Sickle Cell Anaemia (SCA) is the second most common inherited blood disorder that affects red blood cells (haemoglobinopathy) in India. SCA is characterised by abnormal haemoglobin shape as valine replaces glutamic acid at the 6th position of the β chain. The haemoglobin in SCA is called HbS and it makes red blood cells (RBCs) appear like a Sickle. SCA is most commonly seen in the African and American Black population. In India it is highly prevalent in aboriginal tribes e.g. Teli Mahar Kunbhi of central India (Orissa, Chattisgarh, Vidarbha) and Gujarat.
MedPiper Technologies and JournoMed had conducted a webinar on 25th February, 2022 titled “An Overview of Sickle Cell Anaemia, Treatment and Prevention” where the speaker Dr. Bharat Parmar highlighted the issues, control, and treatment of Sickle Cell Anaemia. Dr. Bharat Parmar is a Professor and Head of Paediatrics Department at the Zydus Medical College and Hospital, Dahod, Gujarat.
Causes of Sickle Cell Anaemia
In the oxygenated state, HbS remains in the normal shape. In the deoxygenated state, abnormal coupling of the HBS globin chains occurs which causes the RBCs to become sickle-shaped. In prolonged hypoxic (low oxygen) states, the sickle RBCs clump (sludge) together which blocks the blood vessels leading to pain and VOC. However, the pathophysiology of SCD goes beyond just RBCs. Due to hypoxia, there is formation of reactive oxygen species (ROS) within the RBCs, which activates abnormal cellular signalling. This in turn causes cellular dehydration making the pliable RBCs become rigid and sickle shaped.
VOC is a classical hallmark of SCA and it occurs due to multicellular adhesion. These sickle shaped RBCs stick to the inner endothelium of the blood vessels and cause vascular damage. The platelets and white blood cells (WBCs) also stick on to the sickle RBCs and further aggravate the damage via cell activation and sustained inflammation.
The endothelial cells of the blood vessels and circulating platelets produce P-selectin in excess. High amounts of P-selectin enhances the static adhesion of the sickle RBCs to the blood vessels which augment the blocking of the blood vessels and cause tissue ischemia. The degree of sickle RBC adhesion correlates with vaso-occlusion and severity of the disease.
Manifestations in Sickle Cell Anaemia
Some of the common characteristics of sickle cell anaemia include:
- Chronic Haemolysis which can lead to Chronic Anaemia
- Vaso-occlusive crisis (VOC) where the sickle shaped cells stick to the inner surface of the blood vessels which blocks the blood flow and increases pain
- Splenomegaly or an enlarged spleen due excess amounts of dead RBCs
- Multi-organ dysfunctions due to sustained inflammation
- Early Death
Clinically Visible VOC is a painful episodic event which lasts upto 10 days and it manifests as extreme pain in the joints and severities. Since VOC is associated with inflammation, the damage worsens after each episode progressing to serious end organ damage. One or more VOC episodes in a year is associated with an increased risk of death.
Subclinical and silent VOC occurs throughout a person’s life which could potentially lead to acute and chronic complications. Some of these complications include: retinopathy, heart disease, lung diseases, infections, hypertension, nephropathy, chronic pain, priapism, impotence, chronic anaemia, acute chest syndrome and overt or silent strokes. Haemolytic anaemia is another hallmark of SCA where the patients suffer from hypoxia and may develop gallstones due to excess bilirubin production. Splenomegaly also occurs which makes the patient susceptible to infections.
SCA may be of Homozygous or Heterozygous type. Homozygous SCA manifest beyond 4-6 months of age as high amounts of foetal haemoglobin prevents early manifestations. Heterozygous SCA is asymptomatic and is normally seen in extreme hypoxic conditions. Techniques like peripheral smear, sickling test, haemoglobin solubility test and haemoglobin electrophoresis help in detecting SCA.
Management of Sickle Cell Anaemia
Some of the approaches to treating and managing SCA include:
- Analgesics to help manage pain
- Prevention and early treatment of precipitating events, such as fever, infections, dehydration, acidosis and hypoxia due to any cause including high altitude.
- Obtaining adequate sleep and monitoring tiredness
- Reduce stress and adapt better emotional coping mechanisms as stress can exacerbate the pain
- Folic acid supplementation to increase erythropoietic activity.
- Preventing infections by taking Pneumococcal, meningococcal and H. influenzae B vaccines.
- Maintain warmer temperatures since cold temperatures can trigger vasoconstriction which further reduces blood flow and increases hypoxia thus contributing to VOCs.
- Blood transfusions increases oxygen carrying capacity, restores blood volume and reduces sickle erythropoiesis. However, the complications associated with long-term blood infusions such as iron overload and transfusion reactions are extremely detrimental to the patient.
- Hydroxyurea is a myelosuppressive agent that stimulates foetal haemoglobin production which reduces HbS polymerisation. It also metabolises to Nitric Oxide which is a vasodilator and increases oxygen flow.
- Crizanlizumab is a monoclonal antibody that blocks P-selectin and its ligand binding association which in turn prevents sticking of the erythrocytes to the endothelium.
Scientists are exploring newer treatment modalities such as stem cell transplantation, bone marrow transplantation and recombinant human erythropoietin in order to avoid severe side effects and tackle the complications associated with long-term blood transfusions. Since SCA is an inheritable condition, genetic counselling, carrier detection, and antenatal diagnosis is essential in all cases to prevent further morbidity in the family.
Author: Parvathi Nair