It’s time for a look at the latest review from EBMedicine. This post focuses on the following article:
Hanlon D (2010). An Evidence-Based Approach to Managing the Anticoagulated Patient in the Emergency Department. Emergency Medicine Practice, 13(1). [Abstract and subscription link]
This is a really great review of many of the problems posed by anticoagulated patients in the emergency department:
“This issue of Emergency Medicine Practice focuses on the challenge of evaluating and managing the anticoagulated patient using the best available evidence from the literature. The main complication of this therapy is hemorrhage, which can be life-threatening, depending on its location. This issue also addresses the patient taking antithrombotic or antiplatelet agents and includes discussions of prothrombin complex concentrates and the off-label use of recombinant activated factor VII (rFVIIa).”
In general, the advice regarding reversal of INR in the over-anticoagulated patient is in keeping with Australian guidelines (Australian readers should refer to these MJA guidelines while reading this review). As well as providing a lucid discussion, the review is packed with useful summary tables and flow charts, and the pitfall scenarios and suggested cost-effective strategies provided in this edition are particularly high yield.
Here are some Q&As based on aspects of Hanlon’s review, so you can decide if you need to read it, or you can consolidate your learning once you’ve read it!
Q1. What proportion of patients anticoagulated with warfarin that present to to the emergency department have either sub- or supra-therapeutic INRs?
A prospective study of 300 ED patients on warfarin found that:
- 43% had sub-therapeutic INRs
- 29% were supra-therapeutic
So, only 28% had therapeutic INRs…
It rarely hurts to check an anticoagulated patient’s INR!
Q2. What are the important hemorrhagic complications to consider in an anticoagulated patient?
Important hemorrhagic complications include:
- hematuria (most common)
- intracranial hemorrhage (most devastating)
- spinal epidural hematoma
- retroperitoneal hemorrhage (only 2/3 have abdominal pain)
- rectus sheath hematoma
- compartment syndrome (consider in any limb trauma)
Q3. Which anticoagulated patients need, or do not need, a CT head following a head injury?
There is remarkably little evidence to guide us in dealing with this common and often difficult problem.
A conservative approach is to perform a CT head on all anticoagulated patients following a head injury, unless the INR is subtherapeutic. However at least one small study supports the recommendation that a CT head may not be required if the patient is GCS15 and has no focal neurological deficit. However, the evidence for this recommendation is very weak.
Patients on antiplatelet drugs (such as aspirin or clopidogrel) probably also have a higher risk of intracranial bleeds as well as worse outcomes, however there is little evidence to guide us on their management either.
Unless the head injury was really trivial, order a CT head in anticoagulated patients following head injury.
Q4. You decide to perform a CT head on an anticoagulated patient who fell and hit their head. When should you perform the scan? If it is normal, does the patient still need observation in hospital?
Delayed intracranial hemorrhage is a recognised complication of head injury in anticoagulated patients.
It is probably best to get the CT head as soon as is feasible. However, even if an initial CT head is normal, observation for 6-12 hours and consideration of a repeat CT head is warranted due to the risk of delayed intracranial hemorrhage.
Again, there is little evidence to guide us on this one.
Q5. IV vitamin K has a ‘black box’ warning. How, and when, should it be administered?
Even when intravenous vitamin K has been diluted and given slowly there have been reports of severe anaphylactoid reactions and cardiorespiratory arrest. In light of this, if given, vitamin K should be diluted and administered no faster than 1mg/min.
IV vitamin K should only be given in the context of life-threatening hemorrhage in an anticoagulated patient. Use oral vitamin K whenever possible, unless GI absorption is likely to be compromised.
Q6. Protamine is used to correct coagulopathy caused by which agent(s)? What dose should be given?
Protamine is a reversal agent for heparin. It also reverses about 60% of the effect of low-molecular weight heparin. The maximum dose of protamine is 50mg IV given over 5-10 minutes.
- 1mg protamine for each 100 units of heparin administered — this review advises this dose based on the amount of heparin given in the past 4 hours. Others advise hslving the dose after 1 hour, and quartering it after 2 hours (see Critical Care Drug Manual — Protamine).
- 1mg protamine for each 1 mg of enoxaparin administered — the dose of protamine sulphate should be halved when one half-life has elapsed since the last LMW heparin dose.
Q7. What are Fox’s sign and Bryant’s sign?
Along with the more commonly recognised Grey-Turner and Cullen’s sign, they are signs of retroperitoneal hemorrhage. All tend to occur late.
- Grey-Turner’s sign — flank echymosis
- Cullen’s sign — periumbilical echymosis
- Fox’s sign — echymosis of the upper thigh with a sharp demarcation below the inguinal ligament
- Bryant’s blue scrotum sign — scrotal echymosis
Q8. What is closure time?
Closure time is a measurement of platelet function that replaces the measurement of bleeding time. Citrate-anticoagulated blood is placed in a cartridge with a special membrane, and time-to-clot is assessed. Two types of membrane are used: collagen/ epinephrine and collagen/ ADP. Aspirin will prolong clotting time on the former membrane, but not the latter.
Q9. Compare and contrast fresh frozen plasma with prothrombin complex concentrate.
FFP, or fresh frozen plasma, requires a group and screen like any other blood product. It restores factors II, VII, IX and X in the anticoagulated patient with serious hemorrhage. As it needs to be thawed, there can be a delay of 30-45 minutes prior to it being ready for administration. The dose is 10-15 mL/kg, which may represent a significant fluid load in patients that are elderly and frail, or have heart failure.
PCC, or prothrombin complex concentrate, is a 3 factor pooled plasma product that has a small volume. It is rich in factors II, IX and X, but deplete in factor VII compared to FFP. It provides faster, and perhaps more complete INR reversal than FPP alone, though it is usually used with a lower dose of FFP (e.g. 150-300 mL). PCC is more expensive than FFP and may cause thromboembolic complications, so is best reversed for life-threatening hemorrhage in the anticoagulated patient. In Europe, a 4 factor PCC (containing Factor VII) is available.
According to Australian guidelines, the recommended dose of Prothrombinex-HT for life-threatening hemorrhage in the patient with an elevated INR is 25–50 IU/kg.
Q10. Describe the clinical effects and potential uses of desmopressin.
Desmopressin increases platelet adherence by promoting the release of von Willebrand’s factor. It is inexpensive and does not carry blood-borne viruses. It is primarily used in von Willebrand’s disease and mild hemophilia A. It may have a role in other conditions resulting in abnormal primary hemostasis (formation of the platelet plug) such as acquired bleeding disorders, uremic platelet dysfunction, and patients on anti-platelet drugs (e.g. aspirin, clopidogrel). The dose is 0.3 mcg/kg IV and adverse effects include flushing, hypotension, tachycardia and headache.
Finally, we should remind readers that anticoagulation issues have been covered many times on LITFL. To learn more, or test yourself, you might want to check out these links:
- The Future of Anticoagulation
- Toxicology Conundrums —
015: Little Johnny and Grandad’s warfarin, 016: Warfarin Deliberate Self-Poisoning and 021: Supratherapeutic INR
- Hematology Hoodwinker 002 —
Recombinant Factor 7a to the rescue?!
- Critical Care Drug Manual —
Aspirin, Clopidogrel, Enoxaparin, Heparin, Protamine, Tranexamic Acid, Vitamin K, Warfarin Sodium