Hematology Flashcards
1
Q
What are the most common complications of lead poisoning in infants and children?
A
- Neurotoxicity can lead to long standing behavioral problems and developmental delay or regression.
- Hemolytic anemia
2
Q
How does anemia result from lead poisoning?
A
- There is inhibition of ferrochelatase and aminolevulinic acid dehydratase in heme synthesis pathway.
- Protoporphyrin IX cannot combine with Fe2+ to form heme due to ferrochetolase inhibition.
- Instead it incorporates zinc ion and leads to elevated zinc protoporphyrin levels.
- ALA levels are also increased and accumulated.
3
Q
Who is at risk for lead poisoning?
A
- Impoverished children residing in deteriorating urban houses built before 1978.
- Young children are particularly susceptible via inhalation and ingestion of lead based paint dust or chips from crawling and mouthing behaviors.
4
Q
What is the cause of paroxysmal nocturnal hemoglobinuria (PNH)?
A
- An acquired mutation of the phosphatidylinositol glycan class A (PIGA) gene within a clonal population of multipotent hematopoietic stem cells.
- Gene is involved in the synthesis of glycosylphosphatidylinositol (GPI) anchor, necessary for the attachment of CD55 and CD59.
5
Q
What does CD55 and CD59 do?
A
Help inactivate complement and prevent the membrane attack complex from forming on normal cells.
6
Q
What is von Willebrand Disease? How is it inherited? What does it cause and lead to? Which factor is decreased? What happens to pTT?
A
- Most common inherited bleeding disorder
- Autosomal dominant with variable penetrance
- Causes coagulation pathway abnormalities due to decreased factor VIII activity (prolonged pTT)
- Leads to impaired platelet function (prolonged bleeding time)
7
Q
How does Acute Hemolytic Transfusion Reaction present?
A
- Presents with fever, chills, hypotension, dyspnea, chest and back pain and hemoglobinuria (red/brown urine).
- May develop DIC and ARF
- Occurs within minutes to hours after blood transfusion
- Due to ABO incompatibility between donor and recipient
8
Q
What is the mechanism behind an Acute Hemolytic Transfusion Reaction?
A
- Antibody-mediated (type II) hypersensitivity reaction
- Anti-ABO antibodies, mainly IgM in the recipient bind to corresponding antigens and transfused donor erythrocytes leading to complement activation
- Anaphylatoxins (C3a and C5a) cause vasodilation and symptoms of shock
- Formation of MAC (C5b-C9) leads to compliment-mediated cell lysis
9
Q
What is protamine used for and what is its action?
A
- Used for reversal of heparin
- Binds and chemically inactivates heparin
10
Q
What is fresh frozen plasma used for and what is its action?
A
- Rapidly reverses warfarin induced anticoagulation
- Used for life threatening bleeding
- Contains all the coagulation factors
11
Q
What is Vitamin K?
What is it used for?
What is its action and on which factors?
A
- Procoagulant
- Can reverse warfarin, however it takes time to for the clotting factors to resynthesize
- Vitamin K epoxide reductase is inhibited by warfarin
- Causes g-carboxylation of glutamic acid residues of clotting factors II, VII, IX and X, protein C and S
- Neonates lack enteric bacteria which produce vitamin K
12
Q
What is Warfarin?
What is it used for?
What is its action and on which factors?
What does it cause?
A
- Most common long term anticoagulation agent
- Used in venous thrombosis and pulmonary thromboembolism
- Inhibits vitamin K dependent g-carboxylation of the glutamic acid residues of clotting factors II, VII, IX and X
- Causes production of dysfunctional coagulation proteins
13
Q
Disseminated Intravascular Coagulation in Pregnancy
What causes it?
How does it present?
A
- Due to release of tissue factor (thromboplastin) from an injured placenta (placental abruption) into the maternal circulation
- Presents with bleeding from incision sites, intravenous line sites and mucosal surfaces due to rapid consumption of clotting factors and platelets
- May present with vaginal bleeding, uterine tenderness, retroplacental hematoma and fetal demise
- Placental abruption may result from severe hypertension
14
Q
When is Clopidogrel used?
A
- When a patient has asthma allergy
- It irreversibly blocks P2Y12 component of ADP receptors on the platelet surface and prevents platelet aggregation
- As effective as aspirin for cardiovascular events in patients with coronary artery disease
- Ex patient with stable angina with allergy to aspirin
15
Q
What is Cilostazol used for?
A
A phosphodiesterase inhibitor used in patients with peripheral vascular disease
16
Q
What is the cause of hereditary spherocytosis?
A
- Defective binding of the red cell cytoskeleton to the plasma membrane
- Due to mutation involving ankyrin, band 3 or spectrin proteins
17
Q
What causes acquired spherocytosis?
A
- Usually caused by autoimmune hemolytic anemia
18
Q
What do red blood cells look like in spherocytosis?
A
- They are round, smaller and have more intensely staining cytoplasm due to membrane loss and red cell dehydration
- Have elevated Mean Corpuscular Hemoglobin Concentration
19
Q
What are the serum findings in hemolysis?
A
- Elevated lactate dehydrogenase
- Reticulocytosis
- Decreased Haptoglobin
20
Q
What are the major clinical manifestations of Factor V laiden?
A
- Deep vein thrombosis
- Cerebral vein thrombosis
- Recurrent pregnancy loss
- 50% of patients with untreated DVTs will develop pulmonary embolism
21
Q
What is Factor V laiden?
What risk does it lead to?
What does cause?
A
- Most common cause of inherited thrombophilia
- Heterozygote prevalence of 1-9% in caucasians
- 5-10 x the risk of developing thrombosis
- Homozygotes have 50-100X the risk of developing thrombosis
- Increased thrombin production due to decreased activated protein C
22
Q
What does protein C do?
A
- It restricts clot formation
- Inactivates factors Va and VIIIa
- Factor Va is a cofactor for the conversion of prothrombin to thrombin
23
Q
Which is a cofactor in the conversion of prothrombin to thrombin?
A
Factor Va
24
Q
Persistent circulating levels of factor Va lead to what?
A
- Increased thrombin production
- Since factor Va converts prothrombin to thrombin
25
The presence of erythroid precursor cells in organs such as the liver and spleen is a sign of?
- Extra-medullary hematopoiesis
- Characterized by erythropoietin-stimulated, hyperplastic marrow cell invasion of extramedullary organs
- Caused by chronic hemolytic anemias such as Beta-thalassemia
26
What is the action of von Williebrand factor?
| Where is it synthesized?
- Binds glycoprotein Ib receptors on platelets after endothelial damage and carries factor VIII prolonging its half-life
- Synthesized on endothelial cells and megakaryocytes
27
What does von Williebrand deficiency lead to?
- Decreased platelet adhesion and aggregation causes easy bruising and mucocutaneous bleeding
- Patients may complain of gingival bleeding or heavy menses
- Also leads to functional deficiency of factor VIII
- Results in prolonged bleeding time after minor surgeries
- PTT may be normal or prolonged
28
What is the treatment for menorrhagia caused by von Williebrand disease?
- Combined oral contraceptives first line
| - Desmopressin can also be used which stimulates vWF release from endothelium
29
What are platelets?
Where do they originate?
How long do they last?
What does a deficiency in them lead to?
- AKA thrombocytes that are responsible for bleeding from the skin and mucosal surfaces.
- Originate from the bone marrow from megaryocytes
- They last 4-7 days in circulation
- Deficiency leads to petechiae, purpura, ecchymoses and mucosal bleeding
30
What is petechia?
Dot hemorrahe
31
What is purpura?
Palpable hemorrhage
32
What is ecchymoses?
Bruising that is not palpable
33
What is thrombocytopenia?
| What is the most common cause?
- Too few platelets or thrombocytes < 150,000
- Viral infections and then drugs
-
34
What is idiopathic thrombocytopenic purpura?
| How is it treated?
- Viruses sit on top of platelet
- Platelet is recognized as foreign by immune system
- Body makes antibodies against your own platelets
- Splenomegaly results from sequastration of platelets
- In children, 90% resolve spontaneously
- In adults, 90% remain chronic
- It can precede lupus in adolescent females
- Treated with steroids
- Do not transfuse platelets because they will be destroyed
35
One unit of platelets will raise the platelet count by how much?
7,000 - 10,000
36
If platelet count is 150,00 - 350,000, is it normal?
Yes
37
Someone presents with lupus and a platelet count below 40,000, what do you do?
Begin steroids
38
The risk of spontaneous bleeding begins when the platelet count is what?
How do you treat this?
< 20,000
- Begin plasmapharesis (plasma filtration and replacement) or IV gammaglobulins (they block the antibodies that would have of attacked the platelets)
39
The risk of spontaneous intracranial bleeding begins when the platelet count is what?
How do you treat this?
< 10,000
| Perform a splenectomy which will raise the count over 100,000
40
What are the three most common viruses that cause thrombocytopenia?
1. Parvovirus B19
- 90% of the time
2. Hepatitis C
- Patient with lots of blood transfusions
3. Hepatitis E
- Pregnant women
41
What are the most common drugs that cause thrombocytopenia?
1. AZT
- Patient with HIV
2. Vinblastine
- Chemotherapy for cancer
3. Chloramphenicol
- Antibiotic for infection
4. Benzene
- Work in a factory
42
What do the clotting factors do in general?
Stop bleeding into cavities of the body
43
What are the large cavities of the body that can hold lots of blood when someone bleeds internally?
- Intracranial
- Mediastinum
- Pleural
- Pericardium
- Abdominal
- Pelvis
- Retroperitoneum
- Thighs
44
If a patient is bleeding into a cavity, what kind of defect do they have? Clotting factor or platelet defect?
Clotting factor defect
45
If a patient is bleeding from their skin or mucosal surface, what kind of defect do they have? Clotting factor or platelet defect?
Platelet defect
46
What is the intrinsic clotting system?
Is there trauma?
Most common cause?
- It is when blood vessels expose their basement membrane with out any trauma involved.
- Usually due to vasculitis
- Number one reason for forming clots
47
What is the extrinsic clotting system?
- It is when blood vessels expose their basement membrane due to external trauma.
48
How do we measure the intrinsic pathway?
PTT
49
How do we measure the intrinsic pathway?
PT
50
A left shift in the hemoglobin dissociation curve is caused by?
1. Decreased H+ (increased pH)
2. Decreased 2,3-BPH
3. Decreased temperature
51
A right shift is caused by?
1. Increased H+ (decreased pH)
2. Increased 2,3 BPG
3. Increased temperature
52
Do Hemoglobins with a high oxygen affinity have increased or decreased P50?
Decreased P50
Represented by a leftward shift
There is reduced ability to reduce the oxygen within tissues and leads to erythropoietin secretion and erythrocytosis.
53
What protein acts as a signal to the platelets that there is a break in the endothelium?
What does it result in?
- Glycoprotein 1B (GP1B)
| - Attraction of platelets for them to anchor
54
When platelets anchor to endothelium, what do they release?Initially and then later?
1. Initially release glycoprotein 2B3A (GP2B3A)
- Attracts more platelets to the site
2. Later release thromboxane A2 and serotonin
- Thromboxane vasoconstrictor and promotes more platelet aggregation
(This is and Epidural Hematoma)
55
What is Bernard-Soulier syndrome?
- Defective glycoprotein 1B
- Leads to defect in platelet plug formation
- Platelets can not bind to vWF
- Results in large platelets
- Platelet count is unchanged or decreased
- Bleeding time is increased
- Usually occurs in adults
56
What is Glanzman's Thrombesthenia?
Congenital absence of Glycoprotein IIb:IIIa
- Defect in platelet integrin
- Platelets can not interact with each other and aggregate
- Leads to defective platelet plug formation
Labs show no platelet clumping
- Usually occurs in childhood
57
What do platelets utilize as energy?
ADP
58
What are three drugs that block ADP?
Ticlopidine: causes agranulocytosis and seizures
Dipyridamole: causes vasodilation (used after MI)
Clopidogrel (plavix): Best after stent placements
59
Clopidogrel is used when?
| What is most common side effect?
For acute arterial clots
When aspirin can not be used or patient is
- Causes TTP (Thrombotyc Thrombocytopenic Purpura)
