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[1].
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[1][5].
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[1][6]. 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[7].
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[1]. 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[1].
reduction in vision There will be proliferative retinopathy with retinal ischemia following vascular blockage[1].
Chronic bone pain, swelling, redness and limiting movements There can be osteomyelitis associated with sickle cell disease, commonly with salmonella species[2].
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[4].
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[3].
References
  1. KATO GJ, HEBBEL RP, STEINBERG MH, GLADWIN MT. Vasculopathy in Sickle Cell Disease: Biology, Pathophysiology, Genetics, Translational Medicine and New Research Directions Am J Hematol [online] 2009 Sep, 84(9):618-625 [viewed 16 September 2014] Available from: doi:10.1002/ajh.21475
  2. EBONG WW. Acute osteomyelitis in Nigerians with sickle cell disease. Ann Rheum Dis [online] 1986 Nov, 45(11):911-915 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1002018
  3. FULDA KG, LYKENS K. Ethical issues in predictive genetic testing: a public health perspective J Med Ethics [online] 2006 Mar, 32(3):143-147 [viewed 16 September 2014] Available from: doi:10.1136/jme.2004.010272
  4. BOND LR, HATTY SR, HORN ME, DICK M, MEIRE HB, BELLINGHAM AJ. Gall stones in sickle cell disease in the United Kingdom. Br Med J (Clin Res Ed) [online] 1987 Jul 25, 295(6592):234-236 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1247079
  5. SAVITT TL. The Invisible Malady: Sickle Cell Anemia J Natl Med Assoc [online] 1981 Aug, 73(8):739-746 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2552684
  6. ALIYU ZY, TUMBLIN AR, KATO GJ. Current therapy of sickle cell disease Haematologica [online] 2006 Jan, 91(1):7-10 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2204144
  7. MAGNUS S, HAMBLETON I, MOOSDEEN F, SERJEANT G. Recurrent infections in homozygous sickle cell disease Arch Dis Child [online] 1999 Jun, 80(6):537-541 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1717938
  8. MINNITI CP, ECKMAN J, SEBASTIANI P, STEINBERG MH, BALLAS SK. Leg Ulcers in Sickle Cell Disease Am J Hematol [online] 2010 Oct, 85(10):831-833 [viewed 16 September 2014] Available from: doi:10.1002/ajh.21838

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[1][2].
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[1][3].
Examination of joints for limited movements and tenderness over the spine Due to infarction of bones, hips, shoulders and vertibrae can affect commonly[6].
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[5].
Features of chronic liver disease like jaundice, generalized oedema, wasting, ascitis Chronic liver failure can occur with micro infarctions[4].
Dyspnoea On general examination patient will be dyspnoic due to severe anaemia or micro vascular infarction in lungs[7].
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[8].
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[9].
Reduced vision There will be proliferative retinopathy with retinal ischemia following vascular blockage[1].
Bone tenderness, warmth, swelling, redness and limitation of movements. There can be osteomyelitis associated with sickle cell disease, commonly with salmonella species[10].
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[11].
Splenomegally with abdominal tenderness In splenic sequestration there will be enlarged spleen. This is commonly present in infants. These patients will be very ill[9].
Cardiovascular system examination loud second heart sound in pulmonary area can be identified in long term lung damage resulting pulmonary hypertension[12].
References
  1. KATO GJ, HEBBEL RP, STEINBERG MH, GLADWIN MT. Vasculopathy in Sickle Cell Disease: Biology, Pathophysiology, Genetics, Translational Medicine and New Research Directions Am J Hematol [online] 2009 Sep, 84(9):618-625 [viewed 16 September 2014] Available from: doi:10.1002/ajh.21475
  2. SAVITT TL. The Invisible Malady: Sickle Cell Anemia J Natl Med Assoc [online] 1981 Aug, 73(8):739-746 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2552684
  3. RADHAKRISHNAN K, THACKER AK, MALOO JC, EL-MANGOUSH MA. Sickle cell trait and stroke in the young adult. Postgrad Med J [online] 1990 Dec, 66(782):1078-1080 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2429781
  4. SANTI L, MONTANARI G, BERARDI S, PATTI C, FRIGERIO M, SAMA C, CARACENI P, BERNARDI M. Liver Cirrhosis in a Patient with Sickle Cell Trait (Hb S?+ Thalassemia) without Other Known Causes of Hepatic Disease Case Rep Gastroenterol [online] , 3(3):275-279 [viewed 16 September 2014] Available from: doi:10.1159/000235235
  5. JADAVJI T, PROBER CG. Dactylitis in a child with sickle cell trait Can Med Assoc J [online] 1985 Apr 1, 132(7):814-815 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1345873
  6. OKPALA I, TAWIL A. Management of pain in sickle-cell disease J R Soc Med [online] 2002 Sep, 95(9):456-458 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1279994
  7. ATHANASOU NA, HATTON C, MCGEE JO, WEATHERALL DJ. Vascular occlusion and infarction in sickle cell crisis and the sickle chest syndrome. J Clin Pathol [online] 1985 Jun, 38(6):659-664 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC499264
  8. FEMI-PEARSE D, ODUNJO EO. Renal cortical infarcts in sickle-cell trait. Br Med J [online] 1968 Jul 6, 3(5609):34 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1991262
  9. MAGNUS S, HAMBLETON I, MOOSDEEN F, SERJEANT G. Recurrent infections in homozygous sickle cell disease Arch Dis Child [online] 1999 Jun, 80(6):537-541 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1717938
  10. EBONG WW. Acute osteomyelitis in Nigerians with sickle cell disease. Ann Rheum Dis [online] 1986 Nov, 45(11):911-915 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1002018
  11. Sickle-cell anaemia in infancy. Br Med J [online] 1978 Jun 3, 1(6125):1439-1440 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1604958
  12. KATO GJ, ONYEKWERE OC, GLADWIN MT. PULMONARY HYPERTENSION IN SICKLE CELL DISEASE: Relevance to Children Pediatr Hematol Oncol [online] 2007, 24(3):159-170 [viewed 16 September 2014] Available from: doi:10.1080/08880010601185892

Differential Diagnoses

Fact Explanation
Thalassaemia This is a genetic disorder which resulting reduction of alpha or beta globin chain synthesis. This leads to severe anaemia, hepatosplenomegaly and bone marrow hyperplasia, these patient are having a characteristic thalassemic facies and they will present early( before one year) with anaemic features and will require more blood transfusions than sickle cell disease[1].
Hereditory spherocytosis This is another hereditory haemolytic anaemia which causes defect in red blood cell membrane. So it lossess the biconcave shape of the red blood cells leading to extravascular haemolysis. Patient will present with anaemia, Jaundice, splenomegaly, pigment gall stones and aplastic crises. In here osmotic fragility will be increased and in blood picture there will be microsperocytes[2].
Autoimmune haemolytic anaemia This is caused by antibodies produced inside the body against own red blood cells.There are two types, 'warm' and 'cold' types. Patients will present with haemolytic anaemia with various severity. The direct antibody test will be positive due to IgG, IgG and compliment or IgA on the cells[3].
congenital heart disease complicated with pulmonary hypertension congenital valvular heart diseases( eg mitral stenosis, tricuspid regurgitation) can ultimately lead to pulmonary hypertension with right heart failure. On examination there will be a charcteristic murmur on auscultation in these patients, but will not present in sickle cell disease other than features of pulmonary hypertension[4].
Septic arthritis In septic arthritis, patients will present with fever, severe pain in affected joint, pseudo paralysis of the joint due to severe pain, swelling, warmth and readness of the joint[5]. This will be an acute presentation not like in sickle cell disease which is a gradually developing osteomyelitis[7].Bone ischemia also not an acute presentation as septic arthritis.
lower respiratory tract infection In a lower respiratory tract infection there will be pleuritic type chest pain, high fever and cough with sputum production[6]. In pulmonary infarctions in sickle cell disease, patients will present with pleuritic type chest pain, fever, cough but there will not be sputum production. These will be a gradually progressing symptoms not like in lower respiratory tract infection[8].
Other causes of Chronic liver disease In chronic liver disease patient will have loss of appetite, nausea, vomiting, jaundice and some times associated splenomegaly similer to chronic liver disease occur in sickle cell disease. In other causes there will be a history of chronic alcohol use, past history of hepatitis or other cause[9][10].
Diabetes mellitus In diabetes mellitus, patient will present with polyurea, nocturnal urea and excessive thirst. Patient will have high fasting/ post prandial blood sugar levels[12]. In kidneys infarction of medulla with papillary necrosis may lead to fail in concentrating urine causing high urine out put, dehydration and nocturnal enuresis[11].
Strokes due to vascular blockage with thrombus/ atherosclerotic plaque. In brain strokes there will be features of paralysis, paresthesia, seizures and cranial nerve palsy.All patients despite of the primary cause will present with these symptoms. Past medical history and investigation findings will help to differentiate the cause. In sickle cell disease patients will usually present with gradually developing symptoms due to multiple micro vascular infarctions but in other ischemic conditions will present acutely with macro vascular vascular blockage[13][14].
References
  1. SCRIVER CR, BARDANIS M, CARTIER L, CLOW CL, LANCASTER GA, OSTROWSKY JT. Beta-thalassemia disease prevention: genetic medicine applied. Am J Hum Genet [online] 1984 Sep, 36(5):1024-1038 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1684522
  2. BOLTON-MAGGS P. Hereditary spherocytosis; new guidelines Arch Dis Child [online] 2004 Sep, 89(9):809-812 [viewed 17 September 2014] Available from: doi:10.1136/adc.2003.034587
  3. SOKOL RJ, BOOKER DJ, STAMPS R. The pathology of autoimmune haemolytic anaemia. J Clin Pathol [online] 1992 Dec, 45(12):1047-1052 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC494994
  4. EVANS W, SHORT DS. PULMONARY HYPERTENSION IN CONGENITAL HEART DISEASE Br Heart J [online] 1958 Oct, 20(4):529-551 [viewed 20 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC491805
  5. SHIRTLIFF ME, MADER JT. Acute Septic Arthritis Clin Microbiol Rev [online] 2002 Oct, 15(4):527-544 [viewed 20 September 2014] Available from: doi:10.1128/CMR.15.4.527-544.2002
  6. LIM W, VAN DER EERDEN MM, LAING R, BOERSMA W, KARALUS N, TOWN G, LEWIS S, MACFARLANE J. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study Thorax [online] 2003 May, 58(5):377-382 [viewed 20 September 2014] Available from: doi:10.1136/thorax.58.5.377
  7. EBONG WW. Acute osteomyelitis in Nigerians with sickle cell disease. Ann Rheum Dis [online] 1986 Nov, 45(11):911-915 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1002018
  8. YOUNG RC JR, CASTRO O, BAXTER RP, DUNN R, ARMSTRONG EM, COOK FJ, SAMPSON CC. The Lung in Sickle Cell Disease: A Clinical Overview of Common Vascular, Infectious, and Other Problems J Natl Med Assoc [online] 1981 Jan, 73(1):19-26 [viewed 20 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2552608
  9. GORDON SG. Chronic Liver Disease J Gen Intern Med [online] 2000 Feb, 15(2):142 [viewed 20 September 2014] Available from: doi:10.1046/j.1525-1497.2000.11050a.x
  10. SANTI L, MONTANARI G, BERARDI S, PATTI C, FRIGERIO M, SAMA C, CARACENI P, BERNARDI M. Liver Cirrhosis in a Patient with Sickle Cell Trait (Hb S?+ Thalassemia) without Other Known Causes of Hepatic Disease Case Rep Gastroenterol [online] , 3(3):275-279 [viewed 20 September 2014] Available from: doi:10.1159/0002352
  11. NATH KA, KATUSIC ZS. Vasculature and Kidney Complications in Sickle Cell Disease J Am Soc Nephrol [online] 2012 May, 23(5):781-784 [viewed 20 September 2014] Available from: doi:10.1681/ASN.2011101019
  12. PARK H, KIM YG, LEE JW, PARK JS. Newly diagnosed diabetes mellitus patients presenting with proliferative diabetic retinopathy as an initial sign Int J Ophthalmol [online] , 7(1):173-178 [viewed 20 September 2014] Available from: doi:10.3980/j.issn.2222-3959.2014.01.32
  13. KATO GJ, HEBBEL RP, STEINBERG MH, GLADWIN MT. Vasculopathy in Sickle Cell Disease: Biology, Pathophysiology, Genetics, Translational Medicine and New Research Directions Am J Hematol [online] 2009 Sep, 84(9):618-625 [viewed 20 September 2014] Available from: doi:10.1002/ajh.21475
  14. LAAKSO M. Cardiovascular Disease in Type 2 Diabetes From Population to Man to Mechanisms: The Kelly West Award Lecture 2008 Diabetes Care [online] 2010 Feb, 33(2):442-449 [viewed 20 September 2014] Available from: doi:10.2337/dc09-0749

Investigations - for 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[1].
Reticulocyte count Due to frequent red blood cell turnover, there will be increased reticulocyte count up to 10-20%[5].
Blood picture This will show sickle cells and target cells. If associated splenic atrophy is present there will be Howell-jolly bodies[2].
Screening test for sickling This will be positive in a deoxygenated state of blood with dithionate and Na2HPO4[3].
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[4].
Serum bilirubin level This will be increased with the excess haemoglobin break down[6].
References
  1. BAKLOUTI F, DELAUNAY J. Unusual low sickle cell hemoglobin level Haematologica [online] 2013 Jun, 98(6):e64 [viewed 16 September 2014] Available from: doi:10.3324/haematol.2013.087973
  2. DAVIS LR. Changing blood picture in sickle-cell anaemia from shortly after birth to adolescence. J Clin Pathol [online] 1976 Oct, 29(10):898-901 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC476210
  3. Detecting sickle haemoglobin. Br Med J [online] 1972 Apr 29, 2(5808):246 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1788991
  4. GERALDINE M, JUSTIN V, SHEILA U, VENKATESH T. Haemoglobin electrophoresis in diagnosing a case of sickle cell anaemia associated with ?-thalassemia Indian J Clin Biochem [online] 2001 Jul, 16(2):211-212 [viewed 16 September 2014] Available from: doi:10.1007/BF02864864
  5. AARON W BERNARD, VENKAT A, LYONS MS. Full blood count and reticulocyte count in painful sickle crisis Emerg Med J [online] 2006 Apr, 23(4):302-303 [viewed 16 September 2014] Available from: doi:10.1136/emj.2006.035154
  6. COSTA DB, MIKSAD RA, BUFF MS, WANG Y, DEZUBE BJ. Case of fatal sickle cell intrahepatic cholestasis despite use of exchange transfusion in an African-American patient. J Natl Med Assoc [online] 2006 Jul, 98(7):1183-1187 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569475

Investigations - Fitness for Management

Fact Explanation
Full blood count useful in assessing the degree of anaemia which is helpful in deciding further treatment[1].
Trans cranial Doppler ultrasonography This will give evidence of an abnormal blood flow suggesting arterial stenosis[2].
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[3].
Chest X ray Patients with recurrent chest symptoms (dyspnoea), chest infections this is useful as lungs may develop fibrosis[4].
Blood grouping and cross matching This is useful during the treatments before transfusions[5].
References
  1. BAKLOUTI F, DELAUNAY J. Unusual low sickle cell hemoglobin level Haematologica [online] 2013 Jun, 98(6):e64 [viewed 16 September 2014] Available from: doi:10.3324/haematol.2013.087973
  2. ENNINFUL-EGHAN H, MOORE RH, ICHORD R, SMITH-WHITLEY K, KWIATKOWSKI JL. Transcranial Doppler Screening and Prophylactic Transfusion Program Is Effective in Preventing Overt Stroke in Children With Sickle Cell Disease J Pediatr [online] 2010 Sep, 157(3):479-484 [viewed 16 September 2014] Available from: doi:10.1016/j.jpeds.2010.03.007
  3. CHIEN S, USAMI S, BERTLES JF. Abnormal rheology of oxygenated blood in sickle cell anemia J Clin Invest [online] 1970 Apr, 49(4):623-634 [viewed 16 September 2014] Available from: doi:10.1172/JCI106273
  4. AL-MULHIM AF. PATTERN OF PULMONARY MANIFESTATIONS IN PATIENTS WITH SICKLE CELL DISEASE AND FEVER J Family Community Med [online] 2004, 11(3):109-113 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410080
  5. YAZDANBAKHSH K, WARE RE, NOIZAT-PIRENNE F. Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management Blood [online] 2012 Jul 19, 120(3):528-537 [viewed 17 September 2014] Available from: doi:10.1182/blood-2011-11-327361

Investigations - Followup

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[1] .
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[2].
CT/ MRI scanning This is useful in assessing the status of all organs as sickle cell disease affects multiple systems[3].
Renal function tests like serum creatinine. blood urea and serum electrolytes In kidneys infarction of medulla with papillary necrosis may leads to renal failure[4].
Liver function tests like AST, ALT, serum bilirubin levels Chronic liver failure can occur with micro infarction[5].
Bone X ray This is useful in assessing the bony complications such as osteomyelitis. Site will depend on clinical presentation[6].
References
  1. BAKLOUTI F, DELAUNAY J. Unusual low sickle cell hemoglobin level Haematologica [online] 2013 Jun, 98(6):e64 [viewed 16 September 2014] Available from: doi:10.3324/haematol.2013.087973
  2. YOUNG RC JR, RACHAL RE, REINDORF CA, ARMSTRONG EM, POLK OD JR, HACKNEY RL JR, SCOTT RB. Lung Function in Sickle Cell Hemoglobinopathy Patients Compared With Healthy Subjects J Natl Med Assoc [online] 1988 May, 80(5):509-514 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2625764
  3. WOOD JC. Magnetic resonance imaging measurement of iron overload Curr Opin Hematol [online] 2007 May, 14(3):183-190 [viewed 16 September 2014] Available from: doi:10.1097/MOH.0b013e3280d2b76b
  4. ROCHA LB, DA SILVA JN GB, DAHER ED, ROCHA HA, ELIAS DB, GONçALVES RP. Kidney dysfunction and beta S-haplotypes in patients with sickle cell disease Rev Bras Hematol Hemoter [online] 2013, 35(3):171-173 [viewed 16 September 2014] Available from: doi:10.5581/1516-8484.20130052
  5. ISICHEI UP. Liver function and the diagnostic significance of biochemical changes in the blood of African children with sickle cell disease. J Clin Pathol [online] 1980 Jul, 33(7):626-630 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1146173
  6. DA SILVA JUNIOR GB, DAHER ED, DA ROCHA FA. Osteoarticular involvement in sickle cell disease Rev Bras Hematol Hemoter [online] 2012, 34(2):156-164 [viewed 17 September 2014] Available from: doi:10.5581/1516-8484.20120036

Investigations - Screening/Staging

Fact Explanation
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[1].
References
  1. FULDA KG, LYKENS K. Ethical issues in predictive genetic testing: a public health perspective J Med Ethics [online] 2006 Mar, 32(3):143-147 [viewed 17 September 2014] Available from: doi:10.1136/jme.2004.010272

Management - General Measures

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[1].
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[2].
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[3].
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[4].
Good hygienic practices These patients are at risk of getting frequent infections. So good hygienic practices are very important, especially regarding the dental hygien[5].
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[ 6].
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[7].
References
  1. CANTOR AB, MILLER MC III, LARISEY L, MURPHY E. A Study of Media Effectiveness for Sickle Cell Anemia Education in a Rural Community J Natl Med Assoc [online] 1979 Nov, 71(11):1055-1057 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2537543
  2. MURRAY N, MAY A. Painful crises in sickle cell disease--patients' perspectives. BMJ [online] 1988 Aug 13, 297(6646):452-454 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1833896
  3. NDEFO UA, MAXWELL AE, NGUYEN H, CHIOBI TL. Pharmacological Management of Sickle Cell Disease P T [online] 2008 Apr, 33(4):238-243 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730092
  4. ENWONWU CO. Nutritional Support in Sickle Cell Anemia: Theoretical Considerations J Natl Med Assoc [online] 1988 Feb, 80(2):139-144 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2625736
  5. LAURENCE B, GEORGE D, WOODS D, SHOSANYA A, KATZ RV, LANZKRON S, DIENER-WEST M, POWE N. The association between sickle cell disease and dental caries in African Americans Spec Care Dentist [online] 2006, 26(3):95-100 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1786275
  6. COBER MP, PHELPS SJ. Penicillin Prophylaxis in Children with Sickle Cell Disease J Pediatr Pharmacol Ther [online] 2010, 15(3):152-159 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018247
  7. FULDA KG, LYKENS K. Ethical issues in predictive genetic testing: a public health perspective J Med Ethics [online] 2006 Mar, 32(3):143-147 [viewed 17 September 2014] Available from: doi:10.1136/jme.2004.010272

Management - Specific Treatments

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[1].
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[3]. 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[4]. 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[5] should be consider in symptomatic severe anaemia and exchange transfusion[6] need to be considered in presence of features with visceral sequestration crisis, severe chest crisis, central nervous system involvement and with repeated painful episodes[2] .
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[7][8].
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[9].
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[10].
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[11].
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[12].
References
  1. BROZOVIć M, ANIONWU E. Sickle cell disease in Britain. J Clin Pathol [online] 1984 Dec, 37(12):1321-1326 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC499005
  2. STUART J. Management of sickle-cell disease J Clin Pathol Suppl (R Coll Pathol) [online] 1974:26-31 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1347201
  3. OKPALA I, TAWIL A. Management of pain in sickle-cell disease J R Soc Med [online] 2002 Sep, 95(9):456-458 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1279994
  4. CLARK MR, MOHANDAS N, SHOHET SB. Hydration of sickle cells using the sodium ionophore Monensin. A model for therapy. J Clin Invest [online] 1982 Nov, 70(5):1074-1080 [viewed 17 September 2014] Available from: doi:10.1172/JCI110695
  5. AZIZ AM, MESHIKHES AW. Blood Transfusion in Patients with Sickle Cell Disease Requiring Laparoscopic Cholecystectomy JSLS [online] 2011, 15(4):480-485 [viewed 17 September 2014] Available from: doi:10.4293/108680811X13176785203996
  6. VAN DE PETTE JE, PEARSON TC, SLATER NG. Exchange transfusion in life-threatening sickling crises J R Soc Med [online] 1982 Oct, 75(10):777-780 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1438110
  7. SIDDIQUI A, AHMED S. Pulmonary manifestations of sickle cell disease Postgrad Med J [online] 2003 Jul, 79(933):384-390 [viewed 17 September 2014] Available from: doi:10.1136/pmj.79.933.384
  8. MAK V, DAVIES S. The pulmonary physician in critical care o Illustrative case 6: Acute chest syndrome of sickle cell anaemia Thorax [online] 2003 Aug, 58(8):726-728 [viewed 17 September 2014] Available from: doi:10.1136/thorax.58.8.726
  9. BROZOVIć M, DAVIES S. Management of sickle cell disease. Postgrad Med J [online] 1987 Aug, 63(742):605-609 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2428428
  10. ENNINFUL-EGHAN H, MOORE RH, ICHORD R, SMITH-WHITLEY K, KWIATKOWSKI JL. Transcranial Doppler Screening and Prophylactic Transfusion Program Is Effective in Preventing Overt Stroke in Children With Sickle Cell Disease J Pediatr [online] 2010 Sep, 157(3):479-484 [viewed 17 September 2014] Available from: doi:10.1016/j.jpeds.2010.03.007
  11. NDEFO UA, MAXWELL AE, NGUYEN H, CHIOBI TL. Pharmacological Management of Sickle Cell Disease P T [online] 2008 Apr, 33(4):238-243 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730092
  12. SHENOY S. Hematopoietic stem-cell transplantation for sickle cell disease: current evidence and opinions Ther Adv Hematol [online] 2013 Oct, 4(5):335-344 [viewed 17 September 2014] Available from: doi:10.1177/2040620713483063