Anti-coagulation

Question 1

HEMOSTATIC DISORDERS

Answer 1

• Thrombotic disorders such as acute myocardial infarction, deep vein thrombosis, pulmonary embolism, and acute ischemic stroke are treated with drugs such as anticoagulants and fibrinolytics
• Coagulation involves both cellular (platelet) and protein-based (coagulation factors) components
• Arterial thrombosis usually consists of a platelet-rich clot
  therefore NSAID therapy is beneficial
• Venous thrombosis is commonly triggered by blood stasis or inappropriate activation of the coagulation cascade; clots are
  fibrin-based with negligible platelets

Question 2

ANTI-HEMOSTATIC AGENT DRUG CLASSES

Answer 2

• Anticoagulants
• Platelet Inhibitors

Question 3

COAGULATION PATHWAY

Answer 3

• The hemostatic process begins with the development of a
  platelet clot, subsequently reinforced by further activation
  of the coagulation cascade, culminating in the generation of a fibrin plug
• The coagulation cascade consists of 13 factors comprising
  two interrelated pathways that commonly unite to produce a fibrin plug
• Tissue factor (extrinsic) pathway: responds to bleeding from tissue trauma
• Contact activation (intrinsic) pathway: responds to damage of blood cells or the exposure of blood to collagen; particularly involved in inflammatory pathways
• Negative feedback within the coagulation cascade is
  achieved by the activation of antithrombin
• Drugs acting within the extrinsic pathway (which is most important in vivo) affect the synthesis of vitamin K-
  dependent coagulation factors
• Drugs acting within the intrinsic pathway inhibit the activity of coagulation factors
• Once activated, clotting factors are denoted by the same number with a lower case “a” e.g. X ➙ Xa

Question 4

Indication of warfarin (Vit K antagonist)

Answer 4

• DVT/PE therapy: 2-5 mg PO qd
• Pre/Post Stroke: calculated

Question 5

Mechanism of action of warfarin

Answer 5

• Vitamin K is an essential cofactor which is oxidized during the activation of vitamin K-dependent coagulation factors (II, VII,IX, X)
• Warfarin inhibits vitamin K epoxide reductase which is
  responsible for recycling oxidized vitamin K for re-use

Question 6

Adverse reactions of warfarin (vt K antagonism/)

Answer 6

Common: Bleeding/bruising, headache, dizziness, pruritus,
edema, dermatitis, fever, paresthesias, alopecia

Serious:
CV: syncope, vasculitis, hemorrhage, cholesterol embolism
Hematology: anemia

Question 7

Topical opthalmic drug interactions

Answer 7

• NSAIDs: additive hemorrhagic risk
• Contraindications
  • Pregnancy
  • Active bleeding
• Ocular: Recent ocular surgery
• Cautions
  • Hypertension
  • Diabetes

Question 8

FACTOR Xa INHIBITORS

Answer 8

• Injectable (Heparin-based)
  
  • Enoxaparin [Lovenox®]
  • Dalteparin [Fragmin®]
• Oral
  
  • Apixaban [Eliquis®]
  • Rivaroxaban [Xarelto®]
  • Edoxaban [Savaysa®]
  • Betrixaban [Bevyxxa®]

Question 9

Indications of enoxaparin

Answer 9

• Post-op DVT prophylaxis: 2.5 mg
• Unstable angina: calculated subcutaneous injection

Question 10

Mechanism of action of enoxaparin

Answer 10

• Fractionated, heterogeneous low molecular weight heparin
  (LMWH) extracted from porcine intestinal mucosa
• Binds to the circulating anticoagulant antithrombin and
  accelerates its irreversible inactivation of clotting Factor-Xa
  much more so than Factor-IIa (thrombin)

Question 11

Unfractionated vs Fractionated heparin

Answer 11

• Heparin = glycosaminoglycan (GAG), found in mast cells
• Unfractionated = mixture of GAGs (so wide variety of molecular weights)
  ● Targets both factor 10a and factor 2 (so less selective and therefore less predictable)
• Fractionated = low molecular weight
  ● Selective, targeting only factor 10a
  ● Factor 10a = where the extrinsic and intrinsic pathways unite, so LMWH is a potent drug (it doesn’t matter
  what the source of bleeding is- factor 10a will inhibit the coagulation cascade for both pathways)