THROMBOSIS

Thrombosis
A thrombosis is the development of a thrombus consisting of platelets.
A thrombus is a blood clot in the vein, artery or heart.
Deep

Vein Thrombosis
Common type of thrombosis
A blood clot in a vein of the leg
Causes leg gets red, painful and swollen. This swelling is called edema

Possible causes of thrombosis can be:

Slow blood circulation
Damaged wall of the blood vessel
Changes in the composition of the blood
Some hereditary disorders that increase chance of thrombosis
Pulmonary Embolism
Dangerous complication of thrombosis
Clots that dislodge and go to the lungs
Treatment of thrombosis
Anticoagulants
An anticoagulant is a drug that helps prevent the clotting (coagulation) of blood
These drugs tend to prevent new clots from forming or an existing clot from enlarging
They dont dissolve a blood clot
Can also be given to certain people at risk for forming blood clots
Classification of anticoagulants
Used in vivo
Used in vitro

USED IN VIVO:
A. Parenteral anticoagulants:
o Heparin
o Heparinoids
Danaparoid
o Hirudins
Lepirudin
B. Oral anticoagulants:
Coumarin derivatives:
o Warfarin
Indandione derivatives:
o Phenindione
USED IN VITRO:
A. Heparin (150 U to prevent clotting of 100 ml blood)
B. Calcium complexing agent
Sodium citrate (1.65 g for 350 ml of blood)
Sodium oxalate (10 mg for 1 ml of blood)

Heparin
Heparin is a non-uniform mixture of straight chain mucopolysaccharides with MW of 10,000 to
20,000
It contains polymers of two sulfated disaccharide
D-glucosamine-L-iduronic acid
D-glucosamine-D-glucuronic acid
It carries strong electronegative charges and is the strongest organic acid present in the body
PHARMACOLOGICAL ACTION
Heparin is a powerful and instantaneously acting anticoagulant, effective both in vivo and in vitro
Heparin produces its anticoagulant effect by activating plasma antithrombin III (AT III a serine
proteinase inhibitor) and may be other similar cofactors
PHARMACOKINETICS
Heparin is a large, highly ionized molecule; therefore not absorbed orally.
Injected i.v. it acts instantaneously, but after s.c. injection anticoagulant effect develops after 60
min.
Heparin does not cross blood-brain barrier or placenta.
It is metabolized in liver by heparinase and fragments are excreted in urine.
Heparin released from mast cells is degraded by tissue macrophages.
ADVERSE EFFECT
1. Bleeding due to overdose is the most serious complication of heparin therapy. Haematuria is
generally the first sign.
2. Thrombocytopenia is another common problem.
3. Reversible alopecia is infrequent.
4. Osteoporosis and Spontaneous fractures may develop on long-term use of relatively high doses.
5. Hypersensitivity reactions are rare.
CONTRAINDICATIONS
1. Bleeding disorders, heparin induced thrombocytopenia.
2. Severe hypertension, intracranial hemorrage.
3. Subacute bacterial endocarditis, large, tuberculosis.
4. Chronic alcoholics, renal failure.
5. Aspirin and other antiplatelet drugs should be used very cautiously during heparin therapy.
HEPARIN ANTAGONIST: Protamine sulfate
It is a strongly basic, low molecular weight protein obtained from the sperm of certain fish.
Given i.v. it neutralizes heparin weight for weight, i.e. 1 mg is needed for every 100 U of heparin.
In the absence of heparin, protamine itself acts as a weak anticoagulant by interacting with
platelets and fibrinogen.
Excess protamine also has an anticoagulant effect.
ORAL ANTICOAGULANTS
Oral anticoagulants are medicines used for people who are at risk of developing abnormal blood
clotting.
The oral anticoagulants are a class of pharmaceuticals that act by antagonizing the effects of
vitamin K.
Recemic Warfarin sodium
Bishydroxycoumarin(Dicumarol)
Acenocoumarol(Nicomalone)
Ethylbiscoumacetate

Phenindione

Clinical use of vitamin K

Treatment and/or prevention of bleeding:
- Resulting from use of oral anticoagulant drugs (e.g. warfarin) as vitamin K is a procoagulant drugs
WARFARIN
Warfarin is a synthetic derivative of coumarin, a chemical found naturally in many plants, like,
woodruff (Galium odoratum, Rubiaceae), and at lower levels in licorice, lavender, species.
Warfarin is prescribed to people with an increased tendency for thrombosis or in those individuals
that have already formed a blood clot (thrombus).
Warfarin is contraindicated in pregnancy, as it passes through the placental barrier and may cause
bleeding in the fetus.
Mechanism of action
Warfarin is an analogue of Vitamin K. Warfarin inhibits the vitamin K-dependent synthesis of
biologically active forms of the calcium-dependent clotting factors II, VII, IX and X, as well as the
regulatory factors protein C.
Adverse effects
Bleeding
Alopecia
Dermatitis
Urticaria
Hematuria

Use of anticoagulants
The aim of using anticoagulants is to prevent thrombus extension and embolic complications by
reducing the rate of fibrin formation
Thrombolytics (Fibrinolytics)
These drug are use to lyse thrombi(clot)

Streptokinase
Urokinase
Anistreplase
tissue Plasminogen Activators (t-PA)
o Alteplase
o Reteplase
o Tenecteplase

Fibrinolysis
Endothelial cells secrete tissue plasminogen activator (t-PA) at sites of injury.
t-PA binds to fibrin and cleaves plasminogen to plasmin, resulting in fibrin digestion. Plasminogen
activator inhibitors-1 and -2 (PAI-1, PAI-2) inactivate t-PA; a2-antiplasmin (a2-AP) inactivates
plasmin.
Mode

of action
Plasmin is an endogenous fibrinolytic enzyme that degrades clots by splitting fibrin into fragments.
Plasmin itself cannot be used because naturally occurring inhibitors in plasma prevent its effects.
Fibrinolytic drugs catalyze the conversion of precursor plasminogen into active plasmin.
Rapidly lyse or break down thrombi.

Antiplatelet Drugs
Platelets play such a critical role in thromboembolic disease that it is no surprise that antiplatelet
drugs are of immense therapeutic value.
Aspirin
Aspirin irreversibly inhibit COX (up to the life-time of the platelets 8-10 days).
Both PGI2 and TXA2 synthesis are inhibited.
To separate this action aspirin in small dose 75-100 mg/day inhibits TXA2 synthesis without
significant effect on the endothelial PGI2.
This low dose of aspirin may also causes peptic ulcer bleeding in patients > 60 years.
Dipyridamole
It inhibits phosphodiesterase enzyme, so increasing intraplatelet cAMP.
It may also increase PGI2 in vascular endothelium.
It has coronary VD activity.
Ticlodipine
Ticlopidine inhibits ADP- dependent platelet aggregation.
It is more effective than aspirin, but aspirin is safer and less expensive.
It is used to prevent stroke in patient who are intolerant to aspirin.
A/E: neutropenia (do WBC count / 2 weeks), GIT upset especially diarrhea.
Clopidogrel
It acts like ticlopidine, but not associated with neutropenia.
It is more effective and more expensive than aspirin, but safer than ticlopidine.
Epoprostenol
It is a prostacyclin.
Used during renal dialysis to prevent platelet loss.
It is used with or without heparin.
It is a potent VD.

Other antiplatelet drugs

Dazoxiben: It inhibits TXA2, but not PGI2. it is being evaluated in cardiac diseases.
Sulphinpyrazone: It is a uricosuric agent and has an antiplatelet effect.
Fish oil: (omega 3-marine triglyceride): It may form abnormal thromboxane.
TREATMENT OF THROMBOEMBOLISM

Non Pharmacological Treatment

Few things you can do by yourself to prevent thrombosis:
Get sufficient exercise
Strive for a healthy lifestyle
QUIT SMOKING! Smoking is a high risk factor for thrombosis
Also try to maintain a healthy weight
Live and eat healthy
Eat minimal saturated fats. Eat plenty of fruits and vegetables.

I can do all things through Christ who gives me

strength. Phil. 4:13 [