Bivalirudin
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Bivalirudin

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Bivalirudin is a specific and reversible direct thrombin inhibitor (DTI). It is a synthetic congener of the naturally occurring drug hirudin. It is a DTI that overcomes many limitations seen with indirect thrombin inhibitors, such as heparin. It is a short, synthetic peptide that is potent, highly specific, and a reversible inhibitor of thrombin. It inhibits both circulating and clot-bound thrombin, while also inhibiting thrombin-mediated platelet activation and aggregation. It has a quick onset of action and a short half-life. It does not bind to plasma proteins (other than thrombin) or to red blood cells. Therefore, it has a predictable antithrombotic response. It does not require a binding cofactor such as antithrombin and does not activate platelets.

Category
Peptide Inhibitors
Catalog number
BAT-010039
CAS number
128270-60-0
Molecular Formula
C98H138N24O33
Molecular Weight
2180.32
Bivalirudin
IUPAC Name
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[2-[[2-[[2-[[2-[[(2S)-1-[(2S)-2-[[(2S)-1-[(2R)-2-amino-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]acetyl]amino]acetyl]amino]acetyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-carboxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoic acid
Synonyms
Hirulog; Hirulog I; Angiomax; Hirulog-1; Hirulog1; Hirulog 1; BG8967; BG 8967; BG-8967; LS-172701; LS172701; LS 172701
Appearance
White to Off-white Powder
Purity
> 95%
Density
1.52 g/cm3
Sequence
FPRPGGGGNGDFEEIPEEYL
Storage
Store at -20°C
Solubility
Soluble in DMSO
InChI
InChI=1S/C98H138N24O33/c1-5-52(4)82(96(153)122-39-15-23-70(122)92(149)114-60(30-34-79(134)135)85(142)111-59(29-33-78(132)133)86(143)116-64(43-55-24-26-56(123)27-25-55)89(146)118-67(97(154)155)40-51(2)3)119-87(144)61(31-35-80(136)137)112-84(141)58(28-32-77(130)131)113-88(145)63(42-54-18-10-7-11-19-54)117-90(147)66(45-81(138)139)110-76(129)50-107-83(140)65(44-71(100)124)109-75(128)49-106-73(126)47-104-72(125)46-105-74(127)48-108-91(148)68-21-13-38-121(68)95(152)62(20-12-36-103-98(101)102)115-93(150)69-22-14-37-120(69)94(151)57(99)41-53-16-8-6-9-17-53/h6-11,16-19,24-27,51-52,57-70,82,123H,5,12-15,20-23,28-50,99H2,1-4H3,(H2,100,124)(H,104,125)(H,105,127)(H,106,126)(H,107,140)(H,108,148)(H,109,128)(H,110,129)(H,111,142)(H,112,141)(H,113,145)(H,114,149)(H,115,150)(H,116,143)(H,117,147)(H,118,146)(H,119,144)(H,130,131)(H,132,133)(H,134,135)(H,136,137)(H,138,139)(H,154,155)(H4,101,102,103)/t52-,57+,58-,59-,60-,61-,62-,63-,64-,65-,66-,67-,68-,69-,70-,82-/m0/s1
InChI Key
OIRCOABEOLEUMC-GEJPAHFPSA-N
Canonical SMILES
CCC(C)C(C(=O)N1CCCC1C(=O)NC(CCC(=O)O)C(=O)NC(CCC(=O)O)C(=O)NC(CC2=CC=C(C=C2)O)C(=O)NC(CC(C)C)C(=O)O)NC(=O)C(CCC(=O)O)NC(=O)C(CCC(=O)O)NC(=O)C(CC3=CC=CC=C3)NC(=O)C(CC(=O)O)NC(=O)CNC(=O)C(CC(=O)N)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)C4CCCN4C(=O)C(CCCNC(=N)N)NC(=O)C5CCCN5C(=O)C(CC6=CC=CC=C6)N
1. Comparison of Anticoagulation Strategies in Patients Requiring Venovenous Extracorporeal Membrane Oxygenation: Heparin Versus Bivalirudin
Ryan M Rivosecchi, Aris R Arakelians, John Ryan, Holt Murray, Raj Ramanan, Hernando Gomez, Dennis Phillips, Christopher Sciortino, Peter Arlia, Danielle Freeman, Penny L Sappington, Pablo G Sanchez Crit Care Med. 2021 Jul 1;49(7):1129-1136. doi: 10.1097/CCM.0000000000004944.
Objectives: Extracorporeal membrane oxygenation is a life-sustaining therapy for severe respiratory failure. Extracorporeal membrane oxygenation circuits require systemic anticoagulation that creates a delicate balance between circuit-related thrombosis and bleeding-related complications. Although unfractionated heparin is most widely used anticoagulant, alternative agents such as bivalirudin have been used. We sought to compare extracorporeal membrane oxygenation circuit thrombosis and bleeding-related outcomes in respiratory failure patients receiving either unfractionated heparin or bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation support. Design: Retrospective cohort study. Setting: Single-center, cardiothoracic ICU. Patients: Consecutive patients requiring venovenous extracorporeal membrane oxygenation who were maintained on anticoagulation between 2013 and 2020. Internventions: IV bivalirudin or IV unfractionated heparin. Measurements and main results: Primary outcomes were the presence of extracorporeal membrane oxygenation in-circuit-related thrombotic complications and volume of blood products administered during extracorporeal membrane oxygenation duration. One hundred sixty-two patients receiving unfractionated heparin were compared with 133 patients receiving bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation. In patients receiving bivalirudin, there was an overall decrease in the number of extracorporeal membrane oxygenation circuit thrombotic complications (p < 0.005) and a significant increase in time to circuit thrombosis (p = 0.007). Multivariable Cox regression found that heparin was associated with a significant increase in risk of clots (Exp[B] = 2.31, p = 0.001). Patients who received bivalirudin received significantly less volume of packed RBCs, fresh frozen plasma, and platelet transfusion (p < 0.001 for each). There was a significant decrease in the number major bleeding events in patients receiving bivalirudin, 40.7% versus 11.7%, p < 0.001. Conclusions: Patients receiving bivalirudin for systemic anticoagulation on venovenous extracorporeal membrane oxygenation experienced a decrease in the number of extracorporeal membrane oxygenation circuit-related thrombotic events as well as a significant decrease in volume of blood products administered.
2. Bivalirudin in pediatric extracorporeal membrane oxygenation
Lindsay M Ryerson, Ali B V McMichael Curr Opin Pediatr. 2022 Jun 1;34(3):255-260. doi: 10.1097/MOP.0000000000001131.
Purpose of review: This review summarizes the current literature surrounding the use of bivalirudin as an alternative anticoagulant for pediatric extracorporeal membrane oxygenation (ECMO) patients. Recent findings: Recent single center studies describe that bivalirudin may be associated with decreased blood product transfusion, decreased cost and similar clinical outcomes for pediatric ECMO patients who have failed unfractionated heparin (UFH) anticoagulation. aPTT is the most common test to monitor bivalirudin but has several limitations. Other tests including dilute thrombin time (dTT) and viscoelastic assays are promising but more study is needed. Current evidence suggests that bivalirudin is a well tolerated and effective alternative anticoagulant for pediatric ECMO patients who have failed UFH anticoagulation but prospective studies are needed to confirm these results. Summary: Bivalirudin is a promising alternative anticoagulant for pediatric ECMO patients who have failed UFH. Large prospective, multicenter studies are needed to confirm safety and efficacy.
3. Comparison of Bivalirudin Versus Heparin for Maintenance Systemic Anticoagulation During Adult and Pediatric Extracorporeal Membrane Oxygenation
Troy G Seelhammer, John K Bohman, Phillip J Schulte, Andrew C Hanson, Devon O Aganga Crit Care Med. 2021 Sep 1;49(9):1481-1492. doi: 10.1097/CCM.0000000000005033.
Objectives: To provide a comparative analysis of conventional heparin-versus bivalirudin-based systemic anticoagulation in adult and pediatric patients supported on extracorporeal membrane oxygenation. Design: Retrospective chart review study of adult and pediatric patients receiving extracorporeal membrane oxygenation from January 1, 2014, to October 1, 2019. Setting: A large, high-volume tertiary referral adult and pediatric extracorporeal membrane oxygenation center. Patients: Four hundred twenty-four individuals requiring extracorporeal membrane oxygenation support and systemically anticoagulated with either unfractionated heparin (223 adult and 65 pediatric patients) or bivalirudin (110 adult and 24 pediatric patients) were included. Interventions: None. Measurements and main results: Digital data abstraction was used to retrospectively collect patient details. The majority of both groups were cannulated centrally (67%), and the extracorporeal membrane oxygenation type was predominantly venoarterial (84%). The adult bivalirudin group had a greater occurrence of heparin-induced thrombocytopenia (12% vs 1%; p < 0.01) and was more likely to require postcardiotomy extracorporeal membrane oxygenation (36% vs 55%; p < 0.01). There were no statistical differences between the groups in regards to age, sex, and extracorporeal membrane oxygenation initiation location. The main finding was a reduced mortality in the adult bivalirudin group (odds ratio, 0.39; p < 0.01), whereas no difference was noted in the pediatric group. A significant reduction in the composite transfusion requirement in the first 24 hours was noted in the pediatric bivaluridin group with an odds ratio of 0.28 (p = 0.02). Groups did not differ in regard to laboratories per day, anticoagulant dose adjustments, or ischemic complications. Conclusions: When compared with heparin-based systemic anticoagulation, bivalirudin demonstrated feasibility and safety as established by the absence of increases in identifiable adverse outcomes while manifesting substantial improvements in hospital mortality in adult patients. Further studies are necessary to corroborate these findings and further elucidate the role of bivalirudin during extracorporeal membrane oxygenation support.
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