vaso occlusive episodes resulting in infarcts are often seen in bones and joints
  • "fish mouthing" (abnormalities of the vertebrae) are characteristic of SCD
  • growth disturbances and osteopenia may occur due to hyperplasia of the bone marrow
  • avascular necrosis of hip and shoulder causes chronic pain (particularly in adults) (1)
  • SCD patients also are at an increased risk of infection and failure of prosthesis
  • osteomyelitis is also more common (may be difficult to differentiate from infarction)
    
    
• impaired nutrition and growth
  • growth impairment becomes evident after 6 months of age and is usually caused by
    • decreased absorption of nutrients and/or
    • an increase in the metabolic rate
    • poor appetite associated with febrile or painful episodes
  • a delay in puberty may be seen - by about 6 months in HbSC patients and by 2-3 years in HbSS patients
  • pituitary and/or primary gonadal deficiencies may be seen in patients who are on long-term transfusion programmes (due to iron overload)
    
    
• neurological conditions
  • epilepsy
    • seizures occur in 10-15% of patients with SCD (10 times the incidence of general population)
    • associated with cerebrovascular disease and silent infarction o chronic headaches
    • common in SCD patients
    • may be secondary to migraine, benign intracranial hypertension, hypertension, sleep apnoea or tension (2)
  • cognitive impairment
    • mild cognitive impairment may be seen in children with silent infarcts (seen on MRI scan) (3)
    • in adults evidence of cognitive abnormalities is thought to be due to covert infarctions
      
      
• chronic lung disease (4)
  • chronic sickle lung disease
    • may be associated with a history of acute chest syndrome or with low level pulmonary damage which occurs during painful episodes (5)
    • divided according to the presence of chest pain, degree of hypoxia, chest X-ray and lung function test findings
  • obstructive sleep apnoea
    • common in SCD and may be caused by tonsillar hypertrophy or other causes of sleep disordered breathing
    • increased painful episodes and increased neurological events can also be associated with overnight hypoxia
  • pulmonary hypertension
    • one third of adults with SCD will develop pulmonary hypertension
    • is thought to be due to chronic haemolysis which releases free haemoglobin, causing a deficiency of nitric oxide. This in turn leads to acute and chronic pulmonary vasoconstriction
    • both chronic sickle lung disease and pulmonary hypertension are predominantly seen in adulthood although it is increasingly being recognised in older children and adolescents
      
      
• chronic leg ulcers (6)
  • relatively uncommon in children, commonly seen during adolescence, prevalence increases with age
  • almost all ulcers are seen in the ankle region (near the malleolus) and are bilateral.
  • can be painless or very painful
  • recurrence is high
  • HbSS genotype is more likely to develop leg ulcers
    
    
• chronic renal disease (7)
  • renal complications are common specially with increasing age
  • renal failure primarily due to SCD is rare in childhood
  • sickle nephropathy
    • presentation may range from painless haematuria, proteinuria and progressive loss of function to end stage renal disease (ESRD)
  • renal medullary carcinoma
    • occurs in patients with sickle cell trait and young patients with sickle cell anaemia
      
      
• priapism (8)
  • very common and 89% of males with sickle cell anaemia will have had at least one episode of priapism by adulthood
  • obstruction of the venous drainage of the penis by vaso-occlusion leads to painful, persistent erection
  • can present as an "acute" attack (which requires hospital admission) or a self limiting "stuttering" episode
    
    
• eye complications (9)
  • proliferative retinopathy
    • accounts for around 73% of sudden visual loss in SCD patients
    • caused by recurrent microvascular occlusion which leads to ischemia and growth of new blood vessels
    • can lead to vitreous haemorrhage and retinal detachment
    • commonly seen in young adults between the ages 15-29 years
  • non proliferative retinopathy
    
    
• gallstones (10)
  • seen in over 50% of children with SCD
  • usually asymptomatic or commonly presents with intermittent abdominal pain

Reference

1. Martí-Carvajal AJ, Solà I, Agreda-Pérez LH. Treatment for avascular necrosis of bone in people with sickle cell disease. Cochrane Database Syst Rev. 2019 Dec 5;(12):CD004344.
2. Sickle Cell Society 2008. Standards for the clinical care of adults with sickle cell disease in the UK
3. NHS Sickle Cell and Thalassaemia Screening Programme 2009. Sickle cell and Thalssaemia. Handbook for laboratories
4. Castro O, Gladwin MT. Pulmonary hypertension in sickle cell disease: mechanisms, diagnosis, and management. Hematol Oncol Clin North Am. 2005 Oct;19(5):881-96.
5. Naik RP, Smith-Whitley K, Hassell KL, et al. Clinical outcomes associated with sickle cell trait: a systematic review. Ann Intern Med. 2018 Nov 6;169(9):619-27.
6. National Heart, Lung, and Blood Institute. Evidence-based management of sickle cell disease: expert panel report, 2014. Sep 2014 [internet publication].
7. Liem RI, Lanzkron S, D Coates T, et al. American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease. Blood Adv. 2019 Dec 10;3(23):3867-97.
8. Arduini GAO, Trovó de Marqui AB. Prevalence and characteristics of priapism in sickle cell disease. Hemoglobin. 2018 Mar;42(2):73-77.
9. Leitão Guerra RL, Leitão Guerra CL, Bastos MG, et al. Sickle cell retinopathy: What we now understand using optical coherence tomography angiography. A systematic review. Blood Rev. 2019 May;35:32-42.
10. Bonatsos G, Birbas K, Toutouzas K, et al. Laparoscopic cholecystectomy in adults with sickle cell disease. Surg Endosc. 2001 Aug;15(8):816-9.