Posts filed under Hematology

Bad Blood

  Written by:  Ade Akhetuamhen ,  MD (NUEM PGY-2)  Edited by:  Spenser Lang, MD (NUEM Alum ‘18)  Expert commentary by : Matthew Levine, MD

Written by: Ade Akhetuamhen, MD (NUEM PGY-2) Edited by: Spenser Lang, MD (NUEM Alum ‘18) Expert commentary by: Matthew Levine, MD


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Expert Commentary

Dr Akhetuamhen has provided a nice quick reference for topical hemostatic agents (THAs).  These agents have become more relevant in recent years, particularly in prehospital care, as the prehospital emphasis has shifted from resuscitating hemorrhage more towards hemorrhage control.  Much of our knowledge of these dressings come from battlefield studies of major hemorrhage.  Their use has been formally endorsed by the American College of Surgeons Committee on Trauma in 2014, particularly for junctional site hemorrhaging.  Dr Akhetuamhen has listed the properties of the ideal THA.  No current product fulfills all of these criteria.

Much of what we know about these agents comes from military studies.  There are limitations to these studies. There are fewer human studies, and these tend to be retrospective, observational, and based on questionnaires.  The possibility of reporting bias exists in these studies and study design made it impossible to control for the type of wound.  There are far more animal studies.  Animal studies allow for the ability to control for wound type, but are more difficult to simulate real life wounds from missiles or shrapnel.

Hemcon and Quickclot products were the earliest products studied by the military and became the early THA gold standards after they were determined to be more effective than standard gauze.  An earlier concern for Quickclot was exothermic reactions from the activated products that caused burns to patients.  As Quickclot transitioned its active ingredient from zeolite to kaolin, this concern diminished.  Quickclot is available in a roll called Combat Gauze that is favored by the military and available in our trauma bay.

Finally, there are some important practical tips for using these products.  THAs are not a substitute for proper wound packing and direct pressure.  Most topical hemostatic agent failures in studies were from user failure!  THAs must come into contact with the bleeding vessel to work.  Simply applying the THA over the bleeding areas does not mean it is contacting the bleeding vessel.  The product may need to be trimmed, packed, shaped or molded in order to achieve this.  Otherwise it is simply collecting blood.  After it is properly applied, pile gauze on top of it and give firm direct pressure for several minutes before checking for effectiveness. 

See what THA(s) you have available in your trauma bay, it is nice to know ahead of time before presented with a hemorrhaging patient what you have and in what form (a roll, sponge, wafer, etc).  Find out how the product is removed.  It may not be relevant to the patient’s ED stay but at some point the dressing needs to come off.   Some are left to fall off on their own.  The chitosan products are removed by soaking them.  When soaked, the chitosan turns slimy and can be slid off atraumatically.

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Matthew Levine, MD

Assistant Professor of Emergency Medicine

Northwestern Medicine


How to Cite this Blog

[Peer-Reviewed, Web Publication]   Akhetuamhen A, Lang S (2018, October 29). Bad Blood.  [NUEM Blog. Expert Commentary by Levine M]. Retrieved from http://www.nuemblog.com/blog/bad-blood


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Posted on October 29, 2018 and filed under Hematology.

Supratherapeutic INR

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Written by: Luke Neill, MD (NUEM PGY-3) Edited by: Logan Weygandt, MD (NUEM Alum '17) Expert commentary by: Abbie Lyden, PharmD BCPS


Expert Commentary

This is an excellent post on the management of supratherapeutic INR in patients taking vitamin K antagonist therapy – and as you described, there is not a one-size-fits-all approach. Warfarin is notorious for being one of the most difficult medications to manage based on narrow therapeutic index, variable dose response, clinically significant diet- and drug- drug interactions, delayed onset and offset of action and the need for frequent monitoring. Fortunately, warfarin does have an antidote in vitamin K. Yet, the choice of when to administer this antidote (and weaknesses of said antidote), along with other therapies including prothrombin complex concentrates (PCCs) and fresh frozen plasma, are not straightforward and depend upon a number of factors. In addition to your excellent teaching points, I have outlined some additional considerations below.

Life-threatening bleeding

In the setting of life-threatening bleed, guidelines dictate our therapeutic approach, which involves holding warfarin and administering 4-factor PCC and intravenous vitamin K (10mg slow infusion over 20-60 minutes)1.

Minor bleeding

The management of life-threatening bleeding is clear and requires aggressive therapy. But how do we manage the patient who has a moderately elevated INR but only a minor bleed? In the setting of minor bleeding (such as intermittent epistaxis), the goal is restore the INR to target range, without leading to subtherapeutic anticoagulation, thus introducing the risk of thrombosis. There is general consensus regarding holding a dose of warfarin in these scenarios but the choice to administer vitamin K has been debated. The choice of approach should depend upon the perceived risk of bleeding, extent of bleed, site of bleed, INR level (and trend in INR), comorbidities (including indication for anticoagulation) and risk of thromboembolism. The downsides to administering vitamin K are worth mentioning as they are sometimes superseded by our focus on providing active treatment (unquestionably necessary in the case of life-threatening bleed).  Excessive vitamin K dosing may result in warfarin resistance for 1-2 weeks which may require extensive bridging therapy once anticoagulation is restarted. For patients with high thromboembolic risk, poor adherence to medications, higher INR goals or comorbidities, this can become complicated and is certainly not without risk.

Elevated INR without bleeding

The 2012 ACCP guidelines recommend administration of oral vitamin K (2.5-5mg) to patients without an active bleed who have an INR>10 (1). Other experts and the 2008 ACCP guidelines use a more conservative cutoff of 9 (2). For those patients with INRs between 4.5 and 10 without evidence of bleeding, the 2012 ACCP guidelines suggest against the routine use of vitamin K. In this post, you make a great point regarding the management of INRs 5-9 without bleeding. That is, the administration of vitamin K may or may not be administered, depending on the risk of bleeding. Low dose vitamin K administration should be more strongly considered in patients with high risk bleed (elderly, prior bleed) and lower risk of thromboembolism. A retrospective review of 633 patients with elevated INR >6 identified risk factors for slow spontaneous lowering of supratherapeutic INR, including older age, higher index INR, lower warfarin maintenance dose, decompensated heart failure and active cancer (3). Knowledge of these risk factors may help guide decision-making when considering whether or not to administer vitamin K.

Urgent Surgery/Procedure

Patients meriting further discussion are those taking vitamin K antagonists who require urgent (same day) surgeries or invasive procedures. These patients are managed in a similar fashion to those with life threatening bleeding – that is to say, vitamin K (10mg IV) and 4-factor PCC. Of note, for those patients who can wait 24 hours, low dose vitamin K (1-2.5mg PO) is generally adequate for INR reversal. In these cases, 4-factor PCC and intravenous vitamin K can be avoided.

Specific Treatments

With regards to the specific treatments to reverse supratherapeutic INR, some points to keep in mind:

  1. Vitamin K (phytonadione): typically administered intravenous or orally.

  • For life-threatening bleed, intravenous vitamin K is preferred due to the faster onset of action (which is still delayed, ~3-8 hours) but faster than oral (onset ~24 hours)

  • Subcutaneous administration is generally avoided if possible due to erratic absorption

  • Intramuscular administration is generally avoided due to the risk of hematoma in an anticoagulated or overanticoagulated patient

2. Prothrombin complex concentrate (PCC):

  • 4-factor PCCs (factors II, VII, IX, X): preferred first line therapy for life-threatening bleed

  • Activated PCC (aPCC): factor VII is mostly present in the activated form, which is potentially more prothrombotic than unactivated PCC

  • Some PCC products contain heparin and should NOT be administered in a patient with a history of heparin-induced thrombocytopenia

In short, patients with life-threatening bleed taking vitamin K antagonist therapy require urgent evaluation and treatment with PCC and IV vitamin K. Treatment with PCC is paramount as INR can be corrected within 30 minutes, as opposed to several hours after IV vitamin K administration (onset dependent upon liver synthesis of new coagulation factors). For those patients with supratherapeutic INR without bleeding and patients with minimal bleed, a more gentle approach is indicated, which involves omission of warfarin dose +/- low doses of oral vitamin K to ensure correction of INR and prevention of bleeding but not subtherapeutic anticoagulation. Lastly, it is important to identify if there are additional explanations for the supratherapeutic INR by verifying if the patient was taking the appropriate dose of warfarin or whether they have recent dietary changes or new medications which may interact. If therapy is to be resumed, these questions are particularly helpful when deciding how and when to restart anticoagulation. 

  1. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e152S.

  2. Ansell J, Hirsch J, Hylek E, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133(6 Suppl):160S.

  3. Hylek EM, Regan S, Go AS, Hughes RA, Singer DE, Skates SJ. Clinical predictors of prolonged delay in return of the international normalized ratio to within the therapeutic range after excessive anticoagulation with warfarin. Ann Intern Med. 2001;135(6):393.

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Abbie Lyden, PharmD BCPS

Clinical Pharmacist, Emergency Medicine | Associate Professor, Pharmacy Practice

Residency Program Director, PGY2 EM Pharmacy

Northwestern Memorial Hospital


How To Cite This Post

[Peer-Reviewed, Web Publication]   Neill L, Weygandt L (2018, October 8). Supratherapeutic INR.  [NUEM Blog. Expert Commentary by Lyden A]. Retrieved from http://www.nuemblog.com/blog/supratherapeutic-inr


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Posted on October 8, 2018 and filed under Hematology.

Transfusion Reactions In The ED

Blood products, despite what may be commonly believed, are a scarce and valuable resource.  While overall, there are many systems to ensure the safety of the products, any transfusion poses a certain degree of risk. We review the spectrum of transfusion reactions, from the common to the uncommon.