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Prolonged Clotting Time Evaluation

Educational Podcast From ARUP Laboratories

LabMind: An Interview With Dr. Karen Moser: Solving Coagulation Mysteries One Patient at a Time

Medical Experts

Contributors critically edit at least some content for accuracy and integrity, and approve any content they edit for publication.
Authors frame content, identify key sources of information, draft and/or critically edit and revise content to ensure medical accuracy and integrity, and review and approve content for publication.

Contributor

Moser

Karen A. Moser, MD

Associate Professor of Pathology (Clinical), University of Utah

Medical Director, Hemostasis/Thrombosis, ARUP Laboratories

Contributor

Rodgers III

George M. Rodgers III, MD, PhD

Professor of Internal Medicine and Adjunct Professor of Pathology (Clinical), University of Utah

Medical Director, Hemostasis/Thrombosis, ARUP Laboratories

Contributor

Smock

Kristi J. Smock, MD

Professor of Pathology (Clinical), University of Utah

Chief Medical Director, ARUP Institute for Clinical and Experimental Pathology

Medical Director, Hemostasis/Thrombosis, ARUP Laboratories

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.¹

Kamal AH, Tefferi A, Pruthi RK. How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults. Mayo Clin Proc. 2007;82(7):864-873.

Symptoms associated with prolonged clotting times depend on the underlying etiology.^{2

Kruse-Jarres R, Singleton TC, Leissinger CA. Identification and basic management of bleeding disorders in adults. J Am Board Fam Med. 2014;27(4):549-564.} Prolonged clotting times of unclear etiology require further evaluation to determine the cause and exclude clinically significant bleeding disorders.^{2

Kruse-Jarres R, Singleton TC, Leissinger CA. Identification and basic management of bleeding disorders in adults. J Am Board Fam Med. 2014;27(4):549-564.} 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^{3

Hayward CPM. How I investigate for bleeding disorders. Int J Lab Hematol. 2018;40 Suppl 1:6-14.} 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.

Quick Answers for Clinicians

Which laboratory tests should be used for the workup of prolonged clotting times?

Appropriate testing depends on the clinical presentation (bleeding, thrombosis, or asymptomatic presentation), underlying medical conditions and medications, and which clotting times are prolonged (eg, prothrombin time [PT], activated partial thromboplastin time [aPTT]).²

Kruse-Jarres R, Singleton TC, Leissinger CA. Identification and basic management of bleeding disorders in adults. J Am Board Fam Med. 2014;27(4):549-564.

Additional testing might include lupus anticoagulant evaluation, fibrinogen, d-dimer, factor assays, Bethesda assays, or von Willebrand factor testing, depending on the clinical scenario.

What factors can affect coagulation test results?

Anticoagulant medications frequently interfere with coagulation testing.²

Kruse-Jarres R, Singleton TC, Leissinger CA. Identification and basic management of bleeding disorders in adults. J Am Board Fam Med. 2014;27(4):549-564.

Refer to Impacts of Common Anticoagulants on Coagulation Testing for more information. Therapies using blood products and coagulation factor replacement can also affect 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.²

Kruse-Jarres R, Singleton TC, Leissinger CA. Identification and basic management of bleeding disorders in adults. J Am Board Fam Med. 2014;27(4):549-564.

Laboratory Testing

Initial Testing

Obtaining a CBC with platelet count may be useful (eg, to help identify or exclude quantitative platelet abnormalities).¹

Kamal AH, Tefferi A, Pruthi RK. How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults. Mayo Clin Proc. 2007;82(7):864-873.

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.¹

Kamal AH, Tefferi A, Pruthi RK. How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults. Mayo Clin Proc. 2007;82(7):864-873.

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.¹

Kamal AH, Tefferi A, Pruthi RK. How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults. Mayo Clin Proc. 2007;82(7):864-873.

PT, aPTT, and Platelet Count Results and Associated Causes
PT	aPTT	Platelet Count	Potential Cause
↑	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.¹

Kamal AH, Tefferi A, Pruthi RK. How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults. Mayo Clin Proc. 2007;82(7):864-873.

Refer to Impacts of Common Anticoagulants on Coagulation Testing for possible interferences with different coagulation tests based on the specific drug administered.