B&l_Maloney: Anticoagulants

Front 1

What are the 2 major types of thrombi?

Back 1

Red and White thrombi

Front 2

HEMOSTASIS
↓
Initiation of coagulation
↓
Thrombin
↓
Fibrin
↓
Thrombus
Stasis of clotting factors

Back 2

red thrombus

Front 3

Where do red thrombi tend to occur?

Back 3

Atria

Veins

Front 4

**Red Thrombi**

Fibrinolysis

Immediate anticoagulation (IV)

Long term anticoagulation (Oral)

Very general tx of what?

Back 4

DVT

Front 5

**Red Thrombi**

Immediate anticoagulation(IV)

Long term anticoagulation (oral)***

Very general tx of what?

Back 5

Atrial Fibrillation

Front 6

What's being formed here?

Back 6

White Thrombus

Front 7

Where do white thrombi tend to occur?

Back 7

Arteries

Front 8

A-Fib & DVT

White or Red Thrombus?

Back 8

Red Thrombus

Front 9

STEMI, NSTEMI/Unstable angina/Percutaneous coronary intervention (PCI)

White or Red Thrombus?

Back 9

White Thrombus

Front 10

What do you target to stop the effects of Red Thrombi?

Back 10

Thrombin

Thrombus

Front 11

What do you target to stop the effects of White Thrombi?

Back 11

Platelet Aggregation

Thrombus

Thrombin

Front 12

What is the main difference between
the pharmacological treatment of
STEMI and NSTEMI?

Back 12

Use of Thrombolytics for STEMI (total occlusion of vessel)

We don't want to use thrombolytics with NSTEMIs due to the threat of bleeding

Front 13

Heparin

Factor Xa inhibitors

Direct thrombin inhibitors

Warfarin

These are classes of?

Back 13

Anticoagulants

Front 14

What are the "-parins"?

Enoxaparin**
Dalteparin
Tinzaparin

Back 14

Low Molecular Weight Heparin
(LMWH)

Front 15

Name the two types of Heparin agents

Back 15

Unfractionated Heparin

LMW Heparin

Front 16

MOA for Unfractionated Heparin?

Back 16

Accelerates the reaction between:
-Antithrombin and thrombin
-Antithrombin and Factor Xa**

Front 17

Unfractionated Heparin or LMWH?

-Subcutaneous (usually) or IV
-Predictable anticoagulant effect
-No monitoring of the aPTT
-Can be used at home
-Expensive

Back 17

LMWH

Front 18

Unfractionated Heparin or LMWH?

-IV (usually) or subcutaneous
-Unpredictable anticoagulant effect
-Monitor the aPTT

Back 18

UFH

Front 19

MOA LMW Heparin?

Back 19

Accelerates the reaction between:
-Antithrombin and Factor Xa

Front 20

What accelerates the reaction between AT and factor IIa (thrombin) or factor Xa by at least 1000 fold?

Back 20

Heparin

Front 21

What forms a ternary complex?

Back 21

UFH

note: need at leas 18 saccharide units

Front 22

What is the Anticoagulant of choice during pregnancy?

Back 22

Subcutaneous unfractionated heparin

or LMWH

Front 23

This needs to be monitored via aPTT

Back 23

UFH

Front 24

What drug Prevents thrombosis
**Prophylaxis and treatment**

Back 24

Heparin

Front 25

You suspect a patient is having Thromboembolism during pregnancy. What would you use to treat?

Back 25

Heparin (safe for preggers)

Front 26

What could you use for immediate anticoagulation during a STEMI?

Back 26

Heparin

Front 27

What would you use for these?

-Pulmonary embolism

-Deep vein thrombosis

-Thromboembolism during pregnancy***

-Postoperative venous thrombosis

-Arterial embolism (eg. from atrial fibrillation)

-ST-elevation myocardial infarction (STEMI)

-Unstable angina (UA) and Non ST-elevation myocardial infarction (NSTEMI)***

-Percutaneous coronary interventions (PCI)

Back 27

Heparin

Front 28

Type I – rapid, mild, transient

Type II – delayed, sustained, severe

These describe?

Back 28

Heparin Induced Thrombocytopenia
(HIT)

Front 29

UFH and to a lesser extent, LMWH
binds to plasma proteins including
platelet factor 4 (PF4)

Where does PF4 come from?

Back 29

Platelets

Front 30

Summary of Type II HIT
look this over....

Back 30

-Platelet factor 4 is released from activated platelets and binds to heparin

-Antibodies are produced to the heparin-PF4 complex

-These antibodies bind to the heparin-PF4 complex

-This immune complex (heparin-PF4-IgG) binds to platelet Fc receptors resulting in platelet activation

Front 31

What will happen to the platelet count
with HIT type 2?

Back 31

platelets DECREASE

Front 32

What is the predominant clinical
presentation with HIT type 2?

Back 32

Thrombosis

Front 33

Treatment for HIT?

Back 33

**Heparin must be stopped**

-Thrombosis can be treated with other
agents-->Direct thrombin inhibitors

Front 34

-Platelet count can decrease by 50%

- Thromboembolic complications
(limb loss 20-30%)

These are complications of?

Back 34

HIT

Front 35

What causes HIT more often? UHF or LMWH?

Back 35

UHF--> 1-5%

LMWH --> ~1%

Front 36

Should you give enoxaparin (LMWH) to
a patient who has HIT?

Back 36

NO

Even though it doesn't cause HIT as often LMWH should be avoided!

Front 37

Osteoporosis can occur with patients taking heparin for _____ months

Back 37

3-6

Front 38

**Osteoporosis**

UHF causes _______ and decreased _______

Back 38

bone reabsorption AND ↓ bone formation

Front 39

**Osteoporosis**

LMWH only causes _____________

Back 39

↓ bone formation

Front 40

-Active Bleeding

-Thrombocytopenia

-Coagulation disorders

-Increased risk of hemorrhage

-Avoid after surgery of brain, spinal cord, or eye*****

Contraindications for?

Back 40

Heparin

Front 41

A patient on Heparin is having life threatening bleeding? What is the Heparin antidote?

Back 41

Protamine Sulfate

Front 42

What are some precautions when using Protamine sulfate (Heparin antidote)?

Back 42

Can have anticoagulant effects

**Anaphylactic reactions** - diabetics who take protamine containing insulin

Front 43

Synthetic pentasaccharide sequence of heparin that is a selective factor Xa
inhibitor

Back 43

Fondaparinux

Front 44

Longer half life than LMWH
-17-21 hours
-Does not require monitoring

Clincal Use:
Prophylaxis of DVT in patients undergoinghip fracture surgery, hip or knee replacement surgery or abdominal surgery who are at risk for thromboembolic complications

Used for Acute DVT and Acute PE (Combined with Warfarin)

Back 44

Fondaparinux

Front 45

Hirudin - anticoagulant

Where does this come from?

Back 45

Salivary glands of leeches

Front 46

What are the 2 Thrombin Inhibitors (IV)?

Back 46

Lepirudin
-Recombinant derivative of hirudin

Bivalirudin
-Bivalent analog of hirudin

Front 47

What is the ORAL Thrombin inhibitor that is an alternative to Warfarin?

Back 47

Dabigatran

Front 48

"-rudin"

Back 48

Thrombin Inhibitors (IV)

Front 49

What is Dabigatran? What drug is it an alternative to?

Back 49

Oral Thrombin inhibitor

ALTERNATIVE TO WARFARIN

Front 50

-Directly bind to and inhibit thrombin

-Effects are independent of anti-thrombin

-Inhibits soluble (i.e. free) and fibrin-bound (i.e. in a clot) thrombin

This is the MOA of??

Back 50

Thrombin Inhibitors

Front 51

Clinical Use of Thrombin Inhibitors:

Heparin induced Thrombocytopenia

Back 51

Lepirudin

**Argatroban**

Front 52

Clinical Use of Thrombin Inhibitors:

Heparin-induced thrombocytopenia
undergoing percutaneous coronary
intervention (PCI)

Back 52

Bivalirudin

Front 53

Which Thrombin Inhibitor can cause allergic rxns including anaphylaxis?

Back 53

Lepirudin

Front 54

Which Thrombin Inhibitor can cause Dyspepsia and gastritis?

Back 54

Dabigatran (ORAL)

Front 55

What is an oral anticoagulant?

Back 55

Warfarin (Coumadin)

Front 56

MOA of Warfarin (Coumadin)?

Back 56

Vitamin K antagonist
Inhibits the synthesis of Vitamin K dependent clotting factors in the liver
-Factors II, VII, IX and X

-Inhibits the synthesis of protein C and protein S

Front 57

______ inhibits vitamin KO reductase,
thereby blocking the formation of vitamin vitamin KH2.

**This prevents the carboxylation (and hence production) of vitamin K dependent coagulation factors**

Back 57

Warfarin

Front 58

What happens if vitamin K
stays in the oxidized form?

Back 58

prevents the carboxylation (and hence production) of vitamin K dependent coagulation factors (X, IX, VII, II)

Front 59

Why does it take so long to get a peak
anticoagulant effect of warfarin?

A. Warfarin has a long half life

B. Poor bioavailability of warfarin

C. Long half life of preexisting clotting factors

D. Rapid loss of protein C and protein S

Back 59

C. Long half life of preexisting clotting factors

Front 60

The following describe the pharmokinetics of ______:

97% bound to plasma proteins
-Mainly albumin

Metabolized in liver

Narrow therapeutic index

Dosages vary greatly

Back 60

Warfarin

Front 61

T/F

If you eat foods high in Vit. K the effectiveness of Warfarin decreases

Back 61

TRUE

Front 62

Prevent thrombosis
-Takes 3-5 days to be effective
-Start in conjunction with Heparin

Back 62

Warfarin

Front 63

This drug is monitored with PT

Back 63

Warfarin

Standardized PT time = International
Normalized Ratio (INR)

Front 64

This drug can be used to prevent Thromboembolism in patients with:

-Chronic atrial fibrillation
-***Prosthetic heart valve***
-People at risk following surgery, trauma or
cancer

Back 64

Warfarin

Front 65

How would you use heparin and
warfarin to anticoagulate a
person who develops a DVT?

Back 65

Start both warfarin and heparin at the SAME time

warfarin= DELAYED

heparin= IMMEDIATE

**Stop Heparin once INR is in normal range**

Front 66

A patient is scheduled for an
angioplasty. What anticoagulant may be administered just prior to the procedure?

Back 66

UFH

Enoxaprin

Bivalirudin

Front 67

**Skin necrosis--from widespread
thrombosis**
-Occurs early in therapy (within the first 10 days)

-**Possibly due to reduced activity of Protein C**

This is an adverse effect of?

Back 67

Warfarin

Front 68

What is Protein C?

Back 68

Endogenous anticoagulant

With a half life of only 8 hours
(Less than most of the other vitamin
K dependent clotting factors)

Front 69

**Purple toe syndrome**
-Usually occurs within 3-10 weeks

-Release of **cholesterol microemboli** from atheromatous plaques

Adverse effect of?

Back 69

Warfarin

Front 70

A syndrome characterized by nasal
hypoplasia and stippled epiphyseal
calcifications that resemble chondrodysplasia punctata.
(Bone Problems)

Assosciated with?

Back 70

1st Trimester Use of Warfarin

Front 71

Is warfarin teratogenic?

Back 71

YES

**Especially in 1st Trimester**

(not as common in 2nd and 3rd trimesters)

Front 72

When would you consider using warfarin in a pregnant patient?

Back 72

When she has a mechanical heart valve

Front 73

This drug:

-When used alone, it can cause venous limb gangrene or multicentric skin necrosis

-The rapid loss of the endogenous
anticoagulant, protein C, can cause a **hypercoagulated state**

Back 73

Warfarin

**Heparin Induced Thrombocytopenia**

Front 74

A 47-year-old male with a history of atrial fibrillation that is being treated with metoprolol and warfarin presents to the emergency department with a nose bleed. His INR is measured at 9.3 (target 2.0-3.0). How can youstop the bleeding (i.e. stop/counteract the effects of warfarin)?

Back 74

GIVE VITAMIN K

Then, clotting factors, frozen plasma, prothromin concentrate

Front 75

A 67-year-old female with hypertension, heart failure, and chronic kidney disease (CKD stage 3) was admitted with chest pain and shortness of breath. Her ECG was normal, however, there is suspicion of a UTI. She was started on unfractionated heparin (UFH) infusion for suspicion of a pulmonary embolism. She also was noted to have exacerbation of her heart failure (ejection fraction 25%). She began treatment for the UTI with ceftriaxone. On hospital day 7, her platelet count declined from 289 x 109/L on admission to 75 x 109/L. The aPTT prior to starting heparin was 28 seconds (normal 20-35 sec) and is now 57 sec (therapeutic range 48-71 sec). What drug change would you most likely make?

Back 75

PATIENT HAS HIT

Stop UFH, Start Lepirudin

Front 76

Know this...

Back 76

It's for anti-platelet stuff

Front 77

Name a Cyclooxygenase Inhibitor

Back 77

Aspirin

Front 78

MOA of Cyclooxygenase Inhibitors (Aspirin)?

Back 78

Irreversibly inhibits cyclooxygenase
-Greater inhibition of COX-1 than COX-2

Blocks the production of TxA2
-Platelets

Front 79

Do you want to inhibit the production of
PGI2 or TxA2 when using Aspirin?

Back 79

TxA2 !!!

Inhibiting PGI2 would cause Vasocontriction and platelet aggregation

Front 80

PGI2

-Platelet Aggregation and causes Vasoconstiction

or

-Inhibits platelet aggregation and causes Vasodilation

Back 80

-Inhibits platelet aggregation and causes Vasodilation

Front 81

Why is cyclooxygenase inhibited for
only a short time in endothelial cells
and forever in the platelet?

Back 81

Platelets lack nuclei and can't make more proteins...

Endothelial cells HAVE NUCLEI...

Front 82

Other than Aspirin, What is the MOA of other NSAIDs, like ibuprofen?

Back 82

Reversibly Inhibit COX-1 and COX-2

Front 83

Can we use COX-2 inhibitors for anti-platelet therapy?

Back 83

NO

Potentially Cardiotoxic

Apsirin negates any GI benefit from using a COX-2

(COX-2's are easier on the stomach)

Front 84

Adverse Effect:
**GI irritation and Bleeding**

Back 84

Aspirin

-Inhibits the synthesis of prostaglandins that promote secretion of bicarbonate and mucous

Front 85

Name the ADP Receptor Antagonists (2)

Back 85

Clopidogrel
Prasugrel

Front 86

"-grel"

Back 86

Clopidogrel

Prasugrel

**ADP Receptor Antagonists**

Front 87

GP IIb/IIIa Receptor Antagonist?

Back 87

Abciximab

Front 88

It's 2 AM... here... have fun

Back 88

Front 89

Which of the following agents may be used for the secondary prevention of an acute MI? (select all that apply)

A. Abciximab
B. Aspirin
C. Clopidogrel
D. Dalteparin

Back 89

Clopedigrel

Front 90

Which of the following agents may be used to prevent thrombosis during PCI? (select all that apply)

A. Abciximab
B. Aspirin
C. Clopidogrel
D. Dalteparin
E. Warfarin

Back 90

A. Abciximab
B. Aspirin
C. Clopidogrel
D. Dalteparin

Front 91

Which Thrombolytic is isolated from Streptococci?

Back 91

Streptokinase

Front 92

What is t-PA?

Back 92

Tissue Type Plasminogen Activator

breaks up clots...

Front 93

What are the recombinant t-PA thrombolytics?

Back 93

Alteplase

Reteplase

Tenecteplase

Front 94

"-plase"

Back 94

Recombinant t-PA Thrombolytics

Front 95

MOA of thrombolytics?

Back 95

Catalyze the formation of plasmin fromplasminogen

- Plasmin degrades fibrin

-Helps promote dissolution of a clot

Front 96

These agents are Not for unstable angina or NSTEMI

**Increased risk of death, MI and bleeding**

Back 96

Thrombolytics

Front 97

If a patient has an extensive, proximal DVT

or

Pulmonary Embolism (hemodynamically unstable)

What would you use?

Back 97

Thrombolytic

these break up clots

Front 98

This thrombolytic can cause and allergic anaphylaxis and hypotension

Back 98

Streptokinase