Anemia Flashcards
the WHO defines anemia as?
♀ Hct < 41% /Hg < 4,000,000/mm3
Different institutions will have slight variations to reference ranges
Anemia
an indication of an underlying disease process
It is characterized by a decrease in RBC Mass Leading to a Decrease in Oxygen Carrying Capacity
Which organ produces blood cells?
The Bone Marrow (BM)
To facilitate adequate RBC production, the BM must be able to Maintain Homeostatic balance of?
Macrophages that supply Fe++ for Hgb production
Fibroblasts to support BM integrity
Adipocytes that store energy as fat
Osteoblasts and osteoclasts supporting the boney trabeculae
Precursors of Blood Cell Production
Maintain vascular integrity as a conduit between BM and peripheral circulation
Maintain erythroid stem cells responsive to Erythropoietin
Erythropoietin
regulating hormone
Secreted by kidney
Governs day-today RBC production
O2 availability is main EPO stimulus
EPO binds to erythroid precursor receptors
EPO levels should increase in proportion to anemia severity
Erythropoietin is inversely related to?
HCT
What does Erythropoietin do?
Increases RBC production (4-5x) and speed maturity of RBCs
Iron, B12, folate are needed substrates
What is the lifespan of a RBC in peripheral blood?
Lifespan of an RBC in Peripheral Blood is 120 days
Epidemiology of Erythropoiesis
African Americans have relatively lower RBC mass
Older adults Have a Deceased RBC mass
20% have <12 g/dL
Tissue hypoxia and ↑ cardio output
Increased falls, confusion, frailty, muscle weakness
Athletes can present with?
“Dilutional Pseudoanemia”—increased energy demand, increases O2 demand—with initial Plasma Vol increase followed
Changes in Plasma Volume May Decreases or Increase RBC Concentration Regardless of RBC Mass
Acute Bleeding– Decrease Intra-vascular Volume– Normal Hgb and Hct (Concentration)
When Normal Volume is Restored the patient will demonstrate Anemia
Dehydration:
Pregnancy:
How does pregnancy cause changes in plasma volume?
Plasma volume increases faster that RBC mass, therefore the patient may appear falsely anemic.
How does dehydration cause changes in plasma volume?
presents with normal or elevated Hgb & Hct, but once hydrated the Hgb & Hct may Reveal the Patient to be Anemic ( Decreased RBC Mass)
Reticulocyte
immature RBC that is Stained with Methylene Blue and reveals residual Ribosomal RNA as beads of tiny deep blue precipitates.
What does the clinical presentation of anemia depend on? (4)
Rapidity of Onset
Severity
Patient’s Physiologic Age & Co-morbidities
Physiologic Responses e.g. increase in 2,3-diphosphoglycerate
What are some symptoms of anemia?
DOE Fatigue Palpitations Headache Tinnitus Chest pain (esp. in patients with CAD) Esophageal rings: Schatzki’s rings in Chronic Fe Deficiency Spooning of Nails (Fe Deficiency) Picas (Fe Deficiency) Neuropathies (B12 Deficiency)
What are some clinical signs of anemia?
Tachycardia Orthostatic hypotension Hypotension if acute Systolic ejection murmur Pallor:
Where are you going to look for pallor in anemic patients?
Palmar creases If lighter than surrounding skin Hg < 8g/dL Best physical sign indicator Palpebral conjunctiva Skin Oral mucous membranes Nail beds
What are 4 GI signs associated with anemia?
Jaundice
Positive stool guaiac
Splenomegaly
Hepatomegaly
What are 3 MSK signs associated with anemia?
Pale, cold extremities
Bone tenderness
Frontal Bossing
Microcytic (and hypochromic) Anemia
Mean Corpuscular Volume (MCV) < 80 mm3
Main Causes of microcytic anemia
Thalassemia minor/major
Iron Deficiency Anemia
Most common cause anemia
Anemia of Chronic Diseases/Inflammatory Diseases
Sideroblastic Anemias and Pb Poisoning
Iron deficiency anemia epidemiology
Accounts for 50% of Anemias Worldwide
Accounts for > 800,000 Deaths/year Worldwide
> 70% of Iron Deficiency Anemia Deaths are in Africa & Asia
Lab evaluations for iron deficiency anemia
Serum Iron, Fe: Iron Bound to Transferrin in the Serum
Total Iron Binding Capacity, TIBC: Total Transferrin in the Serum
Fe/TIBC is the % Saturation of Iron to Iron Binding Capacity (Transferrin)
Serum Ferritin: A Rough Estimate of Iron Stored in the Reticuloendothelial System
Causes (DDX) of Iron Deficiency Anemia
GI Bleeding*** Excessive Menstruation Malnutrition & Dietary Insufficiency Celiac sprue Crohn’s Disease Subtotal gastrectomy Pregnancy Growth Spurts in Childhood Blood Donation, Blood Loss in Dialysis & Factious Auto-phlebotomy
Specific Clinical Manifestations of Iron Deficiency Anemia
Angular Cheilosis PICA Koilonychia (spoon nails) Plummer-Vinson Syndrome Fe++ def anemia, esophageal webs, dysphagia and atrophic glossitis
inital eval of someone you suspect is anemic?
CBC Ferritin level Wright-stained Peripheral Smear Degree of Anisocytosis and Poikilocytosis (Increased RDW) decreased Fe increased TIBC Saturation < 10% Ferritin < 20 ng/dL
Treatment of Iron deficiency
oral iron supplement
-ferrous sulfate = MC
can also be given IV or IM
Why would iron be given IM or IV?
Patients Intolerant to Oral Preparation
If More Rapid Correction of Fe Deficiency Anemia is Needed
If Patient Cannot Absorb Oral Iron
If Chronic Blood Loss Fe Loss > Oral Repletion is Possible
Patients on Dialysis
Why can the treatment fail?
Unidentified blood loss Non-adherence Incorrect diagnosis GI malabsorption Achlorhydria PPIs Crohn’s etc. S/P Gastrectomy
Side effects of iron supplements?
Constipation, black stools, nausea, bloating abdominal pain, & diarrhea
What increases iron absorption?
vit c–> orange juice
Alpha-Thalassemia:
↑prevalence in Malaria Regions:
Southeast Asia & China
Beta-Thalassemia:
↑ prevalence in Mediterranean populations (Southern Italy, Greece & North Africa)
Thalassemia Syndromes
Genetic disorder characterized by inadequate production of either the Alpha or Beta-globin chain of hemoglobin
What are Heinz bodies?
Are precipitants of excess Alpha chains in Beta-Thalassemia
Are precipitants of excess Beta chains in Alpha-Thalassemia
They Impair DNA synthesis RBC Production
They Damage RBC Membrane RBC Destruction
Thalassemia Clinical features
Positive family history
History of life-long hypochromic, microcytic anemia not responsive to Fe++
From silent carrier status to profound anemia:
Depends on genetic defects
Complications of Beta-Thalassemia Major (Cooley’s Anemia)
Growth retardation Severe anemia Abnormal facial structure Pathologic fractures & Osteopenia Hepatosplenomegaly Jaundice and bilirubin gall stones High out put CHF Short life span (< 30 years)
What lab findings confirm the diagnosis of Cooley’s anemia?
Hg electrophoresis
increase Hgb F (in both Thalassemias)
Hgb A decrease Beta Thal, but ↑ Hgb A2
Hgb H in severe Alpha Thalassemia
What would be seen on peripheral smear for Cooley’s anemia?
Small, pale RBCs
Target cells
Nucleated erythroblasts
Basophilic stippling
Thalassemia Treatment
Transfusions + deferoxamine (to prevent iron overload)
Keep Hgb >12 g/dL
Splenectomy
Experimental Allogeneic Hematopoietic Stem Cell Transplantation (BM transplant) in severe cases
Avoid Iron containing Supplements
Iron Overload can cause what?
Heart Failure Liver Failure Pancreatic Failure with DM & Malabsorption Other Endocrine Abnormalities Skin Pigmentation
How do you treat iron overload?
Iron chelation therapy extends life expectancy by reducing iron overload IV Desferal (deferoxamine)
Thalassemia Patient Education
Genetic counseling
Testing of parents
Prenatal diagnosis for severe forms of Thalassemia
Normochromic Normocytic Anemias causes?
Causes: Anemia of Chronic Disease Early Fe++ deficiency Myelodysplasia or Marrow Failure Acute Blood Loss Anemia Associated with Renal Failure
Normochromic Normocytic Anemias
Definition:
MCV 80-100 mm3
Anemia of Chronic/Inflammatory Disease
Reticulocyte Production Index is Low
Normal or Increased Ferritin
“Normal” Fe/TIBC (Transferrin Saturation) BUT….
Low Levels of Transferrin ( Low TIBC) &
Low serum iron
decreased Fe++ release to BM from storage sites
Iron Remains Sequestered in the RE System:
Treatment of Anemia of Chronic Disease
Treatment of the Underlying condition is Most Important
Fe++ supplements +/- help
Erythropoietin
There is decreased response to Erythropoietin
Anemia of Renal Failure: a Normocytic Normochromic Anemia
Erythropoietin deficiency
Uremic toxins interfere with RBC production and survival
Hemodialysis (causes hemolysis and blood loss)
Responds well to Erythropoietin & Iron
Hemolytic Anemias intrinsic causes?
RBC defects)
G6PD deficiency
Sickle Cell
Hereditary spherocytosis
Hemolytic Anemias extrinsic causes?
Immune hemolytic anemia** Drug-induced hemolytic anemia** Thrombotic thrombocytopenic purpura Hemolytic Uremic Syndrome Disseminated intravascular coagulation Mechanical hemolysis d/t cardiac valve difunction Hypersplenism
Hemolytic anemia clinical features?
May Be Associated with Jaundice, Gallstones or Splenomegaly
May Have Symptoms Consistent with Tissue Hypoxia, similar to other anemia related syndromes: Pallor, SOB, Tachycardia
Sickle Cell Anemias?
Point mutation of the Beta-globin chain of Hb A molecule—with abnormal replacement of glutamine (hydrophilic) with valine (hydrophobic) HbS
Short arm of chromosome 11 mutation
Pathophys of sickle cell anemia?
HbS becomes sickled when deoxygenated—producing structural cellular damage
Sickled Hgb can return to Its Normal Configuration when re-oxygenated
Sickle Cell disease vs sickle cell trait?
Sickle Cell Disease
Homozygous Hemoglobin S
Sickle Cell Trait:
Heterozygous for Hgb A & Hgb S
Little tendency to sickle unless there’s severehypoxia—usually asymptomatic
Sickle cell anemia complications?
hemolysis splenic sequestration microvascular occlusion bone infarcts osteomyelitis priaprism blindness
How do you diagnose sickle cell anemia?
Hg Electrophoresis
Will detect Hb S
Trait will have 40% Hb S
Disease >95% Hb S
Smear
Sickled cells, hemolysis, reduced RBC count
Reticulocytosis
Nucleated RBCs
Target Cells
Holly Jolly Bodies due to Autosplenectomy
Treatment of sickle cell anemia?
Prevent Sickle Cell crises by monitoring for conditions that demand O2 from RBCs
Infection
Exercise
Climate extremes
Dehydration during periods of physiologic/emotional distress
Bone marrow transplant**
Treatment for sickle cell crisis?
IV Hydration
Supplemental oxygen
Analgesics—Morphine
Transfusion for Hct < 30% ( Hgb < 10 g/dL)
R/O Occult Infections, MI or Pulmonary Emboli
Supportive care for sickle cell anemia?
Folic acid qd
Pneumococcal and H. flu vaccination
Penicillin prophylaxis
Ophthalmological monitoring against retinopathy
Orthopedic Care
Careful Monitoring of Renal, Pulmonary and Cardiac Function
Pain Management
Autoimmune Hemolytic Anemias
occurs when antibodies directed against the person’s own red blood cells (RBCs) cause them to burst (lyse), leading to insufficient plasma concentration
2 types of Autoimmune Hemolytic Anemias
IgG or IgM mediated have different disease courses
Warm AIHA—IgG mediated
Autoimmune Hemolytic Anemias
More common than cold AIHA
IgG binds to RBC at > 37⁰C
Results in extravascular hemolysis—especially in spleen or liver
Cold AIHA—IgM mediated
Autoimmune Hemolytic Anemias
IgM binds to RBC in temperatures < 37⁰C
Produces complement fixation & activation leading to intravascular hemolysis—within blood vessels
Causes of Warm AIHA- IgG mediated?
Primary or Idiopathic
Secondary to lymphoid malignancies, collagen vascular disease (SLE), viral infections, or drugs
Causes of Cold AIHA- IgM mediated?
Idiopathic
Lymphoproliferative diseases, e.g. Waldenstrom’s Macroglobulinemia
Mycoplasma pneumoniae
Infectious mononucleosis (EBV infection)
Clinical signs of Autoimmune Hemolytic Anemia
Jaundice
Splenomegaly
Fatigue
Pallor
Diagnosis of Autoimmune Hemolytic Anemias (6)
Positive Direct Coombs Test Elevated reticulocyte count Blood smear reveals immature RBCs Free serum hemoglobin (hemoglobinemia) and hemoglobinuria—indicates intravascular hemolysis Unconjugated (indirect) bilirubin is high Total bilirubin can rise to 4 mg/dL Elevated serum LDH indicates hemolysis Low or Absent Haptoglobin
Treatment of AIHA (6)
Treat Underlying Disease Lymphoma, Mycoplasma pneumonia, EBV Immunosuppressive medications Steroids: Prednisone Cyclophosphamide Rituximab (Anti-CD 20 Ab) RBC transfusions Folate Splenectomy
Vitamin B12 deficiency
Most common cause is of B12 deficiency is impaired GI absorption due to lack of intrinsic factor produced by gastric parietal cells
Pernicious Anemia
is lack of Intrinsic Factor (IF) due to auto-antibody destruction of Gastric Parietal Cell
Clinical Presentation of Vitamin B12 deficiency
Can take >3 years to show up Macrocytic Hypoproliferative Anemia Weakness, faintness, pallor of skin and mucous membranes Dyspnea after slight exertion Atrophic Glossitis and stomatitis Neuropathy
Lab Findings for Vitamin B12 deficiency anemia
Blood smear shows marked macrocytic RBCs (MCV >100 mm3)
Low serum B12 (< 250 pg/mL)
High methylmalonic acid (high only in B12 def.)
High homocysteine (elevated in both B12 and folate def.) levels
Anisocytosis, poikilocytosis, macro ovalocytes and hypersegmented PMNs
Low Reticulocyte Count
Elevated LDH and indirect bilirubin
Deficiency in Erythropoiesis will result in
Ineffective RBC Production
Defective and fragile RBCs
Asynchronous maturation between cytoplasm and nucleus
Treatment for B12 deficiency anemia
1mg B12 (cyanocobalamin) IM qd x 7 days then q wk x 4-8 weeks then monthly for life—for pernicious anemia
If treatment is delayed greater than 6 months neurological problems may not respond to treatment
Folate can reverse hematologic abnormalities of B12 deficiency, but not neurologic symptoms
It is therefore Essential to obtain BOTH B12 & Folate Levels in Macrocytic Anemias.
Causes of Folate def anemia?
Inadequate Folate intake Alcoholics anorectic persons elderly diet low in meat, fruit and vegetables (leafy green vegetables—do not over cook veggies)
Folate deficiency anemia?
Body stores sufficient for 2-3 months
Decrease folic acid causes impaired RBC maturation and early destruction
when are times the body requires an increase in folate?
Pregnancy Chronic Hemolytic Anemias Malignancy Dialysis infants and children
Clinical Presentation of Folate def anemia?
Symptoms from dietary deficiency can be seen in a few months—quicker than B12 deficiency
Atrophic Glossitis and Angular cheilosis
anemia symptoms related to poor tissue oxygenation
Lab findings for folate def anemia?
Macro-ovalocytes
Hypersegmented PMNs
B12 levels are normal
Low Levels of Serum folate ( < 5.4 ng/ml)
Treatment for folate definciency anemia?
1-5 mg/day Folic Acid usually PO
Avoidance of alcohol and folic acid antagonists
Treat causes of malabsorption
Must rule out B12 deficiency
Deficiency can cause spontaneous abortion or fetal neurologic defects
