What is being tested?

The activated partial thromboplastin time (APTT or PTT) is a functional measure of the intrinsic and common pathways of the coagulation cascade. When blood vessel walls or body tissues are injured, bleeding occurs and a process known as haemostasis initiates. Platelets (small cell fragments) stick and clump at the site of the injury. When this happens, the coagulation cascade begins and coagulation factors are activated in a step-by-step process. The body uses the coagulation cascade to produce blood clots to seal off injuries to blood vessels and tissues, to prevent further blood loss, and to give the damaged areas time to heal. The cascade consists of a group of coagulation factors. These proteins are activated sequentially along either the extrinsic (tissue related) or intrinsic (blood vessel related) pathways. The branches of the pathway then come together into the common pathway, and complete their task with the formation of a stable blood clot. When a person starts bleeding, these three pathways have to work together.

Each component of the coagulation cascade must be functioning properly and be present in sufficient quantity for normal blood clot formation. If there is an inherited or acquired deficiency in one or more of the factors, or if the factors are functioning abnormally, then stable clot formation will be inhibited and excessive bleeding and/or clotting may occur.

The aPTT test measures the length of time (in seconds) that it takes for clotting to occur when reagents are added to plasma (liquid portion of the blood) in a test tube.

The aPTT is used to evaluate the following coagulation factors:

• XII
• XI
• IX
• VIII
• X
• V
• II (prothrombin)
• I (fibrinogen)

How is it used?

The aPTT test is used when someone has unexplained bleeding or clotting. Along with the PT test (which evaluates the extrinsic and common pathways of the coagulation cascade), the aPTT is often used as a starting place when investigating the cause of a bleeding or thrombotic (blood clot) episode. It is often used with recurrent miscarriages which may be associated with lupus anticoagulant, anticardiolipin or antiphospholipid antibodies. The aPTT and PT tests are also sometimes used as pre-surgical screens for bleeding tendencies, although numerous studies have shown that they are not always useful for this purpose.

The aPTT is also used to monitor heparin anticoagulant therapy. However it cannot monitor therapy with newer 'low molecular weight heparin' (LMWH) or other anticoagulants such as oral direct thrombin inhibitors (Dabigatran). LMWH effect may be measured using an anti Xa level test. APTT may also be affected by the newer, direct anti-Xa inhibitors, such as Rivaroxaban and Apixaban, but cannot be used to monitor these agents.

If the aPTT is prolonged, and the cause is not due to heparin contamination or to other pre-analytical problems such as an insufficient or clotted blood sample, then the aPTT is followed by mixing studies to decide whether there is deficient Coagulation Factor(s) or an inhibitor to coagulation is present. Mixing is a procedure where the patient's plasma is mixed with pooled normal plasma (a combination of blood from different donors that has normal amounts of all of the clotting factors in it). If the patient has a factor deficiency, mixing it with the pooled normal plasma should provide enough of the missing factor(s) for the aPTT to 'correct' - to clot within the normal time frame. If it does correct, specific coagulation factor testing is done to determine which factor(s) is deficient. If it does not correct, then the prolonged aPTT may be due to a specific or non-specific inhibitor. Further testing may then be done to check for antibodies to specific factors or to identify non-specific inhibitors occurring in antiphospholipid syndrome.

When is it requested?

The aPTT may be requested, along with other tests such as a PT test, when a patient presents with

• Unexplained bleeding or bruising
• Thromboembolism (blood clot)
• An acute condition such as disseminated intravascular coagulation (DIC) that can cause both bleeding and clotting as coagulation factors are activated and used up at a rapid rate.
• A chronic condition such as liver disease, as the liver is the source of most coagulatin factors
• When a woman has had recurrent miscarriages
• As part of an evaluation for antiphospholipid syndrome or lupus anticoagulant

It may be used as part of a pre-surgical evaluation for bleeding tendencies, especially if the surgery carries an increased risk of blood loss and/or if the patient has a clinical history of bleeding - such as nosebleeds and bruising that may indicate the presence of an inherited or acquired factor deficiency or of an acquired inhibitor.

When a patient is on intravenous (IV) or injection heparin therapy, the APTT is ordered at regular intervals to monitor the degree of anticoagulation. When a person is switched from heparin therapy to longer-term warfarin therapy, the two are overlapped and both the APTT and PT are monitored until the patient has stabilised.

What does the result mean?

Normal aPTTs may reflect normal clotting function but moderate single factor deficiencies may still exist. They will not be reflected in the aPTT until they have decreased to 30 to 40% of normal. Also some lupus anticoagulants may be present that will not prolong the usual aPTT result. If a lupus anticoagulant (LA) is suspected, an LA-sensitive aPTT can be used to test for it, or a similar test called the dilute Russell Viper venom test (DRVVT).

A prolonged aPTT usually means that clotting is taking longer to occur than expected (but is associated with increased risk of blood clots if due to a lupus anticoagulant) and may be caused by a variety of factors (see the list below). Often, this suggests that there may be a coagulation factor deficiency or a specific or non-specific inhibitor affecting the body's clotting ability. Coagulation factor deficiencies may be acquired or inherited. Several factors are vitamin K dependent. If a person has liver disease, causing vitamin K deficiency, they may have one or more factor deficiencies. Inherited factor deficiencies may involve the quantity and/or function of the factor produced.

Inhibitors may be antibodies that specifically target certain coagulation factors, such as Factor VIII antibodies, or they may be non-specific inhibitors, such as lupus anticoagulants that bind to chemicals called phospholipids found on the surface of platelets. Since phospholipids assist in the clotting process, and since the aPTT test reagents (chemicals used to run the tests) contain phospholipids, such antibodies may prolong the aPTT even though they are usually associated with thrombosis instead of bleeding.

The administration of heparin will also prolong an aPTT, either as part of anticoagulation therapy or as a contaminant. Heparin is a drug that is given intravenously (IV) or by injection to prevent and to treat thromboembolism (blood clots that block blood vessels). When it is given in therapeutic doses it must be monitored - too much and the patient will bleed excessively, too little and the patient may continue to clot. The aPTT is used to monitor heparin therapy and occasionally to monitor other therapeutic anticoagulants such as hirudin.

A decreased aPTT may result be due to:

• Elevated Factor VIII. This may occur during an acute phase reaction - the blood's reaction to acute tissue inflammation or trauma. This is usually a temporary change that is not monitored with the aPTT. When the condition causing the acute phase reaction is resolved, the aPTT will return to normal levels.
• Advanced cancer (ovarian, pancreatic, colon)
• Disseminated intravascular coagulation (DIC)- in the early stages of DIC, there are ciculating procoagulants that shorten the aPTT

Sometimes a traumatic or difficult blood collection may result in activation of the coagulation pathway in the sample, resulting in a shortened aPTT time. In this case a recollection of the blood sample may be required to obtain an accurate result.

Prolonged APTT tests may be due to:

• Pre-analytical problems. These may include:
  1. Insufficient sample - there must be enough blood collected. The anticoagulant to blood ratio must be 9:1
  2. Patients with high or low haematocrit levels may have an altered APTT
  3. Heparin contamination. This is the most common problem - especially when blood is collected from intravenous lines that are being kept 'open' with heparin flushes
  4. Clotted blood samples - especially if taking the blood sample was difficult or prolonged
• Inherited or acquired factor deficiencies. Some factor deficiencies cause bleeding (eg. Haemophilia A or B), others - contact factors - prolong the aPTT in vitro but do not cause bleeding and have little clinical significance. Prolonged aPTTs due to factor deficiencies usually 'correct' after being mixed with pooled normal plasma.
• A non-specific inhibitor such as the lupus anticoagulant (LA). If the LA does prolong the aPTT, LA sensitive aPTT or dilute Russell Viper venom test (DRVVT) it will not correct with normal plasma mixing but it will usually correct if an excess of phospholipid is added to the sample.
• A specific inhibitor. Although these are relatively rare, these are antibodies that attack a particular factor. They may develop in someone with a bleeding disorder who is receiving factor replacements (such as Factor VIII which is used to treat haemophilia A) or spontaneously as an autoantibody. The specific inhibitor will prolong the aPTT and it will not correct with mixing.
• Heparin anticoagulant therapy (the target aPTT is usually 1.5 to 2.5 times longer than that of a 'normal' control sample (referred to as the 'aPTT ratio').
• Warfarin anticoagulation therapy. The aPTT is relatively insensitive to warfarin and not used to monitor therapy, but it may be affected by it.
• Increased PTT levels may also be seen with von Willebrand's disease, which can lead to reduced levels of Factor VIII.
   aPTT results are often interpreted with results of the PT in determining which condition may be present.
   

Is there anything else I should know?

Once heparin is started, the laboratory work-up of an abnormal aPTT is difficult. Often when a patient presents with unexplained bleeding or clotting, an aPTT will be ordered along with other bleeding and hypercoaguability tests before treatment is begun. If this is not feasible, some investigational testing may have to wait until the current condition has resolved.

Other testing that may be done along with an aPTT includes:

• platelet counts - which should always be monitored during heparin therapy to detect heparin-induced thrombocytopenia (HIT) promptly
• dilute Russell Viper venom test - to investigate for lupus anticoagulants
• reptilase test - an aPTT-like test unaffected by heparin used to confirm this as the cause of an abnormal aPTT
• thrombin time testing - this is sometimes ordered to help rule out heparin contamination
• fibrinogen testing, which may be done to rule out hypofibrinogenaemia as a cause of aPTT prolongation.

As different laboratories use varied reagents for testing of the aPTT, differing aPTT results may be seen across laboratories. As reagents vary in their sensitivities to coagulation factors, if aPTT is used for monitoring purposes, it is preferable to use the same laboratory consistently.

Common questions

• Is the APTT test always used to monitor heparin therapy?

In some situations it is not used.

1. When very high doses of heparin are used, as may occur during open heart surgery, the APTT loses its sensitivity - it will not clot. At this intense level of anticoagulation the activated clotting time (ACT) is used as a monitoring tool instead of APTT.
2. LMWH (low molecular weight heparin), which is a newer form of heparin cannot be monitored by the APTT, but does not usually require monitoring. If it does, an anti Xa level assay can be used.
3. In patients with antiphospholipid antibodies, the APTT is unreliable and anti Xa levels should be monitored.
    Should everyone have their APTT checked?

This is not usually necessary. The APTT is not used as a routine general screening test. It is used when someone has symptoms of abnormal bleeding or clotting. Asymptomatic patients are usually only screened prior to surgery - and then only if their doctor believes it is necessary to evaluate their risk of excessive bleeding during the procedure.

• How can I change my APTT?

The APTT is not something you can change through lifestyle changes (unless perhaps you have a vitamin K induced factor deficiency). It is a reflection of the integrity of your clotting system. If your APTT is prolonged due to acquired factor deficiencies, then addressing the underlying condition may bring the results to near normal levels. If they are prolonged due to a temporary or acute condition they should return to normal on their own within a short time period.

More information

RCPA Manual: APTT