David L. McGlasson, MS, MLS(ASCP)

Choosing Wisely is a United States-based health educational campaign led by the American Board of Internal Medicine Foundation (ABIMF) and the Consumers’ Union to reduce the prevalence of unnecessary diagnostic tests and treatments.1 The Choosing Wisely campaign goal is to disseminate information for clinicians and patients that provides diagnostic care that is evidence based, not duplicative, and provides necessary clinical care that does not harm the patient.

It compels recognized medical specialty societies to identify tests or procedures commonly used in their areas of expertise that may or may not be necessary in treating patients’ issues.

Over 80 medical specialty societies currently participate in this program. They have put forth more than 600 recommendations of overused tests and treatments that clinicians and patients need to discuss. The campaign and society recommendations have been included in nearly 300 journal articles and more than 10,000 medical articles since the program launched in 2012. The Choosing Wisely group initially organized the creation of lists of five and later ten recommendations of overused tests or procedures. Each of the recommendations had to have evidence based clinical guidelines and expert opinion. The society then shares this data with their society members as well as organizations who can publicize to national, state and local groups to physicians and patients. They can then discuss the information and data to see if this improves their situation and needs in treatment plans.

As of April 2018, there were 552 recommendations of procedures to peruse and assess whether they are really needed for patient care. There are several articles that affirm or question the use of the aims of the Choosing Wisely campaign.2

Since this blog is primarily one that is called CLOT CLUB, I concentrated on every society that put forth recommendations that were relevant to Hemostasis/Thrombosis. The following will deal with submissions by each society.

Note that these items are provided solely for informational purposes and are not intended as a substitute for consultation with a medical professional. Patients with any specific questions about the items on this list or their individual situation should consult their physician.



06.10.20: Don’t order a factor V Leiden (FVL) mutation assay as the initial test to identify a congenital cause for a thrombotic event. First order a phenotypic activated protein C resistance (APCR) ratio assay.

“There exist several acquired APCR conditions such as elevated factor VIII and antibody mediated APCR that can lead to thrombotic events such as deep venous thrombosis or pulmonary embolism. Further, several factor V Leiden-independent mutations may be associated with thrombosis. Best practice guidelines recommend testing for APCR using one of several phenotypic clot based APCR ratio assays as an initial assay and following up positive APCR ratio results with the molecular factor V Leiden assay. Most currently available phenotypic tests are economical, have a greater than 95% concordance with molecular testing and up to 99% clinical sensitivity. Based on Medicare reimbursement rates, switching to initial-phase phenotypic testing and relying on its negative predictive value with follow-up genotypic testing on APCR-positive samples could result in a 75% reduction in costs. Although the FVL mutation assay is often ordered to determine the cause of venous thromboembolic disease, the APCR ratio assay provides greater clinical sensitivity at a lower cost. In instances when clot-based thrombosis risk testing is indicated during acute thrombosis, line-associated thrombosis, or anticoagulant therapy, the APCR is compromised and the FVL mutation assay is used as a primary assay.”

Further reading: diapharma.com

09.13.21: Do not use viscoelastic testing to determine blood product transfusions in trauma patient resuscitation without an established, institutional treatment algorithm in place.

“Currently, many trauma patients presenting to emergency departments are resuscitated through blood product transfusions guided by conventional coagulation tests (CCTs) only. Acute care organizations that utilize viscoelastic testing (VET) in conjunction with CCTs do not commonly have treatment algorithms in place to guide blood transfusions in trauma patients, which can result in the overuse of blood products. When assessing the number of hospitals that have institutional massive transfusion protocols (MTP), one study documented that only 9% of surveyed facilities utilize VET in their MTPs.

Several recent studies compared patient outcomes in facilities that incorporate viscoelastic methodologies into their MTPs against those that did not. Mortality and blood product transfusion rates were measured and positive correlations between CCTs in conjunction with VET versus CCTs-only were found. Not only did viscoelastic-guided resuscitation result in higher survival rates and fewer transfused blood products, but also identified those at risk for hyperfibrinolysis, which is a limitation of CCTs. Apart from positive patient outcomes with VET+CCT, another study found that MTP trauma patients guided by VET-only versus CCT-only had no difference in patient outcomes.

When observing the opportunity of replacing CCTs with VET for trauma activations in the Emergency Department, the reviewed literature seems to be inconclusive. A study of 1,974 major trauma activations argues that rapid thromboelastography methods, a form of VET, are better predictors for massive transfusions; however, another study argued that, because VET testing takes longer to perform than CCTs, VET should not be the sole tool to assess coagulopathies in these patients. Ultimately, the inconsistencies in evidence to date do not support one testing approach over the other, but some data does suggest that a combined approach may be beneficial towards patient outcomes – when properly followed.”

09.13.21: Do not order a protein S activity assay for measuring protein S function. Instead, order free protein S antigen.

“Thrombophilia has numerous causes, including protein S deficiency, of which there are 3 recognized types. Type I and type III are quantitative defects while type II is a qualitative defect.

Types of Heterozygous Protein S Deficiency

Type Free Protein S Antigen  Total Protein S Antigen  Functional Protein S Activity
 I Decreased  Decreased Decreased
II Normal  Normal Decreased
III Decreased Normal Decreased

Type II is extremely rare and is not considered a risk factor for thrombophilia. While functional protein S activity is commonly measured to detect protein S deficiency, there are problems with this test. It is a clot-based assay and has a large coefficient of variation; the test is affected by patients who have factor V Leiden mutation or lupus anticoagulant. On the contrary, free protein S antigen assay is more specific for detecting true deficiencies and only free protein S has anticoagulant activity. Measuring free protein S antigen provides more reliable results, when testing for protein S deficiency is clinically warranted.”

Further reading: diapharma.com

09.13.21: Do not order a homocysteine assay as part of the thrombophilia work up.

“For long it was thought that elevated homocysteine was associated with cardiovascular diseases. That in turn could lead to coronary artery disease, heart attacks, strokes, clots in veins causing deep vein thrombosis (DVT) and pulmonary embolism (PE), and pregnancy complications among others. But in 2010 the American Heart Association declared that elevated homocysteine levels were not considered to be a major risk factor for cardiovascular disease. Subsequently, in 2013, the American College of Obstetricians and Gynecologists recommended that fasting homocysteine levels should not be ordered as part of work up for venous thromboembolism. Homocysteine is a breakdown product of methionine that can be recycled by the human body with the help of the enzyme methylene tetrahydrofolate reductase (MTHFR) to reuse in building proteins. A mutation of the MTHFR gene (C677T) impairs its ability to process folate that may lead to elevated homocysteine levels. An elevated homocysteine level is not a clotting disorder and should not be included in thrombophilia testing panels.”

09.13.21: Avoid routine prothrombin time (PT) and partial thromboplastin time (PTT, APTT) pre-operative screens on asymptomatic patients, use instead a history-based bleeding assessment test.

“The 1989 Medical Necessity Project of the Blue Cross and Blue Shield Association endorsed by the American College of Physicians found that at least 70% of PT and PTT tests were not clinically indicated. Subsequently, nine observational studies, including three prospective trials, reported that PT and PTT positive predictive values for bleeding complications ranged from 0.03 to 0.22, whereas computed 95% confidence intervals for each assay generates a 2.5% false positive rate. A review of 27,737 PT and PTT results over two decades showed that only 8% of PTs and PTTs were clinically indicated based on current or prior patient history of bleeding. A study of general hospital unregulated coagulation screening requests produced few abnormal results with no evidence that they were associated with an increased bleeding risk. In this study, all bleeding cases could be attributed to an underlying condition. The risk of intraoperative bleeding is best predicted from a careful history that includes a questionnaire-based bleeding assessment test (BAT).

New Recommendation that is being readied for peer-review: Do not order a single test for lupus anticoagulant (LA) testing. Order both the diute Russell Viper venom test (DRVVT) and an LA-sensitive activated partial thromboplastin time (PTT) test. Do not order IgA Isotypes for anticardiolipin (aCL) and anti-beta-2-glycoprotein-1 (aB2-GP1) antiphospholipid (aPL) antibody testing, instead order the IgG and IgM isotypes.”

Further reading: Clot Club 



11.07.22: Do not measure the INR in patients who are taking an anti-Xa inhibitor

“Anti-Xa inhibitors (e.g., rivaroxaban [Xarelto®], apixaban [Eliquis®]) are commonly prescribed anticoagulants. Their indications include (but are not limited to): reducing the risk of stroke or systemic embolism in patients with nonvalvular atrial fibrillation; treating deep venous thromboembolism (DVT) and pulmonary embolism; and DVT prophylaxis. Bleeding is a common complication from anti-Xa inhibitor use that may require reversal with andexanet alfa, prothrombin complex concentrate, or plasma. While the INR is commonly used to measure the anticoagulation effect of vitamin K antagonists (e.g., warfarin), it is insensitive for anti-Xa inhibitors, potentially leading to inappropriate patient management decisions.”

11.07.22: Don’t employ a specific direct oral anticoagulant (DOAC) reversal agent without identifying the DOAC and estimating its plasma concentration.

“In 2015, the US FDA approved idarucizumab as a reversal immunoglobulin specific for the direct thrombin inhibitor dabigatran. In 2018, andexanet alfa was approved as a factor Xa mimetic reversal agent for the direct anti-Xa oral anticoagulants rivaroxaban and apixaban. Clinicians employ reversal agents to control major bleeding associated with presumed DOAC overdose when compression, blood product support, and antifibrinolytics are ineffective, often in preparation for an invasive procedure. A reversal agent should be employed only when the clinician can identify the DOAC using, for instance, an anti-Xa assay* or dilute thrombin time [DTT] assay*, establish the likelihood that it is the bleeding source, and estimate its dose or plasma concentration. In addition to their documented risk of ischemic complications, reversal agents are maintained in collaborative inventory systems with controlled access, owing to scarcity and costs. Andexanet alfa, for instance, costs $27,500 for a low dose regimen and $49,500 for a high dose, and CMS reimbursement is limited to 50% of the low dose investment. A rapid urinary “dipstick” detection device* is a viable point-of-care alternative to the anti-Xa or DTT assays as the stick distinguishes dabigatran from the anti-Xa inhibitors.6 For those facilities that do not offer a rapid turnaround DOAC assay specific to the agent, clinicians must establish the DOAC identity and time of the most recent dosage by history before establishing treatment. Healthcare systems shall collaborate with the laboratory medicine service to develop strategies that ensure efficacy and stewardship of reversal agents.”



10.19.17: Do not test for Protein C, Protein S, or Antithrombin (ATIII) levels during an active clotting event to diagnose a hereditary deficiency because these tests are not analytically accurate during an active clotting event.

“These assays may be useful to test for an acquired deficiency (i.e., disseminated intravascular coagulation) in consumptive coagulopathies. These tests are not analytically accurate during an active clotting event. Moreover they are not clinically actionable at the time of an acute clot, because the same therapeutic intervention (anticoagulation) is performed regardless of the results. Deferral to the outpatient/non-acute setting allows for the testing to be done at a time when the results would change patient management, i.e., ceasing or continuing anticoagulation. Because anticoagulation may also impact the determination of results (e.g., Protein C and Protein S decrease on warfarin, while ATIII is elevated), testing while on anticoagulants may also yield misleading results and should be avoided.”

02.21.13: Don’t use bleeding time test to guide patient care.

“The bleeding time test is an older assay that has been replaced by alternative coagulation tests. The relationship between the bleeding time test and the risk of a patient’s bleeding has not been established. Further, the test leaves a scar on the forearm. There are other reliable tests of coagulation available to evaluate the risks of bleeding in appropriate patient populations.”

02.03.15: Don’t test vitamin K levels unless the patient has an abnormal international normalized ratio (INR) and does not respond to vitamin K therapy.

“Measurements of the level of vitamin K in the blood are rarely used to determine if a deficiency exists. Vitamin K deficiency is very rare, but when it does occur, a prolonged prothrombin time (PT) and elevated INR will result. A diagnosis is typically made by observing the PT correction following administration of vitamin K, plus the presence of clinical risk factors for vitamin K deficiency.”

09.04.19: Do not perform a hypercoagulable workup in patients taking direct factor Xa or direct thrombin inhibitors.

“Direct oral anticoagulants (DOACs) such as dabigatran etexilate, rivaroxaban, apixaban, edoxaban, and betrixaban often interfere with clot-based or chromogenic coagulation assays and may lead to inaccurate results or render the test uninterpretable. Affected tests include many commonly ordered tests on hypercoagulable workup panels: Lupus anticoagulant (LA) panels, activated protein C resistance, protein C and protein S activity, antithrombin activity, and specific factor activity levels. These tests should not be done in patients taking DOACS. If there is a compelling reason to perform these tests, great caution must be taken to avoid acting on a false result. For instance, specimens should be collected at the medication trough, and potential test interference should be considered prior to ordering. The potential for interference is dependent on test methodology, drug mechanism of action, and drug concentration. For patients suspected clinically to have antiphospholipid antibody syndrome, the lupus anticoagulant panel may be uninterpretable, but ELISA-based anticardiolipin and anti-beta2 GP1 antibody testing is unaffected. Genetic testing, such as PCR for factor V Leiden, is also unaffected.”



12.04.13: Don’t test for thrombophilia in adult patients with venous thromboembolism (VTE) occurring in the setting of major transient risk factors (surgery, trauma or prolonged immobility).

“Thrombophilia testing is costly and can result in harm to patients if the duration of anticoagulation is inappropriately prolonged or if patients are incorrectly labeled as thrombophilic. Thrombophilia testing does not change the management of VTEs occurring in the setting of major transient VTE risk factors. When VTE occurs in the setting of pregnancy or hormonal therapy, or when there is a strong family history plus a major transient risk factor, the role of thrombophilia testing is complex, and patients and clinicians are advised to seek guidance from an expert in VTE.”

09.01.20: Do not monitor anti-platelet agent inhibition of platelet activity using platelet function or genetic testing.

“Available evidence does not support the use of these laboratory tests to guide the dose of aspirin or clopidogrel in patients with so-called aspirin or clopidogrel “resistance.” Study results do not provide support for the concept of changing antiplatelet therapy based on the results of platelet function monitoring tests. Thus, high on-treatment platelet reactivity (higher than expected platelet reactivity seen in patients receiving antiplatelet therapy) may be a non-modifiable clinical risk factor in patients treated with anti-platelet agents. The American Heart Association has not recommended either platelet function testing or genetic testing at the present time.

**This recommendation is not one all special coagulation laboratories agree with. For example, the University of Alabama Birmingham Special Coagulation Laboratory monitors their subjects on anti-platelet medications due to LVAD systems every 3 months to check the efficacy of the drug regimen.”

12.03.14: Don’t test or treat for suspected heparin-induced thrombocytopenia (HIT) in patients with a low pre-test probability of HIT.

“In patients with suspected HIT, use the “4T’s” score to calculate the pre-test probability of HIT. This scoring system uses the timing and degree of thrombocytopenia, the presence or absence of thrombosis, and the existence of other causes of thrombocytopenia to assess the pre-test probability of HIT. HIT can be excluded by a low pre-test probability score (4T’s score of 0-3) without the need for laboratory investigation. Do not discontinue heparin or start a non-heparin anticoagulant in these low-risk patients because presumptive treatment often involves an increased risk of bleeding, and because alternative anticoagulants are costly.”



07.10.15: Don’t order MTHFR genetic testing for the risk assessment of hereditary thrombophilia.

“The common MTHFR gene variants, 677C>T and 1298A>G, are prevalent in the general population. Recent meta-analyses have disproven an association between the presence of these variants and venous thromboembolism.”



12.09.19: Don’t perform routine pre-operative hemostatic testing (PT, aPTT) in an otherwise healthy child with no prior personal or family history of bleeding.

“Preoperative hemostatic screening in healthy pediatric patients with no personal or family history of excessive bleeding does not effectively identify those who will have unexpected surgical bleeding. Artifacts or disorders that do not affect bleeding risk may be identified, such as factor XII deficiency or an infection-associated, transient lupus anticoagulant. Hemostatic testing adds cost and may introduce additional stress, either due to blood sampling or if a child has “abnormal” results.”

12.09.19: Don’t order thrombophilia testing on children with venous access (i.e., peripheral or central) associated thrombosis in the absence of a positive family history.

“Testing for inherited forms of thrombophilia does not influence the initial management of a first episode of provoked venous thrombosis and should not be performed routinely. The results of such testing have not been shown to either predict recurrence of venous thrombosis or inform the intensity or duration of anticoagulant therapy. Thrombophilia testing has substantial financial cost, and a positive result has the potential for misinterpretation of risk assessment leading to undue psychological distress or impact on childbearing plans, as well as possible life insurance discrimination for affected patients.”



12.03.13: Don’t routinely order thrombophilia testing on patients undergoing a routine infertility evaluation.

“There is no indication to order these tests, and there is no benefit to be derived in obtaining them in someone that does not have any history of bleeding or abnormal clotting and in the absence of any family history. This testing is not a part of the infertility workup. Furthermore, the testing is costly, and there are risks associated with the proposed treatments, which would also not be indicated in this routine population.”



09.21.21: Avoid hemodilution and unnecessary blood draws to avoid dilutional coagulopathy and iatrogenic anemia.

“Excessive fluid administration causing hemodilution and unnecessary phlebotomy reduce hemoglobin levels and may unnecessarily trigger red blood cell transfusions based on a numeric threshold despite adequate oxygen carrying capacity. Replacing blood loss with intravenous fluids which do not contain adequate clotting factors (i.e. crystalloids, colloids and packed red blood cells) may lead to dilutional coagulopathy causing a bleeding diathesis. Routine blood draws should be avoided, and if necessary, blood laboratory investigations should be consolidated when appropriate, using minimal volume withdrawal and closed loop collecting systems.”

**This one hits close to home for me.  I once worked at a university hospital with a special coagulation laboratory, and a large Hematology service affiliated with a medical school.  One day we had to work up a 4-year-old female child with Wiskott-Aldrich Syndrome (WAS).  This is a rare genetic immunodeficiency disorder that impairs the child’s immune system from working properly.  It also causes thrombocytopenia, making the patient at risk for bleeding.  The disorder occurs mostly in males. In addition, the subject may have eczema and our subject had albinism.  When you get a rare case, everyone wants blood.  I was working up the child in our special coagulation laboratory and was asked 4 times to go back and get more specimen on this small child.  I had already drawn at least 50 mL of blood.  But I was not going to be responsible for making this child more anemic than she already was on admission and causing more trauma in the venipunctures.  This is a case where an opportunity to study a disorder like this is an opportunity, but the patient has to be considered first to prevent harm. In other words, here would have been an ideal situation to consolidate the laboratory services in a treatment plan before starting the work-up.



Each of the individual societies’ recommendations were developed under the leadership of that organization’s Choosing Wisely Committee. Check the web pages for each group to see how they determined to give their recommendations for selection of the topics that they deemed important enough to put forward to suggest to clinicians and patients better their health care plan.



  1. Cassel, CK Et al:” Choosing Wisely-Helping Physicians and Patients Make Smart Decisions About Their care.” JAMA 2012. 307(17):1801-1802.
  2. http://www.choosingwisely.org/wp-content/uploads/2015/01/Choosing-Wisely-Recommendations.pdf