Presentation on theme: "SICKLE CELL ANEMIA Nada Mohamed Ahmed , MD, MT (ASCP)i."— Presentation transcript:
1 SICKLE CELL ANEMIANada Mohamed Ahmed ,MD, MT (ASCP)i
2 HEMOLYTIC ANEMIA Hereditary IntracorpuscularWITHIN THE RED CELLHEMOLYTIC ANEMIAExtracorpuscularOUTSIDE THE RED CELLHereditaryAcquiredAUTO-IMMUNE1. Warm Ab2. Cold Ab3. Transfusion reactions4. Drug associatedNON-IMMUNE1. Hypersplenism2. Infections (Malaria),,3-mechanical trauma to RBCs4. Liver dz (Spur cell)1. Membrane defects- Hereditary spherocytosis- Hereditary elliptocytosis- Hereditary pyropoikilocytosis- Hereditary stomatocytosis2. Enzyme defects-G6PD3. -Hemoglobin defects-.Hemoglbinopathies(sickle cell disorders)- Hb SS, CC, SC & S-B-- ThalassemiasMembrane defectsPNH
3 OBJECTIVESDefinition Causes and Genetics design Classification Pathogenesis Lab diagnosis
4 What is Sickle cell Disease Sickle Cell disease: is a genetic disorder that affects erythrocytes (RBC) causing them to become sickle or crescent shaped.The effects of this condition due to an abnormality of the hemoglobin molecules found in erythrocytes.
5 The origin of Sickle Cell anemia The change in cell structure arises from a change inthe structure of hemoglobin.A single change in an amino acid causes hemoglobinto aggregate.
6 Genetics design It’s autosomal recessive blood disease. You inherit it from your parents.*The gene defect is a known mutation of a single nucleotide.*The person that receives the defective gene from both his parents will develop Sickle-cell disease.An autosomal recessive disorder means two copies of an abnormal gene must be present in order for the disease or trait to develop.*The person who receives only one defective gene from either one of his parents will develop Sickle-cell trait.
7 Causes Sickle CellIs caused by a point mutation in the β-globin chain of haemoglobin, causing the amino acid glutamic acid to be replaced with the c amino acid valine at the sixth position.
8 Types of HemoglobinNormalHb AHb A2Hb FAbnormal (350)Hb SHb CHb E
9 Haemoglobin A two alpha two beta A2 two delta F two gamma Normally, humans haveOf these, Haemoglobin A makes up around 96-97% of the normal haemoglobin in humans.HaemoglobinAtwo alphatwo betaA2two deltaFtwo gamma
11 Common types of Sickle Cell Disorders ClassificationCommon types of Sickle Cell DisordersType of anaemiaHemoglobin variationcommentSickle Cell AnemiaSickle haemoglobin (HbS) + Sickle haemoglobinMost Severe – No HbAHemoglobin S-C diseaseSickle haemoglobin (HbS) + (HbC)Mild form of Sickle Cell DisorderSickle Cell TraitSickle haemoglobin (S) + Normal haemoglobin (A)
12 Sickle Cell Anemia vs. Sickle Cell Trait People who have sickle cell anemia are born with it; means inherited, lifelong condition. They inherit two copies of sickle cell gene, one from each parent. Sickle cell trait is different from sickle cell anemia . People with sickle cell trait don’t have the condition, but they have one of the genes that cause the condition. People with sickle cell anemia and sickle cell trait can pass the gene on when they have children.Sickle cell anemia is an inherited, lifelong condition. People who have sickle cell anemia are born with it. They inherit two copies of the sickle cell gene, one from each parent. People who inherit a sickle cell gene from one parent and a normal gene from the other parent have a condition called sickle cell trait.Sickle cell trait is different from sickle cell anemia. People with sickle cell trait don’t have the condition, but they have one of the genes that cause the condition. Like people with sickle cell anemia, people with sickle cell trait can pass the gene on when they have children. To learn more about sickle cell trait, see the section on causes of sickle cell anemia.
13 Sickle Cell TraitSickle haemoglobin (S) + Normal haemoglobin (A) in RBCAdequate amount of normal Hb (A) in red blood cellsRBC remain flexibleCarrierDo Not have the symptoms of the sickle cell disorders,with exceptions:Pain when Less Oxygen than usualMinute kidney problems
14 Mechanism of Pathogenesis When sickle hemoglobin (HbS) gives up its oxygen to the tissues, HbS sticks togetherForms long rods form inside RBCRBC become rigid, inflexible, and sickle-shapedUnable to squeeze through small blood vessels, instead blocks small blood vesselsLess oxygen to tissues of bodyRBCs containing HbS have a shorter lifespanNormally 20 daysChronic state of anaemia
22 This test is simple and quick, used to identify the presence of HbS. Sickling TestMethod:1) A sample of venous blood or capillary blood may be collected for this test.2) Mixing blood with the reducing agent, sodium metabisulphite, will induce sickling in susceptible cells.3) the results can be viewed under a microscope after 20 minutes.This test is simple and quick, used to identify the presence of HbS.Negative TestHbAPositive TestHbSNormal RBCSickled RBC
23 Sickle Solubility Test (SST) A rapid and inexpensive technique used to screen for the presence of sickling hemoglobins, can be used at home.A positive result must be confirmed by another method (HPLC or electrophoresis) to confirm the presence of Hb S and to distinguish Hb AS (carrier state) from Hb SS (sickle cell disease).Disadvantage: Other insoluble hemoglobins, such as Hb C-Harlem, will also give a positive result.Method1) Erythrocytes are lysed by saponin.2) The released hemoglobin is reduced by sodium hydrosulfite in a phosphate buffer.3) Reduced HbS is characterized by its turbidity ( insolubility).
24 Sickle Solubility Test (SST The presence of HbA under these same conditions results in a clear red solution. The resulting tactoids of HbS causes the solution to remain turbid.
25 Hemoglobin Electrophoresis test * Haemoglobin electrophoresis will differentiate between homozygous and heterozygous conditions.* Hemoglobin types have different electrical charges and move at different speeds.*HbAS: Has both HbA and HbS.Shows 2 bands*HbSS: Is less negative by 2 compared to HbA .Migrates slower than HbA
26 DNA analysis This test is used to investigate alterations and mutations in the genes that produce hemoglobin components.It may be performed to determine whether someone has one or two copies of the Hb S mutation or has two different gene mutations.Genetic testing is most often used for prenatal testing:amniocentesis “14 to 16 weeks”.
27 Screening 16 and 18 weeks of the pregnancy Prenatal TestingAmniocentesis16 and 18 weeks of the pregnancysmall risk of causing a miscarriage (1 in 100)
28 Signs and Symptoms of Sickle Cell Anemia JaundicePain EpisodesAnemiaInfectionsUlcers on the LegsEye Problems
29 What Are the Signs and Symptoms of Sickle Cell Anemia? The signs and symptoms of sickle cell anemia vary. Some people have mild symptoms. Others have very severe symptoms and often are hospitalized for treatment. Sickle cell anemia is present at birth, but many infants don’t show any signs until after 4 months of age.
30 Signs and Symptoms Related to Anemia The most common symptom of anemia is fatigue (feeling tired or weak). Other signs and symptoms of anemia include:Shortness of breathDizzinessHeadacheColdness in the hands and feetPale skinChest pain
31 What Are the Signs and Symptoms of Sickle Cell Anemia? Signs and Symptoms Related to Pain Sudden pain throughout the body is a common symptom of sickle cell anemia. This pain is called a "sickle cell crisis." Sickle cell crises often affect the bones, lungs, abdomen, and joints. A sickle cell crisis occurs when sickled red blood cells form clumps in the bloodstream. (Other cells also may play a role in this clumping process.) These clumps of cells block blood flow through the small blood vessels in the limbs and organs. This can cause pain and organ damage.