P&t--E2--Lecture 46-Hemolyticanemia1

Front 1

What is hemolytic anemia definition

Back 1

Short red blood cell (RBC) life span
- associated with accumulation of hemoglobin catabolism due to RBC destruction
- associated with inc erythropoiesis and reticulocytosis

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RBCs made where

Back 2

bone marrow

Front 3

RBCs survive how long

Back 3

100-120 days

Front 4

Early RBCs have ribosomes, stain with reticulin called

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reticulocytes

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normal reticulocyte %

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1%

Front 6

with early hemolysis we see what reticulocyte %

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higher % >1%

Front 7

Consequences of RBC hemolysis

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Anemia – pallor, shortness of breath, etc
Expansion of marrow space w/ skeletal deformity
**(tower skull)
Growth retardation
Funny looking RBC
Increased reticulocytes
Increased bilirubin, uric acid, and LDH
Bilirubin gall stones
Splenomegally

Front 8

First step to diagnosis of hemolytic anemia

Back 8

First step: identify presence of Hemolysis

Front 9

Hemolytic anemias have what shape and size RBCs?

Back 9

- sickle
- spherocyte
- shistocyte
- acanthocyte
- stomatocyte
- Heinz bodies

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Acanthocytes

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– liver disease, abetaliproteinemia, postsplenectomy

Front 11

Basophilic stippling

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– lead tox, thalassemia

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Bite cells

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– G6PD def, oxidant drug hemolysis

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Burr cells

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– uremia, ulcers, gastric CA

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Cabot’s ring

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– splenectomy, megaloblastic, hemolytic

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Howell-Jolly bodies

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- splenectomy, megaloblastic, hemolytic

Front 16

Lab Diagnosis of hemolytic anemia look for

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Low HB < 12 g/dl
Low Hct < 33%
reduced number of RBCs
Blood smear
---normochromic normocytic
---microcytic hypochromic (MCV < 80 fL)
---macrocytic (MCV>100 fL)
RBC shape, fragments….
Reticulocyte count

Front 17

Key diagnostic features of Hemolytic Anemia?

Back 17

Reticulocytosis
Blood smear: hypochromic microcytic anemia
Signs of heme degradation

Front 18

What is Extravascular Hemolysis

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removal of RBC by the Reticuloendothelial system (spleen macrophages)

Front 19

What is intravascular hemolysis?

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destruction of RBC in the circulation with free hemoglobin release.

Front 20

Lab values for intravascular hemolysis

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SERUM:
Inc Indirect and direct Bilirubin
Inc LDH
Inc Free hemoglobin
Haptoglobin depleted
Inc Methemoglobin
URINE
--Bilirubin (common)
--Hemosiderinuria
--Hemoglobinuria

Front 21

Intravascular hemolysis is associate with what immune activation

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complement activation
- thus we see the free hemoglobin release
- Buffer proteins that transport hemoglobin (haptoglobin) is thus dec

Front 22

Lab values for extravascular hemolytic anemia

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SERUM:
--Direct Bilirubin
--LDH
--Haptoglobin low
URINE
--Bilirubin RARE

Front 23

Second step in making diagnosis of hemolytic anemia?

Back 23

Identify the mechanism of hemolysis
---Intrinsic defect or intracorpuscular
---Extrinsic defect or extracorpuscular

Front 24

Intrinsic hemolytic anemias include

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1- Abnormal RBC membrane
***spherocytosis, elliptocytosis
2- Enzyme disorder
***G6PD or pyruvate kinase
3- Abnormal Hemoglobin
***Sickle cell, Thalassemias

Front 25

External factors include

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antibodies and thrombosis

Front 26

Key membrane abnormalities

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Hereditary spherocytosis
Hereditary elliptocytosis
Paroxysmal nocturnal hemoglobinuria

Front 27

Hereditary spherocytosis is what

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Defect of the RBC membrane (mut in ankyrin protein)
- renders the erythrocytes spheroidal
- susceptible to splenic sequestration and destruction
- autosomal dominant

Front 28

Spherocytosis is a ____vascular mechanism

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extravascular mechanism of HA

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hereditary spherocytosis

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defects in membrane to cytoskeleton binding lead to membrane separation and loss as microvesicles. Small dense microspherocytic RBCs result that have reduced osmotic fragility.

Front 30

Diagnosis of spherocytosis

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1) Blood smear:
Anemia, Spherocytosis
2) Osmotic fragility test 
3) Bone marrow:
increased erythropoiesis,
4) Clinically:
jaundice (Bilirubin), splenomegaly

Front 31

Management of Spherocytosis

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Because of the hyperactive bone marrow
To prevent aplastic anemia, Folic Acid treatment is recommended
Splenectomy in symptomatic patients

Front 32

Hereditary Elliptocytosis

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Autosomal Dominant inherited defect
Elliptical RBC and variation in RBC shape (Poikilocytosis)

Front 33

Paroxysmal nocturnal hemoglobinuria (PNH)

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-- hyperactivation of the complement system
RBC membrane defect of :
--- Decay accelerating factor (DAF),
--- CD59 (membrane inhibitor of lysis)
both factors protect RBC from complement damage

Front 34

Patients with PNH have heightened sensitivity of complement because of the loss of ____

Back 34

DAF

Front 35

What test shows inc sensitivity to complement

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sucrose hemolysis test

Front 36

Inherited enzyme deficiencies for HA

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Glucose-6-Phosphate Dehydrogenase (G-6-PD) Deficiency (X-linked)

Front 37

What happens in G6PD deficiency

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RBC membranes are sensitive to oxidants;
inability to neutralize oxidation.

Front 38

How to diagnose enzyme defects

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G-6-Pd is assessed by submitting RBC to oxidative stress
- may be a result of antimalarial drugs, primaquine
----trigger HA after 3 days of therapy
- Other : sulfonamides, nitrofurantoin, fava beans

Front 39

Heinz bodies are seen in

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G6PD HA
- denaturation with precipitates
- also see bite cell formation

Front 40

Pyruvate kinase deficiency

Back 40

(autosomal recessive)
Involving the energy-producing step of the glycolytic pathway, defective
result in extravascular hemolysis in the spleen.

Front 41

RBC microvesiculation is related to

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low ATP concentrations is seen with PK deficiency

Front 42

Diagnosis of HA wrap up: Steps 1 and 2

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First step: identify presence of Hemolysis
Second step: identify the mechanism of hemolysis
intrinsic defect or intracorpuscular
extrinsic defect or extracorpuscular

Front 43

Extrinsic Hemolytic Anemia are typically

Back 43

Non immune mediated
or
Immune Mediate

Front 44

Non immune hemolytic anemia typically classified as

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mechanical hemolysis

Front 45

Non immune hemolytic anemia seen with

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Physical trauma
- Prosthetic heart valves (macroangiopathies)
- HUS, TTP, DIC (microangiopathies)
Schistocytes, fragmented RBCs

Front 46

Microangiopathic are associated with

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microthrombi

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macroangiopathic are associated with

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prosthetic valves

Front 48

Mechanical valves cause hemolysis how?

Back 48

- RBCs hitting the metal
--also see infusion pump generated hemolysis

Front 49

Diagnosis of TTP- thrombotic, thrombocytopenic, purpura

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F - Fever
A - Anemia
T - Thrombocytopenia
R - Renal dysfunction--elevated creatinine
N - Neurologic changes

Front 50

TTP - Thrombotic Thrombocytopenic Purpura what is the modern DX

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Thrombocytopenia
Schistocytes
Elevated LDH
elevation of vWF in circulation

Front 51

what is generally considered the cause of the hemolysis in TTP

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Low platelet count is considered the cause of the hemolysis

Front 52

Treat TTP with

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Plasma exchange

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Non- immune/non-mechanical causes of HA

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Infection (Malaria, Babesia, Streptococcus, H. I., Clostridium Perfringens)
Chemical trauma (medications)
Hypersplenism (increased phagocytosis)

Front 54

Hemolytic Anemia: Infections

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Malaria--africa
Babesiosis---martha's vineyard
Bartonellosis (Oroya fever)
Clostridium Perfringens
***look for travel history

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Hemolytic Anemia: Chemical Exposures

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Strong oxidants - UDMH
Oxidants with G-6-PD deficiency
Snake venom
Lead
Chlorine in hemodialysis fluid
Chloramine in hemodialysis fluid
Arsenic
**stop the exposure

Front 56

Hemolytic Anemia: key associated organ diseases

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Liver Disease
Hypersplenism

Front 57

Extrinsic Hemolytic Anemia can be

Back 57

Non immune mediated
Immune Mediated

Front 58

Transfusion related hemolysis is an

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immune hemolysis

Front 59

Examples of Immune mediated hemolysis

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Transfusion-based immunity
-- ABO incompatibility
-- Delayed transfusion reactions caused by Rh, Kell, Duffy, Kidd, etc
Hemolytic disease of the newborn
Autoimmune hemolytic anemias

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Ultimate test to understand the HA is the

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Coombs Test
- will identify an immune antibody attack of RBC surface

Front 61

Symptoms of immune mediated hemolysis

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fever, hypotension, hemoglobinuria, flank pain, constriction of chest

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Acute hemolytic transfusion reactions, frequency and symptoms:

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1 in 600 to 1/ 25K components
death associated with ABO mismatch
Clinical Findings: pain at site of infusion, chest pain, flank pain, back pain, hypotension,hemoglobinemia, hemoglobinuria, hypotension, acute renal fail, DIC

Front 63

Only need a few ccs of incompatible cells to cause

Back 63

shock, renal failure, death...

Front 64

Acute hemolysis is due to

Back 64

due to complement binding and activation

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in immune mediated hemolysis testing hemosideriuria is obsolete

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but drops and then rises in a few days

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in immune mediated hemolysis hemoglobin will

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rise and fall over a couple days

Front 67

Acute vs delayed hemolytic transfusion reactions

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Acute: Usually ABO antigen mismatch, IgM antibodies, and intravascular hemolysis +/- complement anaphylatoxins leading to shock
Delayed: Minor antigens, IgG antibodies, and extravascular hemolysis.

Front 68

Red cells coated with antibodies are hemolyzed by what cells and where

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- macrophages in the spleen

Front 69

Alloimmune hemolytic anemia.

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(due to allo antibodies)
induced by transfusion, pregnancy

Front 70

Autoimmune hemolytic anemia

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(due to auto antibodies)
inappropriate immune response

Front 71

2 types of HA due to autoantibodies

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- warm reacting at 37 deg
- cold reacting only active at 30 deg or less

Front 72

Warm AIHA at 37 C

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extravascular hemolysis, IgG mediated, through phagocytosis in the spleen
IgG circulating in autoimmune disease (SLE)
Drug induced IHA
methyl-dopa, penicillin, quinidine and salicylates

Front 73

Cold AIHA below 30 C

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intravascular, IgM mediated, complement mediated
associated with infections
(mycoplasma pneumoniae, antibody directed against I-antigen)
Cold agglutinin disease and Raynaud ‘s Phenomenon

Front 74

Acquired membrane defect causing AIHA

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Paroxysmal Cold Hemoglobinuria

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Paroxysmal Cold Hemoglobinuria see

Back 75

IgG antibody directed against P- RBC antigen, binds at cold temperature,
binding complement, intra vascular hemolysis, active at 37 C

Front 76

Hemolytic Disease of the Newborn

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*Mother exposed to fetal RBC antigens which she lacks and to which she forms a humoral immune response (other than ABO Ag)
*Maternal IgG antibodies cross the placenta and hemolyze fetal RBCs
Elevated bilirubin
Fetal anemia
Fetal compensatory extramedullary hematopoiesis

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Mother’s Blood type is: A Rh (+)
Baby’s Blood type is: O Rh (+)
Baby Red blood cells are compatible with Mom?

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Baby’s RBCs are coombs positive
Baby is Jaundiced and anemic (Hct 25%)

Front 78

Hydrops Fetalis & Hemolytic Disease of the Newborn

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Antigen neg mom
Sensitized to antigen pos baby by fetomaternal hemorrhage or previous pregnancy
Makes antibodies
cross the placenta

Front 79

Hydrops Fetalis & Hemolytic Disease of the Newborn Treatments

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Intra-uterine and/or Exchange Transfusion
- Select Rare RBCs ABO Compatible but negative for Antigen which is present on baby’RBCs

Front 80

Hemolytic anemias definition

Back 80

“Decreased levels of erythrocytes circulating in the blood (anemia) because of their increased destruction (hemolysis)”