antithrombins

Summary

Summary: Endogenous factors and drugs that directly inhibit the action of THROMBIN, usually by blocking its enzymatic activity. They are distinguished from INDIRECT THROMBIN INHIBITORS, such as HEPARIN, which act by enhancing the inhibitory effects of antithrombins.

Top Publications

  1. Larsen T, Rasmussen L, Skjøth F, Due K, Callréus T, Rosenzweig M, et al. Efficacy and safety of dabigatran etexilate and warfarin in "real-world" patients with atrial fibrillation: a prospective nationwide cohort study. J Am Coll Cardiol. 2013;61:2264-73 pubmed publisher
    ..We found no evidence of an excess of bleeding events or MI among dabigatran-treated patients in this propensity-matched comparison against warfarin, even in the subgroup with ?1-year follow-up. ..
  2. Kadoglou N, Moustardas P, Katsimpoulas M, Kapelouzou A, Kostomitsopoulos N, Schafer K, et al. The beneficial effects of a direct thrombin inhibitor, dabigatran etexilate, on the development and stability of atherosclerotic lesions in apolipoprotein E-deficient mice : dabigatran etexilate and atherosclerosis. Cardiovasc Drugs Ther. 2012;26:367-74 pubmed publisher
    ..The plaque-stabilizing effects of chronic thrombin inhibition might be the result of the favorable modification of inflammatory mechanisms. ..
  3. Wanek M, Horn E, Elapavaluru S, Baroody S, Sokos G. Safe use of hemodialysis for dabigatran removal before cardiac surgery. Ann Pharmacother. 2012;46:e21 pubmed publisher
    ..The routine use of preoperative hemodialysis in patients on dabigatran is not recommended; however, the potential efficacy in such circumstances is supported by the successful results in this case. ..
  4. Snipelisky D, Kauffman C, Prussak K, Johns G, Venkatachalam K, Kusumoto F. A comparison of bleeding complications post-ablation between warfarin and dabigatran. J Interv Card Electrophysiol. 2012;35:29-33 pubmed publisher
    ..In our cohort, bleeding-related complications 48 h and 1 week post-ablation were similar for warfarin and dabigatran. Dabigatran is associated with more intraprocedural variability in ACT than warfarin. ..
  5. Lechtenberg B, Freund S, Huntington J. GpIbα interacts exclusively with exosite II of thrombin. J Mol Biol. 2014;426:881-93 pubmed publisher
    ..The interaction of thrombin with GpIbα thus serves to recruit thrombin activity to the platelet surface while leaving exosite I free for PAR-1 recognition. ..
  6. Figueiredo A, de Sanctis D, Gutiérrez Gallego R, Cereija T, Macedo Ribeiro S, Fuentes Prior P, et al. Unique thrombin inhibition mechanism by anophelin, an anticoagulant from the malaria vector. Proc Natl Acad Sci U S A. 2012;109:E3649-58 pubmed publisher
    ..These findings have implications for the design of novel antithrombotics. ..
  7. Mosier P, Krishnasamy C, Kellogg G, Desai U. On the specificity of heparin/heparan sulfate binding to proteins. Anion-binding sites on antithrombin and thrombin are fundamentally different. PLoS ONE. 2012;7:e48632 pubmed publisher
    ..This provides a foundation for understanding specificity of interaction at an atomic level, which will greatly aid the design of natural or synthetic H/HS sequences that target proteins in a specific manner. ..
  8. Spannagl M, Bauersachs R, Debus E, Gawaz M, Gerlach H, Haas S, et al. [Dabigatran therapy--perioperative management and interpretation of coagulation tests]. Hamostaseologie. 2012;32:294-305 pubmed publisher
    ..A distinct feature of dabigatran is the possibility of effectively removing dabigatran from the circulation by haemodialysis...
  9. Morrow D. Antithrombotic therapy to support primary PCI. N Engl J Med. 2008;358:2280-2 pubmed publisher

More Information

Publications67

  1. Zhang D, Wang Z, Zhao X, Lu W, Gu J, Cui Y. Pharmacokinetics, pharmacodynamics, tolerability and safety of single doses of bivalirudin in healthy chinese subjects. Biol Pharm Bull. 2011;34:1841-8 pubmed
    ..The findings of this study suggest that the same dosing regimens of bivalirudin may be administered to Chinese and Caucasian patients. Ongoing and future studies in large populations may add further information. ..
  2. Feistritzer C, Kaneider N, Sturn D, Wiedermann C. Syndecan-4-dependent migration of human eosinophils. Clin Exp Allergy. 2004;34:696-703 pubmed
    ..Ligation of syndecan-4 with anti-thrombin III induces eosinophil migration and deactivates motility toward chemokines. These observations suggest that syndecan-4-dependent signalling may control eosinophil locomotion. ..
  3. Anton A, Teruel R, Corral J, Minano A, Martínez Martínez I, Ordonez A, et al. Functional consequences of the prothrombotic SERPINC1 rs2227589 polymorphism on antithrombin levels. Haematologica. 2009;94:589-92 pubmed publisher
    ..6%; p=0.001; respectively). Our results identified a functional effect of the rs2227589 polymorphism not explained by its linkage with the promoter polymorphism that support the moderate thrombotic risk associated with the A allele. ..
  4. Arora U, Dhir M. Direct thrombin inhibitors (part 1 of 2). J Invasive Cardiol. 2005;17:34-8 pubmed
  5. Dementiev A, Petitou M, Herbert J, Gettins P. The ternary complex of antithrombin-anhydrothrombin-heparin reveals the basis of inhibitor specificity. Nat Struct Mol Biol. 2004;11:863-7 pubmed
    ..The protein-protein and protein-oligosaccharide interactions together explain the basis for heparin activation of antithrombin as a thrombin inhibitor. ..
  6. Srivastava S, Goswami L, Dikshit D. Progress in the design of low molecular weight thrombin inhibitors. Med Res Rev. 2005;25:66-92 pubmed
    ..Recent developments in small molecule inhibitors of Protease Activated Receptor-1 (PAR-1) which can be helpful for the treatment of thrombotic and vascular proliferative disorders, have also been discussed. ..
  7. Eriksson B, Dahl O, Huo M, Kurth A, Hantel S, Hermansson K, et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, double-blind, non-inferiority trial. Thromb Haemost. 2011;105:721-9 pubmed publisher
    ..The risk of bleeding and safety profiles were similar. ..
  8. Undas A, Gissel M, Kwasny Krochin B, Gluszko P, Mann K, Brummel Ziedins K. Thrombin generation in rheumatoid arthritis: dependence on plasma factor composition. Thromb Haemost. 2010;104:224-30 pubmed publisher
    ..Simulations of thrombin formation suggest that blood plasma composition, i.e. a marked increase in FVIII, somewhat counterbalanced by free TFPI, contributes to the prothrombotic phenotype in RA patients. ..
  9. Chappell D, Jacob M, Hofmann Kiefer K, Rehm M, Welsch U, Conzen P, et al. Antithrombin reduces shedding of the endothelial glycocalyx following ischaemia/reperfusion. Cardiovasc Res. 2009;83:388-96 pubmed publisher
    ..We investigated the influence of antithrombin on glycocalyx subjected to ischaemia/reperfusion...
  10. Lincoff A, Bittl J, Kleiman N, Sarembock I, Jackman J, Mehta S, et al. Comparison of bivalirudin versus heparin during percutaneous coronary intervention (the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events [REPLACE]-1 trial). Am J Cardiol. 2004;93:1092-6 pubmed
    ..52). This trial represents the largest prospective dataset of bivalirudin administered concomitantly with planned GP IIb/IIIa blockade and provides evidence of the safety and efficacy of this combined antithrombotic approach. ..
  11. Oldgren J, Alings M, Darius H, Diener H, Eikelboom J, Ezekowitz M, et al. Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in relation to the CHADS2 score: a subgroup analysis of the RE-LY trial. Ann Intern Med. 2011;155:660-7, W204 pubmed publisher
    ..Higher CHADS(2) scores were associated with increased risks for stroke or systemic embolism, bleeding, and death in patients with atrial fibrillation receiving oral anticoagulants. Boehringer Ingelheim. ..
  12. Figueiredo A, Clement C, Zakia S, Gingold J, Philipp M, Pereira P. Rational design and characterization of D-Phe-Pro-D-Arg-derived direct thrombin inhibitors. PLoS ONE. 2012;7:e34354 pubmed publisher
  13. Iba T, Saito D, Wada H, Asakura H. Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: a prospective multicenter survey. Thromb Res. 2012;130:e129-33 pubmed publisher
    ..The risk of severe bleeding is less than 2%, and concomitant administration of heparin did not increase the risk. The survival in AT1500 group was 65.2%, while that in AT3000 group was 74.7%. ..
  14. Langdown J, Belzar K, Savory W, Baglin T, Huntington J. The critical role of hinge-region expulsion in the induced-fit heparin binding mechanism of antithrombin. J Mol Biol. 2009;386:1278-89 pubmed
    ..A new analysis of the individual structural changes provides a plausible mechanism for propagation of conformational change from the heparin binding site to the remote hinge region in beta-sheet A. ..
  15. Di Nisio M, Middeldorp S, Buller H. Direct thrombin inhibitors. N Engl J Med. 2005;353:1028-40 pubmed
  16. Nielsen V, Lyerly R, Gurley W. The effect of dilution on plasma coagulation kinetics determined by thrombelastography is dependent on antithrombin activity and mode of activation. Anesth Analg. 2004;99:1587-92, table of contents pubmed
    ..Thus, our data indirectly support the concept that decreases in AT activity cause dilution-mediated hypercoagulability in plasma. Finally, celite activation permits quantification of dilution with TEG. ..
  17. Li W, Johnson D, Esmon C, Huntington J. Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin. Nat Struct Mol Biol. 2004;11:857-62 pubmed
    ..A notably close contact interface, comprised of extensive active site and exosite interactions, explains, in molecular detail, the basis of the antithrombotic properties of therapeutic heparin. ..
  18. Uchiba M, Okajima K, Kaun C, Wojta J, Binder B. Inhibition of the endothelial cell activation by antithrombin in vitro. Thromb Haemost. 2004;92:1420-7 pubmed
    ..Such an inhibitory effect of AT on TNF-alpha-induced endothelial cell activation might at least partly contribute to its anti-inflammatory activity. ..
  19. Testa L, Bhindi R, Agostoni P, Abbate A, Zoccai G, van Gaal W. The direct thrombin inhibitor ximelagatran/melagatran: a systematic review on clinical applications and an evidence based assessment of risk benefit profile. Expert Opin Drug Saf. 2007;6:397-406 pubmed
    ..According to individual clinical settings, X/M was associated with a lower risk of MB but a prohibitive higher risk of HT in those clinical settings requiring prolonged treatment. ..
  20. Weitz J. Factor Xa or thrombin: is thrombin a better target?. J Thromb Haemost. 2007;5 Suppl 1:65-7 pubmed
    ..Several oral factor Xa inhibitors also are being tested. Is thrombin a better target for new oral anticoagulants than factor Xa? Only time will tell! ..
  21. Warkentin T. Bivalent direct thrombin inhibitors: hirudin and bivalirudin. Best Pract Res Clin Haematol. 2004;17:105-25 pubmed
    ..Further work is required to define the scope of clinical thrombosis problems that could benefit from these novel agents. ..
  22. Schoots I, Levi M, van Vliet A, Maas A, Roossink E, van Gulik T. Inhibition of coagulation and inflammation by activated protein C or antithrombin reduces intestinal ischemia/reperfusion injury in rats. Crit Care Med. 2004;32:1375-83 pubmed
    ..These observations suggest that activated protein C or antithrombin reduces ischemia/reperfusion-induced intestinal injury, both through their anticoagulant and anti-inflammatory effects. ..
  23. Yang Y, Chien D, Wu M, FitzGerald J, Grossman J, Hahn B, et al. Novel autoantibodies against the activated coagulation factor IX (FIXa) in the antiphospholipid syndrome that interpose the FIXa regulation by antithrombin. J Immunol. 2009;182:1674-80 pubmed
    ..Because FIXa is an upstream procoagulant factor, impaired AT regulation of FIXa might contribute more toward thrombosis than the dysregulation of the downstream FXa and thrombin. ..
  24. Gonano C, Sitzwohl C, Meitner E, Weinstabl C, Kettner S. Four-day antithrombin therapy does not seem to attenuate hypercoagulability in patients suffering from sepsis. Crit Care. 2006;10:R160 pubmed
    ..This finding supports recent data showing that modulation of coagulatory activation in septic patients by AT does not occur before one week of therapy. ..
  25. Fareed J, Jeske W. Small-molecule direct antithrombins: argatroban. Best Pract Res Clin Haematol. 2004;17:127-38 pubmed
  26. Corral Rodríguez M, Bock P, Hernández Carvajal E, Gutiérrez Gallego R, Fuentes Prior P. Structural basis of thrombin-mediated factor V activation: the Glu666-Glu672 sequence is critical for processing at the heavy chain-B domain junction. Blood. 2011;117:7164-73 pubmed publisher
    ..Modeling experiments indicate that FVa2, and likely also FVa3, wrap around thrombin in productive thrombin·FV complexes that cover a large surface of the activator to engage the active site. ..
  27. Isaacs R, Newton C, Cutrona K, Mercer S, Payne L, Stauffer K, et al. Design, synthesis and SAR of a series of 1,3,5-trisubstituted benzenes as thrombin inhibitors. Bioorg Med Chem Lett. 2011;21:1536-40 pubmed publisher
    ..Optimization of this lead afforded a novel potent series of biaryl 1,3,5-trisubstituted benzenes with excellent functional anticoagulant potency. ..
  28. Iba T, Kidokoro A, Fukunaga M, Nagakari K, Suda M, Yoshikawa S, et al. Antithrombin ameliorates endotoxin-induced organ dysfunction more efficiently when combined with danaparoid sodium than with unfractionated heparin. Intensive Care Med. 2005;31:1101-8 pubmed
    ..The elevation of ALT and BUN significantly improved only in the AT/DA group. ONCLUSION: Organ dysfunction can thus be alleviated by even moderate doses of AT replacement when co-administered with DA. ..
  29. Lehr T, Haertter S, Liesenfeld K, Staab A, Clemens A, Reilly P, et al. Dabigatran etexilate in atrial fibrillation patients with severe renal impairment: dose identification using pharmacokinetic modeling and simulation. J Clin Pharmacol. 2012;52:1373-8 pubmed publisher
  30. Boekholdt S, Kramer M. Arterial thrombosis and the role of thrombophilia. Semin Thromb Hemost. 2007;33:588-96 pubmed
    ..We conclude that thrombophilia screening in unselected patient populations with myocardial infarction or ischemic stroke is not justified. ..
  31. Ganetsky M, Babu K, Salhanick S, Brown R, Boyer E. Dabigatran: review of pharmacology and management of bleeding complications of this novel oral anticoagulant. J Med Toxicol. 2011;7:281-7 pubmed publisher
    ..We present an article that reviews the pharmacokinetics, clinical trial literature, and consensus guidelines regarding this novel oral anticoagulant. ..
  32. Lau A, Berry L, Mitchell L, Chan A. Effect of substrate and fibrin polymerization inhibitor on determination of plasma thrombin generation in vitro. Thromb Res. 2007;119:667-77 pubmed
    ..In vitro plasma thrombin generation is delayed and increased by slow-acting substrate and fibrin polymerization inhibitor. ..
  33. Levi M, van der Poll T. Inflammation and coagulation. Crit Care Med. 2010;38:S26-34 pubmed publisher
    ..Conversely, activated coagulation proteases may affect specific cellular receptors on inflammatory cells and endothelial cells and thereby modulate the inflammatory response. ..
  34. Iba T, Nakarai E, Takayama T, Nakajima K, Sasaoka T, Ohno Y. Combination effect of antithrombin and recombinant human soluble thrombomodulin in a lipopolysaccharide induced rat sepsis model. Crit Care. 2009;13:R203 pubmed publisher
    ..Survival was significantly better only in AT/TM group (P < 0.01). The coadministration of AT and rhsTM might be effective for the treatment of severe sepsis. ..
  35. Zocco M, Di Stasio E, De Cristofaro R, Novi M, Ainora M, Ponziani F, et al. Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development. J Hepatol. 2009;51:682-9 pubmed publisher
    ..A reduced portal flow velocity seems to be the most important predictive variable for PVT development in patients with cirrhosis. ..
  36. Chang X, Yamada R, Sawada T, Suzuki A, Kochi Y, Yamamoto K. The inhibition of antithrombin by peptidylarginine deiminase 4 may contribute to pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2005;44:293-8 pubmed
    ..Local inhibition of antithrombin activity in RA synovium might lead to the excessive angiogenesis, fibrin deposition and inflammation of the tissue. ..
  37. Guerrero J, Teruel R, Martinez C, Arcas I, Martínez Martínez I, de la Morena Barrio M, et al. Protective role of antithrombin in mouse models of liver injury. J Hepatol. 2012;57:980-6 pubmed publisher
    ..AT may also act via a previously unrecognized antiapoptotic effect. The clinical implications of AT deficiency in patients with liver disease should be further addressed. ..
  38. Hohnloser S, Oldgren J, Yang S, Wallentin L, Ezekowitz M, Reilly P, et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation. 2012;125:669-76 pubmed publisher
    ..Treatment effects of dabigatran were consistent in patients at higher and lower risk of myocardial ischemic events. ..
  39. Lee I, Kratz M, Schirmer S, Baumhakel M, Bohm M. The effects of direct thrombin inhibition with dabigatran on plaque formation and endothelial function in apolipoprotein E-deficient mice. J Pharmacol Exp Ther. 2012;343:253-7 pubmed publisher
    ..Interference with the coagulation system might provide a therapeutic target to modify atherosclerotic disease progression. ..
  40. Taoka Y, Okajima K, Uchiba M. Antithrombin reduces compression-induced spinal cord injury in rats. J Neurotrauma. 2004;21:1818-30 pubmed
    ..Such therapeutic effects of AT might be mediated by its promoting the endothelial release of PGI2. These findings strongly suggest AT as a potential agent for treating SCI in the clinical setting. ..
  41. Kaneider N, Feistritzer C, Gritti D, Mosheimer B, Ricevuti G, Patsch J, et al. Expression and function of syndecan-4 in human platelets. Thromb Haemost. 2005;93:1120-7 pubmed
    ..From these data it is concluded that syndecan-4 may play important roles in the regulation of inflammatory effects of platelets. ..
  42. Gibson C, Morrow D, Murphy S, Palabrica T, Jennings L, Stone P, et al. A randomized trial to evaluate the relative protection against post-percutaneous coronary intervention microvascular dysfunction, ischemia, and inflammation among antiplatelet and antithrombotic agents: the PROTECT-TIMI-30 trial. J Am Coll Cardiol. 2006;47:2364-73 pubmed
    ..Ischemic events and biomarkers for myonecrosis, inflammation, and thrombin generation did not differ between agents. ..
  43. Choi G, Vlaar A, Schouten M, Van T Veer C, van der Poll T, Levi M, et al. Natural anticoagulants limit lipopolysaccharide-induced pulmonary coagulation but not inflammation. Eur Respir J. 2007;30:423-8 pubmed
    ..Natural inhibitors of coagulation prevent bronchoalveolar activation of coagulation, but do not induce major alterations of the pulmonary inflammatory response in rat endotoxaemia. ..
  44. Stone G, Witzenbichler B, Guagliumi G, Peruga J, Brodie B, Dudek D, et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med. 2008;358:2218-30 pubmed publisher
    ..ClinicalTrials.gov number, NCT00433966 [ClinicalTrials.gov].). ..
  45. Henry B, Connell J, Liang A, Krishnasamy C, Desai U. Interaction of antithrombin with sulfated, low molecular weight lignins: opportunities for potent, selective modulation of antithrombin function. J Biol Chem. 2009;284:20897-908 pubmed publisher
  46. Witzenbichler B, Mehran R, Guagliumi G, Dudek D, Huber K, Kornowski R, et al. Impact of diabetes mellitus on the safety and effectiveness of bivalirudin in patients with acute myocardial infarction undergoing primary angioplasty: analysis from the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute My. JACC Cardiovasc Interv. 2011;4:760-8 pubmed publisher
    ..Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966). ..
  47. Choi G, Hofstra J, Roelofs J, Rijneveld A, Bresser P, van der Zee J, et al. Antithrombin inhibits bronchoalveolar activation of coagulation and limits lung injury during Streptococcus pneumoniae pneumonia in rats. Crit Care Med. 2008;36:204-10 pubmed
    ..Anticoagulant treatment attenuates pulmonary coagulopathy during S. pneumoniae pneumonia. Antithrombin seems to exert significant lung-protective effects in pneumococcal pneumonia in rats. ..
  48. Stella J, Stella R, Iaffaldano R, Stella D, Erickson K, Bliley R. Anticoagulation with bivalirudin during percutaneous coronary intervention for ST-segment elevation myocardial infarction. J Invasive Cardiol. 2004;16:451-4 pubmed
  49. Parodi G, Antoniucci D, Nikolsky E, Witzenbichler B, Guagliumi G, Peruga J, et al. Impact of bivalirudin therapy in high-risk patients with acute myocardial infarction: 1-year results from the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial. JACC Cardiovasc Interv. 2010;3:796-802 pubmed publisher
    ..HORIZONS-AMI trial; NCT00433966). ..
  50. Eres A. Use of bivalirudin as the foundation anticoagulant during percutaneous peripheral interventions. J Invasive Cardiol. 2006;18:125-8 pubmed
    ..Ischemic and bleeding events were low and comparable to those reported in the literature, suggesting that bivalirudin is safe to use in this population. ..
  51. Lee C, Ansell J. Direct thrombin inhibitors. Br J Clin Pharmacol. 2011;72:581-92 pubmed publisher
    ..This review discusses the clinical indications and efficacy of these direct thrombin inhibitors as well as future directions in anticoagulant therapy. ..
  52. Sinauridze E, Romanov A, Gribkova I, Kondakova O, Surov S, Gorbatenko A, et al. New synthetic thrombin inhibitors: molecular design and experimental verification. PLoS ONE. 2011;6:e19969 pubmed publisher
    ..5 years at room temperature and at 4°C. The high efficacy, stability and low acute toxicity reveal that the inhibitors that were developed may be promising for potential medical applications. ..
  53. Koh C, Kumar S, Kazimirova M, Nuttall P, Radhakrishnan U, Kim S, et al. Crystal structure of thrombin in complex with S-variegin: insights of a novel mechanism of inhibition and design of tunable thrombin inhibitors. PLoS ONE. 2011;6:e26367 pubmed publisher
    ..Our results encourage that variegin and the variants show strong potential for the development of tunable anticoagulants. ..
  54. Kaseno K, Naito S, Nakamura K, Sakamoto T, Sasaki T, Tsukada N, et al. Efficacy and safety of periprocedural dabigatran in patients undergoing catheter ablation of atrial fibrillation. Circ J. 2012;76:2337-42 pubmed
    ..9%; P<0.05). ?Dabigatran at a dose of 110mg twice daily was safe for AF ablation in patients with a relatively low risk of thromboemboli, suggesting that it may become an alternative to warfarin in those patients. ..
  55. Babuin L, Pengo V. Argatroban in the management of heparin-induced thrombocytopenia. Vasc Health Risk Manag. 2010;6:813-9 pubmed
    ..The investigators performed a pooled analysis of these studies, which showed that most (?95%) patients achieved a satisfactory outcome from the procedure and adequate anticoagulation (coprimary end points). ..
  56. Okabayashi K, Wada H, Ohta S, Shiku H, Nobori T, Maruyama K. Hemostatic markers and the sepsis-related organ failure assessment score in patients with disseminated intravascular coagulation in an intensive care unit. Am J Hematol. 2004;76:225-9 pubmed
    ..We conclude that the SOFA score is useful for predicting outcome in DIC patients in the ICU, and that hemostatic parameters, especially plasma AT levels, are also useful markers for organ failure and clinical outcome. ..
  57. Huntington J. Shape-shifting serpins--advantages of a mobile mechanism. Trends Biochem Sci. 2006;31:427-35 pubmed
    ..Recent crystal structures reveal the intricate conformational rearrangements involved in protease inhibition, activity modulation and the unique molecular pathology of the remarkable shape-shifting serpins. ..
  58. Raghuraman A, Mosier P, Desai U. Finding a needle in a haystack: development of a combinatorial virtual screening approach for identifying high specificity heparin/heparan sulfate sequence(s). J Med Chem. 2006;49:3553-62 pubmed