View source for Anticoagulant

__NOTOC__
{| class="infobox" style="float:right;"
|-
| [[File:Siren.gif|30px|link=Anticoagulation therapy resident survival guide]]|| <br> || <br>
| [[Anticoagulation therapy resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
|}
{{CMG}}

==Overview==
An '''anticoagulant''' is a substance that prevents [[blood coagulation|coagulation]]; that is, it stops [[blood]] from clotting. A group of pharmaceuticals called anticoagulants can be used ''in vivo'' as a medication for [[thrombosis|thrombotic]] disorders. Some chemical compounds are used in medical equipment, such as [[test tube]]s, [[blood transfusion]] bags, and renal dialysis equipment.  They also have military applications, whereby their introduction into the wounds of enemy soldiers will make their treatment significantly more difficult.

==As medications==
Anticoagulants are given to people to stop thrombosis (blood clotting inappropriately in the blood vessels). This is useful in primary and secondary prevention of [[deep vein thrombosis]], [[pulmonary embolism]], [[myocardial infarction]]s and [[stroke]]s.

==Vitamin K antagonists==
The oral anticoagulants are a class of [[pharmacology|pharmaceuticals]] that act by antagonizing the effects of [[vitamin K]]. 

Examples include:
* [[Warfarin_administration_and_monitoring|Warfarin]]

It is important to note that they take at least 48 to 72 hours for the anticoagulant effect to develop fully. In cases when any immediate effect is required, [[heparin]] must be given concomitantly. Generally, these anticoagulants are used to treat patients with [[deep-vein thrombosis]] (DVT), [[pulmonary embolism]] (PE),  [[atrial fibrillation]] (AF), and mechanical [[prosthetic heart valve]]s.

====Adverse effects====
Patients aged 80 years or more may be especially susceptible to bleeding complications with a rate of 13 bleeds per 100 person-years.<ref name="pmid17515465">{{cite journal |author=Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S |title=Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation |journal=Circulation |volume=115 |issue=21 |pages=2689-96 |year=2007 |pmid=17515465 |doi=10.1161/CIRCULATIONAHA.106.653048}}</ref>

These oral anticoagulants are used widely as poisons for mammalian pests, especially rodents. (For details, see [[rodenticide]] and [[warfarin]].)

====Available agents====
The most important oral anticoagulants are:
* [[Warfarin]] (Coumadin).  This is the main agent used in the U.S. and UK
* [[Acenocoumarol]] and [[phenprocoumon]] This is used more commonly outside the U.S. and the UK
* [[Phenindione]]

==Heparin and derivative substances==
 {{main|Heparin}}
[[Heparin]] is a biological substance, usually made from pig intestines. It works by activating [[antithrombin III]], which blocks thrombin from clotting blood. Heparin can be used ''[[in vivo]]'' (by injection), and also ''[[in vitro]]'' to prevent blood or plasma clotting in or on medical devices. Vacutainer brand test tubes containing heparin are usually colored green.

====Low molecular weight heparin====
[[Low molecular weight heparin]] is a more highly processed product that is useful as it does not require monitoring of the [[APTT]] [[coagulation]] parameter (it has more predictable plasma levels) and has fewer side effects.

====Ultra low molecular weight heparin====
[[Ultra low molecular weight heparin]]

==Direct Acting Oral Anticoagulants==
The direct acting oral anticoagulants act in various locations of the [[coagulation cascade]].

*The role of direct acting oral anticoagulants for the treatment of pulmonary embolism has been reviewed by the [[Cochrane Collaboration]].<ref name="pmid26636644">{{cite journal| author=Robertson L, Kesteven P, McCaslin JE| title=Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of pulmonary embolism. | journal=Cochrane Database Syst Rev | year= 2015 | volume= 12 | issue=  | pages= CD010957 | pmid=26636644 | doi=10.1002/14651858.CD010957.pub2 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26636644  }} </ref>
*Recommendations for safe usage have been made by [http://thrombosiscanada.ca/?p=1400 Thrombosis Canada].<ref name="pmid26121536">{{cite journal| author=Gladstone DJ, Geerts WH, Douketis J, Ivers N, Healey JS, Leblanc K| title=How to Monitor Patients Receiving Direct Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Practice Tool Endorsed by Thrombosis Canada, the Canadian Stroke Consortium, the Canadian Cardiovascular Pharmacists Network, and the Canadian Cardiovascular Society. | journal=Ann Intern Med | year= 2015 | volume= 163 | issue= 5 | pages= 382-5 | pmid=26121536 | doi=10.7326/M15-0143 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26121536  }} </ref>
* "An elevated PT for anti-Xa inhibitors and an elevated aPTT for dabigatran suggest clinically relevant drug effect at the time of testing" but "Up to 50% of people taking a direct Xa inhibitor with clinically relevant anticoagulation effect can have a normal PT"<ref>Sholzberg M, Xu Y. Coagulation Test Interpretation in a Patient Taking Direct Oral Anticoagulant Therapy. JAMA. Published online September 14, 2018. {{doi|10.1001/jama.2018.13998}}</ref>.
* These agents can probably be reversed with prothrombin complex concentrate according to case series of patients<ref name="pmid30157037">{{cite journal| author=Levy JH, Douketis J, Steiner T, Goldstein JN, Milling TJ| title=Prothrombin Complex Concentrates for Perioperative Vitamin K Antagonist and Non-vitamin K Anticoagulant Reversal. | journal=Anesthesiology | year= 2018 | volume=  | issue=  | pages=  | pmid=30157037 | doi=10.1097/ALN.0000000000002399 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30157037  }} </ref>

===Factor Xa Inhibitors===
===Direct factor Xa Inhibitors===
Factor Xa Inhibitors, "xabans" include:
* [[Apixaban]]
* [[Rivaroxaban]]

Factor Xa inhibitors can be reversed by [[andexanet]].<ref name="pmid30730782">{{cite journal| author=Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH et al.| title=Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. | journal=N Engl J Med | year= 2019 | volume= 380 | issue= 14 | pages= 1326-1335 | pmid=30730782 | doi=10.1056/NEJMoa1814051 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30730782  }} </ref><ref name="pmid26559317">{{cite journal| author=Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL et al.| title=Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. | journal=N Engl J Med | year= 2015 | volume=  | issue=  | pages=  | pmid=26559317 | doi=10.1056/NEJMoa1510991 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26559317  }} </ref>

====Pentasaccharides====
Pentasaccharides are synthetic sugar composed of the five sugars (pentasaccharide) in heparin that bind to [[antithrombin III]] and so are indirect inhibitors of [[factor Xa]]. They are smaller molecules than low molecular weight heparin. Pentasaccharides may help prevent [[venous thromboembolism]]<ref name="pmid27797404">{{cite journal| author=Dong K, Song Y, Li X, Ding J, Gao Z, Lu D et al.| title=Pentasaccharides for the prevention of venous thromboembolism. | journal=Cochrane Database Syst Rev | year= 2016 | volume= 10 | issue=  | pages= CD005134 | pmid=27797404 | doi=10.1002/14651858.CD005134.pub3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27797404  }} </ref> and [[heparin-induced thrombocytopenia]]<ref name="pmid27793877">{{cite journal| author=Aljabri A, Huckleberry Y, Karnes J, Gharaibeh M, Kutbi HI, Raz Y et al.| title=Cost-effectiveness of anticoagulants for the management of suspected heparin-induced thrombocytopenia in the US. | journal=Blood | year= 2016 | volume=  | issue=  | pages=  | pmid=27793877 | doi=10.1182/blood-2016-07-728030 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27793877  }} </ref>.

Examples include:
* [[Fondaparinux]] (short acting)
* [[Idrabiotaparinux]] (long-acting
* [[Idraparinux]] (long-acting)

===Direct thrombin inhibitors===
{{main|direct thrombin inhibitor}}
Direct thrombin inhibitors include:<ref name="pmid16148288">{{cite journal |author=Di Nisio M, Middeldorp S, Büller HR |title=Direct thrombin inhibitors |journal=N. Engl. J. Med. |volume=353 |issue=10 |pages=1028-40 |year=2005 |pmid=16148288 |doi=10.1056/NEJMra044440}}</ref>
* [[Argatroban]]
* [[Bivalirudin]]
* [[Dabigatran]]
* [[Lepirudin]]

An oral direct thrombin inhibitor, [[ximelagatran]] (Exanta®) was denied approval by the [[Food and Drug Administration]] (FDA) in September 2004 [http://www.fvleiden.org/ask/73.html] and was pulled from the market entirely in February 2006 after reports of severe liver damage and heart attacks. [http://www.astrazenecaclinicaltrials.com/article/512052.aspx]

[[Idarucizumab]]can reverse dabigatran.
===Reversal of DOACS===

A consensus statement<ref name="pmid30916798">{{cite journal| author=Cuker A, Burnett A, Triller D, Crowther M, Ansell J, Van Cott EM et al.| title=Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum. | journal=Am J Hematol | year= 2019 | volume= 94 | issue= 6 | pages= 697-709 | pmid=30916798 | doi=10.1002/ajh.25475 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30916798  }} [https://www.jwatch.org/na49227/2019/05/30/reversal-direct-oral-anticoagulants Comment in JWatch]</ref> and [[clinical practice guideline]]s are available to guide reversal decisions<ref name="pmid32750627">{{cite journal| author=Milling TJ, Pollack CV| title=A review of guidelines on anticoagulation reversal across different clinical scenarios - Is there a general consensus? | journal=Am J Emerg Med | year= 2020 | volume= 38 | issue= 9 | pages= 1890-1903 | pmid=32750627 | doi=10.1016/j.ajem.2020.05.086 | pmc=9245126 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32750627  }} </ref>.

[[Prothrombin complex concentrate]] (PCC) can reverse DOACs but can be prothrombotic.

[[Antifibrinolytic]]s such as [[tranexamic acid]] and [[epsilon-aminocaproic acid]] can reverse DOACs.

[[Ciraparantag]] ([[aripazine]]) can reverse many anticoagulants including [[Factor Xa Inhibitor]]s ([[edoxaban]]<ref name="pmid27853809">{{cite journal| author=Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso MA, Brown K | display-authors=etal| title=Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban. | journal=Thromb Haemost | year= 2017 | volume= 117 | issue= 2 | pages= 238-245 | pmid=27853809 | doi=10.1160/TH16-03-0224 | pmc=6260118 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27853809  }} </ref>) and [[heparin]]s.

====Reversal of Factor Xa Inhibitors ====

[[Andexanet Alfa]] can reverse [[Factor Xa Inhibitor]]s<ref name="pmid30730782">{{cite journal| author=Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH et al.| title=Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. | journal=N Engl J Med | year= 2019 | volume= 380 | issue= 14 | pages= 1326-1335 | pmid=30730782 | doi=10.1056/NEJMoa1814051 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30730782  }} (ANNEXA-4 trial)</ref><ref name="pmid36802876">{{cite journal| author=Milling TJ, Middeldorp S, Xu L, Koch B, Demchuk A, Eikelboom JW | display-authors=etal| title=Final Study Report of Andexanet Alfa for Major Bleeding With Factor Xa Inhibitors. | journal=Circulation | year= 2023 | volume= 147 | issue= 13 | pages= 1026-1038 | pmid=36802876 | doi=10.1161/CIRCULATIONAHA.121.057844 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=36802876  }} </ref><ref name="pmid26559317">{{cite journal| author=Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL et al.| title=Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. | journal=N Engl J Med | year= 2015 | volume=  | issue=  | pages=  | pmid=26559317 | doi=10.1056/NEJMoa1510991 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26559317  }} </ref>.

[[Ciraparantag]] ([[aripazine]]) can reverse ([[edoxaban]]<ref name="pmid27853809">{{cite journal| author=Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso MA, Brown K | display-authors=etal| title=Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban. | journal=Thromb Haemost | year= 2017 | volume= 117 | issue= 2 | pages= 238-245 | pmid=27853809 | doi=10.1160/TH16-03-0224 | pmc=6260118 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27853809  }} </ref>).

====Reversal of Direct thrombin inhibitors (DTIs) ====

[[Idarucizumab]] is a [[monoclonal antibody]] that specifically reverses [[dabigatran]]<ref name="pmid28693366">{{cite journal| author=Pollack CV, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA | display-authors=etal| title=Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. | journal=N Engl J Med | year= 2017 | volume= 377 | issue= 5 | pages= 431-441 | pmid=28693366 | doi=10.1056/NEJMoa1707278 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28693366  }} </ref><ref name="pmid26095746">{{cite journal| author=Pollack CV, Reilly PA, Eikelboom J, Glund S, Verhamme P, Bernstein RA | display-authors=etal| title=Idarucizumab for Dabigatran Reversal. | journal=N Engl J Med | year= 2015 | volume= 373 | issue= 6 | pages= 511-20 | pmid=26095746 | doi=10.1056/NEJMoa1502000 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26095746  }} </ref>.

==Anticoagulants outside the body==
[[Medical laboratory|Laboratory]] instruments, test tubes, blood transfusion bags, and medical and surgical equipment will get clogged up and become nonoperational if blood is allowed to clot. Chemicals can be added to stop blood clotting. Apart from heparin, most of these chemicals work by [[chelation|binding]] [[calcium]] ions, preventing the [[coagulation]] proteins from using them.

* [[EDTA]] is denoted by mauve or purple caps on Vacutainer brand test tubes. This chemical strongly and irreversibly binds calcium. It is in a powdered form.
* [[Citrate]] is usually in blue Vacutainer tube. It is in liquid form in the tube and is used for coagulation tests, as well as in blood transfusion bags. It gets rid of the calcium, but not as strongly as EDTA. Correct proportion of this anticoagulant to blood is crucial because of the dilution. It can be in the form of [[sodium citrate]] or [[Acid-citrate-dextrose|ACD]].
* [[Oxalate]] has a similar mechanism to citrate. It is the anticoagulant used in [[fluoride]] (grey top) tubes.

''For the meaning of more colors, see [[Vacutainer#including coagulants]].''

==References==
<references/>

==Interesting Links==
*[http://www.4s-dawn.com/dawnac Software for Managing Anticoagulation Patients]

==See also==
* [[Anticoagulation in pregnancy]]

{{Antithrombotics}}
{{Major Drug Groups}}


[[Category:Anticoagulants]]
[[Category:Drugs]]

[[ca:Anticoagulant]]
[[de:Antikoagulation]]
[[es:Anticoagulante]]
[[eu:Antikoagulante]]
[[fr:Anticoagulant]]
[[it:Anticoagulante]]
[[nl:Anticoagulans]]
[[ja:抗凝固薬]]
[[nn:Antikoagulant]]
[[pl:Leki przeciwzakrzepowe]]
[[pt:Anticoagulante]]
[[sr:Антикоагуланс]]
[[fi:Antikoagulantti]]
[[sv:Antikoagulantia]]
[[tr:Antikoagülan]]
[[uk:Антикоагулянт]]
[[ru:Антикоагулянты]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}