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Module 6 ICS 2


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Define anemia.
A reduction in the total number of RBCs, amount of Hb in the circulation, or circulating RBC mass
General causes of anemia?
1. decreased RBC production

2. increased RBC destruction or loss
What is the physiologic result of anemia?
Impaired oxygen delivery gives rise to physiologic consequences secondary to tissue hypoxia as well as compensatory mechs to correct anoxia
Criteria for anemia in adults?
RBC x 10(12)/L <4.0 <4.5

Hb (g/dl) <12 <14

Hct (%) <37 <40
Compare and contrast normocytic, microcytic, and macrocytic RBCs.
Based on Mean Corpuscular Volume (MCV) --

normocytic: 80-100fl

microcytic: <80fl

macrocytic: >100fl
What is RDW?
Red cell distribution width.

-- a measure of RBC size variability, or ANISOCYTOSIS
-- anemic d/o's can be classified on the basis of RDW
When is RDW more often elevated?
Iron deficiency anemia

(less likely in thalassemia or anemia of chronic disease)
What is RPI? What does it measure?
Reticulocyte count/Retic productions index
-- percentage of total RBCs that are reticulocytes

Measures: bone marrow productivity
What are reticulocytes?
young RBCs, newly produces
-- distinguishable by their gray-pink color on smears
-- show a network (reticulum) of blue granules when stained w/ special stains like Methylene Blue
Symptoms of slow anemia vs. acute anemia?
SLOWLY -- few symptoms since the homeostatic mechs provide remarkable adaptation

ACUTE -- weakness, fatigue, palpitations, lightheadedness
Blood loss in a "typical" menstrual cycle?
What drugs may induce BM suppression? Hemolytic anemia? GI bleeding?



GI BLEEDING: ASA, NSAIDs, recreational drugs
Name some concurrent illnesses in which pts may experience anemia
chronic infections
inflamm disease
renal or hepatic failure
endocrine d/o's
How can eating habits cause anemia?
1. Folic acid deficiency due to poor dietary intake
-- anorexia assoc w/ cancer
-- elderly w/ severe depression
-- alcoholics w/ hx of binge drinking

2. post gastrectomy pts w/ achlorhydria
-- develop vitamin B12 malabsorption although anemia may take years to develop

3. food picas
What are the classic symptoms of anemia? Other indicators?

-- jaundice and dark urine are indicators of hemolysis

-- dysphagia may be sign (esophageal webs)

-- gait or balance difficulties may signify the neuro disorder assoc w/ pernicious anemia
What are the classic physical finding with anemia?
pallor (skin, mucous mbrns)
postural hypotension

palmar creases appear pink in fully opened hand unless Hb is <7gm/dl -- useful guide to presence of severe anemia
What skin and mucous mbrn findings w/ anemia?
-- tongue can be devoid of papillae and sore
-- koilonychia (spoon shaped fingernails)

-- jaundice - "lemon yellow" tint due to simultaneous pallor and jaundice
-- can also have tongue completely devoid of papillae that is often also sore

-- gingival hypertrophy

-- dark line of lead sulfide deposited in gums and at base of teeth
CV findings w/ anemia?
postural hypotension
flow murmurs
Spleen findings w/ anemia?
may be enlarged concomitantly w/ anemia due to:

-- primary hematologic disease - lymphoma, leukemia, autoimmune hemolytic anemia

-- secondary to infection, inflammation
Liver findings w/ anemia?
Exam liver size and for stigmata of chronic liver disease:
spider angiomata, gynecomastia, palmar erythema, testicular atrophy, caput medusae
Neurologic findings w/ anemia?
Vitamin B12 deficiency impairs:
spinal cord
peripheral n fxn (especially vibratory and proprioception)

Severe chronic deficiency may lead to irreversible neuro dysfxn
List causes of hypochromic microcytic anemia.
MCV < 80fl

iron deficiency
lead poisoning
chronic disease
sideroblastic anemia
Blood smear cells seen in iron deficiency?
pencil (cigar) cells

high RDW

sometimes thrombocytosis
Typical labs of iron deficiency anemia?
↓ iron


Fe/TIBC < 10%

↓ ferritin

Confirm if necessary w/ BM stores (absent in iron deficiency)
Blood smear cells seen with thalassemias?
target cells
Typical labs of thalassemias?
confirm presence of target cells w/ Hb electrophoresis

high A2 ± F hemoglobins for B thalassemias
Blood smear cells seen w/ lead poisoning?
course basophilic stippling
Typical labs of lead poisoning
Confirm w/ lead level, free erythrocyte protoporphyrin
Blood smear cells seen w/ anemia of chronic disease.
More are normochromic
Typical labs of anemia from chronic disease?
↓ Fe


Fe/TIBC > 15%

↑ ferritin

BM iron stores increased and present in RE cells
Blood smear cells seen w/ sideroblastic anemia?
ringed sideroblasts demonstrated by Prussian Blue staining of BM RBC precursors
Typical labs seen w/ sideroblastic anemia?
↑ Fe



↑ ferritin
List list causes of macrocytic anemia.
MCV > 100fl

B2/folic acid deficencies
Liver disease
Cancer chemotherapy
Blood smear of B12/folic acid deficiency would show?


hypersegmented PMNs
Typical labs of B12/folic acid deficiency?
↓ serum B12, RBC folate

↑ indirect bilirubin


↑ uric acid

↑ serum iron


Helpful test to confirm PERNICIOUS anemia is anti-IF antibody -- highly specific but only positive in 75%
Treatment of B12/folate deficiency anemia?
usually responds rapidly and dramatically to B12 or folate

Schilling test best done 6-8 wks after B12 replacement to correct malabsorption due to megaloblastic GI epithelium
Blood smear of liver disease would show?
macrocytosis secondary to abnormal lipid composition in the RBC membrane

round macrocytes (as opposed to oval in B12/folate)

may also see target and/or spur cells (acanthocytes)
Blood smear of cancer chemo would show?
many cytotoxic drugs or antimetabolites used in chemo drugs impair DNA synth and produce a defect in hematopoiesis that resembles B12 or folate deficiency
Target cells?
liver disease


autoimmune hemolytic anemia

hereditary spherocytosis
fragmented RBCs seen in fragmentation hemolysis:



cardiac valve hemolytic anemia

malignant HTN

massive venous thromboembolism
bone marrow infiltration:
- tumor
- infection (granulomas)
- fibrosis
Leukoerythroblastic blood smear?
refers to presence of both immature WBC and nucleated RBCs, often accomp by teardrop-shaped RBCs
-- correlates w/ highly infiltrative process of the bone marrow
Howell-Jolly bodies?
nuclear remnants seen in post-splenectomy patients
Sickle cells?
sickle cell anemia
Rouleaux formation?
"Rouleaux" are stacked RBCs caused by coating individ cells by charged proteins that neutralize the normally negative charge that by repulsion keeps RBCs from agglutinating

-- multiple myeloma when RBCs become coated by the + charged paraproteins
Describe how RPI classifies anemias.
RPI ≥ 2 favors destruction problem

RPI ≤ 2 favors production problem
Laboratory parameters of hemolysis include?
↑ indirect bilirubin
↓ haptoglobin

**haptoglobin can be low in liver disease where the problem is decreased synth, NOT hemolysis

** ineffective erythropoiesis seen in megaloblastic anemias can produce same chemical abnormalities so one must always have in mind clinical context
What does the Coombs test measure?
Antibodies bound to the RBC surface

-- direct Coombs test is (+) in autoimmune hemolytic anemia and hemolytic transfusion rxns
Disorders assoc w/ decreased production of RBCs?
renal failure
chronic diseases (infection, inflamm, malignant)
nutritional deficiencies
myelodysplasia ("pre-leukemia")
aplastic anemia/pure red cell aplasia
endocrine d/o's (thyroid, pituitary)
Disorders assoc w/ increased destruction of RBCs?
hemolytic transfusion rxn
immune hemolysis
RBC fragmentation
Hereditary spherocytosis
RBC enzyme defects
Miscellaneous (burns, drowning)
Clinical use of blood transfusions?
RBC transfusion is always symptomatic and supportive rather than definitive therapy for anemias
-- only use when no definitive trtmt for the underlying cause OR when severity and clinical manifestations deem necessary

**signif risks incl allosensitization, transfusion rxns, infection transmission, iron overload
Iron deficiency may occur as a result of...?
inadequate dietary intake
-- almost exclusively problem of infants and children and of pregnancy and lactation
malabsorption (duodenal)

chronic blood loss

OR combination of above
In an adult, Fe deficiency is almost always assoc w/...?
blood loss
In pregnancy, the avg iron loss totals about...?

diversion of Fe to fetus, blood lost at delivery and lactation
Preferred mode of iron therapy?
oral route -- most economical, highest dosage, most safely, in readily assimilated form (ferrous sulfate FeSO4)
Approp dose of oral iron prep?
should provide 150-200mg of elemental iron/day

Usually 3-4 tablets per day

Ex: one 320mg FeSO4 tablet contains 66mg elemental Fe
How soon can we achieve normal RBC parameters after beginning treatment?
usually after 6 wks (if no concurrent blood loss)

continue therapy for 4-6mos to ensure full replacement of total body iron stores
When is parenteral iron indicated?
rarely indicated

- patients whoh cannot absorb oral iron
- patients unable to follow instructions or comply w/ oral therapy

**frequency of systemic rxns high
Approach to megaloblastic anemia?
pending definitive dx, empiric B12 and folate therapy can be initiated w/o harm

Once dx established, consider possible etiologies.
Etiologies of B12 deficiency?
Nutritional - vegans
Pernicious anemia
-- bacterial overgrowth
-- D.latum fish tapeworm
-- pancreatic insuff
-- tropical/nontropical sprue
-- Crohn's, intestinal lymphoma
-- transport d/o's
-- metabolic d/o's (rare)
Etiologies of folate deficiency?
nutritional causes
-- decreased intake
-- increased requirement: pregnancy, lactation, hemolysis

Describe the B12 treatment.
1. daily injections of 100μg for 5-7 days THEN
2. weekly injections for 3-4 weeks THEN
3. 1000μg monthly for life

Correction is rapid: BM abnormalities corrected w/in 24-72h and reticulocytosis occurs by 4-6d

Rapid reversal of ineffective erythropoiesis by B12 causes rapid cellular uptake of K and may result in severe hypokalemia -- monitor levels

Reversal of neuro manif is unpredictable and variable; persisting >6mos likely permanent
Describe the folate treatment.
oral folic acid 1mg daily

course of response similar to B12 deficiency

duration depends on clinical situation
What if pt does not respond to B12 or folate?
evaluate for concurrent iron deficiency
What is DIC?
Disseminated Intravascular Coagulation
-- occurs when coag system is activated by generation of excessive thrombin in the circulation

Catastrophic bleeding d/o characterized by:
-- depletion of procoag factors
-- thrombocytopenia
-- activation of fibrinolytic system
Causes of DIC?
obstetrical complications
- retained dead fetus
- absorption placentae
- amniotic fluid embolism

septic shock
How is DIC anemia characterized?
fragmentation hemolysis
-- schistocytes present in circulation
Prolonged PT, PTT, and TT

Presence of fragments of cross-linked fibrinogen (d-dimer) in circulation

Presence of fibrin/fibrinogen fragments (fibrin degradation products, FDP) in circulation
address underlying cause

supportive care of blood, platelets, plasma transfusion
What is TTP?
Thrombotic thrombocytopenic purpura

Characterized by:
-- microantiopathic hemolytic anemia (fragmentation hemolysis)
-- thrombocytopenia
-- fever
-- renal manifest
-- neuro manifest

May present as isolated syndrome or can be assoc w/ infection, malig, meds, vasculitis, preggers, etc.
Pathogenesis of TTP?
related to absence of vWF cleaving protease activity
-- abnormally large vWF multimers in circulation
-- platelet hyperaggregability
clinical picture

hemolysis w/ plentiful schistocytes

coag studies are NORMAL
plasma exchange -- removes unusually large vWF multimers and provides missing protease activity


**platelet transfusions CONTRAINDICATED b/c can contribute to disease progression
What is AIHA?
Autoimmune hemolytic anemia

-- may be primary (25%), secondary (60%) or drug induced
-- secondary assoc w/ systemic immunologic d/o's like SLE, cancer, or infection
Pathogenesis of AIHA?
binding of autoantibodies ± complement to the RBC surface and destruction of coated RBCs in the spleen

-- 75% of RBC autoantibodies are IgG and react w/ RBC at 37C (warm autoantibodies)
-- 25% are IgM and react at temps <37C (cold agglutinins)
Characteristic cell of AIHA?
Warm agglutinin AHIA Tx?
directed toward eradication of autoantibody and/or reduction of RBC rate of destruction

1. corticosteroids (DOC)
-- 75% respond, but half relapse when tapered off

2. splenectomy (TOC) for pts who fail (1)
-- removes major site RBC destruction and source of autoAb production
-- 2/3 have beneficial response to splenectomy

3. Fail to respond to (1) and (2) -- try other immunosuppressive agents, macrophage poisons, RE blockade w/ IV Ig
-- use of synth androgen, danazol, may prove useful
Cold agglutinin AHIA Tx
frequently have assoc malignancies or infect diseases
-- direct Tx toward underlying dz

**corticosteroids and splenectomy are relatively ineffective
**cold avoidance may be addtnl impt aspect of dz management

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