Exam 4: Coagulation

Question 1

What are the 5 inherited risk factors for DVT?

Answer 1

1. Antithrombin III deficiency
2. Protein C deficiency
3. Protein S deficiency
4. Sickle cell anemia
5. Activated protein C resistance

Question 2

What are the 6 acquired risk factors for DVTs?

Answer 2

1. Bedridden
2. Surgery/trauma
3. Obesity
4. Estrogen use
5. Malignancies
6. Chronic venous insufficiency

Question 3

What is DIC?

Answer 3

Disseminated Coagulation
Overstimulation of the blood clotting mechanism

Question 4

What usually causes DIC?

Answer 4

Bacterial sepsis (gram-negative bacteria)

Question 5

What are the 4 causes of DIC?

Answer 5

1. Massive tissue injury
2. Malignancy (cancer)
3. Bacterial sepsis
4. Abruptio Placentae

Question 6

What are the 2 ways we regulate coagulation?

Answer 6

1. Fibrin inhibition
2. Fibrinolysis (breaking down fibrin)

Question 7

What are protease inhibitors?

Answer 7

Enzymes that rapidly inactivate coagulation proteins

Question 8

What 3 things break down active clotting factors?

Answer 8

1. A1-antiprotease
2. A2-macroglobulin
3. A2-antiplasmin

Question 9

What are the 4 types of coagulation modifier drugs?

Answer 9

1. Anticoagulants
2. Antiplatelet drugs
3. Thrombolytic drugs
4. Antifibrinolytic drugs

Question 10

What are the 9 contraindications for taking heparin? What question do we normally think of when thinking of contraindications?

Answer 10

Will this patient likely bleed out? If so, that is a contraindication
1. Active bleeding
2. Hemophilia
3. Thrombocytopenia (decreased plts)
4. Severe HTN
5. Intracranial hemorrhage
6. Infective endocarditis
7. Active TB
8. GI ulcers
9. Advanced hepatic disease

Question 11

What 3 things do blood vessels normally do when there is damage?

Answer 11

1. Vasoconstriction
2. Form platelet plugs
3. Regulate coagulation and fribinolysis

Question 12

What are the 4 phases of thrombogenesis?

Answer 12

1. Adhesion
2. Aggregation
3. Secretion
4. Cross-linking of adjacent platelets

Question 13

What is the difference between the extrinsic and intrinsic pathway?

Answer 13

Extrinsic - exposes tissue factor
Intrinsic - damage endothelium

Question 14

What is Virchow’s triad?

Answer 14

1. Stasis
2. Hypercoagulability
3. Endothelial injury

Question 15

What are the characteristics of white thrombi?

Answer 15

Thrombi in high-pressure arteries w/ abnormal endothelium
Only plt and fibrin crosslinking
Cause ischemia downstream
Forms fibrin clot

Question 16

What are the characteristics of red thrombi?

Answer 16

Thrombi in low pressure veins
RBC build up around the white thrombus
There is lots of fibrin and a long tail b/c of the build up
They usually become detached and lead to pulmonary emboli

Question 17

What are the treatments for DIC?

Answer 17

1. Plasma transfusions (w/ plts or clotting factors)
2. Treat the underlying cause

Question 18

What are the 3 indirect thrombin inhibitors?

Answer 18

1. Heparin
2. LMW Heparin
3. Fondapurinux

Question 19

What are the 2 direct thrombin inhibitors?

Answer 19

1. Lepirudin (Hirudin)
2. Argatroban (Pradaxa)

Question 20

How do indirect thrombin inhibitors work?

Answer 20

They inactivate factor Xa and enhance antithrombin activity

Question 21

What is heparin’s MOA?

Answer 21

Binds and activates antithrombin; enhancing its activity and blocking thrombin

Question 22

What is the MW of unfractionated/unpurified heparin?

Answer 22

5-30,000

Question 23

Where is Heparin extracted from?

Answer 23

Pig intestinal mucosa and cow lung (porcine and bovine)
Family of molecules w/ different molecular weights

Question 24

What is the difference between LMW heparin and unfractionated?

Answer 24

LMW heparin is more specific for factor Xa

Question 25

How can you recognize LMW heparin drugs?

Answer 25

-parin

Question 26

What are the major toxicities of heparin?

Answer 26

BLEEDING HIT and TTP

Question 27

What is HIT?

Answer 27

Heparin induced thrombocytopenia; heparin is recognized by the immune system and makes antibodies against it causing the body to get rid of platelets

Question 28

Who is more prone to hemorrhage while taking heparin?

Answer 28

Elderly women and patients with renal failure

Question 29

What two lab tests do we do to monitor bleeding/coagulation time?

Answer 29

aPTT and PT

Question 30

What is PT and aPTT?

Answer 30

Prothrombin time - assesses the extrinsic system Activated partial thromboplastin time - monitors the intrinsic pathway

Question 31

Explain PT

Answer 31

Looks at the extrinsic system Tissue factor is added and we record the time it takes to clot We compare these numbers to normal patients (INR) and see the difference

Question 32

What is a normal INR?

Answer 32

0.8-1.2

Question 33

Explain aPTT

Answer 33

Looks at the intrinsic system We add phospholipids to induce the intrinsic pathway

Question 34

What is a normal aPTT?

Answer 34

35-45 seconds

Question 35

What is the reversal for heparin?

Answer 35

STOP THE DRUG Give protamine sulfate

Question 36

How does protamine sulfate work?

Answer 36

Since it is positively charged, it binds together w/ negatively charged heparin and gets rid of the heparin

Question 37

What are the effects of protamine sulfate on LMW and fondaparinux?

Answer 37

Less effect on LMW and no effect on fondaparinux

Question 38

Where does protamine sulfate come from?

Answer 38

Salmon sperm

Question 39

Why do we need to taper protamine sulfate?

Answer 39

Excess can act as an anticoagulant

Question 40

What is fondaparinux?

Answer 40

Pentasaccharide molecule of heparin that is synthetic

Question 41

What is the benefit of fondaparinux?

Answer 41

Less bleeding risks

Question 42

What can fondaparinux be used for?

Answer 42

HIT

Question 43

What is the difference between Hirudin (Lepirudin) and Argatroban/Dabigatran (Pradaxa)

Answer 43

Hirudin binds both to the active and substrate recognition sites of thrombin Pradaxa binds only to the thrombin active site

Question 44

Where do we get hirudin from?

Answer 44

Leeches

Question 45

Where do we get Argatroban and Pradaxa from?

Answer 45

Biological sources

Question 46

What are 3 coumarin anticoagulants?

Answer 46

Warfarin (coumadin) Rivaroxaban (Xarelto) Apixaban (Eliquis)

Question 47

Where was warfarin discovered?

Answer 47

University of wisconsin

Question 48

What was warfarin originally used for?

Answer 48

Rat poison; cause for cattle hemorrhagic disease

Question 49

How is warfarin administered? What is the bioavailability? What is the half life? What is the delay in onset?

Answer 49

Orally; 100%; 36 hours; 8-12 hours

Question 50

What is the MOA of warfarin?

Answer 50

Warfarin blocks the gamma carboxylation of several glutamate residues Warfarin will block vitamin K reductase

Question 51

What 4 clotting factors production are blocked by warfarin?

Answer 51

2, 7, 9, 10 1972

Question 52

What are the 3 main toxicities of warfarin?

Answer 52

1. Hemorrhagic disorder in the fetus 2. Birth defects 3. Cutaneous necrosis

Question 53

What is warfarin's therapeutic range determined by? What's the target ranges for warfarin?

Answer 53

INR; 2-3

Question 54

What are the 3 important things to do when reversing warfarin?

Answer 54

1. Stop the drug and give vitamin K 2. Give FFP that contain clotting factors 3. Give factor 9 concentrates

Question 55

What are rivaroxaban (xarelto) and apixaban (eliquis) specific for? What is the benefit of them? What is their reversal?

Answer 55

Specific for acting on Xa They cause less problems w/ bleeding out There is no reversal

Question 56

What do fibrinolytics do?

Answer 56

Rapidly lyse thrombi and catalyze the formation of serine protease plasmin

Question 57

What are the 3 fibrinolytics?

Answer 57

1. TPA 2. Streptokinase 3. Urokinase

Question 58

Where is TPA produced?

Answer 58

Directly in the spot of damage and recombinantly in the lab

Question 59

Where are streptokinase and urokinase synthesized from?

Answer 59

Streptococci and the kidney

Question 60

What are 3 antiplatelets?

Answer 60

1. Aspirin 2. Clopidogrel (plavix) 3. Abciximab

Question 61

How does ASA work?

Answer 61

COX1 selective; prevents activation of arachidonic acid cascade and produces less TXA This inc. bleeding time and reduces plt aggregation

Question 62

How does clopidogrel (plavix) work?

Answer 62

Irreversibly inhibits the ADP receptor on plts and reduces platelet aggregation

Question 63

What does plavix reduce?

Answer 63

Ischemic events

Question 64

When is plavix generally used?

Answer 64

Angioplasty and stent placements

Question 65

How does abciximab work?

Answer 65

Targets GP2b and 3a = which are the glycoproteins that cause plt aggregation to occur Blocks receptors and blocks aggregation

Question 66

What 3 drugs are used for bleeding disorders?

Answer 66

1. Vitamin K 2. FFP (plasma fractions) 3. Desmopressin

Question 67

Is vitamin k water or fat soluble? Where does it come from? What does vitamin K help with? Where does vit. K work on?

Answer 67

Fat-soluble Leafy green veggies and gut bacteria Helps w/ making residues needed for clotting factors Works on prothrombin, and factors 7,9 and 10

Question 68

What does desmopressin do? What 2 things does it help with?

Answer 68

Inc. factor 8 availability Mild hemophilia A and Von Willebrand disease

Question 69

What are 2 fibrinolytic inhibitors?

Answer 69

1. Aminocaproid acid 2. Tranexamic acid (TXA)

Question 70

What are the 4 uses for aminocaproic acid?

Answer 70

1. Adjunctive hemophilia therapy 2. Bleeding from fibrinolytic therapy 3. Intracranial aneurysms 4. Post-surgical bleeding

Question 71

What does TXA do?

Answer 71

Decreases the risk of death in major bleeding by inhibiting the conversion of plasminogen to plasmin

Question 72

How does aminocaproic acid work?

Answer 72

Competitively inhibits plasminogen activation and stabilizes the clot and prevents it from breaking down