Coagulation Modifying & Anemia Agent Chase Buehler & Samantha Porter

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  • "Drugs that prevent the formation of a clot by inhibiting certain clotting factors."--essentially anticoagulants stops blood from clotting.
  • They prevent new clots from forming and also existing clots from enlarging, but do not have the ability to dissolve a blood clot.
  • Clots have the potential to dislodge and travel through the bloodstream causing complications elsewhere.
    • Ex: If it obstructs a brain vessel-causes a stroke
    • If it goes to the lungs- it is a pulmonary embolism
    • If it goes to a vein in the leg- it is a deep vein thrombosis
  • Anticoagulants are beneficial in certain settings where there is a high likelihood of a clot to form
    • MI, unstable angina, atrial fibrilation, use of indwelling devices, and conditions where blood flow may be slowed and blood may pool

Mechanism of action:

*In some way shape or form, all these drugs interupt the clotting cascade in which all aids in the cessation of clot forming*
*Prophylaxis use ONLY, does NOT break down clots*

  • Binds to a substance called antithrombin III, which turns off three main activating factors (activated factor II, X, and IX)
  • Antithrombin III is the major natural inhibitor of thrombin in the blood.
  • Indicated for prevention and treatment
  • Main effect of Heparin--> Turns off the coagulation pathway and prevents clots from forming.
LMWH (Lovenox, Fragmin, and Innohep)
  • Differ from Heparin- more specific for activating factor X as oppososed to factor II
  • Indicated for prevention and treatment
Warfarin- (Coumadin)
  • Works by inhibiting vitamin K synthesis by bacteria in the GI tract
  • As a result, this inhibits the production of clotting factors II, VII, IX, and X
  • Indicated for prevention
  • Final effect--> Prevention of clot formation
Fondaparinux (Arixtra)
  • Inhibits thrombosis by specific action against factor Xa
  • Currently 4 antithrombin drugs that inhibit thrombin molecules directly


  • Warfarin is strongly contraindicated in pregnant woman
  • LMWH's are contraindicated in patients with an indwelling catheter.
  • Known drug allergy

Adverse Effects:

  • Bleeding is the main complication
  • Heparin effect- Heparin-induced thrombocytopenia (HIT)
    • Two Types:
      • Type I-more gradual reduction in platelets
        • Heparin therapy can normally be continued
      • Type II- acute fall in the number of platelets
        • Heparin therapy must be discontinued
  • Common adverse effects:
    • Heparins-->bleeding, hematoma, nausea, aneamia, fever, edema
    • Fonfaparinux-->bleeding, hematoma, dizziness, confusion, rash, GI distress, UTI, anemia, urinary retention

Toxicity and overdose:

  • Symptoms of toxicity or overdose:
    • hematoma, melena (blood in stool), petechiae, ecchymoses, and gum or mucous membrane bleeding.
  • Heparn or warfarin toxicity- drug should be discontinued immediately!
    • Since heparin has a short half-life, stopping the drug alone may reverse the toxic effects
    • In case of emergency (severe cases)- IV injection of protamine sulface is indicated. This drug reverses its anticoagulation properties.
    • Since warfarin inactivates the vitamin K dependent clotting factors (which are synthesized in the liver), it can take up to 36-42 hours before the liver has the ability to resynthesize enough clotting factors to reverse the warfarin effects.


  • Major mechanism interferes with platelet function
    • Normal platelet function adheres to the collagen formation upon a damaged blood vessel
  • There are 9 commonly current drugs that are antiplatelets: Pletal, Plavix, Remodulin, ReoPro, Integrilin, Asprin, Aggrastat, Agrylin, Persantine

Mechanism of Action

*Alters platelet membrane so platelets cannot clot*

  • Asprin
    • Lasts the lifespan of a platelet (7 days)
    • Prevents the formation of TXA2 (Thromboxane) and prostaglandins by the permanent inhibition of the enzyme cyclooxygenase in the platelets
      • Thromboxane causes blood vessels to constrict and aggregate platelets
  • Persantine
    • Inhibits ADP, platelet factor 4, and thromboxane, all substances that causes platelets to clot
  • Plavix
    • Blocks signals from fibrogen molecules by inhibiting the glycoprotein receptors on the platelet's membrane
  • Pentoxifylline
    • Inhibits serotonin, platelet factor 4, and ADP, also stimulates the release of prostacyclin (helps with dilation and inhibits platelet activation) from the blood vessels
  • Cilstazol
    • Primarily used to inhibit platelet aggregation and vasodilation in the lower extremities
  • GP IIb/IIIa inhibitors (Aggrastat, Integrilin, ReoPro)
    • Blocks the receptor protein on the platelets membrane (GP IIb/IIIa) and by doing so, prevents aggregation of platelets
    • Only available for IV use
      • Extremely fast onset for emergencies


  • Asprin
    • Recommended by the American Stroke Society in doses of 81 to 325mg
  • Plavix
    • Reduce risk of thrombotic strokes, prophylaxis for MIs and post MI prevention of thrombosis.
  • Persantine
    • Adjunct with warfarin to prevent post-op thromboembolic complications
  • GP IIb/IIIa inhibitors
    • Treat acute angina and MI or given during angioplasty
    • Thromboprevention
  • Pentoxifylline
    • Peripheral vascular disease
  • Pletal
    • Pain and cramping in calf muscles
    • Improves exercise tolerance in the elderly


  • Allergies - KDAs
  • Conditions - Thrombocytopenia, active bleeding, leukemia, traumatic injury, GI ulcer, Vitamin K deficiency, or recent stroke

Adverse Effects

  • All drugs pose a risk for serious bleeding episodes
    • CNS - Stimulation, drowsiness, dizziness, confusion, flushing
    • GI - NVD, GI bleeding, heartburn
    • Hematologic - Thrombocytopenia, agranulocytosis, leukopenia, neutropenia, hemolytic anemia, bleeding
  • Plavix
    • CV - Angina, hypertension, edema
    • CNS - Flulike symptoms, headache, dizziness, fatigue
    • GI - Abdominal pain, dyspepsia, diarrhea, nausea
    • Misc. - Epitaxis and integumentary disorders, including rash and pruritis


  • Dangerous drug reactions are possible
  • Common allergic cross-reactivity between Asprin and other NSAIDs
  • Avoid the combined use of Asprin and Heparin with GP IIb/IIIa inhibitors


  • Major mechanism of action-prevent the lysis of fibrin,actually promoting clot formation
    • Fibrin is the substance that helps make a platelet plug insoluble and anchors the clot ot the damaged blood vessel
  • 3 synthetic drugs currently available-aminocaproic acid, tranexamic acid, and desmopressin
    • Drugs available for topic use to stop excessive bleeding
  • Useful drugs in the prevention and treatment of excessive bleeding resulting from systemic hyperfibrinolysis or surgical complications

Mechanism of Action/Drug effects:

*Promotes clot formation*
  • Aminocaproic acid and tranexamic acid- inhibit the breakdown of fibrin, which prevents the destruction of the formed platelet clot
  • Desmopressin- causes increased platelet aggregation and clot formation

Adverse Effects:

  • Typically mild effects
  • Rare occasion of acute cerebrovascular thrombosis and acute MI
  • Do not mix with estrogen or oral contraceptives as additive effects may occur, resulting in increased coagulation

Thombolytic Drugs

  • Lyse thrombi in blood vessels that supply heart with blood (coronary arteries)
  • Reestablishes blood flow to the heart
  • Founded from bacteria in a patients blood which released a substance that broke down fribrin clots
    • Substance was isolated from the beta-hemolytic streptococcus and was named streptokinase
    • Streptokinase and natural occuring urokinase were the first enzymes used for thrombolytic drugs
  • Current drugs - Eminase, Activase, Retavase, TNKase

Mechanism of Action

*Breaks down EXISTING clots*
  • Thombolytics activate the conversion of plasminogen to plasminwhich breaks down the thrombus.
    • Plasmin is a proteolytic enzyme which breaks down protein such as fibrin, fibrogen and platelet factors (substances that form clots)
  • Streptokinase and urokinase have been removed from the U.S. market due to their adverse effects, newer substances carry lesser bleeding chance
  • Tissue plasma activator or t-PA (activase) are naturally occuring, but not at a therapeutic level, current drugs use recombinant DNA techniques to produce extra t-PA for therapeutic effects
    • t-PA converts plasminogen to plasmin*


  • All thrombolytic drugs activate the conversion of plasminogen to plasmin
  • Used for acute MI, arterial thrombosis, DVT, occlusion of shunts or catheters, pulmonary embolism, and acute ischemic stroke


  • KDAs
  • Any other drugs that alter clotting

Adverse Effects

  • Internal, intracranial, and superficial bleeding, hypersensitivity, anaphylactoid reactions, nausea, vomiting, hypotension, and cardiac dyssrhythmia

Toxicity and Management of Overdose

  • Supportive treatment since half-life of thrombolytic drugs are short


  • Increased bleeding when in concurrent use with anticoagulants, antiplatelets, or any other drug affecting platelet function

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