10 - Anemia II (Normocytic, Macrocytic) Flashcards Preview

Hematology > 10 - Anemia II (Normocytic, Macrocytic) > Flashcards

Flashcards in 10 - Anemia II (Normocytic, Macrocytic) Deck (45):

Frequent symptoms for all anemias

- Often asymptomatic
- Fatigue, loss of stamina/exercise intolerance, breathlessness, dizziness, palpitations, headache
- In children: poor feeding and irritability
- ROS should include: bleeding, malaise, fever, weight loss, night sweats, pica


Important components of the history for anemia

- Past Medical History: peptic ulcers, gastric surgery, transfusion, cancer, HIV, rheumatoid arthritis, thyroid disease, renal disease
- Diet
- Drugs--neoplastic drugs or methotrexate
- Alcohol
- Family history--sickle cell, G6PD, thalassemia, bleeding diathesis (hemophilia, von Willebrand)
- Recent travel


Objective Findings of Anemia

Tachycardia, tachypnea, weight loss
Pale skin or mucous membranes, nail changes
Systolic heart murmur
Loss of vibratory sense


The Role of Erythropoietin

- hormone. chemical messenger.
- Produced by renal fibroblasts in response to hypoxia
- Cytokine to marrow erythroid precursors
- Therapeutically available through recombinant production
- Not useful in anemias already Epo-abundant (e.g., iron deficiency)
- Should be co-administered with parenteral (injected) iron


Anemia of Renal Disease

- Usually a normochromic anemia
- Increased RBC destruction—lysis with azotemia (minor contribution)
- Anemia unrecognized by diseased renal fibroblasts
- No erythropoietin surge
- No marrow stimulation: retic count normal or reduced


Sideroblastic Anemias

- Numerous causes; all have the effect of producing ringed sideroblasts in the MARROW
--- need to do a bone marrow biposy to see them (Not PBS)
- Iron stores are sufficient, usually high
- Erythroblasts containing non-heme iron precipitates
- Concentrated in the mitochondria which tend to encircle the nucleus


Types of sideroblastic anemia

- X-linked (XLSA)
- Autosomal recessive (SLC25A38)
- ALA synthase deficiency
- Primary
--- Myelodysplastic Syndrome
- Secondary
--- Ethanol abuse
--- Drug induced (isoniazid, chloramphenicol)
--- Lead poisoning
--- Copper deficiency


Pappenheimer Bodies

Precipitated iron granules
- in finished RBCs
- indicates likely sideroblastic anemia


Sideroblastic Anemia PBS

Poikilocytes (teardrop cells)
- can see pappenheimer bodies


Characteristics of Sideroblastic Anemias

Total body iron overload, insufficient heme iron
May be normocytic
May have dimorphic appearance
May demonstrate hemolytic changes
May show iron deposits (Pappenheimer bodies)
Pyridoxine (coenzyme ALA synthase)
Transfusion to treat anemia; chelation, therapeutic phlebotomy, to treat iron overload
Marrow transplantation
Myelodysplastic Syndrome (covered later)


Types of macrocytic anemia

- megaloblastic (large precursor cells in the bone marrow)

- non-megaloblastic


Causes of megaloblastic anemia

- Vitamin B12 (cobalamin) or folate deficiency
- Drug-related (common drugs: metformin, triamterene, trimethoprim/sulfamethoxazole, valproic acid, zidovudine)


Causes of non-megaloblastic macrocytic anemia

- Hypothyroidism
- Liver disease
- Alcoholism
- Myelodysplasia (abnormal bone marrow) syndromes/preleukemias


problem in Megaloblastic anemia

- Deficiency of B12/folate results in Interruption in DNA synthesis
- Results in failure to proceed beyond G2 growth stage in marrow


characteristics of Megaloblastic anemia

- MCV above 100 fL
- Macroovalocytosis
- Hypersegmented neutrophils on blood smear (>5 % of neutrophils having five lobes or the presence of >1 % of neutrophils with six lobes or more)


B12 (cobalamin) deficiency

- Causes an interference in protein synthesis:
--- Vitamin B12 is a co-factor in the conversion of methylmalonic acid to succinyl CoA and the methylation of homocysteine to methionine
- Incidence: women over 60 y/o
--- true of women and all autoimmune
- Prevalence: highest in African and Asian countries


B12 Deficiency Sx

Paresthesias, sore tongue, change in mental status, ataxia, fatigue, lightheadedness, weakness, anorexia, glossitis, cheilosis


B12 Deficiency PE findings

Decreased position and vibratory sense, disturbances of vision, taste, and smell, Romberg’s sign, Babinski’s sign, neuropathy (vibratory tracts particularly), pallor, edema, jaundice, glossitis, angular cheilosis


B12 Deficiency: Causes

Pernicious Anemia
--- autoantibodies against Intrinsic Factor or atrophy of the cells that produce it


Malabsorption causing B12 deficiency

Partial or total gastrectomy due to lack of acid and pepsin-secreting parietal cells
Zollinger-Ellison syndrome
Ileal disease (Crohn’s)
--- Metformin use-impaired absorption
--- Prolonged use of PPIs for GERD/PUD
Fish tapeworm


B12 Deficiency Implications

- If left untreated, demyelination of the posterior spinal cord can occur, causing spastic ataxia and dementia (?failure of methionine synthase)
- Can lead to infertility in both men and women
- Can cause cervical (Pap) smear abnormalities


Lab results indicating B12 Deficiency

*--- Decreased Hgb & Hct
**--- Increased MCV
Reticulocyte Count decreased
Peripheral Smear
--- Macrocytic RBCs
--- Anisocytosis and poikilocytosis
*--- Hypersegmented neutrophils
Bone Marrow Biopsy—megaloblasts
Serum B12 level low
Serum methylmalonic acid high
Serum homocystine high


Normal B12 Absorption

- Ingested cobalamin freed from bound protein by gastric proteases
- Intrinsic factor produced by parietal cells binds free cobalamin
- Complex is absorbed in terminal ileum


Pernicious Anemia Characteristics

- Hereditary autoimmune disorder-immune-mediated atrophy of the gastric parietal cells
- Results in absent gastric acid and intrinsic factor secretion
- Most common among Northern European and African American populations
- High association with other autoimmune disorders (thyroid, type 1 DM, Addison's disease, autoimmune hemolytic anemia)
- Increased incidence of intestinal type gastric cancer and gastric carcinoid tumors
- Average age of onset is 60 y/o


Pernicious Anemia Diagnosis (labs)

Schilling Test (radiolabeled B12)
--- Obsolete but possibly still on Board exams
Diagnostic labs:
--- Serum B12 level low
--- Parietal cell and intrinsic factor antibody positive (90% and 70%)
--- Serum gastrin level is high; serum pepsinogen 1 level is low (90%)
--- Gastric biopsy shows atrophy of all layers of the body and fundus with absence of parietal and chief cells and replacement by mucous cells


B12 Deficiency Treatment

- B12 1000mcg SC or IM weekly x 1 month, then monthly
- Sublingual or oral B12 1-2 mg po if patient can absorb
- Intranasal gel
--- Absorption inconsistent, expensive, and limited studies regarding efficacy
- K+ levels must be followed closely during treatment
--- Hypokalemia secondary to increased erythropoiesis, cellular uptake of potassium, and increased blood volume
- Response: Bone marrow becomes normoblastic in 12 hours, reticulocytosis in 3-5 days, Hgb normalizes in 2 months or less


Post Gastrectomy Patients

- All total gastrectomy patients need B12 supplementation!
--- b/c taking away intrinsic factor
- 10-15% of partial gastrectomy patients will develop deficiency


Folate (Vitamin B9) Deficiency Anemia

- Inadequate dietary intake: alcoholism, elderly, poor choices
- Increased needs: pregnancy, lactation, prematurity, hemolytic anemia, exfoliative dermatitis, RA, Crohn’s, and dialysis patients
- Malabsorption: celiac disease, IBS, Roux-en-Y gastric bypass
- Drugs such as methotrexate, trimethoprim, Dilantin, OCPs
- Liver disease


Folate Deficiency Anemia sx/signs

similar to B12 deficiency, but no neurologic abnormalities
--- Fatigue, weight loss, lightheadedness, abdominal pain


Folate Deficiency in pregnant women

causes neural tube defects
--- Enriched flour and grains in U.S.


Folate Deficiency Anemia objective findings

Pallor, glossitis, jaundice


Folate Deficiency Diagnostic labs

Low Hgb with macrocytosis
Low serum (2-15mcg/L) and RBC folate
Peripheral smear: Hypersegmented neutrophils
High homocysteine levels
Normal or low B12 level
Normal methylmalonic acid


Folate Deficiency Tx

Consume foods rich in folic acid
Supplement folic acid- 1-5mg/day orally
Correction may take up to 8 wks, common to continue longer


Aplastic Anemia

Bone marrow failure
Many potential causes
May be acute or smoldering
Often normocytic, may be macrocytic


Aplastic Anemia Sx

- Weakness and fatigue (anemia)
- Bacterial or fungal infections (neutropenia)
- Mucosal or skin bleeding or petechiae (thrombocytopenia)


Aplastic Anemia PE Findings

Pallor, petechiae, purpura


Causes of Aplastic Anemia

- Idiopathic
- Autoimmune: Rheumatoid Arthritis, Systemic Lupus Erythematous
- Congenital: defects in the telomere length maintenance or DNA repair (rare)
- Chemotherapy, radiotherapy
- Toxins: benzene, toluene, insecticides
- Drugs: chloramphenicol, phenytoin, carbamazepine, tolbutamide
- Paroxysmal nocturnal hemoglobinuria


Aplastic Anemia Labs

- Pancytopenia
- Early in diagnosis, only two cell lines may be decreased
- Reticulocytopenia always present
- RBC morphology will be normal on peripheral smear (normocytic anemia), but mild macrocytosis may be present
- Bone marrow biopsy
--- Will appear hypocellular
- The more severe the pancytopenia, the worse the prognosis


Aplastic Anemia Treatment

Mild cases—supportive care:
Stop offending agent
Avoid sick individuals
Use stool softeners to prevent risk of rectal bleeding
Aggressively treat fever or infections
Reduce menstrual blood loss through use of OCPs
Erythropoietic or myeloid growth factors
RBC/platelet transfusion-transfuse as little as possible to avoid sensitizing potential transplant candidates

Severe cases—bone marrow transplant


Patients with aplastic anemia will present with ...

symptoms c/w decrease in all blood cell lines (bone marrow is in failure)


CBC of patients with aplastic anemia will reveal ...

anemia, neutropenia, and thrombocytopenia; bone marrow will be hypocellular


*most common causes of macrocytic anemia

folate and Vit B12


*most common cause of vit b12 anemia

pernicious anemia


*most common cause of folic acid deficiency

poor dietary intake (alcoholics, persons with anorexia,those with diet low in fruits/vegetables)


*how to tell folic acid deficiency vs B12 deficiency

- folic acid deficiency presents with no neurologic sx
- B12 deficiency can lead to irreversible neurologic damage