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Pre-Surgical Screening

Prof. Jeanne Isabel, Medical Laboratory Science Program Director, Northern Illinois University, forwarded the following question, posted to the American Society for Clinical Laboratory Science Consumer Forum:

“We run prothrombin time assays with international normalized ratios (PT/INRs) on most all patients pre-procedure regardless of whether they take Coumadin or heparin. I have done some research and this is the general practice but I am wondering if there is a better test. Most of our patients are on Aspirin and/or Plavix or Lovenox rather than Coumadin or heparin. Does the PT/INR reflect the use of these medications or is there a study that would better indicate a risk for bleeding? We do activated clotting times (ACTs) in procedures with the use of heparin. Does that also reflect the anticoagulation affect of Aspirin and Plavix?”

George responded that surgeons and physicians routinely order the PT/INR and the partial thromboplastin time (PTT) in an attempt to reduce the risk of intra-procedural bleeding by identifying potential coagulation disorders in advance. While the PT/INR and PTT are excellent tests for identifying coagulation deficiencies in patients with bleeding symptoms and for monitoring anticoagulant therapy, they are not useful for testing a general, unselected population, as their positive predictive value for intra-operative or post-operative bleeding is only 50%. For a good review, see Segal JB, Dzik WH. Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review. Transfusion 2005;45:1413–25. Segal reviews studies conducted in the 80s and 90s and concludes that a careful history is more likely to identify bleeding risks than the PT/INR and PTT screen. Most of these studies also conclude that screening may be harmful in the sense that in the general population, false positive results outweigh true positives, thus leading to unnecessary delay, additional expense of follow-up tests and rescheduling, and anxiety for the patient.

However, lab scientists can’t convince surgeons and physicians to discontinue the practice of screening, so it is important that we know what our tests can accomplish. The PT/INR and PTT, when one or both are prolonged in the absence of anticoagulant therapy, may indicate a coagulation factor deficiency, most often an acquired deficiency associated with cancer, renal disease, liver disease, or dietary vitamin K deficiency. Occasionally a test may turn up an actual inherited deficiency such as hemophilia or von Willebrand disease, but most of those are detected in early childhood. The PT/INR is sensitive to Coumadin therapy but does not detect heparin, low molecular weight heparin (Lovenox), or fondaparinux (Arixtra) therapy. The PTT detects standard unfractionated heparin therapy but is relatively insensitive to Lovenox and is completely insensitive to Arixtra. The PT/INR is prolonged by the new direct oral anticoagulants rivaroxaban (Xarelto) and apixaban (Eliquis), and the PTT is prolonged by the direct thrombin inhibitor dabigatran (Pradaxa). Neither test is prolonged by the antiplatelet drugs aspirin, Plavix, prasugrel, or ticagrelor.

The Accumetrics VerifyNow instrument, distributed by Fisher Inc, is FDA-cleared to screen for aspirin, Plavix, prasugrel, and ticagrelor, and is a convenient and easy to use point of care tool. The VerifyNow is the only point of care FDA cleared instrument, all the other laboratory assays are complex platelet aggregometry tests, available only in tertiary care facilities. We once used the bleeding time test, however it has a poor predictive value and it leaves scars. Again, a careful history that includes a list of all the common over the counter drugs that contain aspirin is more effective than laboratory testing.

The activated clotting time (ACT) is a time-honored procedure that is excellent for monitoring standard unfractionated heparin, especially at the high doses used during coronary artery bypass graft surgery or cardiac catheterization. It is a point of care test, thus convenient in the operating room. However, it is insensitive to low concentrations of heparin, insensitive to Lovenox or Arixtra, and insensitive to Coumadin. It is also insensitive to aspirin, Plavix, prasugrel, or ticagrelor.

As a laboratory scientist, I wish we could recommend general screening assays. However, except in limited situations such as cholesterol testing, the concept of screening the general unselected population just doesn’t measure up to a careful history for protecting the individual patient.

Comments (5)
Anticoagulant Therapy
Ning Tang
Oct 17, 2014 4:49am

TEG induced by low concentration of TF also seems to be sens
TEG induced by low concentration of TF also seems to be sensitive to nearly clotting factors.

Vadim Kostousov
Oct 9, 2014 6:35am

No, PT is not sensitive to FVIII, FIX, FXI, or FXII due to e
No, PT is not sensitive to FVIII, FIX, FXI, or FXII due to excess amount of added tissue thromboplastin in the assay. The only test that is sensitive to all/most clotting factors is thrombin generation test where low concentration of tissue factor is used.

Oct 9, 2014 2:24am

Continuing with the sensitivities of the tests, according to
Continuing with the sensitivities of the tests, according to the new cascade in which there are no distinctions between extrinsic and common pathways, PT is sensitive to all clotting factors (included those considered of the intrinsic pathway), is that right?

Vadim Kostousov
Oct 7, 2014 6:55am

“Aspirin & clopidogrel appear to have a variable effect
“Aspirin & clopidogrel appear to have a variable effect upon the ACT with some studies reporting a prolongation of the ACT and others very little. GpIIb/IIIa inhibitors significantly prolong the ACT.”

Oct 7, 2014 12:22am

Why is not ACT affected by platelet antiaggregants if it is
Why is not ACT affected by platelet antiaggregants if it is done in whole blood?

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