Innovative hemostasis assays improve quality and reduce cost of patient care

Aug. 22, 2017

Pressures to reduce healthcare costs abound through the healthcare delivery system today. As the total U.S. healthcare expenditure growth continues to increase, the goal of controlling healthcare costs while continuing to provide quality care is paramount. Hemostasis assays enable laboratories to positively impact patient outcomes, while reducing total healthcare expenditures. From new on-demand heparin-induced thrombocytopenia (HIT) antibody testing to optimized assay formats, innovative hemostasis products, both new and established, help laboratories and hospitals achieve better clinical and cost outcomes.

On-demand HIT antibody testing

HIT is a severe adverse reaction to heparin, conferring major risk of thrombotic complications, significant morbidity, and mortality in up to 10 percent of patients.1 The reaction is caused by antibodies directed against a complex of heparin and platelet factor 4. Traditionally, screening for HIT antibodies in suspected patients has been performed using ELISA methodology. An HIT antibody test result, in combination with clinical assessment, allows clinicians to determine the probability of HIT and make decisions regarding heparin therapy continuation. Patients with a high probability of HIT should be switched from heparin to a non-heparin anticoagulant. Many non-heparin anticoagulants such as argatroban, an FDA-approved direct thrombin inhibitor for treatment and prophylaxis of HIT, possess increased bleeding risk profiles and significant cost disadvantages relative to heparin.2

Unnecessary use of non-heparin anticoagulants may be exacerbated when turnaround time (TAT) of HIT antibody testing is delayed, due to batching of ELISA runs or extended TAT of the send-out specimen. Clinicians awaiting HIT antibody test results may switch HIT-suspected patients to non-heparin anticoagulants to avoid complications of HIT, given the significant morbidity and mortality risk. However, because many HIT antibody test results are negative, patients could unnecessarily receive non-heparin treatment and increase hospital stay under this treatment approach.3

On-demand HIT antibody testing directly addresses the challenges of speculative treatment with non-heparin anticoagulant and prolonged hospital stay. By providing rapid results, the fully automated assay allows laboratories enhanced responsiveness to clinicians and patients.

The assay features an analytical TAT of less than 20 minutes. Clinicians receive HIT antibody results in real-time, triaging patients with both laboratory and clinical information to formulate informed treatment decisions. Rapid identification of patients at low probability of HIT reduces hospital costs (e.g., direct pharmacy expenditures) by preventing unnecessary treatment. This translates into patient care and cost-saving benefits.

High specificity D-dimer assays

The fully automated, high specificity D-dimer assay is another noteworthy hemostasis innovation that has been shown to positively impact quality and cost of patient care. Standard D-dimer products, in combination with pre-test probability assessment, have been an efficient means to rapidly assess venous thromboembolism (VTE). Although the high negative predictive value of standard D-dimer products helps exclude VTE in patients with low and moderate pretest probability scores, specificity challenges have resulted in false positives and overutilization of expensive imaging studies to confirm results.

False positive D-dimer results can occur due to clinical factors associated with conditions such as cancer, pregnancy, and advanced age. For example, rheumatoid factor has been shown to produce false positive D-dimer results. Rheumatoid factor antibodies are present in patients with rheumatoid arthritis, a condition associated with advanced age. To address the challenge of false positive D-dimer results associated with rheumatoid factor interference, high specificity assays, engineered with the F(ab’)2 fragment of the monoclonal antibody, more specifically detect the D-dimer domain. The high specificity D-dimer assay avoids rheumatoid factor interference, demonstrating a lower false positive rate versus standard D-dimer assays.4

This hemostasis innovation is also an economical tool in the evaluation of VTE-suspected patients, significantly reducing the high cost of unnecessary imaging studies. In addition to cost savings, full exclusion for deep vein thrombosis and pulmonary embolism ensure optimal patient care, while fewer false positives improve patient experience by limiting unnecessary procedures and anticoagulant treatment.

Enhanced assays featuring liquid format and robust stability Hemostasis laboratories seeking opportunities to reduce costs via improved efficiencies should include assay format and stability in their calculus. Many established hemostasis assays have been reengineered into robust, liquid formats. Using liquid, ready-to-use products as part of a routine hemostasis menu imparts significant cost reductions versus lyophilized formats. Reconstitution costs include labor, as well as costs associated with errors, such as reagent waste.

Assay stability is as important as liquid format. Routine hemostasis products, such PT and aPTT, are available with up to 10-day onboard stability. D-dimer, fibrinogen, and Anti-Xa products are also available with robust stability. Longer stability reduces reagent waste, minimizes reagent management time, and helps ease storage constraints. Less time spent managing reagents frees laboratorians to focus on other important tasks, improving laboratory efficiency.

Anti-Xa testing reduces cost of care

Monitoring unfractionated heparin (UFH) with a chromogenic Anti-Xa assay is increasingly common in hospitals due to the significant patient, quality, and cost-of-care benefits. Accurately monitoring heparin to quickly achieve and maintain therapeutic anticoagulation is critical to patient safety, as inaccurate or inconsistent UFH monitoring may impact patient outcomes. Anti-Xa is a more precise measure of UFH than aPTT in hospitalized patients, resulting in quicker therapeutic anticoagulation and a reduced number of sample draws.5

Fully automated Anti-Xa assays permit routine labs to easily monitor UFH. With a product that features a single calibration curve for UFH and low molecular weight heparin, hemostasis testing is further simplified, saving staff time and lab resources. Innovations in Anti-Xa assays allow for accurate and rapid heparin monitoring, on-demand, 24 hours a day, seven days a week.

Implementing Anti-Xa testing is a cost-effective solution. Using an Anti-Xa assay to monitor UFH has reduced blood transfusions by 4.7 percent for VTE patients, 8.2 percent for ischemic stroke patients, and 17.5 percent for acute coronary syndrome patients versus aPTT monitoring.5 Fewer red blood cell transfusions reduce overall hospitalization cost. These results, combined with studies demonstrating fewer bleeding complications and non-fatal myocardial infarction, and reduced 30-day mortality of high-risk ACS patients, further support the use of Anti-Xa testing to accurately monitor heparin therapy.6, 7

Budgetary constraints across the healthcare supply chain necessitate solutions that deliver quality patient care and control overall expenditures. From reduced pharmacy costs to fewer imaging studies, implementing novel assays within the hemostasis laboratory helps rein in costs across the hospital, while simultaneously delivering better outcomes and enhanced patient satisfaction.


  1. Arnout J, deGaetano G, Hoylaert M, Peerlinck K, Van Geet C, Verhaeghr R, eds. Thrombosis: Fundamental and Clinical Aspects. Leuven, Belgium: Leuven University Press; 2003.
  2. Greinacher A, et al. Heparin-induced thrombocytopenia. Hämostaseologie. 2010;1(Review):17–28.
  3. Caton S, O’Brien E, Pannelay AJ, Cook RG. Assessing the clinical and cost impact of on-demand immunoassay testing for the diagnosis of heparin induced thrombocytopenia. Thrombosis Research. 2016;140:155–162.
  4. Arza B, Sanchez T, Sales M, et al. Analytical performance of the new hemosil d-dimer hs assay that overcomes the rheumatoid factor (RF) interference.
    Paper presented at: XX Congress of The International Society on Thrombosis and
    Haemostasis; 2005 Aug 6–12; Sydney, Australia.
  5. Belk KW, Laposata M, Craver C. A comparison of red blood cell transfusion utilization between anti-activated factor X and activated partial thromboplastin monitoring in patients receiving unfractionated heparin. J Thromb Haemost. 2016;14(11):2148–2157.
  6. Hamilton LA, Abbott GV, Cooper JB. High-risk non-ST elevation acute coronary syndrome outcomes in patients treated with unfractionated heparin monitored using Anti-Xa concentrations versus activated partial thromboplastin time. Hospital Pharmacy. 2013;48(5):389–395.
  7. Price EA, Jin J, Nguyen HM, Krishnan G, Bowen R, Zehnder JL. Discordant aPTT and Anti-Xa values and outcomes in hospitalized patients treated with intravenous unfractionated heparin. Ann Pharmacother. 2013;47(2):151–158.

Tyler Faken, MBA, serves as Hemostasis Product Manager for Instrumentation Laboratory.