Thrombosis Knowledge Centre
Pharmacological Options
Monitoring
Activated partial thromboplastin time (aPTT)
Definition
The aPTT (activated partial thromboplastin time) is a chronometric test measuring how long it takes for plasma to clot after activation of the intrinsic pathway of coagulation. The aPTT is measured on citrated plasma: citrate blocks coagulation by binding calcium.
In order to activate the intrinsic pathway, phospholipid, an activator (such as silica, celite, kaolin, ellagic acid) and calcium (to revert the anticoagulant effect of the citrate) are mixed into the plasma sample. The time to clot formation is the measured. The normal range is 30 to 40 seconds depending on the reagent. The result is compared to that obtained with a control normal plasma.
Clinical use of aPTT
- Unexplained bleeding disorder: the aPTT evaluates the whole coagulation cascade except factor VII
- Pre-surgical screens for bleeding tendencies
- Clinical monitoring of some anticoagulant drugs, notably UFH. LMWH are not monitored using aPTT since this test is not sensitive to the presence of LMWH in plasma. Likewise, it is not used for monitoring VKA. At therapeutic doses, fondaparinux does not substantially affect aPTT.
Monitoring of UFH with aPTT
- The anticoagulant effect of UFH is monitored using the aPTT
- Low levels of UFH, such as those obtained with prophylactic doses, do not substantially affect the aPTT
- Full-dose therapeutic levels of UFH prolong the aPTT
- Due to differences between aPTT reagents and coagulometers, the effect of UFH on aPTT may vary substantially from one laboratory to another
- In patients with VTE or coronary syndromes, the dose of UFH is usually adjusted to prolong the aPTT to a clotting time equivalent to that obtain with a plasma UFH level of 0.35 to 0.7 anti-Xa U/mL
- For many aPTT reagents, this is equivalent to a ‘patient/control aPTT’ ratio of 1.5 to 2.5
- However, the use of a standard therapeutic aPTT range of 1.5 to 2.5 for all reagents and methods of clot detection was shown to result in the administration of subtherapeutic doses of UFH
- Ideally, the therapeutic aPTT range should be calibrated specifically for each aPTT reagent batch/coagulometer
- Various UFH dose-adjustment nomograms have been developed
- The relationship between aPTT prolongation and UFH efficacy or safety is uncertain.
Prothrombin Time (PT) and International Normalised Ratio (INR)
Definition of PT
The Prothrombin Time (PT or Quick time) is a chronometric test measuring how long it takes for plasma to clot after
activation of the extrinsic pathway of coagulation. The PT is measured on citrated plasma: citrate blocks coagulation by binding calcium. In order to activate the extrinsic pathway, tissue factor (thromboplastin) and calcium (to revert the anticoagulant effect of the citrate) are added to the plasma. The time to clot formation is then measured. The normal range is 11 to 13 s depending on the reagent. The result is compared with that obtained with a control normal plasma.
Definition of INR
PT is sensitive to reduction of three of the four vitamin K-dependent coagulation factors that are reduced by VKA (i.e. II, VII, and X). Since the sensitivity of PT reagents to the reduction of vitamin K-dependent coagulation factors is variable, monitoring of VKA treatment with PT is not appropriate.
The INR (or International Normalised Ratio) was designed to standardise the laboratory monitoring of VKA therapy. The INR is determined taking into account the sensitivity of the thromboplastin reagent (i.e. international sensitivity index or ISI) used for measuring PT and is calculated as follows:
- INR = (patient PT/mean normal PT)ISI
- Its value is 1.0 in healthy subjects without VKA
The optimal therapeutic target range for warfarin is not the same for all indications. However, a moderate-intensity INR (2.0 to 3.0) is recommended for most indications.
VKA monitoring in practice
High-quality dose management is essential to achieve and maintain therapeutic efficacy and safety. Structured educational training of the patient is also required. The management of VKA-treated patients is improved if performed in anticoagulation clinics.
Portable instruments measuring INR from a fingerstick sample of capillary whole blood or from non-anticoagulated venous whole blood by the patient at home is a new option that, if validated, may be valuable in properly selected and trained patients.