Introduction:
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare disease affecting 1-4 people per million. The median survival rate is 10-15 years, with 35% of patients diagnosed with PNH dying within five years3. PNH is characterized by thrombocytopenia, leucopenia, and thrombosis . Paroxysmal Nocturnal Hemoglobinuria should be suspected when the patient has hemoglobinuria with a negative Coombs test, aplastic anemia, and myelodysplastic syndrome . PNH often goes undiagnosed and because of the high morbidity associated with PNH, it is necessary to establish an assay able to detect and diagnose PNH. Flow cytometery provides the best methodology for detection of PNH clones and it is both more sensitive and specific than current assays used such as Ham and Sucrose Hemolysis test. In addition, PNH tests are mail out, therefore, there exists potential revenue and cost savings if Baylor Scott and White is able to perform the assay in-house. A multiparameter flow cytometric assay will be modified that will be capable of monitoring and diagnosing PNH clones; thus improving the patient’s likelihood of survival and prognosis.
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a hemolytic anemia that is a result of a somatic mutation in the hematopoietic stem cell that arises from the bone marrow. The somatic mutation occurs in the Phosphatidylinositol glycan complementation group A (PIG-A) gene. PIG-A is responsible for the assembly and production of Glycosylphosphatidylinositol (GPI) proteins which are present on blood cells. The gene encodes for the protein glycosyltransferase which is an integral component in the creation of the GPI anchors present on blood cells (RBC’s) . GPI proteins are necessary in keeping proteins attached to the s...
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...ddition, compensation will be necessary to reduce fluorescent crossover from each individual antibody. After the proper dilutions are determined, and the correct parameters are determined, analysis of patients will begin. The analysis will be completed on patients with PNH and normal patients as well. Because PNH is a rare malignancy, positive PNH specimens will be ordered to assess and confirm the proper parameters were established, and the sensitivity for detection of PNH clones is acceptable.
Data Analysis
The data gathered will assess the sensitivity of the assay with known positive PNH samples, and determine if the proper parameters were established for detection of PNH clones. Histograms and scatter plots will be included in the data analysis to analyze the different clinical findings associated with PNH and also to compare how a normal population appears.
The diminished rate of synthesis amongst the globin chains was first described from Cooley and Lee. However, the term “Thalassemia: was coined by Whipple and Bradford in 1936 (Bain, 2006). The term “Thalassemia” is derived from the Greek words “Thalassa” (sea) and “Heama” (blood) and refers to disorders associated with defective synthesis of the alpha or beta globin subunits of the hemoglobin molecule. Hemoglobin A (a2B2) is inherited. ...
Sickle cell anemia is an inherited disease of red blood cells. Normally red blood cells contain a protein called hemoglobin A, which carries oxygen to all the organs in the body. With sickle cell anemia, however, the body makes a different kind of protein, called hemoglobin S.
Sickle cell anemia is a blood disorder that is inherited from both parents in which the body produces abnormally shaped red blood cells. In sickle cell anemia, the hemoglobin in red blood cells links together; resulting in the red blood cells to become rigid and a C-shaped. These deformed cells block blood and oxygen flow in blood vessels. Sickle cells deteriorate quicker than normal red blood cells, which results in anemia.
A patient with sickle cell has inherited the condition from both parents, and it all starts in the hemoglobin. Hemoglobin is “an iron-containing protein in red blood cells that reversibly binds to oxygen” (Reece, Urry, Cain, Wasserman, Minorsky, & Jackson, 2011). Obviously, hemoglobin is an important substance for oxygen to be transported in red blood cells. However, a patient with sickle cell has irregular hemoglobin cause by inherited genes. This “oxygen delivery” system cannot function properly because a gene
A three-dimensional structure of hemoglobin is determined by X-ray crystallography showed hemoglobin is made up of four polypeptide chains, each of those chains has a very similar three-dimensional structure to the single polypeptide chain in myoglobin. The major type of hemoglobin found in adults (HbA) is made up of two different polypeptide chains: the alpha-chain that consists of 141 amino acids residues, and the beta-chain of 146 residues. Each chain, like that in myoglobin consist of eight alpha-helices and each contains a heme prosthetic group. Therefore, hemoglobin can bind four molecules of oxygen. The four polypeptide chains, two alpha and teo beta, are packed tightly together in a tetrahedral array to form an overall spherically shaped molecule that is held together by multiple noncovalent interactions.
The problem is that sickle cell anemia affects about 72,000 Americans in the United States. Sickle cell anemia is an inherited disease in which the body is unable to produce normal hemoglobin, an iron-containing protein. Abnormal hemoglobin can morph cells that can become lodged in narrow blood vessels, blocking oxygen from reaching organs and tissues. The effects of sickle cell anemia are bouts of extreme pain, infectious, fever, jaundice, stroke, slow growth, organ, and failure.
Handbook of Laboratory and Diagnostic Tests with Nursing Implications (3rd edition). Philadelphia: F.A. Davis Company.
Do individuals X, Y, Z have Sickle Cell Anemia or Sickle Cell trait? In this investigation three DNA samples were tested to see if they had Sickle Cell or carry the Sickle Cell trait. Sickle cell Anemia is a disease of the red blood cells that is inherited from your parents. Sickle Cell is caused by point mutation in which a single base in the ꞵ-globin gene that results in the substitution of valine instead of glutamate in the amino acid chain. The acid change aggravates the blood cells and make them take a sickle shape and lose elasticity. The main purpose of Hemoglobin is to carry oxygen from the lungs to the body’s tissues. To carry out this function a healthy red blood cell has a hollowed circular cavity which allows them to hold nutrients
Yearly, around six hundred to nine hundred people are diagnosed with Aplastic Anemia within the United States. Aplastic Anemia is a autoimmune hematological disorder that causes pancytopenia which is a reduction in major blood components, namely, erythrocytes, leukocytes and platelets. This disease has been labelled as a type of bone marrow failure, that is often due to not one but a variety of disorders that occur simultaneously. Aplastic Anemia can therefore be defined as a bone marrow disorder that is often rare, non contagious, and can often be life threatening.
Sickle cell disease. (2011). In The gale encyclopedia of medicine. Retrieved from Gale Science in Context database. (Accession No. DU2601001701)
Individuals who inherited this disease from their parents do not possess the standard hemoglobin that should be contained in RBC. Hemoglobin is a protein present in RBC, which transports oxygen to all parts of the body (National Heart and Blood Institute, 2017). The disease which impairs the hemoglobin’s responsibility, prevents blood cells from receiving the sufficient oxygen, causes RBC to be sickle shaped. Sickle cell disease precedes to several painful health complications such as VOC (vaso- occlusive crises), which are severe pain recurring episodes, that can lead to irreversible organ damage. Sickle cell anemia causes red blood cells to hemolyze continuously through an individual’s lifetime… hemolysis is the breakdown of red blood cells (Krishnamoorthy, et al. 2017). An experimental study was conducted with SCD Townes mice to test a possible solution for sickle cell anemia. Throughout a seven-week span, mice orally conveyed dosages of 100 mg/kg of DMF. DMF known as dimethyl fumarate is small complex molecule and which binds and activates to enhance Nrf2 to enhance Hbf. “Nrf2 is a transcription factor that triggers cytoprotective and antioxidant pathways to limit oxidative damage, inflammation, and increases HbF” (Krishnamoorthy, et al. 2017). Fetal hemoglobin (Hbf) is the hemoglobin present in fetuses; it is responsible for the transportation of oxygen
Fischbach, Frances, A Manual of Laboratory & Diagnostic Tests, 4th ed., J. B. Lippincott Company, Philadelphia
Its history is long and successful. Additionally, its sensitivity and simplicity, spatial and temporal resolution have all played a part in its importance that has led to its persistence as the gold standard in disease detection (Kiernan, 1999; Boekelheide, K. & Schuppe-Koistinen, I. 2012)
Beckman DXH Hematology analyzers that believe it or not will do the cell count on a