Module 1: Chronic Hemolytic Anemia (Hereditary Spherocytosis) Flashcards Preview

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Flashcards in Module 1: Chronic Hemolytic Anemia (Hereditary Spherocytosis) Deck (40):

What is Anemia and how is it determined?

Reduction (below normal limits) of total circulating red cell mass
--determined from Hb concentration or packed cell volume/hematocrit


Explain MCV,MCH,MCHC and RDW

MCV: average volume of RBC
MCH: average content of Hb per RBC
MCHC: average concentration of Hb in a given volume of packed RBCs
RDW: coefficient of variation of RBC volume/size


Clinically how does anemia present?

Asymptomatic, when mild
--symptomatic: related to poor O2 supply to tissues: weakness, easy fatigability, headaches, fainting, SOB on exertion
--increase pulse, resp rate and SV (Eventually heart failure)
--pallor, nail changes in severe cases


Anemia classification is based on what three things?

1.Degree of hemoglobinization (color)(pinkness): mature RBCs are either normochromatic or hypochromatic
2. Cell size: RBCs are macrocytic, normocytic or microcytic
3. Cell shape: spherocytes, sickled, etc.


Again what is microcytic and macrocytic?

Microcytic (low MCV): small red blood cells (nucleus of lymphocytes is much bigger)
Macrocytic (high MCV): large red blood cells (nucleus of lymphocytes is much smaller)
--remember that MCV is the average volume of RBC


What are the two underlying mechanisms for anemia?

1. Accelerated blood loss/destruction: peripheral
--blood loss: acute hemorrhage or chronic blood loss
--increased rate of destruction= hemolytic anemia
2. Impaired RBC production: bone marrow


The first type of anemia we will discuss will be hemolytic anemia, which is again an increase in the rate of destruction of RBC, what are common features?

Shortened RBC life span
increase erythropoietin and erythropoiesis
accumulation of Hb breakdown products
Erythroid Hyperplasia (increased intramedullary erythroposis): bone marrow is trying to compensate for increased RBCs
Reticulocytosis: increased reticulocyte count
Retention of products of RBC destruction (bilirubin and iron)
Increased rate of RBC destruction


What are the different classifications of hemolytic anemia?

Site: intravascular (inside blood vessel) vs. extravascular (outside blood vessel) -----spleen
Cause: Intrinsic or extrinsic (to RBCs)


What are the intrinsic anemias?

Hereditary Spherocytosis: membrane abnormalities
G6PD: enzyme deficiencies
Sickle Cell and Thalassemaia: Hb synthesis
Paroxysmal Nocturnal Hemoglobinuria: membrane defect


What are the extrinsic anemias?

Ab mediated
Non-immune: damaged endothelium damages RBCs
sequestration :due to hypersplenism


What is intravascular hemolysis due to?

1. Mechanical Injury to RBCs due to: defective cardiac valve or microvascular thrombi
2. Complement fixation of Ab-coated RBCs
3. Infections: intracellular parasites, production of toxins= cell lysis
--Hb products in the blood and urine
--direct damage to the RBC membrane right in the intravascular space


What products do you find in the blood and urine in intravascular hemolysis?

1. Decreased Haptoglobin
2. Increased LDH (non specific marker of cell lysis)
3. Increased Hemoglobinuria (urobilinogen is spilling into the urine)
4. Increased Unconjugated bilirubin


What is Extravascular hemolysis?

Occurs in the actual spleen
--RBCs rendered less deformable (spherocytosis, sickle cell)
--RBCs rendered foreign (by immune mechanism)
--hemolysis in extravascular spleen is most causes of hemolytic anemia


What are the lab values or extravascular hemolysis?

1. Increased LDH
2. Increased Unconjugated Bilirubin (jaundice)
3. Decreased haptoglobin


There are 4 different types of Hemolytic Anemia that will be discussed in this course. The rest of these cards will be explaining these: The first is Hereditary spherocytosis, what type of anemia and hemolysis is this?

Normocytic anemia with predominant extravascular hemolysis (remember this occurs in the actual spleen but outside the blood vessel)
--inherited hemolytic anemia


Is hereditary spherocytosis, autosomal dominant or recessive?

More common is AD but can be AR and this is more severe
--northern europeans (Swedish)


What is the etiology of hereditary spherocytosis?

Defect in the structural proteins that normally maintain biconcave disc so this is why they assume the spherocytic shape


What are the three most important proteins causing structural defects in hereditary spherocytosis?

Band 3


Is hereditary spherocytosis episodic or chronic?



How does a patient with hereditary spherocytosis present?

Conjunctival Pallor
Spleen is massive (LUQ)(dragging sensation)
Sclera are icterus (yellow)
--these symptoms however are for any hemolytic anemia


What bilirubin is responsible for hemolytic anemia and why?

Unconjugated or indirect bilirubin is responsible for all hemolytic anemia because the liver doesn't get enough time to conjugate all the bilirubin


In hereditary spherocytosis what is the pathogenesis?

Biconcave ---- spherocytes to accommodate decreased SA:V ratio --- pack more Hb --- no central pallor ---- increased MCHC and Increased RDW
--spherocytes can deliver O2 normally but spleen recognized them as foreign --- extravascular hemolysis


What is the average RBC lifespan for a spherocyte?

10-20 days


For investigations what is a coombs test and what are the results?

Coomb's Test: how you know whether the hemolysis is due to immunoglobins
--if there is immunoglobin damage to RBC then this is Coomb's Positive
In hereditary spherocytosis the Coomb's test is negative because no immune globin mediated damage


What is the most accurate test for hereditary spherocytosis?

Osmotic Fragility test: RBCs placed in hypotonic solution will eventually burst however in with this disease the membranes rupture faster


What do you see on peripheral blood smear in hereditary spherocytosis?

Spherocytes (again this is due to the lack of those structural proteins)
Reticulocytes (b/c bone marrow is responding so before they are maturing due to all the pressure on bone marrow the retics are just spilling into the blood)
Howell Jolly Bodies (Because the spleen is getting worked too hard)


What do you see in the bone marrow for patients with hereditary spherocytosis?

Erythroid Hyperplasia (many red cell precursors --- normoblasts) basically bone marrow is just making more and more precursors
---also called increased intramedullary erythroposis: again the bone marrow is trying to compensate for the increased RBCs
--seen in every hemolytic anemia
--so spleen is destroying and bone marrow is compensating


Again what do you see elevated in the blood for patients with hereditary sphereocytosis?

1. Increased LDH (marker of cell lysis very non specific)
2. Increased Unconjugated Bilirubin
3. Increased Potassium-- hyperkalemia (most common intracellular iron is potassium so anytime you are breaking the cell potassium is spilling out into the blood)


What specific blood values are normal in hereditary sphereocytosis?

Uric Acid levels are not elevated: because there is no nucleus in the RBC
Conjugated Bilirubin: normal (only time you see elevation is obstruction past the liver)


So for any chronic hemolytic anemia you will see the same complications. Each card will go through each complication with explanation: 1. Left ventricle hypertrophy

1. LV hypertrophy --- LV failure --- RV failure ---CHF


2nd complication of chronic hemolytic anemia?

2. Hepsidin levels are low (negative regulator of iron uptake)
---no folate because folate is getting used up by the bone marrow in trying to make RBCs so patients get folate deficiency which leads to megaloblastic anemia (patients needs to take folate supplements)
---B12 is unaffected because we have huge stores of B12


3rd complication of chronic hemolytic anemia?

3. Aplastic Crisis:
--Parvovirus B19 infects nucleus of normoblasts in the bone marrow when this virus infects them it freezes their growth and therefore can not become reticulocytes nor erythrocytes so now the anemia is getting worse
---results in reticulocytopenia (only time you will see this)
--Parvo only affects RBC linage


Quick review: what are the three chronic hemolytic anemias?

1. Sickle Cell
2. Beta Thalassemia Major
3. Hereditary Spherocytosis


What is aplastic anemia?

Affects Myeloid Stem cells
--results in pancytopenia (Affects WBCs, RBCs, and Platelets)


What is the 4th complication of chronic hemolytic anemia?

4. Encapsulated bacterial infections due to splenic dysfunction


What is the 5th complication of chronic hemolytic anemia?

Bilirubin gallstones ----cholecystitis (jaundice, fever, pain, positive murphys sign)


What is the treatment for chronic hemolytic anemias?

Splenectomy and Folate Supplements


After a splenectomy what does the patients blood smear look like?

Howell Jolly Bodies
NO more rectics because no more hemolysis


A patient with chronic hemolytic anemia need to get certain vaccines, what are they and why?

Again the spleen is in charge of destroying these encapsulated bacterial infections when you dont have the spleen ......not good
--H. Influenza vaccine (HIB)
---N. Meningitis vaccine
---Pneumococcal vaccine


A Coomb's test ( also called antiglobulin test or antihuman globulin test), can be direct or indirect, explain the differences

RBC: patient ; Serum: none; AHG: yes
RBC: reagent; Serum: patient; AHG: yes
--note AHG means antihuman globulin

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