Sickle Cell Anaemia.pptx recomended for you

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this would help you understand basic concept of scikle cell anemia,pathogenesis, clinical features, maganement and investigations to mention but a few.

1. Sickle Cell Anaemia DEPARTMENT OF HEMATOLOGY AND BLOOD TRANSFUSION, COLLEGE OF MEDICAL SCIENCES. AHMADU BELLO UNIVERSITY, ZARIA. HEMATOLOGY TUTORIAL PRESENTATION, BLOCK POSTING. GROUP D. MODERATORS: PROF. A.A BABADOKO, PROF. A.M SULEIMAN, DR. G YAHAYA, DR. U.D ALIYU

2. PRESENTED BY: U18MD1122 U19MD2003 U19MD2005 U19MD2006 U19MD2008 U19MD2009 U19MD2010 U19MD2012

3. OUTLINE: 1. Introduction Definition of Sickle Cell Trait, Sickle Cell Anaemia, Sickle Cell Disorder and Sickle Cell Disease Epidemiology 2. Aetiopathogenesis 3. Common Haplotypes of Sickle Cell Disease 4. Clinical features 5. Types of Crises 6. Investigations 7. Treatment and follow-up Clinical Scenario

4. introduction Sickle Cell Trait ( HbAS ): inheritance of the genes that code for haemoglobin a ( hba ) and haemoglobin s ( hbs ). this is a heterozygous condition Sickle Cell Anaemia ( HbSS ) inheritance of two genes that code for Hb S. this is a homozygous condition Sickle Cell Disorder : inheritance of the gene that codes for hbs and any other abnormal haemoglobin eg HbC , HbD , HbE etc Sickle Cell Disease: this is symptomatic sickle cell anaemia or sickle cell disorder

5. Introduction…cont’d Various accounts highly suggestive of haemoglobinopathies have existed in different African traditions First description of clinical features were by James B Africanus Horton - 1874 in 1904 dr. James Herrick, and his intern Dr. Ernest irons started treating Walter Clement Noel in Chicago.

6. EPIDEMIOLOGY Sickle cell disease ( SCD ) is the most common genetic disease in the world. World wide 20 to 25 million have SCD, 12 to 15 million in sub-Saharan Africa, 5 to 10 million in India and other parts 3 million Over 300,000 babies are born annually ( 400,000 by 2050 ) Majority of these are in sub-Saharan Africa, poor access to medical care and public health strategies High-income countries, the survival has been steadily increasing, often well into adulthood WHO and UN designated SCD as a global public health problem .

7. EPIDEMIOLOGY…cont’d mutations of the globin gene affect approximately 7% of the world’s population sca has five epicenters : benin , senegal,car ( bantu ), cameroon and saudi arabia / india 300 000 children are born with sickle cell disease world wide frequency of sickle cell gene ( hbas ) is 24% in nigeria with 2% of the nigerian population having hbss

8. Nigeria The frequency of the sickle gene (HbS) is 25-30% Prevalence of SCA is 2-3% of the estimated over 140 million population.

9. geographical distribution is identical to that of malaria

10. aetiology The β globin gene is located on chromosome 11 and codes for the production of a 146 amino acid polypeptide Inherited in an autosomal recessive manner A result of a single point mutation in which adenine is replaced by the nucleotide thymine at the 6 th codon of the globin gene in the DNA (GAG → GTG) This leads to the synthesis of the amino acid valine instead of glutamic acid Valine is a neutral amino acid and imparts a hydrophobic interaction

11. The human α and β globin genes are coded for by chromosomes 16 and 11 respectively. Haemoglobin consists of haem and globin components Haemoglobinopathies are inherited disorders of haemoglobin due to structural alterations of the globin polypeptide chain

12. Pathophysiology

13. pathophysiology The pathogenesis of sickle cell revolves around the following: HbS polymerisation Intercellular adhesion Activation of coagulation Erythrocyte membrane abnormalities Pertubation of vasodilatation

14. HAPLOTYPES Haplotypes refer to genes that are closely linked to a particular gene of interest ( the β -globin gene in this case) which are inherited together from a single individual. The Benin and Bantu haplotypes are more severe compared to the Senegal and Arabian haplotypes

15. Haplotype Hemoglobin B-chain Gene Locus

16. clinical features Could be asymptomatic, mild, moderate or severe Generally multi-organ affectation Factors that affect severity are: Genetic: Persistence of hbf , Beta globin gene haplotype, Thalassaemia, Type of HbS variant, Concomitant g6pd

17. environmental: nutrition, infections, compliance with routine medications and hospital visits

18. presentation is rare before 3 months of life. this is when the globin switch starts from the fetal haemoglobin to the adult form painful dactylitis ( hand-foot syndrome ) is usually the first presentation of the disease anaemia and jaundice of varying degrees are present in most patients

19. TISSUE/ORGAN MANIFESTATION(S) BRAIN STROKE EYES RETINOPATHY (IMPAIRED VISION) LUNGS ACUTE CHEST SYNDROME, PULMONARY HYPERTENSION HEART CARDIOMEGALY KIDNEYS HYPOSTHENURIA,PAPILLARY NECROSIS,SICKLE CELL NEPHROPATHY MUSCULOSKELETAL SYSTEM BONE PAINS, OSTEOMYELITIS,AVASCULAR NECROSIS SKIN LEG ULCERS ENDOCRINE SYSTEM DELAYED PUBERTY PLACENTA MISCARRIAGES SPLEEN FUNCTIONAL ASPLENIA,AUTOSPLENECTOMY OTHERS PRIAPISM, INFECTIONS

20. COMPLICATIONS stroke pulmonary hypertension retinal detachment priapism (impotence) leg ulcers sickle cell nephropathy hepatopathy pigment gallstones infertility or subfertility (miscarriages) infections

21. crises These are acute clinical episodes requiring urgent intervention or hospital admission Being replaced by the word ‘episodes’ Precipitated by : Infections, Extremes of weather Dehydration Excessive physical exertion Trauma Dehydration Psychological stress Unknown

22. types of crises Vaso -occlusive Visceral sequestration Aplastic Hyperhaemolytic

23. crises Vaso -occlusive crises are the most frequent form of crises. they are characterized by pain May affect the Bones Spleen Lungs Brain

24. Visceral sequestration : organs affected are the spleen,liver,pelvic girdle and lungs Aplastic crises: this is caused by infection with parvovirus b19 which infects developing erythroblasts in the bone marrow.

25. Hyperhaemolytic crises when there is an increased rate of haemolysis. patients usually present with worsening anaemia and jaundice

26. investigations Can be broadly classified as those that Aid in diagnosis Monitoring of disease Aid in investigation of crises

27. Investigations that aid in diagnosis CBC: HCT, WBC and differential, retics, platelet. MCV, MCH, MCHC BLOOD FILM Sickling test using 2% sodium metabisulfite or sodium dithionite. this however simply detects the presence of hbs and cannot differentiate HbSS from HbAS or even HbSC etc.

28. Haemoglobin electrophoresis: this utilises the differential rates of migration of charged particles (haemoglobin in this instance) across an electric field . alkaline and acidic media may be used. HPLC IEF PCR and RFLP: These may be utilised in prenatal diagnosis using chorionic villus biopsy, amniotic fluid or foetal blood samples

29. Investigations that aid in monitoring sca Urinalysis Urea, electrolytes and creatinine Transcranial doppler ultrasonography Fundoscopy HbF quantification

30. other investigations as may arise Blood culture Stool MCS Urine MCS wound swab MCS CXR Abdominal USS

31. management of crises Adequate hydration Antibiotics in infection Antimalarials Analgesics oral and parenteral Blood transfusion Exchange transfusion in priapism, intractable pains, acute chest syndrome Bed rest

32. other forms of treatment Hydroxyurea Stem cell transplantation Gene therapy

33. treatment steady state Folic acid Proguanil Pneumococcal vaccine Penicillin v prophylaxis Liberal oral fluids

34. Genetic Counseling The process by which patients or relatives at risk of a disorder that may be hereditary are advised of the probability of developing and transmitting it and of the ways in which this may be prevented or ameliorated

35. summary

36. Conclusion Sickle cell anaemia is a very important condition with protean manifestations. Hence a good grasp of this condition is very important for every physician.

37. REFERENCES; TEXTBOOK OF ESSENTIAL HEMATOLOGY; A.V HOFFBRAND ESSENTIALS OF HEMATOLOGY BY; Shirish M Kawthalkar INTERNET RESOURCES, LECTURE NOTES BY PROF. SANI AUWALU TEXTBOOK OF MEDICAL BIOCHEMISTRY; M.N CHATTERJ

38. CLINICAL SCENARIO.. A 28-year-old female, a known SCA patient, was brought to the Haematology Day Care Unit, with fever and bone pains. She has not been regular with clinic follow-ups. On physical examination, she was febrile, dehydrated, severely jaundiced and had long bone tenderness. She also has a history of progressive limping in the last 2 years.   FBC result: HCT 0.18 L/L (0.33-0.51) Retics 11% (0.2-2.5) Platelets 650 x 10 9 /l ( 100-380 x 10^9/L ) WBC 24 x 10 9 /L Neutrophils 78%, Lymphocytes 18%, Monocytes 1%, Eosinophils 3% MCV 67 fl

39. A 28-year-old female, a known SCA patient, was brought to the Haematology Day Care Unit, with fever and bone pains. She has not been regular with clinic follow-ups. On physical examination, she was febrile, dehydrated, severely jaundiced and had long bone tenderness. She also has a history of progressive limping in the last 2 years.   FBC result: HCT 0.18 L/L (0.33-0.51) Retics 11% (0.2-2.5) Platelets 650 x 10 9 /l ( 100-380 x 10^9/L ) WBC 24 x 10 9 /L – Neutrophils 78%, Lymphocytes 18%, Monocytes 1%, Eosinophils 3% MCV 67 fl  

40. What is the most likely diagnosis? List possible predisposing factors. What other history will you be interested in? Enumerate on the clinical findings Interpret the FBC result What other investigations will you do? How will you treat this patient? What is the role of Hydroxyurea in Sickle cell Anaemia Discuss complications of this disease

41. NB: 1 st Presenter will take number 1 and Clinical Scenario ‘b’ 2 nd Presenter will take number 2 and Clinical Scenario ‘a’ 3rd Presenter will take number 3 and Clinical Scenario ‘c’ 4 th Presenter will take number 4 and Clinical Scenario ‘d’ 5 th Presenter will take number 5 and Clinical Scenario ‘e’ 6 th Presenter will take number 6 and Clinical Scenario ‘f’ 7 th Presenter will take number 7 and Clinical Scenario ‘h’ 8 th Presenter will take number 8 and Clinical Scenario ‘g’  

42. THANKS FOR LISTENING