Editing Anticoagulant (section)

==Types==
Several anticoagulants are available. Warfarin, other coumarins, and heparins have long been used.<ref>{{cite journal|last1=Di Minno|first1=Alessandro|last2=Frigerio|first2=Beatrice|last3=Spadarella|first3=Gaia|last4=Ravani|first4=Alessio|last5=Sansaro|first5=Daniela|last6=Amato|first6=Mauro|last7=Kitzmiller|first7=Joseph P.|last8=Pepi|first8=Mauro|last9=Tremoli|first9=Elena|last10=Baldassarre|first10=Damiano|date=July 2017|title=Old and new oral anticoagulants: Food, herbal medicines and drug interactions|journal=Blood Reviews|language=en|volume=31|issue=4|pages=193–203|doi=10.1016/j.blre.2017.02.001|pmid=28196633|doi-access=free|hdl=2434/476466|hdl-access=free}}</ref> Since the 2000s, several agents have been introduced that are collectively referred to as '''direct oral anticoagulants''' ('''DOACs'''), previously named '''novel oral anticoagulants''' ('''NOACs''') or '''non-vitamin K antagonist oral anticoagulants'''.<ref>{{cite journal|last1=Almarshad|first1=Feras|last2=Alaklabi|first2=Ali|last3=Bakhsh|first3=Ebtisam|last4=Pathan|first4=Aslam|last5=Almegren|first5=Mosaad|date=December 2018|title=Use of direct oral anticoagulants in daily practice|journal=American Journal of Blood Research|language=en|volume=8|issue=4|pages=57–72|pmid=30697449|pmc=6334188 }}</ref><ref>{{cite journal|last1=Verdecchia|first1=Paolo|last2=Angeli|first2=Fabio|last3=Aita|first3=Adolfo|last4=Bartolini|first4=Claudia|last5=Reboldi|first5=Gianpaolo|date=April 2016|title=Why switch from warfarin to NOACs?|journal=Internal and Emergency Medicine|language=en|volume=11|issue=3|pages=289–93|doi=10.1007/s11739-016-1411-0|pmid=26972708|s2cid=25807727|issn=1828-0447}}</ref><ref>{{cite journal|last1=Diener|first1=Hans-Christoph|last2=Ntaios|first2=George|last3=O'Donnell|first3=Martin|last4=Easton|first4=J. Donald|date=2018-09-22|title=Non-vitamin-K oral anticoagulants (NOACs) for the prevention of secondary stroke|journal=Expert Opinion on Pharmacotherapy|language=en|volume=19|issue=14|pages=1597–1602|doi=10.1080/14656566.2018.1515913|pmid=30152249|s2cid=52099757|issn=1465-6566}}</ref><ref>{{cite journal|last1=Pol|first1=Derk|last2=Curtis|first2=Claire|last3=Ramkumar|first3=Satish|last4=Bittinger|first4=Logan|date=April 2019|title=NOACs Now Mainstream for the Use of Anticoagulation in Non-Valvular Atrial Fibrillation in Australia|journal=Heart, Lung and Circulation|language=en|volume=28|issue=4|pages=e40–e42|doi=10.1016/j.hlc.2018.03.010|pmid=29861320|s2cid=44103560}}</ref> These agents include direct thrombin inhibitor ([[dabigatran]]) and factor Xa inhibitor ([[rivaroxaban]], [[apixaban]], [[betrixaban]] and [[edoxaban]]), and they have been shown to be as good or possibly better than the coumarins with less serious side effects.<ref>{{cite journal | vauthors = Werdan K, Braun-Dullaeus R, Presek P | title = Anticoagulation in atrial fibrillation: NOAC's the word | journal = Deutsches Ärzteblatt International | volume = 110 | issue = 31–32 | pages = 523–4 | date = August 2013 | pmid = 24069072 | pmc = 3782018 | doi = 10.3238/arztebl.2013.0523 | quote = Things have changed dramatically with the introduction of the new oral anticoagulants (NOACs) – dabigatran, a factor IIa (thrombin) inhibitor, and the factor Xa inhibitors rivaroxaban and apixaban. Clinical trials have shown them therapeutically superior, or at least non-inferior, to VKAs, with less serious side effects. }}</ref> The newer anticoagulants (NOACs/DOACs) are more expensive than the traditional ones and should be used in caring for patients with kidney problems.<ref>{{cite journal|last1=Heine|first1=Gunnar H.|last2=Brandenburg|first2=Vincent|last3=Schirmer|first3=Stephan H.|date=2018-04-27|title=Orale Antikoagulation bei chronischer Nierenerkrankung und Vorhofflimmern|journal=Deutsches Ärzteblatt Online|volume=115|issue=17|pages=287–94|doi=10.3238/arztebl.2018.0287|issn=1866-0452|pmc=5974258|pmid=29789105}}</ref>

===Coumarins (vitamin K antagonists)===<!--this section heading is linked to from [[Warfarin]]-->
{{Further|Vitamin K antagonist}}
These oral anticoagulants are derived from [[coumarin]] found in many plants. A prominent member of this class, [[warfarin]] (Coumadin), was found to be the anticoagulant most prescribed in a large multispecialty practice.<ref>{{Cite journal |vauthors=Efird LE, Chasler J, Alexander GC, McGuire M |date=Jun 21, 2016 |title=Prescribing Patterns of Novel Anticoagulants Within a Statewide Multispecialty Practice |url=https://www.pharmacytimes.com/view/prescribing-patterns-of-novel-anticoagulants-within-a-statewide-multispecialty-practice |journal=American Journal of Pharmacy Benefits |volume=8 |issue=3 |pages=97–102}}</ref> The anticoagulant effect takes at least 48 to 72 hours to develop. Where an immediate effect is required, [[heparin]] is given concomitantly. These anticoagulants are used to treat patients with [[deep-vein thrombosis]] (DVT) and [[pulmonary embolism]] (PE) and to prevent emboli in patients with [[atrial fibrillation]] (AF), and mechanical [[prosthetic heart valve]]s. Other examples are [[acenocoumarol]], [[phenprocoumon]], [[atromentin]], and [[phenindione]].{{citation needed|date=November 2021}}

The coumarins [[brodifacoum]] and [[difenacoum]] are used as mammalicides (particularly as [[rodenticide]]s) but are not used medically.{{citation needed|date=August 2022}}

===Heparin and derivative substances===
Heparin is the most widely used intravenous clinical anticoagulant worldwide.<ref>{{cite journal | vauthors = Linhardt RJ | title = 2003 Claude S. Hudson Award address in carbohydrate chemistry. Heparin: structure and activity | journal = Journal of Medicinal Chemistry | volume = 46 | issue = 13 | pages = 2551–64 | date = June 2003 | pmid = 12801218 | doi = 10.1021/jm030176m }}</ref> [[Heparin]] is a naturally occurring [[glycosaminoglycan]]. There are three major categories of heparin: unfractionated heparin (UFH), low molecular weight heparin (LMWH), and ultra-low-molecular weight heparin (ULMWH).<ref name="Heparin and anticoagulation">{{cite journal | vauthors = Onishi A, St Ange K, Dordick JS, Linhardt RJ | title = Heparin and anticoagulation | journal = Frontiers in Bioscience | volume = 21 | issue = 7 | pages = 1372–92 | date = June 2016 | pmid = 27100512 | doi = 10.2741/4462 }}</ref>  Unfractionated heparin is usually derived from [[pig]] intestines and bovine lungs.<ref>{{cite journal | vauthors = Casu B, Naggi A, Torri G | title = Re-visiting the structure of heparin | journal = Carbohydrate Research | volume = 403 | pages = 60–68 | date = February 2015 | pmid = 25088334 | doi = 10.1016/j.carres.2014.06.023 }}</ref> UFH binds to the enzyme inhibitor [[antithrombin]] III (AT), causing a conformational change that results in its activation.<ref>{{cite journal | vauthors = Seo Y, Andaya A, Leary JA | title = Preparation, separation, and conformational analysis of differentially sulfated heparin octasaccharide isomers using ion mobility mass spectrometry | journal = Analytical Chemistry | volume = 84 | issue = 5 | pages = 2416–23 | date = March 2012 | pmid = 22283665 | pmc = 3296823 | doi = 10.1021/ac203190k }}</ref> The activated AT then inactivates [[factor Xa]], [[thrombin]], and other coagulation factors.<ref>{{cite journal | vauthors = Allingstrup M, Wetterslev J, Ravn FB, Møller AM, Afshari A | title = Antithrombin&nbsp;III for critically ill patients: a systematic review with meta-analysis and trial sequential analysis | journal = Intensive Care Medicine | volume = 42 | issue = 4 | pages = 505–20 | date = April 2016 | pmid = 26862016 | pmc = 2137061 | doi = 10.1007/s00134-016-4225-7 }}</ref> Heparin can be used ''[[in vivo]]'' (by injection), and also ''[[in vitro]]'' to prevent blood or plasma clotting in or on medical devices. In [[venipuncture]], [[Vacutainer]] brand blood collecting tubes containing heparin usually have a green cap.<ref>{{cite journal |vauthors=Brizzee L, Stone A, Palmer MC |title=False lithium toxicity secondary to lithium heparin test tube: A case report and review |journal=Ment Health Clin |volume=10 |issue=3 |pages=90–94 |date=May 2020 |pmid=32420006 |pmc=7213950 |doi=10.9740/mhc.2020.05.090 }}</ref>

====Low molecular weight heparin (LMWH)====
[[Low molecular weight heparin]] (LMWH) is produced through a controlled depolymerization of unfractionated heparin.<ref name="Heparin and anticoagulation"/> LMWH exhibits a higher anti-Xa/anti-IIa activity ratio and is useful as it does not require monitoring of the [[APTT]] [[coagulation]] parameter and has fewer side effects.<ref name="Heparin and anticoagulation"/>

===Synthetic pentasaccharide inhibitors of factor Xa===
* [[Fondaparinux]] is a synthetic sugar composed of the five sugars (pentasaccharides) in heparin that bind to antithrombin. It is a smaller molecule than low molecular-weight heparin.
* [[Idraparinux]]
* [[Idrabiotaparinux]]

=== Direct oral ===
The direct oral anticoagulants (DOACs) were introduced in and after 2008.<ref>{{cite journal|date=2019-07-16|title=Human medicines European public assessment report (EPAR): Pradaxa, dabigatran etexilate, Arthroplasty, Replacement,Venous Thromboembolism, Date of authorisation: 17/03/2008, Revision: 29, Status: Authorised|journal=Case Medical Research|doi=10.31525/cmr-1321569|s2cid=241319098|issn=2643-4652}}</ref> There are five DOACs currently on the market: [[dabigatran]], [[rivaroxaban]], [[apixaban]], [[edoxaban]] and [[betrixaban]].<ref name="DOAC2018">{{cite journal | vauthors = Douxfils J, Ageno W, Samama CM, Lessire S, Ten Cate H, Verhamme P, Dogné JM, Mullier F | title = Laboratory testing in patients treated with direct oral anticoagulants: a practical guide for clinicians | journal = Journal of Thrombosis and Haemostasis | volume = 16 | issue = 2 | pages = 209–19 | date = February 2018 | pmid = 29193737 | doi = 10.1111/jth.13912 | s2cid = 46865986 | url = https://lirias.kuleuven.be/handle/123456789/611680 | doi-access = free }}</ref> They were also previously referred to as "new/novel" and "non-vitamin K antagonist" oral anticoagulants (NOACs).<ref name = udayachalerm>{{cite journal | vauthors = Udayachalerm S, Rattanasiri S, Angkananard T, Attia J, Sansanayudh N, Thakkinstian A | title = The Reversal of Bleeding Caused by New Oral Anticoagulants (NOACs): A Systematic Review and Meta-Analysis | journal = Clinical and Applied Thrombosis/Hemostasis | volume = 24 | issue = 9_suppl | pages = 117S–126S | date = September 2018 | pmid = 30176738 | pmc = 6714855 | doi = 10.1177/1076029618796339 }}</ref>

Compared to warfarin, DOACs have a rapid onset action and relatively short half-lives; hence, they carry out their function more rapidly and effectively, allowing drugs to reduce their anticoagulation effects quickly.<ref name=":1">{{cite web |url=http://www.sdcep.org.uk/wp-content/uploads/2015/09/SDCEP-Anticoagulants-Guidance.pdf |title=Management of Dental Patients Taking Anticoagulants or Antiplatelet Drugs |date=August 2015 |publisher=Scottish Dental Clinical Effectiveness Programme |access-date=2016-03-09 |archive-date=2017-03-28 |archive-url=https://web.archive.org/web/20170328223906/http://www.sdcep.org.uk/wp-content/uploads/2015/09/SDCEP-Anticoagulants-Guidance.pdf |url-status=dead }}</ref>  Routine monitoring and dose adjustments of DOACs are less important than for warfarin, as they have better predictable anticoagulation activity.<ref name=":3" /> DOAC monitoring, including laboratory monitoring and a complete medication review, should generally be conducted before initiation of a DOAC, 1–3 months after initiation, and then every 6–12 months afterwards.<ref name=":4">{{cite journal|last1=Chen|first1=Ashley|last2=Stecker|first2=Eric|last3=A. Warden|first3=Bruce|date=2020-06-15|title=Direct Oral Anticoagulant Use: A Practical Guide to Common Clinical Challenges|journal=Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease|volume=9|issue=13|pages=e017559|doi=10.1161/JAHA.120.017559|issn=2047-9980|pmc=7670541|pmid=32538234}}</ref>

Both DOACs and warfarin are equivalently effective, but compared to warfarin, DOACs have fewer drug interactions, no known dietary interactions, a wider therapeutic index, and have conventional dosing that does not require dose adjustments with constant monitoring.<ref name=":0">{{cite web | url = https://www.bhf.org.uk/heart-matters-magazine/medical/drug-cabinet/novel-anticoagulants | title = Novel anticoagulants | work = Heart Matters Magazine | publisher = British Heart Foundation | access-date = 2016-03-09 | archive-date = 2017-10-26 | archive-url = https://web.archive.org/web/20171026222846/https://www.bhf.org.uk/heart-matters-magazine/medical/drug-cabinet/novel-anticoagulants | url-status = dead }}</ref><ref name=":3">{{cite journal | vauthors = Clark NP | title = Role of the anticoagulant monitoring service in 2018: beyond warfarin | journal = Hematology. American Society of Hematology. Education Program | volume = 2018 | issue = 1 | pages = 348–52 | date = November 2018 | pmid = 30504331 | pmc = 6246023 | doi = 10.1182/asheducation-2018.1.348 }}</ref> However, there is no countermeasure for most DOACs, unlike for warfarin; nonetheless, the short half-lives of DOACs will allow their effects to recede swiftly. A reversal agent for dabigatran, [[idarucizumab]], is currently available and approved for use by the FDA. Rates of adherence to DOACs are only modestly higher than adherence to warfarin among patients prescribed these drugs. Thus, adherence to anticoagulation is often poor despite hopes that DOACs would lead to higher adherence rates.<ref>{{cite journal|last1=Ozaki|first1=Aya F.|last2=Choi|first2=Austin S.|last3=Le|first3=Quan T.|last4=Ko|first4=Dennis T.|last5=Han|first5=Janet K.|last6=Park|first6=Sandy S.|last7=Jackevicius|first7=Cynthia A.|date=2020|title=Real-World Adherence and Persistence to Direct Oral Anticoagulants in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis|journal=Circulation: Cardiovascular Quality and Outcomes|volume=13|issue=3|page=e005969|doi=10.1161/CIRCOUTCOMES.119.005969|issn=1941-7705|pmid=32148102|s2cid=212640015|doi-access=free}}</ref>

DOACs are significantly more expensive than warfarin, but the patients on DOACs may experience reduced lab costs as they do not need to monitor their INR.<ref name=":4" />

====Direct factor Xa inhibitors====
{{main|Direct Xa inhibitor}}
Drugs such as [[rivaroxaban]], [[apixaban]] and [[edoxaban]] work by inhibiting factor Xa directly (unlike heparins and fondaparinux, which work via antithrombin activation).
Also included in this category are [[betrixaban]] from Portola Pharmaceuticals, the discontinued [[darexaban]] (YM150) from Astellas, and, more recently,  the discontinued [[letaxaban]] (TAK-442) from Takeda and [[eribaxaban]] (PD0348292) from Pfizer.
Betrixaban is significant as it was in 2018, the only oral factor Xa inhibitor approved by the FDA for use in acutely medically ill patients.<ref>{{cite journal | vauthors = Lekura J, Kalus JS | title = Overview of betrixaban and its role in clinical practice | journal = American Journal of Health-System Pharmacy | volume = 75 | issue = 15 | pages = 1095–1102 | date = August 2018 | pmid = 29941506 | doi = 10.2146/ajhp170785 | s2cid = 49418996 }}</ref> Darexaban development was discontinued in September 2011; in a trial for prevention of recurrences of myocardial infarction in addition to dual antiplatelet therapy (DAPT), the drug did not demonstrate effectiveness, and the risk of bleeding was increased by approximately 300%.<ref name="Steg">{{cite journal | vauthors = Steg PG, Mehta SR, Jukema JW, Lip GY, Gibson CM, Kovar F, Kala P, Garcia-Hernandez A, Renfurm RW, Granger CB | title = RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome | journal = European Heart Journal | volume = 32 | issue = 20 | pages = 2541–54 | date = October 2011 | pmid = 21878434 | pmc = 3295208 | doi = 10.1093/eurheartj/ehr334 }}</ref> The development of letaxaban for acute coronary syndrome was discontinued in May 2011 following negative results from a Phase II study.<ref>{{cite web | first1 = Joseph | last1 = Dwyer | first2 = Conor | last2 = Walsh | title = First Time European Approval for Xarelto in ACS | publisher = Decision Resources | date = May 2013 | url = http://decisionresources.com/The-Decision-Resources-Blog/May-2013/European-Approval-for-Xarelto-in-ACS-052913 | archive-url = https://web.archive.org/web/20140719173801/http://decisionresources.com/The-Decision-Resources-Blog/May-2013/European-Approval-for-Xarelto-in-ACS-052913 | archive-date=2014-07-19 }}</ref>

====Direct thrombin inhibitors====
{{main|Direct thrombin inhibitor}}
Another type of anticoagulant is the [[direct thrombin inhibitor]].<ref name="pmid16148288">{{cite journal | vauthors = Di Nisio M, Middeldorp S, Büller HR | title = Direct thrombin inhibitors | journal = The New England Journal of Medicine | volume = 353 | issue = 10 | pages = 1028–40 | date = September 2005 | pmid = 16148288 | doi = 10.1056/NEJMra044440 | url = https://pure.uva.nl/ws/files/4020551/45334_205943y.pdf }}</ref> Current members of this class include the bivalent drugs [[hirudin]], [[lepirudin]], and [[bivalirudin]] and the monovalent drugs [[argatroban]] and [[dabigatran]]. An oral direct thrombin inhibitor, [[ximelagatran]] (Exanta), was denied approval by the [[Food and Drug Administration]] (FDA) in September 2004<ref>{{cite web | title = Exanta | work = Ask Dr. Stephan Moll | publisher = The Thrombophilia Awareness Project | url = http://www.fvleiden.org/ask/73.html | archive-url = https://web.archive.org/web/20110525194419/http://www.fvleiden.org/ask/73.html | archive-date = 25 May 2011 }}</ref> and was pulled from the market entirely in February 2006 after reports of severe liver damage and heart attacks.<ref>{{cite web | title = Exanta™ (ximelagatran) Study report summaries | url = http://www.astrazenecaclinicaltrials.com/article/512052.aspx | archive-url = https://archive.today/20060318061448/http://www.astrazenecaclinicaltrials.com/article/512052.aspx | url-status = dead | archive-date = 2006-03-18 | work = AstraZeneca Clinical Trials }}</ref> In November 2010, [[dabigatran Etexilate|dabigatran etexilate]] was approved by the FDA to prevent thrombosis in [[atrial fibrillation]].

==== Relevance to dental treatments ====
As in any invasive procedure, patients on anticoagulation therapy have an increased risk for bleeding, and caution should be used along with local [[hemostasis|hemostatic]] methods to minimize bleeding risk during the operation as well as postoperatively.<ref>{{cite journal | vauthors = Manfredi M, Dave B, Percudani D, Christoforou J, Karasneh J, Diz Dios P, Glick M, Kumar N, Lockhart PB, Patton LL | title = World workshop on oral medicine VII: Direct anticoagulant agents management for invasive oral procedures: A systematic review and meta-analysis | journal = Oral Diseases | volume = 25 | issue = S1 | pages = 157–73 | date = June 2019 | pmid = 31140701 | doi = 10.1111/odi.13086 | s2cid = 169034257 }}</ref> However, with regards to DOACs and invasive dental treatments, there has not been enough clinical evidence and experience to prove any reliable adverse effects, relevance or interaction between these two.<ref>{{cite journal | vauthors = Bensi C, Belli S, Paradiso D, Lomurno G | title = Postoperative bleeding risk of direct oral anticoagulants after oral surgery procedures: a systematic review and meta-analysis | journal = International Journal of Oral and Maxillofacial Surgery | volume = 47 | issue = 7 | pages = 923–32 | date = July 2018 | pmid = 29627150 | doi = 10.1016/j.ijom.2018.03.016 | s2cid = 4697607 }}</ref> Further clinical prospective studies on DOACs are required to investigate the bleeding risk and hemostasis associated with surgical and dental procedures.<ref>{{cite journal | vauthors = Costantinides F, Rizzo R, Pascazio L, Maglione M | title = Managing patients taking novel oral anticoagulants (NOAs) in dentistry: a discussion paper on clinical implications | journal = BMC Oral Health | volume = 16 | page = 5 | date = January 2016 | pmid = 26822674 | pmc = 4731944 | doi = 10.1186/s12903-016-0170-7 | doi-access = free }}</ref>

Recommendations of modifications to the usage/dosage of DOACs before dental treatments are made based on the balance of the bleeding risk of each procedure and also the individual's own bleeding risks and renal functionality.<ref>{{cite journal | vauthors = Kosyfaki P, Att W, Strub JR | title = The dental patient on oral anticoagulant medication: a literature review | journal = Journal of Oral Rehabilitation | volume = 38 | issue = 8 | pages = 615–33 | date = August 2011 | pmid = 21073495 | doi = 10.1111/j.1365-2842.2010.02184.x }}</ref> With low-bleeding-risk dental procedures, it is recommended that DOACs be continued by the patient to avoid any increase in the risk of a thromboembolic event.<ref>{{cite journal | vauthors = van Diermen DE, van der Waal I, Hoogstraten J | title = Management recommendations for invasive dental treatment in patients using oral antithrombotic medication, including novel oral anticoagulants | journal = Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology | volume = 116 | issue = 6 | pages = 709–16 | date = December 2013 | pmid = 24120910 | doi = 10.1016/j.oooo.2013.07.026 }}</ref><ref>{{cite journal | vauthors = Shi Q, Xu J, Zhang T, Zhang B, Liu H | title = Post-operative Bleeding Risk in Dental Surgery for Patients on Oral Anticoagulant Therapy: A Meta-analysis of Observational Studies | journal = Frontiers in Pharmacology | volume = 8 | page = 58 | date = 2017-02-08 | pmid = 28228727 | pmc = 5296357 | doi = 10.3389/fphar.2017.00058 | doi-access = free }}</ref> For dental procedures with a higher risk of bleeding complications (i.e. complex extractions, adjacent extractions leading to a large wound, or more than three extractions), the recommended practice is for the patient to miss or delay a dose of their DOAC before such procedures to minimize the effect on bleeding risk.<ref>{{cite web|url=https://www.sdcep.org.uk/wp-content/uploads/2015/09/SDCEP-Anticoagulants-Guidance.pdf|title=Management of Dental Patients Taking Anticoagulants or Antiplatelet Drugs: Dental Clinical Guidance|website=Scottish Dental Clinical Effectiveness Programme|access-date=2020-01-09|archive-date=2017-03-28|archive-url=https://web.archive.org/web/20170328223906/http://www.sdcep.org.uk/wp-content/uploads/2015/09/SDCEP-Anticoagulants-Guidance.pdf|url-status=dead}}</ref>

===Antithrombin protein therapeutics===
The antithrombin protein is used as a [[Biologic medical product|protein therapeutic]] that can be purified from human plasma<ref name="ThrombateLabel">{{cite web|url=http://www.talecris-pi.info/inserts/thrombate.pdf|title=Thrombate III label|url-status=dead|archive-url=https://web.archive.org/web/20121115050430/http://www.talecris-pi.info/inserts/thrombate.pdf|archive-date=2012-11-15}}</ref> or produced recombinantly (for example, Atryn, produced in the milk of [[Genetic engineering|genetically modified]] goats).<ref>{{cite web|url=https://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm134042.htm|title=Fractionated Plasma Products – ATryn| author = Center for Biologics Evaluation and Research|website=www.fda.gov|date=24 April 2019}}</ref><ref name="ATrynLabel">{{cite web|url=https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM134045.pdf|title=Antithrombin (Recombinant) US Package Insert ATryn for Injection February 3, 2009|website=[[Food and Drug Administration]]}}</ref>

The FDA approves Antithrombin as an anticoagulant for preventing clots before, during, or after surgery or birthing in patients with hereditary antithrombin deficiency.<ref name=ThrombateLabel/><ref name=ATrynLabel/>

===Other===
Many other anticoagulants exist in [[research and development]], [[diagnostics]], or as drug candidates.
* [[Batroxobin]], a [[toxin]] from [[snake]] [[venom]], clots platelet-rich plasma without affecting [[platelet]] functions (cleaves [[fibrinogen]]).
* [[Hementin]] is an anticoagulant protease from the salivary glands of the giant Amazon leech, ''[[Haementeria ghilianii]]''.
* [[Vitamin E]]
* [[Alcoholic beverage]]