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PT1 B2 > Lectures 41 and 42 Hemolytic Anemias > Flashcards

Lectures 41 and 42 Hemolytic Anemias Flashcards

1
Q

What is the definition of Hemolytic Anemia? What are characteristic cellular/lab findings?

A

Increased RBC Destruction

Premature Destruction of RBC (anything less than the normal 100-120 days)
Elevated EPO
Increased Hemoglobin degradation products

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2
Q

Intravascular VS Extravascular Hemolysis:

  • What is the difference?
  • what are some differentiating characteristics?
A

Extravascular – Destruction of the RBC outside of the vasculature, such as in the Phagocytes of the Spleen.
Splenomegaly and jaundice

Intravascular – hemolysis in the vasculature due to complement fixation, parasites, or injury
Findings: Hemoglobinemia, Hemoglobunuria, Hemosiderinuria
Jaundice
No splenomegaly

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3
Q

What are some etiologies of Hemolysis?

A

Red Cell Membrane Disorders – Hereditary Spherocytosis

Enzyme Deficiencies: G6P DHG Deficiency

Acquired Genetic Defects: Paroxysmal Nocturnal Hemoglobinuria

Antibody mediate Destruction

Mechanical Hemolysis

Infections: Malaria, Babesia Microti

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4
Q

What are 2 Red Cell Membrane Disorders?

A

Hereditary Spherocytosis

Hereditary Elliptocytosis (not tested)

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5
Q

hereditary Spherocytosis:

  • Pathophsyiology
  • manifestations
A

Mutations in Spectrin and Ankyrin proteins
Leads to defect in binding of lipid bilayer to the cytoskeleton

Low of Membrane integrity; more rigid; loss of biconcave shape

Cannot escape spleen == Splenomegaly (congestions of the cords of Billroth)

Manifestations – Splenomegaly, low level Chronic Hemolytic Anemia, Pigment Gall Stones

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6
Q

hereditary Spherocytosis:
- Diagnosis
Specific Diagnostic Test
- Treatment

A
  • Osmotic Fragility – cells more susceptible to lysis due to hypotonicity

Treat:
Folate
Splenectomy

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7
Q

Enzyme Deficiencies: Glucose 6 Phosphate Dehydrogenase Deficiency: G6PD –

Pathophysiology:

A

XLR
Defective Enzyme of Glycolysis

Episodic Intra and Extra Vascular Hemolysis:
Hemolysis caused by anything that causes oxidant stress

Inclusions in the RBCs
Some Destroyed by the Spleen
Some lose membrane integrity —- spherocytosis

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8
Q

What are some examples of exposures that can lead to increased oxidatant stress leading to episodic hemolysis in G6P DHG Deficiency?

A

Infection – most commonly

Drugs – anti-malarials; sulfa drugs

Foods – Fava beans in the Mediterranean Variant

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9
Q

Acquired Genetic Defect: Paraoxysmal Nocturnal Hemoglobinuria:

  • pathophysiology
A
  • Defect In PIG A enzyme; which makes GPI (a complement regulator)
  • GPI prevents break down of complement regulators (DAF and CD59) (?)
  • Therefore there is unregulated Complement Activity leading to Thrombosis, platelet dysfunction,

5-10% of patients will go on to devleop AML (leukemia)

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10
Q

Paraoxysmal Nocturnal Hemoglobinuria:

- specificic test

A

Flow Cytometry of GPI Linked Proteins that regulate Complement – CD55 (DAF), CD59, C8 binding protein

Sucrose Hemolysis Testing –

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11
Q

Antibody Mediate Destruction: Hemolytic disease of the New Born

  • Pathophysiology -
  • Treatment
A

Rh Antigen Negative Mom becomes sensitized to Rh Antigen Positive Fetus
Exposure either due to Fetomaternal hemorrhage vs Previous Pregnancy

Mom’s antibodies cross the placenta and cause fetal Anemia

Treatment:
Prophylaxis of Rh negative Moms with Rh Positive Fetus with RhoGAM (RhD Ig)

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12
Q

Mechanical Hemolysis:

- etiologies:

A

Abnormal Heart valves,
Microangiopathic Hemolytic Anemias (MAHAs) = DIC, TTP, HUS,

Bypass/Hemodialysis
Burns
Drowning
Marathons

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13
Q

Mechanical Hemolysis: MAHAs – Thrombocytopenic Purpura (TTP)

  • pathophysiology
  • SEAT (what does this acronym stand for?)
  • Treatment

-

A

SEAT - Shistocytes, Elevated LDH, Altered vWF, Thrombocytopenia

Pathophysiology:
Deficiency of ADAMTS 13 – a Metalloprotease which cleaves vWF before activation by shear stress causes platelet aggregation
Defiency leads to – vWF platelet aggregation and microvascular thrombosis
As RBCs navigate small vessels they are cleaved by Fibrin strands — leading to Schistocytes

Treatment: Plasma Exchange –

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14
Q

Infections and Hemolytic Anemia –

- what two infections ?

A

Malaria – parasitic Infection

Babesia Microti –

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15
Q

Differences in presentation and Peripheral blood smear findings between Malaria and Babesia Microti ?

A

malaria – Paroxysmal Fevers
Smear: Intra-RBC Ring forms
Falciprum – Banana shaped gametocyte

Babesia Microti – Extra-RBC Parasites, ring forms
Destruction of parasites is constant
Therefore fever is not paroxysmal

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16
Q

Classifications of Hemoglobin Abnormalities

A

Deficient Globin Synthesis – Thalassemia Syndromes

Hemaglobinopathies: Structurally abnormal Globins – Sickle Cell Disease, Unstable Hemoglobins

17
Q

what globin subunits make up the following hemoglobin types?

  • Embryonic HGB
  • Fetal HGB
  • HGB A-
  • HGB A2
A

Embryonic Hemoglobin - Zeta and Epsilon

Fetal Hemoglobin – Gamma and Alpha

Hemoglobin A – Alpha and Beta

Hemoglobin A2 – Delta and Alpha

18
Q

Thalassemias — Deficient Globin Synthesis

A

Pathophysiology:

Loss of production of either 1 of the 4 alpha chains or 1 of 2 beta genes

19
Q

What is alpha thalassemia?

What are some ethnic groups that have higher incidence of the condition?

A

Missing 1 or 2 of the 4 alpha genes

36% of AA have a mutation in 1 of the alpha genes
RBCs are Low Normal Size
Usually these people are Asymptomtic

4% of AA have 2 Defective Alpha genes (on different chromosomes)
Small RBCs

5% of SE Asians – loss of both alpha globin genes on the same chromosome; loss of A1 and A2 genes

20
Q

What is Alpha Thalassemia Intermedia ?

Describe the pathology

A

Mixed Alpha I and II Thalassemia
3 Mutant Alpha Globin Genes

With only 1 working Alpha Globin Gene, some Alpha/Beta Tetramers can form but there will be excess Beta Chains

Excess Beta Chains form Beta Tetramers = HGB H
Doesn’t bind O2 very well
Precipitates of Hemoglobin –> Heinz Bodies –> Spleen tries to remove –> Spherocytosis –> Splenic Sequestration/Phagocytosis

21
Q

Alpha Thalassemia Major

A

Mutations in all 4 alpha genes
1/1600 SE Asians

Severe Fetal anemia; Hydrops Fetalis; die in utero

only have Tetramers of Beta chains (hemoglobin H)
or Gamma chains (hemoglobin Barts)

22
Q

What are Beta globin only tetramers called?

What are gamma globin only tetramers called?

A

Beta - HGB H

Gamma - Hemoglobin Barts

23
Q

What is Beta thalasemia, in general?

ethnic groups?

A

Partial or full dysfunction of 1 or both of the beta globin genes

Similar geographic/ethnic distribution to alpha thalassemias

24
Q

Beta Thalassemia Minor:

  • What is the genetic profile of the beta genes?
  • pathophysiology?
A

Beta Thalassemia Minor:
Profile – 1 affected Beta Gene vs 2 partially affected Beta Genes

Some Normal Hemoglobin A
Some Excess Alpha Globin Chains

Precipitate –> Heinz bodies –> spherocytosis –> splenic sequestration

25
Q

Beta Thalassemia Intermedia/Major:
Genetic profile?
Pathophysiology? Manifestations, Smear?

A

Genetic Profile – complete absence of both beta globin genes.

Pathophysiology - Beta globin genes are not expressed until infancy. Therefore manifestations only occur after the decline of Fetal Hemoglobin

Manifesations – Skeletal Deformities (of the skull)
Smear - Lots of variation of the RBC; Nucleated RBCs

26
Q

Beta Thalassemia Intermedia/Major:
Treatment?
Side effect of treatment and subsequent management

A

Dependent on Transfusions

Which can lead to Transfusional Iron Overload

Patients need to be on Chelation therapy to bind excess Iron

27
Q

What is the major Hemoglobinopathy ?

Describe the mutation and how this leads to a misshapen RBC

A

Sickle Cell Disease

Beta Globin Mutation
Substitution: Adenine –> thymine,
Amino Acid Mutation: Glutamine —> Valine

The Hydrophobic Valine: allows Deoxy HGB to form strands –> Fibers –> Fasicles –> Leading to sickle shape of the RBC and loss of bi-concave shape

28
Q

Sickle Cell Disease –

- Mechanisms of Damage

A

Vascular Occlusion: Physical Blocking; sickle cells are rigid and get stuck at bifurcations in small vessels

Vascular Adhesions: Damage the Endothelium; adhere to the endothelium; leading to thrombosis and blockage

29
Q

Sickle Cell Disease –

Pathophysiology and Manifestations

A

Chronic Hemolytic Anemia – Sickle cells can only survive for 10 days. The Free HGB Damages Endothelium and Scavenges Nitric Oxide

Vascular occlusion and adhesion leads to infarction:
- Splenic Infarction: Function Asplenia — Susceptibility to encapsulated organisms (Nisseria, H Flu, Pneumococcus)

  • renal Injury – loss of renal concentrating ability; dehydration; more sickling, crisis
  • Bone infarct (bone capillaries are rigid and more easily obstructed)
  • Pulmonary Infarct – can lead to PNA, infection; exacerbating symptoms
  • Brain Infarct:
  • other infarct: hand/food/penile/priapism
30
Q

What Factors increase sickling and therefore risk of sickle cell crisis?

To what organisms are persons with Functional asplenia susceptible?

What virus is classically associated with onset of aplastic crisis ?

A

Exercise, dehydration, low pH,
Cold Temperatures
Infections

Encapsulated Organisms: Pneumococcus, H. Flu, Nisseria

Virus: Parvovirus B19 (erythemia Infectiosum aka cheek slapped rash)

31
Q

What is the most common cause of death in SCD patients?

A

Infection

32
Q

Treatment and Management of Sickle Cell Disease

A

Screen/Rule out/Prevent Infection:

  • Immunizations for Nisseria and Pneumococcus
  • CXR, UA

Hydrations

Transfusion – shown to prevent stroke

Hydroxyurea Treatment: Induce production of fetal HGB (Gamma and Alpha Globin) which is non sickling

33
Q

what is HGB Electrophoresis & Quantification?

what is the profile of persons with sickle cell disease?

What is the profile of persons with sickle cell trait?

A

Gel Electrophoresis to determine presence of abnormal HGB

Sickle Cell patients: Hemoglobin S; No Hemoglobin A

Sickle Cell Trait: Hemoglobin S; + Hemoglobin A

34
Q

which two hemoglobin abnormalities are susceptible to aplastic crisis caused by Parvovirus B19?

A

Beta Thalassemia Major

Sickle Cell Disease

PT1 B2 (18 decks)

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