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Course 1: Gastroenterology and Hematology > Anemia > Flashcards

Flashcards in Anemia Deck (33)
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1

Bone Marrow Aspirate

  • Mostly fluid
  • Provides best view of fine cellular details

2

Bone Marrow Biopsy

  • Mostly tissue
  • Does not provide as great cellular detail as aspirate 
  • Better detail of infiltrative cells, overall cellularity, and distribution of cells

3

General Signs/Symptoms of Anemia

  • Fatigue
  • Low stamina/decreased exercise tolerance
  • SOB
  • Chest Pain 
  • Pallor (conjuctival, palmar crease, skin, nailbed)

4

Microcytic Anemia

  • Pathophysiology
  • Etiology
  • Labs

Pathology

  • Anemia resulting from a cytoplasmic maturation defect associated with a decrease in Hb synthesis

Etiology

  • Thalassemia
  • Anemia of chronic disease/inflammation
  • Iron deficiency
  • Lead poisoning

Labs

  • MCV <80 fL

 

5

Normocytic Anemia

  • Etiology
  • Labs

Etiology

  • Acute blood loss
  • Bone marrow failure
  • Chronic disease
  • Destruction (hemolysis)

Labs

  • MCV 80-100 fL

6

Marcocytic Anemia

  • Pathophysiology
  • Etiology
  • Labs

Pathology

  • Anemia caused by a nuclear maturation defect associated with decreased Hb synthesis

Etiology

  • Alcoholism (liver disease)
  • B12 deficiency
  • Compensatory reticulocytosis
  • Drugs/Dysplasia
  • Endocrine (hypothyroidism)
  • Folate deficiency/Fetus (pregnancy)

Labs

  • MCV > 100 fL

7

Iron Deficiency Anemia

  • Pathophysiology 
  • Etiology
  • Presentation
  • Labs 
  • Treatment

Pathophysiology

  • Decreased Hb production as a result of iron deficiency --> small, microcytic cells

Etiology

  • Poor intake (ex. vegetarianism), malabsorption (ex. celiac disease), blood loss (ex. heavy menstrual bleeding), increased needs (ex. pregnancy)

Presentation

  • General signs/symptoms of anemia + pica, koilonychia, angular stomatitis, glossitis, blue sclera

Labs

  • Microcytosis
  • Low serum iron
  • High TIBC, 
  • Low transferrin saturation
  • Low ferritin (*APR)
  • Solutuble transferrin receptors high

Treatment

  • Oral iron (start slow - nausea and stomach cramps)
  • IM iron 
  • IV iron (*anaphylaxis)

8

Anemia of Chronic Disease/Inflammation

  • Pathophysiology
  • Etiology
  • Labs
  • Treatment

Pathology

  • Anemia of underproduction due to impaired iron utilization 
    • Hepcidin (which is increased during inflammation) traps iron in enterocytes and macrophages
    • Reduced plasma iron levels make iron unavailable for Hb synthesis
    • Marrow is unresponsive to normal or slightly elevated EPO
  • Mild hemolytic component (RBC survival is decreased)

Etiology

  • Infection, malignancy, inflammatory and rheumatologic disease, chronic renal and liver disease, endocrine disorders (e.g. DM, hypothyroidism)

Labs

  • Normocytic to slightly microcytic cells
  • Elevated acute phase reactants (CRP, platelets)
  • Normal to elevated ferritin 
  • Low serum iron, TIBC (low when stores are high), % saturation
  • Bone marrow should show normal or increased iron stores
  • Normal to low reticulocyte count

Treatment

  • Treat underlying disorder
  • EPO (expensive + potentially dangerous)
  • Red cell transfusion only if symptomatic/severe
  • Iron is of no value in absence of an iron deficiency

9

Pancytopenia

  • Definition
  • Approach

Definition

  • Low levels of RBCs, platelets, and neutrophils

Approach

  • Production
    • Stem cell damage/suppression (chemo, radiation, drugs, toxins, aplastic anemia)
    • Marrow infiltration (malignancies, infections)
    • Nutritional deficiency (B12, folate)
  • Destruction
  • Sequestration in spleen

If all cell lines are low, it indicates a problem with the factory (i.e. the bone marrow). It's time for a bone marrow biopsy!

10

Aplastic Anemia

  • Pathophysiology
  • Etiology
  • Labs 
  • Treatment

Pathophysiology

  • Destruction of hematopoietic cells of the bone marrow leading to pancytopenia and hypocellular bone marrow (normal cellularity = 100-age)

Etiology

  • Inherited (Fanconi's anemia, Shwachman-Diamond syndrome)
  • Acquired (Idopathic (T-cell mediated), radiation and chemo, drugs, toxins (ex. benzene, DDT), infections (ex. HBV, HIV), immune disorders, pregnancy, paroxysmal nocturnal hemoglobinuria, thymona)

Labs

  • Bone marrow should appear hypocellular
  • Pancytopenia
  • Low reticulocyte count

Treatment

  • Immunosuppression (ex. cyclosporine)
  • Hematopoietic (stem) cell transplant

 

11

Warm Autoimmune Hemolytic Anemia (AIHA)

  • Pathophysiology 
  • Etiology
  • Labs
  • Treatment

 

Pathophysiology

  • Immune system produces autoantibodies which attach to and destroy RBCs at temperatures equal to or excess of body temperature

Etiology

  • Idiopathic
  • AI disorder, chronic lymphocytic leukemia, drugs

Labs

  • Blood smear should show spherocytes
  • Positive Direct Coombs Test (IgG and C3 positive)

Treatment

  • Blood transfusion if unstable
  • Suppress immune production of autoantibody (Prednisone, Rituximab)
  • Decrease RBC removal by spleen (splenectomy)
  • Treat underlying cause (if known)

12

Cold Autoimmune Hemolytic Anemia (AIHA)

  • Pathophysiology
  • Etiology
  • Presentation
  • Labs
  • Treatment

 

Pathophysiology 

  • Immune system produces autoantibodies which attach to RBCs at temperature well below normal body temperature (under 37 degrees)
  • Causes agglutination and hemolysis

Etiology

  • Idiopathic
  • Infection, lymphoproliferative disorder

Presentation

  • Painful fingers and toes with purpulish discoloration

Labs

  • Positive Direct Coombs Test (IgG negative, C3 positive)
  • Blood smear may show agglutination

Treatment

  • Warm patient/avoid cold
  • Immunosuppression (Rituximab)
  • Splenectomy ineffective because site of destruction is the liver

13

Paroxysmal Cold Hemoglobinuria

  • Pathophysiology
  • Etiology
  • Treatment

Pathophysiology

  • Rarest type of AIHA
  • Destruction of RBCs results from exposure to cold and even when cold exposure is limited to small area of body (ex. person washes hands with cold water). An Ab binds to RBCs at low temperatures and causes destruction of RBCs after warming.

Etiology

  • Occurs most often after viral illness or in people with syphilis

Treatment

  • Usually self-limiting and resolves in a few weeks
  • Avoid cold exposure

14

Hereditary Spherocytosis (HS)

  • Pathophysiology
  • Etiology
  • Labs
  • Treatment

Pathophysiology

  • Deficiency of RBC membrane proteins (ex. Band 3, spectrin)
  • RBC membrane defects cause bits of membrane to be removed each time RBCs pass through the spleen. This leads to spherical RBCs which are readily removed by the spleen.

Etiology

  • Inherited disorder

Labs

  • Blood smear should show sphereocytes
  • Negative eosin-5-maleimide (EMA) binding test (which detects band 3)

Treatment

  • Folic acid supplementation
  • Supportive blood transfusions if required
  • Splenectomy (warranted with moderate to severe disease)

15

Microangiopathic Hemolytic Anemia (MAHA) a.k.a. Thrombotic Micoangiopathy (TMA)

  • Pathophysiology
  • Etiology
  • Labs

Pathophysiology

  • Anemia caused by destruction of RBCs due to physical shearing as a result of passage through small vessels occluded by systemic microthrombi
  • Characteristically accompanied by thrombocytopenia (reduced peripheral platelets - used up to make microthrombi)

Etiology

  • TTP, HUS, DIC
  • Malignant hypertension, HELLP syndrome, severe pre-eclampsia, vasculitis, drugs (cyclosporin), malignancy, catastrophic antiphospholipid antibody syndrome

Labs

  • Blood smear should show schistocytes 
  • Low platelets (thrombocytopenia)

 

16

Thrombotic Thrombocytopenic Purpura (TTP)

  • Pathophysiology
  • Presentation
  • Labs
  • Treatment

Pathophysiology

  • Characterized by clotting in small vessels of the body, resulting in a low platelet count
  • ADAMTS-13 deficiency --> Excess vWF 

Presentation

  • The Terrible Pentad (TTP)
  • Classic pentad (FAT RNs - fever, anemia (MAHA), thrombocytopenia, renal dysfunction, neurological symptoms)

Labs

  • Blood smear should show shistocytes 
  • Increased closure time
  • Thrombocytopenia
  • Normal fibrinogen

Treatment

  • High mortality if not treated promptly
  • Plasma exchange (to replace ADAMTS-13)

17

Hemolytic Uremic Syndrome (HUS)

  • Pathophysiology 
  • Etiology
  • Presentation
  • Labs
  • Treatment

Pathophysiology

  • Toxin-mediated hemolysis occuring in kidney

Etiology

  • Often associated with diarrheal illness
  • More common in children

Presentation

  • DART (bloody diarrhea, anemia - MAHA, renal failure, thrombocytopenia)

Labs

  • Blood smear should show schistocytes
  • Increased closure time
  • Thrombocytopenia
  • Increased creatinine

Treatment​

  • Supportive care +/- dialysis
  • Eculizumab (blocks complement activation)

18

Disseminated Intravascular Coagulation (DIC)

  • Pathophysiology
  • Etiology
  • Labs
  • Treatment

Pathophysiology

  • Widespread inappropriate activation of both platelets aggregation and coagulation yielding the generation of microthrombi throughout the micro-vasculature.
  • DIC can then result in rapid consumption of platelets and coagulation factors, yielding bleeding in other parts of the vasculature.

Etiology

  • Death is coming!
  • Usually serious and life-threatening etiologies (sepsis, trauma, malignancies, pregnancy complications)

Labs

  • Blood smear should show schistocytes
  • Increased closure time
  • Increased PT and PTT (using up CFs - bleeding lasts longer)
  • Thrombocytopenia
  • Decreased fibrinogen (being consumed ***different from TTP/HUS)
  • Elevated D-dimer

Treatment

  • Treat underlying cause
  • Supportive blood and platelet transfusions
  • Plasma and cryoprecipitate transfusions (to replace deficient clotting factors and fibrinogen)

19

G6PD Deficiency

  • Pathophysiology
  • Etiology
  • Presentation
  • Labs
  • Treatment

Pathophysiology

  • W/o G6PD, cannot create NADPH which is needed to protect RBCs from oxidative stress. In turn, Hgb gets oxidized and denatures. This Hgb deposits as Heinz bodies. The spleen then takes "bites" at the cells to remove Heinz bodies (extravascular hemolysis).

Etiology

  • Genetic deficiency

Presentation

  • Episodic hemolysis precipitated by oxidative stress, drugs, infection, and certain food (ex. fava beans)

Labs

  • Low G6PD
  • Heinz bodies and bite cells

Treatment

  • Avoid known triggers
  • Folic acid

20

In what population groups is Thalassemia most common?

Asians, Indians, and Middle Eastern peoples

21

Describe the compositions of HbA, HbA2, and HbF

  • HbA = 2 alpha, 2 beta
  • HbA2 = 2 alpha, 2 delta
  • HbF = 2 alpha, 2 gamma

22

Describe Alpha Thalassemia and Genotypes

Decreased synthesis of alpha chains

  • aa/aa = normal
  • aa/a- = silent carrier
    • No anemia, normal to borderline low MCV, normochromic
  • aa/-- or a-/a- = alpha thalassemia trait
    • Cis is more prevalent in SE Asia (2 cis parents have 1/4 chance of having a baby with hydrops fetalis)
    • Mild microcytic hypochromic hemolytic anemia
  • a-/-- = Hb H (beta4)
    • Moderate microcytic hypochromic hemolytic anemia
    • May have splenomegaly
  • --/-- = Hb Barts (gamma4) --> hydrop fetalis
    • Often fatal for fetus

23

Diagnosis of Alpha Thalassemia

Diagnosis

  • Since alpha chains are a component of HbF, we can identify alpha thalassemia prior to birth
  • Check ethnicity and family history
  • Peripheral blood smear to check for Hb H bodies
  • Hb electrophoresis and/or HPLC to check for Hb H and/or Hb Barts

24

Treatment of Alpha Thalassemia

1,2 deletions

  • No treatment, genetic counselling, avoid excess iron

3 gene deletions

  • Variable transfusion requirements
  • Iron chelation therapy

4 gene deletions

  • Generally lethal in-utero (some cases of survival w/ intrauterine transfusion)
  • LT transfusion requirement (iron overload risk --> iron chelation therapy)

Bone marrow transplant

25

Define Beta Thalassemia and Genotypes

Decreased synthesis of beta chains

  • B/B = normal
  • B/B+, B/Bo = beta thalassemia trait/minor
    • Mild anemia
  • B+/B+, B+/Bo = beta thalassemia intermedia
    • Moderately severe anemia
    • Extramedullary hematopoiesis, leg ulcers, gallstones, thrombosis, pulmonary hypertension, growth retardation
  • Bo/Bo = beta thalassemia major
    • Severe anemia
    • Iron-induced organ damage, stunted growth and development, hepatosplenomegaly due to extramedullary hematopoiesis, hair-on-end skull x-ray, gallstones from increased Hb metabolism

26

Diagnosis of Beta Thalassemia

  • Since beta chains aren't made in high amounts until ~6 months of age, we can't make a diagnosis until then
  • Check ethnicity and family history
  • Hb electrophoresis and/or HPLC to check for high levels of HbA2 and/or HbF

27

Treatment of Beta Thalassemia

Minor

  • No treatment, genetic counselling, avoid excess iron

Intermedia

  • Variable transfusion requirements (accompanied by iron chelation)
  • Induction of HbF with hydroxyurea

Major

  • Life long transfusion and iron chelation, monitoring for organ dysfunction
  • Bone marrow transplantation
  • Therapies in the horizon include gene therapy and gene editing

28

HbE Hemoglobinopathy

  • Abnormal Hb
  • Hb A/E = normal Hb, minimal microcytosis
  • Hb E/E = mild asymptomatic anemia
  • Hb E/Beta thalassemia may have severe anemia like beta thalassemia major (so you must study the spouse to rule out beta thalassemia!)

29

HbC Hemoglobinopathy

  • Hb C/C = mild/moderate hemolytic anemia, splenomegaly, rare pain crisis and organ damage
  • Hb C/S = more significant symptoms

30

Pathophysiology of Sickle Cell Disease

 

  • Disease caused by mutation in beta globin gene --> "sickle" shaped RBCs
  • Autosomal recessive
  • Mutations in both beta globin genes = HbSS (sickle cell disease)
  • In one beta globin gene = HbAS (sickle cell trait, malaria advantage)