Macrocytic Anemias
What are some of the causes of macrocytic anemia - Normoblastic Maturation?
Alcoholism, liver disease, hematologic disease and malignancies, hemolysis ("shift" macrocytosis), acute blood loss ("shift" macrocytosis) and hypothyroidism
What is found in leafy green vegetables, liver, meats and certain fruits, stored in the liver at minimal amounts for a few months?
Folate or pteroylglutamic acid.
Which lab test uses HPLC, GC-MS or fluorescence polarization immunoassay to measure the substance in patient's plasma or serum, it is an early detector of B12 deficiency and has predictive value for increased risk of MI and venous thrombosis?
Homocysteine.
Which cause of folic acid deficiency is due to tropical and no-tropical sprue?
Impaired absorption.
What are the types of macrocytic anemias?
Macrocytic anemia with normoblastic maturation Macrocytic anemia with megaloblastic maturation
What can occur in absence of magaloblastic anemia and is irreversible if allowed to advance?
Neurologic abnormalities.
What is seen in the bone marrow of megaloblastic anemia?
Often hypercellular, M:E ratio 1:1 or lower due to increased but ineffective erythropoiesis, defective RBC's are destroyed in marrow, and megaloblastic changes seen in other cells lines (giant bands, metamyelocytes, and hyperlobulated megakaryocytes.
When differentiating between macrocytic anemias, what do you look for in the peripheral blood smears?
Oval macrocytes and hypersegmented PMNs, polychromasia,and a high enough retic count to explain increased MCV.
What is found in the peripheral blood of macrocytic anemia?
Pancytopenia, extreme aniso/poik (teardrops, schistocytes, spherocytes and targets) macroovalocytes, inclusions such as basophilic stippling, howell jolly bodies and cabot rings, nRBC's - appear megaloblastic, and hypersegmented neutrophils - pathognomonic for megaloblastic dyspoiesis
What causes a B12 deficiency when gastirc mucosa fail to secrete IF due to auto-antibodies against If, parietal cells, IF/B12 complex and binding sites?
Pernicious anemia.
When differentiating between macrocytic anemias using immunoassays for serum B12, folate and red cell folate levels, why is red cell folate levels are more reliable than serum folate levels?
Red cell folate levels are not affected by recent intake of folate rich foods but sensitivity and specificity of current methods are less than optimal.
What are the serum B12, serum folate, and red cell folate results of someone with a B12 and folate deficiency?
Serum B12 - L Serum folate - L Red cell folate - L
What are the symptoms of neurologic abnormalities resulting from B12 deficiency?
Starts with numbness of feet and fingers, gait disturbances, perversion of taste, smell and vision, dementia mimicking alzheimer disease and psychotic depression and mental illness resembling paranoid schizophrenia.
What can cause a B12 deficiency by hereditary lack or abnormal transcobalamin II?
Transport protein defects.
What are some causes of B12 deficiency?
inadequate intake and/or impaired absorption
Which anemia involves macroovalocytes in PB, nuclear cytoplasm asynchrony, cytoplasm maturing faster than nucleus due to impaired DNA synthesis, and fewer cell divisions?
Macrocytic Anemia - Megaloblastic Maturation
What type of macrocytic anemia has large round cells in PB with a possibility of polychromasia and red cell precursors showing normoblastic maturation in bone marrow?
Macrocytic Anemia - Normoblastic Maturation
What are the serum B12, serum folate, and red cell folate results of someone with a B12 deficiency?
Serum B12 - L Serum folate - N or I Red cell folate - L
What are the serum B12, serum folate, and red cell folate results of someone with a folate deficiency?
Serum B12 - N* (possible false decrease in B12 deficiency) Serum folate - L** (possible false increase with hemolysis or coexisting B12 deficiency) Red cell folate - L
What does it mean if 40% of patients have increased urine MMA levels?
Serum B12 levels are normal but show lab and clinical evidence of B12 deficiency.
What is the absorption, transport and storage mechanism of folate?
The mucosal cells of the duodenum and jejunum absorb and convert the polyglutamic form to monoglutamic form which is then absorbed into the portal cierculation and transported to tissues and the liver by alpha 2 macro globulin, albumin and transferrin.
What are the results of someone whose parietal cells have atrophied due to pernicious anemia in a gastric analysis?
There is an absence of free HCl in gastric juices after histamine stimulation which is indirect evidence for lack of IF.
What does decreased rate of appearance of iron in the Hgb of circulating erythrocytes in the blood chemistry analysis indicate?
There is evidence of ineffective erythropoiesis.
What is the blood chemistry of one with megaloblastic anemia?
slight to moderate increase in bilirubin, marked increased in LD-1 & 2 with a plasma increased plasma iron turnover with a decreased rate of a appearance of iron in the Hgb of circulating erythrocytes.
What is macrocytic anemia?
Any anemia with an elevated MCV.
What are some causes of macrocytic anemia - megaloblastic maturation?
B12 or folate deficiency and hematologic malignancies such as MD's and MDS's (rare).
What can cause B12 deficiency due to bacteria colonizing in intestine and taking then B12 before it is absorbed?
Blind loop syndrome (competing intestinal flora and fauna).
What is the significance of B12 and folate?
Both are cofactors in several key reactions leading to synthesis of thymidine triphosphate and susequently to DNA
What can cause B12 deficiency by competing with its host for ingested B12?
Diphyllobothrium latum.
Which cause of folate deficiency is due to the use of folate antagonist used in cancer therapy (methotrexate), anticonvulsants (dilantin) and antituberculosis (INH) depressing serum folate levels?
Drugs.
What are some examples of intestinal disorders that may cause B12 deficiency?
Gastrectomy, chronic gastritis, sprue, inflammatory bowel disease and ileal resection.
Which laboratory test evaluates the secretion of IF and HCl from parietal cells, testing for the presence or absence of free HCl in gastric juices after histamine stimulation?
Gastric analysis.
What substance is increased in patients with B12 or folate deficiency?
Homocysteine.
Which cause of B12 deficiency is common due to intestinal disorders, competing intestinal flora and fauna, transport protein defects, and Pernicious anemia?
Impaired absorption.
What is found in nature, in most animal tissues, is present in meat, liver, seafood, eggs and milk and has a 3-6yr store primarily in the liver?
B12 (Cyanocobalamin)
What are the causes of folic acid deficiency?
Inadequate intake, increased utilization, impaired absorption, and drugs.
Which cause of B12 deficiency is extremely rare unless patient is a strict vegetarian?
Inadequate intake.
Which cause of folic acid deficiency is a leading cause due to poor diet, overcooked vegetables, poverty, alcoholism and old age?
Inadequate intake.
Which cause of folic acid deficiency is due to chronic proliferation of cells as in hemolytic anemia, leukemia, metastatic cancer, pregnancy, infancy and young children resulting in depleted folate stores?
Increased utilization.
Which laboratory test was historically used to evaluate ability of patient's intestinal tract to absorb once a B12 deficiency was established?
Schilling test.
Which laboratory test is a specific test for measuring increase excretion of MMA in urine or serum using GC-MS and is an indirect indication of decreased B12?
Methylmalonic Acid.
What are some clinical manifestations of macrocytic anemia-megaloblastic maturation?
Mild to severe anemia. Few symptoms until hct is severely depressed such as weakness, fatigue, pallor, epithelial abnormalities (sore tongue), etc. and neurological abnormalities such as numbness, tingling of extremities, gait abnormality which can become permanent and may be present prior to macrocytosis and anemia.
What does it mean when LD-1 and 2 are markedly elevated (1>2) in blood chemistry analysis?
medullary destruction of megaloblasts and extramedullary destruction of red cells are both increased.
