Laboratory Control of Anticoagulants, Thrombolytic and Anti-Platelet Therapy.

INTRODUCTION
Anticoagulants are classes of drugs that work to prevent coagulation (clotting) of blood. They can be used in-vivo as a medication for thrombotic disorders. Some are also used in medical equipment such as test tubes, blood transfusion bags and renal dialysis.

Thrombosis  is the formation of a blood clot (thrombus) inside a blood vessel, obstructing the flow of blood through the circulatory system.

When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot (haemostasis) to prevent blood loss. If that mechansim causes too much clotting, the clot breaks free forming an ‘embolus’.

Platelets are the smallest of the blood cells functioning along with the coagulation factors to stop bleeding.
Anticoagulant Therapy: This is a medication  used to slow the blood clotting process. It is either used to prevent a clot formed or to treat clots that have already formed.

An example of a mostly used anticoagulant drug is Warfarin.

INDICATIONS FOR ANTICOAGULANT  THERAPY

Anticoagulant Therapy is indicated for the following clinical conditions:
a.Deep Vein Thrombosis: Blood clot in one of the Large veins in the leg or arm.
b. Pulmonary Embolus: Blood clot forming or traveling to the lungs.

c. Atrial Fibrillation (Irregular heart Rhytm): Occurs when the atria do not contract simultaneously, causing blood not to flow

through them as rapidly as it should making the blood more likely to clot.

 If a clot becomes dislodged it can travel to the brain and result in a stroke. Warfarin administration can reduce the risk of stroke by 60-70%.

d. Mechanical Heart Valves: Patients fitted with mechanical heart valve will need long term anticoagulation treatment to prevent blood clots forming on the valve. 

LABORATORY CONTROL OF ANTICOAGULANT THERAPY

The importance of regular laboratory tests is to ensure adequate dosage is administered from time to time to prevent bleeding tendencies.

Dosage may change from time to time depending on outcome of laboratory tests.

The blood tests to monitor the clotting is called INR (International Normalised Ratio).

A patient not on warfarin should have a normal INR between 0.9 and 1.3, while a patient on warfarin should have an INR range of 0.2 to 3.0, 2.5 to 3.5, or 3.0 to 4.0.

The result of the INR will determine the warfarin dose to be administered for patient to keep the INR within the desired range.

When a patient first starts taking warfarin, the INR will be checked every few days and dose of warfarin will be presecribed according to the results.

A major test to monitor patients on warfarin anticoagulation is the Prothrombin Time (PT).

PROTHROMBIN TEST (PT) PROCEDURE

It is a screening test for the extrinsic clotting system i.e factor VII. It also detects deficiencies of factors V, X, Prothrombin and Fibrinogen. It is mainly used to monitor atients receiving warfarin anticoagulation.

Principle: Plasma or capillary blood is added to a thromboplastin and calcium chloride reagent at 37°C and the time taken for a clot to form is measured. 

 

The clotting time in seconds is converted to the INR, usually by a  reference table provided by the manufacture of the reagent or from the formula.

INR =     PT Patient

                (  ----------------)isi

                  PT Control

That is Prothrombin ratio to the power of the ISI.

ISI: International Sensitivity Index.

Method of Prothrombin Time

Perform test in duplicate if using patient plasma.

1. Pipette 0.25ml of thromboplastin/Calcium reagent into a small glass tube. Place in a 37°C water bath for 1-2 minutes.

2. Add 0.05ml of plasma, mix and start the stop-watch. Hold the tube in the water bath and tilt the mixture back and forth looking for clot formation.

3. When a clot forms, stop the stop-watch & record the time in seconds. Convert the clotting time to the INR using the table provided by the manufacturer.

Prothrombin Time (PT) Reference Range.

Normal plasma samples for patients clot is 11-16 

Seconds.

 Causes of a Prolonged PT Tests

-   Treatment with oral anticoagulant drugs

(Vitamin k antagonists) such as Warfarin.

Liver disease

Disseminated Intravascular Coagulation (DIC)

ASSOCIATED RISK WITH ANTICOAGULANT THERAPY

The main risk of taking warfarin is bleeding.

In a patient receiving oral anticoagulants, PT is usually maintained between one and a half and two times the normal control.

THROMBOLYTIC THERAPY

It is a treatment used to break up dangerous clots inside blood vessels. They are commonly used to treat Ischemic Strokes ( A clot in blood vessel in the brain).

 INDICATIONS FOR THROMBOLYTIC THERAPY

It is usually used to treat clots in a 

Lung artery  (Pulmonary Embolism)

Deep Veins of the Leg (Veep Vein Thrombosis – DVT)

Heart (Myocardial infarction).

Blood clots can build up inside a blood vessel and sometimes break off and travel through blood stream and get dislodged in a blood vessel & obstruct normal blood flow.

They can extent to heart or lungs startving the organ and can be life threatening.

LABORATORY CONTROL OF THROMBOLYTIC THERAPY

Medical laboratory tests will be done to see if blood is clotting normally.

An Echocardiogram (ECG) test to find out whether there is a clot in the heart.

An Angiograhpy that creates a picture of the blood vessel can be done.

Although bleeding time has been considered primarily to reflect platelet function. It also reflects the interraction of platelets with vessel wall and coagulation pathways. 

Therefore bleeding time has been considered  potential predictor of clinical bleeding during thrombolysis.  

Several bleeding time tests (bt) during thrombolytic therapy may provide  valuable information regarding safety and efficacy.

BLEEDING TIME PROCEDURE.

This procedure measures the time required to form  a clot and stop bleeding after a standardized skin incision.

Bleeding time may be measured by one of four methods : Duke, Ivy, Template and modified template.

  IVY METHOD

Wrap  the pressure curve around the upper arm and inflate the cuff to 40mmhg.

Select an area on the forearm free of superficial veins and cleanse it with antiseptic.

Allow the skin to dry completely before making the incision.

Make three small punctures with a disposable lancet.

Start the stop-watch immediately.

Blot each site with filter paper every 30secs until the bleeding stops.

Average the bleeding time of the three punctures and record the result.

Normal Range of Bleeding Time in this method is 1 to 7minutes.

ANTIPLATELET THERAPY

This is a treatment with a drug that decreases the formation of platelets.

The most commonly recommended anti-platelet therapy is low-dose acetylsalicylic acid (ASA).

INDICATIONS FOR ANTIPLATELET THERAPY

Management of acute ischemic stroke and for the prevention of stroke.

Treatment with aspirin decreases the risk of other cardiovascular events in a wide range of patients with established disease. 

Associated Risks with Anti-Platelet Therapy.

Just like in others, the main risk associated with Anti-platelet therapy is BLEEDING.

Therefore knowing when to stop dosage administration is significant.

Laboratory Control of Anti-Platelet Therapy

When a person is on an anti-platelet medication, such as aspirin or quinine, the results of platelet testing reflect the platelet response to the medication. Platelet Count is measured in this case.

 Patient’s clinical history and results of coagulation tests such as PT and APTT are used to determine the overall risk of excessive bleeding in pre-surgical patients during an invasive procedure. 

Conclusion

The choice of method in the laboratory control of anticoagulant, thrombolytic and Antiplatelet therapy is a case in point.

The physician responsible for a patient with thrombo-embolic disease should be aware of a number of interrelated aspects of anticoagulant therapy, particularly selection of the patient to be treated, the complications of therapy, and the method of laboratory control.

Recommendation

 Relevant laboratory testing should be done before, during and after anticoagulant, thrombolytic and anti-platelet therapies to ensure patient’s overall safety and treatment efficacy.