Taking an anticlotting drug? If you need a procedure, be prepared

Be careful out there, your doctor has a lot to think about when doing this. And getting it wrong will hurt you, not the doctor. 
https://www.health.harvard.edu/blog/anticlotting-drug-procedure-safety-2017110112659

Posted November 01, 2017, 10:30 am

Julie Corliss, Executive Editor, Harvard Heart Letter

Millions of people with cardiovascular disease take drugs that help prevent blood clots, which can lodge in a vessel and choke off the blood supply to part of a leg, lung, or the brain. These potentially lifesaving medications include warfarin (Coumadin) and a class of drugs called non-vitamin K antagonist oral anticoagulants or NOACs. Examples include dabigatran (Pradaxa) and rivaroxaban (Xarelto).
However, if you’re taking one of these drugs and need an invasive procedure — anything from a tooth extraction to a hip replacement — managing the risks can be tricky, says cardiologist Dr. Gregory Piazza, assistant professor of medicine at Harvard Medical School. “There’s a higher-than-normal risk of bleeding during and after the procedure, because your blood doesn’t clot as easily,” he says.
But stopping an anticlotting drug is also risky. Doing so increases the chance of a blood clot, especially if you have surgery, which also leaves you more prone to a clot. “Walking the tightrope between these two extremes can be a challenge for clinicians,” says Dr. Piazza. They need to consider if, when, and how long a person might need to stop taking their anticlotting medication. And the answer hinges on many different factors.

Different risk levels

Each year, about one in 10 people taking a NOAC requires a planned invasive procedure. These include diagnostic tests and treatments that require a doctor to use an instrument to enter the body. Some are more risky than others, of course. Minor procedures such as a skin biopsy aren’t very worrisome, because you can compress and bandage the wound, says Dr. Piazza.
Tooth extractions can bleed a fair amount. Compresses and topical treatments are usually sufficient for controlling the bleeding, although your doctor might suggest skipping your anticoagulant the day of the procedure.

Biopsies, injections, and surgeries

Deciding to stop an anticoagulant for a colonoscopy is more complicated. A diagnostic colonoscopy isn’t likely to cause bleeding. But if the doctor has to remove any polyps from the colon, the risk of bleeding rises. Other procedures that require careful planning for people on anticoagulants include breast and prostate biopsies, as well biopsies of internal organs, such as the kidney or liver, which can lead to hard-to-detect internal bleeding.
Another common procedure (especially in older people) is a steroid injection in the spinal column to treat back pain. This, too, may cause undetected and potentially dangerous bleeding around the spinal column in people taking anticoagulants.
People nearly always have to stop taking anticlotting medications a few days prior to any type of elective surgery. Sometimes, doctors will use injectable, short-acting anticlotting drugs right before and immediately after the operation. This technique, called bridging, helps them better balance the degree of blood clotting during that critical window of time.

A key conversation

In addition to the procedure itself, other factors that affect anticoagulant decisions include a person’s age, any other health problems or medications they take, and whether they’re taking warfarin (which stays in the body for days) or a NOAC (which may lose some of its effect after about 12 hours). Because of all these variables, the best strategy is to make sure that the doctor slated to perform your procedure talks directly with the doctor who prescribed your anticoagulant, says Dr. Piazza. “If that conversation doesn’t take place, patients can have problems with either bleeding or clotting,” he says. Many physicians who do procedures aren’t as familiar with NOAC prescribing guidelines, so they may mistakenly keep people off these medications for a week or more, putting them at risk for a clot.

Why we need to fund newer blood-thinning agents to prevent strokes

Stupidity reigns once again. We don't need better blood thinning agents, we need to solve why clotting occurs and stop that. What triggers the clotting? You go after the primary problem, not the secondary problems. Does no one understand cause and effect?
http://medicalxpress.com/news/2014-11-fund-blood-thinning-agents.html
Care gaps are emerging due to disharmony between healthcare reimbursement policies and evidence-based clinical guideline recommendations, cautions a group of Canadian physicians. Writing in the Canadian Journal of Cardiology, they use the example of stroke prevention in atrial fibrillation (AF) to make a case for engaging with policy-makers to address the growing barriers to patients' access to optimal care.
Stroke is a costly disease, imposing a significant human, societal, and economic burden. AF affects about one in eight people over age 75 and increases the risk of stroke five-fold by causing local blood clots in the heart that can break off and go to the brain. These strokes can be prevented by blood-thinning drugs ("anticoagulants"). Traditionally, the only effective blood-thinning available for AF was based on a compound (warfarin) that inhibits the production in the body of vitamin-K dependent clotting factors.
Warfarin was originally introduced (and is still employed) as a rat poison, and requires very careful use and close safety monitoring in humans. A newer set of compounds, which act directly on clotting factors (called "Direct Acting AntiCoagulants," or DOACs), has been introduced over the last few years. DOACs are simpler to use than warfarin and clinical trials consistently show that they are safer; however, they cost more. Thus, while national guidelines like those of the Canadian Cardiovascular Society generally recommend the preferential use of DOACs, government healthcare funders have been reluctant to provide patients with unrestricted access based on physician prescription.
Stroke in the setting of AF carries an 80% probability of death or disability. In Canada, healthcare expenditures are the single largest category of public expenses with a growth rate that overshadows the rate of economic growth. A recent Canadian stroke costing study reported the average overall cost per patient of the first year of stroke as over CAN$74,000. The initial three months accounted for just over half the overall cost and was driven primarily by hospitalization and rehabilitation. Subsequent costs, such as continuing rehabilitation, homecare, and paid caregivers, contribute substantially to the overall cost of stroke to society. Thus, any extra costs of paying for DOACs must be weighed against the overall health expenditure savings that they produce via their superior value in stroke prevention.

"Although two-thirds of AF-related strokes are preventable with appropriate anticoagulation drugs, these have historically been under-prescribed and poorly managed for the Canadian population with AF," says lead investigator James A. Stone, MD, PhD, Clinical Professor of Medicine at the University of Calgary. "National and international guidelines endorse these drugs as first line therapy for this indication. However, no Canadian province has provided these drugs on an unrestricted basis. These decisions appear to be founded on silo-based cost assessment - the drug costs rather than the total system costs - and thus overlook several important cost-drivers in stroke."
While national guidelines in Canada endorse DOACs (dabigatran, rivaroxaban, and apixaban) in preference to warfarin for stroke prevention and reduction of the risk of intracranial bleeding, and hence the first line therapy for this indication, the Canadian Agency for Drugs and Therapeutics in Health (CADTH) has recommended that these agents receive reimbursement only if warfarin cannot be used (e.g., due to allergy) or after an initial attempt with warfarin therapy has been unsuccessful.
"This places healthcare providers in an awkward position," says Dr. Stone. "They are required to treat many patients in a manner that is discordant with national guidelines and this may have a deleterious clinical impact given recent evidence of heightened risk of both ischemic stroke and bleeding in the first month of initiating warfarin therapy."
According to the authors, CADTH appears to have considered only direct costs such as drug acquisition, the cost of anticoagulation level management itself, treatment costs for bleeding, and avoidable stroke, rather than a more global assessment that includes the cost of the outcome to the patient and indirect costs such as costs associated with undergoing blood clotting assessment, lost productivity due to stroke, and longer-term expenses of caring for individuals who have experienced stroke.
"It is within our personal and professional capacity to direct our efforts at prevention of diseases such as stroke that have such significant human and economic consequences. Appropriate anticoagulation of individuals with AF is an extremely effective means of accomplishing this," notes Dr. Stone.
"Cost containment is essential. However, we must ensure that we consider a complete assessment of costs when we make policy decisions and not limit the scope to select budget silos, and ensure that all stakeholders can understand how and why funding decisions are made. We have a responsibility to our patients to engage with policy-makers in addressing and resolving this barrier to optimal patient care. There needs to be a collaborative approach between funding agencies and clinical practice guideline groups in an effort to clearly defined clinical practice strategies, in any preventative or disease treatment paradigm, that lead to the best cost utility," he concludes.

Snake Venom Helps Hydrogels Stop the Bleeding

Possible use in hemorrhagic stroke? We'll never know because no one in stroke is planning or running a strategy.

Snake Venom Helps Hydrogels Stop the Bleeding

A nanofiber hydrogel infused with snake venom may be the best material to stop bleeding quickly, according to Rice University scientists.
The hydrogel called SB50 incorporates batroxobin, a venom produced by two species of South American pit viper. It can be injected as a liquid and quickly turns into a gel that conforms to the site of a wound, keeping it closed, and promotes clotting within seconds.
Rice chemist Jeffrey Hartgerink, lead author Vivek Kumar and their colleagues reported their discovery in the American Chemical Society journal ACS Biomaterials Science and Engineering. The hydrogel may be most useful for surgeries, particularly for patients who take anti-coagulant drugs to thin their blood.
“It’s interesting that you can take something so deadly and turn it into something that has the potential to save lives,” Hartgerink said.
Batroxobin was recognized for its properties as a coagulant – a substance that encourages blood to clot – in 1936. It has been used in various therapies as a way to remove excess fibrin proteins from the blood to treat thrombosis and as a topical hemostat. It has also been used as a diagnostic tool to determine blood-clotting time in the presence of heparin, an anti-coagulant drug.
“From a clinical perspective, that’s far and away the most important issue here,” Hartgerink said. “There’s a lot of different things that can trigger blood coagulation, but when you’re on heparin, most of them don’t work, or they work slowly or poorly. That obviously causes problems if you’re bleeding.
“Heparin blocks the function of thrombin, an enzyme that begins a cascade of reactions that lead to the clotting of blood,” he said. “Batroxobin is also an enzyme with similar function to thrombin, but its function is not blocked by heparin. This is important because surgical bleeding in patients taking heparin can be a serious problem. The use of batroxobin allows us to get around this problem because it can immediately start the clotting process, regardless of whether heparin is there or not.”
The batroxobin combined with the Rice lab’s hydrogels isn’t taken directly from snakes, Hartgerink said. The substance used for medicine is produced by genetically modified bacteria and then purified, avoiding the risk of other contaminant toxins.
The Rice researchers combined batroxobin with their synthetic, self-assembling nanofibers, which can be loaded into a syringe and injected at the site of a wound, where they reassemble themselves into a gel.
Tests showed the new material stopped a wound from bleeding in as little as six seconds, and further prodding of the wound minutes later did not reopen it. The researchers also tested several other options: the hydrogel without batroxobin, the batroxobin without the hydrogel, a current clinical hemostat known as GelFoam and an alternative self-assembling hemostat known as Puramatrix and found that none were as effective, especially in the presence of anti-coagulants.
The new work builds upon the Rice lab’s extensive development of injectable hydrogel scaffolds that help wounds heal and grow natural tissue. The synthetic scaffolds are built from the peptide sequences to mimic natural processes.
“To be clear, we did not discover nor do any of the initial investigations of batroxobin,” Hartgerink said. “Its properties have been well-known for many decades. What we did was combine it with the hydrogel we’ve been working on for a long time.
“We think SB50 has great potential to stop surgical bleeding, particularly in difficult cases in which the patient is taking heparin or other anti-coagulants,” he said. “SB50 takes the powerful clotting ability of this snake venom and makes it far more effective by delivering it in an easily localized hydrogel that prevents possible unwanted systemic effects from using batroxobin alone.”
SB50 will require FDA approval before clinical use, Hartgerink said. While batroxobin is already approved, the Rice lab’s hydrogel has not yet won approval, a process he expects will take several more years of testing.
The National Institutes of Health and the Welch Foundation supported the research.
Source: Rice University

Evaluate the reversal of the anticoagulant effects of dabigatran by IV administration of 5.0g idarucizumab in patients treated with dabigatran etexilate who have uncontrolled bleeding or require emergency surgery or procedures.

So maybe my friend who refused to go on Pradaxa because of no reversal agent might be able to change her mind.
The trial here:
https://clinicaltrials.gov/show/NCT02104947

A discussion of preliminary results here:

NOAC Antidote Promising in Phase III Trial

Idarucizumab restored clotting in most patients on the new oral anticoagulant (NOAC) dabigatran (Pradaxa) who had serious bleeding or required urgent surgery, according to interim results of the phase III RE-VERSE AD trial.
The median maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours of administration was 100%, based on central laboratory analysis of dilute thrombin time or ecarin clotting time.

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"Idarucizumab normalized the test results in 88% to 98% of the patients, an effect that was evident within minutes," Charles V. Pollack Jr., MD, of the Pennsylvania Hospital in Philadelphia, and colleagues found.