Common Side Effects Of Anticoagulants

🖨️ Print post

Life-threatening blood clots (thrombosis) are associated with events like stroke, heart at­tack and pulmonary embolism (PE). To break down existing clots or prevent clots from form­ing, doctors rely heavily on a pharmacopoeia of anticoagulant and antiplatelet drugs, together colloquially referred to as blood thinners. As “commonly prescribed medications,” doctors frequently recommend them for individuals with atrial fibrillation (AF), often a precursor to coronary thrombosis,¹ or for patients under­going elective surgeries such as knee or hip replacements or heart valve replacements.² Eight million Americans take prescription anticoagu­lants,³ and hospitals routinely administer them to a third of all patients.²

Joint replacements can potentially cause clots to form in the legs, a condition called deep vein thrombosis (DVT), which sometimes leads to PE. Together, DVT and PE are referred to as venous thromboembolism (VTE). Cohort stud­ies that looked at VTE in the U.S. in the early 2000s reported an annual incidence in adults of around one in one thousand.⁴ Currently, around nine hundred thousand Americans develop VTE every year, and one to three hundred thousand of those die.⁵ In addition, anywhere from one-fifth to one-half of individuals with DVT develop “post-thrombotic syndrome,” manifesting as leg pain, heaviness, swelling or ulcers.⁶

Somewhat surprisingly, medical authori­ties accept some iatrogenic blame for VTE, attributing 42 to 52 percent of such events to the exogenous “triggering factors”⁴ of hospitaliza­tion and surgery—including joint replacements.⁷ Among people who have had a total knee or hip replacement, VTE is the third most frequent rea­son for unplanned readmissions to the hospital,⁸ and among all surgical patients, the medical literature describes VTE as the most common preventable cause of death.⁹

Anticoagulants, by definition, interfere with normal clotting pro­cesses.² This means, ironically, that their top risk and most worrisome adverse event is “unwanted and sometimes dangerous bleeding.”³ None of the blood thinners developed over the past century have escaped this apparently inevitable mirror-image problem. Colorfully comparing blood thinners to Goldilocks’ porridge, a November 2024 People’s Pharmacy article titled “Patients Walk a Dangerous Tightrope on Blood Thinners” explained it this way: “If the dose is too high, the risk of bleeding goes up dangerously, as if the porridge were scalding hot. Too low, and the medicine loses its ability to prevent blood clots, as if the porridge were too cold to be satisfying. The ‘just right’ dose with an anticoagulant must strike a balance between clot prevention and bleeding control.”¹⁰ Unfortunately, the drugs at their disposal make it difficult for clinicians and patients to strike the “just right” note.

The oldest anticoagulant is heparin, which has occupied a long-standing spot on the World Health Organization’s Model List of Essential Medicines¹¹ and is in use worldwide.¹² It first arrived on the clinical scene in the 1930s as unfractionated heparin (UFH), which doctors administer intravenously.¹³ However, UFH’s “broad and unpredictable” bioactivity¹⁴ requires continuous monitoring to ensure that it performs its anticoagula­tion job without veering too far in the opposite direction.

Clinicians were pleased when fractionated low molecular weight heparin (LMWH) emerged in the 1970s, because it seemed to promise more predictability and offered patients the possibility of subcutaneous self-administration at home.¹⁵ However, both UFH and LMWH some­times produce a delayed type of allergic reaction called heparin-induced thrombocytopenia¹⁶ (HIT), which, in an estimated 1 percent of recipients, triggers a dangerous “chain reaction of clotting.”² Because of its dosing, monitoring and dispensing logistics and adverse event profile, the Insti­tute for Safe Medication Practices and other organizations continue to classify heparin as a “high-risk” medication that can potentially cause significant harm.¹⁷

Heparin came to particular public notice in 2008 when tainted hepa­rin manufactured in China resulted in hundreds of severe reactions that killed dozens,¹⁸ described in alarming detail in the 2018 pharmaceutical exposé China Rx.¹⁹ The Pew Charitable Trusts cites these events as “a tragic example of the risks resulting from an increasingly globalized and complex pharmaceutical manufacturing system,” with 80 percent of ac­tive pharmaceutical ingredients (APIs) manufactured overseas.²⁰ In 2022, PharmacyChecker observed that drug marketers are under no obligation to disclose country of manufacture.²¹ PharmacyChecker’s research of the top one hundred brand-name prescription drugs found that the vast majority are made overseas, often in Europe; most generic drugs and their APIs are made in China and other Asian countries.

In the 1940s, scientists identified a natural substance in moldy hay (coumarin) that pro­duced an oxidized poison called dicumarol; in 1948, a “particularly potent” synthetic deriva­tive entered the market as a rodenticide, dubbed “warfarin” in honor of its research funder, the Wisconsin Alumni Research Foundation (WARF).²² Six years later, warfarin (brand name Coumadin) not only was the most popular rat poison in the world but gained regulatory ap­proval as a human anticoagulant that could be administered either intravenously or orally; re­searchers had discovered that it lessened clotting by reducing the action of vitamin K. Initially, as one account decorously puts it, “The association of the name ‘warfarin’ with rat poison did lead to some hesitancy among doctors to recom­mend it and among patients to take it,”²³ but by the 1960s, warfarin had become the “reference treatment” for VTE events.²⁴

As with heparin, “over-anticoagulation” with Coumadin (or generic warfarin) is a seri­ous concern.²⁵ The drug also interacts poorly with other medications such as antibiotics. De­scribing the need for warfarin to be “carefully calibrated,” a 2015 ProPublica report docu­mented appalling deaths and injuries caused by Coumadin in nursing homes, characterizing the facilities for seniors as “a perfect setup for bad things happening.”²⁶ An expert interviewed by ProPublica called Coumadin “the most danger­ous drug in America” because “it’s so easy to get wrong.” The report also suggested that most of the harms caused by the drug go undocumented and uninvestigated.

A 2019 study documented problems among patients “doubling up on blood thinners,” look­ing at people who were taking both aspirin and warfarin.²⁷ A whopping forty-seven million Americans take aspirin for blood thinning purposes.²⁸ Among those taking the combo, 5.7 percent had a major bleeding event within a year, versus a still-suboptimal 3.3 percent of individuals taking warfarin only.²⁹ The lead author remarked, “Nearly 2,500 patients who were prescribed warfarin were taking aspirin without any clear reason. . . . No doctors really own the prescribing of aspirin, so it’s possible it got overlooked.”²⁷ (In a 2018 Wise Traditions article, Dr. Tom Cowan gives multiple reasons to question the wisdom of taking daily aspirin, even at very low doses.³⁰)

The 2010s introduced further dangers when pharma brought a new class of drugs called “direct oral anticoagulants” (DOACs) to market. The word “direct” refers to the fact that through the biotech trick of “fabricat[ing] small molecules designed to fit into the active component of clotting enzymes, like a key into a lock,” the drugs directly inhibit coagulation proteins.²⁴ Leading drugs in the DOAC category include Eliquis (apixaban), co-owned by Bristol Myers Squibb (BMS) and Pfizer,³¹ and Xarelto (rivaroxaban), jointly developed by Johnson & Johnson (J&J) and Bayer; both work by inhibit­ing an enzyme called activated factor X (FXa), an important blood clotting enzyme.³² Pradaxa (dabigatran), made by German manufacturer Boehringer Ingelheim, inhibits thrombin, deemed “the key enzyme in the coagulation cascade.”³³

DOACs became blockbusters right out of the gate.³⁴ A 2022 article about anticoagulant history and trends argued that DOACs have “substantially facilitated VTE treatment,” ap­provingly speculating that “in the coming de­cades DOACs will most likely be more and more prescribed instead of other anticoagulants.”²⁴ Another 2022 study that compiled data from eighty-eight U.S. health systems confirmed the trend, documenting dramatic changes in anti­coagulant use among adults with AF between 2011 (the year when FDA approved Xarelto) and 2020, with DOAC use rising from 4.7 to 47.9 percent and warfarin use declining from 52.4 to 17.7 percent.³⁵ The authors noted that two out of three “high-risk” AF patients were on anti­coagulants (Some studies have drawn attention to the problem of anticoagulant overprescribing in AF patients.³⁶)

By 2018, Xarelto had become Bayer’s top-selling drug,³⁷ but thanks to strategic in­vestments in marketing and “patient education initiatives,”³⁸ Eliquis has now raced ahead to be­come the undisputed leader of the DOAC pack.

According to trade rag Fierce Pharma, Eliquis has been a “reliable growth driver” for its two owners ever since its debut in 2012 for AF and then with expanded indications in 2014 for DVT and PE.³⁹ The drug’s steadily rising sales gave it (as of 2021 when it was competing with Covid injections) the enviable status of being the fifth top-selling pharma product worldwide.³⁹ In the U.S. that year, an estimated four million patients filled an Eliquis prescription, causing the drug to jump fifteen ranks in a single year to become the thirty-third most prescribed medication in the American market.⁴⁰ By 2023, Eliquis had claimed 41 percent of the U.S. anticoagulant sector, settling in as a “preferred choice” over options such as Coumadin⁴¹ and beating out Xarelto despite the latter’s earlier market entry.

The three leading DOACs (Eliquis, Xarelto and Pradaxa) come with two boxed warnings— the most serious type of safety-related warning that the Food and Drug Administration (FDA) is willing to issue. The first warning is bad enough; patients taking one of the blood thin­ners who undergo certain spinal procedures could develop spinal or epidural blood clots that might cause long-term or permanent paralysis. Even worse, however, is the conundrum faced by patients who want to stop taking a DOAC; doing so may increase their risk of blood clots, stroke or PE! Eliquis’s manufacturers advise doctors to “consider another anticoagulant if they take a patient off [the drug] before treat­ment is completed for any reason other than ‘pathological bleeding.’”⁴²

Drugwatch discreetly suggests that BMS and Pfizer may have fudged their data during a China-based clinical trial for Eliquis called the ARISTOTLE study. After it came to light that during the trial “patients received the wrong medicines, records were secretly changed and ‘serious adverse events’ went unreported,”⁴³ the FDA delayed its approval for nine months—but then went ahead and gave Eliquis a green light anyway. The manufacturers’ dubious claims about the drug’s supposedly superior safety profile have proved to be persuasive for both clinicians and patients, but Drugwatch reminds the public that “some patient records simply dis­appeared prior to site visits by the inspectors”:

“[The FDA medical team leader] specifical­ly noted that the statistical results for lower overall deaths stemming from use of the drug ‘might not be valid’; meaning taking Eliquis may result in just as many deaths as other blood thinners, but since data was missing or included errors, it is impossible to know for sure.”⁴³

Older adults are more likely to have condi­tions that increase their risk of Eliquis side ef­fects.⁴⁴ This fact seems to have gone unnoticed, because Eliquis is a particular favorite among the Medicare population. Medicare typically covers Eliquis under Medicare Advantage (Part C) or Medicare Part D, even though it ranks among the ten most expensive Medicare drugs. In August 2024, the federal government an­nounced with great fanfare that it had negoti­ated a lower price, though the reduction from a $521 list price (based on a thirty-day supply) to $231 will not take effect until 2026.⁴⁵ One should not feel too sorry for the manufacturers’ projected reduction in profits, because they have steadily increased the price of Eliquis—by 124 percent—since its launch.⁴⁶ The government watchdog group Accountable.US reported on manufacturer hypocrisy last year; describing the argument by BMS and seven other pharma giants that Medicare price reductions would impede their research and development (R&D) efforts, Accountable pointed out that the compa­nies’ spending on “political activity, executive compensation and handouts to wealthy inves­tors” far outstripped their modest spending on R&D.⁴⁷ Moreover, they added, American seniors and patients are subject to the highest prescrip­tion drug prices in the world.

Older adults also have been bamboozled by the marketing hype about Eliquis’s favorable “patient-focused attributes”—for example, its oral mode of administration and more “lenient” monitoring. The University of Michigan cau­tions health care providers that Eliquis and other DOACs “have their own complicated dosing schemes that can vary based on factors such as kidney function and select interactions between drugs,” adding, “Any health system that aims to improve safe and effective DOAC prescribing must address the ongoing prescribing period which can last months to years.”⁴⁸ Unfortunately, studies show that many doctors have limited experience in managing bleeding risks.⁴⁹

According to a 2021 article published in The Hospitalist, over one hundred thousand individuals experience DOAC-related “major bleeding” each year in the U.S. and European Union.⁵⁰ Commenting on a study that found an extremely high mortality rate (17.7 percent) among patients who had access to “reversal agents” (that is, antidotes), one of the researchers said, “The lesson is to prevent these bleeding events because once they appear, even if you give an antidote, the outcome is poor, particu­larly for intracranial bleeding.”⁵⁰ In a December 2024 study that compared the risk of mortality between DOAC and warfarin users in the UK and Hong Kong, the researchers found that as long as careful monitoring took place, warfarin use “was associated with a lower hazard of all-cause mortality, compared with DOAC use,” although they also acknowledged that analysis of cause-specific mortality might reveal a more complex picture.⁵¹

When DOACs fail, they fail spectacularly. A People’s Pharmacy reader described her mother’s rapid decline after taking Xarelto for two months; her mother ended up in a coma, and when doctors subjected her to abdominal sur­gery, she lost five pints of blood; four days after she was sent back into surgery for cauterization of her arteries, she died from internal bleeding in the stomach and head.¹⁰ It is not hard to find similar stories about Eliquis.^52,53

The alarming scale of bleeding-related in­juries and deaths experienced by patients taking one of the three leading DOACs has given rise to thousands of lawsuits, with users alleging that the manufacturers intentionally understated the drugs’ risks. In 2014, Boehringer agreed to a $650 million Pradaxa-related settlement to resolve over four thousand cases; this was followed in 2019 by a paltry $775 million settle­ment for nearly twenty-five thousand Xarelto-related lawsuits; J&J/Bayer admitted no liability but stated that their product liability insurance would help cover the settlement costs.³⁷

In the case of Eliquis, plaintiffs alleged not only that the two manufacturers had “concealed knowledge of Eliquis’ defects and negligently and fraudulently misrepresented the drug’s safety and risks”⁴³ but also pointed to the manu­facturers’ failure to disclose the disturbing fact that if someone experienced life-threatening internal bleeding, the bleeding essentially was irreversible because, until 2019, Eliquis had no antidote. Right after the FDA conditionally approved a drug called Andexxa (recombinant coagulation factor Xa) as an Eliquis reversal agent, a federal judge conveniently dismissed all Eliquis litigation.⁴³ Drugwatch reported in April 2025 that it was “unaware of any lawyers still accepting Eliquis lawsuits.”

The FDA’s “accelerated approval” for Andexxa allows it to be given to Eliquis and Xarelto users who experience severe or un­controlled bleeding. In 2020, the company Alexion acquired Andexxa’s developer, Portola Pharmaceuticals, for $1.4 billion, and a year later, AstraZeneca scooped up Alexion for $39 billion, apparently anticipating record profits. In late 2024, however, FDA signaled that it was having second thoughts about progressing to full approval, citing “major safety findings.”⁵⁴

Indeed, Andexxa comes with the warning that the medication can cause “some serious health issues.” Side effects listed as “more common” include anxiety or confusion; blue lips, fingernails or skin; breathing difficulties; cardiac symptoms such as chest pain or dis­comfort, tightness in the chest and fast heart­beat; sweating; nausea and vomiting; cough; decreased urine output; dilated neck veins or neck pain; swelling (of face, fingers, feet, arms or legs); dizziness, lightheadedness and faint­ing; double vision; extreme tiredness or weak­ness; headache; inability to move arms, legs or facial muscles; and difficulty speaking, slowed speech or inability to speak.⁵⁵ Information for health care professionals indicates that adverse events affecting the cardiovascular, genitouri­nary, hematologic, immunologic, nervous and respiratory systems are all “very common,” as is death (in up to 15 percent of patients “prior to the day 30 follow-up visit”).⁵⁵

Doctors have also used a warfarin antidote called Kcentra (prothrombin complex concen­trate), made by CSL Behring, as an off-label reversal agent for Eliquis and Xarelto. Its top warnings include thromboembolic complica­tions and serious allergic or anaphylactic-type reactions.⁵⁶

Conveniently, Boehringer makes its own antidote for Pradaxa, covering both ends of the market. Praxbind (idarucizumab) has another lengthy list of serious side effects, many of which are similar to Andexxa’s, with the addi­tion of colorful symptoms such as bone pain, convulsions and seizures, hives, nervousness, nightmares, sudden loss of coordination and coma.⁵⁷

In 2019, a nurse and concerned wife posted an insightful comment at the People’s Pharmacy in response to an article about DOAC antidotes; her comment is worth quoting at length [CAPS in original]:

“Cardiologists love Eliquis—whether they believe it is superior to warfarin or they’re the victims of eloquent marketing. The reality is that this and other similar drugs are fairly new, so if history is any indication, we WILL find unexpected and/or unadvertised effects. Andexxa is VERY new. There’s little data collected to judge just how effective it is in reversing bleeding episodes and avoiding serious outcomes. Praxbind. . . has shown mixed results, and I anticipate that Andexxa will have similar lukewarm performance. As a registered nurse whose spouse recently started Eliquis, I was anxious, and vigi­lant in assessing him for any side effects. He did develop petechiae […] scattered all over his lower legs. Consulting his doctor, a trip to the emergency room and lab tests resulted in physicians shrugging their shoulders, since this is not a KNOWN side effect of Eliquis. . . One note: Eliquis is prescribed in a ‘one size fits all’ dosage. There is no ability to individualize the dose since there is no testing. To my mind, this increases the possibility of both bleeding episodes and clotting problems.”⁵⁸

The very real risks of experiencing major bleeding as a result of taking widely prescribed anticoagulants have significant quality-of-life implications. In a 2020 press release, the National Blood Clot Alliance (NBCA) shared survey results showing that over half (55 percent) of American adults who take anticoagulant medications “very much or somewhat fear experiencing a life-threatening bleed,” and among those, almost three-quarters report feeling “more cautious about routine activi­ties.”⁵⁹ The NBCA summed up the sad findings as follows:

“The results of our survey demonstrate that people are making lifestyle decisions—possibly avoiding activities and hobbies they love—such as gardening or exercising—because they are afraid of experiencing serious or dangerous bleeding as a side effect of their blood thinning medication.”

Among the routine activities that seemed to prompt greater caution were cooking, using sharp tools and knives, shaving, brushing teeth, flossing and going barefoot. Patients also reported feeling worried when engaging in leisure activities such as gardening, working out, traveling or playing with children and grandchildren. Even more tragically, 42 percent reported that blood thinner concerns had “discouraged them from trying new activities.”

There is near unanimity in the medical literature that anticoagulant-related bleeding incidents are unfortunate. Even so, almost no one is offering any answers or transparently educating AF patients, surgery recipients or oth­ers about anticoagulant risks. Still, fewer men­tion natural alternatives for blood clotting such as nattokinase, blackstrap molasses, cayenne, ginger or DMSO.⁶⁰ Instead, some of the medical researchers who are concerned about bleeding think that one solution could be for patients to add drugs like proton-pump inhibitors to their regimen to lessen the risk of gastrointestinal bleeding.²⁷

In 2020, the Lown Institute sounded a rare note of caution in an article about AF patients, warning that “clinicians need to be aware of the potential harms” of blood thinners and arguing that “there is no clear ‘right answer’ for all patients.”⁶¹ The article also reasonably observed, “The goal of patients is their global well-being, a goal that does not necessarily align with the optimal end point for each of their medical conditions. It is the fundamental role of the primary care physician to balance these conflicting concerns.”

Even fans of DOACs admit that their pet drugs have limitations, stating, “The perfect anticoagulant should be well-tolerated by the entire patient population, be orally administered with a wide therapeutic window, and have favor­able absorption, distribution, and elimination. In addition, efficacy of the drug should be easy to test, a proper neutralizing agent should be available, and, perhaps most importantly, the drug should have limited to no side effects such as bleeding.”²⁴ None of the drugs currently in use comes anywhere close to perfection.

---

SIDEBARS

THE CLOTS THAT CONVENTIONAL MEDICINE WON’T TALK ABOUT

In the wake of the Covid injection rollout, strange blood clots began attracting the attention of many professional groups, including embalmers. By mid-2021, morticians were reporting increased clotting across all age groups.⁶² In of­ficial circles, of course, the sudden emergence of weird arterial and venous clots in healthy individuals was and remains “rare” and “unusual,” variously blamed on influences such as coffee,⁶³ hot (or cold) weather⁶⁴ or conveniently elusive scapegoats such as “post-pandemic stress disorder.”⁶⁵

Since Covid, the “prepandemic upward pattern” in anticoagulant prescribing—and, notably, prescribing of Pfizer’s Eliquis—has continued apace (aside from brief disruptions during the early months of 2020). Discussing this, a researcher writing in January 2023 remained mum about the blood clots associated with Pfizer’s Covid shots but suggested that the increased demand for anticoagulants made by Pfizer and others might reflect “both the growing understanding of the relationship between severe COVID-19 and blood clots and the rise in hospitalizations for acute cardiovascular disease after May 2020.”⁶⁶

LIVER TOXICITY: AN OPEN QUESTION

After the use of Eliquis and other DOACs took off, a subset of researchers began sounding the alarm about the drugs’ liver toxicity. A 2023 meta-analysis assembled case reports of DOAC-induced liver injury in twenty-seven patients who experienced symptoms such as jaundice, elevated liver enzymes, elevated bilirubin levels and “features of acute hepatitis and cholestatic injury.”⁶⁷ The average time to onset of liver-related symptoms was around forty days. Although reassuringly commenting that all but one patient (who died) ultimately had favorable outcomes, the authors noted that DOACs’ relatively short track record and rising use require more extensive post-marketing and population-based stud­ies, with the drugs’ liver toxicity “yet to be completely determined.” Other researchers have likewise acknowledged the lack of real-world data on liver injury risks associated with DOACs.⁶⁸

---

REFERENCES

1. Lee AR. Blood clot in heart: cardiac thrombo­sis vs coronary thrombosis. Verywell Health, updated Apr. 24, 2024.
2. Anticoagulants. Cleveland Clinic, reviewed Jan. 10, 2022. https://my.clevelandclinic.org/health/treatments/22288-anticoagulants
3. Living your best life while taking blood thin­ners. National Blood Clot Alliance, n.d. https://www.stoptheclot.org/living-your-best-life-while-taking-blood-thinners/
4. Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol. 2007 Apr;44(2):62-69.
5. Blood clots in the United States. National Blood Clot Alliance, n.d. https://www.stoptheclot.org/blood-clot-information/blood-clots-in-the-united-states/
6. Kahn SR. The post-thrombotic syndrome. Hematology Am Soc Hematol Educ Program. 2016 Dec 2;2016(1):413-418.
7. Teller M. Hip replacement surgery in a throwaway society. Wise Traditions. Fall 2024;25(3):36-42.
8. Data and statistics on venous thromboembolism. CDC, Jan. 27, 2025. https://www.cdc.gov/blood-clots/data-research/facts-stats/index.html
9. O’Donnell M, Weitz JI. Thromboprophylaxis in surgical patients. Can J Surg. 2003 Apr;46(2):129-135.
10. Graedon J. Patients walk a dangerous tightrope on blood thinners. The People’s Pharmacy, Nov. 19, 2024.
11. Web Annex A. World Health Organization Model List of Essential Medi­cines – 23rd List, 2023. In: The selection and use of essential medicines 2023: Executive summary of the report of the 24th WHO Expert Committee on the Selection and use of Essential Medicines, Apr. 24-28, 2023. Geneva: WHO, 2023 (WHO/MHP/HPS/EML/2023.02).
12. Qiu M, Huang S, Luo C, et al. Pharmacological and clinical application of heparin progress: an essential drug for modern medicine. Biomed Phar­macother. 2021 Jul;139:111561.
13. Unfractionated heparin (UFH). National Blood Clot Alliance, n.d. https://www.stoptheclot.org/about-clots/blood-clot-treatment/unfractionated-heparin/
14. Oduah EI, Linhardt RJ, Sharfstein ST. Heparin: past, present, and future. Pharmaceuticals (Basel). 2016 Jul 4;9(3):38.
15. Low molecular weight heparin (LMWH). National Blood Clot Alliance, n.d. https://www.stoptheclot.org/about-clots/blood-clot-treatment/low-molecular-weight-heparin/
16. Heparin-induced thrombocytopenia. Cleveland Clinic, reviewed Aug. 12, 2022. https://my.clevelandclinic.org/health/diseases/24014-heparin-induced-thrombocytopenia
17. Warnock LB, Huang D. Heparin. Treasure Island (FL): StatPearls Publish­ing; 2025 Jan-.
18. Trafton A. Conclusive evidence that tainted heparin caused allergic reac­tions. MIT News, Dec. 3, 2008.
19. Gibson R, Singh JP. China Rx: Exposing the Risks of America’s Dependence on China for Medicine. Prometheus, 2018.
20. Heparin: a wake-up call on risks to the U.S. drug supply. Pew Charitable Trusts, May 16, 2012.
21. Van Beusekom M. Report details where top 100 brand-name Rx drugs are made. CIDRAP News, Jan. 26, 2022.
22. Lim GB. Warfarin: from rat poison to clinical use. Nat Rev Cardiol. 2017 Dec 14.
23. American Chemical Society. The Invention of Warfarin. Washington, DC: National Historic Chemical Landmarks Program, 2022.
24. Heestermans M, Poenou G, Hamzeh-Cognasse H, et al. Anticoagulants: a short history, their mechanism of action, pharmacology, and indications. Cells. 2022 Oct 13;11(20):3214.
25. Tideman PA, Tirimacco R, St John A, et al. How to manage warfarin therapy. Aust Prescr. 2015 Apr;38(2):44-48. Erratum in: Aust Prescr. 2016 Apr;39(2):66.
26. Ornstein C. Popular blood thinner causing deaths, injuries at nursing homes. ProPublica, Jul. 12, 2015.
27. Otman H. More than one-third of patients risk major bleeding by doubling up on blood thinners. Michigan Medicine, Mar. 4, 2019.
28. Yang Q, Parker K. Are you on a blood thinner? If so, here are things you need to know. The State Journal-Register, Feb. 14, 2022 (updated Feb. 15, 2022).
29. Schaefer JK, Li Y, Gu X, et al. Association of adding aspirin to warfarin therapy without an apparent indication with bleeding and other adverse events. JAMA Intern Med. 2019 Apr 1;179(4):533-541.
30. Cowan T. Questioning the safety and effective­ness of daily aspirin use. Wise Traditions. Fall 2018;19(3):34-36.
31. The Bristol-Myers Squibb-Pfizer Alliance is pleased with the U.S. District Court decision to uphold both the composition of matter (COM) patent (US 6,967,208) and formulation patent (US 9,326,945) covering Eliquis®. Bristol My­ers Squibb, Aug. 5, 2020.
32. Steppich B, Dobler F, Brendel LC, et al. Ef­fect of the FXa inhibitors rivaroxaban and apixaban on platelet activation in patients with atrial fibrillation. J Thromb Thrombolysis. 2017 May;43(4):490-497.
33. Ordovás Baines JP, Climent Grana E, Jover Botella A, et al. [Pharmacokinetics and phar­macodynamics of the new oral anticoagulants dabigatran and rivaroxaban]. Farm Hosp. 2009 May-Jun;33(3):125-133. Spanish.
34. Ageno W, Caramelli B, Donadini MP, et al. Changes in the landscape of anticoagulation: a focus on direct oral anticoagulants. Lancet Haematol. 2024 Dec;11(12):e938-e950.
35. Navar AM, Kolkailah AA, Overton R, et al. Trends in oral anticoagulant use among 436 864 patients with atrial fibrillation in community practice, 2011 to 2020. J Am Heart Assoc. 2022 Nov 15;11(22):e026723.
36. HT Staff. Oral anticoagulants overprescribed in AF. The Hospitalist, Apr. 14, 2015.
37. Bellon T. Bayer, J&J settle thousands of U.S. Xarelto lawsuits for $775 million. Reuters, Mar. 25, 2019.
38. McCaffrey K. With more marketing spend be­hind it, Eliquis gains on market leader Xarelto. MM+M, Nov. 2, 2016.
39. Dunleavy K. The top 20 drugs by worldwide sales in 2021. Fierce Pharma, May 31, 2022.
40. ClinCalc DrugStats: Most commonly prescribed medications in 2021. ClinCalc.com, Jan. 1, 2024.
41. Sheridan N. Eliquis marketing strategy 2025: a case study. Latterly.org, n.d.
42. https://www.drugwatch.com/eliquis/
43. https://www.drugwatch.com/eliquis/lawsuits/
44. Marshall H. Eliquis side effects and how to manage them. Medical News Today, updated Mar. 24, 2025.
45. Lovelace B Jr. Medicare announces lower prices on 10 common, high-cost drugs. NBC News, Aug. 15, 2024.
46. Pfizer rakes in millions as Eliquis revenue increased. Accountable, Jul. 30, 2024.
47. Report: PhRMA company R&D spending pales in comparison to other priorities like lobbying and investor giveaways. Accountable, May 9, 2024.
48. Fromson N. Most blood thinner dosing problems happen after initial pre­scription. Michigan Medicine, Jul. 31, 2024.
49. Ciccone MM, Zito A, Devito F, et al. To bleed or not to bleed: that is the question. The side effects of apixaban. Curr Drug Targets. 2018;19(6):581- 584.
50. Wendling P. Reversal agents curb DOAC-related bleeding but deaths still high. The Hospitalist, Jun. 17, 2021.
51. Wang Z, Matthewman J, Tazare J, et al. Risk of mortality between warfarin and direct oral anticoagulants: population-based cohort studies. BMC Med. 2024 Dec 23;22(1):597.
52. Burns T. Eliquis brain bleed caused husband’s death, lawsuit says. Top Class Actions, Mar. 7, 2016.
53. Eliquis and bleeding. Schmidt Firm, n.d. https://www.schmidtlaw.com/eliquis-and-bleeding/
54. Dennis M. Fate of AstraZeneca’s Andexxa unclear as FDA rejects full ap­proval. FirstWord Pharma, Dec. 17, 2024.
55. https://www.drugs.com/sfx/andexxa-side-effects.html
56. https://www.drugs.com/monograph/prothrombin-complex-concentrate-human.html
57. https://www.drugs.com/sfx/praxbind-side-effects.html
58. Comment from Valerie on Sep. 26, 2019, posted at Graedon J. Is there an antidote for Xarelto or Eliquis bleeding? The People’s Pharmacy, Oct. 15, 2019.
59. Majority (55 percent) of Americans taking blood thinners indicate they fear suffering from major bleeding; 73 percent more cautious with routine activities to avoid risk. National Blood Clot Alliance, Jun. 23, 2020. https://www.prnewswire.com/news-releases/majority-55-percent-of-americans-taking-blood-thinners-indicate-they-fear-suffering-from-major-bleeding-73-percent-more-cautious-with-routine-activities-to-avoid-risk-301081396.html
60. https://www.earthclinic.com/mobile/cures/blood-clot-treatment.html
61. Garber J. The harms and benefits of blood thinners for older adults. Lown Institute, Jun. 21, 2020.
62. Dumais JM. Exclusive: 70% of embalmers report finding strange blood clots beginning in mid-2021. The Defender, Jan. 22, 2024.
63. Lin T, Mao H, Jin Y. Caffeinated beverages intake and risk of deep vein thrombosis: A Mendelian randomization study. PLoS One. 2024 Feb 13;19(2):e0298123.
64. Knightly K. Rash of blood clots caused by…the heat? Off-Guardian, Jun. 17, 2022.
65. Knightly K. “Post pandemic stress disorder” … seriously? Off-Guardian, Dec. 3, 2021.
66. Van Beusekom M. Demand for blood thinners rapidly fluctuated amid COVID. CIDRAP News, Jan. 3, 2023.
67. Juneja D, Nasa P, Jain R. Liver injury from direct oral anticoagulants. World J Hepatol. 2023 Jun 27;15(6):841-849.
68. Maura G, Bardou M, Billionnet C, et al. Oral anticoagulants and risk of acute liver injury in patients with nonvalvular atrial fibrillation: a propensity-weighted nationwide cohort study. Sci Rep. 2020 Jul 15;10(1):11624.

This article appeared in Wise Traditions in Food, Farming and the Healing Arts, the quarterly journal of the Weston A. Price Foundation, Summer 2025

🖨️ Print post