Partial Thromboplastin Time (PTT, aPTT)

The PTT is used primarily to investigate unexplained bleeding or clotting. It may be ordered along with a prothrombin time (PT/INR) to evaluate the process that the body uses to form blood clots to help stop bleeding. These tests are usually the starting points for investigating excessive bleeding or clotting disorders.

By evaluating the results of the two tests together, a healthcare practitioner can gain clues as to what bleeding or clotting disorder may be present. The PTT and PT are not diagnostic but usually provide information on whether further tests may be needed.

Some examples of uses of a PTT include:

• To identify coagulation factor deficiency; if the PTT is prolonged, further studies can then be performed to identify what coagulation factors may be deficient or dysfunctional, or to determine if an antibody against a coagulation factor (known as a factor-specific inhibitor) is present in the blood.
• To detect nonspecific autoantibodies (antiphospholipid antibodies), such as lupus anticoagulant; these are associated with clotting episodes and with recurrent miscarriages. For this reason, PTT testing may be performed as part of a clotting disorder panel to help investigate recurrent miscarriages or diagnose antiphospholipid syndrome (APS). A variation of the PTT called the LA-sensitive PTT may be used for this purpose.
• To monitor standard (unfractionated, UF) heparin anticoagulant therapy; however, some labs now use the anti-Xa test to monitor heparin therapy. Heparin is an anticoagulation drug that is given intravenously (IV) or by injection to prevent and to treat blood clots (embolism and thromboembolism). It prolongs PTT. When heparin is administered for therapeutic purposes, it must be closely monitored. If too much is given, the treated person may bleed excessively; with too little, the treated person may continue to clot.
• Based on carefully obtained patient histories, the PTT and PT are sometimes selectively performed before a scheduled surgery or other invasive procedures to screen for potential bleeding tendencies.

The PTT may be ordered along with other tests such as a PT when you have:

• Unexplained bleeding or easy bruising
• A blood clot in a vein or artery
• An acute condition such as disseminated intravascular coagulation (DIC) that may cause both bleeding and clotting as coagulation factors are used up at a rapid rate
• A chronic condition such as liver disease that may affect clotting

A PTT may be ordered:

• As part of an evaluation for lupus anticoagulant, anticardiolipin antibodies, and antiphospholipid syndrome, when you’ve had a blood clot or when a woman has had recurrent miscarriages
• When you are switched from heparin therapy to longer-term warfarin (Coumadin®) therapy, the two are overlapped and both the PTT and PT are monitored until you have stabilized.
• When you have a surgical operation scheduled; you may have a PTT prior to surgery when the surgery carries an increased risk of blood loss and/or when you have a clinical history of bleeding, such as frequent or excessive nose bleeds and easy bruising, which may indicate the presence of a bleeding disorder.

PTT results are typically reported in seconds.

A PTT result that falls within a laboratory’s reference interval usually indicates normal clotting function. However, even with a normal PTT result, mild to moderate deficiencies of a single coagulation factor may be present. The PTT may not be prolonged until the factor levels have decreased to 30% to 40% of normal. On the other hand, lupus anticoagulant may be present but may not prolong the PTT result. If the lupus anticoagulant (LA) is suspected, a more sensitive LA-sensitive PTT or a dilute Russell viper venom time (DRVVT) can be used to test for it. (See below for more about LA-sensitive PTT.)

A prolonged PTT means that clotting is taking longer to occur than normal and may be due to a variety of causes.

A prolonged PTT may be due to:

• Underlying conditions that cause low levels of clotting factors, such as:
  • Liver disease—most coagulation factors are produced by the liver, thus liver disease may cause prolonged PT and PTT. However, PT is more likely to be prolonged than PTT.
  • Vitamin K deficiency—vitamin K is essential for the formation of several clotting factors. Vitamin K deficiencies are rare but can be caused by an extremely poor diet, malabsorption disorders, or prolonged use of certain antibiotics, for example. PT is more likely to be prolonged than is PTT.

• Less common inherited clotting factor deficiencies:
  • von Willebrand disease (vWD) is the most common inherited bleeding disorder and it affects platelet function due to decreased von Willebrand factor. PTT is normal in most cases of vWD but can be prolonged in severe vWD.
  • Hemophilia A and hemophilia B (Christmas disease) are two other inherited bleeding disorders resulting from a decrease in factors VIII and IX, respectively.
  • Deficiencies of other coagulation factors, like factors XII and XI. Deficiency in XI can cause abnormal bleeding, but deficiency of XII is not associated with bleeding risk in the body.
• A nonspecific inhibitor such as the lupus anticoagulant— this is an autoantibody (antiphospholipid antibody) that interferes with the PTT because it targets substances called phospholipids that are used in the PTT. Though they can prolong the PTT result, in the body they are associated with excessive clotting. A person who produces these antibodies may be at an increased risk for a blood clot.
• A specific inhibitor—although relatively rare, these are antibodies that specifically target certain coagulation factors (known as factor-specific inhibitor), affecting how they function. An example is an antibody that targets factor VIII. Factor-specific inhibitors can cause severe bleeding.
• Heparin—is an anticoagulant and will prolong a PTT, either as a contaminant of the sample or as part of anticoagulation therapy. For anticoagulant therapy, the target PTT is often about 1.5 to 2.5 times longer than a person’s pretreatment level. PTT is still being used to monitor standard heparin therapy.
• Warfarin (Coumadin^®) anticoagulation therapy—the PTT is not used to monitor warfarin therapy, but PTT may be prolonged by warfarin at high dose. Typically, the prothrombin time/international normalized ratio (PT/INR) is used to monitor warfarin therapy.
• Other anticoagulants—anticoagulation therapy with direct thrombin inhibitor (e.g., argatroban, dabigatran) or direct factor Xa inhibitor (e.g., rivaroxaban, apixaban)
• Prolonged PTT levels may also be seen with certain types of leukemia, excessive bleeding in pregnant women prior to or after giving birth, or recurrent miscarriages.

Results of the PTT are often interpreted with results of the PT in determining what condition may be present.

A shortened PTT may be due to:

• Disseminated intravascular coagulation (DIC)—in the early stages of DIC, there are circulating procoagulants that shorten the PTT.
• Advanced cancer (ovarian, pancreatic, colon), except when the liver is involved
• An acute-phase reaction: this is a condition causing extensive tissue inflammation or trauma that significantly elevates factor VIII levels. It is usually a temporary change that is not monitored with a PTT. When the condition causing the acute phase reaction is resolved, the PTT returns to normal.

The LA-sensitive PTT (LA-PTT or PTT-LA) is a variant PTT, designed to evaluate the presence of lupus anticoagulant (LA), an antibody associated with clotting episodes and recurrent miscarriages. The LA-PTT uses a low phospholipid reagent that is optimized for detecting lupus anticoagulants and is therefore more sensitive to LA. The test is based on the principle that lupus anticoagulant binds to the phospholipids that are used as one of the reagents in the PTT test, causing an abnormally prolonged clotting time.

Examples of other testing that may be done along with a PTT or in follow up to abnormal results include:

• Platelet count – should always be monitored during heparin therapy to promptly detect any heparin-induced thrombocytopenia
• Thrombin time testing – sometimes ordered to help rule out heparin contamination
• Fibrinogen testing – may be done to rule out a low level of fibrinogen as a cause of a prolonged PTT
• When an initial PTT is prolonged, a second PTT test is performed by mixing the person’s plasma with pooled normal plasma (a collection of plasma from a number of normal donors). If the PTT time returns to normal (“corrects”), it suggests a deficiency of one or more of the coagulation factors in the person’s plasma. If the time remains prolonged, then the problem may be due to the presence of an abnormal factor-specific factor inhibitor (autoantibody) or nonspecific inhibitor, such as lupus anticoagulant.
• Coagulation factor tests – these measure the activity (function) of coagulation factors. They can detect reduced levels of the protein or proteins that don’t work properly (have reduced function). Rarely, the antigen level (quantity) of a coagulation factor may also be measured.
• Dilute Russell viper venom test (DRVVT) – a test that may be done if the presence of lupus anticoagulant is suspected.
• von Willebrand factor – sometimes ordered to help determine if von Willebrand disease (severe form) is the cause of a prolonged PTT.

In a few situations, it is not.

1. When very high doses of heparin are used, as may occur during open-heart surgery, the PTT loses its sensitivity; it will not clot. At this intense level of anticoagulation, the activated clotting time (ACT) can be used as a monitoring tool.
2. Some hospitals now monitor standard (unfractionated) heparin therapy using the chromogenic anti-factor Xa test in lieu of PTT.
3. Low molecular weight heparin (LMWH) is a fast-acting form of heparin often used in the treatment of conditions such as deep vein thrombosis (DVT) prevention. Though generally not requiring monitoring, it must be monitored using the anti-factor Xa test because LMWH typically does not prolong PTT.
4. For people with lupus anticoagulant and clotting and who are being treated with heparin, the PTT is not reliable; thus the anti-factor Xa test must be used to monitor their heparin therapy.

The PTT is not something you can change through lifestyle changes (unless you have a vitamin K deficiency). It is a reflection of the integrity of your clotting system. If your PTT 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 when the acute condition is resolved. Inherited coagulation abnormalities or deficiencies should be closely monitored and may be treated with frequent replacement infusions of the missing clotting factor.

Two anticoagulants often used, low molecular weight heparin (LMWH) and danaparoid, may not prolong the PTT and, if indicated, should be monitored using the heparin anti-factor Xa assay.

Several factors can affect results of a PTT and the interpretation of test results:

• People with high hematocrit levels may have falsely 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 flushes.
• Drugs such as antihistamines, vitamin C (ascorbic acid), aspirin, and chlorpromazine
• In some cases, heparin can unintentionally decrease a person’s platelet count in a complication called heparin-induced thrombocytopenia. When this occurs, substitute anticoagulants such as a direct thrombin inhibitor (e.g., argatroban or bivalirudin) may be given. The PTT test may also be used to monitor these therapies. It does not directly measure the anticoagulants used but measures their effect on blood clotting.