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AIM - Heme/Onc > Hemostasis > Flashcards

Hemostasis Flashcards

1
Q

intrinsic clotting pathway

A

factors 12, 11, 9, 8

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2
Q

extrinsic pathway

A

factor 7
VII:TF complex
Ca required
K dependent

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3
Q

K+ dependent factors

A

2, 7, 9, 10, C, S

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4
Q

common pathway

A

10, 5, 2 (pro/thrombin)

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5
Q

effects of thrombin

A

1) activate platelets
2) cleaves fibrinogen –> fibrin
3) activates factor 13 (crosslinks fibrin)
4) activates cofactors 5, 8, 9

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6
Q

thromboplastin tissue factor

A
  • glycoprotein
  • sub endothelial cells
  • exposed if vasc damage
  • major activator of coagulation system
  • complexes with 7 (VII:TF) –> activate X
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7
Q

factor VIII (8)

A
  • produced in endothelial cells, megakaryocytes
  • bound to vWF –> stabilizes

(vascular injury –> released –> intrinsic pathway)

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8
Q

factor XIII (13)

A
  • crosslinks fibrin
  • stabilizes fibrin plug
  • requires Ca cofactor
  • activated by thrombin
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9
Q

factor XII (12)

A
  • activates factor XI (11)

- activated by contact with negative charges (basis for PTT)

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10
Q

warfarin

A

vitamin K antagonist

anticoagulant

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11
Q

kinins

A
  • vasodilate, incr vasc permeability, pain
  • produced by factor XII (12)
  • degraded by ACE, C1 inhibitor (ACEi incr kinin levels –> angioedema)
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12
Q

antithrombin III

A
  • coagulation inhibitor
  • serine protease inhibitor (serpin)
  • inhibits factors II, VII, IX, X, XI, XII (2, 7, 9, 10, 11, 12)
  • produced in liver
  • activated by endothelium (heparin sulfate)
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13
Q

protein C

A
  • coagulation inhibitor
  • liver glycoprotein
  • activated = APC
  • thrombomodulin + thrombin –> activates to APC
  • cofactor: protein S

-inactivates V, VIII (5, 8)

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14
Q

TFPI

A
  • coagulation inhibitor
  • tissue factor pathway inhibitor
  • inactivates X (10)
  • binds directly to X, or binds to TF:VII to prevent activation of X
  • heparin increases plasma levels of TFPI
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15
Q

plasminogen

A
  • active enzyme: plasmin
  • breaks down fibrin
  • also breaks down clotting factors, fibrinogen
  • activated by: tPA, urokinase
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16
Q

sources of vitamin K

A
  • green leafy vegetables

- bacterial synthesis in gut

17
Q

PT

A

prothrombin time

  • extrinsic system
  • common pathway, factor VII (7)
18
Q

PTT

A

partial thrombin time

  • intrinsic pathway
  • common pathway, factors VIII, IX, XI, XII (8,9,11,12)
19
Q

What is not reflected in PT or PTT?

A

vWF, factor XIII (13)

20
Q

von Willebrand Factor

A
  • glycoprotein
  • endothelial cells (Weibel Palade bodies) and megakaryocytes (alpha granules in platelets)
  • released on vascular injury

1) carrier protein for factor VIII (8)
2) binds platelets to damaged endothelium (adhesion)
3) binds activated platelets together (aggregation)

21
Q

platelet adhesion

A
  • vascular damage exposes collagen
  • subendothelial damage binds vWF
  • vWF binds GPIa on platelets

damaged wall/collagen can bind platelet directly via GPIa/IIa receptor

22
Q

GPIb

A
  • on platelets
  • binds vWF
  • platelet adhesion
23
Q

GPIIb/IIIa receptor

A

-mediates aggregation

  • once platelet activated, GPIIb/IIIa changes shape –> binds fibrinogen or vWF
  • links platelets together
24
Q

platelet secretion

A

activated by

  • binding subendothelial collagen
  • binding activating substances
  • secretion of stored activators causes more activation
25
Q

alpha granules

A

in platelets

  • fibrinogen (aggregation)
  • thrombospondin (aggregation)
  • vWF (adhesion/aggregation)
  • factor V (fibrin clot)
  • platelet factor 4 (heparin antagonist, promotes fibrin clot)
  • beta thromboglobulin (recruits fibroblasts)
  • PDGF (recruits fibroblasts)
  • P selectin (adhesion to phagocytes)
26
Q

dense granules

A

in platelets

  • ADP
  • Ca (cofactor for fibrin formation)
  • serotonin (vasoconstriction)
27
Q

P2Y1

A
  • platelet receptor
  • adenosine binds
  • Ca release
  • platelet shape change
28
Q

P2Y13

A
  • platelet receptor
  • adenosine binds
  • platelet degranulation
  • more aggregation
29
Q

effects of ADP

A

P2Y1

  • Ca release
  • shape change of platelet

P2Y12

  • platelet degranulation
  • more aggregation
30
Q

thromboxane A2

A
  • platelet activator
  • cell membrane lipids –> AA –> TXA2

-last step by COX (inhibited by ASA

31
Q

production of platelets stimulated by

A

GM-CSF
IL-3
IL-6
TPO

32
Q

GPIa/IIa receptor

A
  • on platelets

- collagen from damaged wall can bind to platelet directly

33
Q

platelet activating agents

A
  • thrombin
  • thromboxane A2
  • epinephrine
  • ADP
  • collagen
  • AA
34
Q

platelet shape change

A
  • discoid –> spherical

- long pseudopods

35
Q

major tests for platelet function

A

Aggregation:
-platelet rich plasma plus platelet agonists light transmission

Aggregation + Adhesion
-PFA 100

36
Q

PFA-100

A
  • tests platelet adhesion and aggregation
  • time to clot formation between 2 membranes coated with activators

-affected by thrombocytopenia, anemia

37
Q

tissue factor pathway inhibitor (TFPI)

A

-regulates TF/FVIIa pathway (extrinsic)

38
Q

anti-thrombin III (AT-III)

A

inhibits thrombin, FIX, FX, FXI (intrinsic and common)

39
Q

protein C

A
  • inhibits FV and FVIII (intrinsic and common)

- vitamin K dependent

AIM - Heme/Onc (9 decks)

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