PTT

The PTT test is ordered when someone has unexplained bleeding or clotting. Along with the PT (which evaluates the extrinsic and common pathways of the coagulation cascade), the PTT is often used as a starting place when investigating the cause of a bleeding or thrombotic episode. It may be ordered as part of a panel of sequential tests that is used to look for Lupus anticoagulant to help investigate the cause of recurrent miscarriages, especially when they occur in the second or third trimester. The PTT and PT tests are sometimes used as pre-surgical screens for bleeding tendencies, although numerous studies have shown that they are not generally useful for this purpose.

The PTT is also ordered at intervals to monitor unfractionated (standard) heparin anticoagulant therapy. Heparin is a drug that is given intravenously (IV) or by injection to prevent and to treat thromboemboli. When it is given in therapeutic doses, it must be closely monitored. If given too much, the patient may bleed excessively; too little and the patient may continue to clot. In some cases, heparin can unintentionally decrease a patient’s platelet count in a complication called heparin-induced thrombocytopenia. When this occurs, substitute anticoagulants such as hirudin or argatroban may be given. The PTT test is also used to monitor these therapies. It does not directly measure the anticoagulants used but measures their effect on blood clotting.

If the PTT is prolonged and the cause is not anticoagulant therapy, heparin contamination, or other pre-analytical problems such as an insufficient or clotted blood sample, then the PTT is followed by mixing studies to check for possible coagulation factor deficiencies or inhibitors. 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). If the patient has a factor deficiency, mixing their plasma with pooled normal plasma should provide enough of the missing factor(s) for the PTT to “correct” (clot within the normal time frame). If it does correct, further coagulation factor testing is done to determine those factors that are deficient. If it does not correct, then the prolonged PTT may be due to a specific or nonspecific inhibitor. Further testing may then be done to check for antibodies to specific factors and to identify nonspecific antibodies, such as lupus anticoagulant and anticardiolipin antibodies.

The PTT may be ordered, along with other tests such as a PT, when a patient presents with unexplained bleeding or bruising, a thromboembolism, an acute condition such as disseminated intravascular coagulation (DIC) that may cause both bleeding and clotting as factors are used up at a rapid rate, or with a chronic condition such as liver disease. When the patient has had a thrombotic episode or recurrent miscarriages, the PTT may be ordered as part of an evaluation for lupus anticoagulant or anticardiolipin antibodies.

It may be ordered 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 PTT is ordered at regular intervals to monitor the degree of anticoagulation. When a person is switched from heparin therapy to longer-term warfarin (Coumadin) therapy, the two are overlapped and both the PTT and PT are monitored until the patient has stabilized.

PTT is not useful in monitoring anticoagulant therapy using low-molecular weight heparin.

Normal PTTs may reflect normal clotting function, but moderate single factor deficiencies may still exist. They will not be reflected in the PTT until they have decreased to 30% to 40% of normal. Also lupus anticoagulant may be present but may not prolong the PTT result. If the lupus anticoagulant (LA) is suspected, an LA-sensitive PTT can be used to test for it.

A decreased PTT may result when coagulation factor VIII is elevated. This may occur during an acute phase reaction, a condition causing acute tissue inflammation or trauma. This is usually a temporary change that is not monitored with the PTT. When the condition causing the acute phase reaction is resolved, the PTT will return to normal.

A prolonged PTT means that clotting is taking longer to occur than expected 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 nonspecific 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, for instance, or more rarely a Vitamin K deficiency, he may have one or more factor deficiencies. Inherited factor deficiencies may affect 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 antocoagulant and anticardiolipin antibodies that bind to chemicals called phospholipids found on the surface of platelets. Since phospholipids assist in the clotting process, and since the PTT test reagents (chemicals used to run the tests) contain phospholipids, such antibodies may prolong the PTT even though they are usually associated with thrombosis instead of bleeding.

The administration of heparin will also prolong PTT, either as part of anticoagulation therapy or as a contaminant.

Prolonged PTT tests may be due to:

1. Pre-analytical problems. These may include:
   • Insufficient sample - there must be enough blood collected. The anticoagulant to blood ratio must be 9:1 in the collection tube.
   • Patients with high hematocrit levels may have prolonged PTTs.
   • Heparin contamination. This is the most common problem, especially when blood is collected from intravenous lines that are being kept “open” with heparin washes.
   • Clotted blood samples - the clotting process uses up some of the factors.
2. Inherited or acquired factor deficiencies. Some factor deficiencies cause bleeding while others, called contact factors, prolong the PTT in vitro but do not cause bleeding and have little clinical significance. Prolonged PTTs due to factor deficiencies usually “correct” after being mixed with pooled normal plasma. PTT may be prolonged in von Willebrand’s disease.
3. A nonspecific inhibitor such as the lupus anticoagulant (LA). If the LA does prolong the PTT or LA sensitive PTT, it will not correct with normal plasma mixing, but it will usually correct if an excess of phospholipid is added to the sample.
4. 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 hemophilia A) or spontaneously as an autoantibody. The specific inhibitor will prolong the PTT and it will not correct with mixing.
5. Heparin anticoagulant therapy (the target PTT is often about 1.5 to 2.5 times higher than a patient’s pretreatment level).
6. Warfarin (Coumadin) anticoagulation therapy. The PTT is not used to monitor warfarin therapy, but it may be affected by it.
7. Prolonged PTT levels may also be seen with leukemia.

Once heparin therapy is started, the laboratory work-up of an abnormal PTT is difficult. Often, when a patient presents with unexplained bleeding or clotting, a PTT 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 acute condition has been resolved.

Other testing that may be done along with a PTT includes:

Platelet counts – which should always be monitored during heparin therapy to promptly detect any heparin-induced thrombocytopenia

Thrombin time testing – this is sometimes ordered to help rule out heparin contamination

Fibrinogen testing - this may be done to rule out hypofibrinogenemia as a cause of PTT prolongation.

Patients should avoid high-fatty meals prior to having their blood drawn for a PTT.