COMPLICATIONS OF Sickle cell Disease pptx

Surgery presentation

1. OVERVIEW OF SICKLE CELL DISEASE AND ITS COMPLICATIONS - Dr EZEOKOLI O.EMMANUEL Department of Haematology and Blood Transfusion AE-FUTHA 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 1

2. OUTLINE Introduction Epidemiology Pathophysiology Pathogenesis of SCDx Clinical Manifestations (Sickle Cell Crises & Complications ) Sickle Cell Leg Ulcer Conclusion References 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 2

3. Introduction Sickle cell disease is an autosomal recessive hemoglobinopathy caused by an amino acid substitution from glutamic acid to valine in the beta hemoglobin chain. SCDx is a heterogenous term that encompasses a group of diseases characterised by the presence of haemoglobin S ( HbS ) in combination with another abnormal haemoglobin. Homozygous inheritance of HbS produces the severest form of the disease – sickle cell anaemia (SCA). These manifest clinically as chronic hemolytic anemia, recurrent painful episodes, and chronic organ damage from vasoocclusion . 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 3

4. Epidemiology SCDx is the most common haemoglobin disorder worldwide. Largest number of sufferers are from sub-Saharan Africa Nigeria has the largest number of SCD patients worldwide where incidence is as high as 2-3% of the population ( Ademola SA., 2015) No sex prevalence Pattern of distribution follows that of malaria belt suggesting the sickle trait is the result of adaptive mechanisms to Plasmoduim spp . i nfections . 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 4

5. Pathophysiology GTG instead of GAG HbS is the end-result of a single base substitution  Valine for glutamate Leads to the production of a haemoglobin molecule that is functionally unstable when deoxygenated. Deoxygenated HbS polymerizes and forms tactoids which distort red cell membrane  impaired cation homeostasisCellular d ehydration and shape distortion – sickle shape 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 5

6. Pathogenesis of SCD 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 6

7. Pathogenesis of SCD…2 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 7

8. Pathogenesis of SCD…3 Haemoglobin S polymerization  Cell membrane defects  Sickled cells  Impaired biorheology and increased adhesiveness  Vascular stasis Hypercoagulable state Vascular stasis  more sickling  Haemolysis (Intra- & Exravascular ) Hemolysis-mediated endothelial dysfunction : Hemolysis  N itric oxide depletion  Vasoconstriction RBC and WBC adhesion to endothelium  Vasooclusion  S terile inflammation. Vaso-occlusion  Pain (Acute/chronic), end-organ injury and organ failure in SCD arise due to synergistic effects of molecular, cellular, and biophysical processes. 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 8

9. Clinical Manifestations (Sickle Cell & Crises Complications) 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 9

10. SICKLE CELL CRISES These are periods that puctuatate the typical course of SCDx notwithstanding the chronically ongoing anaemia and vasoocclusion . It is characterised with sudden worsening in the clinical condition of the patient. 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 10

11. SICKLE CELL CRISES…2 Classified as: Vaso -occlusive crises : (acute painful crises and acute chest syndrome). Aplastic anaemia : Parvovirus B19, Epstein-Barr virus , CMV, HIV, S. pneumoniae , salmonella. Hyperhemolytic Crisis : may be one of these events: Delayed hemolytic transfusion reaction Autoimmune hemolysis. G6PD deficiency. Sequestration Crisis: (Spleen or Liver) 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 11

12. Complications Anaemia : Chronic anaemia Acute exercerbation of anaemia Autoimmune hemolytic rxn . Painful episodes: Joint and bone pains Immunosuppression / infections : Splenic dysfunction: esp . encapsulated organisms. 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 12

13. Complications…2 4. Neurological complications: Spinal cord infarction or compression Sensory hearing loss, Vestibular dysfunction TIA , Seizures, stroke (cerebral infarction or haemorrhage ) Spontaneous Epidural Hematoma ( SEH ) SAH Silent stroke P rogressive neurocorgnitive impairment Meningitis. 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 13

14. Complications…3 5. Ophthalmic Complications: Iris atrophy, vitreous haemorrhage and retinal detachment, ↑ IOP Neo-vascularization  proliferative retinopathy Orbital compression syndrome 6. Pulmonary Complications: ACS Pulmonary hypertension Restrictive and obstructive lung disease Chronic interstitial fibrosis. Pneumonia Proliferative retinopathy 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 14

15. Complications…4 7. Cardiac Complications : Left ventricular dilation (an age-dependent loss of cardiac reserve), due to increased stroke volume (though with minimal increase in heart rate) Acute myocardial infarction Right ventricular hypertrophy Diastolic left ventricular dysfunction Left ventricular hypertrophy Cardiac iron overload 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 15

16. Complications…5 8.Hepatobiliary Complications: Vasoocclusion  Acute hepatic cell crisis Acute hepatic sequestration crisis Intrahepatic cholestasis Cholelithiasis Acute or Chronic cholecystitis Transfusional hemosiderosis Viral Hepatitis 9. Gastrointestinal Complications: PUD Duodenal ulcers Acute pancreatitis Ischaemic colitis Ischaemic intestinal necrosis Acute Colonic Pseudo-obstruction ( Ogilvie’s syndrome) . 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 16

17. Complications…6 10.Renal Complications: Hematuria, Papillary necrosis, Hyposthenuria , Nocturnal Enuresis, Proteinuria Renal infarction, Renal Failure, Renal Endocrine (Erythropoietin) Deficiency, UTI/Pyelonephritis. 11. Priapism : Stuttering or prolonged. 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 17

18. Complications…7 12. Pregnancy: Anaemia (Nutritional deficiencies, hemodilution ) Risk to the fetus from abortion Stillbirth Low Birth wt and Increased neonatal death. Frequent painful crisis 13. Growth and Development: Retardation affecting weight more than height delayed sexual maturation. 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 18

19. Complications…8 14 . Musculoskeletal Complications: Expansion of the medullary space Bone marrow infarction Avascular necrosis, Dactylitis / “hand–foot syndrome” Vertebral body infarctions Acute soft head syndrome/ Sickle cell Cephalohematoma / Skull hematoma Osteopenia Epiphyseal infarction Osteomyelitis Septic arthritis. 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 19

20. Complications…9 15. Dermatologic Complications: Leg ulcers Myofascial syndromes 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 20

21. SICKLE CELL LEG ULCERS 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 21

22. Characteristics of SCLU Can either be acute or chronic. Commonly around the malleoli Start mostly as blisters with destruction of the epidermis Hyperpigmented surroundings Slow to heal. High rate of recurrence. Associated with severe unremitting sharp pain and depression. 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 22 ,

23. EPIDEMIOLOGY Prevalence of SCLU: The rate of leg ulcers varies around the world. The incidence increases with age. Rare before 10 years of age, is most frequently seen between 10 and 25 years of age . Commoner in males??? Highest in patients with SS disease than other SCDx

24. Risk factors Type of SCDx : The prevalence of leg ulcers is higher in patients with SS and SS‐alpha thalassemia than among those with SC, SB+, or SB0 genotypes Lower Hemoglobin concentration (<6g/dl) Lower hemoglobin F level Gender: more in males Long standing: Eleveted venous pressure Genetic factors: SNPs in Klotho , TEK, (TGF‐β)/BMP pathway, IL-6 Poor socioeconomic status

25. Pathogenesis ( Venostasis implicated ) Hemolysis‐vascular dysfunction syndrome: free hemoglobin scavenges NO Obstruction of microvessels : induced by sickling of RBCs, stimulates expression of vascular endothelium adhesion elements, platelet aggregation, and release of proinflammatory cytokines, exacerbating the obstruction, ischemia, and necrosis. Venous incompetence/Insufficiency: Venostasis in the calf muscle, Reduced venous filling times in the ankle during exercise. Autonomic dysfunction occurs: Aberrant venous-capillary reflex  build up of fluid and increased pressure, in responses lowered legs. Cutaneous arteriolar-constriction: more pronounced in the ulcer site when the leg is lowered .

26. Pathogenesis… ctd 5. Mechanical obstruction of microcirculation: The marginal circulation of blood around the malleoli is particularly susceptible to this obstruction of microcirculation, making them the most common site for sickle cell leg ulcers . 6. Cutaneous hemosiderosis : By frequent transfusion 7 . Dermatosclerosis : from venous insufficiency. 8 . Bacterial colonization 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 26

27. FEATURES Common symptoms SCLU include: Pain: may be severe, sharp, or stinging Itchy or burning sensation Red wound covered with yellow tissue Green or yellow discharge, if infected Hyperpigmented , oedematous , and warm skin around the ulcer

28. CONCLUSION Sickle cell anaemia is the most common inherited hemoglobinopathy worldwide and is associated with various complications which stem from: polymerization of HbS , heamolysis, hypercoagulable state and vaso -occlusion. The resultant effect of these being divers affectation of most of the organs in the body with a myriad of maladies as the resultant complications. 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 28

29. References Ademola Samson Adewoyin . Management Of Sickle Cell Disease: A Review For Physicians Education In Nigeria (Sub-Saharan Africa). Anaemia, vol. 2015,Article ID 791498, 21 pages, 2015. http://doi.org/10.1155/2015/791498 . Bankole OB., Yusuf AS., Asha MA., Kanu OO., Arigbabu SO. Spontaneous Epidural Haematoma in Sickle Cell Anaemia: Case Report and Literature Review. J Surg Tech Case Rep. 2012 , 4(2): 135- 137. Baruchet S., Delifer JC., Sigalet D., Hong A., Oudjhane K., Chen MF. Pseudomembranous colitis in sickle cell disease responding to exchange transfusion. J Pediatr . 1992;121:915-7. Engelhardt T., Pulitzer DR., Etheredge EE., Ischaemic Intestinal Necrosis As a Cause of Atypical Abdominal Pain in a Sickle Cell Patient. J Natl Med Assoc. 1989;81(10):1077-88. Khosla A., Ponsky TA., Acute Colonic Pseudoobstruction in a Child With Sickle Cell Disease Treated With Neostigmine. J Pediatr Surg. 2008 Dec; 43(12):2281-4. doi : 10.1016/j.jpedsurg.2008.07.030. PMID: 19040954. 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 29

30. References…2 6. Nazem A., Walker M. Sickle cell crisis and the Acute Abdomen. J Natl Med Assoc. 1986;78(8):787-8. 7. Samuel OA., Olisamedua FN., Ijeoma NDA., Peter OU., Uchechukwu OA. Acute Soft Head Syndrome in Children with Sickle Cell Anaemia in Lagos, Nigeria. Indian Journal of Haematology and Transfusion, 2014. 30, S67-S69. https://doi.org/10.1007/s12288-013-0251-6. 8. Shirish M. Kawthalkar . Anaemias Due To Excessive Red Cell Destruction. In: Essentials of Haematology, 2 nd ed. Jaypee Brothers Medical Publishers Ltd, New Delhi. 2013. Page 121-223. 9. Zahir Z., Hajjaj A. Acute soft head syndrome in sickle cell diseasein Qatif Central Hospital, Saudi Arabia- Case Report and Review of the Literature. Open Journal of Internal Medicine 2020; 10135-140. doi : 10.4236/ojim.2020.102014. 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 30

31. References…3 10. Minniti CP, Eckman J, Sebastiani P, Steinberg MH, Ballas SK. Leg ulcers in sickle cell disease. Am J Hematol . 2010;85(10): 831 – 833 . 11. Serjeant GR, Serjeant BE, Mohan JS, Clare A. Leg ulceration in sickle cell disease: medieval medicine in a modern world. Hematol Oncol Clin North Am. 2005;19(5):943-956. http ://dx.doi.org/10.1016/j. hoc.2005.08.005. PMid:16214654 12. Minniti CP, Kato GJ. How we treat sickle cell patients with leg ulcers. Am J Hematol . 2016;91(1):22-30. http://dx.doi.org/10.1002/ ajh.24134 . PMid:26257201 . 2/13/2025 COMPLICATIONS OF SICKLE CELL DISEASE 31

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