Abstract Number: PB1259
Meeting: ISTH 2020 Congress
Background: Bivalirudin, a direct thrombin inhibitor, is an evolving alternative to unfractionated heparin (UFH) for anticoagulation therapy in the pediatric critical care setting. A functional test for bivalirudin associated anticoagulation status is not available.
Aims: Demonstrate the ability of a microliter volume capillary assay to detect the effect of bivalirudin and UFH and quantify the level of anticoagulation using a functional, clot time end point in pediatric critical care patients.
Methods: Under IRB approval, a retrospective analysis of 20 citrated, frozen, bio-banked plasma specimens from 7 anticoagulated pediatric patients was performed. Five patients were on extracorporeal membrane oxygenation, one patient had a sub massive pulmonary embolism and one patient was on a ventricular assist device, providing 11 bivalirudin and 9 UFH samples. (Table 1). 100 µL of each sample was re-calcified in the presence of Coagulo’s reagents (combinations of Factor IIa/Xa), the time to clot at 37oC was measured and the Clotting Time Score (CTS) was calculated using optimized algorithms. Reference clotting time curves for each drug were made using spiked healthy adult samples. The target CTS range was determined by comparison to clinical target drug levels: Bivalirudin (0.7-2.0 ug/mL), UFH (0.2-0.4 IU/mL) (Figure 1A-B).
Results: The CTS range corresponding to clinical target drug levels was 6.0-14.5 (Bivalirudin) and 5.4-15.0 (UFH), providing an assessment of below-, on- or above- target drug range (Figure 1C). Using the CTS, only 25% of samples were within the target range. Bivalirudin samples were on (36%) or above (64%) target while UFH samples were below (56%), on (11%) and above (33%) target.
Conclusions: The CTS range appears independent of the anticoagulant and may be useful to create functional reference ranges to guide anticoagulation therapy. The small sample volume required allows for more frequent testing, reducing the risk of anticoagulation-related complications and iatrogenic blood loss.
| Age | Indication | Drug | Drug Dose Range | No. Samples | Sample 1 (FIIa CTS) | Sample 2 (FIIa (CTS) | Sample 3 (FIIa CTS) | Sample 4 (FIIa CTS) | % Samples Within Target Range (UFH CTS 6.0-14.5) (Bivalirudin CTS 5.4-15) |
| 5 days | ECMO (VA ECMO) | UFH | 24-25 U/kg/hr | 2 | High (18.0) | Low (4.0) | 0% | ||
| 9 months | ECMO (VA ECMO) | UFH (x2), Bivalirudin (x2) | 28-38.5 U/kg/hr; 0.28-0.7 mg/kg/hr | 4 | Target (8.9) | Low (3.10 | Target (11.7) | High (19.9) | 50% |
| 11 years | ECMO (VV ECMO) | Bivalirudin | 0.65-0.82 mg/kg/hr | 2 | Low (1.5) | High (17.2) | 0% | ||
| 9 months | ECMO (Berlin) | UFH | 16-20 U/kg/hr | 3 | High (18.5) | Target (13.2) | High (19.9) | 33% | |
| 11 months | ECMO (Jarvik) | Bivalirudin | 0.72-0.82 mg/kg/hr | 3 | High (14.6) | Target (14.1) | High (15.0) | 33% | |
| 17 years | Sub Massive Pulmonary Embolism | UFH | 10-18 U/kg/hr | 3 | Low (5.5) | High (24.6) | Low (-3.1) | 33% | |
| 18 years | Ventricular Assist Device (LVAD) | Bivalirudin | 0.22-0.3 mg/kg/hr | 3 | High (21.3) | High (21.6) | Target (13.4) | 33% |
[Patient Descriptive Statistics]
[Factor IIa inhibition related Clotting Time Score (CTS) analysis of Bivalirudin and UFH Patient samples]
To cite this abstract in AMA style:
Frydman G, Berger B, Kostousov V, Bruzdoski K, Gokhale A, Navaei A, Hensch L, Hui S-R, Teruya J. Quantitation of Bivalirudin Effect Using Microliter Scale Sample Microfluidic Assay in a Pediatric ECMO Population [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/quantitation-of-bivalirudin-effect-using-microliter-scale-sample-microfluidic-assay-in-a-pediatric-ecmo-population/. Accessed November 29, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/quantitation-of-bivalirudin-effect-using-microliter-scale-sample-microfluidic-assay-in-a-pediatric-ecmo-population/