Anemia Flashcards
Oxygen carrying unit
Heme
Contains iron
Also assists in CO2 transport (can pick up CO, NO)
Laboratory definition of anemia
Hg < 12 g/dL (women), <13 (men)
Hct < 36%, <40%
Can be asymptomatic or symptomatic
General s/s of anemia
Pallor (conjunctiva, skin, membranes)
Tachycardia
Orthrostasis
Weakness, fatigue
How is anemia diagnosed? (Test and associated)
CBC
Using parameters
RBC, MCV, RDW, MCHC
MCV
Tells us the AVERAGE size of the cells
Microcytic (<85)
Normocytic (85-100)
Macrocytic (100+)
What indicies must we use in addition to the MCV to diagnose anima ?
RDW
Tells us the distribution of the cells (11-16% is good)
Narrow RDW = less size difference between the cells
Retic count
Dependent upon degree of anemia
Used in anemia to see if the bone marrow is working
Would expect low if bone marrow not working effectively
Corrected retic count
Bc anemia will give us a typically higher retic count than average we must correct it
Corrected retic > 2%
Normal proliferation
Could be hemolytic or due to acute blood loss
Corrected retic < 2%
Hypoproliferation in bone marrow
Tests comprising iron studies (5)
- Iron (iron levels in serum)
- Transferrin (amount of transferrin in blood)
- TIBC (available transferrin in blood)
- % sat (amount of transferrin with iron)
- Ferritin – impacted by inflammation or infection
Additional tests to evaluate anemia (after iron studies)
B -12 and folate levels
LFTs (specifically LDH)
Haptaglobin
TSH
SPEP/UPEP
DAT
BM bx
Hg.Genetic testing
Mild anemia workup
- Evaluate for heavy blood loss
- Order initial work up (iron studies, b-12 and folate)
- Treat or move towards urgent eval
Severe anemia evaluation
- Evaluate for blood loss (GI bleed – not menstrual at this point)
- Order initial work up + LDH, haptaglobin, retic, DAT
Target cells
Peripheral blood smear
Caused by membrane defect
Thalassemia or liver dz
Peripheral blood smear
Schistocytes
Helmet fragments
Seen in INTRAVASCULAR hemolytic processes (DIC)
Peripheral blood smear
Basophilic stippling
Blue stipples appearance
Seen in lead toxicity (microcytic anemia)
Peripheral blood smear
Rouleaux formation
RBC staked like coins
Due to high paraprotein in blood
Indicates multiple myeloma
Types of microcytic anemias (5)
- Iron deficiency anemia
- Lead poisoning
- Anemia of chronic disease
- Sideroblastic anemia
- Thalassemia
Where is iron absorbed from
Proximal duodenum and moved thru blood by transferrin to marrow
When RBCs are broken down in liver, iron is recycled and carried to marrow
Small amount of iron is lost daily but most of it is retained
MC cause of microcytic anemia
Iron deficiency
Typically hypochromia and can cause thrombocytosis
Epidemiology of IDA
Women of childbearing age (heavy menses)
Vegetarians, infants, pregnancy women, celiac or IBDs
Conditions/symptoms associated with IDA
PICA
RLS/leg cramps
Cold intolerance
Esophageal webs
Chelitits
Koilonychia
Etiology of IDA
Iron loss (menstruation, GI bleed, chronic low grade hemolysis)
Insufficient absorption (poor intake, malabsorption by gut)
IDA
CBC results
Hypochromia
microcytic anemia
+/- thrombocytosis
Peripheral smear
IDA
No structural abnormalities
Uniform size – just small
Iron studies
IDA
Iron: LOW
** Transferrin: HIGH
TIBC: high
% saturation: LOW
Ferritin: LOW
IDA workup (4 steps)
- Women with heavy periods – begin Fe replacement, check
- M/f w/o menses - suspect GI bleed so endoscopy, colonoscopy
- No finding of blood loss yet, will do capsule scope to look at SI
- Nothing yet, workup for malabsorption (celiac)
IDA treatment
Oral Ferrous sulfate (325 mg) given up to 3x/day
Should be taken with vitamin C on empty stomach (to maximize absorption)
Other formulations are available but not great (parentarel venofer if nec. - low anaphylaxis)
How long on IDA treatment before results are seen?
Retic count should increase in 5-10 days, HgB should increase 1-2 gm/2 weeks
Typ. Takes 3-4 months to get to normal
Prevention is done by taking supplemental iron (infants, vegetarians, pregnant)
Caution in treating IDA + remedy
Iron overload
Can happen in transfusion (200mg/unit PRBC)
Can’t get rid of excess iron so will store in improper organs
TReAMENT: chelation or phlebotomy
Disorder caused by genetic defect causing decrease in alpha or beta chain production
Thalassemia
African, Asian, Mediterranean
Alpha thalassemia
Impaired alpha chain production – too many beta chains
May allow malaria prevention
Four subtypes
What does the HgB look like in alpha thalassemia
The Beta chains can form stable tetramers so they will get out into the serum (little effect on erythropoiesis)
BUT beta chains have a high O2 affinity so it can hold, but not release oxygen
Types of alpha thalassemia
- Alpha thalassemia minima
- Alpha thalassemia minor/trait
- Alpha thalassemia/HgH
- Fetal Hydrops
Alpha thalassemia minima
Deletion of 1 alpha gene
Silent carrier
No abnormalities in smear or CBC
Alpha thalassemia Minor
2 genes deleted
Minimal anemia with reduced MCV (minor microcytic anemia)
Alpha thalassemia/ HgH
Significant production of beta tetramers
Microcytic anemia and intravascular hemolysis
Target cells and Heinz bodies on smear
Fetal Hydrops
4 alpha genes are missing
Incompatible with life
HgH disease tetramers (+ symptoms)
B chain tetramers
Soluble but not stable when under stress
They precipitate out but are hemolyized in the vessels
Significant anemia, jaundice with papal leaders splenomegdaly
Significant reticulocytosis
Beta thalassemia
Suppression of beta chain production resulting in over production of alpha chains
Alpha chains are not able to form tetramers so they are destroyed in the marrow
Types of beta thalassemia
- Beta thalassemia minor
2. Beta thalassemia major
Beta thalassemia minor
CBC
Asymptomatic but significant microcytosis
Normalish Hct, Narrow RDW
High RBC counts
Beta thalassemia
Minor
Peripheral smear
Hypochromia
Microcytosis
Target cells and dacrocytes
Beta thalassemia major
Infants fall ill after 6 months of life (due to production of gamma globulin)
Chronic anemia and hemolysis (moderate to severe)
Pts develop failure to thrive, abdominal swelling and jaundice
Extramedullary RBC production –> craniofacial probelms and hepatosplenomegaly
Iron overload, high output heart failure
Thalassemia workup
Genetic testing to determine the gene profile and specific mutation
Treament of Beta thalassemia major
Hypertransfuison therapy (2-4 weeks to suppress extramedullary hematopoiesis)
Iron chelation
Maybe a hematopoietic stem cell transplant
Alphas are monitored and supported
Lead poisoning
Becoming more rare
Can be found in lead paint (old homes), moonshine consumption, lead fume, contamination
Lead poisoning anemia
Interference with HgB synthesis and other effects
Cognitive damage, decreased growth, deposition of lead in other dry symptoms
Lead poisoning anemia results
Microcytic or normocytic anemia with basophilic stippling on smear
Diagnosed by getting lead levels
EDTA chelation treament
What must we rule out with lead poisoning
Iron deficiency anemia as well bc lead will interfere with iron absorption in the gut
Sideroblastic anemia
Nucleated red blood cell precursors with iron rods are released into the blood
Diagnosed with BMbx
Caused by aberrations in processing of iron iron by eruthroblast
Normocytic anemia causes
- Anemia of chronic disease
- Acute blood loss anemia
- Multiple myeloma
- Anemia of CKD
- Myelofibrosis/myelophthsic anemia
- Aplastic anemia
- Pure red cell aplasia
- Thyroid dz
Anemia of chronic disease
Occurs secondary to any inflammatory, infectious, or malignant disease of a long standing nature (HIV, hepatitis, RA, CAD, DM)
Normocytic or microcytic
ACD pathophysiology
Decreased iron + decreased erythropoietin + early RBC death
Inflammation causes increased hepcidin which therefore causes decreased absorption
ACD iron studies
- Serum iron: low
- Transferrin: low/normal
- TIBC: low/normal
- Ferritin : elevated (inflammation)
ACD treatment
Treatment of underlying condition
Can use ESA but not recommended.
Acute blood loss anemia
Symptoms of volume depletion ass. With significant blood loss
Falsely elevated H & H until equiliberation
What kind of things cause acute blood loss anemia?
Surgery
Childbirth
Trauma
GI bleed
Anemia due to multiple myeloma
Plasma cell overproduction suppresses the other cell lines
Causing normocytic anemia, neutropenia, thrombocytopenia
Bone pain (lytic lesions, renal failure, hypercalcemia)
Anemia due to multiple myeloma
Peripheral smear and diagnosis
Smear: Rouleaux formation
Diagnosis w/ SPEP/UPEP
Treatment: treat MM + transfusion support
Anemia of CKD
Normocytic anemia due to decreased erythropoietin
Production in kidney
Only seen once patient is at stage 3 CKD ( GFR < 45%)
Anemia of CKD MC in which patients
Black, male, older
Bc high rates of CKD
Anemia of CKD with multifactorial…
Cocontaminant with folate and IDA due to nutrient deficiency
Also due to decreased RBC survive and blood loss on hemodialysis
Treatment of anemia due to CKD
Titrated erythropoietin stimulation agent (ESA) – keep HgB levels b/t 10-12
Too much ESA can cause cardiac events, raise BP, and cause seizures
Myelophthisic Anemia
Collection of disorders that infiltrate the bone marrow and crowd out normal cellular precursors of RBCs, WBCs, and platelets therefore causing normocytic anemia
Associated with extramedullary hematopoietisis resulting in splenomegdaly
Infiltration processes in myelophthisic anemia
- Metastatic cancers to bone
- Tuberculosis
- Lymphoma/myeloma
- Lipid storage disorders
Symptoms of myelophthisic anemia
Suspected in patients with moderately severe normocytic normochromic anemia
Reticulocytosis occurs (not indicated by increased blood regeneration)
Myelophthisic anemia
Peripheral smear
Immature myeloid cells and nucleated RBCs
Extreme variation in size and shape
Myelophthisic anemia diagnosis and treatment
BM bx
Treat underlying dz
Myeloidfibrosis
Normocytic anemia caused by the deposition of scar tissue in the bone marrow
Replaces the cellular line precursor (low RBCs and all other cell lines)
Myelofibrosis peripheral smear + BMbx
RBC fragments and dacrocytes on smear
Fibrosis in BM - “dry tap_ due to lack of cells
Aplastic anemia
Normocytic anemia with concomitant pancytopenia
Congenital and acquired forms
Diagnosed with BMbx (hypocellular) and treated by removing offending agent
Congenital aplastic anemia
Rare
Fanconi
Cafe-at-lait spots, short stature, aplastic anemia, skeletal abnormalities
Acquired aplastic anemia
Via medications (chemo, sulfa drugs), toxins, infections, radiation, autoimmune
Pure red cell aplasia
Aplastic anemia w/o pancytopenia
Acquired and congenital (Diamond black)
diagnosed with BMbx - low erythroid precursors w/plenty WBC and megakaryocytes
Treat underlying disorder, test for thymoma
Etiologies of acquired pure red cell aplasia
Thymoma Neoplasm Collagen dz Drug (e-mycin, isoniazid) Autoimmune Infection (parvo, EBV, hepatitis)
Normocytic anemia workup
- Chemistry panel and TSH
- SPEP/UPEP
- Peripheral smear
If diagnosis still unknown do BMbx (aspiration and trephine)
Macrocytic anemia
MCV > 100 and corrected retic of <2%
Two categories : megoblastic and non megoblastic
Non megoblastic macrocytic anemia (list)
Anemia with normal WBC nuclei
- Liver dz
- Chronic alcohol use
- Hypothyroidism
Megaloblastic macrocytic anemias
Abnormally slow nuclear maturation of RBC precursors and hypersegmented neutrophils
- Vitamin B12 def.
- Folate def.
- Drugs
- Myelodysplastic syndrome
Medications that cause macrocytosis
Chemotheraputic agents
Metformin
Anticonvulsants
B-12 absorption
Completely thru diet
In terminal ileum
Req. intrinsic factor (secreted by parietal cells in stomach)
Body has many stores of B12 and takes a long time to develop
Etiologies of B12 def.
Due to malabsorption or dietary deficient
- Bacterial overgrowth
- Inflammatory disease in terminal ileum (esp. chron’s)
- Poor dietary intake (vegans)
Pernicious anemia
Caused by strophic gastritis and lack of parietal cell production
While the person is consuming enough B12, lack of intrinsic factor means it is not picked up - so it is a lack of b12
Atrophic gastritis
Typically the cause of pernicious anemia
Body produces auto-antibodies to parietal cells therefore they are tagged by Abs and removed before they can preform their action in the intestine
Can also be seen in patients with partial gastretomy
S/s of b12 anemia (CNS)
Degeneration of spinal cord before macrocytosis
Symmetrical lower extremity parenthesis, loss of vibratory and proprioception, weakness
Spasticity and Babinski signs (ataxia - esp in dark)
Dementia, irritability, memory loss
Other B12 anemia s/s
Atrophic glossitits
Flattening fo intestinal villi
Skin change
How is b12 def. diagnosed? Treated?
Low vitamin b12 levels
Also methylmalonic acid level (if elevated = B12 problems)
Treatment: vitamin b12 intramuscular injection
Folate deficiency anemia
Rapid macrocytic anemia +/- leukopenia and thrombocytopenia
Cofactors in DNA replication and division
Causes of folate def. anemia
- Nutritional def./malabsorption
- Alcoholism/Cirrhosis
- Pregnancy
- Medications
Folate anemia diagnosis and treatment
D: RBC folate levels and homocysteine levels (elevated in def.)
T: supplemental folate
Myelodysplastic anemia
Group of clonal disorders that affect prescursors of RBC, WBC, and platelets
Marrow is hypercellular or hypocellular and maturation is impaired
Causes anemia, +/- pancytopenia
May not be known or secondary to chemotherapty and radiation
Diagnosis of myelodysplastic syndrome
Typically premalignant, +70
Found incidentally, cytopenia on CBC
Made via BMbx and treated with medications depending on subtype
Peripheral smear of Myelodysplastic syndrome
Bi-lobed hyposegmented neutrophils –> Pseudo-Pleger Huet Cells
Why does liver disease cause macrocytic anemia?
Increased cholesterol and phospholipid deposition in the cell wall
Alcohol macrocytic anemia
Alcohol is toxic to bone marrow – delays maturation
Additionally often have b12 or folate deficiency and liver disease
Symptoms will persist months after cessation
Hemolytic anemias
Anemia caused by lysis of EBCs
Always associated with elevated corrected retic count if only disease present
Divided by cause of hemolysis: intracorpuscular and extracorpuscular
Or by site of hemolysis: extravascular, intravascular, intramedullary
Intracorpuscular hemolytic anemia
Hemolysis caused by RBC problem
- membrane defects
- enzyme defects
- hemoglobinopathies
Extracorpuscular hemolytic anemia
Hemolysis due to extrinsic issue
- Autoimmune
- Microangiopathic
- Mechanical valve
Extravascular hemolytic anemia
RBCs are removed by liver and spleen prematurely
Seen in autoimmune anemia
INTRAVASCULAR hemolytic anemia
RBC lysis within the vascular system
Seen in microangiopathic
Intramedullary hemolytic anemia
Destruction of RBCs within the marrow
Seen in thalassemia major
Hemolysis workup (results) 4
- LDH (elevated)
- Indirect Bilirubin (elevated)
- Haptaglobin (low/absent)
- Retic count (elevated)
Following blood workup, next step in hemolytic workup
Peripheral smear
Spherocytes in peripheral smear of hemolytic anemia suggest which type?
extravascular
Schistocytes in peripheral smear of hemolytic anemia suggest which type?
INTRAVASCULAR
ABCs of hemolytic anemia
A - Air (low oxygen)
B- shape
C- synthesis
D- defective enzymes
E - hostile environment
