DRUGS AFFECTING COAGULATION
I.
HEMOSTATIC AGENTS
1. Local measures - applying directly on soft tissues and bony structures
- dressings - sterile cotton gauze (to stop bleeding by exerting pressure on injured vessels)
- electrocautery
- microfibrillar collagen or collagen sheets (applying on broad bleeding surfaces)
- accelerates the aggregation of platelets and plays a role a physical barrier
- gelatin sponge - absorbs blood and accelerates the aggregation of platelets
- denatured cellulose (as gauze or sponge) - serves as a physical plug and local procoagulant
- clotting factors - thrombin, fibrin glue
- astringents and styptics - chemicals with vasoconstrictive and protein-denaturing ability
 f.e.: aluminium, zinc, iron and silver salts, tannic acid
 used for gingival retraction
2. Systemic measures
clotting factors:
factor VIII (antihemophilic factor) - used in the treatment of hemophilia A (genetically based disorder of coagulation,
deficiency in factor VIII)
factor IX - used in the treatment of hemophilia B (deficiency in factor IX)
cryoprecipitate - protein fraction of blood plasma, primarily composed of factor VII, fibrinogen and vWF - used in
the treatment of Von Willebrand’s disease.
3. Vitamin K – stimulates synthesis of clotting factors (VII, IX, X, II-thrombin) by the liver. Used orally or i.v.
4. Antagonists of fibrinolytic system (via inhibition of plasminogen activators)
aminocaproic acid AMICAR 500 mg, 1000 mg Tablets; AMICAR Oral Solution, 0.25 g/mL
tranexamic acid Cyklokapron intravenous injection; LYSTEDA Tablets
Indications: in enhancing hemostasis when fibrinolysis contributes to bleeding (associated with surgical
complications following heart surgery, hematological disorders, acute and life-threatening abruptio placentae;
hepatic cirrhosis; and neoplastic diseas. As local measures – existing or susceptible bleeding in hemophilic
patients
II.
ANTIPLATELET DRUGS - inhibitors of platelet aggregation
1. Aspirin
30-150 mg once daily, loading dose in ACS 300-325 mg (best in chewable formulation)
 inhibitor of Thromboxane A2 synthesis (by inhibition of cyclooxygenase activity)
- side effects: gastrointestinal irritation and bleeding, allergic reactions
- indications: primary and secondary prevention of thrombotic events in patients with coronary
and cerebrovascular atherosclerosis
- contraindications: gastric ulcers, allergy to aspirin
2. Antagonists of P2Y12 receptors (ADP-receptors)
Used if Aspirin is not tolerated or with Aspirin in high level of thrombosis risk
 Thienopyridines – irreversal blockers

Ticlopidine (Ticlid) Clopidogrel (Plavix) Prasugrel (Effient)
- side effects: hemorrhages, hypercholesterolemia, neutropenia, thrombocytopenia, aplastic anemia
- Newer agents – reversal blockers of P2Y12receptors
- Tikagrelor (oral) (BRILINTA™, Brilique) Kangrelor (i.v.)
3. Inhibitors of GP IIb/IIIa receptor complex
- they directly inhibit platelet receptors for fibrinogen (GP IIb/IIIa receptor)
- drugs available: Abciximab ReoPro (i.v.), Eptifibatide Integrelin (i.v.), Tirofiban Aggrastat (i.v.)
 indications: prophylaxis of restenosis after PTCA (Percutaneous Transluminal Coronary Angioplasty) or
other percutaneous coronary intervention; treatment of acute coronary syndromes in combination with
fibrinolytics
 side effects: hemorrhages, thrombocytopenia, allergic reactions
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III.
ANTICOAGULANTS
1. Inhibitors of clotting factors activity
Heparins
A. HMWH (High Molecular Weight Heparin)
 also called standard heparin, unfractionated heparin (UFH)
mechanism of action: inhibition of thrombin (factor IIa by antithrombin (AT)
Antithrombin - natural inhibitor of coagulation factors
routs of administration: i.v. (immediate onset of action); s.c.( onset of action delayed 1-2 h)
 therapy monitored by APTT (Activated Partial Thromboplastin Time)
normal value 37-46 sec, therapeutic value 1,5-2,5 times the control value (60-80 sec)
B. LMWH (Low Molecular Weight Heparin)
 also called fractionated heparin
 mechanism of action: inhibition of Xa by AT.
 laboratory monitoring is not done routinely (more stable and dose-related action)
 given once daily in doses determined by manufacturer
- examples of drug s available: Enoxaparin, Dalteparin, Nadroparin
C. Indications for heparin therapy
 treatment and short term prevention of arterial and venous thrombosis and pulmonary embolism
f.e.: adjunct therapy of coronary occlusion with acute myocardial infarction
 treatment and short term and long term prophylaxis of embolization during atrial fibrillation
 prophylaxis of postoperative thromboembolism
 treatment of DIC (disseminated intravascular coagulation)
 blood transfusions, hemodialysis, extracorporeal circulation during open-heart surgery to prevent
blood clotting
D. Adverse effects
 bleeding
treatment:
discontinuation of the drug
administration of antidote: protamine sulfate (1mg per each 100 U of heparin)
fresh frozen plasma or whole blood (in massive bleeding)
 thrombocytopenia
 abnormalities of hepatic function tests, osteoporosis, allergic reactions
Direct thrombin inhibitors
• dabigatran etexilate (oral), hirudin, desirudin, bivalirudin,
• hirugen, hirulog,
• argatroban (oral)
Xa inhibitors
• fondaparynux,
• rivaroxaban (oral), apixaban, darexaban, betrixaban
Direct thrombin inhibitors and Xa inhibitors do not cause immunological thrombocytopenia – indicated in patients
with HIT instead heparins.
Their disadvantage: there are no specific antidotes to stop their anticoagulant action while serious bleeding.
2. Anticoagulants – inhibitors of coagulation factors synthesis
Antagonists of Vitamine K
 most common preparations: warfarin, acenocoumarol
 mechanism of action:
inhibition of hepatic synthesis of Vitamin K-dependent clotting factors (II, VII, IX, X) in the liver
 onset of action delayed 2-12 hours, full anticoagulant activity after 5-7 days of therapy
 therapy monitored by PT (Prothrombin Time) or better INR (International Normalized Ratio)
 therapeutic level of PT (usually 1,5-2,5 times the control value) or INR (usually 2,0-2,5) is dependent
upon the indication for anticoagulation therapy
Dosage - is individually titrated to the amount required to increase the PT or INR to therapeutic value.
Usually: Warfarin or Acenocoumarol – starting dose 5 mg on 1st-5th day, next – according to obtained INR: 0-5 mg
 adverse effects
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bleeding (treatment - see table)
anorexia, nausea, vomiting, diarrhea
skin necrosis – thrombotic disease
purple toes syndrome - microembolization
Treatment of overdosing of warfarin
according to INR value and degree of blood lose: adjusting a dosage or discontinuation of the drug
Antidote: vitamin K1
fresh frozen plasma or concentrate of vitamin K-dependent
clotting factors (i.e. Prothromplex)
Indications for oral anticoagulant therapy
A. Long-term prophylaxis of venous thromboembolic diseases
 pulmonary embolism *
 deep venous thrombosis *
B. Acute myocardial infarction *
* Following initial treatment with heparin
C. Long-term prophylaxis of arterial embolism in patients with mitral valve disease, prosthetic heart valves, atrial
fibrillation.
IV.
THROMBOLYTIC/Fibrinolytic/ DRUGS
1. Streptokinase, Urokinase
2. Recombinant tissue plasminogen activator (alteplase, r-tPA)
3. Tenecteplase, Lanoteplase
Mechanism of action:
activation of the fibrinolytic system by stimulating the conversion of inactive
plasminogen to plasmin
Indications for thrombolytic therapy

treatment of acute myocardial infarction - by lysis of thrombi in coronary artery

treatment of acute, venous and arterial thromboembolic diseases
Adverse effects of the thrombolytic enzymes
 bleeding
 febrile reactions
 allergic reactions, such as serum sickness ( streptokinase)
 dysrhythmias (due to sudden reperfusion of heart muscle after dissolution of a clot in coronary artery)
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