Chapter 34: Coagulation Disorders Flashcards

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1
Q

Where does thrombogenesis usually occur and what will this lead to?

A

Thrombogenesis occurs in the blood vessels.

This will lead to:
Vasoconstriction
Formation of Platelet Plugs
Regulation of Coagulation and Fibrinolysis

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2
Q

What are the four phases of platelets?

A
  1. Adhesion to wounded area
  2. Aggregation- binding
  3. Secretion- pro-coagulation proteins to stablize clot
  4. Cross-linking of adjacent platelets
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3
Q

In a normal healthy vasculature, what will act as a anti-thrombogenesis?

A

PGI2 or prostacyclin

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4
Q

When there is a wall defect what two proteins are exposed in the vascular layer?

When these proteins bind to platelets, what receptors will they specifically bind to?

What will happen after the proteins are bound to the platelet?

How are platelets cross-linked?

A

Collagen and von Willebrand Factor

Collagen will bind to GP1a and vWF GP1b of the platelets.

Platelet will become activated and release ADP, TXA2, and 5-HT which will aid in clotting process and activate additional platelets and cause degranulation.

Platelets are cross-linked with Fibrin binding to the GP IIb/IIIa receptors.

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5
Q

How is fibrin produced?

A

The clotting cascade activates thrombin which activates fibrinogen that is converted into a fibrin clot. (platelet-fibrin pattern)

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6
Q

What factor does the intrinsic and extrinsic pathway activate?

A

Factor X.

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7
Q

Describe the Extrinsic Pathway

A
  1. Trauma will expose tissue factor
  2. Tissue factor will active Factor 7 (VIIa) (produced in the liver)
  3. Addition tissue factor will cause VIIa to activate Factor X.
  4. Common Pathway
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8
Q

Describe the Intrinsic Pathway

A
  1. Damage surface will activate Factor XII
  2. Factor XII will activate Factor XI
  3. Factor XI will activate Factor IX
  4. Factor IX will activate Factor X
  5. Common Pathway
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9
Q

Describe the Common Pathway

A
  1. Factor X is activated. Xa will convert Prothrombin to Thrombin
  2. Thrombin converts Fibrinogen to Fibrin
  3. Fibrin with the help of Factor XIII will cross link the fibrin clot
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10
Q

What factor will Thrombin activate?

A

Thrombin will activate Factor VIII
Which will activate the common pathway to make even more of a stable clot.

Factor VIII deficiency is called hemophilia

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11
Q

What does Tissue Factor Peptide Inhibitor do?

What dose antithrombin do?

A

TFPI will inhibit Factor VII.

Antithrombin will inhibit Factor X and Thrombin.

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12
Q

What does protein C do?

A

Protein C will inhibit Factor VIII .

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13
Q

What is a problem that can form with clots?

A

Deep Vein Thrombosis
-forms in large veins of the lower limbs
-serious and potential fatal

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14
Q

What is the Virchow’s Triad?

A

Factors that predisposes an individual to developing a blood clot.
1. Stasis - decrease blood flow (bed ridden patients)
2. Endothelial Injury -damage to the inside of the blood vessel
3. Hypercoagulability - blood clots are likely

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15
Q

What is DIC?

What is the result of DIC?

A

Overstimulation of the blood clotting mechanism.

DIC will use up all the clotting factors which will lead to spontaneous bleeding.

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16
Q

What is the cause of DIC?

What is the treatment for DIC?

A

Cause:
Massive Tissue Injury (crush injury)
Malignancy
Bacterial Sepsis
Abruptio Placentae

Treatment:
FFP
Treat underlying cause
10-50% mortality

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17
Q

What are the two major systems in regulation of coagulation?

A

Fibrin Inhibition
Fibrinolysis

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18
Q

What are the protease inhibitors?

A

They rapidly inactivate the coagulation proteins
-Alpha 1 (antiprotease)
-Alpha 2 (macroglobulin/ antiplasmin)
-Antithrombin

These function to prevent clot formation all over the body

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19
Q

How does the Fibrinolytic System work?

A

When the clot forms, the fibrinolytic system will convert inactive plasminogen to plasmin through tPA released from injured cells.

Plasmin will degrade the fibrin clot.

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20
Q

What is the function of Plasmin.

A

Remodel the thrombus
Limits the extension of the thrombus.

Plasmin will also:
Break down Fibrinogen to degradation products
Break down Fibrin to Fibrin split products

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21
Q

What are ways to activate plasminogen?

A

Tissue Plasminogen Activator (tPA)
Urokinase from the kidneys
Streptokinase

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22
Q

In cases that we want a clot to stabilize what will protect clots from Lysis?

A

Aminocaproic Acid will block plasminogen from turning into plasmin

Usually used after surgery to prevent clot breakdown.

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23
Q

What are the four groups of coagulation modifiers?

A
  1. Anticoagulants - inhibit formation of clotting factors, prevent clot formation.
  2. Anti-platelet Drugs- inhibit platelet aggregation, prevent platelet plugs
  3. Thrombolytic Drugs (Fibrinolytic)- lyse (breakdown) existing clots
  4. Hemostatic or Anti-fibrinolytic Drugs- promote blood coagulation
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24
Q

Heparin
Class:
MOA:
Effect:

A

Heparin
Class: Anticoagulation Parenteral
MOA: Binds and activates Antithrombin, increase activity 1000x
Effect: Prevent Venous Thrombosis

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25
Q

Warfarin
Class:
MOA:
Effect:

A

Warfarin
Class: Anticoagulant Oral
MOA: Decrease synthesis of clotting factors
Effect: Prevent Venous Thrombosis

26
Q

Aspirin
Class:
MOA:
Effect:

A

Aspirin
Class: Anti-platelet Drug
MOA: Decrease platelet aggregation
Effect: Prevent Arterial Thrombosis

27
Q

Streptokinase
Class:
MOA:
Effect:

A

Streptokinase
Class: Thrombolytic Drug
MOA: Fibrinolysis
Effect: Breakdown Thrombi

28
Q

Name 8 Anti-coagulants

A

Heparin
Hirudin
Warfarin
Streptokinase
t-PA
Aspirin
Clopidogril
Abciximab

(HAS WATCH)

29
Q

Name 5 Pro-coagulants

A

Vitamin K
FFP
Demopressin Acetate
Aminocaprioic Acid
Tranexamic acid

(VDAFT)

30
Q

What are indirect thrombin inhibitors?

Examples.

A

These drugs will activate and enhance antithrombin activity which will inactivate Factor X.

Unfractionated Heparin (High Molecular Weight) - wraps around entire complex of ATIII/Thrombin/Factor Xa for inhibition

Less effect (less side effects):
LMW heparin (Binds to ATIII/Factor Xa)
Fondaparinux (Binds to ATIII only)

31
Q

What are toxicities associated with Heparin?

A

Bleeding
-monitor aPTT (activated partial thromboplastin time)
-LMW heparins more predictable plasma levels
-Elderly women and pt w/ renal failure more prone to hemorrhage

Transient Thrombocytopenia
-Heparin induced thrombocytopenia (HIT)

32
Q

What to do if someone has HIT?

A

Caused by Antibody to heparin
D/C heparin
Platelets, FFP

33
Q

What are the two main laboratory test for clotting time?

A

Prothrombin Time (PT)
-assess function of the extrinsic system (Factor VII)and common pathway of the coagulation cascade
-addition of tissue factor (III)
-Time to clot compared to control (INR)
Normal INR: 0.8-1.2 Warfarin Target: 2-3

aPTT
- assess the function of the intrinsic system and common pathway
-Phospholipid added to induce intrinsic pathway
-Normal: 35-45 seconds

34
Q

How do you reverse heparin?

A

D/c drug
Give protamine sulfate (high positive charge molecule)
-heparin is negatively charge and bind with reversal.
-Protamine by itself is an anticoagulant
-Less effect on LMW, effect for HMW Heparin
-No effect on fondaparinux

35
Q

What are the contraindications of heparin?

A

Active bleeding
Hemophilia
Thrombocytopenia
Severe HTN
Intracranial Hemorrhage
Infective endocarditis
Active TB
GI ulcers
Advanced Hepatic Disease

(AGHASTIIA)

36
Q

How do direct thrombin inhibitors work?

A

Bind to both active and substrate recognition sites of thrombin.

Hirudin

37
Q

What is the Pharmacokinetics of Warfarin?

MOA?

A

100% oral availability
Protein binding 99%
Long half life 36 hours

MOA: Targets and inhibits Vitamin K reductase, decreasing synthesis of clotting factors

38
Q

How long of a delay is the onset of action for Warfarin?

How do you reverse warfarin?

Warfarin Toxicity?

A

8-12 hours
Start low, go slow

Reversal:
Stop the drug
large dose of Vit K
FFP
Factor IX concentrates

Toxicity: Hemorrhagic disorder in the fetus, birth defects, cutaneous necrosis

39
Q

What are some newer drugs that can be used in place of warfarin?

What is the downside to this?

A

These new drugs will target Factor X or Thrombin

Eliquis (Apixaban)
Xarelto (Rivaroxaban)

No reversal, Vitamin K won’t work.

40
Q

How do Fibrinolytics work?

A

Rapidly lyse thrombi
Catalyze the formation of serine protease plasmin

41
Q

How does aspirin work?

A

Aspirin is a COX inhibitor and prevent TXA2 from being produce.
Increase Bleeding Time

42
Q

What does TXA2 do?

A

Causes platelet changes
(shape, degranulate, aggregate)

43
Q

How does Clopidogrel (Plavix) and Ticlopidine (Ticlid) work?

What are the Adverse Drug Effects of these two drugs?

A

Irreversibly inhibit ADP receptors on platelets
Reduce platelet aggregation

ADR:
Nausea
Indigestion (Dyspepsia)
Diarrhea
Hemorrhage
Leukopenia - low WBC count
TTP
(LT. HIND)

Thrombocytopenic Purpura (TTP) Microvascular clots- Ticlopidine - give FFP, ADAMST13

44
Q

What are the IIb/IIIa Receptor Blockers?

A

Anti-platelets that target the IIb/IIIa receptor complex.
Antibodies to prevent cross linking from occuring.
Overall effect: inhibit platelet aggregation.

Abciximab- monoclonal antibody

45
Q

Where do you find Vitamin K?

What does it confer activity on?

A

They are fat soluble vitamins found in leafy green vegetables and gut bacteria.

Confers activity on Prothrombin, Factor VII, IX, and X

46
Q

When do you use plasma fractions?

A

Deficiencies in plasma coagulation factors like Hemophilia and Antithrombin Deficiency

47
Q

What are Fibrinolytic Inhibitors used for?

A

Aminocarproic acid competitively inhibits plasminogen activation.

Used for:
Adjunctive hemophilia therapy
Bleeding from Fibrinolytic therapy
Intracranial Aneurysms
Post surgical bleeding

48
Q

Heparin
Category:
Class:
Target:
Result:
Disorder:

A

Heparin
Category: Anticoagulant
Class: Indirect Thrombin Inhibitor
Target: Antithrombin (+) activates
Result: Clot prevention
Disorder: Venous Thrombosis

49
Q

Hirudin
Category:
Class:
Target:
Result:
Disorder:

A

Hirudin
Category: Anticoagulant
Class: Direct Thrombin Inhibitor
Target: Thrombin (-) inactivates
Result: Clot prevention
Disorder: Venous Thrombosis

50
Q

Warfarin
Category:
Class:
Target:
Result:
Disorder:

A

Warfarin
Category: Anticoagulants
Class: Direct Thrombin Inhibitor (Vit K)
Target: Thrombin (-) inactivates
Result: clot prevention
Disorder: Venous Thrombosis

51
Q

Rivaroxaban/ Apixaban
Category:
Class:
Target:
Result:
Disorder:

A

Rivaroxaban/ Apixaban
Category: Anticoagulants
Class: Factor Xa Inhibitor
Target: Factor Xa
Result: Clot Prevention
Disorder: Stroke, VTE

52
Q

Streptokinase
Category:
Class:
Target:
Result:
Disorder:

A

Streptokinase
Category: Thrombolytic
Class: Bacterial
Target: Plasminogen (+) activates
Result: Clot Lysis
Disorder: MI, PE

53
Q

t-PA
Category:
Class:
Target:
Result:
Disorder:

A

t-PA
Category: Thrombolytic
Class: rHuman
Target: Plasminogen (+) activates
Result: Clot Lysis
Disorder: MI, PE

54
Q

Aspirin
Category:
Class:
Target:
Result:
Disorder:

A

Aspirin
Category: Antiplatelet Aggregation
Class: COX inhibitor
Target: Platelet prostaglandin
Result: Anti-aggregation
Disorder: Arterial Thrombus

55
Q

Clopidogrel
Category:
Class:
Target:
Result:
Disorder:

A

Clopidogrel
Category: Antiplatelet Aggregation
Class: ADP inhibitor
Target: ADP receptor
Result: anti-aggregation
Disorder: Coronary Stent

56
Q

Abciximab
Category:
Class:
Target:
Result:
Disorder:

A

Abciximab
Category: Antiplatelet Aggregation
Class: Antibody
Target: IIb/IIIa
Result: anti-aggregation
Disorder: acute coronary syndrome

57
Q

Vitamin K
Category:
Class:
Target:
Result:
Disorder:

A

Vitamin K
Category: Hemostatic
Class: Factor replenish
Target: Oxidation/reduction
Result: Normal factor production
Disorder: Warfarin OD, Vit K def

58
Q

Plasma (fractions)
Category:
Class:
Target:
Result:
Disorder:

A

Plasma
Category: Hemostatic
Class: Factor replenish
Target: Multiple
Result: Normal Clotting Cascade
Disorder: Hemophilia

59
Q

Aminocaproic acid/ Tranexamic Acid
Category:
Class:
Target:
Result:
Disorder:

A

Aminocaproic acid/ Tranexamic Acid
Category: Hemostatic
Class: Fibrinolytic Inhibitor
Target: Plasminogen (-) inactivates
Result: Stable clot
Disorder: Post Surgical

60
Q

For a aPTT test, what is added to the blood induce the intrinsic pathway?

For a PT test, what is added to the blood to induce the extrinsic pathway?

A

Phospholipid

Tissue Factor

61
Q

Beside Hirudin, what is also a direct thrombin inhibitor?

A

Digabatran (Pradaxa)