Sickle Cell Anemia PDF

Learning Objectives Sickle cell syndrome • Description of Sickle Cell Syndrome • Cause of SCD • Types of SCD • Mutation of HbA • Sickling process • Mutation effects • Signs and symptoms • Non-Pharmacological and Pharmacological treatment Sickle Shape Sickle cell syndrome • It is an autosomal rec...

Learning Objectives Sickle cell syndrome • Description of Sickle Cell Syndrome • Cause of SCD • Types of SCD • Mutation of HbA • Sickling process • Mutation effects • Signs and symptoms • Non-Pharmacological and Pharmacological treatment Sickle Shape Sickle cell syndrome • It is an autosomal recessive genetic disorders that are characterized by the presence of at least one sickle hemoglobin (HbS) gene and the red blood cells changed into sickle shape which allow them to be easily destroyed. Types of Hemoglobin's Inheritance pattern for sickle cell disease • A 25%, or 1 in 4, chance of inheriting two normal hemoglobin A genes. This child does not have sickle cell trait or disease. • A 50%, or 1 in 2, chance of inheriting one normal hemoglobin A gene and one hemoglobin S gene. This child has sickle cell trait. % 90 / % <2 2-Ser • A 25%, or 1 in 4, chance of inheriting two hemoglobin S genes. This child has sickle cell disease. Causes of Sickle Disease ➢It causes by defective hemoglobin, which is the oxygen-carrying protein. ➢Hemoglobin in RBCs made of four peptide chain which bind to heme group ➢Different hemoglobin have different peptide chains. ➢Hemoglobin A (HbA) made of two alpha and two beta globin peptide chain ➢The mutation in beta globin peptide chain is responsible of the sickle disease Sickling process Mutation of HbA • Normal HbA is composed of two α-chains and two β-chains (α2β2). • A single substitution of the amino acid valine for glutamic acid at the β-polypeptide chain is responsible for the production of a defective form of hemoglobin called HbS. • The chemical differences in the β-chain are responsible for RBC sickling and its associated sequelae. Sickling process Henze Body and sickling 8 • Repeated sickling of RBCs damages their cell membranes results in anemia?? • Free hemoglobin in plasma is bound by a molecule called haptoglobin, therefore Low level is a sign of intravascular hemolysis • Increase level of unconjugated bilirubin causes jaundice, bilirubin gallstones and scleral icterus. • Hb S activate the formation of superoxide anion which destruct the fatty acids of cell membrane and Hb S • Formation of meta Hb S which accumulated to form Henz Bodies • Henz bodies precipitated toward cell membrane results in alteration of phophotidylserine’s Phosphatidylserine is a phospholipid that protects the cells in your brain Sickling effects Types of Sickle disease - • Blood vessel occlusion • Abdominal pain • Joints pain Sickle Cell Trait (SCT): It is the heterozygous form (HbAS) of SCD in which a person inherits one normal adult • Anemia hemoglobin (HbA) gene and one HbS gene. These individuals are carriers of the SCT and • Vsconcosntruction usually asymptomatic. • Metabolic disorders Sickle Cell Anemia (SCA): • Fever • Tachycardia • It is the homozygous (HbSS) state of SCD in which a person inherits two abnormal HbS genes. Video • Sickle cell disease (SCD) is a chronic illness that is associated with frequent crisis symptoms. Common symptoms includes: Intersive • Excruciating musculoskeletal pain • Life-threatening pneumonia-like illness • Cerebrovascular accidents • Splenic and renal dysfunction. • Organ damage Signs and symptoms of SCT • Generally asymptomatic • Females may have frequent urinary tract infections • Hematuria may occur spontaneously • Normal Hgb values HbS gene and Malaria gig • Having the HbS gene protects heterozygous carriers from succumbing to Plasmodium falciparum (malaria) infection. Clinical manifestations of SCD ❑ Impaired circulation ❑Destruction of RBCs • Consequently, persons with heterozygous sickle gene have a selective ❑Vascular stasis your veins can't send the blood from your legs back to your heart advantage in tropical regions where malaria is endemic. (Heterozygous advantages) Signs and symptoms of SCD Can be Identified by neonatal screening before 2 months of age • Slow-healing ulcers after trauma or infection • Painful vasoocclusive crises • Weakness and fatigue • Dactylitis before age 1 year • Chronic hemolytic anemia is common • May develop infarction of the spleen, liver, bone marrow, • Enlargement of spleen and heart kidney, brain, and lungs • Gallstones • Scleral icterus - • Hgb 7.0 to 10.0 g/dL • Priapism in males Therapeutic options The goals of treatment are to: • Reduce or eliminate the patient’s symptoms • Decrease the frequency of sickle crises • Decreased hospitalizations and decreased morbidity • Increase the hemoglobin level to the patient’s baseline • Increase the HbF concentration • Decrease the HbS concentration • Prevent infectious complications -> Beautierre nit 2012 Gamma 22 ↳ my itution happen • Pain management • Prevent central nervous system (CNS) damage here only Non-pharmacologic Therapy viscosity + Pharmacologic Therapy allut metabolism -> • Avoid smoking and excessive alcohol intake. ↑ lnce radical - • Maintain adequate hydration to help decrease blood viscosity. • Avoid extreme temperature changes. ↳ 2 • Immunizations her baking • Penicillin and cardiac function, are required to monitor for organ damage. 3 • Folic acid vaceit influen 4 • Hb F inducer Grat PCV 13: Prevnar Immunizations PCV 13-valent • Influenza vaccine should be administered to SCD patients 6 months of age and older, including adult patients. 6th wee Vaccin • Regular examinations, including ophthalmic, dental, renal, pulmonary, • The pneumococcal conjugate is routinely administered to infants and children and provides good protection against the 13 most common isolates seen in this Types of vaccines Two pneumococcal vaccines are available 1- The 13-valent pneumococcal conjugate vaccine (PCV 13: Prevnar) 2- The 23-valent polysaccharide vaccine (PPSV 23: Pneumovax 23) Brachch Spectrum age range. Alber6wet · necht -> 2 mor Scenel dan to he • Administer the first dose of PCV 13 between 6 weeks and 6 months of age, followed by two additional doses at 2-month intervals and a fourth dose at 12 to 15 months of age. - r monte PPSV 23: Pneumovax 23 Dose regimen • The 23-valent polysaccharide vaccine is indicated for children older than 2 years and adults. Because PPSV 23 is a • The dose of PPSV 23 should be separated from the last dose of PCV 13 by at least polysaccharide vaccine, children younger than 2 years do not respond well. · 2 months. It dat alter Behere are • 23-Valent pneumococcal polysaccharide vaccine (PPV 23) contains the 23 most common isolates of S. pneumoniae seen • This second dose should be administered 5 years after the first PPSV 23 dose. in older children and adults. • It is recommended that children with SCD receive both • All adults with SCD should be vaccinated with both PCV 13 as well as PPSV 23. vaccines, with a dose of PPSV 23 administered after the child turns 2 years of age. Dose regimen Immunizations with penicillin Ath • Adults and children who have not previously received PCV 13 or PPSV 23 should receive ellicay i Vaccin ad two monthy one dose of PCV 13 followed by a single dose of PPSV 23 at a minimum of 8 weeks later then an additional dose of PPSV 23 at least 5 years after the previous PPSV 23 dose. incute Treatment Are The use of pneumococcal vaccine in combination with penicillin prophylaxis in SCD patients has dramatically decreased the rates of • If an adult or child with SCD has already received at least one dose of PPSV 23, they should additionally receive one dose of PCV 13 at least 1 year after the dose of PPSV 23. morbidity and mortality Penicillin Penicillin • Penicillin V potassium (Penicillin VK) is typically initiated at age 2 months, with a dose of 125 mg orally twice daily until age 3 years, then 250 mg orally twice daily until 5 years of age. • Penicillin-allergic patients may receive erythromycin 10 mg/kg twice daily. • Amoxicillin 20 mg/kg/day divided every 12 hours (maximum of 250 mg/dose) can also be used. • Penicillin prophylaxis usually is not continued in children older than 6 years • The intramuscular use of benzathine penicillin 600,000 U every 4 weeks from age 6 months to 6 years is also an option for nonadherent patients. importance Folic Acid in but may be considered in patients with a history of invasive pneumococcal infection or surgical splenectomy. so patient can continue . Fetal Hemoglobin Inducers DNA systlegis • Folic acid supplementation with 1 mg daily is generally recommended in adult SCD patients, women considering pregnancy, and any SCD patient with chronic hemolysis. • Hb F induction in patients with SCD, especially those with frequent crises, has been shown to decrease RBC sickling and RBC adhesion. Hbf - Hershbin inder - Same Gamma Hydroxyurea (Hydroxycarbamide) Role of Hb F in SD Actions of Hydroxyurea • It is the major oxygen carrier hemoglobin present during gestation. • It consist of 60-80% of total hemoglobin in newborns. • It decreased sharply during child and Adult stages ➢increases Hb F levels ➢increasing the number of Hb F-containing Premature RBL reticulocytes, thus diluting the abnormal hemoglobin S (HbS). ➢It has antioxidant properties ➢reduction of neutrophils and monocytes ↓ inflammation by FIDA Not approved ➢increased intracellular water content leading to increased -> Hydroxyurea is also used off-label to treat red cell deformability. ➢decreased red cell adhesion to endothelium ➢increased levels of nitric oxide Vasodilator agent ❖ Chronic myelogenous leukemia Problem in Bam marrow ❖ Polycythemia vera ↑RBL Dose adjustment • Hydroxyurea reduced the frequency of hospitalizations and the incidences of pain, acute chest syndrome (ACS), and blood transfusions • Doses should start at 10 to 15 mg/kg daily in a single oral dose, which can be increased after 8 to 12 weeks if blood counts are stable, and there are • Hydroxyurea treatment should be considered in all infants 9 months of age no side effects. • Doses can be increased by 5 mg increments up to 35 mg/kg/day. and older. Side effect • Myelosuppression • Hydroxyurea is available in 200-, 300-, 400-, and 500-mg capsules to liquid Platelets synfresis • Skin ulcer • Leukemia and as 1000-mg tablet. said Coment from ↳ - Ove Davat • Extemporaneous liquid preparations can be prepared for children who cannot swallow capsules. • Hydroxyurea is excreted in breast milk and should be avoided in lactating mothers. Hydrangume Drug interactions • Increase risk of bleeding with Salicylate • Increase uric acid with Probenecid • Decrease CD4 count with HIV medications destellanticit b D latelets syntlegis CD4 count Azacytidine and Deoxycytidine (decitabine) • Normal CD4 count for healthy adults and • Both induce HbF by inhibiting methylation of DNA, preventing the teens: 500 to 1,200 cells per cubic millimeter. • Low CD4 count: Below 500 cells per cubic switch from γ- to β-globin production. • Decitabine appears to be safer and more potent than 5-azacytadine. millimeter. • If you have HIV, a low CD4 count means that HIV has weakened your immune system. • They used for patients who do not respond to hydroxyurea, or cannot tolerate the side effects of hydroyurea, although it has not been approved by the FDA for this indication. OFF label dry .