Clinical Aspects of Anemia Flashcards
Work Up of Anemia
Rule out hemorrhage vs sequestration (rare)
Etiology can be found with the H&P, Reticulocyte count, CBC and the Peripheral Smear
Then classify as either:
Hypoproliferative (not making them)
Hemolytic (survival defect)
Production Defects
Reticulocyte count- Decreased
Morphology- Normal
Etiology-
Decreased Erythropoeitin
Bone Marrow Failure
Examples- Chronic Renal Disease Anemia from Bone Marrow Damage Anemia of Chronic Disease (ACD) Anemia of Hypometabolic states: hypothyroidism, Addison Disease, hypogonadism, and panhypopituitarism
Anemia of Chronic Disease
Is the most common cause of anemia in the hospitialized medical patient
Inflammation leads to production of IL-6 which then produces hepcidin. This then decreases the release of iron from macrophages.
Causes- most common:
Chronic rheumatic
Infectious
neoplastic
Iron Studies for Fe Deficiency and ACD
Fe Deficiency: low Fe, low ferritin, high TIBC, low transferrin saturation (bound), and high soluble transferrin receptor (unbound)
Anemia of Chronic Disease: low Fe, low high ferritin (acute phase reactant), low TIBC, low/normal transferrin saturation, and normal soluble transferrin receptor
Maturation Defect: Cytoplasmic
Reticulocyte count- Decreased
Morphology- Hypochromic, Microcytic
Etiology
Impaired Hgb synthesis
Protoporphyrin deficiency
Globin synthesis deficiency
Examples
Fe Deficiency
Sideroblastic anemia
Thalassemias
Iron Deficiency PE
Fatigued, tachycardic, dyspnea, cheilosis, esophageal webs (Plummer-Vinson), pica
History: pregnancy, diet, family history
Normal Volume
Low MCV
Fe Deficiency: Labs
Fe is essential for Hb production and a deficiency will lead to impaired erythropoeisis.
Red cells are microcytic and hypochromic
Reticulocyte count is low
Serum Fe and ferritin are low
Transferrin levels are high with elevated TIBC
You must pursue the etiology
Siderblastic Anemia
Moderate to severe anemia- Hb 4-10 mg/dl
Indices Serum Iron is elevated Serum Ferritin is elevated TIBC is normal Reticulocyte count is low MCV is low
Smear will show anisocytosis and poiklocytosis
Bone Marrow will show erythyroid hyperplasia with a maturation arrest.
**Prussian Blue stain of the marrow will show the mitochondrial iron deposition which will result in the ringed sideroblasts.
Types of Sideroblastic Anemia: Hereditary
Hereditary
Congenital X-linked- ALAS-2 mutations
ALAS is a rate limiting enzyme in heme biosynthesis
Mitochondrial cytopathy
Autosomal recessive sideroblastic anemia involves mutations in the SLC25A38 gene
Types of Sideroblastic Anemia: Acquired
Acquired
Myelodysplasia
Copper deficiency- copper is needed for iron metabolism
Pyridoxine deficiency- can be caused by isoniazid
Drugs/Toxins
Toxins- Lead, Zinc, auto-antibodies
Drugs- Ethanol, Isoniazid, Cycloserine, Chloramphenicol, Busulfran
Copper chelators- Penicillamine, Trientene- These meds are used for the treatment of Wilson’s disease.
Sideroblastic Anemia: Tx
Rule out reversible causes
Eliminate any drugs that may be causing it
Transfusion
Need to watch out for iron overload
Pyridoxine therapy
Little downside to using it, may help the anemia
Alpha Thalassemia
Due to gene deletion with reduced alpha chain synthesis
Severity is determined by absence of 1-4 alpha chains
Deletion of all 4 chains (β4) results in hydrops fetalis - fatal
Seen in people of China and SE Asia
Microcytosis worse than degree of anemia
Hb H of requires frequent transfusions throughout life
Alpha Thalassemia: 4 Deletion Types
1) α- Thalassemia trait- 1 loci affected, asymptomatic, no hematologic abnormalities.
2) α- Thalassemia Minor- 2 loci affected, asymptomatic, MCV low, little to no anemia.
3) HbH- 3 loci affected, unpaired β chains form β4 tetramers called HbH, these form inclusions in peripheral cells. Intermediate anemia with avoidance of transfusions until adulthood.
4) Hb Barts- 4 loci affected, no effective hemoglobin, causes death in utero.
Beta Thalassemia
Due to a point mutations
Alpha chain hemoglobins are unstable in the absence of beta chains and precipitate which damages RBC membranes
Peripheral RBC destruction
Hyperplastic bone marrow due to anemia
Greek and Mediterranean predominance
Low MCV common
Hb electrophoresis
Homozygous is Major, asymptomatic until 6 months then major issues leading to early death by 20-30 years old
Heterozygous is Minor, microcytic anemia but normal life expectancy, odd peripheral smear.
Beta Thalassemia: Three Categories
β- thalassemia- three categories
1) β- thalassemia minor- mild or no anemia with a disproportionate degree of microcytosis.
* *2) β- thalassemia major- Cooley anemia- Have no β chain production. This forms insoluble α chains which precipitate into inclusion bodies. These cause death within the marrow and splenic removal which causes a severe anemia. This will cause high erythropoeitin levels which then cause erythroid hyperplasia. If this is severe, it can cause extramedullary hematopoiesis. These patients are usually transfusion dependent and develop iron overload.
3) β- thalassemia intermedia- homozygous. Can range from asymptomatic to transfusion dependent. Minor defects of β globin production with α-thalassemia trait lead to decreased inclusion bodies.
