Sickle Cell Disease (SCD)


Sickle cell disease (SCD) has presented with both acute and chronic complications throughout the disease’s natural history. 

Acute Complications

Infections – Vaso-occlusive phenomena are a hallmark of SCD. These events occur early in the spleen and lead to progressive atrophy of the organ. Splenic function deteriorates as early as 6 months of age and eventually leads to complete autosplenectomy by the age of 5 years. The spleen plays a major defensive role against encapsulated organisms such as Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type B. Infections with these organisms are a major cause of mortality in patients with SCD, and preventative measures include vaccination and prophylactic penicillin.1 Mortality in SCD has been greatly reduced since the advent of the pneumococcal vaccine in 2000.2   

Acute pain – One of the most common manifestations of vaso-occlusion is acute pain, which is explained by a cascade of events initiated by the polymerization of hemoglobin S (HbS). Polymerization of abnormal hemoglobin disfigures the shape of erythrocytes and decreases their flexibility, leading to trapping of sickled cells, leukocytes, and platelets in the microcirculation. Inflammatory cytokines such as CXCL1 (C-X-C motif ligand 1; a neutrophil chemoattractant) are liberated as a result, and they subsequently recruit and activate neutrophils. The ensuing ischemia due to occluded blood vessels and inflammation from cytokine release manifests as acute debilitating pain, which often requires the administration opioid analgesics to control.3 

Life-threatening vaso-occlusive events – Vaso-occlusion spares no organ and can produce potentially life-threatening complications depending on which organ system is involved. Vaso-occlusion can result in acute coronary syndrome, stroke, multiorgan failure, priapism, renal dysfunction, and acute chest syndrome. Acute chest syndrome occurs in 10% to 20% of patients with SCD who are hospitalized for acute pain and can lead to acute respiratory failure and death. 

Acute splenic sequestration crisis (ASSC) – ASSC is characterized by an acute drop in hemoglobin by 2 mg/dL accompanied by acute splenomegaly.4 This is primarily seen in young children who have not undergone autosplenectomy, however, case reports of ASSC have been reported in adults with less common forms of SCD (for example, HbS-β thalassemia) in which splenic function is partially preserved into adulthood.5 It is thought to be caused by the mechanical obstruction of a larger draining vein in the spleen, resulting in rapid trapping/sequestering of red blood cells within the spleen. Severe anemia is the most feared complication of ASSC, as it can lead to cardiovascular collapse; however, survival has improved significantly since the 1980s.4 

Chronic complications

Ischemic complications – Vaso-occlusive events are associated with avascular necrosis of the hip in 13% of patients and refractive eye disorders in around 27% of patients.6  

Anemia – The presence of HbS leads to sickling and reduced lifespan of erythrocytes and hemolysis, resulting in anemia. Anemia can be exacerbated by ASSC,5 aplastic crisis,7 and hyperhemolytic crisis.8 Complications related to anemia include gallstones, heart disease, and chronic leg ulcers.6 

Poor quality of life (QOL) – QOL may be greatly reduced in patients with SCD due to frequent hospitalization, chronic pain, stigmatization, and anemia.6 Patients with SCD scored lower in bodily pain, vitality, and social functioning than the general population on a health-related QOL questionnaire. Interestingly, the mental health of patients with SCD was not worse than that of the general population.9 

References

1. Brousse V, Buffet P, Rees D. The spleen and sickle cell disease: the sick(led) spleen. Br J Haematol. 2014;166(2):165-176. doi:10.1111/bjh.12950

2. Data & statistics on sickle cell disease. Centers for Disease Control and Prevention. Accessed November 11, 2021.

3. Darbari DS, Sheehan VA, Ballas SK. The vaso-occlusive pain crisis in sickle cell disease: definition, pathophysiology, and management. Eur J Haematol. 2020;105(3):237-246. doi:10.1111/ejh.13430

4. Kane I, Nagalli S. Splenic sequestration crisis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Accessed November 11, 2021.

5. Naymagon L, Pendurti G, Billett HH. Acute splenic sequestration crisis in adult sickle cell disease: a report of 16 cases. Hemoglobin. 2015;39(6):375-379. doi:10.3109/03630269.2015.1072550

6. Andong AM, Ngouadjeu EDT, Bekolo CE, et al. Chronic complications and quality of life of patients living with sickle cell disease and receiving care in three hospitals in Cameroon: a cross-sectional study. BMC Hematol. 2017;17:7. doi:10.1186/s12878-017-0079-7

7. Conrad ME, Studdard H, Anderson LJ. Aplastic crisis in sickle cell disorders: bone marrow necrosis and human parvovirus infection. Am J Med Sci. 1988;295(3):212-215. doi:10.1097/00000441-198803000-00009

8. Madu AJ, Ugwu AO, Efobi C. Hyperhaemolytic syndrome in sickle cell disease: clearing the cobwebs. Med Princ Pract. 2021;30(3):236-243. doi:10.1159/000512945

9. McClish DK, Penberthy LT, Bovbjerg VE, et al. Health related quality of life in sickle cell patients: The PiSCES project. Health Qual Life Outcomes. 2005;3:50. doi:10.1186/1477-7525-3-50

Reviewed by Debjyoti Talukdar, MD, on 11/12/2021.