Jump to content

Anticoagulant

From Wikipedia, the free encyclopedia
(Redirected fromBlood thinners)

Anticoagulant
Drug class
Coagulation cascade and major classes of anticoagulants
Class identifiers
ATC codeB01
External links
MeSHD00534-class
Legal status
In Wikidata

Ananticoagulant,commonly known as ablood thinner,is achemical substancethat prevents or reduces thecoagulationofblood,prolonging theclotting time.[1]Some occur naturally inblood-eatinganimals, such asleechesandmosquitoes,which help keep the bite area unclotted long enough for the animal to obtain blood.[2][3]

As a class ofmedications,anticoagulants are used intherapyforthrombotic disorders.[4]Oralanticoagulants (OACs) are taken by many people inpillortabletform, and variousintravenousanticoagulantdosage formsare used in hospitals.[5][6]Some anticoagulants are used in medical equipment, such as sample tubes,blood transfusionbags,heart–lung machines,anddialysisequipment.[7][8]One of the first anticoagulants,warfarin,was initially approved as arodenticide.[9]

Anticoagulants are closely related toantiplatelet drugsandthrombolyticdrugs by manipulating the various pathways of blood coagulation.[10]Specifically, antiplatelet drugs inhibit platelet aggregation (clumping together), whereas anticoagulants inhibit specific pathways of the coagulation cascade, which happens after the initial platelet aggregation but before the formation of fibrin and stable aggregated platelet products.[11][12]

Common anticoagulants include warfarin andheparin.[13]

Medical uses

[edit]

The use of anticoagulants is a decision based on the risks and benefits of anticoagulation.[14]The biggest risk of anticoagulation therapy is the increased risk of bleeding.[15]In otherwise healthy people, the increased risk of bleeding is minimal, but those who have had recent surgery,cerebral aneurysms,and other conditions may have too great a risk of bleeding.[16][17]Generally, the benefit of anticoagulation is preventing or reducing the progression of a thromboembolic disease.[18]Some indications for anticoagulant therapy that are known to have benefit from therapy include:

In these cases, anticoagulation therapyprevents the formationor growth of dangerous clots.[30]

The decision to begin therapeutic anticoagulation often involves the use of multiple bleeding risk predictable outcome tools as non-invasive pre-test stratifications due to the potential for bleeding while on blood thinning agents.[15]Among these tools areHAS-BLED,[31]ATRIA,[32]HEMORR2HAGES,[33]andCHA2DS2-VASc.[34]The risk of bleeding using the risk assessment tools above must then be weighed against thrombotic risk to formally determine the patient's overall benefit in starting anticoagulation therapy.[35]

There is no evidence to indicate that adding anticoagulant therapy to standard treatment has a benefit for people with cerebral small vessel disease but not dementia, and there is an increased risk of a person with this disease experiencing a bleed with this approach.[36]

Adverse effects

[edit]

The most serious and common adverse side effects associated with anticoagulants are increased risk of bleeding, both nonmajor and major bleeding events.[37]The bleeding risk depends on the class of anticoagulant agent used, the patient's age, and pre-existing health conditions. Warfarin has an estimated incidence of bleeding of 15-20% per year and a life-threatening bleeding rate of 1-3% per year.[38]Newer non-vitamin K antagonist oral anticoagulants appear to have fewer life-threatening bleeding events than warfarin.[39][40]Additionally, patients aged 80 years or more may be especially susceptible to bleeding complications, with a rate of 13 bleeds per 100 person-years.[41]Bleeding risk is especially important to consider in patients with renal impairment and NOAC therapy because all NOACs, to some extent, are excreted by the kidneys.[42]Thus, patients with renal impairment may be at higher risk of increased bleeding.[43]

In people with cancer, a systematic review has found warfarin had no effect on death rate or the risk of blood clots.[44]However, it did increase the risk of major bleeding in 107 more people per 1000 population and minor bleeding in 167 more people per 1000 population.[44]Apixaban had no effect on mortality, recurrence of blood clots in blood vessels, or major or minor bleeding. However, this finding comes only from one study.[44]

Nonhemorrhagic adverse events are less common than hemorrhagic adverse events but should still be monitored closely.[39]Nonhemorrhagic adverse events of warfarin include skinnecrosis,limb gangrene, and purple toe syndrome.[45]Skin necrosis and limb gangrene are most commonly observed on the third to eighth day of therapy.[46][47]The exact pathogenesis of skin necrosis and limb gangrene is not completely understood but it is believed to be associated with warfarin's effect on inhibiting the production of protein C and protein S.[48][49]Purple toe syndrome typically develops three to eight weeks after initiation of warfarin therapy.[50][51]Other adverse effects of warfarin are associated with depletion of vitamin K, which can lead to inhibition of G1a proteins and growth arrest-specific gene 6, which can lead to increased risk of arterial calcification and heart valve, especially if too much Vitamin D is present.[52][53]Warfarin's interference with G1a proteins has also been linked to abnormalities in fetal bone development in mothers who were treated with warfarin during pregnancy.[54][55]Long-term warfarin and heparin usage have also been linked to osteoporosis.[56][45]

Another potentially severe complication associated with heparin use is called heparin-induced thrombocytopenia (HIT).[57]There are two distinct types: HIT 1) immune-mediated and 2) non-immune-mediated.[57]Immune-mediated HIT most commonly arises five to ten days after exposure to heparin.[58]Pathogenesis of immune-mediated HIT is believed to be caused by heparin-dependent immunoglobulin antibodies binding to platelet factor 4/heparin complexes on platelets, leading to widespread platelet activation.[59]

Interactions

[edit]

Foods andfood supplementswith blood-thinning effects includenattokinase,lumbrokinase,beer,bilberry,celery,cranberries,fish oil,garlic,ginger,ginkgo,ginseng,green tea,horse chestnut,licorice,niacin,onion,papaya,pomegranate,red clover,soybean,St. John's wort,turmeric,wheatgrass,andwillowbark.[60][61][62]Many herbal supplements have blood-thinning properties, such asdanshenandfeverfew.[63]Multivitamins that do not interact with clotting are available for patients on anticoagulants.[64]

However, some foods and supplements encourage clotting.[65]These includealfalfa,avocado,cat's claw,coenzyme Q10,and dark leafy greens such asspinach.[66][67]Excessive intake of the food mentioned above should be avoided while taking anticoagulants, or if coagulability is being monitored, their intake should be kept approximately constant so that anticoagulant dosage can be maintained at a level high enough to counteract this effect without fluctuations in coagulability.[68][69]

Grapefruitinterferes with some anticoagulant drugs, increasing the time it takes for them to be metabolized out of the body, and should be eaten with caution when on anticoagulant drugs.[70]

Anticoagulants are often used to treat acutedeep-vein thrombosis.[71][72]People using anticoagulants to treat this condition should avoid usingbed restas a complementary treatment because there are clinical benefits to continuing to walk and remaining mobile while using anticoagulants in this way.[73]Bed rest while using anticoagulants can harm patients in circumstances in which it is not medically necessary.[73]

Types

[edit]

Several anticoagulants are available. Warfarin, other coumarins, and heparins have long been used.[74]Since the 2000s, several agents have been introduced that are collectively referred to asdirect oral anticoagulants(DOACs), previously namednovel oral anticoagulants(NOACs) ornon-vitamin K antagonist oral anticoagulants.[75][76][77][78]These agents include direct thrombin inhibitor (dabigatran) and factor Xa inhibitor (rivaroxaban,apixaban,betrixabanandedoxaban), and they have been shown to be as good or possibly better than the coumarins with less serious side effects.[79]The newer anticoagulants (NOACs/DOACs) are more expensive than the traditional ones and should be used in caring for patients with kidney problems.[80]

Coumarins (vitamin K antagonists)

[edit]
Further information:Vitamin K antagonist

These oral anticoagulants are derived fromcoumarinfound in many plants. A prominent member of this class,warfarin(Coumadin), was found to be the anticoagulant most prescribed in a large multispecialty practice.[81]The anticoagulant effect takes at least 48 to 72 hours to develop. Where an immediate effect is required,heparinis given concomitantly. These anticoagulants are used to treat patients withdeep-vein thrombosis(DVT) andpulmonary embolism(PE) and to prevent emboli in patients withatrial fibrillation(AF), and mechanicalprosthetic heart valves.Other examples areacenocoumarol,phenprocoumon,atromentin,andphenindione.[citation needed]

The coumarinsbrodifacoumanddifenacoumare used as mammalicides (particularly asrodenticides) but are not used medically.[citation needed]

Heparin and derivative substances

[edit]

Heparin is the most widely used intravenous clinical anticoagulant worldwide.[82]Heparinis a naturally occurringglycosaminoglycan.There are three major categories of heparin: unfractionated heparin (UFH), low molecular weight heparin (LMWH), and ultra-low-molecular weight heparin (ULMWH).[83]Unfractionated heparin is usually derived frompigintestines and bovine lungs.[84]UFH binds to the enzyme inhibitorantithrombinIII (AT), causing a conformational change that results in its activation.[85]The activated AT then inactivatesfactor Xa,thrombin,and other coagulation factors.[86]Heparin can be usedin vivo(by injection), and alsoin vitroto prevent blood or plasma clotting in or on medical devices. Invenipuncture,Vacutainerbrand blood collecting tubes containing heparin usually have a green cap.[87]

Low molecular weight heparin (LMWH)

[edit]

Low molecular weight heparin(LMWH) is produced through a controlled depolymerization of unfractionated heparin.[83]LMWH exhibits a higher anti-Xa/anti-IIa activity ratio and is useful as it does not require monitoring of theAPTTcoagulationparameter and has fewer side effects.[83]

Synthetic pentasaccharide inhibitors of factor Xa

[edit]
  • Fondaparinuxis 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

[edit]

The direct oral anticoagulants (DOACs) were introduced in and after 2008.[88]There are five DOACs currently on the market:dabigatran,rivaroxaban,apixaban,edoxabanandbetrixaban.[89]They were also previously referred to as "new/novel" and "non-vitamin K antagonist" oral anticoagulants (NOACs).[90]

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.[91]Routine monitoring and dose adjustments of DOACs are less important than for warfarin, as they have better predictable anticoagulation activity.[92]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.[93]

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.[94][92]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.[95]

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.[93]

Direct factor Xa inhibitors

[edit]
Main article:Direct Xa inhibitor

Drugs such asrivaroxaban,apixabanandedoxabanwork by inhibiting factor Xa directly (unlike heparins and fondaparinux, which work via antithrombin activation). Also included in this category arebetrixabanfrom Portola Pharmaceuticals, the discontinueddarexaban(YM150) from Astellas, and, more recently, the discontinuedletaxaban(TAK-442) from Takeda anderibaxaban(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.[96]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%.[97]The development of letaxaban for acute coronary syndrome was discontinued in May 2011 following negative results from a Phase II study.[98]

Direct thrombin inhibitors

[edit]
Main article:Direct thrombin inhibitor

Another type of anticoagulant is thedirect thrombin inhibitor.[99]Current members of this class include the bivalent drugshirudin,lepirudin,andbivalirudinand the monovalent drugsargatrobananddabigatran.An oral direct thrombin inhibitor,ximelagatran(Exanta), was denied approval by theFood and Drug Administration(FDA) in September 2004[100]and was pulled from the market entirely in February 2006 after reports of severe liver damage and heart attacks.[101]In November 2010,dabigatran etexilatewas approved by the FDA to prevent thrombosis inatrial fibrillation.

Relevance to dental treatments

[edit]

As in any invasive procedure, patients on anticoagulation therapy have an increased risk for bleeding, and caution should be used along with localhemostaticmethods to minimize bleeding risk during the operation as well as postoperatively.[102]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.[103]Further clinical prospective studies on DOACs are required to investigate the bleeding risk and hemostasis associated with surgical and dental procedures.[104]

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.[105]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.[106][107]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.[108]

Antithrombin protein therapeutics

[edit]

The antithrombin protein is used as aprotein therapeuticthat can be purified from human plasma[109]or produced recombinantly (for example, Atryn, produced in the milk ofgenetically modifiedgoats).[110][111]

The FDA approves Antithrombin as an anticoagulant for preventing clots before, during, or after surgery or birthing in patients with hereditary antithrombin deficiency.[109][111]

Other

[edit]

Many other anticoagulants exist inresearch and development,diagnostics,or as drug candidates.


Reversal agents

[edit]

With the growing number of patients taking oral anticoagulation therapy, studies into reversal agents are gaining increasing interest due to major bleeding events and the need for urgent anticoagulant reversal therapy.[112]Reversal agents for warfarin are more widely studied, and established guidelines for reversal exist due to a longer history of use of warfarin and the ability to get a more accurate measurement of anticoagulation effect in a patient via measuring the INR (International Normalized Ratio).[113]In general, vitamin K is most commonly used to reverse the effect of warfarin in non-urgent settings.[114]However, in urgent settings or settings with extremely high INR (INR >20), hemostatic reversal agents such as fresh frozen plasma (FFP),recombinant factor VIIa,and prothrombin complex concentrate (PCC) have been utilized with proven efficacy.[115]Specifically with warfarin, four-factor PCC (4F-PCC) has been shown to have superior safety and mortality benefits compared to FPP in lowering INR levels.[112]

Although specific antidotes and reversal agents for DOACs are not as widely studied,idarucizumab(for dabigatran) andandexanet alfa(for factor Xa inhibitor) have been used in clinical settings with varying efficacy.[90]Idarucizumab is a monoclonal antibody, approved by the US FDA in 2015, that reverses the effect of dabigatran by binding to both free and thrombin-bound dabigatran.[116][117]Andexanet alfa is a recombinant modified human factor Xa decoy that reverses the effect of factor Xa inhibitors by binding at the active sites of factor Xa inhibitor and making it catalytically inactive.[118][119]Andexanet alfa was approved by the US FDA in 2018.[120]Another drug called ciraparantag, a potential reversal agent for direct factor Xa inhibitors, is still under investigation.[121]Additionally, hemostatic reversal agents have also been used with varying efficacy to reverse the effects of DOACs.[122][123]

Coagulation inhibitor measurement

[edit]

ABethesda unit(BU) is a measure of bloodcoagulation inhibitoractivity. It is the amount of inhibitor that will inactivate half of acoagulantduring the incubation period.[124]It is the standard measure used in the United States and is so named because it was adopted as a standard at a conference inBethesda, Maryland.[125]

Laboratory use

[edit]

If blood is allowed to clot,laboratoryinstruments, blood transfusion bags, and medical and surgical equipment will get clogged up and non-operational. In addition, test tubes used for laboratory blood tests will have chemicals added to stop blood clotting. Besides heparin, most of these chemicalsbindcalciumions, preventing the coagulation proteins from using them.

  • Ethylenediaminetetraacetic acid(EDTA) strongly and irreversibly chelates (binds) calcium ions, preventing blood from clotting.
  • Citrateis in liquid form in the tube and is used for coagulation tests and blood transfusion bags. It binds calcium but not as strongly as EDTA. The correct proportion of this anticoagulant to blood is crucial because of the dilution, which can be reversed with the addition of calcium. Formulations include plainsodium citrate,acid-citrate-dextrose,and more.
  • Oxalatehas a mechanism similar to that of citrate. It is the anticoagulant used in fluoride/oxalate tubes to determine glucose and lactate levels. The fluoride inhibitsglycolysis,which can throw off blood sugar measurements. Citrate/fluoride/EDTA tubes work better in this regard.[126]

Dental considerations for long-term users

[edit]

Dental practitioners play an important role in the early detection of anticoagulant overdose through oral manifestations, as the patient does not show any symptoms. Dental treatment of patients taking anticoagulant or antiplatelet medication raises safety concerns in terms of the potential risk of bleeding complications following invasive dental procedures. Therefore, certain guidelines for the dental care of patients taking these drugs are needed.

Detecting overdose

An overdose of anticoagulants usually occurs in people who have heart problems and need to take anticoagulants in the long term to reduce the risk of stroke from their high blood pressure.

AnInternational Normalised Ratio (INR)test would be recommended to confirm the overdose so that the dosage can be adjusted to an acceptable standard. The INR test measures the time it takes for a clot to form in a blood sample relative to a standard.

An INR value of 1 indicates a level of coagulation equivalent to that of an average patient not taking warfarin, and values greater than 1 indicate a longer clotting time and, thus, a longer bleeding time.

Assessing bleeding risk

There are two main parts to the assessment of bleeding risk:

  • Assessment of the likely risk of bleeding associated with the required dental procedure
  • Assessment of the patient's individual-level bleeding risk

Managing bleeding risk

A patient who is on anticoagulants orantiplateletmedications may undergo dental treatments which are unlikely to cause bleeding, such as local anesthesia injection, basic gum charting, removal of plaque, calculus and stain above the gum level, direct or indirect fillings which are above the gingiva,root canal treatment,taking impression for denture or crown and fitting or adjustment oforthodontic appliances.For all these procedures, it is recommended that the dentist treat the patient following the normal standard procedure and taking care to avoid any bleeding.

For a patient who needs to undergo dental treatments which are more likely to cause bleeding, such as simple tooth extractions (1-3 teeth with small wound size), drainage of swelling inside the mouth, periodontal charting,root planing,direct or indirect filling which extends below the gingiva, complex filling, flap raising procedure, gingival recontouring and biopsies, the dentist needs to take extra precautions apart from the standard procedure. The recommendations[127]are as follows:

  • if the patient has another medical condition or is taking other medication that may increase bleeding risk, consult the patient's general medical practitioner or specialist
  • if the patient is on a short course of anticoagulant or antiplatelet therapy, delay the non-urgent, invasive procedure until the medication has been discontinued
  • plan treatment for early in the day and week, where possible, to allow time for the management of prolonged bleeding or re-bleeding if it occurs
  • perform the procedure as traumatically as possible, use appropriate local measures and only discharge the patient oncehemostasishas been confirmed
  • if travel time to emergency care is a concern, place particular emphasis at the time of the initial treatment on the use of measures to avoid complications
  • advise the patient to takeparacetamol,unless contraindicated, for pain relief rather thanNSAIDssuch asaspirin,ibuprofen,diclofenacornaproxen
  • provide the patient with written post-treatment advice and emergency contact details
  • follow the specific recommendations and advice given for the management of patients taking different anticoagulants or antiplatelet drugs

There is general agreement that in most cases, treatment regimens with older anticoagulants (e.g., warfarin) and antiplatelet agents (e.g.,clopidogrel,ticlopidine,prasugrel,ticagrelor,and/or aspirin) should not be altered before dental procedures. The risks of stopping or reducing these medication regimens (i.e.,thromboembolism,stroke,myocardial infarction) far outweigh the consequences of prolonged bleeding, which can be controlled with local measures. In patients with other existing medical conditions that can increase the risk of prolonged bleeding after dental treatment or receiving other therapy that can increase bleeding risk, dental practitioners may wish to consult the patient's physician to determine whether care can safely be delivered in a primary care office. Any suggested modification to the medication regimen before dental surgery should be done in consultation and on the advice of the patient's physician.

Based on limited evidence, the consensus appears to be that in most patients who are receiving the newer direct-acting oral anticoagulants (i.e., dabigatran, rivaroxaban, apixaban, or edoxaban) and undergoing dental treatment (in conjunction with usual local measures to control bleeding), no change to the anticoagulant regimen is required. In patients deemed to be at higher risk of bleeding (e.g., patients with other medical conditions or undergoing more extensive procedures associated with higher bleeding risk), consideration may be given, in consultation with and on advice of the patient's physician, to postponing the timing of the daily dose of the anticoagulant until after the procedure; timing the dental intervention as late as possible after last dose of anticoagulant; or temporarily interrupting drug therapy for 24 to 48 hours.

Research

[edit]

A substantial number of compounds are being investigated for use as anticoagulants. The most promising ones act on thecontact activation system(factor XIIaandfactor XIa); it is anticipated that this may provide agents that prevent thrombosis without conferring a risk of bleeding.[128]

As of November 2021,the direct factor XIa inhibitormilvexianis in Phase II clinical trials for the prevention of an embolism after surgery.[129]

See also

[edit]

References

[edit]
  1. ^"Overview: Anticoagulant medicines".Health A to Z.NHS.26 July 2021.Retrieved2 June2023.
  2. ^Azzopardi EA, Whitaker IS, Rozen WM, Naderi N, Kon M (October 2011)."Chemical and mechanical alternatives to leech therapy: a systematic review and critical appraisal".Journal of Reconstructive Microsurgery.27(8).Thieme Medical Publishers:481–6.doi:10.1055/s-0031-1284233.eISSN0743-684X.PMID21780018.S2CID260192613.
  3. ^Ha YR, Oh SR, Seo ES, Kim BH, Lee DK, Lee SJ (April 2014)."Detection of heparin in the salivary gland and midgut of Aedes togoi".The Korean Journal of Parasitology.52(2). The Korean Society for Parasitology and Tropical Medicine: 183–8.doi:10.3347/kjp.2014.52.2.183.eISSN2982-6799.PMC4028456.PMID24850962.
  4. ^Yoo HH, Nunes-Nogueira VS, Boas, PJ (7 February 2020)."Anticoagulant treatment for subsegmental pulmonary embolism".The Cochrane Database of Systematic Reviews.2020(2): CD010222.doi:10.1002/14651858.CD010222.pub4.ISSN1469-493X.PMC7004894.PMID32030721.
  5. ^Cohen AT, Hamilton M, Mitchell SA, Phatak H, Liu X, Bird A, et al. (2015-12-30). ten Cate H (ed.)."Comparison of the Novel Oral Anticoagulants Apixaban, Dabigatran, Edoxaban, and Rivaroxaban in the Initial and Long-Term Treatment and Prevention of Venous Thromboembolism: Systematic Review and Network Meta-Analysis".PLOS One.10(12): e0144856.Bibcode:2015PLoSO..1044856C.doi:10.1371/journal.pone.0144856.PMC4696796.PMID26716830.
  6. ^Almutairi AR, Zhou L, Gellad WF, Lee JK, Slack MK, Martin JR, et al. (July 2017)."Effectiveness and Safety of Non-vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation and Venous Thromboembolism: A Systematic Review and Meta-analyses".Clinical Therapeutics.39(7): 1456–1478.e36.doi:10.1016/j.clinthera.2017.05.358.PMID28668628.
  7. ^Banfi G, Salvagno GL, Lippi G (2007-01-01)."The role of ethylenediamine tetraacetic acid (EDTA) as in vitro anticoagulant for diagnostic purposes".Clinical Chemistry and Laboratory Medicine.45(5): 565–76.doi:10.1515/CCLM.2007.110.PMID17484616.S2CID23824484.
  8. ^Dobrovolskaia MA, McNeil SE (May 2015)."Safe anticoagulation when heart and lungs are" on vacation "".Annals of Translational Medicine.3(Suppl 1): S11.doi:10.3978/j.issn.2305-5839.2015.02.03.PMC4437941.PMID26046056.
  9. ^Pirmohamed M(November 2006)."Warfarin: almost 60 years old and still causing problems".British Journal of Clinical Pharmacology.62(5): 509–11.doi:10.1111/j.1365-2125.2006.02806.x.PMC1885167.PMID17061959.
  10. ^Patel S, Singh R, Preuss CV, Patel N (2020)."Warfarin".StatPearls.StatPearls Publishing.PMID29261922.Retrieved2020-01-23.
  11. ^Iqbal AM, Lopez RA, Hai O (2020)."Antiplatelet Medications".StatPearls.StatPearls Publishing.PMID30725747.Retrieved2020-01-23.
  12. ^Harter K, Levine M, Henderson SO (January 2015)."Anticoagulation drug therapy: a review".The Western Journal of Emergency Medicine.16(1): 11–7.doi:10.5811/westjem.2014.12.22933.PMC4307693.PMID25671002.
  13. ^Winslow R, Johnson A (2007-12-10)."Race Is on for the Next Blood Thinner".The Wall Street Journal.p. A12.Retrieved2008-01-06....in a market now dominated by one of the oldest mainstay pills in medicine: the blood thinner warfarin. At least five next-generation blood thinners are in advanced testing to treat or prevent potentially debilitating or life-threatening blood clots in surgery and heart patients. First candidates could reach the market in 2009.
  14. ^Djulbegovic M, Lee AI (September 2018). "An Update on the" Novel "and Direct Oral Anticoagulants, and Long-Term Anticoagulant Therapy".Clinics in Chest Medicine.39(3): 583–593.doi:10.1016/j.ccm.2018.04.010.PMID30122182.S2CID52039169.
  15. ^abParks AL, Fang MC (July 2017). "Scoring Systems for Estimating the Risk of Anticoagulant-Associated Bleeding".Seminars in Thrombosis and Hemostasis.43(5): 514–524.doi:10.1055/s-0037-1598061.PMID28359135.S2CID1981707.
  16. ^Zhu X (February 2017)."The hemorrhage risk of prophylactic external ventricular drain insertion in aneurysmal subarachnoid hemorrhage patients requiring endovascular aneurysm treatment: a systematic review and meta-analysis".Journal of Neurosurgical Sciences.61(1): 53–63.doi:10.23736/S0390-5616.16.03244-6.PMID25963956.
  17. ^Banerjee K, Poddar K, Mick S, White J, Krishnaswamy A, Johnston D, et al. (November 2017). "Meta-Analysis of Usefulness of Anticoagulation After Transcatheter Aortic Valve Implantation".The American Journal of Cardiology.120(9): 1612–1617.doi:10.1016/j.amjcard.2017.07.059.PMID28844512.
  18. ^"Blood Thinners".medlineplus.gov.Retrieved2020-01-23.
  19. ^Sharma M, Cornelius VR, Patel JP, Davies JG, Molokhia M (July 2015)."Efficacy and Harms of Direct Oral Anticoagulants in the Elderly for Stroke Prevention in Atrial Fibrillation and Secondary Prevention of Venous Thromboembolism: Systematic Review and Meta-Analysis".Circulation.132(3): 194–204.doi:10.1161/CIRCULATIONAHA.114.013267.PMC4765082.PMID25995317.
  20. ^Moustafa A, Ruzieh M, Eltahawy E, Karim S (2019)."Antithrombotic therapy in patients with atrial fibrillation and coronary artery disease".Avicenna Journal of Medicine.9(4): 123–128.doi:10.4103/ajm.AJM_73_19.PMC6796304.PMID31903386.
  21. ^Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, et al. (February 2016). "Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report".Chest.149(2): 315–352.doi:10.1016/j.chest.2015.11.026.PMID26867832.
  22. ^Kapil N, Datta YH, Alakbarova N, Bershad E, Selim M, Liebeskind DS, et al. (May 2017)."Antiplatelet and Anticoagulant Therapies for Prevention of Ischemic Stroke".Clinical and Applied Thrombosis/Hemostasis.23(4): 301–318.doi:10.1177/1076029616660762.PMID27461564.S2CID43296498.
  23. ^Skelley JW, White CW, Thomason AR (January 2017). "The use of direct oral anticoagulants in inherited thrombophilia".Journal of Thrombosis and Thrombolysis.43(1): 24–30.doi:10.1007/s11239-016-1428-2.PMID27734187.S2CID24650202.
  24. ^Poli D, Antonucci E, Pengo V, Migliaccio L, Testa S, Lodigiani C, et al. (September 2018). "Mechanical prosthetic heart valves: Quality of anticoagulation and thromboembolic risk. The observational multicenter PLECTRUM study".International Journal of Cardiology.267:68–73.doi:10.1016/j.ijcard.2018.04.042.PMID29957264.S2CID49588203.
  25. ^Almony GT, Lefkovits J, Topol EJ (May 1996)."Antiplatelet and anticoagulant use after myocardial infarction".Clinical Cardiology.19(5): 357–65.doi:10.1002/clc.4960190506.PMID8723593.S2CID103327.
  26. ^Konstantinides SV, Barco S, Lankeit M, Meyer G (March 2016)."Management of Pulmonary Embolism: An Update".Journal of the American College of Cardiology.67(8): 976–90.doi:10.1016/j.jacc.2015.11.061.PMID26916489.
  27. ^Dong Z, Zheng J (September 2017)."Anticoagulation after coronary stenting: a systemic review".British Medical Bulletin.123(1): 79–89.doi:10.1093/bmb/ldx018.PMID28910988.S2CID3800129.
  28. ^Lander H, Zammert M, FitzGerald D (September 2016). "Anticoagulation management during cross-clamping and bypass".Best Practice & Research. Clinical Anaesthesiology.30(3): 359–70.doi:10.1016/j.bpa.2016.07.002.PMID27650345.
  29. ^Thomas I, EncisoSilva J, Schlueter M, Greenberg B (2016), Bauersachs J, Butler J, Sandner P (eds.), "Anticoagulation Therapy and NOACs in Heart Failure",Heart Failure,vol. 243, Springer International Publishing, pp. 515–535,doi:10.1007/164_2016_126,ISBN978-3-319-59658-7,PMID28233177
  30. ^Raschi E, Bianchin M, De Ponti R, De Ponti F, Ageno W (June 2017). "Emerging therapeutic uses of direct-acting oral anticoagulants: An evidence-based perspective".Pharmacological Research.120:206–218.doi:10.1016/j.phrs.2017.03.026.PMID28366835.S2CID36716760.
  31. ^"HAS-BLED Score for Major Bleeding risk".MDCalc.Retrieved2014-08-15.
  32. ^"ATRIA Bleeding Risk".MDCalc.Retrieved2014-08-15.
  33. ^"HEMORR₂HAGES Score for Major Bleeding Risk".MDCalc.Retrieved2020-01-23.
  34. ^"CHA2DS2-VASc".MDCalc.Retrieved2014-08-15.
  35. ^Zhu W, He W, Guo L, Wang X, Hong K (September 2015)."The HAS-BLED Score for Predicting Major Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation: A Systematic Review and Meta-analysis".Clinical Cardiology.38(9): 555–61.doi:10.1002/clc.22435.PMC6490831.PMID26418409.
  36. ^Kwan J, Hafdi M, Chiang LL, Myint PK, Wong LS, Quinn TJ (2022-07-13). Cochrane Dementia and Cognitive Improvement Group (ed.)."Antithrombotic therapy to prevent cognitive decline in people with small vessel disease on neuroimaging but without dementia".Cochrane Database of Systematic Reviews.2022(7): CD012269.doi:10.1002/14651858.CD012269.pub2.PMC9281623.PMID35833913.
  37. ^Yee J, Kaide CG (August 2019)."Emergency Reversal of Anticoagulation".The Western Journal of Emergency Medicine.20(5): 770–783.doi:10.5811/westjem.2018.5.38235.PMC6754204.PMID31539334.
  38. ^Zareh M, Davis A, Henderson S (November 2011)."Reversal of warfarin-induced hemorrhage in the emergency department".The Western Journal of Emergency Medicine.12(4): 386–92.doi:10.5811/westjem.2011.3.2051.PMC3236169.PMID22224125.
  39. ^abAgeno W, Donadini M (November 2018)."Breadth of complications of long-term oral anticoagulant care".Hematology. American Society of Hematology. Education Program.2018(1): 432–438.doi:10.1182/asheducation-2018.1.432.PMC6245998.PMID30504343.
  40. ^Ageno W, Mantovani LG, Haas S, Kreutz R, Monje D, Schneider J, et al. (January 2016). "Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study".The Lancet. Haematology.3(1): e12-21.doi:10.1016/S2352-3026(15)00257-4.PMID26765643.
  41. ^Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S (May 2007)."Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation".Circulation.115(21): 2689–96.doi:10.1161/CIRCULATIONAHA.106.653048.PMID17515465.S2CID8881388.
  42. ^Turpie AG, Purdham D, Ciaccia A (September 2017)."Nonvitamin K antagonist oral anticoagulant use in patients with renal impairment".Therapeutic Advances in Cardiovascular Disease.11(9): 243–256.doi:10.1177/1753944717714921.PMC5562140.PMID28651452.
  43. ^Weir MR, Kreutz R (October 2018)."Influence of Renal Function on the Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of Non-Vitamin K Antagonist Oral Anticoagulants".Mayo Clinic Proceedings.93(10): 1503–1519.doi:10.1016/j.mayocp.2018.06.018.PMID30286834.S2CID52922296.
  44. ^abcKahale LA, Hakoum MB, Tsolakian IG, Matar CF, Barba M, Yosuico VE, et al. (2017-12-29)."Oral anticoagulation in people with cancer who have no therapeutic or prophylactic indication for anticoagulation".Cochrane Database of Systematic Reviews.12(12): CD006466.doi:10.1002/14651858.cd006466.pub6.ISSN1465-1858.PMC6389337.PMID29285754.
  45. ^abAgeno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G (February 2012)."Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines".Chest.141(2 Suppl): e44S–e88S.doi:10.1378/chest.11-2292.PMC3278051.PMID22315269.
  46. ^Verhagen H (2009-04-24). "Local haemorrhage and necrosis of the skin and underlying tissues, during anti-coagulant therapy with dicumarol or dicumacyl".Acta Medica Scandinavica.148(6): 453–67.doi:10.1111/j.0954-6820.1954.tb01741.x.PMID13171021.
  47. ^Weinberg AC, Lieskovsky G, McGehee WG, Skinner DG (August 1983). "Warfarin necrosis of the skin and subcutaneous tissue of the male external genitalia".The Journal of Urology.130(2): 352–4.doi:10.1016/S0022-5347(17)51147-7.PMID6876290.
  48. ^Broekmans AW, Bertina RM, Loeliger EA, Hofmann V, Klingemann HG (June 1983). "Protein C and the development of skin necrosis during anticoagulant therapy".Thrombosis and Haemostasis.49(3): 251.doi:10.1055/s-0038-1657378.PMID6688309.S2CID38261767.
  49. ^Grimaudo V, Gueissaz F, Hauert J, Sarraj A, Kruithof EK, Bachmann F (January 1989)."Necrosis of skin induced by coumarin in a patient deficient in protein S".BMJ.298(6668): 233–4.doi:10.1136/bmj.298.6668.233.PMC1835547.PMID2522326.
  50. ^Talmadge DB, Spyropoulos AC (May 2003). "Purple toes syndrome associated with warfarin therapy in a patient with antiphospholipid syndrome".Pharmacotherapy.23(5): 674–7.doi:10.1592/phco.23.5.674.32200.PMID12741443.S2CID28632135.
  51. ^Raj K, Collins B, Rangarajan S (September 2001). "Purple toe syndrome following anticoagulant therapy".British Journal of Haematology.114(4): 740.doi:10.1046/j.1365-2141.2001.03107.x.PMID11564060.S2CID20482173.
  52. ^Adams J, Pepping J (August 2005)."Vitamin K in the treatment and prevention of osteoporosis and arterial calcification"(PDF).American Journal of Health-System Pharmacy.62(15): 1574–81.doi:10.2146/ajhp040357.PMID16030366.
  53. ^Danziger J (September 2008)."Vitamin K-dependent proteins, warfarin, and vascular calcification".Clinical Journal of the American Society of Nephrology.3(5): 1504–10.doi:10.2215/CJN.00770208.PMC4571144.PMID18495950.
  54. ^Pettifor JM, Benson R (March 1975). "Congenital malformations associated with the administration of oral anticoagulants during pregnancy".The Journal of Pediatrics.86(3): 459–62.doi:10.1016/S0022-3476(75)80986-3.PMID1113236.
  55. ^Hall JG, Pauli RM, Wilson KM (January 1980). "Maternal and fetal sequelae of anticoagulation during pregnancy".The American Journal of Medicine.68(1): 122–40.doi:10.1016/0002-9343(80)90181-3.PMID6985765.
  56. ^Gage BF, Birman-Deych E, Radford MJ, Nilasena DS, Binder EF (January 2006)."Risk of osteoporotic fracture in elderly patients taking warfarin: results from the National Registry of Atrial Fibrillation 2".Archives of Internal Medicine.166(2): 241–6.doi:10.1001/archinte.166.2.241.PMID16432096.
  57. ^abBaroletti SA, Goldhaber SZ (August 2006)."Heparin-induced thrombocytopenia".Circulation.114(8): e355-6.doi:10.1161/CIRCULATIONAHA.106.632653.PMID16923760.
  58. ^Warkentin TE, Greinacher A, Koster A, Lincoff AM (June 2008). "Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)".Chest.133(6 Suppl): 340S–380S.doi:10.1378/chest.08-0677.PMID18574270.
  59. ^Linkins LA, Hu G, Warkentin TE (October 2018)."Systematic review of fondaparinux for heparin-induced thrombocytopenia: When there are no randomized controlled trials".Research and Practice in Thrombosis and Haemostasis.2(4): 678–683.doi:10.1002/rth2.12145.PMC6178656.PMID30349886.
  60. ^Wittkowsky AK (September 2001). "Drug interactions update: drugs, herbs, and oral anticoagulation".Journal of Thrombosis and Thrombolysis.12(1): 67–71.doi:10.1023/A:1012742628628.PMID11711691.S2CID22447084.
  61. ^Rui TQ, Zhang L, Qiao HZ, Huang P, Qian S, Li JS, et al. (January 2016). "Preparation and Physicochemical and Pharmacokinetic Characterization of Ginkgo Lactone Nanosuspensions for Antiplatelet Aggregation".Journal of Pharmaceutical Sciences.105(1): 242–249.doi:10.1016/j.xphs.2015.10.002.PMID26852855.
  62. ^Yun YP, Do JH, Ko SR, Ryu SY, Kim JH, Song HC, et al. (October 2001). "Effects of Korean red ginseng and its mixed prescription on the high molecular weight dextran-induced blood stasis in rats and human platelet aggregation".Journal of Ethnopharmacology.77(2–3): 259–264.doi:10.1016/S0378-8741(01)00303-8.PMID11535373.
  63. ^Choi S, Oh DS, Jerng UM (2017-08-10). Borrelli F (ed.)."A systematic review of the pharmacokinetic and pharmacodynamic interactions of herbal medicine with warfarin".PLOS ONE.12(8): e0182794.Bibcode:2017PLoSO..1282794C.doi:10.1371/journal.pone.0182794.ISSN1932-6203.PMC5552262.PMID28797065.
  64. ^Kurnik D, Lubetsky A, Loebstein R, Almog S, Halkin H (November 2003). "Multivitamin Supplements May Affect Warfarin Anticoagulation in Susceptible Patients".Annals of Pharmacotherapy.37(11): 1603–1606.doi:10.1345/aph.1D102.ISSN1060-0280.PMID14565795.S2CID43777757.
  65. ^Harder S, Thürmann P (June 1996). "Clinically Important Drug Interactions with Anticoagulants: An Update".Clinical Pharmacokinetics.30(6): 416–444.doi:10.2165/00003088-199630060-00002.ISSN0312-5963.PMID8792056.S2CID22389544.
  66. ^Lippi G, Mattiuzzi C, Franchini M (April 2016). "Vegetables intake and venous thromboembolism: a systematic review".Blood Coagulation & Fibrinolysis.27(3): 242–245.doi:10.1097/MBC.0000000000000427.ISSN0957-5235.PMID27023878.S2CID33380206.
  67. ^"Avocado: Health Benefits, Uses, Side Effects, Dosage & Interactions".RxList.Retrieved2020-01-23.
  68. ^Dentali F, Crowther M, Galli M, Pomero F, Garcia D, Clark N, et al. (2016-05-27). "Effect of Vitamin K Intake on the Stability of Treatment with Vitamin K Antagonists: A Systematic Review of the Literature".Seminars in Thrombosis and Hemostasis.42(6): 671–681.doi:10.1055/s-0036-1581105.ISSN0094-6176.PMID27232386.S2CID24822900.
  69. ^"Warfarin Uses, Dosage, Side Effects".Drugs.com.Retrieved2020-01-23.
  70. ^Sullivan DM, Ford MA, Boyden TW (1998-08-01). "Grapefruit juice and the response to warfarin".American Journal of Health-System Pharmacy.55(15): 1581–1583.doi:10.1093/ajhp/55.15.1581.ISSN1079-2082.PMID9706183.
  71. ^Di Nisio M, van Es N, Büller HR (December 2016). "Deep vein thrombosis and pulmonary embolism".The Lancet.388(10063): 3060–3073.doi:10.1016/S0140-6736(16)30514-1.PMID27375038.S2CID25712161.
  72. ^Koehl JL, Hayes BD, Al-Samkari H, Rosovsky R (2020-01-23). "A comprehensive evaluation of apixaban in the treatment of venous thromboembolism".Expert Review of Hematology.13(2): 155–173.doi:10.1080/17474086.2020.1711731.ISSN1747-4086.PMID31958251.S2CID210842354.
  73. ^abAmerican Physical Therapy Association(15 September 2014),"Five Things Physicians and Patients Should Question",Choosing Wisely:an initiative of theABIM Foundation,American Physical Therapy Association,retrieved15 September2014,which cites
  74. ^Di Minno A, Frigerio B, Spadarella G, Ravani A, Sansaro D, Amato M, et al. (July 2017)."Old and new oral anticoagulants: Food, herbal medicines and drug interactions".Blood Reviews.31(4): 193–203.doi:10.1016/j.blre.2017.02.001.hdl:2434/476466.PMID28196633.
  75. ^Almarshad F, Alaklabi A, Bakhsh E, Pathan A, Almegren M (December 2018)."Use of direct oral anticoagulants in daily practice".American Journal of Blood Research.8(4): 57–72.PMC6334188.PMID30697449.
  76. ^Verdecchia P, Angeli F, Aita A, Bartolini C, Reboldi G (April 2016). "Why switch from warfarin to NOACs?".Internal and Emergency Medicine.11(3): 289–293.doi:10.1007/s11739-016-1411-0.ISSN1828-0447.PMID26972708.S2CID25807727.
  77. ^Diener HC, Ntaios G, O'Donnell M, Easton JD (2018-09-22). "Non-vitamin-K oral anticoagulants (NOACs) for the prevention of secondary stroke".Expert Opinion on Pharmacotherapy.19(14): 1597–1602.doi:10.1080/14656566.2018.1515913.ISSN1465-6566.PMID30152249.S2CID52099757.
  78. ^Pol D, Curtis C, Ramkumar S, Bittinger L (April 2019). "NOACs Now Mainstream for the Use of Anticoagulation in Non-Valvular Atrial Fibrillation in Australia".Heart, Lung and Circulation.28(4): e40–e42.doi:10.1016/j.hlc.2018.03.010.PMID29861320.S2CID44103560.
  79. ^Werdan K, Braun-Dullaeus R, Presek P (August 2013)."Anticoagulation in atrial fibrillation: NOAC's the word".Deutsches Ärzteblatt International.110(31–32): 523–4.doi:10.3238/arztebl.2013.0523.PMC3782018.PMID24069072.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.
  80. ^Heine GH, Brandenburg V, Schirmer SH (2018-04-27)."Orale Antikoagulation bei chronischer Nierenerkrankung und Vorhofflimmern".Deutsches Ärzteblatt Online.115(17): 287–294.doi:10.3238/arztebl.2018.0287.ISSN1866-0452.PMC5974258.PMID29789105.
  81. ^Efird LE, Chasler J, Alexander GC, McGuire M (Jun 21, 2016)."Prescribing Patterns of Novel Anticoagulants Within a Statewide Multispecialty Practice".American Journal of Pharmacy Benefits.8(3): 97–102.
  82. ^Linhardt RJ (June 2003). "2003 Claude S. Hudson Award address in carbohydrate chemistry. Heparin: structure and activity".Journal of Medicinal Chemistry.46(13): 2551–64.doi:10.1021/jm030176m.PMID12801218.
  83. ^abcOnishi A, St Ange K, Dordick JS, Linhardt RJ (June 2016). "Heparin and anticoagulation".Frontiers in Bioscience.21(7): 1372–92.doi:10.2741/4462.PMID27100512.
  84. ^Casu B, Naggi A, Torri G (February 2015). "Re-visiting the structure of heparin".Carbohydrate Research.403:60–8.doi:10.1016/j.carres.2014.06.023.PMID25088334.
  85. ^Seo Y, Andaya A, Leary JA (March 2012)."Preparation, separation, and conformational analysis of differentially sulfated heparin octasaccharide isomers using ion mobility mass spectrometry".Analytical Chemistry.84(5): 2416–23.doi:10.1021/ac203190k.PMC3296823.PMID22283665.
  86. ^Allingstrup M, Wetterslev J, Ravn FB, Møller AM, Afshari A (April 2016)."Antithrombin III for critically ill patients: a systematic review with meta-analysis and trial sequential analysis".Intensive Care Medicine.42(4): 505–520.doi:10.1007/s00134-016-4225-7.PMC2137061.PMID26862016.
  87. ^Brizzee L, Stone A, Palmer MC. False lithium toxicity secondary to lithium heparin test tube: A case report and review. Ment Health Clin. 2020 May 7;10(3):90-94. doi: 10.9740/mhc.2020.05.090. PMID: 32420006; PMCID: PMC7213950.
  88. ^"Human medicines European public assessment report (EPAR): Pradaxa, dabigatran etexilate, Arthroplasty, Replacement,Venous Thromboembolism, Date of authorisation: 17/03/2008, Revision: 29, Status: Authorised".Case Medical Research.2019-07-16.doi:10.31525/cmr-1321569.ISSN2643-4652.S2CID241319098.
  89. ^Douxfils J, Ageno W, Samama CM, Lessire S, Ten Cate H, Verhamme P, et al. (February 2018)."Laboratory testing in patients treated with direct oral anticoagulants: a practical guide for clinicians".Journal of Thrombosis and Haemostasis.16(2): 209–219.doi:10.1111/jth.13912.PMID29193737.S2CID46865986.
  90. ^abUdayachalerm S, Rattanasiri S, Angkananard T, Attia J, Sansanayudh N, Thakkinstian A (September 2018)."The Reversal of Bleeding Caused by New Oral Anticoagulants (NOACs): A Systematic Review and Meta-Analysis".Clinical and Applied Thrombosis/Hemostasis.24(9_suppl): 117S–126S.doi:10.1177/1076029618796339.PMC6714855.PMID30176738.
  91. ^"Management of Dental Patients Taking Anticoagulants or Antiplatelet Drugs"(PDF).Scottish Dental Clinical Effectiveness Programme. August 2015. Archived fromthe original(PDF)on 2017-03-28.Retrieved2016-03-09.
  92. ^abClark NP (November 2018)."Role of the anticoagulant monitoring service in 2018: beyond warfarin".Hematology. American Society of Hematology. Education Program.2018(1): 348–352.doi:10.1182/asheducation-2018.1.348.PMC6246023.PMID30504331.
  93. ^abChen A, Stecker E, A Warden B (2020-06-15)."Direct Oral Anticoagulant Use: A Practical Guide to Common Clinical Challenges".Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease.9(13): e017559.doi:10.1161/JAHA.120.017559.ISSN2047-9980.PMC7670541.PMID32538234.
  94. ^"Novel anticoagulants".Heart Matters Magazine.British Heart Foundation. Archived fromthe originalon 2017-10-26.Retrieved2016-03-09.
  95. ^Ozaki AF, Choi AS, Le QT, Ko DT, Han JK, Park SS, et al. (2020)."Real-World Adherence and Persistence to Direct Oral Anticoagulants in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis".Circulation: Cardiovascular Quality and Outcomes.13(3): e005969.doi:10.1161/CIRCOUTCOMES.119.005969.ISSN1941-7705.PMID32148102.S2CID212640015.
  96. ^Lekura J, Kalus JS (August 2018). "Overview of betrixaban and its role in clinical practice".American Journal of Health-System Pharmacy.75(15): 1095–1102.doi:10.2146/ajhp170785.PMID29941506.S2CID49418996.
  97. ^Steg PG, Mehta SR, Jukema JW, Lip GY, Gibson CM, Kovar F, et al. (October 2011)."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".European Heart Journal.32(20): 2541–54.doi:10.1093/eurheartj/ehr334.PMC3295208.PMID21878434.
  98. ^Dwyer J, Walsh C (May 2013)."First Time European Approval for Xarelto in ACS".Decision Resources. Archived fromthe originalon 2014-07-19.
  99. ^Di Nisio M, Middeldorp S, Büller HR (September 2005)."Direct thrombin inhibitors"(PDF).The New England Journal of Medicine.353(10): 1028–40.doi:10.1056/NEJMra044440.PMID16148288.
  100. ^"Exanta".Ask Dr. Stephan Moll.The Thrombophilia Awareness Project. Archived fromthe originalon 25 May 2011.
  101. ^"Exanta™ (ximelagatran) Study report summaries".AstraZeneca Clinical Trials.Archived fromthe originalon 2006-03-18.
  102. ^Manfredi M, Dave B, Percudani D, Christoforou J, Karasneh J, Diz Dios P, et al. (June 2019). "World workshop on oral medicine VII: Direct anticoagulant agents management for invasive oral procedures: A systematic review and meta-analysis".Oral Diseases.25(S1): 157–173.doi:10.1111/odi.13086.PMID31140701.S2CID169034257.
  103. ^Bensi C, Belli S, Paradiso D, Lomurno G (July 2018). "Postoperative bleeding risk of direct oral anticoagulants after oral surgery procedures: a systematic review and meta-analysis".International Journal of Oral and Maxillofacial Surgery.47(7): 923–932.doi:10.1016/j.ijom.2018.03.016.PMID29627150.S2CID4697607.
  104. ^Costantinides F, Rizzo R, Pascazio L, Maglione M (January 2016)."Managing patients taking novel oral anticoagulants (NOAs) in dentistry: a discussion paper on clinical implications".BMC Oral Health.16:5.doi:10.1186/s12903-016-0170-7.PMC4731944.PMID26822674.
  105. ^Kosyfaki P, Att W, Strub JR (August 2011). "The dental patient on oral anticoagulant medication: a literature review".Journal of Oral Rehabilitation.38(8): 615–33.doi:10.1111/j.1365-2842.2010.02184.x.PMID21073495.
  106. ^van Diermen DE, van der Waal I, Hoogstraten J (December 2013). "Management recommendations for invasive dental treatment in patients using oral antithrombotic medication, including novel oral anticoagulants".Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology.116(6): 709–16.doi:10.1016/j.oooo.2013.07.026.PMID24120910.
  107. ^Shi Q, Xu J, Zhang T, Zhang B, Liu H (2017-02-08)."Post-operative Bleeding Risk in Dental Surgery for Patients on Oral Anticoagulant Therapy: A Meta-analysis of Observational Studies".Frontiers in Pharmacology.8:58.doi:10.3389/fphar.2017.00058.PMC5296357.PMID28228727.
  108. ^"Management of Dental Patients Taking Anticoagulants or Antiplatelet Drugs: Dental Clinical Guidance"(PDF).Scottish Dental Clinical Effectiveness Programme.Archived fromthe original(PDF)on 2017-03-28.Retrieved2020-01-09.
  109. ^ab"Thrombate III label"(PDF).Archived fromthe original(PDF)on 2012-11-15.
  110. ^Center for Biologics Evaluation and Research (24 April 2019)."Fractionated Plasma Products - ATryn".www.fda.gov.
  111. ^ab"Antithrombin (Recombinant) US Package Insert ATryn for Injection February 3, 2009"(PDF).Food and Drug Administration.
  112. ^abTornkvist M, Smith JG, Labaf A (February 2018). "Current evidence of oral anticoagulant reversal: A systematic review".Thrombosis Research.162:22–31.doi:10.1016/j.thromres.2017.12.003.PMID29258056.
  113. ^Hanley JP (2004-11-01)."Warfarin reversal".Journal of Clinical Pathology.57(11): 1132–1139.doi:10.1136/jcp.2003.008904.ISSN0021-9746.PMC1770479.PMID15509671.
  114. ^Makris M, Greaves M, Phillips WS, Kitchen S, Rosendaal FR, Preston EF (March 1997). "Emergency oral anticoagulant reversal: the relative efficacy of infusions of fresh frozen plasma and clotting factor concentrate on correction of the coagulopathy".Thrombosis and Haemostasis.77(3): 477–480.doi:10.1055/s-0038-1655992.ISSN0340-6245.PMID9065997.S2CID45458169.
  115. ^Chai-Adisaksopha C, Hillis C, Siegal DM, Movilla R, Heddle N, Iorio A, et al. (September 2016). "Prothrombin complex concentrates versus fresh frozen plasma for warfarin reversal A systematic review and meta-analysis".Thrombosis and Haemostasis.116(11): 879–890.doi:10.1160/TH16-04-0266.ISSN0340-6245.PMID27488143.S2CID4733615.
  116. ^Pakraftar S (2014)."Dabigatran etixilate and traumatic brain injury: Evolving anticoagulants require evolving care plans".World Journal of Clinical Cases.2(8): 362–6.doi:10.12998/wjcc.v2.i8.362.ISSN2307-8960.PMC4133427.PMID25133148.
  117. ^Ryn Jv, Stangier J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, et al. (2010). "Dabigatran etexilate – a novel, reversible, oral direct thrombin inhibitor: Interpretation of coagulation assays and reversal of anticoagulant activity".Thrombosis and Haemostasis.103(6): 1116–1127.doi:10.1160/TH09-11-0758.ISSN0340-6245.PMID20352166.S2CID37404563.
  118. ^Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, et al. (2015-12-17)."Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity".New England Journal of Medicine.373(25): 2413–2424.doi:10.1056/NEJMoa1510991.ISSN0028-4793.PMID26559317.
  119. ^Connolly SJ, Milling TJ, Eikelboom JW, Gibson CM, Curnutte JT, Gold A, et al. (2016-09-22)."Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors".New England Journal of Medicine.375(12): 1131–1141.doi:10.1056/NEJMoa1607887.ISSN0028-4793.PMC5568772.PMID27573206.
  120. ^Reed M, Tadi P, Nicolas D (2020),"Andexanet Alfa",StatPearls,StatPearls Publishing,PMID30137783,retrieved2020-01-23
  121. ^Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso MA, Brown K, et al. (February 2017)."Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban".Thrombosis and Haemostasis.117(2): 238–245.doi:10.1160/TH16-03-0224.ISSN0340-6245.PMC6260118.PMID27853809.
  122. ^Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M (2011-10-04)."Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate: A Randomized, Placebo-Controlled, Crossover Study in Healthy Subjects".Circulation.124(14): 1573–1579.doi:10.1161/CIRCULATIONAHA.111.029017.ISSN0009-7322.PMID21900088.S2CID961167.
  123. ^Marlu R, Hodaj E, Paris A, Albaladejo P, Crackowski J, Pernod G (2012). "Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: A randomised crossover ex vivo study in healthy volunteers".Thrombosis and Haemostasis.108(8): 217–224.doi:10.1160/TH12-03-0179.ISSN0340-6245.PMID22627883.S2CID28694620.
  124. ^"Bethesda unit".Biology Online.Retrieved2009-02-14.
  125. ^Schumacher HR (2000).Handbook of Hematologic Pathology.Informa Health Care.p. 583.ISBN978-0-8247-0170-3.
  126. ^Norman M, Jones I (May 2014). "The shift from fluoride/oxalate to acid citrate/fluoride blood collection tubes for glucose testing — The impact upon patient results".Clinical Biochemistry.47(7–8): 683–685.doi:10.1016/j.clinbiochem.2014.01.011.PMID24463230.
  127. ^"Management of Dental Patients Taking Anticoagulants or Antiplatelet Drugs – New guidance from SDCEP | Scottish Dental".15 September 2015.Retrieved2020-02-20.
  128. ^Fredenburgh JC, Weitz JI (12 October 2020)."New Anticoagulants: Moving Beyond the Direct Oral Anticoagulants".Journal of Thrombosis and Haemostasis.19(1): 20–29.doi:10.1111/jth.15126.PMID33047462.S2CID222320654.
  129. ^Weitz JI, Strony J, Ageno W, Gailani D, Hylek EM, Lassen MR, et al. (November 2021)."Milvexian for the Prevention of Venous Thromboembolism".The New England Journal of Medicine.385(23): 2161–2172.doi:10.1056/NEJMoa2113194.PMC9540352.PMID34780683.S2CID244132392.
[edit]
Retrieved from "https://en.wikipedia.org/w/index.php?title=Anticoagulant&oldid=1247503276"