Coagulants and Anticoagulants.

Coagulants  

“The drugs which promote blood coagulation & used in the treatment of hemorrhagic disorders are called as coagulants”

Haemostatics

“These are pharmacological agents when administered stop/arrest bleeding & used to control oozing of blood from capillary vessel” 

Classification:

1.     Vitamin K analog: 

                               e.g.  Vitamin K₁ (Phytonadione) 

                                       Vitamin K₃ (Menadione), 

                                       Phytomenadione

            2.       Potent Coagulants:

                                e.g. Ethamsylate, 

                                       Tranexamic acid, 

                                       Adrenochrome, 

                                  Monosemicarbazone.

            3.        Haemostatics for hemophilia:

                                e.g. Fibrinogen, 

                                       Antihaemophilic globulin (AHG).

            4.        Flavonoids:  

                                 e.g. Rutin.

            5.        Topical Coagulants: 

                                e.g. Tannic acid, 

                                       Haemocoagulase, 

                                      Gelatin Sponge, 

                                      Oxidized cellulose.

               Therapeutic Uses and Doses  :

S.No.	Drug(Brand Name)& Therapeutic Uses	Dose	Adverse effects
	Phytomenadione(Kapilin/Kenadion) Ø  Liver cirrhosis associated bleeding Ø  Overdose of oral anticoagulants Ø  Salicylate poisoning	0.5-5mg/day IM/IV	Breathlessness, hypotension, fatigue, Allergic reactions after IM/&SC administration, Phlebitis.
2	Antihaemophilic globulin (AHG) + Fibrinogen. Ø  Haemophilia
3	Ethamsylate (Sylat) Ø  Menorrhagia Ø   Control of hemorrhage after surgery Ø  Treatment & prophylaxis of periventricular hemorrhage in low birth-weight neonates Ø   Epistaxis Ø  Haematuria Ø   Hematemesis	250-500mg oral every 4-6 hr 12.5/kg IM/IV Inj. every 4-6 hr	Skin rash, Headache, Hypotension.
4	Tranexamic acid (Tx) ØShort-term management of haemorrhage associated with dysmenorrhoea.	1-1.5g bid-qid oral  0.5-1g or 10mg/kg tid	Diarrhea, nausea, vomiting, disturbance in color vision, thromboembolism & thrombosis.

           

MOA of coagulants

1    1.   Phytomenadione is Vitamin analog which promotes hepatic synthesis of clotting factors.

2.       Ethamsylate stops hemorrhage from small blood vessels by stabilizing the capillary wall & correcting abnormal platelet adhesion.

3.      Tranexamic acid is an antifibrinolytic agent that competitively inhibits the breakdown of fibrin clots. It also prevents binding of the activation of plasminogen to fibrin (fibrinolysis). 

      

        Anticoagulants

“           The drugs which reduce coagulation of blood in intact blood vessels & used in prophylactic treatment of venous thrombosis are called as anticoagulants”.

     

         

       Oral anticoagulants

“         The drugs which reduce coagulation of blood & used for prophylactic treatment of venous thrombosis & related disorders effectively on oral administration are called as oral anticoagulants”.

        

      Classification

1.                    Parenteral anticoagulants (Fast acting anticoagulants directly acting)

                               e.g. Heparin,

                                       Low molecular weight heparin (LMWH)-

                                       Enoxaparin, 

                                       Parnaparin.

                            2 .            Oral anticoagulants (Slow acting anticoagulants directly acting):        

      

         e.g. A) Coumarin derivatives e.g. Warfarin sodium, 

                                                                        Dicumarol

                              B) Indandione derivatives. e.g. Phenindion.

        

S.No.	Drug (Brand Name ) & Therapeutic Uses	Dose	Adverse effect
1	Heparin (V-Parin/Thrombophob) Ø  Deep vein thrombosis Ø   Pulmonary embolism Ø  Management of unstable angina Ø  Prevention of re-occlusion of coronary arteries following thrombolytic therapy	5000-25000 qid  IV/SC	Skin necrosis (SC injection), slight fever, slight haematuria, thrombocytopenia, epistaxis, osteoporosis, alopecia, hypersensitivity reactions.
2	Enoxaparin (Enoxaparin/Clexane) Ø  Deep vein thrombosis Ø   Pulmonary embolism Ø  Management of  unstable angina Ø  Prevention of clotting in the extracorporeal circulation during hemodialysis. Parnaparin (Fluxum)	20- 80 mg bid SC 3200-6400 IU bid SC	Erythema, thrombocytopenia, MI bleeding, irritation at Inj site
3	Warfarin (Warf) Ø  Prophylaxis in coronary thrombosis Ø  Cerebral thrombosis, Ø   Pulmonary embolism Ø   Myocardial infarction	1-5 mg OD oral	Hepatic dysfunction, pancreatitis alopecia, purple toes, Hypersensitivity, rash, diarrhea

       

Mechanism of action

• Heparin increases the inhibitory action of antithrombin III (AT III) on clotting factors IX a, X a, XI a, XII a & thrombin. This results in inhibition of conversion of prothrombin to thrombin & fibrinogen to fibrin. It also inhibits platelet aggregation & prolongs bleeding time.
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• It has been suggested that at very low doses heparin reduces postoperative increase in platelet adhesiveness.
• Enoxaparin increases the inhibitory action of antithrombin III (AT III) on clotting factors X a & thrombin.
• Warfarin inhibits synthesis of vitamin K dependent coagulation factors VII, IX, X & XI including anticoagulation protein C & its cofactor protein.

  Contraindications of parenteral anticoagulants:

1.      Peptic ulcer: ( Will precipitate gastric bleeding.)

2.      Haemophilia: ( Will worsen the situation)

3.      Threatened abortion (Will increase the chance of abortion.)

4.      Thrombocytopenia. ( Will increase chances of bleedings.)

   Fibrinolytics

• The drugs which activate blood plasminogen (profibrinolysin) to causes lysis of thrombus (blood clot) in intact blood vessels (especially coronary artery) & used in the curative treatment of acute myocardial infarction & acute thrombosis are called as fibrinolytic.
•  e. g. Streptokinase, Urokinase

Mechanism of action:-

• They activate blood plasminogen (profibrinolysin) to plasmin (fibrinolysin). Plasmin causes lysis of blood clot & removes the blockade in blood flow. Their action is curative rather than prophylactic.
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S.No.	Drug(Brand name)& Therapeutic uses	Dose	Adverse effect
1	Streptokinase (Streptase/Fibrokinase) Ø  Acute MI Ø  Coronary thrombosis Ø  Pulmonary embolism	1-15 lakh IU  slow IV infusion	Fever,chills,back pain, abdominal pain anaphylaxis,arrhythmia,acute renal failure
2	Urokinase (Uni-Kinase) Ø  Acute MI Ø  Coronary thrombosis Ø  Pulmonary embolism	2.5-10L IU slow IV infusion	Drug induced fever safer than streptokinase. (Aspirin should not be given for fever)

Antiplatelet drug

• The drugs which inhibit thromboxaneA₂& ADP to prevent the formation of platelet plug in intact blood vessels & used in prophylactic treatment of arterial thrombosis are called as antiplatelet drugs.
•  E.g. Aspirin, 
• Clopidogrel, 
• Dipyridamole, 
• Ticlopidine.

Mechanism of action-

• Damaged endothelium releases thromboxane A2& ADP which causes platelet aggregation. Antiplatelet drugs inhibit thromboxane A₂& ADP release & thereby prevent the formation of the platelet plug. Aspirin & dipyridamole inhibits thromboxane A₂ while clopidogrel, ticlopidine inhibit ADP from binding to its receptors ADP receptor. 

S.No.	Drug(Brand Name) & Therapeutic uses	Dose	Adverse effect
1	Aspirin (Ecosprin) Ø  As prophylaxis in thromboembolic disorders like MI, coronary thrombosis, pulmonary embolism & cerebral thrombosis (stroke)	75- 150 mg OD Oral	Nausea, dizziness, skin rash
2	Clopidogrel (Clopi tab) Ø  As prophylaxis in thromboembolic disorders like MI, coronary thrombosis, pulmonary embolism & cerebral thrombosis (stroke)	75mg OD Oral	Epigastric distress, skin rash.