Anemias Flashcards
What anemias are microcytic?
iron deficiency, anemia of chronic disease, thalassemia, sideroblastic anemia, hemoglobinopathies (sickle cell)
What is the major cause of iron deficiency in affluent countries?
blood loss (Upper GI examples: Peptic ulcer disease, esophageal varices, gastritis) or Lower GI examples: Hemorrhoids, diverticula, colorectal cancer, Inflammatory Bowel Disease)
What is the most specific test for iron deficiency?
serum ferritin, normal is around 15-200 ng/mL. There is no clinical situation other than iron deficiency in which extremely low values of serum ferritin are seen.
What are symptoms of anemia highly dependent on?
the rate of blood loss… the more acute, the more symptoms appear. With chronic loss, usually takes substantial loss before patient becomes symptomatic
What is pagophagia?
pica for ice; this is considered quite specific for the iron deficiency state
What disease processes does microcytic anemia in the context of low or normal RDW indiciate?
Anemia of chronic disease or thalassemia
When does anemia of chronic disease occur?
Occurs in the setting of chronic inflammatory diseases and malignancy. Believed to involve trapping of iron by activated macrophages, which renders the iron unavailable for erythropoiesis.
How could you differentiate between anemia of chronic disease and iron deficiency anemia?
total iron binding capacity (TIBC) is high in IDA and low in ACD. ACD ferritin is high and IDA ferritin is low
What diseases are commonly associated with anemia of chronic disease?
Rheumatoid arthritis, SLE, HIV, TB, Carcinomas, Lymphomas, Leukemias
What is seen on a megaloblastic anemia blood smear?
presence of oval macrocytes and hypersegmented neutrophils
What is seen on a nonmegaloblastic anemia blood smear?
absence of neutrophil hypersegmentation along with the presence of round macrocytes
What disease processes are associated with megaloblastic macrocytic anemias?
Abnormalities of DNA metabolism (B12 deficiency, Folate deficiency, Drug side effects)
Why are the features of RBCs identical in folate and B12 deficiencies?
The two vitamins are intertwined biochemically so the final common pathway that impairs DNA synthesis in hematopoietic cells is the same when either vitamin is deficient
How can you differentiate between folate and B12 deficiencies?
Neurological symptoms occur only with B12 (Cobalamin) deficiency
What five factors does absorption of B12 depend on?
Adequate dietary intake. Acid-pepsin in the stomach. Pancreatic proteases. Gastric secretion of a functional intrinsic factor. An ileum with functioning Cobalamin-Intrinsic Factor receptors
What can interfere with absorption of B12?
vegan diet, gastrectomy/bariatric surgery, gastritis, pernicious anemia, crohn’s disease, ileal resection, pancreatic insufficiency
What is pernicious anemia?
Autoimmune disease. Parietal cells fail to secrete enough intrinsic factor to absorb vitamin B12
What are symptoms of pernicious anemia?
Weakness, glossitis (enlarged, usually smooth tongue), paresthesias of extremities, GI symptoms such as diarrhea, nausea, vomiting, and pain; severe anemia can reveal signs of cardiac failure
How should you evaluate pernicious anemia?
Review patient’s drug list. Measurement of serum B12 and folate. Peripheral blood smears to look for megaloblasts (macroovalocytes) and hypersegmented neutrophils
How do you differentiate between B12 deficiency and folate deficiency with lab tests?
Serum concentrations of homocysteine (HC) as well as serum and urinary concentrations of methylmalonic acid (MMA) are elevated in B12 deficiency. In comparison, only homocysteine (HC) is elevated in folate deficiency.
What is the treatment for B12 deficiency?
Parenteral B12 administration, Sublingual B12.
Initially, give 1000microgram injections daily for several days, followed by weekly administration, then monthly administration. Vegans can take oral therapy 25-100micrograms daily
What is an important caveat to remember when before treating a suspected folate deficiency?
A person treated with folate who has a B12 deficiency may have their symptoms masked, which is bad because neurological damage from the B12 deficiency can be irreversible
What is the most common cause of folate deficiency?
nutritional due to poor diet and/or alcoholism
What drugs can interfere with folate metabolism?
Trimethoprim, Methotrexate, Phenytoin
What are causes of nonmegaloblastic macrocytic anemias?
Alcoholism, Liver Disease, Aplastic Anemia, Drug-Induced, Myelodysplastic Syndrome, Pregnancy, Myeloma, Hypothyroidism
What show ups on a peripheral smear with anemia due to liver disease.
multiple target cells which have an area of central density surrounded by a halo of pallor
What’s in the differential diagnosis for normocytic anemia?
normal pregnancy, overhydration, renal disease, marrow problems, *mixed anemia (iron and vitamin B12 deficiency), acute blood loss, liver disease (can be macrocytic), systemic inflammation, zero production (Aplastic anemias [can be macrocytic]), endocrine disorder (hypothyroidism), HEMolytic anemias
Why is it important to order a peripheral smear?
a mixed anemia would usually show up with a normal MCV because you have microcytic cells from an iron deficiency and macrocytic cells from a B12 deficiency the mean corpuscular volume may be normocytic
What does a reticulocyte count tell you?
Reflects the ability of the bone marrow to produce mature red blood cells. an increase in the reticulocyte count provides evidence that the bone marrow is adequately responding to the anemia
When is the reticulocyte count most useful?
in the context of a normocytic anemia: Acute Blood Loss, Hemolytic Anemia, Response to Iron, Folate, or B12 Replacement
What are lab tests indicative of hemolysis?
decreased haptoglobin, elevated indirect bilirubin, elevated lactate dehyrdogenase
What is the purpose of the direct Coombs’ Test?
helps to differentiate between immune and nonimmune hemolytic anemias
What determine’s a positive Coombs’ test?
When the red blood cells of a patient are coated with immunoglobulin or complement, addition of antihuman antibodies will cause agglutination (indicates possibility of immune hemolysis)
What does G6PD do?
helps red blood cells resist oxidant stress
Describe G6PD deficiency?
X-Linked Disorder-Fully expressed in affected males
Women who are heterozygous will contain both normal and G6PD RBCs. Affected patients are usually asymptomatic, but may have episodic anemia while a few have chronic hemolysis
What is microangiopathic hemolytic anemia?
Occurs when capillaries are partially occluded by fibrin, which leads to fragmentation of red cells
Peripheral smear characteristically shows schistocytes and helmet cells
What is warm autoimmune hemolytic anemia?
Most cases involve IgG autoantibodies. Can vary from mild to a particularly severe anemia. Peripheral blood smear shows polychromasia and spherocytes. Often is idiopathic but may be caused by underlying diseases such as RA and SLE
What are spherocytes?
small, dark, dense hyperchromic red cells without central pallor. These findings are compatible with hereditary spherocytosis or autoimmune hemolytic anemia
What is hereditary hemochromatosis?
an increase in intestinal iron absorption results in deposits of excessive amounts of iron in with eventual tissue damage and impaired function of organs (liver, pancreas, heart, joints, and pituitary)
What is the HFE defect?
substitution of tyrosine for cysteine. MHC-I-like protein that interacts with the transferrin receptor. Mutants have altered interaction with the transferrin receptor
What is the liver pathology in HFE defect?
Usually the first organ affected. Hepatomegaly present in 95% of symptomatic pts
What is the cardiac patholgy in HFE defect?
Presenting problem in 15% of pts. Mostly CHF and arrhythmias
What is the pancreatic pathology in HFE defect?
Causes diabetes in 65% of pts. Affected pts tend to have a family history of diabetes
What is the skin pathology in HFE defect?
Excessive skin pigmentation is present in 90% of symptomatic pts. Metallic or slate grey hue is characteristic and due to increased iron and melanin in the dermis.
What is pituitary pathology in HFE defect?
Hypogonadism can develop in men and women.
Decreased libido, impotence, amenorrhea, testicular atrophy, and gynecomastia.
What is the joint pathology in HFE defect?
Arthritic changes in 25-50% of symptomatic pts.
Often starts in the hands (MCP joints of index and middle finger). Pseudogout can occur.
What lab results diagnose HFE?
Transferrin saturation >50%, Ferritin elevated (>1000 usually associated with cirrhosis).
What is treatment of HFE defect?
500 mL of blood lowers the iron content by 200-250mg. May take one to two years of 1/wk to 2/wk blood draws to achieve normal ferritin and transferrin saturation.
