Activated partial thromboplastin time (APTT)
Description:
The activated partial thromboplastin time (APTT) is a screening test which isolates the 'intrinsic' and 'common' pathways of the in vitro coagulation cascade model. Coagulation factors and cofactors within each pathway operate in concert to generate a fibrin clot end-point, the time taken to form the clot being the APTT.
Patient plasma is first incubated with a contact activator to activate FXII and commence the intrinsic pathway. Although not a significant reaction in vivo with respect to bleeding, the activated FXII (FXIIa) activates FXI independently of thrombin, which proceeds to activate FIX independently of FVIIa/TF. FIXa generates FXa to begin the 'common' pathway which generates thrombin via the prothrombinase complex to form a fibrin clot. The APTT reagent also contains the 'partial' thromboplastin, comprising phospholipid but not tissue factor, which facilitates reactions involving the vitamin K dependent factors of both pathways but excludes FVII. The process of timing to clot formation begins upon the addition of calcium ions to replace those removed by the tri-sodium citrate anticoagulant and thereby facilitate functioning tenase and prothrombinase complexes.
Our routine APTT reagent, used on automated analysers employing photo-optical clot detection, is lupus anticoagulant insensitive. For rare occasions where interfering factors compromise APTT analysis on the automated analysers, we have an alternative reagent used on a semi-manual coagulometer employing a mechanical clot-detection technique.
Patient plasma is first incubated with a contact activator to activate FXII and commence the intrinsic pathway. Although not a significant reaction in vivo with respect to bleeding, the activated FXII (FXIIa) activates FXI independently of thrombin, which proceeds to activate FIX independently of FVIIa/TF. FIXa generates FXa to begin the 'common' pathway which generates thrombin via the prothrombinase complex to form a fibrin clot. The APTT reagent also contains the 'partial' thromboplastin, comprising phospholipid but not tissue factor, which facilitates reactions involving the vitamin K dependent factors of both pathways but excludes FVII. The process of timing to clot formation begins upon the addition of calcium ions to replace those removed by the tri-sodium citrate anticoagulant and thereby facilitate functioning tenase and prothrombinase complexes.
Our routine APTT reagent, used on automated analysers employing photo-optical clot detection, is lupus anticoagulant insensitive. For rare occasions where interfering factors compromise APTT analysis on the automated analysers, we have an alternative reagent used on a semi-manual coagulometer employing a mechanical clot-detection technique.
Clinical details:
An elevated APTT can be due to one or more of the following:
● hereditary or acquired deficiencies of factors II, V, VIII, IX, X, XI, XII, prekallikrein, high molecular weight kininogen, fibrinogen
● some sub-types of von Willebrand disease (due to the associated FVIII deficiency)
● autoantibodies/inhibitors against the above coagulation factors
● vitamin K deficiency
● liver disease
● disseminated intravascular coagulation
● lupus anticoagulant
● anticoagulant therapy with vitamin K antagonists, UFH, LMWH, fondaparinux, direct thrombin inhibitors, direct-FXa inhibitors
An APTT below the reference range can be due to:
● elevated FVIII, FIX or fibrinogen
● activated sample
Unexpectedly elevated APTTs additionally receive a mixing test, which is an APTT performed on a mixture of equal volumes of patient and normal plasma. Most factor deficiencies will return into the reference range as the normal plasma supplies a sufficient level of the missing or reduced factor(s) to restore a normal clotting time. Conversely, most inhibitors will exert their effect on the normal plasma as well as the patient plasma and the APTT remains elevated.
● hereditary or acquired deficiencies of factors II, V, VIII, IX, X, XI, XII, prekallikrein, high molecular weight kininogen, fibrinogen
● some sub-types of von Willebrand disease (due to the associated FVIII deficiency)
● autoantibodies/inhibitors against the above coagulation factors
● vitamin K deficiency
● liver disease
● disseminated intravascular coagulation
● lupus anticoagulant
● anticoagulant therapy with vitamin K antagonists, UFH, LMWH, fondaparinux, direct thrombin inhibitors, direct-FXa inhibitors
An APTT below the reference range can be due to:
● elevated FVIII, FIX or fibrinogen
● activated sample
Unexpectedly elevated APTTs additionally receive a mixing test, which is an APTT performed on a mixture of equal volumes of patient and normal plasma. Most factor deficiencies will return into the reference range as the normal plasma supplies a sufficient level of the missing or reduced factor(s) to restore a normal clotting time. Conversely, most inhibitors will exert their effect on the normal plasma as well as the patient plasma and the APTT remains elevated.
Reference range:
"Ratio: 0.8 -1.2 Seconds: 21.6 - 27.5"
Synonyms or keywords:
APTT, APTTr, PTT
Units:
Standard reporting format is ratios
Reporting of clotting time is also available
Department:
Location:
Sample type and Volume required:
External requests: Citrated platelet poor plasma
800µL x 1 aliquot
Internal requests: please refer to EPR label
800µL x 1 aliquot
Internal requests: please refer to EPR label
Turnaround time:
4 hours
Special sample instructions:
The sample should be analysed within 4 hours of venepuncture. Please ensure sample tubes are filled exactly to the fill-line as underfilling creates a dilution error and leads to inaccurate results.
Contacts:
Diagnostic Haemostasis and Thrombosis Department
St Thomas': 020 7188 2797; Guy's: 020 7188 7188 ext. 53860
St Thomas' Hospital
North Wing - 4th and 5th Floors
Westminster Bridge Road
London SE1 7EH
Laboratory opening times
24/7
Guy's Hospital
Southwark Wing - 4th Floor
Great Maze Pond
London SE1 9RT
Outside core hours, contact Duty Haemostasis Biomedical Scientist
North Wing - 4th and 5th Floors
Westminster Bridge Road
London SE1 7EH
Laboratory opening times
24/7
Guy's Hospital
Southwark Wing - 4th Floor
Great Maze Pond
London SE1 9RT
Outside core hours, contact Duty Haemostasis Biomedical Scientist
Last updated: 03/10/2022