Coagulation tests

Several laboratory tests can be used to evaluate the coagulation system. They're used in the evaluation of bleeding disorders.

Summary

Parameter	Coagulation factors evaluated	Function examined	Normal range	Elevated result in
Prothrombin time and INR	I (fibrinogen), II (prothrombin), V, VII, or X	Extrinsic pathway, common pathway, vitamin K-dependent factors	15 – 20 seconds (PT), 1.0 (INR)	Vitamin K deficiency, liver disease, DIC, warfarin therapy, coagulation factor deficiency
aPTT	I (fibrinogen), II (prothrombin), V, VIII, IX, X, XI, and XII	Intrinsic pathway, common pathway	25 - 33 seconds	Liver disease, DIC, unfractionated heparin therapy, coagulation factor deficiency, haemophilia
Thrombin time	I (fibrinogen)	Last step of common pathway	17 - 21 seconds	Fibrinogen disorder, thrombin inhibitor therapy
Clotting time	VIII, IX, XI, XII	Intrinsic pathway	5 – 8 minutes	Vitamin K deficiency, haemophilia, unfractionated heparin therapy, fibrinogen disorders
Bleeding time	None	Primary haemostasis (platelet function, vascular response)	2 – 4 minutes	Platelet disorder, von Willebrand disease

Prothrombin time and international normalised ratio (INR)

The prothrombin time (PT) evaluates the function of the extrinsic pathway, common pathway, and the vitamin K-dependent factors. It’s normally 15 – 20 seconds. It’s determined by seeing how long it takes for blood to clot after calcium and thromboplastin (phospholipid and tissue factor) has been added to the blood.

The problem with prothrombin time is that the result varies significantly from lab to lab, depending on equipment and substrates used. As such, the prothrombin time is rarely evaluated alone, but the INR is used instead.

The international normalised ratio (INR) is a standardised form of prothrombin time which is normalised so that the result is similar between different laboratory methods and equipments. The prothrombin time is first measured and then normalised by a specific equation and factor. INR is generally used instead of prothrombin time for the same indications.

Indications:

• Monitor warfarin therapy
• Evaluate liver synthetic function (in case of suspected liver failure)
• Evaluate for disseminated intravascular coagulation
• Evaluate coagulation factor deficiency

Warfarin

Warfarin is a vitamin K antagonist used as an anticoagulant. It was previously widely used, but the direct oral anticoagulants have replaced warfarin for most indications.

When warfarin is used for atrial fibrillation, the warfarin dose should be adjusted so that the INR is between 2.0 and 3.0. When warfarin is used for mechanical heart valves, the INR should rather be between 2.5 and 3.5.

Liver failure

The liver synthesizes both (pro-)coagulant and anti-coagulant factors. When there is liver failure, the INR elevates due to decreased levels of pro-coagulant factors in the blood. The levels of anti-coagulant factors increase as well but not enough to offset it.

Disseminated intravascular coagulation

In DIC, the INR increases due to consumption and therefore decreased levels of coagulation factors.

Coagulation factor deficiency

Several coagulation factors can be congenitally or acquired deficient. The PT and INR are prolonged in case of deficiency of fibrinogen (factor I) and factors II, V, VII, or X.

Activated partial thromboplastin time (aPTT)

The activated partial thromboplastin time (aPTT) evaluates the intrinsic and common pathways of coagulation. It's measured by taking the time it takes for plasma to clot when exposed to a reagent which contains phospholipids, silica, and a thromboplastic material without tissue factor. This material activates contact factor, initiating the intrinsic pathway.

The aPTT varies depending on the specific reagent used and different instruments. There is no normalised form of aPTT (as INR is to PT). As such, the normal range varies from lab to lab and cannot be compared with other labs.

Indications:

• Monitor unfractionated heparin therapy (not low molecular weight heparin)
• Evaluate liver synthetic function (in case of suspected liver failure)
• Evaluate for DIC
• Evaluate for deficiency of coagulation factors I (fibrinogen), II (prothrombin), V, VIII, IX, X, XI, and XII
  • This includes haemophilia A, B, and C, the congenital deficiency of factors VIII, IX, and XI, respectively

Thrombin time

The thrombin time evaluates the function of the common pathway alone, more specifically, the final step where fibrinogen is converted to fibrin. It's determined by adding thrombin to citrated plasma and measuring the time to clotting. It's mostly used to evaluate for fibrinogen disorders.

The thrombin time is prolonged in case of disorders of fibrinogen, unfractionated heparin, low molecular weight heparin, and direct thrombin inhibitors.

Clotting time

The clotting time evaluates the function of the intrinsic pathway. It’s normally 5 – 8 minutes. It’s determined by putting a drop of blood on a prewarmed piece of glass and checking how long it takes for a clot to form.

The clotting time is neither sensitive nor specific nor standardised nor reproducible and is therefore no longer used clinically. Other coagulation tests, like PT, INR, and aPTT are used instead.

Bleeding time

The bleeding time evaluates the function of the vasoconstriction and platelet plug formation. It’s normally 2 – 4 minutes. It’s determined by puncturing the finger and measuring the time it takes for it to stop bleeding.

The bleeding time is neither sensitive nor specific nor standardised nor reproducible and is therefore no longer used clinically. Other coagulation tests are used instead, such as platelet aggregation test.