ACTIVATED PARTIAL THROMBOPLASTIN TIME (APTT) - plasma
Also known as partial thromboplastin time with kaolin, PTTK, this tests the intrinsic and common pathways. 4.5 ml blood is added to 0.5 ml citrate. The sample must not be collected into heparinised syringes or tubes, or from heparinised lines.
Method: Recalcification of platelet-poor plasma at 37°C in the presence of an activator and platelet substitute. Measure time to clot.
Reference interval: Commonly 25-35 seconds, but varies with reagents and method. The therapeutic interval for continuous infusion heparin is generally 1.5-2.5 x the baseline or control APTT, but also varies with the reagents used and should be checked with the laboratory.
Application: Inappropriate as a routine preoperative screening test, due to its limited sensitivity and specificity. Used as an initial test when the personal and/or family history suggests a coagulation factor deficiency or when the history suggests a coagulation factor inhibitor or a lupus inhibitor. A baseline APTT prior to heparin therapy may detect a lupus inhibitor. The APTT is used to monitor full-dose continuous infusion IV heparin therapy but should not be used to monitor “prophylactic” subcutaneous heparin or low molecular weight heparin.
Interpretation: A normal APTT does not exclude mild, but clinically significant, coagulation factor deficiency (e.g. as in mild haemophilia, von Willebrand's disease) as many reagents give a prolonged APTT only at coagulation factor levels of 30%. An isolated prolongation of the APTT (PT normal) suggests deficiency of factor VIII, IX, XI or XII. Prolongation of both the APTT and PT suggests factor X, V, II or I (fibrinogen) deficiency, all of which are rare. The APTT is normal in factor VII deficiency (PT prolonged) and factor XIII deficiency. A prolonged APTT which is not corrected by the in vitro addition of normal plasma suggests a coagulation factor (VIII or IX) inhibitor or a lupus inhibitor. Artefactual prolongation of the APTT may be due to the presence of heparin in the sample, difficult or slow collection, addition of an incorrect volume of blood to the tube, delay in mixing blood with the citrate anticoagulant, suboptimal specimen storage or a prolonged interval between collection and testing.
PROTHROMBIN TIME (PT) - plasma
This tests the extrinsic and common pathways. 4.5 ml blood is added to 0.5 ml citrate.
Method: Recalcification of platelet-poor plasma at 37°C in the presence of a reagent with “tissue factor” activity. Measure time to clot.
Reference interval: Reagent dependent; prothrombin time generally 11-15 seconds.
Application: More sensitive than the APTT for the detection of coagulation factor deficiencies due to vitamin K deficiency, liver disease. Screen for deficiency of factor VII and, with APTT, factors X, V, II, I. The results are expressed as an international normalised ratio (INR) when the test is used to monitor oral anticoagulant therapy. The INR is not, however, valid for other patients, especially those with liver disease.
Interpretation: An abnormal result is most often due to liver disease, vitamin K deficiency or oral anticoagulant therapy.
INTERNATIONAL NORMALISED RATIO (INR) - plasma
4.5 ml blood is added to 0.5 ml citrate.
Method: The result for the prothrombin time is expressed as a ratio (clotting time for patient plasma divided by time for control plasma); a correction factor (International Sensitivity Index) is applied to the prothrombin ratio (as the sensitivity of commercial thromboplastin reagents is variable) and the result issued as an INR.
Therapeutic interval: Therapeutic interval for oral anticoagulant therapy: 2.0-4.5.
British Society for Haematology recommended therapeutic intervals
Prophylaxis of deep venous thrombosis (DVT), including high risk surgery: 2.0-2.5. Prophylaxis of DVT for hip surgery, surgery for femoral fracture; treatment of DVT, pulmonary embolism, transient ischaemic attacks: 2.0-3.0. Recurrent DVT and pulmonary embolism; arterial disease including myocardial infarction, arterial grafts, cardiac prosthetic valves and grafts: 3.0-4.5.
The European literature recommends an INR of 2.5-4.8, with a level of 3.6-4.8 for mechanical valves.
Application: Monitoring oral anticoagulant therapy. The INR should not be used for patients with liver disease; results in this situation should be expressed as a prothrombin time.
Interpretation: The therapeutic intervals represent the levels at which therapy should be effective without an excessive risk of bleeding. Although expression of the results as an INR “corrects” for reagent variability, this is not entirely satisfactory and some of the differences in the literature may relate to reagent sensitivity. The recommendation that an INR of 2.5-3.5 is sufficient for mechanical valves may also relate to the reduced thrombogenicity of modern valves.
THROMBIN TIME - plasma
4.5 ml blood is added to 0.5 ml citrate.
Method: Thrombin is added to platelet-poor plasma at 37°C; the clotting time is recorded.
Reference interval: Typically 14-16 seconds.
Application: Investigation of possible acquired or inherited disorders of haemostasis; occasionally indicated in the investigation of unexplained thrombosis.
Interpretation: Prolonged in afibrinogenaemia, hypofibrinogenaemia, dysfibrinogenaemia. Prolonged by heparin (corrects with protamine), fibrin degradation products, paraproteins (partial correction with protamine)
Activated clotting time
This may be performed as a ‘bedside’ test. Whole blood is incubated at 37oC with celite. It is used to quantify the heparin effect, for example during cardiac surgery. The normal range is 100-140 seconds. It is prolonged by thrombocytopenia, warfarin and aprotonin.
Prolongation of both INR and APTT
There is a common pathway and feedback amplification of the coagulation mechanism, and thus isolated deficiencies of factors II, V and X and multiple deficiencies such as disseminated intravascular coagulation will prolong both APTT and INR. Warfarin therapy will also prolong both APTT and INR. Heparin does not prolong the INR, since heparinase is included within the INR reagent.
A tourniquet is inflated to 40 mmHg and three nicks are made in the volar aspect of the forearm. Blood blotted from beyond the edge of each wound should clot within 2.5-9.5 minutes. This is a simple test of platelet function. It is abnormal in von Willebrand's disease and may be prolonged by aspirin therapy.
Desmopressin is a synthetic analogue of vasopressin (without the vasoconstrictive properties). DDAVP increases factor VIII and von Willebrand’s factor and facilitates haemostasis by increasing platelet quality and adhesiveness. The therapeutic dose is 0.3 µg/kg IV or SC before and shortly after surgery.
Click here to view our new resource on thromboelastography monitoring.