Pharm Test 4

Question 1

What is thrombogenesis

Answer 1

formation of thrombi

Question 2

What is hemostasis?

Answer 2

The ability of the body to stop itself from bleeding out

Question 3

Part of hemostasis is _____________

Answer 3

thrombogenesis

Question 4

what is fibrin?

Answer 4

a net that traps the platelet plugs and traps red blood cells at site of injury “glue”/”morter”

Question 5

What happens when we have a larger injury in the vessels?(pharm)

Answer 5

it can expose collagen and (von Willebrand factor) vWF.
When these are exposed they act with glycoproteins that are on platelet cell surfaces and this sets up platelet coagulation or thrombogenesis
Eventually this will lead to clotting cascade

Question 6

what is a red thrombus and where do they occur?

Answer 6

A lot of fibrin with a long tail and with RBC’s trapped in it that occurs in slow moving vessels like veins

Question 7

what is a white thrombus?

Answer 7

a thrombus with more fibrinogen or platelets in it that occurs in high pressure arteries d/t damaged or plaque buildup in the endothelium

Question 8

What is a thromboembolism?

Answer 8

a thrombus that has broken off of the vessel it was made it and is now moving through the body

Question 9

what happens in response to damage of Blood vessels

Answer 9

• vasoconstriction d/t serotonin
• formation of platelet plugs
• degranulation of platelet aggregation which leads to the activation of more platelets
• That forms a fibrin clot
• tight regulation of coagulation and fibrinolysis

Question 10

what are the phases of platelets?

Answer 10

Adhesion
Aggregation
Secretion
Cross-linking of adjacent platelets

Question 11

what causes adhesion?

Answer 11

Exposure of collagen and von willebrand factor cause platelets to adhere to surface

Question 12

what is the secretion related to platelets?

Answer 12

They secrete substances,
primarily serotonin,
adenosine diphosphate,
and thromboxane A2
and they encourage additional cross linking of platelets

Question 13

what is cross-linking?

Answer 13

formation this cross linked platelet clot or thrombocyte clot

Question 14

Where does PGI2 aka prostacyclin come from?

Answer 14

The blood vessel lining is made up of endothelial cells which normally produce prostaglandin I2 or PGI2 (aka prostacyclin)

Question 15

what does PGI2/prostacyclin do?

Answer 15

it inhibits platelet aggregation

Question 16

When is PGI2 activated?

Answer 16

During the normal state of endothelial cell, if there’s no damage, is to inhibit platelet aggregation because we don’t want clots forming when there shouldn’t be clots forming

Question 17

Why is there a black box warning for CV events on NSAIDs?

Answer 17

NSAIDs inhibit prostaglandin synthesis, so they are actually “proclot”

Question 18

How does aspirin work?

Answer 18

aspirin targets specifically the platelets themselves by inhibiting thromboxane A2

Question 19

what receptor does collagen bind to?

Answer 19

glycoprotein 1-A receptor.

Question 20

what receptor does Von Willebrand factor bind to?

Answer 20

glycoprotein 1-B

Question 21

what results in the activation and release of soluble mediators

Answer 21

Collagen binding to platelets at the glycoprotein 1-A receptor.
Von willebrand factor binding to platelets at the glycoprotein 1-B.

Question 22

which soluble mediators are released d/t the binding of Collagen and vWF to platelets?

Answer 22

1. adenosine (ADP)
2. thromboxane A-2
3. serotonin (5 HT)

Question 23

What are the steps to platelet aggregation?

Answer 23

1. Damage exposes collagen and von willebrand factor
2. Collagen binds to platelets specifically at the glycoprotein 1-A receptor.
   Von willebrand factor binds to platelets at the glycoprotein 1-B receptor.
3. adenosine(ADP), thromboxane A-2, and serotonin(5 HT) is released
4. Serotonin causes vasoconstriction of smooth muscle on vessels and it binds to serotonin receptors on other platelets which activates those platelets.
   ADP and thromboxane A2 also bind to additional receptors on other platelets that are going to activate more platelets
5. Once the second platelet is activated it degranulates and releases additional ADP, thromboxane A2 and 5 HT.

It’s a positive feedback mechanism where multiple platelets are going to join together to be cross linked into this network

Question 24

what does fibrinogen do and where is it produced?

Answer 24

Fibrinogen turns into fibrin which holds platelets together! Fibrinogen is produced through the coagulation cascade.

Question 25

what is required in order to form a stable clot that's going to prevent us from bleeding out?

Answer 25

both platelet aggregation and coagulation cascade

Question 26

what is the common pathway?

Answer 26

Where the intrinsic and extrinsic pathways meet in the coagulation cascade

Question 27

What are the steps in the common pathway?

Answer 27

1. Factor 10 is activated. 2. Factor 10 activates the inactive form of thrombin (aka prothrombin) to its active form called thrombin. 3. Thrombin increases the release of more thrombin, it activates platelets, and it converts the inactive form of fibrinogen into the active form of fibrin. 4. Fibrin helps platelets aggregate together and it forms a mesh network to trap platelets.

Question 28

What are the steps in the intrinsic pathway?

Answer 28

Damage to the surface activates factor XII(12) XII activates factor XI(11) XI activates factor IX(9) IX + VIII(8) activates factor X(10) this starts the common pathway

Question 29

What are the steps in the extrinsic pathway?

Answer 29

Trauma activates factor VII(7) VII activates factor X(10) this starts the common pathway

Question 30

what is another name for the intrinsic pathway?

Answer 30

contact activation

Question 31

what is another name for the extrinsic pathway?

Answer 31

Tissue factor

Question 32

What all does thrombin do when activated?

Answer 32

1. It increases the release of more thrombin 2. It activates platelets 3. It converts the inactive form of fibrinogen into the active form of fibrin.

Question 33

Which number is the contact factor?

Answer 33

XII (12)

Question 34

which number is the tissue factor?

Answer 34

VII(7)

Question 35

What is Virchow's triad?

Answer 35

stasis endothelial injury hypercoagulability

Question 36

What causes DVTs and PEs most often?

Answer 36

Red thrombi

Question 37

What are the inherited risk factors for DVTs?

Answer 37

Antithrombin III deficiency Protein C deficiency Protein S deficiency Sickle cell anemia Activated protein C resistance

Question 38

What are the aquired risk factors for DVTs?

Answer 38

Bedridden Surgery/trauma Obesity Estrogen use Malignancies Chronic venous insufficiency

Question 39

What is DIC?

Answer 39

Over stimulation of the blood clotting mechanism and risk of impaired blood flow Clots are formed all over the body. Using up all of the platelets and clotting factors which leads to spontaneous bleeding

Question 40

what is the mortality rate of DIC?

Answer 40

10% to 50%

Question 41

What causes DIC?

Answer 41

* Massive tissue injury * Malignancy (cancers) * Bacterial sepsis / bacterial infection - usually gram negative bacteria b/c of endotoxins it produces * Abruptio placentae

Question 42

What are the treatments for DIC?

Answer 42

Plasma transfusions or transfusion of clotting factors Treat the underlying cause

Question 43

What is HIT?

Answer 43

thrombocytopenia due to HMW heparin admin

Question 44

what causes HIT?

Answer 44

Heparin induced thrombocytopenia (HIT) is a clinicopathological syndrome that occurs when heparin dependent IgG antibodies bind to heparin/platelet factor 4 complexes to activate platelets and produce a hypercoagulable state. Heparin is being recognized by our immune system and we are making antibodies that target thrombocytes and get rid of our platelets

Question 45

How long does it take for HIT to occur?

Answer 45

7-10 days after heparin administration

Question 46

Treatment for HIT?

Answer 46

Stop heparin monitor PT PTT, INR and platelets

Question 47

What is the pathway for fibrinolysis?

Answer 47

Plasminogen → plasmin (active form) → breaks down fibrin into FSP and fibrinogen into degradation products ○ tPA activates plasminogen into plasmin (active form) ○ Urokinase and streptokinase also do this ^^

Question 48

What is TTP?

Answer 48

Thrombotic thrombocytopenic purpura You dont have enough of the ADAMTS13 enzyme, and since insufficient, body makes blood clots. Results in low platelets Heparin can cause TTP

Question 49

Treatment for TTP

Answer 49

steroids, plasma exchange, immune lowering meds

Question 50

What are the 2 main regulation systems of coagulation?

Answer 50

Fibrin inhibition Fibrinolysis

Question 51

What are the proteases made by the liver that rapidly inactivate the coagulation proteins?

Answer 51

alpha₁-antiprotease alpha₂-macroglobulin alpha₂-antiplasmin antithrombin

Question 52

After the clot is formed, how do we break it down? (fibrinolytic system)

Answer 52

plasminogen is activated into plasmin by TPA (tissue plasminogen activator) urokinase streptokinase+ activator=anistreplase to break down fibrin

Question 53

what are the 2 main functions of plasmin?

Answer 53

Breaks down fibrin into split products (picked up by D-Dimer) Breaks down fibrinogen locally.

Question 54

What can we use to keep a clot from breaking down? how does it work?

Answer 54

Aminocaproic acid transischemic acid (TXA) inhibits the breakdown of plasminogen to plasmin

Question 55

List the four classes of coagulation modifier drugs, how they work, and examples of each.

Answer 55

Anticoagulant- **Parenteral: heparin Oral: Warfarin** Inhibit the action or formation of clotting factors Prevent clot formation Antiplatelet drugs- **Aspirin** Inhibit platelet aggregation Prevent platelet plugs Thrombolytic drugs (Fibrinolytic)-**Streptokinase** Lyse (break down) existing clots Hemostatic or Antifibrinolytic drugs Promote blood coagulation

Question 56

How does an indirect thrombin inhibitor work? Examples of this type of drug?

Answer 56

Enhances antithrombin activity Inactivates factor Xa Unfractionated heparin LMW heparin Fondaparinux (Arixtra)

Question 57

What is the difference in the different types of heparin?

Answer 57

How purified they are: Unfractionated heparin Less purified but more effective LMW heparin More purified but less effective Fondaparinux (Arixtra) → pentasaccharide complex – 5 carbs stuck together Less effective than molecular weight or unfractionated heparin

Question 58

How does a direct thrombin inhibitor work? Examples of this type of drug?

Answer 58

they directly inhibit thrombin by binding to active sites on thrombin Bind to both active and substrate recognition sites of thrombin: * Hirudin (Lepirudin is recombinant form) from leeches - saliva from leeches prevents clotting from occurring * Bivalirudin (Angiomax) Bind only to thrombin active sites - * Argatroban * Melagatran * Dabigatran (Pradaxa)

Question 59

Explain the difference between HMW, LMW, and Fondaparinux heparins, and the use of each.

Answer 59

They all have a Pentasaccharide sequence. Heparin: Binds and activates AT Enhances activity (1000x) Has a High molecular weight fractions (Unfractionated) Extracted from porcine intestinal mucosa and bovine lung LMW Heparin More purified form of heparin More specific for factor Xa Less effect on thrombin Less effective on coagulation in general Examples (-parin) Fondaparinux (Arixtra) Synthetic Not as effective (selective for factor X) Less bleeding risks Useful for HIT

Question 60

What are the toxicities and contraindications for HMW heparin?

Answer 60

Bleeding Transient thrombocytopenia Heparin induced thrombocytopenia (HIT) Hemophilia Thrombocytopenia Severe hypertension Intracranial hemorrhage Infective endocarditis Active TB GI ulcers Advanced hepatic disease

Question 61

What is the reversal for heparin? How does it work?

Answer 61

protamine sulfate- made from salmon sperm now synthetic It is highly positive so binds to the highly negatively charged heparin thereby inactivating it

Question 62

What is the normal INR? What is the warfarin target?

Answer 62

0.8-1.2 2-3

Question 63

What is Prothrombin time?

Answer 63

The time it takes to clot

Question 64

what is the normal aPTT?

Answer 64

35-45 seconds

Question 65

List the oral anticoagulants

Answer 65

warfarin (coumadin) Factor X inhibitors

Question 66

MOA of heparin

Answer 66

Blocks the γ-carboxylation of several glutamate residues (vitamin K dependent) Targets 2,7,9,10 Binds and activates antithrombin

Question 67

Where was warfarin discovered and what was it initially used for?

Answer 67

Discovered by University of Wisconsin as cause for cattle hemorrhagic disease Wisconsin Alumni Research Foundation -arin originally meant as rat poison

Question 68

Pharmacokinetics of warfarin

Answer 68

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

Question 69

What are the fibrinolytic drugs?

Answer 69

Streptokinase urokinase t-PA - alteplase

Question 70

What are the targets for aspirin?

Answer 70

COX-1 Selective - platelet TXA2 causes platelets to change shape, Granule release, and Aggregation Inhibition of TXA2 synthesis increases bleeding time

Question 71

MOA of Clopidogrel (plavix) and ticlopidine (Ticlid)

Answer 71

Irreversibly inhibits ADP receptor on platelets causing reduction in platelet aggregation

Question 72

MOA of Abciximab

Answer 72

IIb/IIIa receptor blocker found in the common pathway Inhibits platelet aggregation

Question 73

How can bleeding disorders be treated with Vitamin K?

Answer 73

Necessary for efficient blood coagulation Fat soluble vitamin Comes from: Leafy green vegetables Gut bacteria Confers activity on: Prothrombin (primarily affect this) Factors VII, IX, and X

Question 74

How can bleeding disorders be treated with plasma fractions?

Answer 74

We can give plasma to treat bleeding disorders; replaces clotting factors. Whatever they are missing, we can isolate that factor and give to patient

Question 75

How can bleeding disorders be treated with desmopressin acetate?

Answer 75

Desmopressin Increases factor VIII activity Good for Mild hemophilia A Also good for von Willebrand disease

Question 76

How can bleeding disorders be treated with aminocaproic acid(fibrolytic inhibitor)

Answer 76

Competitively inhibits plasminogen activation Stabilizes clot; prevents clot breakdown Use Adjunctive hemophilia therapy Bleeding from fibrinolytic therapy Intracranial aneurysms Post surgical bleeding

Question 77

How can bleeding disorders be treated with Tranexamic acid (TXA)

Answer 77

Helps to stabilize clot and prevent clot breakdown→helps blood to clot to stop bleeding Decreased risk of death in major bleeding Used for: Trauma, heavy menstrual bleeding, postpartum, epistaxis So used for more massive bleeds MOA Antifibrinolytic Inhibits plasminogen->plasmin