Sickle. cell disease SCD, Diagnosis and Prevention.pptx

Diagnosis and prevention

1. Sickle cell disease

2. Learning objectives definition genetics pathophysiology clinical manifestation/complications management of the disease-comprehensive health care management of the complications of the disease

3. Definition , genetics and types A group of clinico -pathologic conditions in which the disease is attributed to the presence of Hb S in the absence of HbA eg SS,SC, SE etc, or HbS in excessive of HbA eg S β +. It is an autosomal recessive (codominant) disease due single base pair change (thymine for adenine) at the 6 th position (now 7 th position) of the β chain resulting in the replacement of valine for glutamic acid Inheritance may be homozygote SS or compound heterozygote SC, SD Punjab , SO Arab , S β + , S β -

4. Geographic distribution and prevalence African descent, Mediterranean, Middle East Saudi-Arabia, India, Caribbean, 50% of the world SCD children are in Nigeria, India and Democratic Republic of Congo Prevalence is 2.8% (3/100) in the newborn population in Benin, 1/396 US African American, 1/2,647 birth in USA

5. Sickle cell polymorhysm 5 SCD polymorhysm Senegal –associated with mild disease Cameroun (Eton) Benin-associated with moderately severe disease Bantu-associated with severe disease Saudi Arabia/India-associated with mild disease

6. Pathophysiology The packaging of 32-34g/dl of Hb within the Red cell requires that it remain extra soluble to enable function. In SCD, following deoxygenation of the Hb , there is hydrophobic interaction with each other resulting in the crystalization of the Hb (polymerization). This is also referred to as sickling . Following re-oxygenation, this sickling is reversed and the Hb is depolymerized . The polymerization of the de-oxygenated HbS is the pry event in the molecular pathogenesis of SCD

7. With repeated sickling and un- sickling there is damage to the red cell membrane resulting in the loss of deformability of the red cells and production of dense red cells. The rate and extent of polymer formation is dependent on the red cells degree of deoxygenation , the intracellular Hb concentration , concentration of HbF The loss of deformability is responsible for the chronic anemia seen in SCD. The life span of the sickle cell is 10-20 days. These rigid red cells are also responsible for the the vaso -occlusive events that is the hallmark of the disease .

8. Other pathologic process include hemolysis associated reduction in nitric acid bioavailability, chronic inflammation, oxidative stress, altered red cell adhersive properties, activated white blood cells and platelets, altered hemostasis including platelet activation, thrombin activation, lowered anticoagulants, impaired fibrinolysis and increased blood viscosity In addition patients with SCD have several immunologic abnormality. They have functional asplenia as early as 3- 6 mo of life They lack opsonin (alternate pathway abn ) and thus are unable to handle diplococci organisms like H.influenza , pneumococcus , salmonella

9. Clinical presentation Anemia is usually common to most patients with SCD because of the chronic hemolysis However, the other problems are usually complication of the disease. Patients with SCD are pale, they maybe jaundiced, with bossing of the skull and maxillary prognatism , long thin extremities, pot-belly because of splenomegaly, failure to thrive or stunted growth-classic SCD statue

10. Diagnosis History- hand & foot syndrome or recurrent bone pains, recurrent jaundice, family history of sibbling death, O/E- sickle cell facies/features, palor , jaundice, hepato-splenomegaly, long thin extremities failure to thrive, delayed secondary sexual xteristics Lab- Sickling test is a screening test. Cannot differentiate carrier from disease patient Prenatal diagnosis-16-18wks gestation via amniocentesis or chorionic villous sampling Newborn screening- HPLC, iso -electric focusing Hemoglobin electrophoresis-acid electrophoresis (0-6mo), alkaline (>6mo)

11. Acute Complications Vaso-occulsive events- precipitated by physical stress, dehydration, infections, hypoxia, acidosis, cold, swimming in non heated pool for prolong period bone pain, Hand and foot syndrome, acute chest syndrome, cerebro -vascular accidents, abdominal crisis, priaprism , papillary necrosis Anemic crisis Acute sequestration crisis Hyperhemolytic crisis Megaloblastic crisis Aplastic crisis due to parvo virus B19 infection Infective- especially by encapsulated organisms-sepsis, osteomyelitis , meningitis, pneumonia etc

12. Bone pain crisis. Site of pain is usually in the sites of hematopoiesis In children <3 years, usually occurs in the hands and feet where hematopoiesis occurs . This is called hand and foot syndrome/dactylitis In children older than 3 years, the pain is at the long bones, sternum, ribs, pelvic bones and the vertebral column

13. Abdominal crisis Occurs as a result of microvascular occlusion of tthe mesenteric blood vessels this can result in ischemia/infarction in the liver, spleen, lymph node Results in abdominal pain and distention that usually mimic acute abdomen

14. Acute chest syndrome it is now the leading cause of death defined as the development of a new infiltrate accompanied by symptoms including fever, chest pain, tachypnea, cough, hypoxemia, and wheezing it is caused by infection or infarction (hypoventilation), and or fat embolization and iatrogenic overhydration 50% of ACS is due to infections -organisms include viruses, atypical bacterial like mycoplasma pnemoniae , chylamidia , streptococcus pneumoniae infartion usually follows hypoventilation- follow splinting during pain crisis involving the ribs, sternum or following abdominal crisis fat embolization occurs in bone pain crisis - infartion results in mobilization of marrow fat into the circulation then the chest

15. ACS cont’d Risk of ACS is directly proportional to the HB level and WBC count, higher in children with asthma. Lab finding: increased WBC HB drops by at least 1.5g/dl increase platelet

16. Stroke May be infarctive or hemorrhagic In children it is usually infarctive, while the hemorrhagic type occurs in older children and adults due to intracranial arterial stenosis or occlusion, usually involving the vessels in the circle of Willis most common in homozygous SS (11% prevalence), especially between the age of 2-5 yrs

17. stroke cont’d symptoms include focal motor deficits- hemiplagia , gait abnormality speech defect altered mental status seizures headaches loss of vision Second stroke usually recur within 3yrs of a first episode

18. Anemic complication- Acute splenic sequestration crisis (ASSC) ASSC and infections were the commonest causes of death in infancy and early childhood ASSC is most common between the age of 5 and 24 month May occur with fever or infection There is rapid pooling of large amount blood in the spleen leading to splenomegaly, hypovolemia, severe palor , and shock Child is pale and has fatigue Lab: worsened anemia which may vary from moderate to severe - reticulocytosis , - wbc and PLT may drop,

19. Aplastic crisis Can affect any age May occur in association with bone pain crisis and or ASSC Due to parvo virus B 19 infection Bone marrow ceases to produce blood for 7-14 day leading to reticulocytopenia, worsening anemia PLT and WBC are not affected usually terminates spontaneously after 10 days

20. Management of SCD Comprehensive health care treatment, consisting of Parental counselling and education Early diagnosis-newborn screening Adequate hydration Adequate nutrition Early recognition and treatment of fever-emergency Early recognition of enlarged spleen and treatment Immunization Prophylactic medication-Penicillin V, Vitamine C, Bco , Malarial prophylactic drugs, Folic acid, 3 monthly deworming Regular hospital follow up

21. Treatment of complications Bone pain- identify possible cause and treat Determine the pain severity-mild, moderate , severe Hydrate orally or with IVF-4.3%D/S at 120% maintenance Give analgesia- depending on the severity of pain, narcotic analgesia for severe pain, and NSAID for mild to moderately severe pain CVA, Acute Chest Syndr , Priaprism - CVA, do exchange blood txn , then hypertranfusion

22. Infection- pneumonia, meningitis, osteomyelitis /septic arthritis. Treat with antibiotic Anemic crisis- transfuse if decompensating . Give packed red cells for ASC

23. Acute chest syndrome- pre-EBT radiograph

24. ACS- Post EBT radiograph

25. Chronic complication Avascular necrosis of head of femur or humerus Nephropathies eg nephrotic syndrom Chronic organ damage- eg liver (sickle cell hepatopathy ) Leg ulcers Retinopathies CVA with stroke and other neurologic deficits like cortical blindness, mental retardation, seizure disorder etc