Capped antithrombin III dosing is cost effective in the management of asparaginase-associated thrombosis.

Asparaginase therapy induces a transient antithrombin III (ATIII) deficiency, which contributes to the risk of asparaginase-induced thrombosis. At Cincinnati Children's Hospital Medical Center, management of asparaginase-induced thrombosis includes ATIII supplementation during therapeutic anticoagulation with enoxaparin. Due to the expense associated with ATIII, a capped dosing approach for ATIII was evaluated in this population. Peak ATIII levels were obtained following capped doses to evaluate response. In this pilot evaluation, 11 patients received a total of 138 capped doses for a total cost savings of $803 782. This pilot evaluation represents the first reported analysis of capped ATIII dosing in oncology patients.

Identification of Cost-Saving Opportunities for the Use of Antithrombin III in Adult and Pediatric Patients.

Thrombate III is a human plasma-derived antithrombin III (AT-III) often utilized in patients on extracorporeal membrane oxygenation (ECMO) with suspected AT-III-mediated heparin resistance. It is supplied as 500-U and 1000-U vials, costing US$4.66 per unit. Literature is limited in describing the clinical value of AT-III in relation to its high cost. The primary objective was to determine conditions of use and associated cost of potentially unnecessary utilization of AT-III at The Johns Hopkins Hospital. Secondary objectives included evaluating the effect of AT-III on anticoagulation parameters and the overall cost utilized and wasted on AT-III. A retrospective cohort study was performed. The primary end point was the total cost associated with potentially unnecessary utilization of AT-III. There were 326 doses of AT-III administered to 65 patients in 2014. There were 177 (54%) potentially unnecessary doses associated with a cost of US$541 634. Antithrombin III repletion significantly increased median AT-III levels in non-ECMO and ECMO patients compared to baseline (non-ECMO: 62% vs 81%, P < .01; ECMO: 63% vs 81%, P < .01); however, 37.3% of ECMO and 49% of non-ECMO patients had therapeutic anticoagulation monitoring parameters prior to administration. A total cost of US$688 478 was spent on administered AT-III and US$417 194 (38%) was wasted. Utilizing restriction criteria and a new dosing strategy potentially results in estimated annual savings of US$556 000. Utilizing restriction criteria and alternative dosing strategies to mitigate waste and unnecessary use has the potential to result in significant cost savings.

Retrospective evaluation of antithrombin III supplementation in neonates and infants receiving enoxaparin for treatment of thrombosis.

BACKGROUND: Thromboembolic events are occurring at increasing rates in neonates and infants. At Children's Mercy Hospitals and Clinics, antithrombin III (AT3) concentrates are often used in combination with enoxaparin to supplement physiologically low AT3 levels. Theoretically, AT3 enhances the anticoagulant activity of enoxaparin and results in decreased time to therapeutic anti-Xa levels. No data exist on use of AT3 for this indication. PROCEDURE: This retrospective study compared time to therapeutic anti-Xa levels in patients <1 year of age receiving enoxaparin with AT3 (Group 1) and without AT3 (Group 2) for treatment of thrombosis. Primary objective was to compare time to therapeutic anti-Xa levels (0.5-1 U/ml) between groups. Secondary objectives included comparison of the initial and therapeutic dose of enoxaparin, enoxaparin dose changes, AT3 supplementation, and level monitoring. Bleeding events and cost were also evaluated. Statistical tests included Schuirmann's two one-sided tests for equivalence and general linear models/logistic regression for independent effects of age, critical illness, and timing of AT3. RESULTS: Mean time to therapeutic anti-Xa levels were not equivalent between Groups 1 and 2 (80.7 vs. 65.2 hours; P = 0.28). Initial enoxaparin dose and number of dose changes were equivalent. Group 1 required higher doses of enoxaparin to achieve therapeutic anti-Xa levels. Age, critical illness, and timing of AT3 had no effect on time to therapeutic anti-Xa levels. Bleeding events were not equivalent between Groups 1 and 2 (14.3% vs. 3.9%; P = 0.55). CONCLUSION: Supplementation with AT3 did not decrease time to therapeutic anti-Xa levels, added significant cost, and was associated with increased bleeding events.

Heparin dose response is independent of preoperative antithrombin activity in patients undergoing coronary artery bypass graft surgery using low heparin concentrations.

BACKGROUND: Unfractionated heparin's primary mechanism of action is to enhance the enzymatic activity of antithrombin (AT). We hypothesized that there would be a direct association between preoperative AT activity and both heparin dose response (HDR) and heparin sensitivity index (HSI) in patients undergoing coronary artery bypass graft surgery. METHODS: Demographic and perioperative data were collected from 304 patients undergoing primary coronary artery bypass graft surgery. AT activity was measured after induction of general anesthesia using a colorimetric method (Siemens Healthcare Diagnostics, Tarrytown, NY). Activated coagulation time (ACT), HDR, and HSI were measured using the Hepcon HMS Plus system (Medtronic, Minneapolis, MN). Heparin dose was calculated for a target ACT using measured HDR by the same system. Multivariate linear regression was performed to identify independent predictors of HDR. Subgroup analysis of patients with low AT activity (<80% normal; <0.813 U/mL) who may be at risk for heparin resistance was also performed. RESULTS: Mean baseline ACT was 135 ± 18 seconds. Mean calculated HDR was 98 ± 21 s/U/mL. Mean baseline AT activity was 0.93 ± 0.13 U/mL. Baseline AT activity was not significantly associated with baseline or postheparin ACT, HDR, or HSI. Addition of AT activity to multivariable linear regression models of both HDR and HSI did not significantly improve model performance. Subgroup analysis of 49 patients with baseline AT <80% of normal levels did not reveal a relationship between low AT activity and HDR or HSI. Preoperative AT activity, HDR, and HSI were not associated with cardiac troponin I levels on the first postoperative day, intensive care unit duration, or hospital length of stay. CONCLUSION: Although enhancing AT activity is the primary mechanism by which heparin facilitates cardiopulmonary bypass anticoagulation, low preoperative AT activity is not associated with impaired response to heparin or to clinical outcomes when using target ACTs of 300 to 350 seconds.

Cost reduction of perioperative coagulation management in cardiac surgery: value of "bedside" thrombelastography (ROTEM).

OBJECTIVE: Demographic changes and aggressive platelet inhibition have resulted in a marked increase in blood- and coagulation product expenditure and costs in cardiac surgery. We analyzed "bedside" coagulation test (ROTEM) in order to verify clot forming quality for the purpose of finding a cost-effective treatment path. METHODS: Annual treatment costs of all cardiosurgical patients were analyzed before (729 patients) and after (693 patients) implementation of "bedside" ROTEM. Cumulative numbers and costs of platelet concentrates (PltC), fresh frozen plasma (FFP), red blood cell units (RBC), and coagulation factors: pooled coagulation concentrates (PCC), recombinant factor VIIa (rFVIIa), factor XIII (FXIII), and fibrinogen were assessed. Average monthly numbers and costs were compared. Number of resternotomies and early mortality was assessed and compared in both periods. RESULTS: After ROTEM implementation cumulative RBC expenditure showed 25% decrease while PltC exhibited 50% decrease. FFP expenditure remained unchanged. PCC, FXIII were markedly reduced (-80%) while rFVIIa were entirely omitted. Fibrinogen, however, increased two-fold. Cumulative average monthly costs of all blood products decreased from 66,000 euro to 45,000 euro (-32%). Coagulation factor average monthly costs decreased from 60,000 euro to 30,000 euro (-50%) yielding combined savings of 44%. In contrast, average monthly costs for ROTEM were 1.580 euro. Total number of resternotomies decreased from 6.6% to 5.5% while early mortality (5.9%; 6.0%) remained stable. CONCLUSION: Cumulative costs for treatment of perioperative coagulation disorders can be reduced by "bedside" ROTEM analysis to achieve a selective substitution management. Saved costs for blood- and coagulation products clearly outweighed the expenses of ROTEM. Adequate differential coagulation management can therefore be cost-effective.

Surgery and adjuvant therapy in patients with diffuse peritonitis: cost analysis.

In a prospective, randomized, controlled trial the effect of high dose intravenous antithrombin III and intraabdominal donor serum was analyzed in 36 patients with diffuse secondary peritonitis. The direct cost for treatment was 25,370 euros per patient, and the post acute hospital care costs and societal costs were 6273 euros. The cost for intensive care of these patients accounted for approximately 83% of the direct costs, while the expenditures for operating theater and general wards accounted for 9% each. The most expensive factors were staff, medication, and blood products. The hospital incurred a deficit of 3696 euros for each patient after reimbursement from public health insurance companies. Quality of life as assessed by the gastrointestinal quality of life index (GIQI) showed a good outcome. On average 11 quality adjusted life years (QALY) were achieved. The cost per QALY was 2631 euros. Use of adjuvant therapy was associated with a reduced duration of intensive care unit (ICU) treatment, times on mechanical respiration, and hemofiltration; the cost of treatment was reduced by 6614 euros per patient. The additional cost of antithrombin III (5155 euros) was more than offset by the savings made when adjuvant therapy was used.