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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

2 ways the vascular system inhibits spontaneous hemostasis

A
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8
Q

Role of WVF in primary hemostasis

A
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9
Q

Why is vit K needed by coagulation factors ?

A
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10
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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11
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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12
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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13
Q

Bernard Soulier

A

GPIb deficiency
- affects adhesion in PLT plug for MAJOR injuries

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14
Q

VonWillebrand Disease

A

vWF deficiency
- affects adhesion in PLT plug for MAJOR injuries

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15
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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16
Q

Glanzmann’s Thrombasthenia

A

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

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17
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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18
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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19
Q

What blocks cyclooxygenase and prevents thromboxane A2 production ?

A

ASPIRIN leads to impaired PLT function

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20
Q

What is TF and where is it found ?

A

a transmembrane protein in the endothelium

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21
Q

What are coagulation factors ? Where are they made ?

A

proteins synthesized by the liver

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22
Q

Define zyomgen

A

Inactive form of enzymes (coagulation factors)

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23
Q

Define serine protease

A

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

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24
Q

Define cofactor

A

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

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25
Q

Which coagulation factors are serine proteases ?

A

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

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26
Q

Which coagulation factors are cofactors ?

A

FV and FVIII

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27
Q

Which clotting factors are vit-K dependent ? What is the function of vit K in the synthesis of these factors ?

A

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

28
Q

Where are the components of vWF/VIII complex produced ? What are their functions ? What cleaves the complex ?

A
  • 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
29
Q

Which factors are involved in the extrinsic pathway ?

A

VII + TF + Ca2+ = TF:VIIa
TF:VIIa + PF3 + X = Xa

INCLUDING factors in COMMON PATHWAY

30
Q

Which factors are involved in the intrinsic pathway ?

A

Prekallikrein + HMWK = Kallikrein
Kallikrein + HMWK = XII
XII + collagen = XIIa
XIIa + HMWK + XI = XIa
XIa + Ca2+ + IX = IXa
IXa + (VIIIa + PF3 + Ca2+) + X = Xa

31
Q

Which factors are involved in the common pathway ?

A

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)

32
Q

Function of fibrinolytic system

A
  • normally removes fibrin clots that are no longer required
  • begins hours after coagulation
  • gradual enzymatic cleavage of fibrin = soluble FDPs
33
Q

Plasminogen: site of synthesis

A

Liver

34
Q

Plasminogen: activation

A

activated by TPA/ Tissue plasminogen activator

35
Q

Plasminogen: mechanism of action

A

must be activated into plasmin to cleave fibrin
- promotes fibrinolysis

36
Q

Plasminogen: target

A

To cleave FIBRIN in clots and FIBRINOGEN

37
Q

Function + source of TPA

A

Tissue Plasminogen Activator:
- secreted by damaged endothelial cells
- promotes fibrinolysis; plasmin to cleave fibrin = FDPs

38
Q

Activation, function + location of Urokinase

A
  • secreted by kidney
  • activated by fibrin and plasmin
  • promotes fibrinolysis in renal collecting ducts
39
Q

Activation, function + location of Plasminogen Activator Inhibitor 1

A
  • secreted by endothelial cells, megakaryocytes, fibroblasts, smooth muscle, monocytes, etc.
  • increased in high levels of TPA
  • prevents fibrinolysis; inhibits TPA and Urokinase
40
Q

Function + source of α2-Antiplasmin

A
  • secreted by liver + PLTs
  • prevents fibrinolysis; irreversibly binds plasmin
41
Q

Function, activation and source of TAFI

A

Thrombin-activatable Fibrinolysis Inhibitor:
- secreted by liver
- activated by thrombin/ thrombomodulin
- prevents fibrinolysis; prevents plasmin formation

42
Q

What are FDPs ?

A

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

43
Q

What is the clinical utility of measuring D-dimers ?

A
  • measures fibrinolysis activity
  • Detects DIC
44
Q

Describe TFPI mechanism of action and what factors it inhibits

A

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

45
Q

Describe the Protein C system; how is it activated ? What does it inhibit ? What is its role in fibirinolysis ?

A
  • 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)
46
Q

Describe how Antithrombin inhibits coagulation/ which factors it inhibits

A
  • activated by heparin sulfate from endothelial cell surface
  • inhibits all serine proteases: Kallikrein, II/ prothrombin, XII, XI, X, IX, plasmin)
47
Q

What tube/ anticoagulant is used for coagulation testing ?

A

Sodium citrate

48
Q

Principle of aPPT test in vitro

A

In citrated plasma (blue top), the addition of a platelet substitute, factor XII activator, and CaCl2 allows for formation of a stable clot

49
Q

Is an instrument that uses mechanical end-point detection prone to interference from hemolysis ? Why/ why not ?

A
50
Q

How does hemolysis affect coagulation test results, if at all ?

A
51
Q

Troubleshooting when QC = 1-3S: First and Second step

A
52
Q

How does a high Hct affect coagulation test results ? How can it be corrected ?

A
53
Q

How are D-dimers measured on conventional coagulation instruments ?

A

Immunoassays based on fragment sizes

54
Q

Factors in TENASE complex. What do they activate ?

A

VIIIa
PF3
Ca2+

  • activates factor X
55
Q

Which factors are included in the prothrombinase complex ? What do they activate ?

A

Va + PF3 + Ca2+
- activates prothrombin/II to thrombin

56
Q

What is PF3 ? What is its role in coagulation ?

A

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

57
Q

Differentiate products when plasmin cleaves fibrin vs fibrinogen

A

Plasmin cleaves Fibrin = X, Y, D, E, D-dimers
Plasmin cleaves Fibrinogen = only X, Y, D, E

58
Q

Fibrinogen and FDPs by kDa

A

Fibrinogen > X > Y > D > E

59
Q

TFPI: Source

A
  • secreted by endothelial cells
  • 80% bound to vessel walls
  • 20% circulating bound to LDL
60
Q

How is ZPI activated ? What does it inhibit ?

A

Protein Z-dependent Protease Inhibitor:
- requires cofactors (protein Z, PF3, Ca2+) to DEGRADE factor X
- by itself, it can inhibit XIa

61
Q

Glycoprotien IIb/IIIa complex

A
  • A receptor for fibrinogen on the platelet membrane
  • It allows PLT binding of fibrinogen and vWF to bind other PLTs
62
Q

Glycoprotien Ib/IX/V

A
  • A receptor for vWF on the platelet membrane.
  • It allows PLT binding of vWF to vascular walls for PLT adhesion.
63
Q

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

A

b.
A specific serine protease to increase its activity

64
Q

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

a.
Release of serotonin

c.
Formation of a hemostatic plug

65
Q

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

a.
Activates factors V and VIII

c.
Activates Factor XIII

d.
Activates factor XI

66
Q
A

MLSCI330 Hematology (10 decks)

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