Sickle Cell Disease

Hematology

Clinicals - History

Fact Explanation
Introduction This is a one of haemoglobinopathy characterized by mutation in the beta-globin Chain(single amino acid molecular disorder). This is an inherited condition. Introduction
This is a one of haemoglobinopathy characterized by mutation in the beta-globin Chain(single amino acid molecular disorder). This is an inherited condition.
Features of anaemia like easy fatiguability and lethargy As there is a mutation in beta globin chain there will be abnormal haemoglobin production causing severe haemolytic anaemia. Clinical presentation can be vary from normal life to severe crisis with deaths.
In aplastic crisis with sudden reduction in bone marrow production, patient may present with sudden onset features of anaemia due to sudden fall in haemoglobin level.
Features of anaemia like easy fatiguability and lethargy
As there is a mutation in beta globin chain there will be abnormal haemoglobin production causing severe haemolytic anaemia. Clinical presentation can be vary from normal life to severe crisis with deaths.
In aplastic crisis with sudden reduction in bone marrow production, patient may present with sudden onset features of anaemia due to sudden fall in haemoglobin level.
Features of hypoperfusion in various organs with micro vascular occlusion. These due to hypoperfusion with painful vaso-occlusive crises associated with sickle cell disease. These can occur in more frequently with infections, acidosis, dehydration and situations leading to deoxygenation like high altitude, surgeries, vigorous exercise and cold exposure. Abnormal red blood cells will sickle in above mentioned situations. blocking small blood vessels leading to ischemic/ hypoperfusion symptoms in various organs.
Eg:
In brain strokes can occur giving features of paralysis, paresthesia and cranial nerve palsy.
In spinal cord, features of infarction like limb paralysis, paresthesia, bladder/ bowel dysfunction.
In bones, ischemic pain at site of the joint/back pain and fractures.
In lungs there will be shortness of breath and pleuritic type chest pain.
In mesentry, acute abdominal pain will be the presentation.
In digits( hand- foot syndrome), painful fingers and toes with small bone infarction
In kidneys infarction of medulla with papillary necrosis may lead to fail in concentrating urine causing high urine out put, dehydration and nocturnal enuresis.
Chronic liver failure with micro infarction causing loss of appetite, yellowish discoloration of eyes.
In penis, erectile dysfunction will be the presentation.
Splenic infarction leads to recurrent infections like upper/ lower respiratory tract infections and diarrheal illnessess.
Features of hypoperfusion in various organs with micro vascular occlusion.
These due to hypoperfusion with painful vaso-occlusive crises associated with sickle cell disease. These can occur in more frequently with infections, acidosis, dehydration and situations leading to deoxygenation like high altitude, surgeries, vigorous exercise and cold exposure. Abnormal red blood cells will sickle in above mentioned situations. blocking small blood vessels leading to ischemic/ hypoperfusion symptoms in various organs.
Eg:
In brain strokes can occur giving features of paralysis, paresthesia and cranial nerve palsy.
In spinal cord, features of infarction like limb paralysis, paresthesia, bladder/ bowel dysfunction.
In bones, ischemic pain at site of the joint/back pain and fractures.
In lungs there will be shortness of breath and pleuritic type chest pain.
In mesentry, acute abdominal pain will be the presentation.
In digits( hand- foot syndrome), painful fingers and toes with small bone infarction
In kidneys infarction of medulla with papillary necrosis may lead to fail in concentrating urine causing high urine out put, dehydration and nocturnal enuresis.
Chronic liver failure with micro infarction causing loss of appetite, yellowish discoloration of eyes.
In penis, erectile dysfunction will be the presentation.
Splenic infarction leads to recurrent infections like upper/ lower respiratory tract infections and diarrheal illnessess.
Features of visceral sequestration Sickling inside the organs and pooling of the blood can be present as a crisis. this is usually associated with severe exacerbstion of anaemia.
Eg;
Acute sickle chest syndrome may present with chest pain, difficulty in breathing
Pooling inside the spleen may cause abdominal pain.
Features of visceral sequestration
Sickling inside the organs and pooling of the blood can be present as a crisis. this is usually associated with severe exacerbstion of anaemia.
Eg;
Acute sickle chest syndrome may present with chest pain, difficulty in breathing
Pooling inside the spleen may cause abdominal pain.
Ulcers of the lower limbs This is due to the ischemia with vascular blockage. Ulcers of the lower limbs
This is due to the ischemia with vascular blockage.
reduction in vision There will be proliferative retinopathy with retinal ischemia following vascular blockage. reduction in vision
There will be proliferative retinopathy with retinal ischemia following vascular blockage.
Chronic bone pain, swelling, redness and limiting movements There can be osteomyelitis associated with sickle cell disease, commonly with salmonella species. Chronic bone pain, swelling, redness and limiting movements
There can be osteomyelitis associated with sickle cell disease, commonly with salmonella species.
Features suggestive of gall stones With excessive haemoglobin breakdown, there will be increased chance of pigment gall stone formation. Symptomatic patient will have fever, biliary colicks, nausea and vomiting. Features suggestive of gall stones
With excessive haemoglobin breakdown, there will be increased chance of pigment gall stone formation. Symptomatic patient will have fever, biliary colicks, nausea and vomiting.
Family history of similer disease condition As this is a hereditary condition with autosomal recessive inheritance. there will be family history of diagnosed sickle cell disease. Family history of similer disease condition
As this is a hereditary condition with autosomal recessive inheritance. there will be family history of diagnosed sickle cell disease.

Clinicals - Examination

Fact Explanation
Pallor As there is a mutation in beta globin chain there will be abnormal haemoglobin production causing severe haemolytic anaemia. In examination patient will be pale. Pallor
As there is a mutation in beta globin chain there will be abnormal haemoglobin production causing severe haemolytic anaemia. In examination patient will be pale.
Central nervous system examination to detect any muscle/sensory weakness and cranial nerve palsy These nervous system signs suggestive of strokes, spinal cord infarction are due to hypoperfusion with painful vaso-occlusive crises in sickle cell disease. These can occur in more frequently with infections, acidosis, dehydration and situations leading to deoxygenation like high altitude, surgeries, vigorous exercise and cold exposure. Abnormal red blood cells will sickle in above mentioned situations. blocking small blood vessels leading to ischemic/ hypoperfusion symptoms in various organs. Central nervous system examination to detect any muscle/sensory weakness and cranial nerve palsy
These nervous system signs suggestive of strokes, spinal cord infarction are due to hypoperfusion with painful vaso-occlusive crises in sickle cell disease. These can occur in more frequently with infections, acidosis, dehydration and situations leading to deoxygenation like high altitude, surgeries, vigorous exercise and cold exposure. Abnormal red blood cells will sickle in above mentioned situations. blocking small blood vessels leading to ischemic/ hypoperfusion symptoms in various organs.
Examination of joints for limited movements and tenderness over the spine Due to infarction of bones, hips, shoulders and vertibrae can affect commonly. Examination of joints for limited movements and tenderness over the spine
Due to infarction of bones, hips, shoulders and vertibrae can affect commonly.
Examination of digits for tenderness, swelling and length of digits Digits can be affected( hand-foot syndrome) by infarction of the small bones. Dactilitis caused by sickle cell disease may leads to marked shortening of digits as it can affect the growth of epiphysis in childhood. Examination of digits for tenderness, swelling and length of digits
Digits can be affected( hand-foot syndrome) by infarction of the small bones. Dactilitis caused by sickle cell disease may leads to marked shortening of digits as it can affect the growth of epiphysis in childhood.
Features of chronic liver disease like jaundice, generalized oedema, wasting, ascitis Chronic liver failure can occur with micro infarctions. Features of chronic liver disease like jaundice, generalized oedema, wasting, ascitis
Chronic liver failure can occur with micro infarctions.
Dyspnoea On general examination patient will be dyspnoic due to severe anaemia or micro vascular infarction in lungs. Dyspnoea
On general examination patient will be dyspnoic due to severe anaemia or micro vascular infarction in lungs.
Features if dehydration like dry skin and mucous membranes In kidneys infarction of medulla with papillary necrosis may lead to fail in concentrating urine causing dehydration. Features if dehydration like dry skin and mucous membranes
In kidneys infarction of medulla with papillary necrosis may lead to fail in concentrating urine causing dehydration.
Fever If the patient is having fever this is most suggestive of an ongoing infection. Splenic infarctions leads to recurrent infections and presence of infections can exacerbate the condition. Fever
If the patient is having fever this is most suggestive of an ongoing infection. Splenic infarctions leads to recurrent infections and presence of infections can exacerbate the condition.
Reduced vision There will be proliferative retinopathy with retinal ischemia following vascular blockage. Reduced vision
There will be proliferative retinopathy with retinal ischemia following vascular blockage.
Bone tenderness, warmth, swelling, redness and limitation of movements. There can be osteomyelitis associated with sickle cell disease, commonly with salmonella species. Bone tenderness, warmth, swelling, redness and limitation of movements.
There can be osteomyelitis associated with sickle cell disease, commonly with salmonella species.
Ulcers in lower limb with necrotic surrounding micro vascular infarctions with sickle cell disease may cause leg ulcers commonly in medial aspect of the ankle. Ulcers in lower limb with necrotic surrounding
micro vascular infarctions with sickle cell disease may cause leg ulcers commonly in medial aspect of the ankle.
Splenomegally with abdominal tenderness In splenic sequestration there will be enlarged spleen. This is commonly present in infants. These patients will be very ill. Splenomegally with abdominal tenderness
In splenic sequestration there will be enlarged spleen. This is commonly present in infants. These patients will be very ill.
Cardiovascular system examination loud second heart sound in pulmonary area can be identified in long term lung damage resulting pulmonary hypertension. Cardiovascular system examination
loud second heart sound in pulmonary area can be identified in long term lung damage resulting pulmonary hypertension.

Investigations - Diagnosis

Fact Explanation
Full blood count haemoglobin level will be low, in between 6-9g/dl. This is useful in assessing the level of anaemia. There will be increased WBC counts in an ongoing infection. Full blood count
haemoglobin level will be low, in between 6-9g/dl. This is useful in assessing the level of anaemia. There will be increased WBC counts in an ongoing infection.
Reticulocyte count Due to frequent red blood cell turnover, there will be increased reticulocyte count up to 10-20%. Reticulocyte count
Due to frequent red blood cell turnover, there will be increased reticulocyte count up to 10-20%.
Blood picture This will show sickle cells and target cells. If associated splenic atrophy is present there will be Howell-jolly bodies. Blood picture
This will show sickle cells and target cells. If associated splenic atrophy is present there will be Howell-jolly bodies.
Screening test for sickling This will be positive in a deoxygenated state of blood with dithionate and Na2HPO4. Screening test for sickling
This will be positive in a deoxygenated state of blood with dithionate and Na2HPO4.
Haemoglobin electrophoresis Hb SS will be present and Hb A will be absent in homozygous disease. This is useful in diagnosing the disease and distinguish homozygous and heterozygous status. Haemoglobin electrophoresis
Hb SS will be present and Hb A will be absent in homozygous disease. This is useful in diagnosing the disease and distinguish homozygous and heterozygous status.
Serum bilirubin level This will be increased with the excess haemoglobin break down. Serum bilirubin level
This will be increased with the excess haemoglobin break down.

Investigations - Management

Fact Explanation
Full blood count this is helpful in follow up to assess patient's current condition of anaemia, improvement with treatments and deterioration in crises . Full blood count
this is helpful in follow up to assess patient's current condition of anaemia, improvement with treatments and deterioration in crises .
pulmonary function test This is useful during followup as pulmonary function is deteriorating with the time. This should be performed especially in patients with recurrent chest infections. pulmonary function test
This is useful during followup as pulmonary function is deteriorating with the time. This should be performed especially in patients with recurrent chest infections.
CT/ MRI scanning This is useful in assessing the status of all organs as sickle cell disease affects multiple systems. CT/ MRI scanning
This is useful in assessing the status of all organs as sickle cell disease affects multiple systems.
Renal function tests like serum creatinine. blood urea and serum electrolytes In kidneys infarction of medulla with papillary necrosis may leads to renal failure. Renal function tests like serum creatinine. blood urea and serum electrolytes
In kidneys infarction of medulla with papillary necrosis may leads to renal failure.
Liver function tests like AST, ALT, serum bilirubin levels Chronic liver failure can occur with micro infarction. Liver function tests like AST, ALT, serum bilirubin levels
Chronic liver failure can occur with micro infarction.
Bone X ray This is useful in assessing the bony complications such as osteomyelitis. Site will depend on clinical presentation. Bone X ray
This is useful in assessing the bony complications such as osteomyelitis. Site will depend on clinical presentation.
Full blood count useful in assessing the degree of anaemia which is helpful in deciding further treatment. Full blood count
useful in assessing the degree of anaemia which is helpful in deciding further treatment.
Trans cranial Doppler ultrasonography This will give evidence of an abnormal blood flow suggesting arterial stenosis. Trans cranial Doppler ultrasonography
This will give evidence of an abnormal blood flow suggesting arterial stenosis.
arterial partial pressure of oxygen This will give an idea about oxygenation of arterial blood in sickle cell disease, especially in a crises as there is low oxygen affinity. arterial partial pressure of oxygen
This will give an idea about oxygenation of arterial blood in sickle cell disease, especially in a crises as there is low oxygen affinity.
Chest X ray Patients with recurrent chest symptoms (dyspnoea), chest infections this is useful as lungs may develop fibrosis. Chest X ray
Patients with recurrent chest symptoms (dyspnoea), chest infections this is useful as lungs may develop fibrosis.
Blood grouping and cross matching This is useful during the treatments before transfusions. Blood grouping and cross matching
This is useful during the treatments before transfusions.
genetic testing with karyotyping This is very important in this hereditary disease for genetic screening is susceptible individuals. This can be done either in prenatally or in new born babies. genetic testing with karyotyping
This is very important in this hereditary disease for genetic screening is susceptible individuals. This can be done either in prenatally or in new born babies.

Management - Supportive

Fact Explanation
Health education Health education is very important as this is a familial life long conditions with episodic exacerbations. patient and family should educate about the disease, symptoms in exacerbatons, preventive methods, treatment options available and possible complications. Health education
Health education is very important as this is a familial life long conditions with episodic exacerbations. patient and family should educate about the disease, symptoms in exacerbatons, preventive methods, treatment options available and possible complications.
Avoid precipitating factors Patient should be educate regarding the possible precipitating factors like infections, acidosis, dehydration and situations leading to deoxygenation like high altitude, surgeries, vigorous exercise and cold exposure. Important of avoidance should be stressed. Avoid precipitating factors
Patient should be educate regarding the possible precipitating factors like infections, acidosis, dehydration and situations leading to deoxygenation like high altitude, surgeries, vigorous exercise and cold exposure. Important of avoidance should be stressed.
Folic acid As there is haemolytic anaemia with this haemoglobinopathy, patient is at risk of folic acid deficiency. Folic acd suppliment( 5mg daily) is important. Folic acid
As there is haemolytic anaemia with this haemoglobinopathy, patient is at risk of folic acid deficiency. Folic acd suppliment( 5mg daily) is important.
Good general nutritional supplement Due to excessive haemolysis with the disease patient should be given well balanced diet with all macro and micro nutrients to prevent any nutritional deficiency. Good general nutritional supplement
Due to excessive haemolysis with the disease patient should be given well balanced diet with all macro and micro nutrients to prevent any nutritional deficiency.
Good hygienic practices These patients are at risk of getting frequent infections. So good hygienic practices are very important, especially regarding the dental hygien. Good hygienic practices
These patients are at risk of getting frequent infections. So good hygienic practices are very important, especially regarding the dental hygien.
Prophylactic antibiotics and immunization Splenic infarction with microvascular thrombi leads to recurrent infections and with it there is poor protection against capsulated organisms.So life long prophylactic oral antibiotics( at least until puberty) like penicillin/ Erythromycin if penicillin allergic is recommended.
Immunization should be done against Pneumococcal , Haemophilus influenzae type b, Meningococcal and influenza.
Prophylactic antibiotics and immunization
Splenic infarction with microvascular thrombi leads to recurrent infections and with it there is poor protection against capsulated organisms.So life long prophylactic oral antibiotics( at least until puberty) like penicillin/ Erythromycin if penicillin allergic is recommended.
Immunization should be done against Pneumococcal , Haemophilus influenzae type b, Meningococcal and influenza.
Genetic counselling This is one of important aspect as this is a hereditary disorder.prenatal testing can be done in fetuses at risk and newborns at risk. Genetic counselling
This is one of important aspect as this is a hereditary disorder.prenatal testing can be done in fetuses at risk and newborns at risk.

Management - Specific

Fact Explanation
Admit the patient hospital admissions should be avoided as much as possible, but it will be needed in some conditions haemoglobin level less then 5mg/dl, WBC count less than 5x109/L or more than 30 x 109/L, temperature more than 40 Celsius, severe pain and features of dehydration. Admit the patient
hospital admissions should be avoided as much as possible, but it will be needed in some conditions haemoglobin level less then 5mg/dl, WBC count less than 5x109/L or more than 30 x 109/L, temperature more than 40 Celsius, severe pain and features of dehydration.
Management of sickle cell crisis Pain management is very important as this is associated with severe pain. This can be give appropriately. paracetamol. NSAIDs and opiates can be given.
Cannulate the patient and send blood for investigations(crossmatching, FBC, reticulocyte count, blood culture). Chest x ray will be needed in the present of chest symptoms( dyspnoea, chest pain).
Rehydration should be done with oral/ Iv fluids( 3L in 24 hours) depending on the patient's condirtion.
Patient should be kept warm.
oxygen can be given if arterial oxygen partial pressure drops of if the oxygen saturation is less tan 95%.
If patient is having fever, ill health or chest symptoms broad spectrum antibiotics should be start after sending blood/ other appropriate specimen for culture and ABST.
Pack cell volume and reticulocyte count should be measure twice a daily. Size of the spleen and liver also need to be examined twice a daily.
Blood transfusion should be consider in symptomatic severe anaemia and exchange transfusion need to be considered in presence of features with visceral sequestration crisis, severe chest crisis, central nervous system involvement and with repeated painful episodes .
Management of sickle cell crisis
Pain management is very important as this is associated with severe pain. This can be give appropriately. paracetamol. NSAIDs and opiates can be given.
Cannulate the patient and send blood for investigations(crossmatching, FBC, reticulocyte count, blood culture). Chest x ray will be needed in the present of chest symptoms( dyspnoea, chest pain).
Rehydration should be done with oral/ Iv fluids( 3L in 24 hours) depending on the patient's condirtion.
Patient should be kept warm.
oxygen can be given if arterial oxygen partial pressure drops of if the oxygen saturation is less tan 95%.
If patient is having fever, ill health or chest symptoms broad spectrum antibiotics should be start after sending blood/ other appropriate specimen for culture and ABST.
Pack cell volume and reticulocyte count should be measure twice a daily. Size of the spleen and liver also need to be examined twice a daily.
Blood transfusion should be consider in symptomatic severe anaemia and exchange transfusion need to be considered in presence of features with visceral sequestration crisis, severe chest crisis, central nervous system involvement and with repeated painful episodes .
Management of acute chest syndrome Pulmonary micro infarctions, chest infections may involved complete segments and patients will have pain, fever, dyspnoes, wheezing and cough. Pain management should be done appropriately. Oxygen should be given with monitoring partial pressure of oxygen in arteries and oxygen saturation. Empirical antibiotics should be started after taking blood and sputum samples for culture and ABST. Chest X ray need to be taken.Bronchodilators like salbutamol will give symptomatic relief in wheezing. Blood transfusion/ exchange transfusion is indicated. Management of acute chest syndrome
Pulmonary micro infarctions, chest infections may involved complete segments and patients will have pain, fever, dyspnoes, wheezing and cough. Pain management should be done appropriately. Oxygen should be given with monitoring partial pressure of oxygen in arteries and oxygen saturation. Empirical antibiotics should be started after taking blood and sputum samples for culture and ABST. Chest X ray need to be taken.Bronchodilators like salbutamol will give symptomatic relief in wheezing. Blood transfusion/ exchange transfusion is indicated.
Management during pregnancy Routine blood transfusions is recommended through out the pregnancy in patients with history of frequent exacerbations and more attention should be given to avoid precipitating factors. Management during pregnancy
Routine blood transfusions is recommended through out the pregnancy in patients with history of frequent exacerbations and more attention should be given to avoid precipitating factors.
Prophylactic blood transfusion This will be needed in patients with frequent crises or patients with major organ damage/ abnormal findings in doppler studies. Transfusion will be continued prophylactically over several months. Iron chelation will be needed in the presence of iron overload following this long term transfusions. Prophylactic blood transfusion
This will be needed in patients with frequent crises or patients with major organ damage/ abnormal findings in doppler studies. Transfusion will be continued prophylactically over several months. Iron chelation will be needed in the presence of iron overload following this long term transfusions.
Hydroxyurea This is indicated in patients with three or more painful crises with in a year. Hydroxyurea is useful in preventing the complications by increasing HbF and total hemoglobin concentrations and by reducing the adhesion of sickled cells to the endothelium. Hydroxyurea
This is indicated in patients with three or more painful crises with in a year. Hydroxyurea is useful in preventing the complications by increasing HbF and total hemoglobin concentrations and by reducing the adhesion of sickled cells to the endothelium.
Stem cell transplantation This is indicated in patients with most severe disease complications causing reduced quality of life and impaired life expectancy. This is proven to be curative. Stem cell transplantation
This is indicated in patients with most severe disease complications causing reduced quality of life and impaired life expectancy. This is proven to be curative.

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