Neoplasia/Hematology - Mechanisms of Disease - Hemostasis Flashcards
What are the main components of primary hemostasis?
Platelet adhesion and aggregation
What are the main components of secondary hemostasis?
Plasma clotting factors leading to fibrin formation
What are the main components of tertiary hemostasis?
Fibrin cross-linking and eventual fibrinolysis
Platelet activity is mostly part of _________ hemostasis.
Platelet activity is mostly part of primary hemostasis.
The clotting cascade is mostly part of _________ hemostasis.
The clotting cascade is mostly part of secondary hemostasis.
What do platelet dense granules contain?
Ca2+;
ADP;
ATP;
serotonin
What do platelet alpha granules contain?
Many factors:
vWF
Fibrinogen
Thromboglobulin
Thrombospondin
PDGF
PF4
P-selectin
Which platelet granules contain PDGF, PF4, and P-selectin?
(The āPās)
Alpha granules
Where is PF3 when the platelet is inactivated?
And when it is activated?
The inner membrane layer;
the outer membrane layer
PF3 is expressed by activated platelets to induce what process?
Thrombin formation
(uniting primary and secondary hemostasis)
What is the full name of the glycoprotein that connects platelets to vWF?
gpIb/V/IX
gp______ connects platelets to vWF on exposed collagen.
gpIb/V/IX connects platelets to vWF on exposed collagen.
gp______ connects platelets together on fibrinogen chains.
gpIIb/IIIa connects platelets together on fibrinogen chains.
Why do platelets and clotting factors normally not interact with undamaged endothelium?
Negative charge repulsion
What substance is expressed on endothelial cell surfaces to reduce coagulation?
Thrombomodulin
What substances are secreted by endothelial cell surfaces to reduce coagulation?
Nitric oxide;
serotonin;
prostacyclin;
heparin-like molecules
True/False.
In low shear stress conditions, platelets can bind directly to collagen without vWF as an intermediary.
True.
Via gpIa/IIa.
vWF is produced by what cell type(s)?
Megakaryocytes;
endothelial cells
What role does vWF play in secondary hemostasis?
Factor VIII stabilization
True/False.
vWF is produced as very large multimers that require cleavage for proper function.
True.
Where is vWF stored after synthesis?
Weibel-Palade bodies
What enzyme cleaves the ultra-high molecular weight vWF multimers into smaller multimers?
ADAMTS13
True/False.
Only small or intermediate vWF multimers (cleaved) have significant hemostatic function.
False.
Only large vWF multimers have significant hemostatic function.
Binding of platelet gpIb/V/IX to vWF leads to secretion of what in particular?
ADP and serotonin
(causing platelet activation and vasoconstriction, respectively)
What does ADP-activation in platelets cause to occur?
Expression of gpIIb/IIIa
Platelet gpIIb/IIIa can bind what substances in particular?
Fibrinogen;
vWF
What are the steps of platelet activity in clot formation?
- Plug/adhere wound
- Aggregate together
- Initiate clotting cascade
What is the normal blood count range for platelets?
150,000 - 450,000
Which have a higher MPV, young or mature platelets?
Young
(younger platelets are larger)
What two tests allow for assessment of platelet function?
Bleeding time;
PFA-100
What types of bleeding are typically seen in disorders of primary hemostasis?
Mucosal bleeds;
petechiae;
purpura;
immediate intra-operative (within minutes);
post-operative
Glanzmann thrombasthenia is an inherited deficiency of what?
Platelet gpIIb/IIIa
Bernard-Soulier syndrome is an inherited deficiency of what?
Platelet gpIb/V/IX
What inherited platelet disorder does not typically result in thrombocytopenia?
Glanzmann thrombasthenia
What is the generic name for Plavix?
Clopidogrel
Name a few conditions in the following categories that can cause thrombocytopenia:
Immune reactions
Organ dysfunctions
Thrombotic conditions
ITP;
splenomegaly, aplastic anemia, MDS, etc.;
DIC, TTP, HIT
True/False.
Hepatic and renal dysfunction can both lead to platelet dysfunction.
True.
How can myeloproliferative diseases lead to platelet dysfunction?
Bone marrow crowding
(can produce ineffective and/or decreased platelets)
_______________ is an inherited deficiency of platelet gpIIb/IIIa.
Glanzmann thrombasthenia is an inherited deficiency of platelet gpIIb/IIIa.
_______________ is an inherited deficiency of platelet gpIb/V/IX.
Bernard-Soulier syndrome is an inherited deficiency of platelet gpIb/V/IX.
True/False.
Bernard-Soulier syndrome and Glanzmann thrombasthenia are typically characterized by thrombocytopenia.
False.
Bernard-Soulier syndrome is typically characterized by thrombocytopenia; Glanzmann thrombasthenia is typically characterized by a normal CBC.
Gray platelet disorder is an inherited deficiency of _________ platelet granules.
Gray platelet disorder is an inherited deficiency of alpha platelet granules.
All the following disorders are characterized (in part) by deficiencies of _________ platelet granules:
- Hermansky-Pudlak syndrome*
- Chediak-Higashi syndrome*
- TAR syndrome*
- Wiscott-Aldrich syndrome*
All the following disorders are characterized (in part) by deficiencies of dense platelet granules:
- Hermansky-Pudlak syndrome*
- Chediak-Higashi syndrome*
- TAR syndrome*
- Wiscott-Aldrich syndrome*
How do the platelets appear if alpha granules are deficient?
Enlarged, gray
(gray platelet syndrome ā thrombocytopenia may be present)
Name an inherited disorder of primary hemostasis that is the most common inherited bleeding disorder and does not directly involve platelet alterations.
vWF disease
How does vWF deficiency typically present?
Similar to platelet disorders
(mucosal bleeding, petechiae, etc. ā severe cases may also result in factor VIII dysfunction)
What is the inheritance pattern for the most common form of vWF disease?
Autosomal dominant
Type 3 vWF disease involves a complete absence of vWF.
How does this uncommon form present?
What is its inheritance pattern?
Similar to hemophilia (factor VIII dysfunction);
autosomal recessive
What substance is a cofactor for vWF and can be used to evaluate vWF function and concentration?
Ristocetin
What is the vWF multimers test used to assess?
The size of vWF multimers
(small, medium, large)
A patient with vWF disease has ristocetin added to a sample of their blood.
What will happen?
No coagulation
vWF is an acute phase reactant, and so a workup for vWF disease should not be done in what scenarios?
Pregnancy (2nd or 3rd trimester);
strenuous exercise;
stressful situations