Clotting time tests such as prothrombin time [PT] and/or activated partial thromboplastin time [aPTT] are commonly performed in an outpatient or hospital setting to evaluate the hemostatic system for a variety of reasons. Symptoms associated with prolonged clotting times depend on the underlying etiology. Prolonged clotting times of unclear etiology require further evaluation to determine the cause and exclude clinically significant bleeding disorders. Using panel tests with reflex testing to investigate unexpected prolonged clotting times can reduce the number of times blood will need to be drawn to establish a diagnosis and can lead to more rapid diagnosis. It is important to note that anticoagulant medications may affect testing, as can a recent blood transfusion or factor replacement therapy, and appropriate specimen handling is critical to ensure the accuracy of results.
Indications for Testing
Individuals who have been noted to have a prolonged clotting time [based on results of tests such as PT and/or aPTT] should undergo further evaluation if the cause of the prolonged clotting time is uncertain.
Laboratory Testing
Initial Testing
Obtaining a CBC with platelet count may be useful [eg, to help identify or exclude quantitative platelet abnormalities]. The following tests, which are available as components of a reflex panel in some laboratories, are appropriate for patients with prolonged PT and/or aPTT but no strong clinical or laboratory evidence of a specific hemostasis disorder:
- PT, aPTT
- Dilute Russell viper venom time [DRVVT]
- Lupus anticoagulant reflexive testing
- Fibrinogen
- D-dimer
Observed patterns in the initial test results determine which additional or reflexive testing should be performed; these tests may include coagulation factor assays, Bethesda assays, and/or von Willebrand factor testing.
Condition-Specific Testing
Condition-specific testing is preferred in cases of a known coagulation disorder or strong clinical suspicion for a particular disorder. In patients with a bleeding presentation, consider testing for factor deficiencies, such as hemophilia A or B or rare factor deficiencies. The patterns of the PT and aPTT results should guide test selection. As shown in the table below, normal PT and aPTT results are seen in some bleeding disorders.
In patients with a thrombotic presentation, consider lupus anticoagulant testing.
In patients with an asymptomatic presentation, consider lupus anticoagulant testing, testing for factor deficiencies not associated with a bleeding presentation [eg, factor XII, prekallikrein, and high-molecular-weight kininogen [HMWK] deficiencies], and testing for mild factor deficiencies.
PT, aPTT, and Platelet Count Results and Associated Causes↑ | N | N | FVII deficiency or inhibitor; in some cases, warfarin, vitamin K deficiency, liver disease, DIC, or oral direct Xa inhibitors |
N | ↑ | N | Deficiency or inhibitor of intrinsic pathway, eg, FVIII, FIX, FXI [associated with clinical bleeding], or FXII, prekallikrein, HMWK [not associated with clinical bleeding]; VWD types with low FVIII activity; heparin; in some cases, oral direct thrombin inhibitor, or lupus anticoagulant in patients with asymptomatic or thrombotic presentation |
↑ | ↑ | N | Warfarin, vitamin K deficiency; liver disease; DIC; high heparin concentration; direct thrombin inhibitor; direct Xa inhibitor; common pathway deficiency versus inhibitor [FII, FV, FX, fibrinogen]; rare lupus anticoagulants with hypoprothrombinemia; multiple factor deficiencies |
↑ | ↑ | ↓ | DIC; severe liver disease; rare cases of heparin-induced thrombocytopenia |
N | N | ↓ | Thrombocytopenia [decreased production, increased destruction, or splenic sequestration of platelets] |
N | N | N | Vascular abnormalities; VWD; qualitative platelet disorder; mild factor deficiency; dysfibrinogenemia; FXIII deficiency; fibrinolytic disorders; in some cases, direct oral anticoagulants |
DIC, disseminated intravascular coagulation; F, factor [eg, factor VII, or FVII]; N, normal; VWD, von Willebrand disease |
Test Interference
Coagulation tests may be inaccurate in the presence of anticoagulant drugs or other interfering substances. Refer to Impacts of Common Anticoagulants on Coagulation Testing for possible interferences with different coagulation tests based on the specific drug administered.