How do doctors manage Sickle cell anaemia

  • 02 Jul, 2019
  • 414

Management of sickle cell disease starts right from the neonatal period. Early diagnosis helps to prevent complications. If the diagnosis is missed and appropriate treatment is not given, death may occur due to sepsis and pneumonia. A small dried blood spot (DBS) for analysis, is collected from cord blood or the infant’s heel/toe to detect abnormal sickle hemoglobin (Hemoglobin S, HbS) by hemoglobin electrophoresis.  The next step after diagnosis is the education of the parents and family. The disease is explained to them and the importance of antibiotic prophylaxis is stressed to prevent severe infections. Guidelines recommend penicillin prophylaxis and pneumococcal vaccine to prevent pneumococcal infection in children.

Possible treatment options like hydroxyurea and transfusions can be considered. Blood transfusion is needed to maintain hemoglobin (Hb) levels and to reduce HbS levels. Hydroxyurea decreases crises in patients with severe sickle cell crisis. Consultation for stem cell transplantation, if needed, may be given by experts.

Fever in these children should never be treated at home by family as it can mask severe infection. The parents should learn to recognize signs and symptoms of ASSC: pallor, fussiness or irritability, and tender splenomegaly. As the child grows older, parents must be vigilant and learn to identify symptoms of pain, respiratory distress, acute chest syndrome, and stroke. Mild pain may be managed at home with oral hydration, massage, self-relaxation techniques, and pain killers, as advised by the physician. Severe pain requires aggressive management in a hospital setting. Other severe complications are acute chest syndrome and stroke which need proper treatment.

Education must be continued in adolescents and adults to generate self-awareness and self-care. They must be taught the importance of preventing these complications and at the same time try to have a normal and productive life.

References 

Patrick T. McGann et al,  Current Management of Sickle Cell Anemia, Cold Spring Harb Perspect Med. 2013 Aug; 3(8): a011817.

https://www.nhlbi.nih.gov/files/docs/guidelines/sc_mngt.pdf


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Sicke Cell Disease - Diagnosis

  • 19 Jun, 2019
  • 429

Sickle cell disease is  a genetic disorder that affects the red blood cell pigment hemoglobin which is responsible for the delivery of oxygen cells throughout the body. Millions are affected worldwide with this increasingly global problem. The person suffering from this disorder  has atypical hemoglobin molecules called hemoglobin S. The red blood cells are distorted into a sickle or crescent shape.

Signs and symptoms manifest early in childhood (within the first year) and are due to sickling of red blood cells. Due to abnormal shape, there is a premature breakdown of red blood cells (life span reduced to 16 –20 days from 100–120 days).

 The reduction of the red blood cell number leads to anemia. The consequences of anemia are shortness of breath, fatigue, malnutrition, delayed growth, and development in children.  The intensity of symptoms varies - mild to very serious – from person to person. 

The patients suffer from repeated infections and pain in the joints, abdomen and painful swelling of hands and feet with fever (hand-foot syndrome). Pain is due to blocking of small blood vessels by the abnormal sickle-shaped cells. The skin appears pale and the child may suffer from jaundice due to the rapid breakdown of red blood cells. Serious infections like pneumonia can lead to death in infants. Enlargement of spleen due to trapping of sickle cells can be life-threatening. Damage to the retina can lead to vision loss. In the long run, reduced oxygen supply to organs (due to the blocking of blood vessels and reduced number of red blood cells) causes damage to major organs like lungs, kidneys, spleen, and brain (stroke). These patients have a higher incidence of leg ulcers, deep vein thrombosis, and pulmonary embolism. Serious complications like pulmonary hypertension and heart failure may occur in adulthood.

References

https://www.nejm.org/doi/pdf/10.1056/NEJMra1510865

https://ghr.nlm.nih.gov/condition/sickle-cell-disease

https://www.cdc.gov/ncbddd/sicklecell/treatments.html

https://www.uspharmacist.com/article/sickle-cell-disease-pain-management


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Sickle Cell Anemia - An Overview

  • 13 Jun, 2019
  • 602

Sickle cell disease is a common blood related to genetic disease worldwide. The abnormality is in the hemoglobin gene which is found in 5–7% of the population worldwide. These abnormal hemoglobin molecules polymerize within the red blood cells. The red cells are deformed into a sickle (or crescent) shape and get hemolysed. 

The inheritance is autosomal recessive (means two copies of an abnormal gene must be present - both the mother and the father must pass the defective form of the gene for a child to be affected). If only one parent passes the abnormal gene, the child will have sickle cell trait. The body will produce both normal and abnormal hemoglobin and they become carriers of the abnormal gene. They have some sickle cells, but no symptoms. When the gene is inherited in the homozygous state, it is called sickle cell anemia. Other types of disease are hemoglobin sickle disease, sickle beta plus thalassemia, sickle beta zero thalassemia, hemoglobin SD Punjab disease, hemoglobin SO Arab disease, and others.

Sickle cell disease is believed to have originated in Asia and Africa due to mutation of the beta-globin gene of hemoglobin. Migration and interracial marriages have led to the spread of the disease to other parts of the world. In sub-Saharan Africa, this disease provides a survival advantage against Plasmodium falciparum malaria.

The life span of red blood cells in sickle cell disease is reduced to 16–20 days while it is 100–120 days in normal individuals. These abnormal red cells block blood flow in small vessels. Hence, enough oxygen cannot be carried to all cells of the body. The clinical features vary but most people suffer from anemia, pallor, jaundice, joint pain, abdominal pain, painful swelling in hands and feet, repeated infection, delayed growth in children, vision changes, etc.

Please follow our upcoming blogs to know more about the disease.

References 
Adewoyin AS, Management of Sickle Cell Disease: A Review for Physician Education in Nigeria (Sub-Saharan Africa), Anemia. 2015; 2015: 791498


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Treatment Options for Gaucher's disease

  • 21 Aug, 2018
  • 1043

Gaucher’s disease is a rare metabolic disease, a type of Lysosomal storage disorder (LSD). It is the commonest LSD worldwide as well as in India. An enzyme deficiency leads to excess glycolipid glucocerebroside throughout the body including spleen, liver, bone marrow, brain, osteoclasts and less commonly in lungs, skin, kidneys, conjunctivae and heart. It is important to meet the right specialist who can offer the best treatment to your child. Your pediatrician will refer you to the specialist depending on the type of disease - a haematologist for management of visceral, haematological and bone conditions. Type 2 (Neuronopathic disease) is best managed by a Pediatric neurologist. The patient will be referred to other doctors like medical geneticist, orthopedician and neuro-ophtalmologist. The three types of Gaucher disease (GD) are - type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (subacute neuronopathic). Enzyme replacement Therapy (ERT) has offered hope to symptomatic patients of GD 1 and GD 3. It reduces the liver and spleen size and bone symptoms, and improves blood counts. It is not very effective in type 2 as it does not cross blood brain barrier. The parents and family need to be explained about the chronic and progressive nature of Gaucher disease. Psychological counseling is important for patients and relatives. Since parents may be carriers of the defective gene, prenatal counseling is done to explain that every child has a 25% chance of having the disease. Prenatal diagnosis can be done by enzyme analysis of fetal cells at 16 weeks of pregnancy. Enough emphasis cannot be laid on importance of timely consultation with the right doctor to enable early diagnosis and treatment of this condition. Safe and efficient enzyme substitution therapy and other treatments are available. Right dose and early therapy are effective in stopping disease progression. The visceral and haematological abnormalities can be reduced and irreversible bone deformities may be prevented; on the whole, the patient can be offered a better quality of life.


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Gaucher’s disease – Diagnosis & Treatment

  • 08 Aug, 2018
  • 972

Gaucher's disease is diagnosed by clinical symptoms, examination and laboratory testing. A history of consanguinity in parents must be ruled out. Laboratory testing is recommended in patients with clinical features like hepatosplenomegaly (enlarged liver and spleen), bone problems (bone pain, osteopenia), easy bruising, low platelets or symptoms involving the nervous system. The symptoms have been described earlier and vary depending upon the type of Gaucher's disease. Bone marrow testing is not needed to diagnose Gaucher’s disease. The gold standard for diagnosis of Gaucher’s disease is by a blood test - a specific enzyme test called beta-glucosidase (glucocerebrosidase) leukocyte (BGL) test. Patients with Gaucher's disease have low levels of the enzyme glucocerebrosidase. Other supportive tests are done to see organ involvement. Genetic testing (DNA test) may be done to identify the specific gene mutations. The treatment is aimed at taking care of the enzyme deficiency. Enzyme replacement therapy (ERT) is useful in Gaucher disease type 1 and 3 to reverse the visceral (organ) and hematological (blood) symptoms. ERT has revolutionized the treatment and is the standard of care for this condition. It can partially benefit patients with neurological symptoms. However, most of type 2 (acute neuronopathic)GD patients do not survive beyond 2 years of age and are given supportive treatment. Another method to reduce the accumulation of the toxic substrate glucocerebroside and other glycolipids in the body is inhibition of substrate synthesis. Glucosylceramide synthase inhibitors are oral medications used for this purpose in patients with milder disease (mainly adults). These drugs are used as maintenance therapy after the therapeutic goals have been achieved with ERT. Supportive treatment is needed to take care of organ damage and symptoms. Treatment of anemia and platelet deficiency may require transfusion. In neuronopathic disease, myoclonus (twitches and jerks due to muscle contraction) and epilepsy are managed.


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Gaucher’s disease – Clinical features

  • 06 Aug, 2018
  • 921

Gaucher disease is the most common lysosomal storage disorder. It occurs due to deficiency of the enzyme, glucocerebrosidase. Fat starts getting accumulated in tissue macrophages in various organs. The three types of Gaucher disease are - type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (subacute neuronopathic). The clinical manifestations vary; patients may die in early childhood or live up to old age. Due to recent progress in human genetics, we have a better understanding of such rare diseases. Type 1 Gaucher disease (Non-neuronopathic type 1 GD) is the most common type (94% cases). The patient has hepatosplenomegaly(enlarged liver and spleen, anemia and thrombocytopenia (low platelets). There is massive abdominal distension and complaints of abdominal pain, fatigue, nosebleeds and easy bruising. The child has delayed milestones and growth retardation. Some patients need a blood transfusion. Bone disease may be seen on X-ray. Lungs may also be affected. Type 1 GD has been reported to be associated with increased risk of certain cancers like multiple myeloma and Parkinson disease. Type 2 GD is the most severe form of Gaucher disease, seen at a very young age. It is the acute neuronopathic form, where the nervous system is involved. Sometimes there is life threatening problem at birth. Most infants are detected between 3 to 6 months. There is early onset brain damage. Other neurological symptoms like seizures, spasticity (jerking movements), decreased ability to suck and swallow are seen along with hepatosplenomegaly. The disease progresses very fast, causing death in infancy or early childhood (by 2 years of age). Type 3 GD is the chronic form of Gaucher disease. It has a later onset than type 2 GD. The neurological involvement is milder compared to GD2 and bones and organs also may be affected. In nervous system, the eye involvement is picked up first. Visceral disease in GD3 is often more severe than in GD1. The symptoms are seizures, bone involvement, eye movement disorders, poor coordination and cognition problems, hepatosplenomegaly, respiratory problems and blood disorders.


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Gaucher’s disease – Pathophysiology

  • 02 Aug, 2018
  • 1092

Gaucher’s disease occurs due to deficiency of an enzyme called glucocerebrosidase (also known as acid beta-glucosidase, GBA). This enzyme acts on glucocerebroside, a part of cell membrane. The cause of decreased activity of this enzyme is a gene mutation on chromosome 1. Due to enzyme deficiency, lipids are accumulated in macrophages (large white blood cells that clear unwanted microscopic particles, such as bacteria and dead cells in the body). The macrophages get converted to Gaucher cells. The Gaucher cells infiltrate into various organs like bone marrow, spleen and liver. Three types ofGaucher’sdisease are known. The classification is based on age of onset, symptoms and whether there is neurological involvement. Gaucher disease type 1, (GD1), is characterized by splenomegaly (enlarged spleen), blood disorders, bone involvement and absence of neurological involvement. In Gaucher disease type 2 (GD2), there is hepatosplenomegaly (enlarged liver and spleen) along with neurological involvement within the first year of life. Nervous system involvement is seen right from childhood in Gaucher disease type 3 (GD3). Gaucher cells look like signet rings with crumpled tissue paper appearance. The cell nucleus is pushed to the periphery due to accumulation of lipids. There is direct toxic effect of bioactive lipids on nerve cells, causing cellular injury in the brain. There is neuronal loss and the neurons (nerve cells) look crumpled and shrunken in areas of brain like basal ganglia, midbrain, pons and medulla, cerebellum and hypothalamus. Gaucher cells are seen lying free within cerebral cortex. There is dysfunction of osteoblasts and osteoclasts (bone cells) leading to osteopenia (low bone mineral density due to bone loss). This can lead to bone pains and pathological fractures. In some cases, other organs like skin and lungs are also involved.


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Gaucher’s disease - A Rare Disease in Children

  • 01 Aug, 2018
  • 1774

Gaucher’s disease is a rare genetic disorder due to deficiency of an enzyme (glucocerebrosidase)in the body. It was first described by the French physician Philippe Gaucher in the nineteenth century.The defective gene is present on the first chromosome. Gaucher’s disease is an autosomal recessive type of genetic disorder. This means that the child gets the disease if both the parents carry the defective gene. Gaucher’s disease is a type of Lysosomal storage disorder (LSD). Lysosomal storage disorders (LSDs) are rare metabolic diseases. They occur when there is abnormal storage of undigested cellular debris, proteins, fats, carbohydrates, and nucleic acids within the cell. Fat gets accumulated around vital organs (spleen, liver or bone). The organs become larger in size and cannot function properly. Gaucher’s diseaseis the most common among various Lysosomal storage disorders worldwide as well as in India. Approximately, the Gaucher’s disease cases are seen in 1/57,000 to 1/75,000 births worldwide. The prevalence is higher in individuals of Ashkenazi Jewish descent (75% of the world's Jewish population). There is increased risk of having a child withGaucher’s disease in consanguineous marriages. There are three types of Gaucher’s disease (GD) – type 1, type 2 and type 3. Type 1 (non neuronopathic form of GD) is most common. Type 2 is the acute neuronopathic GD or infantile cerebral GD. Type 3 is called the chronic neuronopathic form. If the child is not treated properly, death may occur within a year or the child may become dependent. GD causes growth delays and increases the risk of Parkinsonism and certain types of cancer. It is important to start right treatment at an early age so that the chances of survival are increased.


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