Red Cell Disorders III Flashcards
What does intrinsic and extrinsic anemia refer to?
Intrinsic anemia refers to the cause of anemia lies within RBC - hemoglobin, enzyme deficiency, membrane defect etc.Extrinsic anemia refers to external factors like antibodies, trauma.
Compare and contrast extravascular and intravascular hemolysis.
Main thing to note: in extravascular hemolysis, the RBCs are being destroyed outside of the blood vessels, so there will be no Hb in the blood or urine.
What are the clinical features of hemolytic anemia.
Clinical features –depend on etiology, severity, and course
- Anemia (usually normochromic, normocytic)
- Extramedullary hematopoiesis
- Jaundice
- Splenomegaly –if extravascular and persistent
- Gallstones
- Hemosiderosis
Explain the terms hemoglobinopathy and thalessemia.
Hemoglobinopathy:
* Structurally abnormal hemoglobin due to mutation in α or β globin gene
* Sickle cell disease
Thalassemia:
* Decreased production of α or βglobin chains due to mutations
* α-thalassemia
* β-thalassemia
Explain sickle cell anemia.
HbS point mutation (SNP), causinga single amino acid replacement in β chain (substitution of glutamic acid with valine).
* Causes extravascular and intravascular hemolysis. Pathogenesis: low O2, high altitude, or acidosis precipitates sickling (deoxygenated HbS polymerizes) leads to anemia and vaso-occlusive disease. Newborns are initially asymptomatic because of increase HbF and decrease in HbS.
* Heterozygotes (sickle cell trait) also have resistance to malaria.
* 8% of African Americans carry an HbS allele. Sickle cells are crescent-shaped RBCs A . “Crew cut” on skull x-ray due to marrow expansion from erythropoiesis (also seen in thalassemias) Coexistence of HbA, HbF prevents sickling
Coexistence of HbC allows sickling
What are the complications associated with Sickle cell disease.
Complications in sickle cell disease:
- Aplastic crisis (due to parvovirus B19).
- Autosplenectomy (Howell-Jolly bodies), increased risk of infection by encapsulated organisms (eg, S pneumoniae).
- Splenic infarct/sequestration crisis.
- Salmonella osteomyelitis.
- Painful crises (vaso-occlusive): Dactylitis (painful swelling of hands/feet), priapism, acute chest syndrome, avascular necrosis, stroke. Renal papillary necrosis (decreased PO2 in papilla) and microhematuria (medullary infarcts).
How is the diagnosis of sickle cell disease made?
Via hemaglobin electrophoresis.
What is the treatment of sickle cell disease.
Blood transfusionHydroxyurea, leads to increased HbF, hydration also helps.Hematopoietic stem cell transplant is potentially curative
Explainβ thalessemia.
Point mutations in splice sites and promoter sequences , leads to decreased β-globin synthesis. Prevalent in Mediterranean populations.
β thalassemia minor (heterozygote):
- β chain is underproduced.
- Usually asymptomatic. Diagnosis confirmed by increased HbA2 (> 3.5%) on electrophoresis.
βthalassemia major (homozygote):
- β chain is absent leads to severe microcytic, hypochromic anemia with target cells and increased anisopoikilocytosis requiring blood transfusion. (2° hemochromatosis).
- Marrow expansion (“crew cut” on skull x-ray)skeletal deformities.
- “Chipmunk” facies.
- Extramedullary hematopoiesis leading to hepatosplenomegaly.
- Risk of parvovirus B19–induced aplastic crisis.
- Increased HbF (α2γ2). HbF is protective in the infant and disease becomes symptomatic only after 6 months, when fetal hemoglobin declines.
- HbS/β thalassemia heterozygote: mild to moderate sickle cell disease depending on amount of β-globin production.
What is the crew cut sign observed on X ray in RBC disorder?
Crew cut sign is observed in X ray due to expansion of facial and cranial bones due to increased hematopoiesis in sickle cell disease and thalessemia.
Explain alpha thalessemia.What is HbH disease?
Defect: α-globin gene deletions, leads to decreased α-globin synthesis.
- cis deletion (both deletions occur on same chromosome) prevalent in Asian populations; trans deletion (deletions occur on separate chromosomes) prevalent in African populations.
- 4 allele deletion: No α-globin. Excess γ-globin forms γ4 (Hb Barts). Incompatible with life (causes hydrops fetalis). 3 allele deletion: inheritance of chromosome with cis deletion + a chromosome with 1 allele deleted leads to HbH disease. Very little α-globin. Excess β-globin formsβ4 (HbH).
- 2 allele deletion: less clinically severe anemia. 1 allele deletion: no anemia (clinically silent).
What are the concequences of having imbalance of alpha, beta or gamma chains in Hb?
- An imbalance of Hb chains leads to apoptosis of RBCs and its precursors in bone marrow so there is decreased hematopoiesis.
- There is also increased destruction of RBCs in spleen leading to extravascular hemolysis.
What pathology is seen in alpha thalessemia in blood smear?
- Hypochromic microcytic anemia
- Target cells
- Variable reticulocyte count
- HbH disease (3-gene deletion) - Elevated HbH (β 4 ) HbBarts disease (4-gene deletion)
- Elevated HbBarts (γ 4 )
- Severe anemia
- Intrauterine death (hydrops fetalis) without intrauterine transfusions
What is the treatment of thalessemias?
- Blood transfusion with iron chelation to avoid development of secondary hemachromatosis.
- Bone marrow transplant is potentially curative.
Explain G6PD deficiency anemia.
- Most common enzymatic disorder of RBCs.
- Causes extravascular and intravascular hemolysis.
- X-linked recessive.
- Defect in G6PD, leads a decrease in NADPH production and subsequently a decrease in ability to reduce glutathione. There is anincrease inRBC susceptibility to oxidant stress.
- Hemolytic anemia followsoxidant stress (eg, sulfa drugs, antimalarials, infections, fava beans).
- Back pain, hemoglobinuria a few days after oxidant stress. Labs: blood smear shows RBCs with Heinz bodies (denatured Hemoglobin)and bite cells.
