Test 2 Continued Flashcards
A normal hemoglobin is composed of what?
4 hemo molecules, and 4 globin polypeptide chains
What are the normal adult hemoglobin’s?
Hgb a Hgb A2 and Hgb F
What does hemoglobin a consist of?
Two alpha and two beta chains it makes up 95 to 98% of hemoglobin
What does hemoglobin A2 consist of?
Two alpha and two Delta chains it makes up 2 to 3% of hemoglobin
What does hemoglobin F consist of?
Two alpha and two gamma chains it makes up less than 1% of hemoglobin
How are hemoglobinopathies acquired?
They are inherited
What genetic mutation occurs in hemoglobinopathies?
Amino acid sequence in the globe and chain is altered
What are the four abnormal functions/alterations that cause hemoglobinopathies
Single amino acid substitution in one of the chains, abnormal synthesis of one of the amino acid chains, fusion of hemoglobin chains, extension of an amino acid
What chain is normally altered in single amino acid substitution?
Beta
How Does a single amino acid substitution in one of the chains change the function?
Little to no effect on the globin chain function
What causes hemoglobin S?
Valine is substituted for glutamic acid at the six position of the beta chain
What causes hemoglobin C?
Lysine is substituted for glutamic acid at the sixth-position of the beta chain
What does abnormal synthesis of one of the amino acid chains result in?
It reduces or completely preclude the synthesis of one or more of the globe in chains (thalassemia)
What does fusion of hemoglobin chains result in?
Two normal genes break, then switch places and fuse together
What is the result of an extension of an amino acid chain?
The globin chains are longer than normal
If someone has hemoglobin disease, which alleles would have been inherited?
Either a homozygous for abnormal jeans or heterozygous for dominant gene that will cause an abnormality
What is an example of a hemoglobin disease?
Sickle cell anemia disease
In hemoglobin trait what alleles would be present?
Heterozygous As
What is an example of a hemoglobin trait?
Sickle cell trait 75% HGBA, 23% HGB S, 2% HGB A2
What is the main way to evaluate hemoglobinopathies?
Hemoglobin electrophoresis
Is hemoglobin electrophoresis a quantitative or qualitative test?
Quantitative
What does hemoglobin electrophoresis identify?
The types of hemoglobin based on electrophoretic mobility
What are three things that the migration of hemoglobins is dependent on in hemoglobin electrophoresis?
PH, time of migration, media used whether it be alkaline or acidic
What are some other ways to evaluate hemoglobinopathies?
DNA based gene analysis, Hgb F flow cytometry, HPLC
What is the proper way to use international nomenclature when naming variant hemoglobin?
1 mutated chain identified 2 amino acid position affected 3 helical position of mutation 4 amino acid substitution Hgb S B6 Glu->Val
Hemoglobin F has a major hemoglobin component at what time in life?
Fetus and newborn
By what age have most people converted the hemoglobin F to hemoglobin a?
Two
What happens to hemoglobin F if it doesn’t convert to hemoglobin a as a patient ages?
It isn’t necessarily harm for however hemoglobin F doesn’t release oxygen as well as hemoglobin a
What is the lifespan of a red blood cell with hemoglobin S?
10 to 20 days
What hemoglobin lessens the severity of sickle cell anemia?
Hemoglobin F
What are two primary test for hemoglobin S?
Newborn screening and solubility testing
In solubility testing does a turbid solution represent Hgb S being present or not present?
HGBS present
What does the amount of in vivo sickling depend on?
Hgb S
If an individual is homozygous for hemoglobin S what are they?
Hemoglobin S anemic
A crisis brings a patient in what are possible causes of a crisis?
Hypoxia, acidosis, dehydration, fever, cold stress And infections
Children are usually symptom-free of hemoglobin S anemia because?
Because of the production of HGBF that ends around six months
What are the laboratory results of sickle cell disease?
Hgb decreased between 5 to 9.5, hematocrit decreased 20 to 25%, red blood cells decreased reticulocytes increased white blood cells increased Bilirubin and lactate dehydrogenase increased
What does a peripheral smear of someone with sickle cell disease show?
Normocytic/normochromic poikilocytosis sickle cells target cells and spherocytes
Anisosytosis. Polychromasia nucleated red blood cells Howell Jolie bodies basophilic stippling and pepper Heimir bodies
80% Hgb S 5% Hgb A2 Hgb F 1-20%
What are treatments for sickle cell disease?
Red blood cell transfusion’s, hydroxyurea, prophylactic antibiotics
In sickle cell trait the individual is heterozygous with what alleles?
Hgb A and S
What are the laboratory results in sickle cell trait?
So you ability test positive, normal peripheral smear, 60% hemoglobin a and 40% hemoglobin S
What happens with hemoglobin C?
Crystals form and give the red blood cells are rectangular shape
What are the laboratory results in hemoglobin C disease?
Hemoglobin 9 to 12 red blood cell lifespan is 38 days peripheral smear normal city/normochromic with target cells, Spherocytes, small folded cells due to hemoglobin see crystals
What do you need to know about hemoglobin c trait?
60% hemoglobin a 40% hemoglobin C with normal peripheral blood smear
What are the laboratory results for hemoglobin SC disease?
Mild to moderate anemia hemoglobin 8 to 10, red blood cells life span of 29 days, peripheral smear will show target cells and possible folded cells
What is thalassemia?
Decreased production of alpha or beta globin chains leading to an excess of other chains
How are thalassemias acquired?
They are inherited
What determines the type of thalassemia an individual has?
The globin chain affected
In Alpha Thalassemia what synthesis is impaired and what access chains are present?
Alpha chain is impaired Causing an excess in beta chains
What is the inherited genes in someone with thalassemia minor?
Heterozygous
People with thalassemia major have inherited how many thalassemia genes?
Two homozygous
When do thalassemias appear in individuals?
After the hemoglobin F synthesis stops at about one year
What are symptoms of thalassemia?
In large spleen, liver, and heart thin and brittle bones due to ineffective erythropoiesis
What is the leading cause of death in patients with thalassemias?
Heart failure and infections
If someone with thalassemia is treated what might occur?
Iron deposits
What is used to treat the iron deposits?
Chelating drugs
What are two kinds of alpha thalassemia’s?
Accumulation of gamma tetramers (Barts hemoglobin) or accumulation of beta tetramers (hemoglobin H)
If someone has only two viable alpha jeans meeting there were two deletions what do they have?
Alpha thalassemia trait
What are the laboratory results of someone with alpha thalassemia trait?
Peripheral smear will show microcytic, hypochromic cells target cells and elliptocytes
How many functioning alpha genes does someone with hemoglobin H disease have?
1
What are the laboratory findings of someone with HGBH?
Microcytic, hypochromic cells, target cells, poikilocytosis, Anisocytosis, schistocytes, basophilic stippling, Hgb H inclusions
What is hydrops fetalis?
The most severe state of Alpha thalassemia with no functioning Alpha genes
No HGBA only Hgb Barts
Hgb Bart has high oxygen affinity resulting in what?
Resistance of delivering oxygen to tissues causing fetus to die of hypoxia
Laboratory findings of hydrops fetalis?
Marked microcytic, hypochromic anemia, marked anisocytosis, marked poikilocytosis, numerous nucleated red blood cells
Beta thalassemia’s results in what?
Extravascular homolysis
Beta thalassemia minor also known as coolies trait laboratory results would include?
Decrease osmotic fragility, microcytic hypochromic cells, basophilic stippling, target cells, elliptocytes, hemoglobin electrophoresis would show an increase in Hgb A2
Betos Alcenia major/Cooleys anemia has a little or no what synthesized?
Hemoglobin a
What are the laboratory findings of someone with thalassemia major?
Severe anemia red blood cell life span of 7 to 22 days Hgb between two and nine, decreased red blood cells MCV osmotic fragility increased white blood cells reticulocytes Billy Rubin total iron binding capacity in serum iron
Peripheral smear would show hypochromic microcytic cells with Marc poikilocytosis literally everything
What are treatments for thalassemia major?
Transfusions, bone marrow and stem cell transplant’s, drugs like hydroxyurea, gene therapy
HGBSB to thalassemia has what percentage of HGBS present?
65 to 95%
What are the lab findings of someone with HGBS beta thalassemia?
Hgb of 8 to 9 with increased reticulocytes peripheral smear will show microcytic hypochromic cells with nucleated red blood cells target cells polychromasia sickle cells and Ani so cytosis Hgb electrophoresis will show three bands present one at HTBS, HGBA2, Hgb F
What differentiates beta thalassemia’s from sickle cell trait?
In beta thalassemia as you’ll see increased Hgb A2in microcytes in sickle cell you’ll see HGBA is the predominant type
What should you look for to differentiate thalassemias from iron deficiency’s?
Thalassemias: RBC increased, basophilic stippling, target cells, serum iron increased, complete transferrin saturation, osmotic fragility decreased
Iron deficiency: RBC decreased, basophilic stippling will only appear after treatment, occasional target cells, osmotic fragility is normal
