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MLSCI330 Hematology > Coagulation/ FIbrinolysis > Flashcards

Coagulation/ FIbrinolysis Flashcards

1
Q

List 4 anticoagulant properties of endothelium

A
  1. secretion of: (prostacyclin, nitric oxide, heparin sulfate, TFPI, TPA)
  2. smooth surface
  3. Protein C receptors = inactivates Va and VIIIa
  4. Thrombomodulin expression = inactivates thrombin
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2
Q

Prostacyclin function

A

PLT inhibitor

NOTE: anticoagulant secretion by endothelium

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3
Q

Nitric oxide function

A

Vascular relaxing (dilation)

NOTE: anticoagulant secretion by endothelium

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4
Q

Heparin sulfate function

A

anticoagulant secretion by endothelium

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5
Q

TFPI function

A

Tissue Factor Pathway Inhibitor: suppresses extrinsic pathway

NOTE: anticoagulant secretion by endothelium

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6
Q

Thrombomodulin source + function

A
  • inactivates thrombin
  • an anticoagulant secretion by endothelium
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7
Q

Role of WVF in primary hemostasis

A
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8
Q

Why is vit K needed by coagulation factors ?

A
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9
Q

What initiates primary hemostasis ?

A

vascular damage = procoagulant factors released from vessel cells, exposed collagen promotes procoagulants to begin primary hemostasis

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10
Q

List 5 pro-coagulant properties of damaged vasculature

A
  1. endothelial cells secrete vWF + up-regulate PLT receptors
  2. exposed collagen = binds vWF and PLTs
  3. vasoconstriction (smooth muscles contract)
  4. PLTs release factors (prostaglandins + prostacyclin)
  5. smooth muscle contain TF = activates FVII
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11
Q

Describe Adhesion stage of platelet plug

A
  • reversible; PLTs BIND VESSEL WALL
    a. MINOR injury = PLTs bind to collagen via GPIa/IIa, GP IV, and GP VI
    b. MAJOR injury = PLTs also bind vWFv via GPIb/IX/V receptors before binding wall
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12
Q

Bernard Soulier

A

GPIb deficiency
- affects adhesion in PLT plug for MAJOR injuries

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13
Q

VonWillebrand Disease

A

vWF deficiency
- affects adhesion in PLT plug for MAJOR injuries

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14
Q

Describe Aggregation stage of platelet plug

A
  • reversible OR irreversible (TXA2 and ADP)
  • PLTs bind other PLTs
  • ADP released during PLT adhesion = exposes fibrinogen receptors on PLTs (GPIIb/IIIa integrin) and P-selectin
  • PLTs aggregate using fibrinogen and Ca2+
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15
Q

Glanzmann’s Thrombasthenia

A

GPIIb/IIIa deficiency
- affects aggregation in PLT plug
- reduced fibrinogen receptors on PLTs

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16
Q

Describe Granule Secretion stage of platelet plug

A
  • simultaneously during adhesion/ aggregation

a. ALPHA granules = via SCC system
- PF4
- B thrombomodulin
- PDGF, endothelial GF, Transforming GF
- Factors V, XI, vWF, fibrinogen

b. DENSE = via exocytosis
- ADP/ ATP
- Ca2+, Mg2+
- serotonin

SSC = surface-connected canalicular

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17
Q

Describe Formation/ Function of Thromboxane A2 in a platelet plug

A

PF3 = PLT phospholipids
- during PLT activation = converted to arachidonic acid = thromboxane A2
- thromboxane A2 = triggers more Ca2+ release = promotes PLT aggregation and vasoconstriction = coagulation

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18
Q

What blocks cyclooxygenase and prevents thromboxane A2 production ?

A

ASPIRIN leads to impaired PLT function

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19
Q

What is TF and where is it found ?

A

a transmembrane protein in the endothelium

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20
Q

What are coagulation factors ? Where are they made ?

A

proteins synthesized by the liver

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21
Q

Define zyomgen

A

Inactive form of enzymes (coagulation factors)

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22
Q

Define serine protease

A

enzymes that cleave proteins = must be activated to participate in reaction ie. IIa/ prothrombin

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23
Q

Define cofactor

A

a substance (other than the substrate) whose presence is essential for the activity of an enzyme

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24
Q

Which coagulation factors are serine proteases ?

A

Kallikrein
IIa (prothrombin)
VIIa
IXa
Xa
XIa
XIIa
Plasmin
Protein C

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25
Which coagulation factors are cofactors ?
FV and FVIII
26
Which clotting factors are vit-K dependent ? What is the function of vit K in the synthesis of these factors ?
II/ prothrombin, VII, IX, X (2790) & Protein C/ S/ Z: - vit K catalyses carboxylation of terminal glutamic acids - carboxyl group binds Ca2+ = allows binding of PF3
27
Where are the components of vWF/VIII complex produced ? What are their functions ? What cleaves the complex ?
- vWF = produced by endothelial cells; complexes with VIII = STABLE - VIII = produced by PLT/ endothelial cells; UNSTABLE by itself - vWF/VIII is cleaved by thrombin = VIIIa in TENASE complex
28
Which factors are involved in the extrinsic pathway ?
VII + TF + Ca2+ = TF:VIIa TF:VIIa + PF3 + X = Xa INCLUDING factors in COMMON PATHWAY
29
Which factors are involved in the intrinsic pathway ?
Prekallikrein + HMWK = Kallikrein Kallikrein + HMWK = XII XII + collagen = XIIa XIIa + HMWK + XI = XIa XIa + Ca2+ + IX = IXa IXa + (VIIIa + PF3 + Ca2+) + X = Xa
30
Which factors are involved in the common pathway ?
X + (TENASE complex [intrinsic]/ PF3 AND TF:VIIa complex [extrinsic]) = Xa Xa + (Va + PF3 + Ca2+) + II/prothrombin = thrombin Thrombin + fibrinogen = fibrin monomer (soluble) Thrombin + XIII = XIIIa XIIIa + Ca2+ +fibrin monomer = fibrin CROSSLINKS (insoluble)
31
Function of fibrinolytic system
- normally removes fibrin clots that are no longer required - begins hours after coagulation - gradual enzymatic cleavage of fibrin = soluble FDPs
32
Plasminogen: site of synthesis
Liver
33
Plasminogen: activation
activated by TPA/ Tissue plasminogen activator
34
Plasminogen: mechanism of action
must be activated into plasmin to cleave fibrin - promotes fibrinolysis
35
Plasminogen: target
To cleave FIBRIN in clots and FIBRINOGEN
36
Function + source of TPA
Tissue Plasminogen Activator: - secreted by damaged endothelial cells - promotes fibrinolysis; plasmin to cleave fibrin = FDPs
37
Activation, function + location of Urokinase
- secreted by kidney - activated by fibrin and plasmin - promotes fibrinolysis in renal collecting ducts
38
Activation, function + location of Plasminogen Activator Inhibitor 1
- secreted by endothelial cells, megakaryocytes, fibroblasts, smooth muscle, monocytes, etc. - increased in high levels of TPA - prevents fibrinolysis; inhibits TPA and Urokinase
39
Function + source of α2-Antiplasmin
- secreted by liver + PLTs - prevents fibrinolysis; irreversibly binds plasmin
40
Function, activation and source of TAFI
Thrombin-activatable Fibrinolysis Inhibitor: - secreted by liver - activated by thrombin/ thrombomodulin - prevents fibrinolysis; prevents plasmin formation
41
What are FDPs ?
Fibrin Degradation Products: - plasmin cleaves fibrin into characteristic fragments: X, Y, D, E and D-dimers - plasmin cleaves fibrinogen into X, Y, D, E - inhibit coagulation cascade
42
What is the clinical utility of measuring D-dimers ?
- measures fibrinolysis activity - Detects DIC
43
Describe TFPI mechanism of action and what factors it inhibits
Tissue Factor Pathway Inhibitor: - requires Protein S as a cofactor - inactivates Xa by complexing into TFPI:Xa - TFPI:FXa binds to TF:VII to prevent further activation of X
44
Describe the Protein C system; how is it activated ? What does it inhibit ? What is its role in fibirinolysis ?
- activated by thrombin/ thrombomodulin complex 1. Inhibits coagulation = activated Protein C combines with cofactor Protein S = Protein C:S complex inhibits Va and VIIIa 2. Promotes fibrinolysis = forms complex with/ deactivates Plasminogen Activator Inhibitor-1 (PAI-1)
45
Describe how Antithrombin inhibits coagulation/ which factors it inhibits
- activated by heparin sulfate from endothelial cell surface - inhibits all serine proteases: Kallikrein, II/ prothrombin, XII, XI, X, IX, plasmin)
46
What tube/ anticoagulant is used for coagulation testing ?
Sodium citrate
47
Principle of aPPT test in vitro
In citrated plasma (blue top), the addition of a platelet substitute, factor XII activator, and CaCl2 allows for formation of a stable clot
48
Is an instrument that uses mechanical end-point detection prone to interference from hemolysis ? Why/ why not ?
49
How does hemolysis affect coagulation test results, if at all ?
50
Troubleshooting when QC = 1-3S: First and Second step
51
How does a high Hct affect coagulation test results ? How can it be corrected ?
52
How are D-dimers measured on conventional coagulation instruments ?
Immunoassays based on fragment sizes
53
Factors in TENASE complex. What do they activate ?
VIIIa PF3 Ca2+ - activates factor X
54
Which factors are included in the prothrombinase complex ? What do they activate ?
Va + PF3 + Ca2+ - activates prothrombin/II to thrombin
55
What is PF3 ? What is its role in coagulation ?
PF3 = PLT phospholipids - during PLT activation = converted to arachidonic acid = thromboxane A2 - thromboxane A2 = triggers more Ca2+ release = promotes coagulation
56
Differentiate products when plasmin cleaves fibrin vs fibrinogen
Plasmin cleaves Fibrin = X, Y, D, E, D-dimers Plasmin cleaves Fibrinogen = only X, Y, D, E
57
Fibrinogen and FDPs by kDa
Fibrinogen > X > Y > D > E
58
TFPI: Source
- secreted by endothelial cells - 80% bound to vessel walls - 20% circulating bound to LDL
59
How is ZPI activated ? What does it inhibit ?
Protein Z-dependent Protease Inhibitor: - requires cofactors (protein Z, PF3, Ca2+) to DEGRADE factor X - by itself, it can inhibit XIa
60
Glycoprotien IIb/IIIa complex
- A receptor for fibrinogen on the platelet membrane - It allows PLT binding of fibrinogen and vWF to bind other PLTs
61
Glycoprotien Ib/IX/V
- A receptor for vWF on the platelet membrane. - It allows PLT binding of vWF to vascular walls for PLT adhesion.
62
What do co-factors bind to in the coagulation process? a. Fibrinolytic factors to slow down clot digestion b. A specific serine protease to increase its activity c. Calcium to aid in platelet aggregation d. Fibrin monomers to cross-link and stabilize the clot
b. A specific serine protease to increase its activity
63
What are the functions of platelets in hemostasis? Select all that apply: a. Release of serotonin b. Release of prostacyclin c. Formation of a hemostatic plug d. Activation of the extrinsic coagulation system
a. Release of serotonin c. Formation of a hemostatic plug
64
Which of the following are functions of thrombin? Select all that apply: a. Activates factors V and VIII b. Activates anti-thrombin c. Activates Factor XIII d. Activates factor XI
a. Activates factors V and VIII c. Activates Factor XIII d. Activates factor XI
65

MLSCI330 Hematology (10 decks)

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