The Role Of Platelets In The Role Of Platelets In ThrombosisThrombosis

By

Valiere Alcena, M.D., F.A.C.P.

Clinical Professor of Medicine Albert Einstein College of Medicine

Bronx, NYand

Adjunct Professor of MedicineNew York Medical College

Valhalla, NYOttawa, Canada August 1, 2003

Abstract: The role of Platelets in The Thrombotic Process A Thrombus is a live saving process when it occurs in the presence of

hemorrhage, and a live threatening process when it occurs at any other time. Platelets play a key role in the formation of thrombosis. In the normal process, when hemorrhage is occurring either as a result

of trauma Or as a result of a surgical procedure, the platelets are the first thing to start

the process of clot formation in an attempt to seal the wound to stop bleeding. Platelets contain different substances within them that cause them to

aggregate to begin Clot formation in diseases such as

1.      Coronary thrombosis. 2.      Cerebrovascular accident. 3.      Deep Vein Thrombophlebitis. 4.      Transient Ischemic Attack. Platelets have the primary role in starting clot formation in

diseases outlined above. Platelets play a crucial secondary role in clot formation in

a the long list of thrombophylic syndromes where clot formation represents the crucial and possible lethal variables.

Why do Platelets form clots?

How platelets form clots? What are the different diseases that are associated with

elevated platelets? Do all elevated platelets syndrome cause thrombosis? If not, why not? How to evaluate elevated platelets? How does elevated platelets ought to be treated? What is the state of the art in the treatment of

thrombosis?

The Role of Platelets in Thrombosis What are plaletelets? Platelets are armorphous –shapeless cells that are

produced in the bone marrow by the megakyryocytes. Inside the platelets are contained several substances. When the platelets are activated, 2 important substances

are released that are key in the formation of a thrombus. 1. Thromboxane A2 2. Cyclooxyganase

There are two types of thrombosis1. Arterial Thrombosis 2. Venous Thrombosis In arterial Thrombosis, thrombus develops

inside vessels that have been damaged by arteriosclorotic plaques or vessels damaged by substances such as homocysteine or Lipoprotein -a.

In Venous Thrombosis, Thrombus develops inside normal blood vessels due slow or stagnant blood flow.

Venous Thrombus also develops as a result of hypercoagulable state, Trousseau Syndrome and chemotherapy associated thrombosis.

In both arterial and venous thrombosis platelets enter into a reaction that starts with adhesion, follows with aggregation, then clot formation (thrombus formation).

Cyclooxygenase and thromboxane A2 participate in this reaction.

Thromboxane A2 is a platelet aggregator and a

vasoconstrictor, it causes clot to form. Cyclooxygenase is the enzyme that mediates

the reaction which leads to platelet aggregation and vesoconstriction, and is inhibited by Aspirin to prevent clot formation.

This reaction also produces Prostacycline which is the natural vasodilator.

Some of the conditions and different disease entities that pre-dispose to the development of both arterial thrombosis and venous thrombosis are:

Arterial Thrombosis: a) Arteriosclerosis b) Thrombophilia- vessel damage c) Elevated Homocystine d) Elevated lipoprotein a e) Anticardiolipin syndrome f) Lupus anticoagulant g)Thrombotic Thrombocytopinic Purpura

Venous Thrombosis: Major consequences deep vein thrombophlebitis (DVT) 2,500,000 individuals develop DVT in the U.S every year. Pulmonary Embolism 600,000 individuals develop pulmonary embolism every year

in the U.S. About 200,000 individuals die of pulmonary embolism every

year in the U.S. 60,000 people die undiagnosed as a result of pulmonary

embolism every year in the U.S. according to Associated Press.

a)  Elevated homocystine b)  Lipoprotein a (explain mechanism of action) c)  Factor V Leiden deficiency d)  Protein S deficiency e)  Protein C deficiency f)   Antithrombin III deficiency g)  B 12 deficiency h)  Folic Acid deficiency i)   Heparin induced thrombocytopenia (mechanism of thrombosis, CVA,

MI, cold limb syndrome) j)   Stopping heparin improperly when beginning treatment with Coumadin,

etc.

Some of the different diseases that pre-dispose to the development of both arterial thrombosis and venous thrombosis are:

1. Troussau syndrome (in cancer of different types-explain mechanism) 2. Polycythemia Vera

3. Secondary Polycythemia 4. Essential Thrombocytemia 5. Thrombocytosis (when associated with myeloproliferative disorder) 6. Nephrotic syndrome 7. AIDS 8. Sickle cell anemia (this occurs via several mechanisms-explain)

9. Chronic renal failure 10. Pregnancy 11. Immobilization 12. Post orthopedic surgery of the knee and hip 13. Post major abdominal surgery 14. Post radical prostatectomy for prostate cancer 15. Age above 55 16. Long Airline flights 17. Long travel by train, car, and bus 18. Major trauma, etc.

Some of the medications that can cause thrombosis are:

1. Estrogenic hormone 2. Some chemotherapeutic agents (explain

mechanism) 3. Megace 4. Anabolic steroids

THE ROLE OF PLATELETS IN CORONARY

THROMBOSIS The most common cause of arterial thromboses are coronary

thrombosis leading to acute myocardial infarctions and cerebrovascular accidents.

In the U.S. there are 12,900,000 individuals with coronary artery heart disease and 7,600,000 of these individuals have had myocardial infraction. The incidence of heart attack per year is 540,000 and the incidence of death from heart attack is 192,898 per year. Acute thrombosis plays the primary role in both the causation of acute MI and death resulting from the MI in these individuals.

To prevent the development of acute MI and death from it, one then has to interfere with platelet aggregation by using antiplatelet medications such as Aspirin and Plavix.

Aspirin works to prevent thrombosis by interfering with the

effect of thromboxane A2 on the platelet aggregation reaction, which is mediated by cyclooxygenese. Thromboxane A2 secretes substances that cause platelets to aggregate but in addition causes vasoconstriction to occur. 81 mg of Aspirin or less is needed to block the effect of thromoxane A2 without interfering with the beneficial vasodisilatory effect of prostacycline. It is important to realize that when more than 81 mg of Aspirin are used to treat coronary thrombosis, the adverse effect of thromboxane A2 is prevented, however on the down site the beneficial effect of prostacycline is obliterated. The end result is increased incident of bleeding from too much Aspirin being used while loosing the vasodilitacion effect of prostocycline which is not a good thing.

Plavix Celebrex, and Vioxx, and their effects on

coronary thrombosis

THE ROLE OF PLATELETS IN ISCHEMIC STROKE

In the U.S. each year 700,000 individuals have strokes and

167,661 of them die of the stroke. Platelets play an important secondary role in the thrombosis that occur in the development of ischemic stroke.

The mechanism through which the thrombus is formed in this type of stroke is the same as just described in coronary thrombosis.

However the dose of Aspirin that is used to both treat and prevent ischemic stroke is 325mg as compared to the 81mg used to treat coronary artery disease.

HOW TO DIAGNOSE THROMBOSIS Arterial thrombosis is diagnosed by CT,

MRI, and engiogram. DVT is diagnosed by ultrasound of the

extremities, venogram, and d-Dimer.Pulmonary embolism is diagnosed by Lung

scan, CT, and pulmonary angiogram.(Explain d-Dimer)

HOW TO TREAT THROMBOSIS

DVT is treated with Heparin and Coumadin. (explain how to best use Heparin and how to best use Coumadin)

HOW TO PREVENT THROMBOSIS

1.      Appropriate screening to determine underliying thrombophilias

2.      Appropriate prophylaxtic treatments with Aspirin, Coumadin, and Heparin.

3.      Refrain from using unnecessary estrogenic hormones 4.      Refrain from using unnecessary anabolic steroids 5.      Use of intermittent compression devise in patients post

major surgery and in patients who must lie in bed for long period of time.

6.      Use of Coumadin or Heparin in patients who have had knee replacement or hip replacement surgery.

7.      Use of appropriate prophylaxsis with low molecular weight Heparin in appropriate individuals who are traveling long distances by plane, car, train, or bus.

8.      Use of heparin prophylaxis in appropriate women with documented thrombophylia during pregnancy to protect the mother from forming thrombosis and to prevent spontaneous abortion

9.      Use Lovenox or other Low Molecular weight Heparin in women who are undergoing in vitro fertilization to prevent thrombosis of the placental circulation etc.

Copyright Copyright © 2003 Valiere Alcena, M.D., F.A.C.P.© 2003 Valiere Alcena, M.D., F.A.C.P.

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