Requirement for a Pathologist’s Second Signature Limits Inappropriate Inpatient Thrombophilia Testing

Abstract

Thromboembolism is a condition that leads to the hospitalization of thousands of patients in the United States annually. Recent guidelines suggest that testing for hereditary, acquired and combined forms of thrombophilia be delayed following hospitalization for a first-time acute thrombotic event. Instead, thrombophilia testing would be performed in an outpatient setting, at least 1 month after discontinuation of anticoagulant therapy or 3 months after the thrombotic event, on the understanding that anticoagulation may affect some testing. Here, we provide our experience in instituting a system-wide policy change to limit thrombophilia testing in the inpatient setting. The policy change implemented led to a 90% reduction in number of tests ordered. We discuss the cost savings realized by limiting testing. These changes cost nothing to implement. Overall, limiting inpatient thrombophilia testing improves compliance with testing guidelines, provides better care for patients, and allows our institution to better utilize resources.

Acute venous thromboembolism is a relatively common disease process, affecting approximately 130 people per 100,000 per year.¹ Treatment in the acute setting often involves hospitalization and the administration of anticoagulant and antiplatelet therapies. The etiologies underlying these thrombotic events are varied, encompassing heritable disorders, those that are acquired, and a combination of both. In the case of heritable deficiencies, deficiencies in the anti-thrombotic factors protein C, protein S and antithrombin, as well as mutations in factor V gene and prothrombin promoter, have been described.² Dependent upon the gene of interest, prevalence of such inherited traits exists in up to 7% of the population,³ yet the incidence of thromboembolism is much lower. Thus, heritable risk factors alone are not likely to precipitate a thrombotic event; additional precipitating events such as stasis, trauma, or other underlying disease process are needed to induce venous thrombosis.

Treatment of acute thrombosis often relies upon the manipulation of endogenous clotting factors and platelets to drive the patient to a more anticoagulated state. Because of this, assessment of coagulation factors, which oftentimes relies upon enzymatic assays, cannot reliably be conducted during acute thrombosis and its treatment. Demonstration that a patient possesses a heritable trait associated with increased thrombosis may not be sufficient to positively conclude that a sudden thrombosis is tied specifically to that genetic trait. Identification of a heritable thrombophilic risk factor should not dictate anticoagulant therapy in the acute setting,⁴ and institution of anticoagulant therapy in individuals who harbor a genetic risk factor and are asymptomatic does not influence life expectancy or improve clinical outcomes.^5,6 Moreover, less than half of patients who have a hereditary thrombophilia and have experienced a thrombosis will have an additional thrombosis at a later date once anticoagulation therapy has been withdrawn.^7,8

Numerous reports and letters have addressed the utility of conducting thrombophilia testing in the acute thrombosis setting, and they conclude that those tests are of little value.^2,3,5,9-12 Additionally, guidelines have been published that recommend against performing thrombophilia screening to predict the risk of further venous thrombosis in those with their first episode.^13-15 Overall, both guidelines and reports discourage thrombophilia testing in the acute thrombotic event and recommend that testing be carried out 1 month following the end of anticoagulation therapy or 3 months after a thromboembolism is diagnosed, under the consideration that current anticoagulation therapy may affect the laboratory results.²

To comply with those guidelines, our institution implemented a policy change in the spring of 2015 requiring a second signature from a pathologist to authorize thrombophilia testing in the inpatient setting. We report statistical data of ordering patterns prior to and after this policy change as well as its economic impact. We also examine whether there was a reflexive shift toward outpatient testing following the policy institution. Overall, this report provides our experience toward limiting unnecessary and nonindicated thrombophilia testing.

Materials and Methods

The actions and data collected herein were performed and collected at Nebraska Medicine (University of Nebraska Medical Center, UNMC) in Omaha. Research and opinion papers from the late 2000s and early 2010s recommend that thrombophilia testing in the inpatient setting is inappropriate and potentially harmful to patient care. In compliance with these recommendations, our institution issued a policy change to discourage clinicians from placing thrombophilia testing orders into our electronic health record system. This policy change was implemented on April 29, 2015. Clinicians were notified of this change via a systemwide memo that provided information and justification as to why these tests were no longer freely available to order.

In addition to limiting inpatient testing of enzyme function based (phenotypic) assays, genetic testing for heritable thrombophilia testing was also limited, as those data should not routinely affect care of a patient during an acute thrombotic event. The tests included are provided in Table 1. Should an inpatient clinician attempt to place an inpatient thrombophilia order in the electronic system, a pop-up box would appear instructing the clinician to contact the on-call pathology resident (Figure 1). At that point, a discussion could be conducted regarding the indication for testing in the inpatient setting. An attending pathologist could approve testing for thrombophilia on a case-by-case basis.

Table 1.

Tests Included in Policy Change

Test Code	Test Name
PRLEY	PROTHROMBIN / LEIDEN MUTATION ONLY
PROTH	PROTHROMBIN FACTOR II MUTATION, DNA AMPLIFICATION
LEYDN	FACTOR 5 (V) LEIDEN MUTATION ONLY
PROTCS	PROTEIN C AND S SCREEN
PCACT	PROTEIN C ACTIVITY
PSACT	PROTEIN S SCREEN
CAG	PROTEIN C ANTIGEN, TOTAL
SACT	PROTEIN S ACTIVITY
SAG	PROTEIN S ANTIGEN, TOTAL
APCRST	APC RESISTANCE
MTHF	MTHFR MUTATION STATUS
THMP	THROMBOPHILIA MUTATION PANEL

Figure 1.

Screenshots from the electronic health record after policy change. The top left panel is an example of the built-in message associated with thrombophilia testing orders when orders are queried. The bottom center panel is an example of the pop-up box that is displayed should a clinician attempt to sign orders for thrombophilia testing on inpatients.

Data was obtained from the hospital electronic health record (Epic). All thrombophilia-related testing ordered between April 29, 2014, and April 28, 2016, was culled. Microsoft Excel was used to organize and analyze data for the year before intervention (PRE) and for the year after (POST). The ordering rules modification in our electronic health record was made by our hospital’s information technology department. Prices presented include both reagent cost and technician time for in-house testing or the charge from a reference laboratory to run the assay.

Results

Data of ordering patterns was assessed 1 year prior to the policy change and compared to ordering patterns for 1 year following the policy change (Table 2). Overall, test volumes in the inpatient setting decreased by 90.5% following the intervention. We also assessed whether there was a subsequent increase in outpatient testing following the intervention, which would indicate testing for acute thrombosis in line with recommendations. Interestingly, outpatient testing decreased slightly (9.0%) in the year following the intervention. We next assessed whether allowing testing on a case-by-case basis would increase the proportion of positive cases on inpatients (Table 3) and outpatients (Table 4). Before implementation of the policy change, 6.9% (8/116) of inpatients tested positive for the various tests conducted; 5 positive tests were genetic assays and 3 were enzymatic. Similarly, after the intervention, a single genetic assay representing 9.1% of tests was positive. Outpatient testing showed a slightly higher rate of positive testing at 13.2% and 10.1% for the pre- and postintervention periods, respectively. Most tests ordered on inpatients were genetic-based tests (118/127 = 92.9%) and were not affected by coagulation status (Table 5).

Table 3.

Inpatient Testing: Negative Versus Positive Result

	NEGATIVE	POSITIVE	CANCELED	TOTAL	NEGATIVE (%)	POSITIVE (%)	CANCELED (%)
PRE	108	8	0	116	93.1%	6.9%	0.0%
POST	10	1	0	11	90.9%	9.1%	0.0%
TOTAL	118	9	0	127	92.9%	7.1%	0.0%

Table 4.

Outpatient Testing: Negative Versus Positive Result

	NEGATIVE	POSITIVE	CANCELED	TOTAL	NEGATIVE (%)	POSITIVE (%)	CANCELED (%)
PRE	462	72	11	545	84.8%	13.2%	2.0%
POST	446	50	0	496	89.9%	10.1%	0.0%
TOTAL	908	122	11	1041	87.2%	11.7%	1.1%

Table 5.

Testing by Assay Type

		PRE	POST	TOTAL
INPATIENT	GENETIC	107	11	118
	ENZYME	9	0	9
OUTPATIENT	GENETIC	378	330	708
	ENZYME	167	166	333

Table 6.

Specific Test Utilization and Cost, Inpatient

TEST CODE	TEST COST	PRE	POST	TOTAL	PRE COST	POST COST
PROTH	$190.34	34	4	38	$6,471.56	$761.36
LEYDN	$190.34	38	4	42	$7,232.92	$761.36
THMP	$278.26	35	3	38	$9,739.10	$834.78
CAG	$16.00	3	0	3	$48.00	$0.00
SACT	$41.60	0	0	0	$0.00	$0.00
SAG	$18.83	2	0	2	$37.66	$0.00
APCRST	$27.56	4	0	4	$110.24	$0.00
TOTAL		116	11	127	$23,639.48	$2,357.50
	GENETIC	107	11	118	$23,443.58	$2,357.50
	ENZYME	9	0	9	$195.90	$0.00

Table 2.

Change in Test Volume

	INPATIENT	OUTPATIENT
PRE	116	545
POST	11	496
DELTA (%)	-90.5%	-9.0%

Because we identified a large reduction in the number of tests ordered, we anticipated that dramatic costs savings would also be realized. Tests ordered were itemized in the preintervention and postintervention periods, for both in- and outpatients. Genetic tests, which were the most commonly ordered tests in both in- and outpatients, are generally 10 times more expensive than the phenotypic, “enzyme-based” assays (Tables 6 and 7). Annual inpatient thrombophilia testing cost US $23,639 prior to intervention and US $2,358 after, representing a cost savings of US $21,282. Outpatient testing cost also saw a decrease in accordance with the decreased testing volumes (a decrease of US $11,052).

Table 7.

Specific Test Utilization and Cost, Outpatient

TEST CODE	TEST COST	PRE	POST	TOTAL	PRE COST	POST COST
PROTH	$190.34	125	108	233	$23,792.50	$20,556.72
LEYDN	$190.34	188	175	363	$35,783.92	$33,309.50
THMP	$278.26	65	47	112	$18,086.90	$13,078.22
CAG	$16.00	27	38	65	$432.00	$608.00
SACT	$41.60	69	65	134	$2,870.40	$2,704.00
SAG	$18.83	36	50	86	$677.88	$941.50
APCRST	$27.56	35	13	48	$964.60	$358.28
TOTAL		545	496	1041	$82,608.20	$71,556.22
	GENETIC	378	330	708	$77,663.32	$66,944.44
	ENZYME	167	166	333	$4,944.88	$4,611.78

The residents at UNMC did field increased calls regarding the thrombophilia testing, and they referred clinicians to their attending pathologist when questions arose. Overall, 11 inpatient tests were cosigned by the pathologist for 7 patients, all of them genetic based, with 1 test demonstrating positivity for mutation. Importantly, the patients tested had demonstrated a profound history of venous and/or arterial thrombosis, and 4 of the 7 had a history of transplantation, including kidney (n=1), liver (n=2), and left-ventricular assist device placement (n=1).

Conclusion

Monitoring of hospital expenditures and the stewardship of resources are vital for our healthcare system to continue improving quality of care while still decreasing expense. Assessment of laboratory-use patterns and assurance that they are in line with standards of care are “low-hanging fruit” to drive down costs associated with care and improve outcomes for patients.

The structure of reimbursement currently employed by Medicare provides a hospital a fixed amount for the care of a patient with a given diagnosis; performance of tests that would have no impact upon a patient’s care in the short-term is inappropriate. Rather, once a patient has been discharged from the hospital and is no longer in an acute setting, directed thrombophilia testing may be more appropriately considered to determine whether patients have a heritable thrombophilic risk factor. We had anticipated that outpatient testing would increase in response to the cessation of inpatient testing; however, that did not occur. Some possibilities exist for this observation including no further indication for testing after hospitalization, patients lost to follow-up and follow-up at another institution. In addition, it is possible that education of clinicians regarding the utility of thrombophilia testing limited use in the follow-up setting.^5,6

The cost to implement our policy change was minimal. Rule sets were established such that ordering thrombophilia testing on inpatients required a second signature from a pathologist. Initial contact by the clinician would be made with the pathology resident on call. If the clinician sought to pursue the order further, the clinician was referred to the attending pathologist on call. Following this workflow modification, the overall costs of thrombophilia testing on inpatients decreased by over US $20,000 per year, a savings that could be used for other, more essential resources in those patients’ care.

We acknowledge that our circumstances may not reflect those of the majority of healthcare institutions. We principally serve 1 major medical center within our healthcare system. Moreover, our pathology practice is directly integrated into the healthcare system we serve. For those groups providing services across multiple hospitals/hospital systems and for those who are providing third-party contract services, ensuring strong communication with clinical colleagues will be essential toward implementing a similar policy. Evidence-based practices toward improving patient care, in addition to the associated cost savings, are points of emphasis to begin the process of shifting thrombophilia testing from the inpatient to the outpatient setting.

In conclusion, utilization reviews of laboratory testing are outstanding mechanisms by which to identify and limit costly testing that does not enhance patient outcomes or service. Moreover, modern electronic health record systems facilitate these analyses, which can be conducted at both large and small healthcare facilities.