They examined a year of warfarin reversal data at their hospital. So a patient with an INR of 3. This formula can be used iteratively to figure out how many units will drop the INR to the goal range.
I need something quick and dirty. He calculated the number of plasma units based on some common INR ranges, assuming that the goal was to get it down under 1. Here is the table:. Bottom line: This is a nice little piece of information to tuck into your pocket or phone.
For patients inside the usual therapeutic values, it will take units of plasma to reverse. Background Bleeding patients or those undergoing procedures that are at high risk of bleeding may require correction of their INR.
However, other studies were able to achieve lower average INR values [2,5,6]. The relationship between the INR and percentage of clotting factors present in the blood is not linear see figure [7].
Figure 1: Adapted from Dzik [7]. Since the INR only provides limited information regarding a single aspect of anticoagulation status, complete normalization for the INR to control bleeding is usually not necessary [6]. An INR elevation alone does not indicate a patient is coagulopathic or at an increased risk of bleeding [7].
Additionally, an INR elevation in patients with liver dysfunction likely reflects an overall state of decreased factor production, both procoagulant and anticoagulant factors [8].
Complete normalization of the INR is not required to achieve hemostasis or prevent bleeding from a procedure. Want to learn more about EM Pharmacology? Fresh frozen plasma is ineffective for correcting minimally elevated international normalized ratios. PMID: W arfarin is effectively used in a wide range of thromboembolic disorders for primary and secondary prevention. Common indications for the use of warfarin in the community include stroke prevention in atrial fibrillation AF , preventing thrombus formation in patients with mechanical heart valves MHV , and treatment of venous thromboembolism VTE.
This update of the previous consensus guidelines 11 is again on behalf of the Australasian Society of Thrombosis and Haemostasis ASTH and offers advice on strategies to prevent over-anticoagulation, the principles of warfarin reversal, and bridging anticoagulation therapy in different clinical settings.
In particular, the focus is on managing:. The recommendations draw on available evidence and the clinical experience of the panel of author—practitioners. As Australian and New Zealand-based experts in the field of thromboembolic disorders, we were invited to join the panel leading guideline development. The process included reviewing up-to-date evidence and existing high-quality evidence-based international guidelines for warfarin reversal.
We conducted a face-to-face meeting on 21 March at which specific questions and drafting of the guidelines were discussed. Further revisions were made by consensus via email. All six members of the panel are the authors of this article. We based our recommendations on the body of evidence, with consideration of the strength of evidence, consistency across studies, likely clinical impact, and generalisability and applicability of study findings in the local setting.
Relevant clinical questions guided systematic review of the evidence. The strength of recommendations, designated strong 1 or weak 2 , is based on the quality of the body of evidence, which can be high A , moderate B or low C. Consensus recommendations were reached in an equitable manner. Agreement of all members of the expert panel was required in order to proceed with making the recommendation. Potential conflicts of interest were declared and recorded. Bleeding is the most common complication of warfarin therapy and is related to the INR value.
Although incremental rises in INR increase the risk of bleeding, most intracranial bleeds are in patients with an INR in the therapeutic range; they occur in 0. Elderly patients are generally more sensitive to warfarin and need a lower mean daily dose.
An occurrence suggests an underlying organ-specific lesion and should be appropriately investigated. Alcohol in small to moderate amounts probably has little effect on warfarin metabolism. Among heavy drinkers, however, associated factors such as increased falls, alcohol-induced gastritis, poor diet and poor compliance all increase the risk of bleeding. General principles for preventing high INR include careful therapeutic monitoring and adopting other precautionary measures that can minimise bleeding risk due to high INR Box 2.
Vitamin K 1 is an effective antidote to the anticoagulant effect of warfarin. Despite this, data are lacking to show that its use improves outcome in life-threatening bleeds. Currently, phytomenadione is the only injectable formulation available in Australia and New Zealand. While intravenous or oral routes of administration can be used and are effective in reversing an INR that is raised because of warfarin therapy, the intravenous route achieves a more rapid response compared with oral administration, with an onset of action seen within 6—8 hours.
However, both routes achieve a similar correction of INR by 24 hours. Vitamin K 1 should not be administered by subcutaneous or intramuscular routes. Subcutaneous administration is no more effective than placebo, while intramuscular injection in an over-anticoagulated patient may lead to haematoma and bleeding, and its effect on reversal is unpredictable owing to variable absorption — it can be associated with a prolonged increase of vitamin K 1 plasma levels, which may hinder re-anticoagulation.
Although the absolute incidence is unknown, it is most likely rare. There is no convincing association between anaphylaxis and dose, concentration or rate of administration of vitamin K 1 but the literature suggests that current formulations with mixed micelles of lecithin and glycol are safer than the previous preparations containing polyethylated castor oil.
The latter is due to circulating antihuman leukocyte antigen or antigranulocyte antibodies in plasma. In such patients, supplementing factor VII by administering FFP should ensure optimal reversal of the anticoagulant effect of warfarin.
Prothrombinex-VF is able to completely reverse an excessive INR within 15 minutes, but the infused clotting factors have half-lives similar to endogenous clotting factors. Therefore, vitamin K 1 5—10 mg should be given intravenously with the PCC to sustain the reversal effect. FFP contains all coagulation factors present in whole blood but it is not a factor concentrate, and multiple units may be needed if FFP alone is used for warfarin reversal.
Therefore, FFP should not be used routinely to reverse warfarin anticoagulation; however, where PCC is unavailable and emergency reversal is required, FFP should be used, along with vitamin K 1 to sustain the reversal effect. For patients on warfarin therapy with bleeding in whom the aim is to normalise the INR , vitamin K 1 given intravenously is the preferred treatment because of its faster and predictable onset of action. Consistent with other guidelines, we recommend a dose of 5—10 mg. Among patients with an elevated INR up to There are no randomised studies to guide management of patients whose INR exceeds A recent single-arm study involving outpatients with an INR greater than Many patients on warfarin are outpatients and information on individual patient bleeding risk is frequently not available to laboratory staff who are involved in reporting elevated INR results and attempting to communicate results to patients.
In these settings, good communication between clinical and laboratory staff is essential. When considering how to manage patients receiving warfarin who need surgery, it is important to consider the risk of thrombosis if warfarin is temporarily stopped, relative to the risk of bleeding if it is continued or modified. The perioperative thrombosis risk is determined by the indication for warfarin and the type of surgery, particularly with respect to postoperative VTE.
Box 7 shows our adapted version of a recently published empirical risk stratification scheme for arterial and venous thromboembolism. Bleeding risk is high with cardiac, neurosurgical, cancer-related, orthopaedic or urological operations, and also with certain otherwise minor procedures like colonic polypectomy.
Patients at high risk for arterial and venous thromboembolism should be considered for bridging anticoagulation with therapeutic low molecular weight heparin LMWH or an infusion of unfractionated heparin. It should be noted that quality evidence is lacking to show that bridging with heparin reduces arterial thromboembolism in patients with AF but is associated with increased bleeding see below. Traditionally, warfarin has been stopped 5 days before a major operation. To avoid cancellations because the INR is above this level, the INR can be checked on the day before surgery and vitamin K 1 can be administered if needed.
The above method can be labour intensive. In patients with a stable INR of 2. For patients who need urgent surgery while receiving warfarin therapy, three-factor PCC can effectively reverse the anticoagulant effect. Many dental, dermatological or ophthalmological procedures are associated with a low bleeding risk. Patients with a low bleeding risk need not stop warfarin. Bleeding risk can be minimised after major surgery by adjusting the time when anticoagulant is resumed, according to the anticipated surgical bleeding risk and the extent of intraoperative or immediate postoperative bleeding.
This means that therapeutic LMWH is delayed for 48—72 hours or substituted with prophylactic LMWH in patients having major surgery with a high bleeding risk.
Warfarin can be restarted on the evening of surgery at the previous maintenance dose if there is adequate surgical haemostasis.
The strategies that can be used to manage patients on long-term warfarin therapy during surgery and other invasive procedures are summarised in Box 8.
These strategies are not associated with a delay in re-establishing a therapeutic INR when resuming warfarin after surgery. Grade of recommendation. Quality of supporting evidence.
Strong recommendation, high-quality evidence 1A. Evidence obtained from a systematic review of all relevant randomised controlled trials RCTs or exceptionally strong evidence from observational studies. Strong recommendation, moderate-quality evidence 1B. Evidence from at least one RCT or very strong evidence from observational studies.
Strong recommendation, low-quality evidence 1C. Evidence for at least one critical outcome from observational studies, case series, or RCTs, with serious flaws or indirect evidence. Weak recommendation, high-quality evidence 2A. Evidence obtained from a systematic review of all relevant RCTs or exceptionally strong evidence from observational studies. Weak recommendation, moderate-quality evidence 2B.
Weak recommendation, low or very low-quality evidence 2C. Good practice point GPP. Supporting evidence is insufficient to meet even the lowest grade of evidence. Recommendation is therefore based on consensus opinion of the writing panel of Australasian Society of Thrombosis and Haemostasis.
When starting warfarin therapy, avoid high loading doses of warfarin. In general, it is preferable to start treatment using an initial daily dose of 5 mg, or even lower in elderly patients. Consider potential warfarin—drug interactions.
Avoid concomitant non-steroidal anti-inflammatory drugs and certain antibiotics 2C. Avoid concomitant antiplatelet therapy except where clinical benefit is known, such as mechanical heart valves, acute coronary syndrome, or recent insertion of coronary stents 2C.
Test the INR more frequently after starting, stopping or changing the dose of concomitant medication. Avoid frequent dose adjustments. A change in warfarin dose will take several days to influence the INR, so testing the INR within 24 or 48 hours of a dose change may not truly reflect the steady-state response to the dose adjustment.
Effective patient education can minimise compliance problems. Pharmacogenetic testing to guide warfarin dosing is not necessary 1B Details, Box 1.
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