Hemolytic Anemias

Question 1

What tests help you diagnose hemolytic anemia?

Answer 1

Increased reticulocytes

Increased indirect bilirubin (bilirubin that has not yet been conjugated by the liver; breakdown product of RBC in liver)

Increased LDH

Decreased haptoglobin (soaks up free Hb in the blood so it doesn’t damage tissue; meausre free haptoglobin so when it goes down, it’s bound to Fe)

Urine hemosiderin (indication of free Hb in the blood)

** bold are the most common tests

Question 2

What are the 2 main types of hemolysis?

Answer 2

Intravascular: can be anywhere in the body

Extravascular: in the spleen

Sometimes there’s overlap between the two

Question 3

What is the Coombs test?

Answer 3

Way to look for antibodies that react against RBCs

Cooms positive = antibody mediated

Question 4

Cooms positive v. coombs negative hemolysis

Answer 4

Coombs positive can be warm or cold antibody

Coombs negative can be inherited or acquired

• inherited: RBC enzyme deficiency i.e. G6PD, hemoglobinopathy i.e. sickle cell dz, thalassemias, RBC structure disorder spherocytosis v. elliptocytosis
• acquired: mechanical destruction i.e. disseminated intravascular collagen, TTP, malfunctioning prosthetic valves, RBC infections i.e. malaria or acquired RBC deficiency i.e. paroxysmal nocturnal hemoglobinuria, B12/folate deficiency

Question 5

What are the 2 types of Coombs test?

Answer 5

Direct Coombs tests: 1 step: take pt’s blood & mix it with antihuman antibodies– positive if antibodies link the RBC’s & RBC’s aggreage
tests whether the RBCs have antibodies attached to them

Indirect Coombs test: 2 steps
Test if pt’s serum has antibodies in it
Take pt’s serum, mix with RBC from a blood bank, add anti-human Ig’s, positive if RBC clump together

Usually both are positive

Question 6

What are the two types of antibody mediated hemolytic anemia you can get?

Answer 6

Warm: react against blood cells at body temp
IgG mediated: splenic macrophage picks up IgG tagged RBC, takes bites out of it, lose biconcave disk shape, spherical, gets trapped in spleen
Extravascular hemolysis
Rare, often idiopathic, seen in Hep C, autoimmune dz, lymphomas

Cold: more reactive at a cooler temp i.e. fingers/toes
IgM mediated: you see agglutination if you prep smear at cold temperature
Intra & extravascular hemolysis
Rare, rarely idiopathic: something else is causing them: mycoplasma, EBV/CMV mono, lymphomas

Question 7

How do we treat warm Ab/cold Ab hemolytic anemia?

Answer 7

Warm: corticosteroids = 1st line treatment
2nd line= rituximab, splenectomy
- has a longer half life so plasma exchange doesn’t work

• *Cold: Plasma exchange** to remove the IgM but it’s expensive
• splenectomy does nothing for this

+ treat underlying disorder for both of them

Question 8

What is G6PD deficiency?

Answer 8

Most common RBC enzyme deficiency

Glucose 6 phosphate dehydrogenase: required to regenerate NADPH & glutathione to deal with oxidative stress

Deficiency leaves you less able to deal with oxidative stress –> hemolysis

Bite cells and bilster cells

Question 9

What can trigger oxidative stress/ G6PD deficiency related hemolysis?

Answer 9

Infections

Fava beans

Diabetic ketoacidosis

Anti-malarials

Sulfa meds

Aspirin

Methylene blue

** pt can never have symptoms until they take the wrong med, eat fava beans, etc.

Question 10

Why should you never test for a suspected G6PD deficiency during an acute hemolytic episode?

Answer 10

Because their damaged RBCs will all have been destroyed, so you will get a false negative

Question 11

What is spherocytosis/eliptocytosis?

Answer 11

Sphere shaped or eliptical shaped RBCs due to abnromal cytoplasmic skeleton

Pediatric dz

Treat with splenectomy

Question 12

What is TTP

Answer 12

Thrombotic thrombocytopenic purpura: usually acquired, can be inherited; it’s a hemolytic anemia but also causes thrombocytopenia & is a clotting disorder

Normally: VWF binds platelets which stops bleeding
Ultra large von willembrand multimers get broken up by ADAMTS13, “pac man” enzyme which chews up ULVWM into small VWF

In TTP, you have acquired deficiency of Adamts13, so ULVWM can’t get broken up into VWF –> very sticky, gums up capillaries –> red cells get stuck and get sheared & destroyed in this dz = you get schistocytes (sheared RBCs)

Question 13

What are the diagnostic criteria for TTP?

Answer 13

Based on a clinical diagnosis, bc the test for antibody against ADAMST13 takes too long & it’s a life threatening condition

FATRN: pneumonic

Fever

Anemia: hemolytic anemia, schistocytes on smear

Thrombocytopenia: bc platelets are getting consumed

Renal failure

Neurological dysfunction

Question 14

Which lab studies can you order for TTP?

Answer 14

Dz activity/signs of hemolytic anemia: CBC+retic, bilirubin, LDH, haptoglobin, urinalysis

End organ damage: creatinine, troponin, BNP

Others: PT, aPTT, (these 2 are blood tests looking for coag will be normal in pt with TTP) HIV, ADAMTS13

Question 15

How do you treat TTP?

Answer 15

Steroids: for any dz that has too much immune activity

Plasma exchange: to remove ADAMTS13 antibody but also to add in functional vWF

Rituximab: antibody to CD20, protein expressed on B cells; kills B cells preferentially

Question 16

Malaria

Answer 16

Coombs neg acquired, mechanical form of hemolysis

Intravascular and extravascular process

Parasites inside RBCs

Treat the underlying dz

You can also hook them up to a machine, remove their RBCs, then give them a donor’s RBCs

Question 17

What is PNH?

Answer 17

Paroxysmal Nocturnal Hemoglobinurea

Dark urine in morning, lighter during the day

Complement mediated dz; complement is more active at night in acidemic environment & you get respiratory acidosis at night

RBCs have surface proteins on outside of plasma membrane, anchored by GPI which goes through plasma membrane into cytoskeleton

Complement: part of intrinsic immunity, should be directed against bacteria; but sometimes our RBCs become the target

CD55 & CD59 = anticomplement proteins on RBC surfaces to prevent them from being attacked by complement and hemolysed; these are hooked to RBC by GPI anchor

DNA damage makes anchor not work so CD55&59 not present so RBC not protected against complement & gets spontaneously destroyed by complement

Question 18

What are the major manifestations of PNH?

Answer 18

Intravascular hemolysis

Thrombosis

Bone marrow failure (rare)

Question 19

How do you treat PNH?

Answer 19

Eculizumab

Block complement around C5 = maintains benefits/ protection of complement against bacteria but stops the bad effects that cause PNH

Must give meningococcal vaccine bc pt’s are susceptible to meningococcal infections due to loss of complement