[CA2 M4]: PCOL Coagulation

Clotting factor I

Fibrinogen

Clotting factor II

Prothrombin

Clotting factor III

Tissue factor

Clotting factor IV

Ca+2

Clotting factor V

Labile factor, proaccelerin, accelerator (Ac-) globulin

Clotting factor VII

Stable factor, proconvertin, serum prothrombin conversion accelerator (SPCA), cothromboplastin

Clotting factor VIII

Antihemophilic factor A, antihemophilic globulin (AHG)

Clotting factor IX

Christmas factor, antihemophilic factor B, plasma thromboplastin component (PTC)

Clotting factor X

Stuart-Prower factor

Clotting factor XI

Plasma thromboplastin antecedent (PTA)

Clotting factor XII

Hageman factor

Clotting factor XIII

Fibrin stabilizing factor (FSF), fibrinoligase

Intrinsic Pathway clotting factors

Factors 12, 11, 9, 8

Extrinsic Pathway clotting factors

Factors 3 and 7

Common Pathway clotting factors

Factors 10, 5, 2, 1, 13

Intrinsic tenase complex

Ca+2, factor 8a, factor 9a

Extrinsic tenase complex

Ca+2, factor 3a, factor 7a

Vitamin-K dependent factors (coagulation factors)

Factors 9, 10, 7, 2

Vitamin-K dependent factors (anticoagulation factors)

Proteins C and S

Drug class inhibiting step 2 (primary hemostasis / platelet plug formation)

Antiplatelets

Drug class inhibiting step 3 (secondary hemostasis / coagulation cascade)

Anticoagulants

Drug class inhibiting step 4 (clot stabilization and resorption)

Thrombolytics / fibrinolytics

Drug class: heparin

Indirect thrombin inhibitors - anticoagulants

Drug class: Enoxaparin, dalteparin, tinzaparin, nadroparin

Indirect thrombin inhibitors (LMWH) - anticoagulants

Drug class: Danaparoid

Indirect thrombin inhibitors (LMWH) - anticoagulants

Drug class: Fondaparinux

Indirect thrombin inhibitors (LMWH) - anticoagulants

MOA: activates antithrombin III which binds with factors 2a (thrombin), 9a, 10a

Heparin

MOA: activates antithrombin III which binds with factor 10a (thrombin)

LMWH

LMWH is more selective for which factor

Xa

Clinical applications: DOC for anticoagulation during pregnancy (cannot enter placenta)

Heparin

S/E: bleeding, thrombocytopenia, osteoporosis with chronic use

heparin

Monitored with aPTT

Heparin

Antidote for heparin

Protamine sulfate

Drug class: Lepirudin, bivalirudin, desirudin

Direct thrombin inhibitors (anticoagulants)

Drug class: Argatroban, dabigatran

Direct thrombin inhibitors (anticoagulants)

MOA: binds directly to thrombin and inactivates it

Direct thrombin inhibitors

Clinical applications: anticoagulant in pt with heparin-induced thrombocytopenia (HIT)

Direct thrombin inhibitors

S/E: bleeding, immune reactions, anaphylactic reactions

Direct thrombin inhibitors

From the medicinal leech (Hirudo medicinalis)

Direct thrombin inhibitors

Monoclonal antibody used for reversal of dabigatran toxicity

Idarucizumab

Drug class: rivaroxaban, apixaban

Direct factor Xa inhibitors (anticoagulants)

MOA: inhibits factor Xa, thereby inhibiting the final common pathway

Direct factor Xa inhibitors

Do not require monitoring, no antidotes

Direct factor Xa inhibitors

Drug class: warfarin

Coumadin derivatives (anticoagulants)

Drug class: dicumarol

Coumadin derivatives (anticoagulants)

Drug class: anisindione

Coumadin derivatives (anticoagulants)

MOA: inhibits vit. K epoxide reductase, which is responsible for gamma carboxylation of vit. K dependent clotting factors

Coumadin derivatives

Clinical applications: chronic anticoagulation (DVT, atrial fibrillation, valve replacement)

Coumadin derivatives

S/E: bleeding, teratogenic (bone defects, fetal hemorrhage)

Coumadin derivatives

Monitored with PT

Coumadin derivatives

Antidote for warfarin / coumadin derivatives (slow effect)

Vitamin K

Antidote for warfarin / coumadin derivatives (rapid effect)

Fresh Frozen Plasma

Active ingredient of rodenticides

Dicumarol

Drug class: Streptokinase, urokinase

Fibrinolytics / Thrombolytics

Drug class: Alteplase, Anistreplase, Reteplase, Tenecteplase

Fibrinolytics / Thrombolytics

MOA: tissue plasminogen activator analogs

Fibrinolytics / Thrombolytics

MOA: converts plasminogen to active form, plasmin

Fibrinolytics / Thrombolytics

Effects: promotes clot breakdown

Fibrinolytics / Thrombolytics

S/E: arrhythmias, allergic reactions

Fibrinolytics / Thrombolytics

S/E: allergic reactions

Streptokinase

Loss of effectiveness on 2nd use

Streptokinase

Antidote for Fibrinolytics / Thrombolytics

Aminocaproic acid (traxenamic acid)

Drug class: salicylates

COX inhibitors (antiplatelet)

MOA: nonselective, irreversible COX-1 and 2 inhibitor

Salicylates

Antiplatelet effect due to acetylation of platelet COX enzyme

Salicylates

Effects: prevents TXA2 formation, which reduces platelet aggregation

Salicylates

Effects: reduces formation of inflammatory mediators (e.g. prostaglandins)

Salicylates

Clinical applications: prevention of arterial thrombosis (MI, TIA, CVD), inflammatory disorders

Salicylates

S/E: GIT bleeding and ulcerations, nephrotoxicity, tinnitus, hypersensitivity

Salicylates

Associated with Reye's syndrome in children with viral infections

Salicylates

Prevents uric acid excretion (makes urine more acidic, facilitating reabsorption of uric acid), not used in gout

Salicylates

Drug class: abciximab

GP IIb/IIIa inhibitors (antiplatelets)

Drug class: tirofiban

GP IIb/IIIa inhibitors (antiplatelets)

Drug class: eptifibatide

GP IIb/IIIa inhibitors (antiplatelets)

MOA: interferes with GP IIb/IIIa binding to fibrinogen

GP IIb/IIIa inhibitors

Effect: inhibits platelet aggregation

GP IIb/IIIa inhibitors, ADP receptor antagonists

Clinical applications: used during cardiac surgeries to prevent thrombosis / clot formation

GP IIb/IIIa inhibitors

Drug class: Clopidogrel, prasugrel, ticagrelor

ADP Receptor Antagonists (antiplatelets)

MOA: irreversibly inhibits the binding of ADP to the P2Y12 platelet receptors

ADP Receptor Antagonists

Clinical applications: prevention and treatment of arterial thrombosis (MI, TIA, CVD)

ADP Receptor Antagonists

Drug class: dipyridamole

PDE3 inhibitors (antiplatelets)

Drug class: cilostazol

PDE3 inhibitors (antiplatelets)

MOA: inhibits PDE III and increases cAMP in platelets and blood vessels

PDE3 inhibitors

Clinical applications: prevention of thromboembolic complications during cardiac valve replacement

PDE3 inhibitors

S/E: migraine headache, palpitations

PDE3 inhibitors

Effects: inhibits platelet aggregation, vasodilation

PDE3 inhibitors

MOA: infused to patients with factor deficiencies

Clotting factors

Clotting factors that can be infused to patients

Factors 8, 9, 11

Effects: supplements coagulation cascade with clotting factors, promotes clotting

Clotting factors

Clotting factor given in hemophilia A

Factor 8

Clotting factor given in hemophilia B

Factor 9

Clotting factor given in hemophilia C

Factor 11

Clotting factor given in von Willebrand disease

Factor 8

MOA: known to increase production of vWF and Factor 8

ADH agonists

Drug class: desmopressin, vasopressin, terlipressin

ADH agonists

Clinical applications: von Willebrand disease

ADH agonists

MOA: cationic form is acidic protein and chemically binds to heparin and inhibits its activity

Protamine sulfate

Clinical applications: reversal of excessive anti-clotting activity of unfractionated heparin

Protamine sulfate

T/F: protamine sulfate, vitamin K and FFP promotes clotting

T

MOA: increases supply of reduced vitamin K

Vitamin K1 and K2, FFP