Hemolytic Anemias Flashcards
(77 cards)
1
Q
What are thalessemias?
A
anemia due to insufficient globin production
2
Q
What populations are thalassemias most common in?
A
- Mediterranean
- African
- Asian
3
Q
What are the types and subtypes of thalessemia?
A
α-thalassemia
- silent
- α-thalassemia trait
- HgH disease
- hydrops fetalis
β-thalassemia
- β-thalassemia major
- β-thalassemia intermedia
- β-thalassemia minor
4
Q
What is the mechanism of α-thalassemias?
A
There are four total α genes located in pairs on chromosome 16
- deletion of one or more of the α genes
- the more copies deleted, the more severe the symptoms
5
Q
What is silent carrier α-thalassemia?
(symptoms and course)
A
- deletion of one α gene
- asymptomatic
6
Q
What would expected lab changes be in silent carrier α-thalaseemia?
A
- miniscule reduciton in α-chain (electrophoresis)
- normal hemoglobin structure (electrophoresis)
- mild microcytosis
7
Q
What is α-thalassemia trait?
(symptoms and course)
A
- deletion of two α genes
- asymptomatic
- mild anemia
8
Q
What would expected lab changes be in α-thalaseemia trait?
A
- mild reduciton in α-chain (electrophoresis)
- normal hemoglobin structures, HbA/HbA2 (electrophoresis)
- mild hypochromic, microcytic anemia
9
Q
What is HgH disease?
(symptoms and course)
A
-deletion of three α genes
-moderately severe anemia
- formation of β-globin tetramers (HgH)
- high O2 affinity -> hypoxia
- precipitates and forms inclusions (hemolysis in the spleen)
**most common in Asian populations
10
Q
What would expected lab changes be in HgH disease?
A
- major reduciton in α-chain (electrophoresis)
- abnormal hemoglobin structures, HgH (electrophoresis)
- moderately severe hypochromic, microcytic anemia
11
Q
What subtypes of α-thalassemia trait are there?
(what is the significance?)
A
both clinically identical in the individuals, difference is in children of the individual
Cis (Asians):
- deletions are on same chormosome
- increased risk of HgH in children
Trans (Africans):
- deletions are on different chromosomes
- less risk of HgH in children
12
Q
What is thalassemic hydrops fetalis?
(symptoms and course)
A
- deletion of all four α genes
- lethal in utero
- formation of γ-globin tetramers (hemoglobin Barts)
- high O2 affinity -> hypoxia
13
Q
What would expected lab changes be in thalassemic hydrops fetalis?
A
- absenece of α-chain (electrophoresis)
- abnormal hemoglobin structures, Hg Barts (electrophoresis)
14
Q
What is the mechanism of β-thalassemias?
A
There are two total β genes located on chromosome 11
-mutations resulting no production (β0) or decreased production (β+)
15
Q
What is β-thalassemia minor?
(symptoms and course)
A
one normal gene, one defective gene (β/β+) or (β/β0)
-asymptomatic
16
Q
What would expected lab changes be in β-thalassemia minor?
A
- mildly decreased HbA (electrophoresis)
- mildly increased HbA2 (electrophoresis) (useful in differentiating from iron deficiecny anemia)
- mild hypochromic, microcytic anemia
- target cells
17
Q
What is β-thalassemia intermedia?
(symptoms and course)
A
variable but with at least one partially effective gene (β/β+, β/β0, β+/β+, β+/β0)
- onset shortly after birth (protection by HgF)
- moderately severe anemia, not requiring blood transfusion
18
Q
What would expected lab changes be in β-thalassemia intermedia?
A
- decreased HbA (electrophoresis)
- increased HbA<strong>2</strong> (electrophoresis)
- moderately severe hypochromic, microcytic anemia
19
Q
What is β-thalassemia major?
(symptoms and course)
A
- no effective gene (β0/β0)
- onset shortly after birth (protection by HgF)
- severe anemia, requiring blood transfusions
- secondary hemochromatosis
- hematopoiesis in the skull
- “crew cut” x-ray
- “chipmunk facies”
- extramedullary hematopoiesis
- hepatosplenomegaly
20
Q
What would expected lab changes be in β-thalassemia major?
A
- increased HbF (electrophoresis)
- no/minimal HbA (electrophoresis)
- normal to low HbA2 (electrophoresis)
- severe hypochromic, microcytic anemia
- target cells
- nucleated RBCs
21
Q
What is pernicious anemia?
A
autoimmune gastritis resulting in B12 deficiency
22
Q
What is the common presenation of pernicious anemia?
A
- older adults (median age 60); uncommon under 30
- more common in Scandanavian caucasians; present in all races
- insidious, severe megaloblastic anemia
- glossitis
23
Q
What would expected lab changes be in pernicious anemia?
A
- decreased B12
- increased homocystiene (THF and B12 used in metabolism)
- increased methylmalonic acid (B12 used in metabolism)
- macrocytic anemia
- hypersegmented PMNs
24
Q
What is the mechanism of pernicious anemia?
A
-autoimmune T-cell destruction of gastric parietal cells (produce intrinsic factor)
- intrinsic factor is required for absorption of B12 in the ileum
- B12 is used in DNA precursor synthesis
- decreased DNA synthesis is direct cause of megaloblastic anemia
25
What are possible **complications** with **pernicious anemia**?
- damage to spinal cord (B12 needed in mylein production)
- **decreased sensation**
- **spastic paresis**
- risk of **gastric carcinoma**
26
What are **additional causes of B12 deficiency** that lead to **megaloblastic anemia**?
- **pancreatic insufficiency** (can't remove salivary haptocorrin)
- **fish tapeworm**
- **gastrectomy** (loss of intrensic factor/acid/pepsin)
- achlorhydria (loss of acid, pepsin can't release B12 from food)
- pregnancy (increased use)
- disseminated cancer (increased use)
- **vegans**
27
What is **folate deficiency anemia**?
**macrocytic/megaloblastic** anemia due to **folate deficiency**
28
What is the common **presenation** of **folate deficiency anemia**?
**eldery or alcoholics**
-relatively rapid (months), **severe megaloblastic anemia**
**-glossitis**
29
What are common **causes** of **folate deficiency**?
* inadequate diet
* **alcoholism**
* **elderly**
* increased requirement
* pregnancy
* cancer/hyperactive hematopoiesis
* methotrexate (folate antagonist)
30
What would expected **lab changes** be in **folate deficiency anemia**?
- decreased folate
- increased **homocystiene** (THF and B12 used in metabolism)
- **normal methylmalonic acid** (B12 used in metabolism)
- **macrocytic anemia**
- **hypersegmented PMNs**
31
What is the **mechanism** of **folate deficiency anemia**?
- **folate** is used in **DNA precursor synthesis**
- decreased DNA synthesis is **direct cause of megaloblastic anemia**
32
How are **folate** and **B12** related anemias best **differentiated**?
(**labs, onset, symptoms**)
Both are megaloblastic/macrocytic anemias, display glossitis, and have **elevated homocystiene**
- folate deficiency will have normal methylmalonic acid while **B12** will have **elevated methylmalonic acid** (B12 is used in metabolism)
- methylmalonic acid derivatives are used in making **myelin** so **B12 deficiencies** may develop **demylination symptoms**, folate will not
**B12** will **onset slowly** (high stores in liver), folate will onset more rapidly
**B12** has **neurologic symptoms**, folate has minimal (as above)
33
Why is it important to properly differentiate folate deficiency from B12 deficiency?
Treating B12 deficiency with folate will corrects the anemia but worsen neurologic symptoms.
34
What is **hereditary spherocytosis**?
- defect in **cytoskeletal tethering** proteins (**ankyrin, spectrin, band 3**)
- loss of **membrane blebs** resulitng; disc shape **-\>** spherical shape (**spherocytes**)
- spherocytes traverse cicrulation fine **except spleen where they are destroyed -\> anemia**
**RBC life span** 120 days -\> **10-20 days**
35
What would expected **lab changes** be in **hereditary spherocytosis**?
- **increased RDW** (get smaller over time as more blebs lost)
- **increased MCHC** (same amount of hemoglobin in smaller volume)
- **increased unconjugated bilirubin** (extravascular hemolysis)
- **spherocytes**
36
What is the common **presentation** of **hereditary spherocytosis**?
- **northern European descent**
- anemia
37
What is used to **diagnose** **hereditary spherocytosis**?
**_Osmotic fragility test_**
- normal RBCs will not lyse when exposed to a hypotonic solution
- **spherocytes** will **lyse** in **hypotonic solution** due to increased fragility
38
What are possible **complications** with **hereditary spherocytosis**?
- **gallstones** (bilirubin in extravascular hemolysis)
- **aplastic anemia** with **parvovirus B19**
39
What is the **treatment** for **hereditary spherocytosis**?
What occurs as a result?
**Splenectomy** (only place where spherocytes are lysed)
- \> **anemia resolves**
- \> increased risk of **encapsulated bacterial infections**
- \>**Howell-Jolly bodies** appear in blood (RBCs with nuclear material that are normally cleared by the spleen)
40
What is **sickle cell anemia**?
-homozygous **recessive** mutation of **β-globin** ( hydrophilic **glutamic acid** -\> hydrophobic **valine**) producing **HgS** instead of HgA
41
What would expected **lab changes** be in **sickle cell anemia**?
- **\>90% HbS**
- **increased HbF**
- **no HbA**
**-moderately severe anemia**
-**sickle cells**
**-**target cells and Howell-Jolly bodies (hyposplenism)
- increased **bilirubin**
- decreased haptoglobin
42
What is the **mechanism** of **sickle cell anemia**?
* **deoxygenated** HgS reversibly **polymerizes into needle-like structures**, cells take abnormal **sickle shape** when this occurs
* repeated sickling **decreased membrane integrity** -\> **hemolytic anemia**
* **hemolysis in the spleen** (extravascular - primary)
* hemolysis in vasculature (intravascular)
* sickled cells may **occlude microvasculature**
**protected by HbF** **early in life**
43
What is the common **presentation** of **sickle cell anemia**?
- infants a few months old (HgF protects initially)
- **black**
- **moderately severe anemia**
- **dactylitis** (in children)
- **"crew cut"** head X-ray and **"chipmunk facies"** (expansion of hematopoiesis)
- **pain crisis**
- **hepatomegaly** (extramedullary hematopoiesis)
44
What are potential **complications** of **sickle cell anemia**?
Microvascular occlusions
* **Dactylitis** (swollen hands and feet) (most common **presenting symptom** in **infants**)
* **autosplenectomy** (small, fibrotic spleen) due to repeated occlusions
* increased risk of infection with **encapsulated bacteria** (**H. infulenza** most common cause of \*\***death in children\*\***)
* **Howell-Jolly bodies**
* **acute chest syndrome**: pulmonary occlusions (precipitated by pneumonia)
* **chest pain, SOB, infiltrates**
* most common cause of \*\***death in adults\*\***
* ****renal necrosis -\> **hematuria and protenuria**
* **pain crisis**: severe pain caused by occlusions anywhere (including above)
* **stroke**
* **blindness**
**Aplastic crisis** (**parvovirus B19**)
Gallstones (increased bilirubin)
45
What conditions **precipitate** sickling in **sickle cell anemia**?
**Deoxygenation** of HbS
- **hypoxia**
- **dehydration**
- **acidosis**
46
What is the **treatment** for **sickle cell anemia**?
**hydroxyurea** -\> increased HbF
47
What is **sickle cell trait**?
- **only one** mutated β-globin gene ( hydrophilic glutamic acid -\> hydrophobic valine)
- **\<50% HbS**
48
What would expected **lab changes** be in **sickle cell trait**?
- **\>50% HbA**
- **\<50% HbS**
- **no HbF**
- no anemia
- no sickle cells
- **possible hematuria**
49
What is the common **presentation** of **sickle cell trait**?
**-black**
- **asymptomatic**
- **no anemia**
- hematuria
50
What is the **mechanism** of **sickle cell trait**?
- RBCs with **\<50% HbS** **do not sickle** **except in the renal medulla** (very hypoxic)
- occulusions lead to **hematuria**
51
How can sickle cells be identified in a lab when they aren't currenlty sickled?
- **metabisulfite** will cause all cells with HbS to **sickle, regardless of %**
- identifies **both** sickle cell **disease and traits**
52
What is **hemoglobin C disease**?
-**homozygous recessive** mutation of **β-globin** (**glutamic acid -\> lysine**) producing **HgC** instead of HgA
(ly"C'ine)
53
What is the common **presentation** of **hemoglobin C disease**?
- **black**
- **asymptomatic**
- **mild anemia**
- splenomegaly
- jaundice
54
What would expected **lab changes** be in **hemoglobin C disease**?
- **HbC crystals** in blood
- mild anemia
- increased bilirubin
55
What is **paroxysmal nocturnal hemoglobinuria** (PNH)?
**aquired** mutation in **myeloid stem cells** resulting in loss of GPI resulting in susceptibility of myeloid derived cells (**RBCs, WBCs, and platelets**) to **intravascular** **lysis via complement**
**-mild to moderate anemia**
56
What would expected **lab changes** be in **paroxysmal nocturnal hemoglobinuria**?
flow cytometry shows **no CD55 or CD59**
- hemoglobinemia (after episode)
- hemoglobinuria (after episode)
- hemosiderinuria (delayed)
57
What is the common **presentation** of **paroxysmal nocturnal hemoglobinuria**?
**occasional hematuria** in the **after sleeping**
58
What is the **mechanism** of **paroxysmal nocturnal hemoglobinuria**?
- GPI is used as an anchor for membrane proteins such as DAG (CD55)
- DAG serves to prevent cells in the blood from being lysed by complement
- **loss of GPI** -\> **loss of DAG** -\> **susceptibility to complement mediated lysis**
- **complement** is **activated while sleeping** due to **mild hypoxemia** from shallow breating -\> **RBCs lyse over night** -\> **hemoglobin in urine** the next **morning**
59
What is **G6PD deficiency anemia**?
**X-linked recessive** disorder **reducing half-life** of **G6PD**
-mild to marked **intravascular** anemia
60
What would expected **lab changes** be in **G6PD deficiency anemia**?
after episodes:
- **anemia**
- **hemoglobinemia**
- **hemoglobinuria**
61
What is the common **presentation** of **G6PD deficiency anemia**?
**-African** or **Mediterranean** descent (worse in Mediterranean)
- **intermitent** **anemia** (following exposure to oxidative stress)
- back pain
62
What is the **mechanism** of **G6PD deficiency anemia**?
- **G6PD** is used to **regenerate NADPH**
- NADPH **reduces other substances**, including ROS such as **H2O2**
- RBCs are unable to make new proteins (lack of nucleous)
- normal G6PD outlasts a RBCs life span (120 days)
- **G6PD deficiency varients** have **shorther half-lifes** leaving **older RBCs susceptible** to damage from **ROS**
- periods of **increased oxidative stress** cause **intravascular hemolysis**of **older RBCs with insufficient G6PD**
**-Hgb preciptates** as **_Heinz bodies_**
63
What are the different **variants** of **G6PD deficiency**?
What is their **significance**?
**African** variant:
- less reduced half-life
- mild anemia
**Mediterranean** variant:
-**more reduced half-life**
**-marked anemia**
64
What **screening test** is used to confirm **G6PD deficiency anemia**?
Heinz preparation
- special **stain** that **shows precipitated Hgb** from G6PD deficiency, **Heinz bodies**, that are otherwise unseen
- **\*\*must be performed weeks after an episode** as during an episode cells old enough to have Heinz bodies have already been lysed
65
What is **immune hemolytic anemia**?
IgG or IgM mediated destruction of RBCs
66
What are the **types** of **immune hemolytic anemia**?
- warm agglutinin (IgG)
- cold agglutinin (IgM)
- cold hemolysin (IgG)
67
What is **warm agglutinin anemia**?
What conditions is it **assocaited** with?
**-IgG** mediated **extravascular hemolysis** of RBCs
-occurs at **warm** (body) **temperature**
associated with:
- **SLE**
- **CLL**
- drugs (**penecillin, cephalosporins, methyldopa**)
68
What is the **mechanism** of **warm agglutinin anemia**?
**Extravascular hemolysis**
- **IgG** binds RBCs in warm core blood
- **portions** of IgG bound membrane is **phagocytosed in spleen** -\> **spherocytes**
- spleen removes spherocytes
IgG is either **autoreactive to RBCs** or binds **membrane bound drug**
69
What is **cold agglutinin anemia**?
What conditions is it assocaited with?
- **IgM** mediated **intravascular** hemolysis of RBCs
- occurs at **colder temperatures** (seen in **extremities**)
associated with:
- Mycoplasma pneumoniae
- mononucleosis
70
What is the **mechanism** of **cold agglutinin anemia**?
**Intravascular** hemolysis
- **IgM** binds RBCs in cold blood of extremities
- IgM activates compliment causing some hemolysis
when RBC leaves extremity and warms up, IgM falls off and compliment is no longer activated -\> very mild anemia
71
What is cold hemolysin anemia?
What conditions is it assocaited with?
- **IgG** mediated intravascular hemolysis of RBCs
- occurs at **colder temperatures** (seen in extremities)
children following viral illness
72
What are the main differences between warm and cold agglutinin anemia?
Warn:
- more common
- **IgG** -\> **spleen** -\> **extravascular** hemolysis
- active in **warm, central blood**
- **idopathic or drug induced**
- more severe (can be active more)
Cold:
- less common
- **IgM** -\> **complement** -\> **intravascular** hemolysis
- associated with **certain infections**
- active in **cold extremities**
- very mild anemia
73
What **test** is used to identify **immune hemolytic anemia**?
_Coombs test_
Direct:
- detects **pressence of RBCs coated with Ig or complement**
- tested RBCs w/ added Ab that will bind Fc regions or complement if they are bound to RBC
Indirect:
- detects **pressence of Ab capable of binding RBCs** and identifying target and at what temp
- tested serum added special RBCs with known surface markers
74
What is **microangioplastic hemolytic anemia**?
What conditions is it **associated** with?
RBCs are destroyed by abnormal vasculature (normally thrombi)
- **TTP** (thrombotic thrombocytopenic purpura)
- **HUS** (hemolytic uremic syndrome)
- **DIC** (disseminated intravascular coagulation)
- **HEELP** (hemolysis, elevated liver enzymes, and low platelets)
- **stenosis**
- **mechanical heart valves**
75
What **histological feature** would you expect to see in **microangiopathic hemolytic anemia**?
**Schistocytes**: fragmented RBCs from sheer stress
76
How does **malaria** relate to **anemia**?
Malaria is caused by the ***Plasmodium*** family of protozoa.
**Part** of their **lifecycle occurs in RBCs** and results in **intravascular hemolysis** when they emerge.
77
What **blood disorders** are thought to be **protective for malaria**, hence they have an increased prevalence in regions with malaria?
- sickle cell anemia (African)
- thalassemias (Mediterranean, African, Middle Eastern, and Asian)
- G6PD deficiency (African and Mediterranean)
