Sickle cell comprehensive management-DXN.pptx

A comprehensive management protocol of sickle cell disease

1. Sickle cell anaemia Dr. kajoba Dickson

2. Sickle cell disease (SCD) encompasses a group of hemoglobinopathies characterized by amino acid substitutions in the beta globin chain. Inheritance of 2 abnormal genes responsible for formation of HB.

3. One of the 2 abnormal genes is responsible for formation of HBS Patients have the sickle mutation plus a second beta globin gene mutation, the combination of which causes clinical sickling. These include : Sickle cell anemia (homozygous sickle mutation), Sickle beta thalassemia, Hemoglobin SC disease, and others. It is inherited in an autosomal recessive fashion either in the homozygous state or heterozygous state.

4. Hemoglobin S ( HbS ) results from the substitution of a valine for glutamic acid as the sixth amino acid of the beta-globin chain, which produces a hemoglobin tetramer (alpha2/betaS2) that is poorly soluble when deoxygenated Sickle Cell Trait If the other beta globin gene is normal. It is a benign carrier condition that is not a disease.

5. Sickle cell anemia Sickle cell anemia ( HbSS ), homozygous HbSS , occurs when both β-globin alleles have the sickle cell mutation ( β s). NB: both parents contribute mutated globin chain

6. Epidemiology SCD is one of the most common genetic diseases worldwide. Its highest prevalence is in Middle East, Mediterranean regions, Southeast Asia, and sub-Saharan Africa About 5–7% of the global population carries an abnormal haemoglobin gene. The prevalence of sickle cell trait ranges between 10 and 45% in various parts of sub-Saharan Africa  Uganda, 2016 Prevalence SC trait at 13.3% and SC disease at 0.7%. Ndeezi et al, 2016) Prevalence of ACS in SCA with fever found at 22.7%(256 children)- ( Ochaya , Hume, Bwanga , Tumwine )

7. Haemoglobin types Embronic HB – present upto 6/52 gestation. Gower -1 Gower-2 Portland Feotal HB- predominates thru pregnancy. At term 70-80% Haemoglobin F ( apha 2 and Gamma 2 chains) Adult Hb - reaches adult level at 12 months post natally HbA (2 alpha and 2 betta) HbA2 (2 alpha and 2 sigmoid)

8. Pathophysiology SCA ( HbSS ), homozygous HbSS , occurs when both β-globin alleles have the sickle cell mutation ( β s). HbS is typically as high as 90% of the total hemoglobin SCD HbS is 35-40% of all hemoglobin. heterozygotes where one β-globin allele includes the sickle cell mutation and the 2nd β-globin allele includes a gene mutation other than the sickle cell mutation, such as HbC , β-thalassemia, HbD , and HbOArab

9. FACTORS THAT INCREASE HgbS POLYMERIZATION Decreased oxygen Increased intracellular hemoglobin S concentration (SS > SC, S- thal ) Increased 2,3-DPG Decreased pH Slowed transit time through the circulation Endothelial adhesion

10. FACTORS THAT DECREASE HgbS POLYMERIZATION Lower concentration of HbS (compound heterozygosity for α- thal ) Increased HbF levels Genetic basis Hydroxyurea

11. Clinical Features of Sickle Cell Anemia Painful episodes Pneumococcal disease (pneumonia, meningitis, osteomyelitis) Acute chest syndrome Splenic infarction Splenic sequestration Stroke Osteonecrosis Priapism Frontal bossing Leg ulcers Gallstones Renal abnormalities Osteopenia Nutritional deficiencies Placental insufficiency Pulmonary hypertension Proliferative Retinopathy Dactylitis Jaundice

12. Clinical features The hallmark of SCD is vasoocclusion : this acute , painful aspect of SCD can be triggered by acidosis, hypoxia, dehydratation , infection and fever and exposure to extreme cold. Painful episodes occur most often in the: long bones (limbs, ribs, sternum, vertebra and skull bones) , lungs, liver, penis, eye, central nervous system and urinary tract. Acute chest syndrome describes new respiratory symptoms and findings, often severe and progressive, in a patient with sickle cell disease and new pulmonary infiltrate.

13. Fever and Bacteraemia Fever in a child with sickle cell anemia is a medical emergency, requiring prompt medical evaluation and delivery of antibiotics because of the increased risk of bacterial infection and subsequent high mortality rate Aplastic Crisis Human parvovirus B19 infection poses a unique threat for patients with sickle cell disease because this infection results in temporary red cell aplasia , limiting the production of reticulocytes and causing profound anemia Any child with sickle cell disease, fever, and reticulocytopenia should be presumed to have parvovirus B19 infection until proven otherwise

14. Splenic Sequestration Acute splenic sequestration is a life-threatening complication occurring primarily in infants and young children with sickle cell anemia. Splenic sequestration is associated with rapid spleen enlargement causing left sided abdominal pain and Hb decline of at least 2 g/dL from the patient’s baseline. Sequestration may lead to signs of hypovolemia as a result of the trapping of blood in the spleen and profound anemia, with total Hb falling below 3 g/dL. Sequestration may be triggered by fever, bacteremia, or viral infections.

15. Priapism Priapism, defined as an unwanted painful erection of the penis. Priapism occurs in 2 patterns: prolonged , lasting >4 hr , or stuttering , with brief episodes that resolve spontaneously but may occur in clusters and herald a prolonged event. Priapism in sickle cell disease represents a low-flow state caused by venous stasis from RBC sickling in the corpora cavernosa. Recurrent prolonged episodes of priapism are associated with erectile dysfunction (impotence).

16. Stroke blockage of blood flow or rupture of cerebral vessels. Prevalence of stroke in SCA in Uganda is 6.8% ( Munube et al 2016 ). Ischemic stroke most common btn 2-9 yrs , accounts for 70-80% of CVA in SCD. Haemorrhagic more common in older patients 20-29yrs-accounts for 1-3% of CVA in SCD. Transient ischemic attack (TIA) often precedes stroke

17. Overt stroke is generally secondary to stenosis or occlusion of the internal carotid or middle cerebral artery Strokes may be precipitated by Acute Chest Syndrome, parvovirus infection, or other acute anemic events. Symptoms- Silent cerebral infarct Subtle behavioral changes Academic difficulties Symptoms- Acute Stroke Prolonged headaches Aphasia Hemiparesis Seizures Gait disturbances

18. Patients at high risk of stroke

19. Clinical features/complications

20. Diagnosis New born diagnosis Thin layer/ isoelectric focusing (IEF) high-performance liquid chromatography (HPLC) Sickling test – demonstrates a sickle shaped cell in microscope when abnormal Hb is deprived of oxygen Solubility test – works on principle of abnormal HbS precipitating as a result of its polymerization when exposed to low oxygen concentration Peripheral blood film – sickled cells

21. Sicked cell of peripheral blood film

22. Management Sickle cell crises Predisposing factors include Dehydration Infection Strenuous exercises Extremities of temperatures Psychological stress Traumatic injury like surgery Drugs Sometimes cause is unknown

23. Types of SCD crises 1. Vaso-occlusive crisis (painful crisis) Acute chest syndrome -2nd most common s/S – tachypnoea or DIB, severe chest pain, fever, wheezing, nasal flaring, cough Major cause of death – 25% of death in PLSCD Haemolytic crisis – faster RBC destruction by the spleen Aplastic crisis – sudden reduction in RBC count. Due to Parvo B19 destroying RBC precursors in the BM. s/s- excessive fatigue, tachycardia, excessive pallor, fever, headache Sequestration crisis – spleen becomes clogged and congested with sickled RBC which cant be freely filtered

24. Management :

25. Lab and investigations CBC Blood smear for malaria Urinalysis Blood culture RBS Grouping and x-match CXR Abdominal erect Xray , Uss Plain X-ray of the bones Brain CT LFT RFT NB: investigation depends on the patient presentation

26. General management principles Proper adequate hydration Adequate pain control Treatment of infections Oxygen therapy if needed BT if needed treating any specific concerns as they present

27. Fever <39 – oral antipyretics – PCM, Ibuprofen >39 – Iv/ IM antipyretics e.g iv PCM, im diclo Assess for the cause Pain relief analgesics depending on the pain scale

28. Immediate hydration Maintenance fluid –using parkland formula. Fluid of choice is D5% or NS Acute chest syndrome Oxygen therapy Pain relief Hydration Antibiotic therapy BT Bronchodilators e.g salbutamol nebulization Advanced respiratory support

29. Aplastic crisis BT at 20mls/kg of whole blood or 10ml/kg of PRBC Sequestration Crisis Blood transfusion Surgical removal if 2 or more sequestration crises in a period of 6 months Priapism Pain relief and hydration Minor – oral Etilefrine 25mg daily increased every 2 weeks . Max 100mg Conservative measures: ice pack on the penis and perineum, walking upstairs

30. Major priapism Consult urologist for intracarvenosal phenyl ephedrine 0.5ml in 10-20mls of NS @ 5 minutes up to 1 hour Stroke : Ensure ABC Hx , P/E , labs and CT Urgent BT Prevention - hydroxyurea

31. Acute abdomen Should always be assessed by surgeon Causes Splenic infarction Mesenteric/colonic ischemia Renal /hepatic vein thrombosis Pulmonary inaction or pneumonia Hepatic infarction/ abscess/sequestration Intra-abdominal abscess NB: manage with general principles of analgesia, hydration, antibiotic and reassurance . More specific mx as per cause

32. Health maintenance Non-pharmacological Taking enough fluids Avoiding strenuous exercises Avoiding extreme temperatures Eating balanced diet Avoiding stress Education on early features

33. Pharmacological Folic acid – children 2.5mg daily Prophylactic antibiotics – 3months-2years- 125mg of Pen V twice daily 3-5 years- 250mg twice a day of Pen V Malaria prophylaxis – fansider Below 2 years- 1/2 a tablet monthly 2-5years- 1 table monthly Above 5 years- per body weight

34. Immunisation - as per schedule PCV 13 boaster dose at 12 months Pneumococcal polysaccharide 23 valent vaccine is then started from 2 years with boaster dose 3 years later Hydroxyurea Increases the concentration of foetal Hb thus reducing SCD crises Dose – start 15-20mg/kg once daily.

35. contraindications Pregnancy Kidney impairment or renal disease Liver disease PLT count <100,000cells/mm3 Neutrophil count(not WBC) of less than 2500cells/mm3 Hb>6g/dl Reticulocytes less than 95000cells/mm3 Poor follow up Known Allergies to hydroxyurea

36. Routine medical care Pt should be attached to a given SCD clinic or health centre . Should have CBC, LFTs, RFTs done every 6 months