partial thromboplastin time

Partial thromboplastin time

Partial thromboplastin time also known as activated partial thromboplastin time (aPTT), is the time it takes for a patient’s blood to form a clot as measured in seconds after substances (reagents) are added 1). Partial thromboplastin time (PTT) is used to measure the activity of the intrinsic pathway of the clotting cascade. Partial thromboplastin time tests the function of all clotting factors except VII (tissue factor) and XIII (fibrin stabilizing factor). Partial thromboplastin time is commonly used in clinical practice to monitor patient response to unfractionated heparin infusion to target therapeutic anticoagulation, and as part of a “coagulation panel” to help elucidate causes of bleeding or clotting disorders.

When body tissue(s) or blood vessel walls are injured, bleeding occurs and a process called hemostasis begins. Small cell fragments called platelets stick to and then clump (aggregate) at the injury site. At the same time, a process called the coagulation cascade begins and coagulation factors are activated in a step-by-step process. Through the cascading reactions, threads called fibrin form and crosslink into a net that clings to the injury site and stabilizes it. This forms a stable blood clot to seal off injuries to blood vessels, prevents additional blood loss, and gives the damaged areas time to heal.

Each part of this hemostatic process must function properly and be present in sufficient quantity for normal blood clot formation. If the amount of one or more factors is too low, or if the factors cannot do their job properly, then a stable clot may not form and bleeding continues.

With a partial thromboplastin time, your result is compared to a normal reference interval for clotting time. When your partial thromboplastin time takes longer than normal to clot, the partial thromboplastin time is considered “prolonged.”

When a partial thromboplastin time is used to investigate bleeding or clotting episodes or to rule out a bleeding or clotting disease (e.g., preoperative evaluation), it is often ordered along with a prothrombin time (PT). A healthcare practitioner will evaluate the results of both tests to help rule out or determine the cause of bleeding or clotting disorder.

It is now understood that coagulation tests such as the prothrombin time (PT) and partial thromboplastin time are based on what happens artificially in the test setting (in vitro) and thus do not necessarily reflect what actually happens in the body (in vivo). Nevertheless, they can be used to evaluate certain components of the hemostasis system. The partial thromboplastin time and prothrombin time (PT) tests each evaluate coagulation factors that are part of different groups of chemical reaction pathways in the cascade, called the intrinsic, extrinsic, and common pathways.

  • The partial thromboplastin time 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 prothrombin time (PT) test evaluates the coagulation factors VII, X, V, II, and I (fibrinogen).
activated partial thromboplastin time

In addition to a partial thromboplastin time, what other tests might be done?

Examples of other testing that may be done along with a partial thromboplastin time 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 partial thromboplastin time
  • When an initial partial thromboplastin time is prolonged, a second partial thromboplastin time 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 partial thromboplastin time 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 partial thromboplastin time.

What is an lupus anticoagulant-sensitive partial thromboplastin time and how does it differ from regular partial thromboplastin time?

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

Is the partial thromboplastin time always used to monitor heparin therapy?

In a few situations, it is not. Two anticoagulants often used, low molecular weight heparin (LMWH) and danaparoid, may not prolong the partial thromboplastin time and, if indicated, should be monitored using the heparin anti-factor Xa assay.

  • When very high doses of heparin are used, as may occur during open-heart surgery, the partial thromboplastin time 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.
  • Some hospitals now monitor standard (unfractionated) heparin therapy using the chromogenic anti-factor Xa test in lieu of partial thromboplastin time.
  • 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 partial thromboplastin time.
  • For people with lupus anticoagulant and clotting and who are being treated with heparin, the partial thromboplastin time is not reliable; thus the anti-factor Xa test must be used to monitor their heparin therapy.

How can I change my partial thromboplastin time?

The partial thromboplastin time 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 partial thromboplastin time 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.

Partial thromboplastin time test

The partial thromboplastin time is used primarily to investigate unexplained bleeding or clotting. Partial thromboplastin time may be ordered along with a prothrombin time (PT or 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 partial thromboplastin time and prothrombin time (PT) are not diagnostic but usually provide information on whether further tests may be needed.

Screening for bleeding disorders

Patients with a propensity for bleeding should undergo testing to determine the presence of a clotting disorder. For patients with deficiencies or defects of the intrinsic clotting cascade, the partial thromboplastin time will be elevated. Disorders with an elevated partial thromboplastin time include:

  • Hemophilia A (Factor VIII deficiency)
  • Hemophilia B (Factor IX deficiency)
  • Vitamin K deficiency (both PT and partial thromboplastin time are elevated)
  • Von Willebrand’s disease (partial thromboplastin time can be normal depending on the severity of disease)
  • Disseminated intravascular coagulation (DIC) will demonstrate elevations in prothrombin time, partial thromboplastin time and bleeding time with a decrease in platelet count (PC)

In a patient with elevated partial thromboplastin time and no known reason for it, further evaluation and testing is warranted.

Some examples of uses of a partial thromboplastin time include:

  • To identify coagulation factor deficiency; if the partial thromboplastin time 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, partial thromboplastin time 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 partial thromboplastin time called the LA-sensitive partial thromboplastin time 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 partial thromboplastin time. 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 partial thromboplastin time and prothrombin time (PT) are sometimes selectively performed before a scheduled surgery or other invasive procedures to screen for potential bleeding tendencies.

When is partial thromboplastin time ordered?

The partial thromboplastin time may be ordered along with other tests such as a prothrombin time (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 partial thromboplastin time 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 partial thromboplastin time and PT are monitored until you have stabilized.
  • When you have a surgical operation scheduled; you may have a partial thromboplastin time 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.

Normal partial thromboplastin time

  • Partial thromboplastin time reference range (depending on your local laboratory’s reference interval): around 25 to 35 seconds is considered normal.

What does the partial thromboplastin time test result mean?

Partial thromboplastin time results are typically reported in seconds. A partial thromboplastin time result that falls within a laboratory’s reference interval usually indicates normal clotting function. However, even with a normal partial thromboplastin time result, mild to moderate deficiencies of a single coagulation factor may be present. The partial thromboplastin time 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 partial thromboplastin time result. If the lupus anticoagulant (LA) is suspected, a more sensitive lupus anticoagulant-sensitive partial thromboplastin time or a dilute Russell viper venom time (DRVVT) can be used to test for it.

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

A prolonged partial thromboplastin time 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 prothrombin time (PT) and partial thromboplastin time. However, prothrombin time (PT) is more likely to be prolonged than partial thromboplastin time.
    • 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. Prothrombin time (PT) is more likely to be prolonged than is partial thromboplastin time.
  • 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. partial thromboplastin time 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 partial thromboplastin time because it targets substances called phospholipids that are used in the partial thromboplastin time. Though they can prolong the partial thromboplastin time 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. (See the article on Antiphospholipid Antibodies and Antiphospholipid Syndrome for additional details.)
  • 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 partial thromboplastin time, either as a contaminant of the sample or as part of anticoagulation therapy. For anticoagulant therapy, the target partial thromboplastin time is often about 1.5 to 2.5 times longer than a person’s pretreatment level. partial thromboplastin time is still being used to monitor standard heparin therapy.
  • Warfarin (Coumadin) anticoagulation therapy—the partial thromboplastin time is not used to monitor warfarin therapy, but partial thromboplastin time 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 partial thromboplastin time 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 partial thromboplastin time are often interpreted with results of the prothrombin time (PT) in determining what condition may be present.

Table 1. Causes of abnromal partial thromboplastin time and prothrombin time (PT)

Prothrombin time (PT) resultPartial thromboplastin time resultCommon condition present
ProlongedNormalLiver disease, vitamin K deficiency, decreased or defective factor VII, chronic DIC, warfarin or other vitamin K antagonist (e.g., brodifacoum in some cannabinoids)
NormalProlongedHemophilia A or B (decreased or defective factor VIII or IX) or factor XI deficiency, von Willebrand disease (severe form), factor XII deficiency, or lupus anticoagulant present
ProlongedProlongedDecreased or defective factor I (fibrinogen), II (prothrombin), V or X, severe liver disease, acute DIC
NormalNormal or slightly prolongedMay indicate normal hemostasis; however, prothrombin time (PT) and partial thromboplastin time can be normal in conditions such as mild deficiencies in other factors and mild form of von Willebrand disease. Further testing may be required to diagnose these conditions.

A shortened partial thromboplastin time may be due to:

  • Disseminated intravascular coagulation (DIC)—in the early stages of DIC, there are circulating procoagulants that shorten the partial thromboplastin time.
  • 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 partial thromboplastin time. When the condition causing the acute phase reaction is resolved, the partial thromboplastin time returns to normal.

Several factors can affect results of a partial thromboplastin time and the interpretation of test results:

  • People with high hematocrit levels may have falsely prolonged partial thromboplastin times.
  • 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 partial thromboplastin time test may also be used to monitor these therapies. It does not directly measure the anticoagulants used but measures their effect on blood clotting.

Potential diagnosis

Diagnoses associated with an elevated partial thromboplastin time include:

Hemophilia A (Factor VIII deficiency)

Factor VIII deficiency characterizes Hemophilia A, also known as classical hemophilia. This produces an intrinsic coagulation pathway defect and thus elevated partial thromboplastin time on laboratory studies. It is an X-linked recessive bleeding disorder, thus more commonly seen in males. However, about one-third of cases result from spontaneous genetic mutation. Depending on the severity of disease treatment varies. Some patients are treated with desmopressin to stimulate the release of Von Willebrand factor (WVF) from endothelial cells which is protective of factor VIII.

Hemophilia B (Factor IX deficiency)

Hemophilia B is an X-linked recessive bleeding disorder characterized by factor IX deficiency. This produces an intrinsic coagulation pathway defect and thus elevated partial thromboplastin time on laboratory studies. Patients are usually identified by family history or after evaluation for prolonged bleeding time with dental procedures or minor injury. Unlike hemophilia A, desmopressin has no benefit for these patients.

Vitamin K Deficiency

PT and partial thromboplastin time are elevated with severe deficiency.

Deficiency of vitamin K, a fat-soluble vitamin, causes decreased synthesis of factors II, VII, IX, X, and proteins C and S. Newborns are administered an injection or oral supplementation of vitamin K shortly after birth to prevent risk hemorrhagic disease of the newborn (HDN) from this fat-soluble vitamin deficiency. Oral supplementation of vitamin K reverses coagulopathy in 24 hours; intravenous formulation reverses coagulopathy in 6 hours.

Liver Disease

PT and partial thromboplastin time are elevated with severe disease.

In mild liver disease, only the PT will be elevated. With more severe disease both the PT and partial thromboplastin time will be elevated due to a decreased synthesis of vitamin K dependent clotting factors. Correct with fresh frozen plasma (FFP), not vitamin K.

Von Willebrand Disease

Partial thromboplastin time can be normal depending on the severity of the disease.

Von Willebrand disease is an autosomal dominant deficiency in functional VWF. VWF has 2 functions: binding platelets to the endothelium and protecting Factor VIII. There are 3 types of Von Willebrand disease. Type one is most common (85% of patients) In type 1, there is a deficiency of normal functioning VWF. Type 2 is characterized by the decreased amount of VWF that does not function properly. Type 3 is the least common and most severe, these patients have a total or near-total absence of VWF and low levels of factor VIII.

Disseminated Intravascular Coagulation (DIC)

DIC is characterized by elevations in PT, partial thromboplastin time, and bleeding time (BT) with a decrease in platelet count (PC). It is a consumptive coagulopathy with coagulation and clot lysis occurring simultaneously. Patients suffer consumptive thrombocytopenia, hemolytic anemia, local tissue ischemia and hemorrhage.

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