Fung: Coagulation Flashcards
Disorders of hemostasis can be divided into what two types?
hemorrhagic disorders - excessive bleeding
thrombotic disorders - clot formation
Hemostasis is defined as the balance between what two factors?
clotting and thrombosis
Normal hemostasis occurs in these three steps
- vasoconstriction
- platelet aggregation
- fibrin formation
Reduces blood flow to the area
Mediated by reflex neurogenic mechanisms and augmented by local secretion of endothelin
Transient effect
vasconstriction
Platelets adhere to the endothelium and are activated
This process leads to aggregation and the beginnings of a clot
primary hemostasis
Tissue factor is exposed at the site of vascular injury
Sets in motion a cascade of reactions that leads to thrombin formation
secondary hemostasis
3 layers of the blood vessel
intima
media
adventitia
The intima contains (blank)
The media is a layer of (blank)
The adventitia is rich in (blank)
endothelium
smooth muscle
connective tissue
How does the vascular endothelium actively regulate hemostasis?
inhibits platelets
suppresses coagulation
promotes fibrinolysis
modulates vascular tone and permeability
Upon vascular injury, what is exposed? What is released?
tissue factor is released; collagen and vWF are exposed
What two layers of the blood vessel mediate vasoconstriction?
media and adventitia
Describe the process of primary hemostasis
Vascular damage leads to ezposure of collagen and vWF; platelets adhere, and change shape; platelets release granules containing ADP and TXA2, which recruit additional platelets to the site of injury; aggregation occurs and creates a hemostatic plug
Platelets are derived from (blank) maturation
megakaryocyte
This component of the platelet cytoskeleton bind vWF
GP Ib/V/IX
This component of the platelet cytoskeleton binds fibrinogen and causes platelets to bind together
GP IIb/IIIa
This component of the platelet cytoskeleton initiates platelet activation when bound by ADP
ADP receptor
Which are more numerous in platelets, alpha or dense granules?
alpha
What are the contents of alpha granules?
vWF
fibrinogen
factor V, FXI
What are the contents of dense granules?
ATP
ADP
calcium
serotonin
What do platelets bind to at the site of endothelial injury?
exposed collagen and vWF
Platelet adhesion is mediated by (blank) binding to vWF on the endothelium.
GP Ib/V/IX
What does platelet activation lead to?
shape change
release of alpha and dense granules
initiation of thromboxane A2 pathway
GP IIb/IIIa changes to its active form to cause platelets to adhere to one another
Explain what happens in secondary hemostasis
tissue factor is released
phospholipid complexes are expressed
thrombin is activated
fibrin polymerizes (cross-links)
In the extrinsic pathway, (blank) released w endothelial injury. It is cleaves factor (blank) into factor (blank). Factor (blank) can then act on factor (blank) to make it (blank). 10a then converts prothrombin into (blank). Thrombin converts (blank) to fibrin and allows for cross linking of fibrin.
tissue factor; 7; 7a; 7a; 10; 10a; thrombin; fibrinogen
The intrinsic pathway starts with factor (blank) converting to factor (blank). Factor (blank) is then converted to (blank), and (blank) to (blank). Then, this enters the common pathway causing Factor 10 to convert to 10a, which makes prothrombin convert to thrombin. Thrombin acts of fibrinogen to form fibrin, which ultimately gets cross-linked.
12; 12a; 11; 11a; 9; 9a
Both of these factors convert prothrombin to thrombin.
5a and 10a
Most of the factors in the coagulation cascade are produced in the (blank) except for von Willebrand factor which is produced in the (blank) and (blank)
liver; endothelial cells; megakaryocytes
Summary of coag:
Defect in the vessel wall exposes (blank)
Circulating platelets bind to (blank) and undergo shape change
(blank) allows for aggregation of activated platelets
Aggregated platelets degranulate and activate (blank) which recruits more platelets
Activation of extrinsic and intrinsic pathways eventually converts fibrinogen to (blank)
collagen and vWF; GPIb; GPIIbIIIa/fibrinogen; thromboxane A2; fibrin
These factors inhibit thrombin
thrombin FIXa FXa FXIa FXIIa
These factors inhibit activated C protein
FVa
FVIIIa
Tissue factor pathway inhibitor/extrinsic pathway inhibitor
tissue factor-FVIIa-FXa
This degrades fibrin
plasmin
Two ways to evaluate hemostasis
platelets (platelet count, bleeding time, platelet function, platelet flow cytometry)
coagulation (alpha-PTT, PT, thrombin time)
Used to screen for qualitative platelet disorders or von Willebrand disease
Not a useful test for predicting the risk of bleeding during surgery
Should not be used in patients without a history of excessive bleeding
Normal range is 1.5-9.5 minutes
bleeding time
When is bleeding time prolonged?
von Willebrand disease inherited platelet disorders uremia aspirin ingestion low platelet count
In vitro evaluation of platelet aggregation
Performed on platelet-rich plasma that is exposed to various agonists
Platelet aggregometry
What are some agonists that you would expose platelet-rich plasma to to see if aggregation occurs?
ADP epi arachidonate collagen ristocetin
What is platelet flow cytometry used to diagnose?
deficiencies of platelet surface glycoproteins
disorders of platelet activation
Detects cell surface proteins with fluorescently labeled antibodies
platelet flow cytometry
What is platelet count? What is the normal range for platelets?
actual platelet count determined on automated counters; reference = 140-400,000 cells/mL
Which pathways does the prothrombin time evaluate?
extrinsic and common pathways
When measuring prothrombin time, what is added to plasma to measure the time to clot?
tissue factor and thromboplastin with excess Ca++
If prothrombin time is prolonged, what factors might be deficient or inhibited?
factor 7, 10, 5, 2, fibrinogen
Prothrombin time is used to monitor (blank) therapy
warfarin (coumadin)
**warfarin is an anti-coagulant
Used to reduce interlaboratory variation that results from differing thromboplastin sensitivities to coumadin
INR (international normalized ratio)
What pathways can the activated partial thromboplastin time (alphaPTT) be used to evaluate?
intrinsic and common pathways
When measuring activated partial thromboplastin time, what is added to plasma to measure the time to clot?
phospholipid is added to the plasma with excess Ca++
If the activated partial thromboplastin time is prolonged, what might this indicate a deficiency in?
any of the factors in the common or intrinsic pathways (12, 11, 9, 8, 5, 10, 2, fibrinogen)
Used to monitor heparin, hirudin or argatroban therapy
activated partial thromboplastin time
What is the thrombin time used to test for?
the presence of functional fibrinogen
What are mixing studies used to determine?
the cause of prolonged clotting times
to screen for the presence of inhibitors
Describe a mixing study. How can you tell if the clotting problem is due to a factor deficiency or the presence of an inhibitor?
mix the patient’s plasma with normal test plasma (normal clotting factors); if there is at least 50% activity, the problem was due to a factor deficiency; if there is less than 50% activity, there is an inhibitor present
When are D-dimers formed?
What does their presence indicate?
when fibrin is degraded by plasmin; indicate that fibrin has been formed and degraded
Version of platelet aggregation where patient plasma is added to formalin-fixed normal platelets in the presence of ristocetin
Normal patients will have platelet agglutination
vWF deficient patients will have decreased aggregation
von Willebrand factor assay
This is another name for von Willebrand factor
Ristocetin
T/F: You can perform individual factor assays to show a specific factor deficiency
True
