M. Raguindin et al.: J Extra Corpor Technol 2026, 58, 57--64 59
Table 1. Institutional protocol of bivalirudin for mechanical circulatory support. Renal Function
Initial bivalirudin infusion rate
CrCl > 60 mL / min 0.08 mg / kg / h
CrCl 30--60 mL / min 0.05--0.08 mg / kg / h
CrCl < 30 mL / min or CRRT / iHD
0.03--0.05 mg / kg / h
Low Intensity( Goal aPTT 45--60) High Intensity( Goal aPTT 60--80) Common Uses( but not limited to):
Common Uses( but not limited to):
Early LVAD post-operative days( e. g., Post-op day 0--2) Later LVAD post-operative days( e. g., Post-op day 3 +)
Higher bleeding risk Lower bleeding risk
VV ECMO
High thrombotic risk Patients with additional anticoagulation indication( s)
CrCl: Creatinine clearance; LVAD: Left ventricular assist device.
Table 2. Institutional protocol nomogram for low-dose bivalirudin protocol.
|
MCS low intensity dosing nomogram |
|
aPTT( seconds) |
Dosage adjustments |
Repeat aPTT |
|
Hold infusion |
Drip change |
CrCl > 30 mL / min |
CrCl < 30 mL / min or CRRT / iHD |
aPTT < 45 |
n / a |
Increase infusion rate by 20 % |
aPTT in 2 h |
aPTT in 4 h |
aPTT 45--60 |
n / a |
No change( therapeutic) |
aPTT in 2 h |
aPTT in 4 h |
aPTT 60.1--85 |
Hold infusion |
Decrease infusion rate by 20 % |
aPTT in 2 h |
aPTT in 4 h |
|
for 30 min |
|
|
|
aPTT 85.1--100 |
Hold infusion |
Decrease infusion rate by 30 % |
aPTT in 2 h after resuming |
aPTT in 4 h after resuming |
|
for 30 min |
|
|
|
aPTT 100.1--179.9 |
Hold infusion for 60 min |
Decrease infusion rate by 40 % |
STAT aPTT every hour until aPTT < 100, then aPTT in 2 h after resuming |
STAT aPTT every hour until aPTT < 100, then aPTT in 4 h after resuming |
aPTT > 180 |
Recheck STAT aPTT as soon as infusion held to make sure the value is not an artifact due to bivalirudin contamination |
of specimen. After obtaining follow-up aPTT, adjust via nomogram if applicable. If aPTT remains > 180, contact CT |
Surgery provider to discuss recommendations |
CRRT: Continuous renal replacement therapy; iHD: Intermittent hemodialysis.
once daily once two consecutive aPTTs are within the goal range. Therefore, the primary outcome of this study was time to two consecutive aPTTs within the therapeutic range for the initial goal range.
Safety outcomes of bleeding and venous thromboembolism( VTE) were evaluated. Bleeding was defined as a decrease in hemoglobin of at least 3 g / dL based on the definition from the pre-group( which was previously collected data) to allow for statistical comparison. Major bleeding based on the ELSO guideline, defined as a hemoglobin drop of at least 2 g / dL or transfusion of at least 10 mL / kg of packed red blood cells( PRBCs) in 24 h, was collected in the post-group only for further characterization of clinical significance [ 5 ]. Systemic VTE was defined as a newly diagnosed deep vein thrombosis, pulmonary embolism, thrombotic stroke, or intracardiac thrombus. Incidence of circuit thrombosis was assessed using twice-daily ECMO nurse specialist notes.
Secondary endpoints evaluated in the post-group included percent of aPTTs out of range after achieving two consecutive aPTTs within therapeutic range in the post group; percentage of supratherapeutic and subtherapeutic aPTT values; number of bivalirudin dose adjustments to achieve two consecutive therapeutic aPTTs; and number of bivalirudin aPTT goal adjustments. A subgroup analysis of COVID-19 patients was planned for the post-group.
Statistical analysis
Student’ s T-test or Mann-Whitney U Test was used to compare continuous variables. Medians and interquartile ranges were used in reporting non-parametric data. Categorical variables were compared using the Chi-square or Fisher’ s exact test. Statistical analysis was completed using SAS software, Version 9.4M7.
Results Baseline characteristics
There were 38 patients in the pre-group and 35 patients in the post-group. One patient in the post-group was included twice due to two separate ECMO periods. Baseline patient characteristics between groups were similar( Table 4). Forty percent