Hemostasis Flashcards by hassan gonzales

Hemostasis involves a complex, rapid, localized, integrated interaction between what four processes

blood vessels
platelets
coagualtion cascade
fibrinolysis

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What are the four components of hemostasis activated by endothelial disruption

rapid vasoconstriciton
immediate platelet adherence to collagen
coagulation (intrinsic/extrinsic)
fibrnolysis via tPA

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Platelets are formed by —–, where?

megakaryocytes in bone marrow

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What is the normal platelet amount in plasma

150,000-300,000/uL

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What is the platelet half-life

9-10 days

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What three types of storage granules are released when platelet secretion occurs

alpha granules

dense granules

lysosomal vesicles

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What are the four distinct functions of platelets in response to vascular damage

places seal over endothelium (maintains integrity)

stops initial bleeding via formation of platelet plugs

stabilizes platelet plug

promotes vascular healing

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List the events of platelet adhesion

damaged endothelium with exposed collagen»factor VIII:vWF complex binds exposed collagen to platelet surface receptor (GP Ib)

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List the three main events of platelet aggregation

damaged endothelim initiates coagulation

activation of platelets via dense granule release of ADP»>promotes platelet aggregation

platelet shape change, decreased cAMP activity»exposed GPIIb and GPIIIa receptors for fibrinogen binding sites (calcium dependent)

increased phosphoplipase activity»thromboxane A2 formation

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What are the two pathways of the coagulation pathway that leads to fibrin formation

contact activation pathway (intrinsic)

tissue factor pathway (extrinsic)

*both pathways activate the COMMON FINAL pathway of FACTOR Xa

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What are coagulation factors

serine proteases which act by cleaving downstream proteins

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What are the four clotting factors with calcium-binding properties that are vitamin K dependent

II, VII, IX, X

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What is factor IV

calcium ion

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What test is used to measure the extrinsic pathway

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What test is used to measure the intrinsic pathway

PTT

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What serine protease does factor Xa activate

Thrombin

*prothrombin»>thrombin

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What serine protease does thrombin activate

Fibrin

*fibrinogen»>fibrin

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What four biological mechanisms are in place to control excess coagulation

increased blood flow (washout excess factors)

antithrombin III via heparin induced activity

prostacyclin via inhibiting thromboxane A2

protein C activation»fibinolysis

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What serine proteases does ATIII inhibit

IX, X, XI, XII

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Plasminogen activation results in

formation of plasmin (serine protease) which lyse fibrin clots

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How are the endogenous plasminogen activators classified

intrinsic and extrinsic

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Name the three intrinsic plasminogen activators

factor XIIa

kallikrein

protein C

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Name the two extrinsic plasminogen activators

tPa

urokinase

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Name the two Exogenous plasminogen activators

streptokinase

rt-PA

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How is thrombin involved in fibrinolysis

thrombin in the presence of thrombomodulin activates protein C

What is the main MOA of protein C

inactivates the inhibitor of plasminogen activator *allows plasminogen>>>plasmin conversion

Plasmin has what effect on clots and platelets

lysis of clots (fibrin)>>fibrin split products * cleaves GP receptors

Heparin is classified as an

anticoagulant

What is the MOA of heparin

binds to ATIII causing a conformational change>>>1000X more potent ATIII inhibits IX, X, XII, XII clotting proteases by forming stable complexes with them

Heparin dosaging depends upon

the desired effect

The desired effect of heparin can be classifed as

partial heparinziation complete heparinization

partial heparinization is used in what type of procedure

vascular (CEA, AAA resections) dose generally 100 units/kg

Complete heparinization is used in what type of procedure

CPB dose generally 300-400 unis/kg

1 unit of heparin is equal to ____mg

Heparin follows zero order kinetics, what does this mean for how it is eliminated

a constant AMOUNT of drug is eliminated per unit of time>>>linear rate of elimination and NON-linear decrease in plasma concentration

What enzyme metabolizes heparin and where is it located

heparinase, located in the liver

What tests determine the degree of heparinization

PTT>>for low doses (1.5-2 times pre-heparin value) ACT>>for high doses (400-500 seconds)

What are the three SE of heparin administration

Hemorrhage Allergic rxn (beef/pork preparations) Thrombocytopenia (encourages clot formation)

Thrombocytopenia induced heparin administration is categorized as

mild thrombocytopenia Heparin-induced Thrombocytopenia and Thrombosis (HITT) syndrome

Mild thrombocytopenia caused by heparin results when

platelets drop below 100,000 *resolves on own

HITT syndrome caused by heparin results when

platelets drop below 50,000

HITT occurs do to the formation of

antibodies that attack platelets *large doses of heparin causes upregulation of platelets>>>antibodies attack platelets>>>increased activation>>>thrombosis and thrombocytopenia

Are patient's who receive heparin candidates for regional anesthesia

NOOO!!!!

Fractionated (LMWH) heparins display what type of activity

Antifactor Xa/Antifactor IIa * more pronounced AF Xa activity

What is a prototype of fractionated heparin

enoxaparin | "parins"

Factor Xa inhibitors are classifed as

direct indirect

Name one direct factor Xa inhibitor

Rivaro-Xa-ban *propphylactic prevention of VTE

Name one indirect factor Xa inhibitor

Fondaparinu-X *DVT prophylaxis

Name one Vitamin K antagonist

Warfarin

What is the MOA of Warfarin

nucleus of warfarin is similar to vitamin K so it binds to VK binding site preventing formation of calcium binding sites on clotting factors II, VII, IX, and X

Warfarin is administered

Orally ONLY

What is used to monitor effects of warfarin

PT *effective anticoagulation when PT is twice precoumadin PT

Name a class of drugs that are direct thrombin IIa inhibitors

"aTRoban" Argatroban

What are the three MOA of thrombin inhibitors (IIa)

direct thrombin inhibition inhibition of protein C (fibrinolysis) promotes NO release>>vasodilation

Name three common drugs used as procoagulants

protamine sulfate vitamin K conjugated estrogen

Protamine is a specific antagonist to

heparin

Protamine in the absence of heparin acts as a

anticoagulant

Why must protamine be administered slowly

causes histamine release>>>venodilation>>>decreased SVR

Protamine should not be given when

those taking protamine containing insulins allergic to fish males with vasectomy or infertility

What are the four classification of AntiPlatelet drugs

Cox inhibitors GP IIb/IIIa inhibitors PDE inhibitors ADP antagonists *given to patient's with too many platelets

Name an antiplatelet COX inhibitor

Aspirin *inhibits prostaglandin synthesis by irreversibly inhibiting COX I

Name three anitplatelet GP IIb/IIIa inhibitor

Tirofiban Eptifibatide Abcixmab

Name one antiplatelet PDE inhibitor

Dipyridamole

Name three antiplatelet ADP antagonists

Ticlopidine Clopidogrel Prasugrel

Name a drug that promotes platelet aggregation

Desmopression (DDAVP) *increases the release of factor VIII:vWF from vascular endothelium

Name three antifibrinolytics

E-Aminocaproic Acid (amicar) Tranexamic Acid Aprotinin

Antifibrinolytics should not be given to patients with

DIC

Name the classes of drugs classified as thrombolytics

"KINASE" | "TEPLASE"