Anemia II - Krafts Flashcards
1
Q
What hemoglobinopathy is the most important?
A
Sickle cell
2
Q
What happens to sickle cells in the circulation?
A
- Hemolysis (fragile)
- Vaso-occlusion (get stuck in tiny blood vessels)
- Aggregate and polymerize on deoxygenation
3
Q
What is wrong with the hemoglobin in all Hemoglobinopathies?
A
- Qualitative hemoglobin abnormality
- change in quality
- Structurally abnormal hemoglobin
- often one amino acid away from normal
- usually change in beta-chain
4
Q
What is the best lab test to diagnose Hemoglobinopathies?
A
Hemoglobin Electrophoresis
5
Q
What are the clinical features of Sickle Cell Anemia?
A
- Eight percent of blacks in US are heterozygous (heterozygosity is called sickle cell trait)
- Severity of disease is variable
- Chronic hemolysis (Hb from 6-10)
- Vaso-occlusive disease (acute crisis caused by infection, hypoxia, etc.)
- Increased infections leading to AUTOSPLENECTOMY (recurrent hemorrhage and fibrosis)
6
Q
What five morphological features are present with a Sickle Cell Anemia patient in the “Post-splenectomy blood picture”?
A
- Nucleated RBCs
- Target red cells
- Howell-Jolly bodies (cluster of DNA inside RBC)
- Pappenheimer bodies (RBCs with abnormal granules)
- Slightly increased platelet count (kicked out of spleen)
7
Q
What is the treament for Sicke Cell Anemia?
A
- Prevent triggers (infections, fever, dehydration)
- keep patient well oxygenated
- Vaccinate against encapsulated bugs (especially after they lose their spleen)
- Blood transfusions in severe cases
- Bone marrow transplantation is last resort
8
Q
What is wrong with the hemoglobin in Thalassemia?
A
- Quantitative defect in hemoglobin
- alpha-thal: deletion of alpha chain genes
- 4 genes = 4 chances to mess it up
- results in decreased amount of alpha chains
- beta-thal: defective beta chain genes
- 2 genes = only 2 chances to ruin it
- results in decreased amount of beta chains
- alpha-thal: deletion of alpha chain genes
9
Q
How do the genes in Beta-thalassemia relate to the severity of the defect?
A
- Beta gene: normal gene
- Beta+ gene: produces some Beta chains
- Beta0 gene: produces no Beta chains
- Beta-thalassemia minor (asymptomatic)
- Beta0/Beta OR Beta+/Beta
- Beta-thalassemia intermedia (less severe)
- Beta0/Beta OR Beta+/Beta+
- Beta-thalasemia major (severe)
- Beta0/Beta0 OR Beta0/Beta+
10
Q
How do the genes in Alpha-Thalassemia compare to the severity of the disease?
A
- Problem: alpha-chain genes are absent
- Gene combinations:
- -α/αα = silent (still have 3)
- –/αα OR -α/-α = α-thal trait (Sx variable)
- –/-α = HbH disease (pretty severe)
- –/– = Hydrops fetalis (incompatable with life)
11
Q
What causes the anemia in thalassemia?
A
- α-thalassemia
- not enough α-chains
- see excess unpaired beta, gamma, or delta chains
- Beta-thalassemia
- not enough beta-chains
- excess unpaired α-chains
12
Q
What are the morphologic features of blood in thalassemia?
A
- Hypochromic, microcytic anemia
- Often has minimal decreased anisocytosis (size) and poikilocytosis (shape)
- Target cells
- Basophilic stippling (blue dots in red cells)
13
Q
How can you tell the difference morphologically in Thalassemia and Iron Deficiency Anemia?
A
- IDA
- fair amount of anisocytosis (size variety → increased RDW)
- decreased RBC
- Thalassemia
- minimal amount of anisocytosis (normal/decreased RDW)
- increased RBC
14
Q
What ethnic groups is alpha thalassemia most prevalent in?
A
Asians, blacks
15
Q
What ethnic groups is beta thalassemia most prevalent in?
A
Mediterraneans, Blacks, Asians
16
Q
When does G6PD appear?
A
- after exposure to certain oxidizing agents, like fava beans, or certain medications
- Lack of or decreased G6PD → peroxides → cell lysis
17
Q
Why is G6PD an important enzyme in the body?
A
- It catalyzes the initial step in the pentose phosphate pathway of glycolysis.
- Need G6PD to reduce NADP to NADPH, which in turn keeps glutathione in the reduced state
- reduced glutathione detoxifies hydrogen peroxide and other organic peroxides
18
Q
Why do G6PD-deficient red cells die?
A
- They can’t reduce free radicals (“nasties”)
- Free radicals attack hemoglobin bonds
- Heme breaks away from globin
- Globin denatures, then sticks to red cell membrane → form Heinz body
- Spleen bites out Heinz bodies
19
Q
What areas have the highest incidence of G6PD Deficiency?
A
Areas where malaria is epidemic!
(It may confer a protective advantage against malaria because G6PD-deficient red cells lack the ribose derivatives bugs need to grow. )
20
Q
What is the clinical presentation of G6PD Deficiency?
A
- X-linked
- most males have full disease expression
- heterozygous females are clinically normal
- 10% of black men in US have gene
- Episodic hemolysis
- may present with jaundice from hemolysis
- Spontaneous resolution (new cells better able to handle oxidants)
21
Q
What does the blood morphology in G6PD Deficiency look like?
A
- Without exposure to oxidants, no anemia
- After exposure, get acute hemolysis
- Bite cells, fragments
- Heinz bodies
22
Q
What is the mechanism underlying Microangiopathic Hemolytic Anemia?
A
- red cells are ripped apart by physical trauma
- either fibrin strands snag them or mechanical devices bash them
23
Q
What is the most important thing to consider in Microangiopathic Hemolytic Anemia?
A
- Find out why!
- underlying pathology it may signify:
- artificial heart valve/vessel abnormalities
- disseminated intravascular coagulation (widespread clotting and bleeding)
- thrombotic thrombocytopenia purpura (enzyme deficiency, renal failure, fever, CNS dysfunction)
- hemolytic-uremic syndrome (complication of E.coli infection)
- malignant hypertension
- SLE
- underlying pathology it may signify:
24
Q
How do fragmented cells form in Microangiopathic Hemolytic Anemia?
A
- Get caught on fibrin strand in microcirculation
- Cell is ripped in two
- Larger part becomes helmet cell
- Smaller part becomes a microspherocyte
- Fragments of rip = Schistocytes
25
How can you tell the difference between Acute vs. Chronic Anemia of Blood Loss?
* Acute:
* traumatic
* hemoglobin normal at first (recheck after fluid resuscitation)
* after 2-3 days see reticulocytes
* Chronic:
* causes iron deficiency anemia (hypochromic, microcytic)
26
What three groups of diseases can cause Anemia of Chronic Disease?
* **Infections** (PID, meningitis, chronic UTI)
* **Inflammation** (RA, SLE)
* **Malignancy** (leukemia, lymphoma, MM)
27
When does Anemia of Chronic Disease Develop?
Anemia develops during the first two months of the chronic disease, and doesn't progress thereafter.
28
What is disturbed in Anemia of Chronic Disease? Why?
* **Iron metabolism is disturbed** (iron doesn't get into normoblasts)
* Mucosal cells seem to absorb iron okay, but don't release it well into plasma.
* Can't get iron into hemoglobin
* Hepcidin over-expressed, over-produced
* Shortened RBC life-span
* Impaired marrow response to anemia
29
How can you tell the difference between Anemia of Chronic Disease and Iron Deficiency Anemia?
* IDA:
* low serum iron
* increased TIBC
* low ferritin
* low marrow storage iron
* hypochromic, microcytic
* ACD
* low serum iron
* _low/normal TIBC_
* _high ferritin_
* _high marrow storage iron_
* _normochromic, normocytic anemia with minimal anisocytosis and poikilocytosis_
30
Why is anemia present in end-stage renal failure?
Lack erythropoietin:
Kidneys make most of **erythropoietin**
(hormone that stimulates red cell growth)
31
What type of red cells do you see in Anemia of Renal Disease?
* normocytic, normochromic anemia with minimal anisopoikilocytosis
* The only really unique finding is the occasional presence of **echinocytes**, or "burr" cells, which are red cells with a bunch of short, spiky surface projections.
32
How do you manage Anemia of renal disease?
* If mild, need not treat
* If severe, replace erythropoietin
33
Why is anemia frequent in liver disease?
* shortened red blood cell survival
* impaired bone marrow response typically seen in patients with chronic liver disease
* alcoholic liver disease- folate deficiency (which leads to megaloblastic anemia)
* hemorrhage from upper GI varices or hemorrhoids (which leads to iron deficiency anemia)
* Pure, "uncomplicated" anemia (without the above factors) is actually uncommon.
34
Why do red blood cells not live very long in patients with liver disease?
* congestive splenomegaly that accompanies most cases
* ethanol inhibits erythropoiesis (and the cause of many cases of chronic liver disease is alcoholism)
* small but significant amount of erythropoietin secreted by the liver is diminished
35
What morphologic features are seen in blood with "uncomplicated" Anemia of Liver Disease?
* Mild anemia
* usually normocytic (sometimes macrocytic)
* Poikilocytosis (weird shape)
* target cells
* acanthocytes (spiky surface projections)
36
What are the "complicated" cases of Anemia of Liver Disease?
* Megaloblastosis (from folate deficiency)
* Microcytosis (from iron deficiency)
* 3/4 of patient's with liver disease are anemic
* most cases are "complicated"
* alcohol abusers may get hemolytic episodes that resolve with withdrawal of alcohol
37
What is the clinical presentation of Aplastic Anemia?
* Pallor, dizziness, fatigue (anemia)
* Recurrent infection (leukopenia)
* Bleeding, bruising (thrombocytopenia
* Pancytopenia = all cell lines are down
38
What are the causes of Aplastic Anemia?
* **Idiopathic** (most cases)
* Pregnancy
* Drugs (chemo)
* Viruses
* Fanconi anemia
* hereditary disease characterized by skeletal abnormalities, chromosomal instability, pancytopenia and increased risk of leukemia.
39
What are the blood morphologies seen in Aplastic Anemia?
* Blood = empty
* large spaces between cells on blood smear
* Bone marrow = empty (mostly fat cells)
* little/no hematopoietic precursors in bone marrow
40
What are the treatment options for Aplastic Anemia?
* Avoid further exposure (if known causative agent)
* Give blood products
* Drugs: G-CSF, Prednisone, ATG
* Bone marrow transplant as last resort
* 3-year survival: 70%
41
What is a Heinz body made of?
Denatured globin chains
42
Malignancy, obstetric complications, sepsis and trauma can all cause what findings on a blood smear?
Schistocytes
43
Why are the red cells in sickle cell disease more susceptible to hemolysis?
They possess an abnormal hemoglobin which polymerized upon deoxygenation.
