How to Interpret and Pursue an Abnormal Prothrombin Time, Activated Partial Thromboplastin Time, and Bleeding Time in Adults

doi:10.4065/82.7.864

Mayo Clinic Proceedings

Volume 82, Issue 7, July 2007, Pages 864-873

https://doi.org/10.4065/82.7.864 Get rights and content

The prothrombin time (PT) and activated partial thromboplastin time (APTT) are among the most commonly ordered coagulation tests. In 2005, more than 140,000 PT and more than 95,000 APTT tests were performed at Mayo Clinic. The most common indications for ordering these tests include anticoagulant monitoring, initial evaluation of hemorrhage, and, although not generally indicated, routine preoperative screening. In addition, the bleeding time (BT) test, which is infrequently performed, is still available in certain institutions. Abnormal results from these tests (prolonged PT, APTT, and BT), especially from tests conducted for initial evaluation of hemorrhage or for preoperative screening, may pose a diagnostic dilemma to the nonhematologist. We review the essential factors affecting test results; provide a practical approach to the evaluation of a prolonged PT, APTT, and BT; and offer suggestions on which reflexive tests are appropriate and when to consider a subspecialty consultation.

Section snippets

OVERVIEW OF THE HEMOSTATIC SYSTEM

A basic understanding of the hemostatic system, which has been reviewed in detail,¹ is required to interpret screening coagulation test results. When platelets and clotting factors circulate in an inactive form, blood flows freely through the vascular system. However, vascular injury and the resulting disruption of the endothelium lead to the initiation of a complex hemostatic response broadly classified into primary and secondary hemostatic responses. In primary hemostasis, vascular injury

SCREENING TESTS FOR HEMOSTASIS

The PT, APTT, and BT are screening tests for hemostasis. The BT test has lost favor in recent years, but the PT and APTT remain the most frequently ordered tests in coagulation medicine. To properly manage patients, physicians must determine whether the prolonged PT, APTT, and BT are artifactual, medication related, or representative of hemostatic abnormalities.

PRETEST VARIABLES COMMONLY AFFECTING PT AND APTT

A prolonged PT or APTT, regardless of current or previous bleeding symptoms, warrants further investigation, especially when the patient is not receiving anticoagulant therapy or is not known to have liver disease. An unexpectedly prolonged PT or APTT often correctly prompts physicians to consider artifactual causes of abnormal test results. Certain pretest variables can cause artifactual prolongation of the PT or APTT (or both).

STEPS IN INTERPRETING AND PURSUING PROLONGED PT OR APTT RESULTS

The ordering of a PT or APTT by a physician or health care professional presupposes that a detailed history (including detailed documentation of prescription and nonprescription medications) has been obtained and that a thorough physical examination has been performed. Occasionally, when test results are abnormal, additional focused history and examination are warranted, and laboratory test results are frequently obtained before a patient encounter (eg, routine preoperative coagulation

APTT Corrects

If the prolonged APTT corrects to normal when a mixing study is performed, a coagulation factor deficiency is suggested. In the setting of a normal PT, a deficiency is implied in 1 or more factors in the intrinsic pathway (ie, factors VIII, IX, XI, or XII; high-molecular-weight kininogen [HMWK]; or prekallikrein [PK]) (Figure 2). Clotting factor assays should be performed for factors VIII, IX, XI, and XII to identify the deficiency, determine whether it poses a bleeding risk to the patient, and

APPROACH TO A PROLONGED PT

Like a prolonged APTT, a prolonged PT could reflect either a coagulation factor deficiency state or the presence of an inhibitor; thus, correction with a mixing study suggests a deficiency state, whereas inhibition suggests the presence of an inhibitor (Figure 5).

APPROACH TO PROLONGATION OF BOTH PT AND APTT

Prolongation of both the PT and the APTT implies that factor deficiencies are present in the intrinsic and extrinsic pathways, in the final common pathway, or in all 3 pathways, or that inhibitors are present for both the intrinsic and the extrinsic pathways or for the final common pathway.

BLEEDING TIME

Originally introduced as a screening test for bleeding disorders, BT came to be used as a tool for routine preoperative hemostatic assessment, although data demonstrating its utility were lacking. It measures the time it takes for a standardized incision on the volar aspect of a patient's forearm to stop bleeding, thus providing an estimate of the integrity of vascular, platelet, and fibrin clot formation. A prolonged BT can result from multiple factors, including inappropriate performance of

BLEEDING DISORDERS THAT WILL NOT BE DETECTED WITH THE PT AND APTT TESTS

Because PT and APTT tests are commonly ordered in the evaluation of bleeding symptoms, it is important to recognize bleeding disorders that will not be detected by these assays. These disorders include qualitative platelet defects, which require specialized platelet function testing; von Willebrand disease, which requires assays for von Willebrand factor; factor XIII deficiency, which requires specialized factor XIII screening or functional assays; and deficiency of plasminogen activator

REASONS FOR HEMATOLOGIST/COAGULATIONIST CONSULTATION

Primary care physicians can expedite the evaluation of a prolonged clotting time by ordering the Prolonged Clotting Time Profile. When performed by the Mayo Clinic Special Coagulation Laboratory, this profile generally results in a diagnosis. On diagnosis of congenital bleeding disorders, such as hemophilia A or B, or acquired autoimmune bleeding disorders, such as those caused by factor V or VIII inhibitor, a hematologist/coagulationist should be consulted. Such a consultation should also be

CONCLUSION

Various disorders result in prolongation of the PT and APTT. Some of these disorders increase the risk of bleeding and others the risk of thrombosis, but, more importantly, selected disorders are of no hemostatic consequence. Correlation with the patient's clinical and hemostatic history is critical, and laboratory testing should be pursued especially in the absence of an obvious explanation for the prolongation of the PT or APTT. In our experience, optimal use of a laboratory is made by a

Questions About Prolonged PT, APTT, and BT in Adults

1.
A 45-year-old man with a history of cyanotic congenital heart disease has had multiple hemostatically uneventful surgical corrective procedures in the past. Currently, he is being evaluated for coronary angiography. He states that he has no bleeding symptoms, and physical examination shows no bruises or petechiae. He is receiving no anticoagulant medications. Laboratory data are as follows:
Test Result Reference range
Hemoglobin (g/dL) 20.0 12.0–15.5
Hematocrit (%) 60.0 34.9–44.5
PT (s) 18.0

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Test	Result	Reference range
Hemoglobin (g/dL)	20.0	12.0–15.5
Hematocrit (%)	60.0	34.9–44.5
PT (s)	18.0

CONCISE REVIEW FOR CLINICIANSHow to Interpret and Pursue an Abnormal Prothrombin Time, Activated Partial Thromboplastin Time, and Bleeding Time in Adults

Section snippets

OVERVIEW OF THE HEMOSTATIC SYSTEM

SCREENING TESTS FOR HEMOSTASIS

PRETEST VARIABLES COMMONLY AFFECTING PT AND APTT

STEPS IN INTERPRETING AND PURSUING PROLONGED PT OR APTT RESULTS

APTT Corrects

APPROACH TO A PROLONGED PT

APPROACH TO PROLONGATION OF BOTH PT AND APTT

BLEEDING TIME

BLEEDING DISORDERS THAT WILL NOT BE DETECTED WITH THE PT AND APTT TESTS

REASONS FOR HEMATOLOGIST/COAGULATIONIST CONSULTATION

CONCLUSION

Questions About Prolonged PT, APTT, and BT in Adults

Blood

J Thromb Haemost

Mayo Clin Proc

Biochemistry and physiology of blood coagulation

Thromb Haemost

The coagulation cascade: initiation, maintenance, and regulation

Biochemistry

New insights into how blood clots: implications for the use of APTT and PT as coagulation screening tests and in monitoring of anticoagulant therapy

Semin Thromb Hemost

CONCISE REVIEW FOR CLINICIANS
How to Interpret and Pursue an Abnormal Prothrombin Time, Activated Partial Thromboplastin Time, and Bleeding Time in Adults