EVALUATION OF ANEMIA ANEMIA IS A SIGN OF DISEASE, IT IS NOT A FINAL DIAGNOSIS.
It is defined as "Reduction in either the red blood cell volume (HCT), or the concentration of hemoglobin in the blood." WHEN TO START INVESTIGATION? In general values more than 2SD below the mean warrant investigation. HCT (2sd)
12 - 18 yrs M
However, relying strictly on a numerical definition of anemia may obscure significant pathologic features, examples; 1. Female with C.O.P.D. Hb 13.5 may need detailed W/U if her baseline Hb has been 17.5
2. Patient with dehydration and normal Hct & Hb, may need further examination and his blood
values should be measured after hydration.
3. Patient with a significant CHF might appear Anemic from findings on his initial hemogram, but values may return to normal after diuresis. Anemia may be due to either to increase loss of red cells (hemorrhage or hemolytic) or decrease production of red cells. Increase loss of red cells or destruction is associated (at least in early stage) with effective erythropoiesis and marrow hyperproliferation manifested by elevation of the reticulocyte count. Corrected Reticulocytes % = Raw reticulocytes % X Pt's Hct/45 Reticulocyte Production Index (RPI) = corrected reticulocytes/maturation factor Shift
Each differential diagnosis is guided by: 1. History and physical examination: * Family history; usually suggests an inherited Red cell disorder. * Chronic blood loss; ex. Women of reproductive age should be asked of menstrual flow. Occult bleeding is almost from G.I. tract, since patient will report pulmonary or urinary bleeding. *Drugs/toxin: A. Drugs causing marrow hypoplasia or aplasia; 1.
Antimicrobial drugs; chloramphenicol, sulfas, streptomycin
Anticonvulsant drugs: Dilantin, primidone, carbamazepine
Anti-inflammatory drugs; phenylbutazone, tolbutamide
Oral hypoglycemics; chlorpropamide, tolbutamide
Tranquilizers; chlordiazepoxide, (Librium), meprobamate
Major tranquilizers/ Antiemetics; Thorazine, /Compazine
Miscellaneous; acetazolamide, potassium perchlorate
B. Drugs causing hemolytic anemia: In G6PD; antimicrobial; sulfa, Nalidixic acid & others In immune hemolytic anemia; PCN, sulfa, quinine, methyldopa, levodopa C. Folate antagonists:
D. Porphyrin/heme synthesis antagonists:
E. Drugs causing G.I. loss: Aspirin Nonsteroidal anti-inflammatory agents Alcohol F. Occupation & house hold customs and habits Insecticide, cleansing fluids * Chronic disease/Malignant disease; hepatic, thyroid dysfunction, collagen disease, R.A., etc . Physical Exam: signs of chronic disease; joints disease, liver disease. Lymphadenopathy Pelvic/rectal exams are essential Breast & Abdomen Exam Signs of hemolytic anemia; Jaundice, splenomegaly Neuro exam: vitamin B12 deficiency Blood film: As in the table; (Next page)
1. Since the MCV represents an automated averaging of the size of all red cells in a blood sample,
it is a reliable means of classifying anemias only when red cell population is fairly homogenous. The red cell distribution width; RDW is a calculated index, volumes above normal range (11.5% - 14.5%) correlate with anisocytosis. Thus when the RDW is significantly elevated the MCV is less reliable.
2. Mean Corpuscular Hemoglobin Concentration: MCHC: It's a red cell index values 32 - 36 gm/dl
indicates normochromic and values below this range; hypochromia only is spherocytic disorders is the MCHC increased.
Table 23 -3. Description and Significance of Various Forms of Red Corpuscles Type of Cell Description Physiologic Significance* Clinical Disorders
Larger than normal (>8.5 µm diameter). Well
early loss of nucleus) DNA synthesis-impaired megaloblastic maturation
Diameter increased but MCV normal: often
not it is: (a) well filled with hemoglobin (b) normal shape
Exaggeration of normal central pallor; usually
Hypochromic with central pigment; thin cell
microcytic; surface to volume ratio decreased: no
diseased vessels, and artificial surfaces in the circulation
In various anemia especially megaloblast
In shape of sickle; form assumed especially of
Triangular or helmet-shaped, fragmented or
greatly distorted RBC; smaller than normal
physical agents Also in uremia malignant hypertension
Shape of drop: usually microcytic, often also
Less frequently in other forms of anemia; e.g., thalassemia
RBC with spiny projections on surface Has 5 to
10 spicules of various lengths irregular in
Has 20 to 30 spicules, evenly distributed over
both , as result of changes in plasma or in RBC metabolism
Uniconcave, as contrasted with normal biconcave
RBC, slitlike instead of circular area of central
Dense dehydrated, irregularly contracted may
*RBC, red blood cell: MCV, mean cell volume, LCAT, lecithin cholesterol acytranslerase
Table 24 - 10. Problems in Interpreting Serum Vitamin B12 Levels Falsely high values (concealing deficiency)
Radioassay artifact Abnormal serum binding proteins (liver disease chronic myelocytic leukemia) Vitamin B12 injection preceding specimen collection
Artifact due to radioactivity in serum (e.g., after gallium or technetium scans)
In myeloma or aplastic anemia Normal pregnancy; oral contraceptives Transcobalamin I deficiency ? Severe iron deficiency Drugs interfering with microbiologic assays: antibiotics, chlorpromazine, antifolate drugs High -dose vitamin C
TABLE 2: Ideal Diagnostic Approach to the Patient with a Low Serum Cobalamin Level of Uncertain Etiology 1. Recheck the serum cobalamin level
2. Careful review of the blood smear and, if possible, bone marrow aspirate smear.
3. Careful review of neurologic status.
Include testing for mild neuropathy, memory impairment EEG and evoked potentials are often abnormal even in asymptomatic patients.
Serum or urine methylmalonic acid Serum or urine homocysteine (also abnormal in folate deficiency) (Deoxyuridine suppression test of marrow, if available) (Holotranscobalmin II may be tested, if available; however, interpretation must be very cautious)
5. Schilling test or other test of free-cobalamin absorption.
Avoid dual-isotope test, which sometimes gives falsely normal results. Note whether patient took antibiotics recently, which may inadvertently correct bacterial overgrowth in the gut.
6. If Schilling test result is normal, test food-cobalamin absorption if the test is available. If the latter
is unavailable, gastric analysis for achlorhydria may be helpful sometimes.
Is there folate deficiency? Is the patient positive for HIV? Is the patient taking drugs which intermittently affect cobalamin absorption? Does the patient have R binder deficiency?
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