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Pharmacology Test 4 > Chapter 34: Coagulation Disorders > Flashcards

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
Warfarin Class: MOA: Effect:
Warfarin Class: Anticoagulant Oral MOA: Decrease synthesis of clotting factors Effect: Prevent Venous Thrombosis
26
Aspirin Class: MOA: Effect:
Aspirin Class: Anti-platelet Drug MOA: Decrease platelet aggregation Effect: Prevent Arterial Thrombosis
27
Streptokinase Class: MOA: Effect:
Streptokinase Class: Thrombolytic Drug MOA: Fibrinolysis Effect: Breakdown Thrombi
28
Name 8 Anti-coagulants
Heparin Hirudin Warfarin Streptokinase t-PA Aspirin Clopidogril Abciximab (HAS WATCH)
29
Name 5 Pro-coagulants
Vitamin K FFP Demopressin Acetate Aminocaprioic Acid Tranexamic acid (VDAFT)
30
What are indirect thrombin inhibitors? Examples.
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
What are toxicities associated with Heparin?
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
What to do if someone has HIT?
Caused by Antibody to heparin D/C heparin Platelets, FFP
33
What are the two main laboratory test for clotting time?
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
How do you reverse heparin?
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
What are the contraindications of heparin?
Active bleeding Hemophilia Thrombocytopenia Severe HTN Intracranial Hemorrhage Infective endocarditis Active TB GI ulcers Advanced Hepatic Disease (AGHASTIIA)
36
How do direct thrombin inhibitors work?
Bind to both active and substrate recognition sites of thrombin. Hirudin
37
What is the Pharmacokinetics of Warfarin? MOA?
100% oral availability Protein binding 99% Long half life 36 hours MOA: Targets and inhibits Vitamin K reductase, decreasing synthesis of clotting factors
38
How long of a delay is the onset of action for Warfarin? How do you reverse warfarin? Warfarin Toxicity?
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
What are some newer drugs that can be used in place of warfarin? What is the downside to this?
These new drugs will target Factor X or Thrombin Eliquis (Apixaban) Xarelto (Rivaroxaban) No reversal, Vitamin K won't work.
40
How do Fibrinolytics work?
Rapidly lyse thrombi Catalyze the formation of serine protease plasmin
41
How does aspirin work?
Aspirin is a COX inhibitor and prevent TXA2 from being produce. Increase Bleeding Time
42
What does TXA2 do?
Causes platelet changes (shape, degranulate, aggregate)
43
How does Clopidogrel (Plavix) and Ticlopidine (Ticlid) work? What are the Adverse Drug Effects of these two drugs?
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
What are the IIb/IIIa Receptor Blockers?
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
Where do you find Vitamin K? What does it confer activity on?
They are fat soluble vitamins found in leafy green vegetables and gut bacteria. Confers activity on Prothrombin, Factor VII, IX, and X
46
When do you use plasma fractions?
Deficiencies in plasma coagulation factors like Hemophilia and Antithrombin Deficiency
47
What are Fibrinolytic Inhibitors used for?
Aminocarproic acid competitively inhibits plasminogen activation. Used for: Adjunctive hemophilia therapy Bleeding from Fibrinolytic therapy Intracranial Aneurysms Post surgical bleeding
48
Heparin Category: Class: Target: Result: Disorder:
Heparin Category: Anticoagulant Class: Indirect Thrombin Inhibitor Target: Antithrombin (+) activates Result: Clot prevention Disorder: Venous Thrombosis
49
Hirudin Category: Class: Target: Result: Disorder:
Hirudin Category: Anticoagulant Class: Direct Thrombin Inhibitor Target: Thrombin (-) inactivates Result: Clot prevention Disorder: Venous Thrombosis
50
Warfarin Category: Class: Target: Result: Disorder:
Warfarin Category: Anticoagulants Class: Direct Thrombin Inhibitor (Vit K) Target: Thrombin (-) inactivates Result: clot prevention Disorder: Venous Thrombosis
51
Rivaroxaban/ Apixaban Category: Class: Target: Result: Disorder:
Rivaroxaban/ Apixaban Category: Anticoagulants Class: Factor Xa Inhibitor Target: Factor Xa Result: Clot Prevention Disorder: Stroke, VTE
52
Streptokinase Category: Class: Target: Result: Disorder:
Streptokinase Category: Thrombolytic Class: Bacterial Target: Plasminogen (+) activates Result: Clot Lysis Disorder: MI, PE
53
t-PA Category: Class: Target: Result: Disorder:
t-PA Category: Thrombolytic Class: rHuman Target: Plasminogen (+) activates Result: Clot Lysis Disorder: MI, PE
54
Aspirin Category: Class: Target: Result: Disorder:
Aspirin Category: Antiplatelet Aggregation Class: COX inhibitor Target: Platelet prostaglandin Result: Anti-aggregation Disorder: Arterial Thrombus
55
Clopidogrel Category: Class: Target: Result: Disorder:
Clopidogrel Category: Antiplatelet Aggregation Class: ADP inhibitor Target: ADP receptor Result: anti-aggregation Disorder: Coronary Stent
56
Abciximab Category: Class: Target: Result: Disorder:
Abciximab Category: Antiplatelet Aggregation Class: Antibody Target: IIb/IIIa Result: anti-aggregation Disorder: acute coronary syndrome
57
Vitamin K Category: Class: Target: Result: Disorder:
Vitamin K Category: Hemostatic Class: Factor replenish Target: Oxidation/reduction Result: Normal factor production Disorder: Warfarin OD, Vit K def
58
Plasma (fractions) Category: Class: Target: Result: Disorder:
Plasma Category: Hemostatic Class: Factor replenish Target: Multiple Result: Normal Clotting Cascade Disorder: Hemophilia
59
Aminocaproic acid/ Tranexamic Acid Category: Class: Target: Result: Disorder:
Aminocaproic acid/ Tranexamic Acid Category: Hemostatic Class: Fibrinolytic Inhibitor Target: Plasminogen (-) inactivates Result: Stable clot Disorder: Post Surgical
60
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?
Phospholipid Tissue Factor
61
Beside Hirudin, what is also a direct thrombin inhibitor?
Digabatran (Pradaxa)

Pharmacology Test 4 (5 decks)

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