History

Fact Explanation
Introduction This is a one of haemoglobinopathy characterized by mutation in the beta-globin Chain (in the sixth codon of exon-1 on chromosome 11). So this is an inherited condition causing replacement of the normal glutamic acid with valine acid, forming abnormal aemoglobin molecules (sickle cell hemoglobin) This sickle cell haemoglobin (Hb s) is insoluble and they form crystals ( rigid tubular spiral bodies) when expose to low haemoglobin tension. which deform the red cell from bi-concave shape in to a sickle shape. This process is irreversible causing reduction in life span of the red blood cells. loosing the flexibility of red blood cells causes blockage of micro vasculature. [1][13].
Features of anaemia like easy fatiguability and lethargy As there is a mutation in beta globin chain there will be sickle cell hemoglobin 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, children may present with sudden onset features of anaemia due to sudden fall in haemoglobin level[1][5][14][39].
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: Brain strokes can occur giving features of paralysis, paresthesia and cranial nerve palsy[15][16][17]. In spinal cord, features of infarction like limb paralysis, paresthesia, bladder/ bowel dysfunction[18][19]. In bones, ischemic pain at site of the joint/back pain and fractures following long bone infarction can be seen. patients condition can be progress into osteomyelitis in some patients [20][21]. children may develop myocardial infarctions following hypoperfusion of the myocardium( chest pain, difficulty in breathing, dizziness)[12]. In lungs there will be shortness of breath and pleuritic type chest pain[22]. In mesentry, acute abdominal pain will be the presentation[23]. In digits( hand- foot syndrome), painful fingers and toes with small bone infarction[24][25]. In kidneys infarction of medulla with papillary necrosis may lead to fail in concentrating urine causing high urine out put, dehydration and nocturnal enuresis[26][27][28]. Chronic liver failure with micro infarction causing loss of appetite, yellowish discoloration of eyes[29][30]. Splenic infarction leads to recurrent infections like upper/ lower respiratory tract infections and diarrheal illnessess[7][31][32].
Features of visceral sequestration Sickling inside the organs and pooling of the blood can be present as a painful crisis. this is usually associated with severe exacerbstion of anaemia[1][33][34]. 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][35][36].
Chronic bone pain, swelling, redness and limiting movements There can be osteomyelitis associated with sickle cell disease, commonly with salmonella species[2][37][38].
reduction in vision There will be proliferative retinopathy with retinal ischemia following vascular blockage. So children may present with visual problems[1][40][41].
Features suggestive of gall stones With excessive haemoglobin breakdown, there will be increased chance of pigment gall stone formation. They may be asymptomatic and if they are symptomatic, children will have persistent right hypochondriac pain or may present with acute cholecystitis (fever, biliary colicks, nausea and vomiting)[4][9].
Fever, chest pain and chronic difficulty in breathing Children with sickle cell disease may develop acute chest syndrome or they will have sickle cell chronic lung disease. Acute chest syndrome is characterised by fever and chest pain while in chronic lung disease children will have long term shortness of breath, chest pain exercise intolerance[10][11].
,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].
History suggestive of aplasit crisies patient will have sudden onset anaemic features ( faintishness, easy fatiguability) following aplastic crises. This condition occurs following infection with parvo B19 virus or from folate deficiency. With this there will be a sudden onset fall in haemoglobin due to complete, temporary cessation of red blood cell production[42][43].
Features suggestive of renal failure( early polyurea with later reduced urine out put, haematuria, generalized body swelling) kidney damage can occur following chronic microvascular occlusion (infarction) with sickle cell disease and following haemolysis. In infarctions there will be changes mainly in medulla ( as vasa recta are the sites of sickling take place). papillary necrosis also can be seen and rarely patients can go into end stage renal failure. With the excessive intra vascular haemolysis there will be excessive haemoglobin release in to the circulation. So haptoglobin and hemopexin (protective hemoglobin-scavenging mechanism) will be filled with excessive haemoglobin leaving free haemoglobin in to the circulationlation. So these haemoglobin then bind to nitrogen oxide which useful in smooth muscle relaxation. With limitation of Nitrogen oxide in the circulation also finally leads to kidney damage[44][45][46].
History of infection like pneumonia, meningitis and osteomyelitis These patients are at risk of developing infections ( due to hyposplenism with microinfarctions) especially with encapsulated organisms like Streptococcus pneumoniae, Haemopilus influenzae. also they are more prone to get osteomyelitis by salmonella and other organisms. Risk of infections progressing to sepsis also very high among these children[47][48].
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
  9. CURRò G, MEO A, IPPOLITO D, PUSIOL A, CUCINOTTA E. Asymptomatic Cholelithiasis in Children With Sickle Cell Disease: Early or Delayed Cholecystectomy? Ann Surg [online] 2007 Jan, 245(1):126-129 [viewed 15 October 2014] Available from: doi:10.1097/01.sla.0000242716.66878.23
  10. SIDDIQUI A, AHMED S. Pulmonary manifestations of sickle cell disease Postgrad Med J [online] 2003 Jul, 79(933):384-390 [viewed 15 October 2014] Available from: doi:10.1136/pmj.79.933.384
  11. SYLVESTER K, PATEY R, MILLIGAN P, DICK M, RAFFERTY G, REES D, THEIN S, GREENOUGH A. Pulmonary function abnormalities in children with sickle cell disease Thorax [online] 2004 Jan, 59(1):67-70 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1758855
  12. DE MONTALEMBERT M, MAUNOURY C, ACAR P, BROUSSE V, SIDI D, LENOIR G. Myocardial ischaemia in children with sickle cell disease Arch Dis Child [online] 2004 Apr, 89(4):359-362 [viewed 15 October 2014] Available from: doi:10.1136/adc.2003.027326
  13. NDEFO UA, MAXWELL AE, NGUYEN H, CHIOBI TL. Pharmacological Management of Sickle Cell Disease P T [online] 2008 Apr, 33(4):238-243 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730092
  14. MCGANN PT, WARE RE. Hydroxyurea for sickle cell anemia: What have we learned and what questions still remain? Curr Opin Hematol [online] 2011 May, 18(3):158-165 [viewed 15 October 2014] Available from: doi:10.1097/MOH.0b013e32834521dd
  15. HULBERT ML, FORD AL. Understanding sickle cell brain drain Blood [online] 2014 Aug 7, 124(6):830-831 [viewed 15 October 2014] Available from: doi:10.1182/blood-2014-06-582403
  16. DOWLING MM, QUINN CT, ROGERS ZR, BUCHANAN GR. Acute Silent Cerebral Infarction in Children with Sickle Cell Anemia Pediatr Blood Cancer [online] 2010 Mar, 54(3):461-464 [viewed 15 October 2014] Available from: doi:10.1002/pbc.22242
  17. QUINN CT, MCKINSTRY RC, DOWLING MM, BALL WS, KRAUT MA, CASELLA JF, DLAMINI N, ICHORD RN, JORDAN LC, KIRKHAM FJ, NOETZEL MJ, ROACH ES, STROUSE JJ, KWIATKOWSKI JL, HIRTZ D, DEBAUN MR. Acute Silent Cerebral Ischemic Events in Children with Sickle Cell Anemia JAMA Neurol [online] 2013 Jan, 70(1):58-65 [viewed 15 October 2014] Available from: doi:10.1001/jamaneurol.2013.576
  18. EDWARDS A, CLAY EL, JEWELLS V, ADAMS S, CRAWFORD RD, REDDING-LALLINGER R. A 19-year-old man with sickle cell disease presenting with spinal infarction: a case report J Med Case Rep [online] :210 [viewed 15 October 2014] Available from: doi:10.1186/1752-1947-7-210
  19. SOHAL AS, SUNDARAM M, MALLEWA M, TAWIL M, KNEEN R. Anterior Spinal Artery Syndrome in a Girl With Down Syndrome: Case Report and Literature Review J Spinal Cord Med [online] 2009 Jun, 32(3):349-353 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2718815
  20. HUO MH, FRIEDLAENDER GE, MARSH JS. Orthopaedic manifestations of sickle-cell disease. Yale J Biol Med [online] 1990, 63(3):195-207 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2589295
  21. HERNIGOU P, DALTRO G, FLOUZAT-LACHANIETTE CH, ROUSSIGNOL X, POIGNARD A. Septic Arthritis in Adults with Sickle Cell Disease Often is Associated with Osteomyelitis or Osteonecrosis Clin Orthop Relat Res [online] 2010 Jun, 468(6):1676-1681 [viewed 15 October 2014] Available from: doi:10.1007/s11999-009-1149-3
  22. 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 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2552608
  23. ABADIN SS, SALAZAR MR, ZHU RY, CONNOLLY MM, PODBIELSKI FJ. Small Bowel Ischemia in a Sickle Cell Patient Case Rep Gastroenterol [online] , 3(1):26-29 [viewed 15 October 2014] Available from: doi:10.1159/000197257
  24. Sickle-cell anaemia in infancy. Br Med J [online] 1978 Jun 3, 1(6125):1439-1440 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1604958
  25. NOONAN WJ. Salmonella osteomyelitis presenting as "hand-foot syndrome" in sickle-cell disease. Br Med J (Clin Res Ed) [online] 1982 May 15, 284(6327):1464-1465 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1498378
  26. OKAFOR UH, ANEKE E. Outcome and Challenges of Kidney Transplant in Patients with Sickle Cell Disease J Transplant [online] 2013:614610 [viewed 15 October 2014] Available from: doi:10.1155/2013/614610
  27. JOHN N. A Review of Clinical Profile in Sickle Cell Traits Oman Med J [online] 2010 Jan, 25(1):3-8 [viewed 15 October 2014] Available from: doi:10.5001/omj.2010.2
  28. CROSLEY AP JR, STRICKLAND WH. Renal Function in Sickle Cell Anemia : A Case Report and Review of The Literature J Natl Med Assoc [online] 1961 Jan, 53(1):39-40 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2641843
  29. GLADWIN MT, SACHDEV V. Cardiovascular Abnormalities in Sickle Cell Disease J Am Coll Cardiol [online] 2012 Mar 27, 59(13):10.1016/j.jacc.2011.10.900 [viewed 15 October 2014] Available from: doi:10.1016/j.jacc.2011.10.900
  30. PAPAFRAGKAKIS H, ONA MA, CHANGELA K, SADANANDAN S, JELIN A, ANAND S, DUDDEMPUDI S. Acute liver function decompensation in a patient with sickle cell disease managed with exchange transfusion and endoscopic retrograde cholangiography Therap Adv Gastroenterol [online] 2014 Sep, 7(5):217-223 [viewed 15 October 2014] Available from: doi:10.1177/1756283X14530781
  31. AL-SALEM AH. Splenic Complications of Sickle Cell Anemia and the Role of Splenectomy ISRN Hematol [online] 2011:864257 [viewed 15 October 2014] Available from: doi:10.5402/2011/864257
  32. SHEIKHA A. Splenic syndrome in patients at high altitude with unrecognized sickle cell trait: splenectomy is often unnecessary Can J Surg [online] 2005 Oct, 48(5):377-381 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3211898
  33. GRUNDY R, HOWARD R, EVANS J. Practical management of pain in sickling disorders. Arch Dis Child [online] 1993 Aug, 69(2):256-259 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1029472
  34. MCGANN PT, WARE RE. Hydroxyurea for sickle cell anemia: What have we learned and what questions still remain? Curr Opin Hematol [online] 2011 May, 18(3):158-165 [viewed 15 October 2014] Available from: doi:10.1097/MOH.0b013e32834521dd
  35. VASCONCELOS A, PRIOR AR, FERRãO A, MORAIS A. An adolescent with sickle cell anaemia experiencing disease-related complications: priapism and leg ulcer - a management challenge BMJ Case Rep [online] :bcr1120115146 [viewed 15 October 2014] Available from: doi:10.1136/bcr.11.2011.5146
  36. 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 15 October 2014] Available from: doi:10.1002/ajh.21838
  37. EBONG WW. Acute osteomyelitis in Nigerians with sickle cell disease. Ann Rheum Dis [online] 1986 Nov, 45(11):911-915 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1002018
  38. ADEYOKUNNU AA, HENDRICKSE RG. Salmonella osteomyelitis in childhood. A report of 63 cases seen in Nigerian children of whom 57 had sickle cell anaemia. Arch Dis Child [online] 1980 Mar, 55(3):175-184 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1626764
  39. BRANDOW AM, LIEM R. "Sickle Cell Disease in the Emergency Department: Atypical Complications and Management" Clin Pediatr Emerg Med [online] 2011 Sep 1, 12(3):202-212 [viewed 15 October 2014] Available from: doi:10.1016/j.cpem.2011.07.003
  40. TALBOT JF, BIRD AC, SERJEANT GR. Retinal changes in sickle cell/hereditary persistence of fetal haemoglobin syndrome. Br J Ophthalmol [online] 1983 Nov, 67(11):777-778 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1040197
  41. TALBOT JF, BIRD AC, RABB LM, MAUDE GH, SERJEANT GR. Sickle cell retinopathy in Jamaican children: a search for prognostic factors. Br J Ophthalmol [online] 1983 Nov, 67(11):782-785 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1040199
  42. GOLDSTEIN AR, ANDERSON MJ, SERJEANT GR. Parvovirus associated aplastic crisis in homozygous sickle cell disease. Arch Dis Child [online] 1987 Jun, 62(6):585-588 [viewed 19 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1778435
  43. BROWNELL AI, MCSWIGGAN DA, CUBITT WD, ANDERSON MJ. Aplastic and hypoplastic episodes in sickle cell disease and thalassaemia intermedia. J Clin Pathol [online] 1986 Feb, 39(2):121-124 [viewed 19 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC499663
  44. CRUZ IA, HOSTEN AO, DILLARD MG, CASTRO OL. Advanced Renal Failure in Patients with Sickle Cell Anemia: Clinical Course and Prognosis J Natl Med Assoc [online] 1982 Nov, 74(11):1103-1109 [viewed 19 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2561347
  45. OSEI-YEBOAH CT, RODRIGUES O. Renal Status of Children With Sickle Cell Disease in Accra, Ghana Ghana Med J [online] 2011 Dec, 45(4):155-160 [viewed 19 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283093
  46. ALIYU ZY, TUMBLIN AR, KATO GJ. Current therapy of sickle cell disease Haematologica [online] 2006 Jan, 91(1):7-10 [viewed 19 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2204144
  47. JOHN AB, RAMLAL A, JACKSON H, MAUDE GH, SHARMA AW, SERJEANT GR. Prevention of pneumococcal infection in children with homozygous sickle cell disease. Br Med J (Clin Res Ed) [online] 1984 May 26, 288(6430):1567-1570 [viewed 19 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1441216
  48. LEMBO NJ. Pneumococcal Infections in Children with Sickle Cell Disease: Increased Incidence, Immunological Defects, Vaccine Failure, and Prospects for the Future J Natl Med Assoc [online] 1981 Jan, 73(1):43-45 [viewed 19 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2552622

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].
Icterus With the excessive haemolysis causing excessive billirubin production and chronic liver failure can occur in these patients with micro infarctions both acan cause icterus[4][28][29].
Dyspnoea On general examination patient will be dyspnoic due to severe anaemia or micro vascular infarction in lungs[7].Children with sickle cell disease may also develop acute chest syndrome or they will have sickle cell chronic lung disease. Acute chest syndrome is characterised by fever and chest pain while in chronic lung disease children will have long term shortness of breath, chest pain exercise intolerance[15][16].
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][33][34].
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][26][27].
Examination of joints and bones for limited movements and tenderness over bones Due to infarction of the long bones, joints like hips, shoulders and vertibrae can affect commonly[6][22][23].
Features of chronic liver disease like jaundice, generalized oedema, wasting, ascitis Chronic liver failure can occur with micro infarctions[4][28][29].
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][17][18][19][20][21].
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][30][31][32].
Reduced vision There will be proliferative retinopathy with retinal ischemia following vascular blockage[1][36][37].
Bone tenderness, warmth, swelling, redness and limitation of movements. There can be osteomyelitis associated with sickle cell disease, commonly with salmonella species[10][24][25].
Ulcers in lower limb 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][33][34].
Cardiovascular system examination loud second heart sound in pulmonary area can be identified in long term lung damage resulting pulmonary hypertension[12][35].
Abdominal examination for right hypochondriac tenderness and any associated constitutional symptom. With excessive haemoglobin breakdown, there will be increased chance of pigment gall stone formation. They may be asymptomatic and if they are symptomatic, children will have persistent right hypochondriac pain or may present with acute cholecystitis (fever, biliary colicks, nausea and vomiting)[13][14].
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
  13. 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
  14. CURRò G, MEO A, IPPOLITO D, PUSIOL A, CUCINOTTA E. Asymptomatic Cholelithiasis in Children With Sickle Cell Disease: Early or Delayed Cholecystectomy? Ann Surg [online] 2007 Jan, 245(1):126-129 [viewed 15 October 2014] Available from: doi:10.1097/01.sla.0000242716.66878.23
  15. SYLVESTER K, PATEY R, MILLIGAN P, DICK M, RAFFERTY G, REES D, THEIN S, GREENOUGH A. Pulmonary function abnormalities in children with sickle cell disease Thorax [online] 2004 Jan, 59(1):67-70 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1758855
  16. SIDDIQUI A, AHMED S. Pulmonary manifestations of sickle cell disease Postgrad Med J [online] 2003 Jul, 79(933):384-390 [viewed 15 October 2014] Available from: doi:10.1136/pmj.79.933.384
  17. QUINN CT, MCKINSTRY RC, DOWLING MM, BALL WS, KRAUT MA, CASELLA JF, DLAMINI N, ICHORD RN, JORDAN LC, KIRKHAM FJ, NOETZEL MJ, ROACH ES, STROUSE JJ, KWIATKOWSKI JL, HIRTZ D, DEBAUN MR. Acute Silent Cerebral Ischemic Events in Children with Sickle Cell Anemia JAMA Neurol [online] 2013 Jan, 70(1):58-65 [viewed 15 October 2014] Available from: doi:10.1001/jamaneurol.2013.576
  18. HULBERT ML, FORD AL. Understanding sickle cell brain drain Blood [online] 2014 Aug 7, 124(6):830-831 [viewed 15 October 2014] Available from: doi:10.1182/blood-2014-06-582403
  19. DOWLING MM, QUINN CT, ROGERS ZR, BUCHANAN GR. Acute Silent Cerebral Infarction in Children with Sickle Cell Anemia Pediatr Blood Cancer [online] 2010 Mar, 54(3):461-464 [viewed 15 October 2014] Available from: doi:10.1002/pbc.22242
  20. SOHAL AS, SUNDARAM M, MALLEWA M, TAWIL M, KNEEN R. Anterior Spinal Artery Syndrome in a Girl With Down Syndrome: Case Report and Literature Review J Spinal Cord Med [online] 2009 Jun, 32(3):349-353 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2718815
  21. EDWARDS A, CLAY EL, JEWELLS V, ADAMS S, CRAWFORD RD, REDDING-LALLINGER R. A 19-year-old man with sickle cell disease presenting with spinal infarction: a case report J Med Case Rep [online] :210 [viewed 15 October 2014] Available from: doi:10.1186/1752-1947-7-210
  22. HERNIGOU P, DALTRO G, FLOUZAT-LACHANIETTE CH, ROUSSIGNOL X, POIGNARD A. Septic Arthritis in Adults with Sickle Cell Disease Often is Associated with Osteomyelitis or Osteonecrosis Clin Orthop Relat Res [online] 2010 Jun, 468(6):1676-1681 [viewed 15 October 2014] Available from: doi:10.1007/s11999-009-1149-3
  23. HUO MH, FRIEDLAENDER GE, MARSH JS. Orthopaedic manifestations of sickle-cell disease. Yale J Biol Med [online] 1990, 63(3):195-207 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2589295
  24. ADEYOKUNNU AA, HENDRICKSE RG. Salmonella osteomyelitis in childhood. A report of 63 cases seen in Nigerian children of whom 57 had sickle cell anaemia. Arch Dis Child [online] 1980 Mar, 55(3):175-184 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1626764
  25. EBONG WW. Acute osteomyelitis in Nigerians with sickle cell disease. Ann Rheum Dis [online] 1986 Nov, 45(11):911-915 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1002018
  26. NOONAN WJ. Salmonella osteomyelitis presenting as "hand-foot syndrome" in sickle-cell disease. Br Med J (Clin Res Ed) [online] 1982 May 15, 284(6327):1464-1465 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1498378
  27. Sickle-cell anaemia in infancy. Br Med J [online] 1978 Jun 3, 1(6125):1439-1440 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1604958
  28. PAPAFRAGKAKIS H, ONA MA, CHANGELA K, SADANANDAN S, JELIN A, ANAND S, DUDDEMPUDI S. Acute liver function decompensation in a patient with sickle cell disease managed with exchange transfusion and endoscopic retrograde cholangiography Therap Adv Gastroenterol [online] 2014 Sep, 7(5):217-223 [viewed 15 October 2014] Available from: doi:10.1177/1756283X14530781
  29. GLADWIN MT, SACHDEV V. Cardiovascular Abnormalities in Sickle Cell Disease J Am Coll Cardiol [online] 2012 Mar 27, 59(13):10.1016/j.jacc.2011.10.900 [viewed 15 October 2014] Available from: doi:10.1016/j.jacc.2011.10.900
  30. CROSLEY AP JR, STRICKLAND WH. Renal Function in Sickle Cell Anemia : A Case Report and Review of The Literature J Natl Med Assoc [online] 1961 Jan, 53(1):39-40 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2641843
  31. OKAFOR UH, ANEKE E. Outcome and Challenges of Kidney Transplant in Patients with Sickle Cell Disease J Transplant [online] 2013:614610 [viewed 15 October 2014] Available from: doi:10.1155/2013/614610
  32. JOHN N. A Review of Clinical Profile in Sickle Cell Traits Oman Med J [online] 2010 Jan, 25(1):3-8 [viewed 15 October 2014] Available from: doi:10.5001/omj.2010.2
  33. SHEIKHA A. Splenic syndrome in patients at high altitude with unrecognized sickle cell trait: splenectomy is often unnecessary Can J Surg [online] 2005 Oct, 48(5):377-381 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3211898
  34. AL-SALEM AH. Splenic Complications of Sickle Cell Anemia and the Role of Splenectomy ISRN Hematol [online] 2011:864257 [viewed 15 October 2014] Available from: doi:10.5402/2011/864257
  35. DE MONTALEMBERT M, MAUNOURY C, ACAR P, BROUSSE V, SIDI D, LENOIR G. Myocardial ischaemia in children with sickle cell disease Arch Dis Child [online] 2004 Apr, 89(4):359-362 [viewed 15 October 2014] Available from: doi:10.1136/adc.2003.027326
  36. TALBOT JF, BIRD AC, RABB LM, MAUDE GH, SERJEANT GR. Sickle cell retinopathy in Jamaican children: a search for prognostic factors. Br J Ophthalmol [online] 1983 Nov, 67(11):782-785 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1040199
  37. TALBOT JF, BIRD AC, SERJEANT GR. Retinal changes in sickle cell/hereditary persistence of fetal haemoglobin syndrome. Br J Ophthalmol [online] 1983 Nov, 67(11):777-778 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1040197

Differential Diagnoses

Fact Explanation
Thalassemia 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].
pulmonary hypertension congenital heart disease complicated with 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, child 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].
Congenital Chronic liver disease In children congenital chronic liver disease like biliary atresia and choledochal cyst common than other causes. Children will have loss of appetite, nausea, vomiting, jaundice and some times associated splenomegaly similer to chronic liver disease occur in sickle cell disease[9][10].
Type 1 Diabetes mellitus Children with Type 1 diabetes mellitus 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. Children with hereditory diseases causing thrombotic complications (eg: thrombotic thrombocytopenic purpura) are more prone to develop strokes 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].
Sickling Test 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].
red cell indices(MCV, MCH and MCHC) This is normal in patients with Sickle cell disease, as they are getting normocytic normochromic anaemia. But with the excessive haemolysis, there will be low red cell indices with iron deficiency (due to microcytic hypochromic anaemia). The values of hemoglobin, hematocrit (packed cell volume) and red blood cell counts are useful in calculating this[7][8].
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
  7. ODENHEIMER DJ, WHITTEN CF, RUCKNAGEL DL, SARNAIK SA, SING CF. Heterogeneity of sickle-cell anemia based on a profile of hematological variables. Am J Hum Genet [online] 1983 Nov, 35(6):1224-1240 [viewed 19 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1685962
  8. DOSUNMU AO, BALOGUN TM, ADEYEYE OO, DANIEL FA, AKINOLA RA, ONAKOYA JA, AKINBAMI AA, SAGOE AO, ONADEKO BO. Prevalence of pulmonary hypertension in sickle cell anaemia patients of a tertiary hospital in Nigeria Niger Med J [online] 2014, 55(2):161-165 [viewed 19 October 2014] Available from: doi:10.4103/0300-1652.129661

Investigations - Fitness for Management

Fact Explanation
measure lung volume, forced expiratory volume in 1 second, forced vital capacity (FVC), and peak expiratory flow (PEF). This will be useful in assessing lung function[6][7].
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. Patients with chronic lung disease will have X ray changes similer to interstitial lung disease[4][6][7].
Blood grouping and cross matching This is useful during the treatments before transfusions[5].
Ultrasound scan of the abdomen With excessive haemoglobin breakdown, there will be increased chance of pigment gall stone formation. They may be asymptomatic or symptomatic[8][9].
ECG, echocardiogrm Children can develop myocardial infarctions following hypoperfusion. So these tests will be very useful in assessing the cardiac function[1].
References
  1. DE MONTALEMBERT M, MAUNOURY C, ACAR P, BROUSSE V, SIDI D, LENOIR G. Myocardial ischaemia in children with sickle cell disease Arch Dis Child [online] 2004 Apr, 89(4):359-362 [viewed 15 October 2014] Available from: doi:10.1136/adc.2003.027326
  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
  6. SYLVESTER K, PATEY R, MILLIGAN P, DICK M, RAFFERTY G, REES D, THEIN S, GREENOUGH A. Pulmonary function abnormalities in children with sickle cell disease Thorax [online] 2004 Jan, 59(1):67-70 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1758855
  7. SIDDIQUI A, AHMED S. Pulmonary manifestations of sickle cell disease Postgrad Med J [online] 2003 Jul, 79(933):384-390 [viewed 15 October 2014] Available from: doi:10.1136/pmj.79.933.384
  8. CURRò G, MEO A, IPPOLITO D, PUSIOL A, CUCINOTTA E. Asymptomatic Cholelithiasis in Children With Sickle Cell Disease: Early or Delayed Cholecystectomy? Ann Surg [online] 2007 Jan, 245(1):126-129 [viewed 15 October 2014] Available from: doi:10.1097/01.sla.0000242716.66878.23
  9. 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

Investigations - Followup

Fact Explanation
Full blood count Full blood count 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. Parents/ caregivers should educate about the disease, symptoms in exacerbatons, preventive methods, treatment options available and possible complications[1].
Avoid precipitating factors Parents/ caregivers or elder children 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][14].
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][15].
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][9][10][11].
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][12][13].
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
  8. Prevention and therapy of bacterial infections for children with asplenia or hyposplenia Paediatr Child Health [online] 1999 Sep, 4(6):417-421 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827744
  9. JOHN AB, RAMLAL A, JACKSON H, MAUDE GH, SHARMA AW, SERJEANT GR. Prevention of pneumococcal infection in children with homozygous sickle cell disease. Br Med J (Clin Res Ed) [online] 1984 May 26, 288(6430):1567-1570 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1441216
  10. BERKOVITCH M, PAPADOURIS D, SHAW D, ONUAHA N, DIAS C, OLIVIERI NF. Trying to improve compliance with prophylactic penicillin therapy in children with sickle cell disease Br J Clin Pharmacol [online] 1998 Jun, 45(6):605-607 [viewed 15 October 2014] Available from: doi:10.1046/j.1365-2125.1998.00730.x
  11. Prophylactic antibiotics in children Paediatr Child Health [online] 1999 Oct, 4(7):490-494 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827761
  12. MUTHUSWAMY V. Ethical issues in genetic counselling with special reference to haemoglobinopathies Indian J Med Res [online] 2011 Oct, 134(4):547-551 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237255
  13. NEAL-COOPER F, SCOTT RB. Genetic counseling in sickle cell anemia: experiences with couples at risk. Public Health Rep [online] 1988, 103(2):174-178 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1477975
  14. NDEFO UA, MAXWELL AE, NGUYEN H, CHIOBI TL. Pharmacological Management of Sickle Cell Disease P T [online] 2008 Apr, 33(4):238-243 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730092
  15. MILNE RI. Assessment of care of children with sickle cell disease: implications for neonatal screening programmes. BMJ [online] 1990 Feb 10, 300(6721):371-374 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1662105

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][15][16].
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][13][14][17][18].
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][11].
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][19][20].
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][21][22][23].
Management of nephropathy Patient with nephropathy should be manage according to the usual principles of renal failure management while managing the sickle cell disease. eg: Manage hypertension if associated with. High dose of loop diuretics like furosemide 250mg -2g/24hrs with restriction of fluid intake. Can give erythropoietin, iron supplement for anaemia (response to eruthropoietin is poor in these patients). Dretary control with sodium restriction, if hyperkalemia present potassium restriction will be needed[24][25][26].
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
  13. SYLVESTER K, PATEY R, MILLIGAN P, DICK M, RAFFERTY G, REES D, THEIN S, GREENOUGH A. Pulmonary function abnormalities in children with sickle cell disease Thorax [online] 2004 Jan, 59(1):67-70 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1758855
  14. KNIGHT-MADDEN J, FORRESTER T, LEWIS N, GREENOUGH A. Asthma in children with sickle cell disease and its association with acute chest syndrome Thorax [online] 2005 Mar, 60(3):206-210 [viewed 15 October 2014] Available from: doi:10.1136/thx.2004.029165
  15. HUGH-JONES K, LEHMANN H, MCALISTER JM. Some Experiences in Managing Sickle-cell Anaemia in Children and Young Adults, Using Alkalis and Magnesium Br Med J [online] 1964 Jul 25, 2(5403):226-229 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1817849
  16. SMITH WR, BOVBJERG VE, PENBERTHY LT, MCCLISH DK, LEVENSON JL, ROBERTS JD, GIL K, ROSEFF SD, AISIKU IP. Understanding pain and improving management of sickle cell disease: the PiSCES study. J Natl Med Assoc [online] 2005 Feb, 97(2):183-193 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2568749
  17. 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 15 October 2014] Available from: doi:10.1136/thorax.58.8.726
  18. ANIM SO, STRUNK RC, DEBAUN MR. Asthma morbidity and treatment in children with sickle cell disease Expert Rev Respir Med [online] 2011 Oct, 5(5):635-645 [viewed 15 October 2014] Available from: doi:10.1586/ers.11.64
  19. LANZKRON S, STROUSE JJ, WILSON R, BEACH MC, HAYWOOD C, PARK H, WITKOP C, BASS EB, SEGAL JB. Systematic Review: Hydroxyurea for the Treatment of Adults with Sickle Cell Disease Ann Intern Med [online] 2008 Jun 17, 148(12):939-955 [viewed 15 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256736
  20. THORNBURG CD, CALATRONI A, TELEN M, KEMPER AR. ADHERENCE TO HYDROXYUREA IN CHILDREN WITH SICKLE CELL ANEMIA J Pediatr [online] 2010 Mar, 156(3):415-419 [viewed 15 October 2014] Available from: doi:10.1016/j.jpeds.2009.09.044
  21. LUCARELLI G, ISGRò A, SODANI P, GAZIEV J. Hematopoietic Stem Cell Transplantation in Thalassemia and Sickle Cell Anemia Cold Spring Harb Perspect Med [online] 2012 May, 2(5):a011825 [viewed 15 October 2014] Available from: doi:10.1101/cshperspect.a011825
  22. ANGELUCCI E, MATTHES-MARTIN S, BARONCIANI D, BERNAUDIN F, BONANOMI S, CAPPELLINI MD, DALLE JH, DI BARTOLOMEO P, DE HEREDIA CD, DICKERHOFF R, GIARDINI C, GLUCKMAN E, HUSSEIN AA, KAMANI N, MINKOV M, LOCATELLI F, ROCHA V, SEDLACEK P, SMIERS F, THURET I, YANIV I, CAVAZZANA M, PETERS C. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel Haematologica [online] 2014 May, 99(5):811-820 [viewed 15 October 2014] Available from: doi:10.3324/haematol.2013.099747
  23. SHENOY S. Umbilical Cord Blood: An Evolving Stem Cell Source for Sickle Cell Disease Transplants Stem Cells Transl Med [online] 2013 May, 2(5):337-340 [viewed 15 October 2014] Available from: doi:10.5966/sctm.2012-0180
  24. ALIYU ZY, TUMBLIN AR, KATO GJ. Current therapy of sickle cell disease Haematologica [online] 2006 Jan, 91(1):7-10 [viewed 19 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2204144
  25. CRUZ IA, HOSTEN AO, DILLARD MG, CASTRO OL. Advanced Renal Failure in Patients with Sickle Cell Anemia: Clinical Course and Prognosis J Natl Med Assoc [online] 1982 Nov, 74(11):1103-1109 [viewed 19 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2561347
  26. OSEI-YEBOAH CT, RODRIGUES O. Renal Status of Children With Sickle Cell Disease in Accra, Ghana Ghana Med J [online] 2011 Dec, 45(4):155-160 [viewed 19 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283093