Hemostasis and Coagulation Modifying Drugs Flashcards
(29 cards)
What is Hemostasis?`
-Balance between clot formation and clot breakdown.
Thrombus= clot
3 Phases of Hemostasis?
- Vascular Phase
- vessel contract
-Platelet Phase
* start adhesion
tn phase
*Clotting
Platelets
Starts clotting than escalates clotting.
Functions:
- Formation of platelet plug (primary hemostasis)
- Release of chemicals for clotting (activating) secondary
hemostasis. (from granules) - Active contraction after clot formation.
Prostacyclin and nitric oxide are synthesized by intact endothelial cells and acts as inhibitors of platelet aggregation. (also promotes dilation)
Platelets: Thrombin and Thromboxane A2
Thrombin: An enzyme in blood plasma that causes the clotting of blood converting fibrinogen to fibrin.
Thromboxane A2: a hormone released from platelets. It induces platelet aggregation and arterial contristriction.
Platelet (Plug) Phase
Adhesion: Platelets bind to the vascular subendothelial collagen via vWF
Activation: Damaged tissue releases Tissue Factor (TF)
- Most powerful platelet activator, intiator of coagulation.
- also known a Thromboplastin and factor III
Aggregation: of platelets require ADP and thromboxane A2, platelets start to stick together.
-thromboxabe A2 and ADP help expose the fibrinogen receptors, which becomes modified to bind fibrinogen better.
Firbrin Product: requires extrinsic, intrinsic and final common pathways, final clot formation.
Thromboxane A2 and NSAIDs and ASA
Thromboxane A2 helps platelets clot.
NSAIDs and ASA disrupt hemostatsis by inhibiting TxA2 formation thereby blunting plt activation
* they cause patients to bleed more.
Clot Formation
Trace amounts of thrombin are generated during the initiation phase of coagulation by factor Xa (FXa) via interactions between circulating FVIIa and TF (aka FIII) expressed on subendothelial pericytes and fibroblast.
Fibrinogen
Plasma glycoprotein synthesized in the liver.
Thrombin cleaves the fibrinogen molecules, producing a soluble fibrin monomer which polymerizes to form a loose network in trapping red blood cells and a clot begins to form.
Cofactors
Calcium and Phospholipids:
-Ca required in all three pathways.
Vitamin K
-Adequate amount necessary for the liver to synthesized four of the clotting factors: II, VII, IX, annd X, as well as protein C, and protein S
Regulators
Protein C:
- Physiological anticoagulant
- Vit K depenednt serine protease emzyme.
- Activated by thrombin into activated protein C (APC)
- protein C: halts further thrombin generation by inactivating (Va and VIIIA), works in conjuction w/ protein S.
Antithrombin:
- plasma protein from the liver, inhibits the coagulation enzymes of the intrinsic and common pathways, thrombin
- constantly active
- Increased adhesion in presence of heparin sulfate or administration of heparin.
Regulators:
Tissue Factor Pathway Inhibitor
Plasmin
Prostacyclin
Tissue Factor Pathway Inhibitor
- limits action of TF
- inhibits excessive TF-mediated activationof factor VII and X
Plasmin
- generated by proteolytic cleavage of plasminogen, catalyzed by t-PA
- cleaves fibrin into fibrin degradation products.
Prostacylin:
- released by endothelium
- inhibits platelet activation
Drug Eluting Stent (Antiplatelet Agents)
Needs 12 months of thienopyridine therapy, premature discontinuing can be catastrophic.
Bare Metal Stent (Antiplatelet Agents)
Drug therapy for 6 weeks
Cyclooxygenase Inhibitor: Cox inhibitor
Antiplatelet Agents
Aspirin
Irreversibly acetylates cox = prevents formation of thromboxane A2.
Effects on platelets are irreversible and last for the life o the platelets, 7-10 days.
-platelet inhibitor
Prevents Aggregation.
ADP receptor Pathway Inhibitors (thienopyridines)
Antiplatelet Agents
Plavix
Effient
Irrversibly bind to the platelets P2Y receptor therby blocking adenosine (ADP) binding
Often coupled with Aspirin
DOA: life of the the platelet
Discontinue 7 days before surgery
Platelet transfusion may help reverse
GPIIb-IIIa Antagonist
Antiplatelet Agents
- Repro
- Aggrastat
- Eptifibatide
Bind or competitively inhibits the corresponding fibrinogen receptor that is important for platelet aggregation.
Block fibrinogen binding to platelet GP IIb/IIa receptors that are a common pathway of platelet aggregation,
Wafarin (Coumadin)
Anticoagulant
Competitively inhibits vit K epoxide reductase reduction o vit K
-Narrow therapeutic Index
Reversal: FFP and Vit K and PCC
-Oral or IV vit K takes a day to reverse anticoag effect
Crosses the Placenta
Test: PT and INR
Unfractioned and Low molecular Weight Heparin (Intrinsic pathway)
(Anticoagulant)
-Binds to naturall occuring antithrombin
-Heparin alone has no anticoag effect
-Prevents thrombus formation and extension prophylaxis doesn’t affect clots already present.
-Prevents thrombins consumption of clotting factors.
-Activated partial thromboplastin time (aPTT)
-Anti Xa assay: instead of PTT accounts for extremes in dosing
-ACT (activated clotting time)
-Heparin induced Thrombocytopenia (HIT)
Heparin induced Thrombocytopenia w/ Thrombosis HITT
-development of heparin induced platelet IGG
antibodies to your own platelets.
-Be suspicious if thrombosis worsens/develops,
bleeding time increases, and platelet count drops.
Protamine for Heparin Reversal
Anticoagulant
-Dose of protamine required to antagonize heparin is 1mg for every 100 units of circulating heparin activity.
Give slowly over course of 20 in.
Dangers of Use: IGG/complement mediated hemodynamic catastrophes
-Doesn’t neutralize LMWH
Selective factor 10a Inhibitors
Anticoagulant
-Arixtra
-Alternative for patients with HIT
_prevents DVT & PE
Xarelto
- No easy testing
- PCCs complete reverse
Apixaban
Edoxaban : under investigation
Direct Thrombin Inhibitor
Anticoagulant
- Good for patients with HIT
- Immunologenic: antibodies can form
- Testing: monitored with aPTT and ACT
- Bivalirudin
- commonly used for cardiac interventional procedures
- Safe with HIT
- Argatroban
- Prophylaxis or treatment with HIT patients undergoing PCL
- Not renally cleared, doesn’t make antibodies.
- Prophylaxis or treatment with HIT patients undergoing PCL
- Lepirudin and Deirudin
- Analogs of hirudin, can cause bleeding and allergies.
- Renal Clearance
- Monitor aPTT
- Pradaxa
- measured with thrombin times (TT) ecarin clottingt time (ECT) and aPTT
Antithrombin
Anticoagulant
Naturally occurring anticoagulant
Thrombolytic Agents
- Acts as plasminogen activators to convert the endogenous proenzyme plasminogen to the fibrinolytic enzyme plasmin that lysis clot and other proteins.
- Reversal: FFP, cryoprecipitate, platelets, and antifibrinolytic drugs Amicar
Streptokinase
Thrombolytic Agents
Made by beta hemolytic streptococci, little affinity for fibrin, preformed antibodies may inactivate it.
