Hematology (Acquired Hemolytic Anemias)

Front 1

best indicator of hemolytic anemia is...

Back 1

high retic count

Front 2

when does hemolytic anemia occur?

Back 2

when RBC survival is shortened to <30 days (nl= 120 days)

Front 3

what happens when your direct bilirubin is low and you mostly have elevated indirect/unconjugated bilirubin?

Back 3

If direct bilirubin is low and mostly indirect/unconjugated bilirubin, then you can deduce that you have hemolytic anemia. This unconjugated bilirubin will not be excreted and you’ll have jaundice and icteric sclera (yellow eye). You’ll have only have icteric sclera without yellow pee (it’ll be clear instead).

Front 4

name some causes of indirect (unconjugated) hyperbilirubinemia

Back 4

-hemolytic anemia
-ineffective erythropoiesis
-resorption of hematomas
-liver dz (bc damaged hepatocytes can't conjugate bilirubin anymore)

Front 5

name some causes of direct (conjugated) hyperbilirubinemia

Back 5

-biliary obstruction/stasis
- hepatocellular dz

Front 6

what is the key question in differential dx of bilirubinemia?

Back 6

is the direct or indirect elevated? this will tell you what the etiology of the problem may be.

for example, hemolysis causes INDIRECT hyperbilirubinemia, while hepatocellular dz causes DIRECT hyperbilirubinemia

Front 7

tell me about the difference b/w intrinsic (intracorpuscular) vs. extrinsic (extracorpuscular) abnormaliites as a form of classifying hemolytic anemias

Back 7

intrinsic = usually hereditary (except for PNH, which is acquired intrinsic abnormality), where defect causing HA is in the RBCs themselves (transfused red cells typically have nl life span)

extrinsic = acquired, where RBCs are being destroyed by something outside of themselves (transfused RBCs even have shortened life span bc there's something in the blood or vascular environment that's causing destruction)

Front 8

tell me about the difference b/w intravascular vs extravascular classification of hemolytic anemias

Back 8

intra: rbcs perish in blood stream
extra: rbcs perish in the reticuloendothelial system (lymph nodes/spleen)

Front 9

RBCs leaving bone marrow stain as reticulocytes for about __ hours. normal retic count is about __%.

Back 9

24; 1

Front 10

what would you expect for the routine lab tests for a pt with hemolysis?

Back 10

CBC, especially hgb/hct (down)
Including smear review!
Reticulocyte count (↑)
Indirect bilirubin (↑)

Front 11

What would these lab results indicate?
-LDH (↑)
-Haptoglobin (dec)
-Plasma hemoglobin
-Urine hemoglobin and hemosiderin (iron in tubular cells shed into the urine)

Back 11

tests show intravascular hemolysis

haptoglobin=a protein in plasma that binds free hemoglobin and removes it

Front 12

name 3 congenital causes of hemolytic anemia (and give examples!)

Back 12

1. membrane abnormalities (hereditary spherocytosis/elliptocytosis)
2. enzyme defects (G6PD deficiency)
3. Hb defects (sickle cell, thalassemias)

Front 13

what is this?

Back 13

hereditary spherocytosis

Front 14

name the acquired causes of hemolytic anemia

Back 14

1) Immunologic
Warm antibody, cold agglutinin, allo-immune
2) Fragmentation
-TTP, HUS, DIC, valve hemolysis
3) Infections
-Malaria, Clostridia, Babesiosis
4) Metabolic/osmotic/chemical or physical agents
-Hypophosphatemia, Wilson’s disease, fresh water near drowning, burns
5) Membrane abnormalities
- Paroxysmal nocturnal hemoglobinuria, spur cell anemia
6) Hypersplenism

Front 15

most common cause of ACUTE intravascular hemolytic anemia

Back 15

ABO incompatible transfusion (someone gets wrong blood during transfusion and Ab's kill transfused blood cells)

Front 16

what are some other causes of acute intravascular hemolysis?

what are the sx's?

Back 16

clostridial sepsis; PNH crisis

sx's: chills/fever, dark or red urine, back and/or abdominal pain

Front 17

how can parvovirus complicate chronic hemolytic anemias?

Back 17

cause aplastic crisis

Front 18

what is shown here?

Back 18

microspherocytes where rbcs have no central pallor. normally 1/3 of diameter should have central pallor -- these cells have become spherical. don't know if this is hereditary or acquired problem.

Front 19

what is shown here?

Back 19

microspherocytes where rbcs have no central pallor. normally 1/3 of diameter should have central pallor -- these cells have become spherical. don't know if this is hereditary or acquired problem.

Front 20

what is shown here?

Back 20

microspherocytes as well as spherocytes. bigger ones are reticulocytes.

Front 21

pathophysiology of AIHA (IgG). why is it called warm antibody hemolytic anemia

Back 21

pt produces Ab's to self RBCs. Ab's damage rbcs and these rbcs are removed by macrophages (particualrly in the spleen).

Ab shows max reactivity with rbcs at 37 degrees (body temp).

Front 22

differentiate b/w direct and indirect coomb's tests

Back 22

- direct Coombs test is used to detect these antibodies or complement proteins that are bound to the surface of red blood cells; a blood sample is taken and the RBCs are washed (removing the patient's own plasma) and then incubated with antihuman globulin (also known as "Coombs reagent"). If this produces agglutination of RBCs, the direct Coombs test is positive, a visual indication that antibodies (and/or complement proteins) are bound to the surface of red blood cells. ==> shows that there is presence of auto-antibodies on rbcs themselves!!

The indirect Coombs test is used in prenatal testing of pregnant women, and in testing blood prior to a blood transfusion. It detects antibodies against RBCs that are present unbound in the patient's serum. In this case, serum is extracted from the blood, and the serum is incubated with RBCs of known antigenicity. If agglutination occurs, the indirect Coombs test is positive. ==> detects presence of Ab's in serum

Front 23

pt has pos DAT and pos IgG, pos C3

Back 23

warm autoimmune hemolytic anemia (IgG) aka. AIHA

Front 24

pt has pos DAT, neg IgG, pos C3

Back 24

cold agglutinin dz (IgM)

Front 25

pt has pos IAT, neg DAT

Back 25

caused by prior transfusion

Front 26

causes of AIHA

Back 26

- idiopathic (unknown cause) in 1/3; in children often triggered by viral infeciton
- lymphoproliferative disoders (CLL, lymphomas)
- systemic lupus erythematosus (or other autoimmune dz)

Front 27

tx of warm-Ab AIHA

Back 27

corticosteroids, splenectomy, immunosuppression, transfusion (with caution)

Front 28

what is shown here? what's the pathophysiology?

Back 28

cold agglutin dz (IgM)

- IgM antibodies that are maximally active in colder parts of body are directed towards self-rbcs. IgM avidly fixes complement for rbc destruction. hemolysis is both intravscular (c9 fixation - MAC complex) and extravsasulr (c3 promotes phagocytosis)

Front 29

what are the signs/sx's of cold agglutinin HA?

Back 29

anemia, ischemia of fingers, earlobes

Front 30

causes of cold agglutinin dz

Back 30

- idiopathic
- infections (mycoplasma pneumonia, etc)
- systemic lupus
- lymphoproliferative disorders

Front 31

tx of cold agglutinin dz

Back 31

-infectious: keep warm, gloves, earmuffs
-NOT corticosteroids/splenectomy
- immunomodulatory drugs
- rbc transfusions

Front 32

define: red cell fragmentation syndromes

Back 32

hemolytic anemias where hemolysis is caused by physical forces on flowing blood.

Front 33

should you treat cold agglutinin dz with corticosteroids and splenectomy?

Back 33

no

Front 34

what is shown here?

Back 34

Fragmentation syndromes – smear shows fragmented red cells; presence of spherocytes, but mostly see bizarre, triangular shaped cells. Notice there are no platelets here.

Front 35

define: microangiopathic hemolytic anemias

Back 35

these are disorders of small blood vessels (via fibrin depositions) that induce red cell fragmentation (schistocytes). ie. TTP and HUS.

Front 36

tell me the big differences between TTP and HUS

Back 36

TTP affects adults more than children, more likely to present with cns symptoms, fever.

HUS occurs mainly in children!! less likely to have cns symptoms, more likely to have renal problems! lose a lot more platelets (even though both have thrombocytopenia)

Front 37

pathophys of TTP

Back 37

acquired cases: antibody to ADAMTS13, which allows unusually large vWF to circulate in plasma --> leads to platelet clots, microvascular occlusion

Red blood cells passing the microscopic clots are subjected to shear stress which damages their membranes, leading to intravascular hemolysis and schistocyte formation. Reduced blood flow due to thrombosis and cellular injury results in end organ damage.

Front 38

what is the proper tx of TTP?

Back 38

plasma exchange (for acquired TTP)
PLATELET TRANSFUSIONS ARE CONTRAINDICATED!!!!!

Front 39

pathophys of PNH (paroxysmal nocturnal hemoglobinuria)

Back 39

-mutation in PIG-A gene which impairs ability to form membrane bridges
there are 20 proteins hanging on the surface of the RBC hanging with inositol bridge. Without this bridge, these proteins won’t be there. 2 of those proteins inhibit complement (CD 55 and CD 59). Therefore, complement will kill RBCs abnormally. And you get intravascular hemolysis.

Front 40

dx and tx of PNH

Back 40

dx: flow cytometry
tx: Eculizumab, a monoclonal Ab that binds C5 component of complement to inhibit complement activation (results in less hemolysis)

Front 41

features of hypersplenism

Back 41

-splenomegaly
-reduction in one or more of the blood cell lines leading to anemia, leukopenia, thrombocytopenia, or combination of these
-no morpholgical changes of blood cells on smear

Front 42

what can correct blood cytopenia(s)?

Back 42

splenectomy

Front 43

causes of hypersplenism

Back 43

- portal hypertension
- infectious dz (mono, CMV)
- infiltrative dz of spleen (Gaucher's)
- neoplastic dz (leukemias, lymphomas)
- hemoglobinopathies (SCD, thalassemia)