COGULATION PROFILE

Bleeding time, clotting time, PT, and PTT

Presented By HUSSAIN AKHTAR

WHAT IS COAGULATION?Coagulation is a complex process by which blood forms clots. Blood

must be remain fluid with in the vasculature and yet clot quickly when expose to non endothelial surface at a site of vascular injury.

It is an important part of haemostasis (the cessation of blood loss from a damaged vessel), where in a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel.

Disorders of coagulation can lead to an increased risk of bleeding (hemorrhage) or clotting (thrombosis).

Hemostasis is maintained in the body via three mechanisms: Vascular spasm - Damaged blood vessels. constrictPlatelet plug formation - Platelats adhere

to damaged endothelium to form platelet plug (primary hemostasis) and then degranulate.

Blood Coagulation - Clots form upon the conversion of fibrinogen to Fibrin, and its addition to the platelet plug (secondary hemostasis).

Factor IFibrinogenFactor VIIIAntihemophilic globulin

Factor IIProthrombinFactor IXPartial thromboplastin component

Factor IIIThromboplastin

Factor XStuart-Prower factor

Factor IVCalciumFactor XIPlasma thromboplastin antecedent

Factor VLabile or proaccelerin

Factor XIIHageman factor

Factor VIIStable factor or proconvertin

Factor XIIIFibrin-stabilizing factor

THE CLOTTING MECHANISMINTRINSIC EXTRINSC

PROTHROMBIN THROMBIN

FIBRINOGEN

FIBRIN(II) (III)

(I)V

X

Tisue ThromboplastinCollagen

VII

XIIXI

IXVIII

FIBRINOLYTIC PHASE

ANTICLOTTING MECHANISMS ARE ACTIVATED TO ALLOW CLOT DISINTEGRATION AND REPAIR OF THE DAMAGED VESSEL.

HEMOSTASISDEPENDENT UPON:

Vessel Wall Integrity Adequate Numbers of Platelets Proper Functioning Platelets Adequate Levels of Clotting Factors Proper Function of Fibrinolytic Pathway

So What Causes Bleeding Disorders?

VESSEL DEFECTS

PLATELET DISORDERS

FACTOR DEFICIENCIES

VESSEL DEFECTS VITAMIN C DEFICIENCY BACTERIAL & VIRAL INFECTIONS ACQUIRED

PLATELET DISORDERS THROMBOCYTOPENIA

(INADEQUATE NUMBER OF PLATELETS)

Causes DRUG INDUCED BONE MARROW FAILURE HYPERSPLENISM OTHER CAUSES

THROMBOCYTOPATHY ) ADEQUATE NUMBER BUT ABNORMAL

FUNCTION )

causes UREMIA INHERITED DISORDERS MYELOPROLIFERATIVE DISORDERS DRUG INDUCED(ASPIRIN, NSAIDS)

FACTOR DEFICIENCIES Inherited:

1. HEMHHHHOPHILIA A

2. HEMOPHILIA B

3. VON WILLEBRAND’S DISEASE

Acquired:

1. Anticoagulant therapy

2. Liver diseases

3. DIC

LABORATORY EVALUATIONPLATELET COUNTBLEEDING TIME (BT)Clotting time (CT)PROTHROMBIN TIME (PT)Activated PARTIAL THROMBOPLASTIN

TIME (APTT)

PLATELET COUNT (CBC)

NORMAL 100,000 - 400,000 CELLS/MM3

< 100,000 Thrombocytopenia

50,000 - 100,000 Mild Thrombocytopenia

< 50,000 Sever Thrombocytopenia

BLEEDING TIME

PROVIDES ASSESSMENT OF PLATELET COUNT AND FUNCTION

NORMAL VALUE 2-8 MINUTES

Clotting time - capillary method Material

1. Sterile disposable pricking needle or lancet. 2. Stop watch 3. Dry glass capillary tube (narrow diameter 1 top 2 mm,

minimum 10 cm long.) 4. Cotton Swab of absorbent cotton. 5. Spirit wetted, cotton swab. 6. 70 % v/v ethyl alcohol

Clotting time of whole blood

Clotting Time - Slide Method• The surface of the glass tube

initiates the clotting process. This test is sensitive to the factors involved in the intrinsic pathway

• The expected range for clotting time is 4-10 min.

PROTHROMBIN TIMEPROTHROMBIN TIME

Measures Effectiveness of the Extrinsic Measures Effectiveness of the Extrinsic PathwayPathway

NORMAL VALUENORMAL VALUE 10-15 SECS10-15 SECS

PTThe prothrombin time: is therefore the time required for the plasma

to clot after an excess of thromboplastin and an optimal concentration of calcium have been added.

Measures the function of the Extrinsic Pathway. Sensitive to Factors I, II, V, VII, X.

The PT evaluates patients suspected of having an inherited or acquired deficiency in these pathways.

THE CLOTTING MECHANISMINTRINSIC EXTRINSC

PROTHROMBIN THROMBIN

FIBRINOGEN

FIBRIN(II) (III)

(I)V

X

Tisue ThromboplastinCollagen

VII

XIIXI

IXVIII

When is it ordered?Used to monitor oral anticoagulant therapy (Warfarin /

Coumadin).

When a patient who is not taking anti-coagulant drugs has signs or symptoms of a bleeding disorder.

When a patient is to undergo an invasive medical procedure, such as surgery, to ensure normal clotting ability.

An elevated prothrombin time may indicate the presence of: Vitamin K deficiency(Vitamin K is needed to make prothrombin and other clotting factors) DIC liver disease a deficiency in one or more of the following factors: I, II, V, VII, X. Anticoagulant (warfarin)

INRA PT test may also be called an INR test. INR (international normalized ratio) stands for a way of

standardizing the results of prothrombin time tests, no matter the testing method.

So your doctor can understand results in the same way even when they come from different labs and different test methods.

Using the INR system, treatment with (anticoagulant therapy) will be the same. In some labs, only the INR is reported and the PT is not reported

An INR of 1.0 means that the patient PT is normal.An INR greater than 1.0 means the clotting time is

elevated.INR of greater than 5 or 5.5 = unacceptable high risk of

bleeding,whereas if the INR=0.5 then there is a high chance of having a clot.

Normal range for a healthy person is 0.9–1.3, and for people on warfarin therapy, 2.0–3.0, although the target INR may be higher in particular situations, such as for those with a mechanical heart valve.

PARTIAL THROMBOPLASTIN TIME Measures Effectiveness of the Intrinsic Pathway

NORMAL VALUENORMAL VALUE 25-40 SECS25-40 SECS

PTTThe partial thromboplastin time (PTT) or activated partial

thromboplastin time (aPTT or APTT( is a performance indicator measuring the efficacy of both the "intrinsic" and the common coagulation pathways.

It is also used to monitor the treatment effects with heparin a major anticoagulant.

Kaolin cephalin clotting time (KccT) is a historic name for the activated partial thromboplastin time

THE CLOTTING MECHANISMINTRINSIC EXTRINSC

PROTHROMBIN THROMBIN

FIBRINOGEN

FIBRIN(II) (III)

(I)V

X

Tisue ThromboplastinCollagen

VII

XIIXI

IXVIII

Normal PTT times require the presence of the following coagulation factors:

I, II, III, IV, V, VI, VIII, IX, X, XI, & XII

When is it ordered?When a patient presents with unexplained bleeding or

bruising, It may be ordered as part of a pre-surgical evaluation for

bleeding tendencies, When a patient is on intravenous (IV) or injection heparin

therapy, the APTT is ordered at regular intervals to monitor the degree of anticoagulation.

Prolonged APTT may indicate: Use of heparin.

antiphospholipid antibody:especially lupus anticoagulant, which paradoxically increases propensity to thrombosis

coagulation factor deficiency , e.g hemophilia DICLiver disease

FACTOR DEFICIENCIES Inherited:

1. HEMOPHILIA A

2. HEMOPHILIA B

3. VON WILLEBRAND’S DISEASE

Acquired:

1. Anticoagulant therapy

2. Liver diseases

3. DIC

HEMOPHILIA A (Classic Hemophilia) 80-85% of all Hemophiliacs Deficiency of Factor VIII Lab Results - Prolonged PTT

HEMOPHILIA B (Christmas Disease)

10-15% of all Hemophiliacs Deficiency of Factor IX Lab Test - Prolonged PTT

VON WILLEBRAND’S DISEASE Deficiency of VWF & amount of Factor VIII Factor VIII is bound to vWF while inactive in

circulation; Factor VIII degrades rapidly when not bound to vWF

Lab Results - Prolonged BT, PTT

ANTICOAGULANTS An anticoagulant is a substance that prevents

coagulation; that is, it stops blood from clotting This prevents deep vein thrombosis, pulmonar

embolism, myocardial infarction and stroke.

ANTICOAGULANTS1. Coumadins (Vitamin K antagonists)2. Heparin

Coumadin'sThese oral anticoagulants that antagonize the

effects of vitamin K. Examples include warfarin. It takes at least 48 to

72 hours for the anticoagulant effect to develop. Where an immediate effect is required, heparin must be given concomitantly.

Monitored by PT timesThese anticoagulants are used to treat patients

with deep-vein thrombosis (DVT), pulmonary embolism (PE), atrial fibrillation (AF), and mechanical prosthetic heart valves.

HeparinHeparin is a biological substance. It works by activating antithrombin III, which

blocks thrombin from clotting blood.Heparin Therapy is Monitored by PTT times Low molecular weight heparin is a more highly

processed product that is useful as it does not require monitoring of the APTT coagulation parameter (it has more predictable plasma levels) and has fewer side effects.

Liver Disease Liver Disease can Result in Reduced

Production of Coagulation Factors (I,II,V,VII,IX,X).

DICDisseminated intravascular coagulation (DIC is a

pathological activation of coagulation) blood clotting) mechanisms that happens in response to a variety of diseases

DIC leads to the formation of small blood clots inside the blood vessels throughout the body

The small clots also disrupt normal blood flow to organs (such as the kidneys), which may malfunction as a result

As the small clots consume coagulation proteins and platelets, normal coagulation is disrupted and abnormal bleeding occurs from the skin the gastrointestinal tract, the respiratory tract and surgical wounds.

The PT and APTT are usually very prolonged and the fibrinogen level markedly reduced

High levels of fibrin degradation products, including D-dimer, are found owing to the intense fibrinolytic activity stimulated by the presence of fibrin in the circulation.

Definitive diagnosis depends on the result of DIC:

Thrombocytopenia) prolonged bleeding time) Prolongation of prothrombin time and activated

partial thromboplastin time A low fibrinogen concentration Increased levels of fibrin degradation products

Pre-analytic errors

Problems with blue-top tube Partial fill tubes Vacuum leak and citrate

evaporation

Problems with phlebotomy Heparin contamination Wrong label Slow fill Underfill Vigorous shaking

Biological effects•Hct ≥55 or ≤15•Lipemia, hyperbilirubinemia,

hemolysis

Laboratory errors•Delay in testing•Prolonged incubation at 37°C•Freeze/thaw deterioration