Hemolytic Anemias Part 2 Flashcards
(32 cards)
Thalassemia Syndromes
The thalassemia syndromes are a heterogeneous group of disorders caused by inherited mutations that decrease the synthesis of either the α-globin or β-globin chains that compose adult hemoglobin, HbA (α2β2), leading to anemia, tissue hypoxia, and red cell hemolysis related to the * imbalance in globin chain synthesis.*
Hemoglobin molecule
Hemoglobin A – Tetramer of 4 globin chains + 4 heme
β-Thalassemias
The β-thalassemias are caused by mutations that diminish the synthesis of β-globin chains
β0 mutations, associated with absent β-globin synthesis
β+ mutations, characterized by reduced (but detectable) β-globin synthesis
β-Thalassemias
Peripheral blood smear
Impaired β-globin synthesis results in anemia by two mechanisms.
The deficit in HbA synthesis produces *“underhemoglobinized” hypochromic, microcytic red cells with subnormal oxygen transport capacity.
Even more important is the diminished survival of red cells and their precursors, which results from the imbalance in α- and β-globin synthesis.
severe β-thalassemia
it is estimated that * 70% to 85% of red cell precursors suffer diminished survival, which leads to * ineffective erythropoiesis. Those red cells that are released from the marrow also bear inclusions and membrane damage and are prone to splenic sequestration and * extravascular hemolysis.
β-Thalassemia Major
The anemia manifests 6 to 9 months after birth as hemoglobin synthesis switches from HbF to HbA.
In untransfused patients, hemoglobin levels are 3 to 6 gm/dL
Anisocytosis
Poikilocytosis
Microcytosis
Hypochromia
β-Thalassemia Minor
These patients are usually *asymptomatic. Anemia, if present, is mild. The peripheral blood smear typically shows some red cell abnormalities, including hypochromia, microcytosis, basophilic stippling, and target cells.
Hemoglobin electrophoresis usually reveals an increase in * HbA2 (α2δ2) to 4% to 8% of the total hemoglobin (normal, 2.5% ± 0.3%), which is a reflection of an elevated ratio of δ-chain to β-chain synthesis.
Recognition of β-thalassemia trait is important for two reasons:
It superficially *resembles the hypochromic microcytic anemia of iron deficiency
It has implications for *genetic counseling. Iron deficiency can usually be excluded through measurement of serum iron, total iron-binding capacity, and serum ferritin
old male with iron deficiency anemia is what until proven otherwise?
colon cancer
an anemia that doesnt get better with iron is what until proven otherwise?
thalassemia beta minor
The α-thalassemias are caused by
inherited deletions that result in reduced or absent synthesis of α-globin chains
Alpha Thalassemia Clinical Syndromes
Loss one gene: diminishes the production of the alpha globin
protein slightly and patient is “normal” - Silent Carrier.
- Loss of two genes: Clinically asymptomatic but microcytic red cells, and at most a mild anemia– Alpha thalassemia Trait.
- Loss three genes: Severe anemia, requiring RBC transfusion to survive. Untreated patients die childhood/early adolescence.With three-gene deletion in alpha thalassemia, beta chains (in great excess) begin to associate in tetramers, producing an abnormal hemoglobin, “Hemoglobin H” Disease.
- Loss four genes: Incompatible with life – Hydrops Fetalis
golf ball inclusions are?
hemoglobin H, a 3 gene deletion
What happens in hydrops fatalis
hemoglobin hangs onto the oxygen, baby dies of hypoxia
red cells missing CD 59 and CD55
those things keep complement from lysing your RBCs
makes them susceptible when they’re missing
Paroxysmal Nocturnal Hemoglobinuria
Paroxysmal nocturnal hemoglobinuria (PNH) is a disease that results from * acquired mutations in the phosphatidylinositol glycan complementation group A gene (PIGA), an enzyme that is essential for the synthesis of certain membrane-associated complement regulatory proteins.
Red cells deficient in these GPI-linked factors are abnormally susceptible to lysis or injury by complement
at night pH changes
PNH blood cells are deficient in three GPI-linked proteins that regulate complement activity:
Decay-accelerating factor or CD55
Membrane inhibitor of reactive lysis, or CD59
C8 binding protein
Paroxysmal Nocturnal Hemoglobinuria
manifests as
- intravascular hemolysis, which is caused by the C5b-C9 membrane attack complex.
The hemolysis is * paroxysmal and nocturnal in only 25% of cases; chronic hemolysis without dramatic hemoglobinuria is more typical. The tendency for red cells to lyse at night is explained by a slight decrease in blood pH during sleep, which increases the activity of complement.
The anemia is variable but usually mild to moderate in severity. The loss of heme iron in the urine * (hemosiderinuria) eventually leads to iron deficiency, which can exacerbate the anemia if untreated
leading cause of disease related death in individuals with PNH:
and other complications that arise
Thrombosis.
About 40% of patients suffer from venous thrombosis, often involving the hepatic, portal, or cerebral veins.
About 5% to 10% of patients eventually develop acute myeloid leukemia or a myelodysplastic syndrome, possibly because hematopoietic stem cells have suffered some type of genetic damage.
PNH is diagnosed by … and treated with …
flow cytometry, which provides a sensitive means for detecting red cells that are deficient in GPI-linked proteins such as CD59.
The cardinal role of complement activation in PNH pathogenesis has been proven by therapeutic use of a monoclonal antibody called Eculizumab that prevents the conversion of C5 to C5a.
This inhibitor not only reduces the hemolysis and attendant transfusion requirements, but also lowers the risk of thrombosis by up to 90%
Only acquired hemolytic anemia
PNH
Direct antiglobulin test
= coombs test
antibodies are on the patient’s red cell and –> agglutination
Immunohemolytic Anemias are
caused by
antibodies that bind to red cells, leading to their premature destruction
Commonly referred to as autoimmune hemolytic anemias
warm antibody type
igG
primary (idiopathic)
secondary– autoimmune disorder, drugs, lymphoid neoplasms
About 50% of cases are idiopathic (primary); the others are related to a predisposing condition or exposure to a drug.
Most causative antibodies are of the IgG class
Extremely difficult to treat since patient has antibody against their own reds blood cells. This autoantibody also reacts with all other human red cells……… THERE IS NO COMPATIBLE BLOOD FOR TRANSFUSION
