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) test to evaluate hemostasis, 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.

Several proteins called coagulation factors are involved in hemostasis and the formation of blood clots. When an injury occurs and bleeding begins, some coagulation factors are activated in a sequence of steps (coagulation cascade) that eventually help to form a clot. (See the "What is being tested?" section for more on this.)

The PTT is used to evaluate the coagulation factors XII, XI, IX, VIII, X, V, II (prothrombin), and I (fibrinogen) as well as prekallikrein (PK) and high molecular weight kininogen (HK). A PT test evaluates the coagulation factors VII, X, V, II, and I (fibrinogen). By evaluating the results of the two tests together, a health 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 to a coagulation factor (a specific inhibitor) is present in the blood.
• To detect nonspecific autoantibodies, 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; 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 tests are sometimes selectively performed as pre-surgical or before other invasive procedures to screen for potential bleeding tendencies.

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 specific factor inhibitor (autoantibody) or nonspecific 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 (See the page on Lupus Anticoagulant Testing for more on this.)
• von Willebrand factor – sometimes ordered to help determine if von Willebrand disease is the cause of a prolonged PTT

The PTT may be ordered along with other tests such as a PT when a person has:

• 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 hemostasis

A PTT may be ordered:

• When someone has had a blood clot or when a woman has had recurrent miscarriages, as part of an evaluation for lupus anticoagulant, anticardiolipin antibodies, and antiphospholipid syndrome
• On a regular basis, when a person is on standard (unfractionated) heparin therapy; when someone 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 person has stabilized.
• Prior to surgery when the surgery carries an increased risk of blood loss and/or when the person has 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, 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. Also 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.

A prolonged PTT means that clotting is taking longer to occur than normal and may be due to a variety of causes. Often, this suggests that there may be a coagulation factor deficiency or a specific or nonspecific antibody (inhibitor) affecting the body's clotting ability. Coagulation factor deficiencies may be acquired or inherited.

  Prolonged PTT tests may be due to:

• Inherited factor deficiencies:
  • von Willebrand disease is the most common inherited bleeding disorder and it affects platelet function due to decreased von Willebrand factor.
  • 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
• Acquired factor deficiencies:
  • An example of an acquired deficiency is one due to lack of vitamin K. Vitamin K is essential for the formation of coagulation factors. Vitamin K deficiencies are rare but can occur due to an extremely poor diet, malabsorption disorders, or prolonged use of certain antibiotics, for example.
  • Most coagulation factors are produced by the liver, thus liver disease may cause prolonged PT and PTT. With liver disease and vitamin K deficiency, PT is more likely to be prolonged than is PTT.
• A nonspecific inhibitor such as the lupus anticoagulant—the presence of these inhibitors is usually associated with inappropriate clotting (thrombosis), but can prolong the PTT. See the individual test articles for more on this.
• A specific inhibitor—although relatively rare, these are antibodies that specifically target certain coagulation factors, such as antibodies that target factor VIII. 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. 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.
• Warfarin (Coumadin^®) anticoagulation therapy—the PTT is not used to monitor warfarin therapy, but it may be affected by it. Typically, the PT 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)
• Prolonged PTT levels may also be seen with leukemia, excessive bleeding in pregnant women prior to or after giving birth, or recurrent miscarriages.

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

Shortened PTT tests may be due to:

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

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 prolonged PTTs (in vitro artifact).
• Heparin contamination – this is the most common problem, especially when blood is collected from intravenous lines that are being kept "open" with heparin washes.
• 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 is also used to monitor these therapies. It does not directly measure the anticoagulants used but measures their effect on blood clotting.

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 doctors and laboratories now monitor standard (unfractionated) heparin therapy using the chromogenic anti-factor Xa test.
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.
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 assay must be used to monitor their heparin therapy.