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Exam 4 - Coagulation Flashcards

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1
Q

What are the 3 goals of hemostais?

A
  • To limit blood loss from vascular injury
  • Maintain intravascular blood flow
  • Promote revascularization after thrombosis
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2
Q

What are the 2 stages of hemostatsis?

A

Primary - Platelet plug formation, adequate for minor injuries
Secondary - activation of clotting factors →stabilized crosslinked clot

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3
Q

Anti-clotting mechanisms of endothelial cells:
- are ____ to repel platelets
- produce platelet inhibitors ____ and ____
- excrete ____, which degrades ADP - a platelet activator
- increase ____, an anticoagulant
- produce ____, which inhibits factor Xa and TF-VIIa complex
- Synthesizes ____

A
  • are negatively charged to repel platelets
  • produce platelet inhibitors prostacyclin and nitric oxide
  • excrete adenosine diphosphatase, which degrades ADP - a platelet activator
  • increase protein C, an anticoagulant
  • produce tissue factor pathway inhbitor (TFPI), which inhibits factor Xa and TF-VIIa complex
  • Synthesizes tissue plasminogen activator (t-PA)
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4
Q

What are platelets derived from?

A

Bone-marrow megakaryocytes

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5
Q

Inactive platelet lifespan?

A

8-12 days

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6
Q

How many platelets are used just to maintain vascular integrity?
How many are made daily?

A

10%
120-150 billion

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7
Q

What increases the membrane surface area of platelets?

A

Numerous receptors and surface canalicular system

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8
Q

Damage to the endothelium exposes the underlying ECM which contains what?
What does this cause?

A

Collagen, vWf, glycoproteins
Platelet adhesion and activation

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9
Q

What happens when platelets are activated?

A

Release of alpha granules and dense bodies

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10
Q

What is contained within alpha granules?

A

fibrinogen, factor V, VIII, vWF, and PLT growth factors

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11
Q

What is contained within dense bodies?

A

ADP, ATP, Ca++, serotonin, histamine, and epinephrine

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12
Q

How does platelet aggregation occur?

A

Occurs when granular contents are released - activating additional platelets

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13
Q

Each stage of the clotting cascade require assembly of what?

A

membrane-bound activated tenase-complexes

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14
Q

Each membrane tenase complex is composed of?

A
  1. Substrate
  2. Enzyme
  3. Cofactor
  4. Calcium
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15
Q

Draw the clotting cascade

A
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16
Q

What are the common names for the clotting factors?

A

Foolish People Try Climbing Long Slopes After Christmas, Some People Have Fallen

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17
Q

The TF/VIIa complex activates what?

A

X to Xa
IX to IXa

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18
Q

What is the major role of the intrinsic pathway?

A

Amplifies coagulation to propagate thrombin generation initiated by the extrinsic pathway

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19
Q

What activates factor XII to start the intrinsic pathway?

A

Contact with a negatively charged surface

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20
Q

In the intrinsic pathway, what converts factor X to Xa?

A

IXa + VIIIa + Ca++

Intrinisic tenase complex

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21
Q

What factors does activated thrombin (IIa) activate?

A

V, VII, VIII, and XI

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22
Q

What makes up the prothrombinase complex?
What does it do?

A

Xa + Va + Ca
Converts prothrombin (II) to thrombin (IIa)

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23
Q

How does thrombin generate fibrin?

A

Cleaves fibrinopeptides from fibrinogen to generate fibrin
Fibrin then polymerizes into strands to form basic clot

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24
Q

What does factor XIIIa do?

A

Crosslinks the fibrin strands to stablize the clot - making it resistant to degredation

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25
What is the key step in regulating hemostasis?
Thrombin generation
26
What makes up the intrinsic and and extrisic tenase compexes? What do these facilitate?
Formation of prothrombinase complex
27
What are the 4 major coagulation counter mechanisms?
- Fibrinolysis - Tissue Factor Pathway Inhibitor (TFPI) - Protein C system - Serine Protease Inhibtors (SERPINs)
28
How does fibrinolysis occur?
Endovascular TPA & urokinase convert plasminogen to plasmin
29
How does plasmin cause fibrinolysis?
Plasmin breaks down clots enzymatically, and degrades factors V & VIII
30
How does TFPI function to counter the coagulation cascade?
* Forms complex w/ Xa that inhibits TF/7a complex * Thereby downregulating the extrinsic pathway
31
What does protein C do?
Inhibits factors II, Va, and VIIIa
32
What are the 3 SERPINs and how do they work?
* **Antithrombin (AT)** inhibits thrombin, factors 9a (IXa), 10a (Xa), 11a (XIa), 12a (XIIa) * **Heparin** binds to AT, causing a conformational change that accelerates AT activity * **Heparin cofactor II** inhibits thrombin alone
33
If a bleeding disorder is suspected in a patient, what are the first line labs?
PT and aPTT
34
What is the most common inherited bleeding disorder?
Von Willebrands Disease
35
Patho of vWD?
* Deficiency in vWF, causing defective plt adhesion/aggregation * vWF plays critical role in plt adhesion & prevents degradation of factor 8 (VIII)
36
Lab findings in vWD?
Normal PT and platelets aPTT could be prolonged d/t decreased factor VIII
37
Treeatment for vWD?
DDAVP (increase vWF synthesis) or Factor VIII concentrates
38
What clotting factors are defiecent in hemophilia A and B?
A: Factor VIII deficient B: Factor IX deficient
39
Lab findings in hemophilia?
PT, Plt, and bleeding time normal **PTT prolonged**
40
What is the most significant cause of intraoperative bleeding?
Anticoagulant meds and supplements
41
What meds can increase bleeding that you may not consider?
* Beta-lactam abx * Nitroprusside * NO * NTG * SSRIs
42
Supplements that can cause bleeding?
- Cayenne - Garlic - Ginger - Gingko - Grapeseed oil - SJW - Turmeric - Vitamin E
43
What clotting factors are NOT made in the liver?
I-IV, VIII, XIII
44
Coagulation lab findings in patients with liver disease?
Prolonged PT and PTT Labs don't show lack of anticoagulant factors
45
Why do CKD patients show a baseline anemia?
- Lack of EPO - Plt dysfunction from uremia
46
Treatment of plt dysfunction in CKD?
- Cryo (rich in vWF) - DDAVP - Conjugated estrogens
47
DIC patho?
Depletion of coag factors and plts d/t excessive activation of the extrinsic pathway that overwhelms anticoagulant mechanisms - leading to large amounts of thrombin and microemboli
48
Lab findings in DIC?
↓Plts, prolonged PT/PTT/Thrombin time,↑soluble fibrin & fibrin degradation products
49
Cause of trauma induced coagulopathy?
Activated protein C (from hypoperfusion) decreases thrombin generation
50
What causes "auto heparinization" seen in TIC?
Proteoglycan shedding
51
Factor V leiden patho?
Genetic mutation of factor V leading to activated protien C resistance
52
What prothrombotic state generally presents with venous thrombi?
Thrombophilia
53
What is antiphospholipid syndrome? Sx? Tx?
* Autoimmune disorder w antibodies againest phospholipid binding proteins * Recurrent thrombosis and miscarrage/spontaneous abortion * Often requires life long anticoagulants
54
HIT patho?
Autoimmune response resulting in platelet count reduction as well as activation of the remaining platelets and potential thrombosis
55
What is contraindicated in HIT? How long do the antibodies stay in the circulation?
- Warfarin - decreases protein C and S synthesis - Clear within 3 months
56
What does Prothrombin Time measure?
* Assesses extrinsic and common pathways * Reflects deficiencies in factors I, II, V, VII, X * Used to monitor warfarin levels (WEPT)
57
What is activated Partial Thromboplastin Time (aPTT) measuring?
* Assesses intrinsic and common pathways * Sensitive to factor VIII and IX deficiencies * May be used to monitor heparin
58
What is an anti-factor Xa activity assay?
Provides assessment of heparin and other factor Xa inhibitors (LMWH, fondaparinux)
59
Normal PLT count?
- > 100 K
60
What does activated clotting time (ACT) measure?
- Measures intrinsic and extrinsic pathways - whole clotting time - Normal is 107 +/- 13 secs - Used to measure responsiveness to heparin
61
Fill in this chart
62
MOA of cyclooxygenase inhibitors?
Inhibit COX-1 from forming TXA2 - which is important in plt aggregation
63
What are the COX inhibitors? How long do they affect platelets?
ASA - effects last 7-10 days after d/c NSAIDS - effects last 3 days
64
What are the P2Y12 inhibitors? MOA?
Clopidogrel, Ticlopidine, Ticagrelor, and Cangrelor Inhibit P2Y12-R→preventing GIIb/IIIa expression
65
How long do the antiplatelets effects last for the P2Y12 inhibitors?
* Clopidogrel: anti-plt effects x 7 days after d/c * Ticlopidine: anti-plt effects x 14-21 days after d/c * Ticagrelor & Cangrelor: Short-acting, < 24h activity
66
How do GIIb/IIIa antagonisits work? What drugs are in this class?
- Prevent vWF and fibrinogen from binding to the GIIb/IIIa receptors on platelets - Abciximab, Eptifibatide, Tirofiban
67
Warfarin inhibts...?
Vitamin K dependent clotting factors (2, 7, 9, 10, Protein C & S)
68
What is the drug of choice for valvular afib and valve replacements?
Warfarin
69
Heparin MOA?
Binds to antithrombin (increasing it's activity)→ directly inhibits soluble thrombin and Xa
70
Compare unfractionated heparin and LMWH?
Unfractionated: Short HL, given IV, Fully reversable w/Protamine, Close monitoring required LMWH: Longer HL, dosed BID SQ, No coag testing needed, Protamine only partially effective
71
Can you reverse fondaparinux with protamine?
No
72
What are the direct thrombin inhibitors and their MOA?
* Hirudin, Argatroban, Bivalirudin, Dabigatran * Bind/block thrombin in both soluble & fibrin-bound states
73
What anticoagulant is naturally occuring in leeches?
Hirudin
74
Which direct thrombin inhibitor has the shortest half life and is the DOC for liver/renal impairment?
Bivalirudin
75
What was the first direct oral anticoagulant?
Dabigatran (Pradaxa)
76
Which direct thrombin inhibitor reversibly binds thrombin? What labs are monitored intraop?
Argatroban PTT or ACT
77
What are the direct Xa inhibitors?
Rivaroxaban (Xarelto), Apixaban (Eliquis), Edoxaban (Savaysa)
78
What are the 2 categories or thrombolytics and the drugs in each category?
- Fibrin-specific: Alteplase (tPA), Reteplase, Tenecteplase - Non-fibrin specific: Streptokinase
79
How long should someone wait to have surgery who has received thrombolytic therapy?
10 days
80
What are the **absolute** contraindications to thrombolytic therapy?
81
What are the 2 subclasses of anti-fibrinolytics and the drugs in each?
1. Lysine analogues: Epsilon-amino-caproic acid (EACA) & Tranexamic Acid (TXA) 2. SERPIN: Aprotinin (removed from market d/t renal & cardio toxicity)
82
MOA of lysine analogues?
Binds & inhibits plasminogen from becoming plasmin→impairing fibrinolysis
83
What are the 4 factor replacements used to improve clotting?
- Recombinant VIIa - Prothrombin Complex Concentrate (PCC) - Fibrinogen concentratre - Cryoprecipitate and FFP
84
Which factor replacement increases generation of thrombin?
RfVIIa
85
Which factor replacement contains Vit K factors?
Prothrombin Complex Concentrates
86
When should warfarin be stopped and restarted perioperatively?
Low risk pts: 5 days prior, resumed 12-24hr post op High risk pts: 5 days prior, bridge with heparin through surgery
87
When should UFH and LMWH be stopped and restarted perioperatively?
UFH: stop 4-6h preop, resume >12 h post op LMWH: stop 24 preop, resume 24h post op
88
When should ASA be stopped before surgery?
Moderate and high risk pts: continue ASA Low risk: 7-10 days prior
89
How long should elective surgery be delayed for patients who have bare metal and drug eluting stents post PCI?
Bare metal - 6 weeks Drug-eluting - 6 months
90
Which anticoagulants do we need to worry about when preforming neuraxial anesthesia?
Heparin TID SQ Lovenox qD Warfarin
91
What drug would you give for emergent reversal of warfarin?
PCC (short 1/2 life) Vit K also for more sustained correction
92
Which DOAC has a reversal drug and what is it?
Dabigatran (Pradaxa) - reversed with Idarucizumab
93
Oral factor Xa inhibitors can be reversed with what?
Andexanet

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