Rosen & Barkin's 5-Minute Emergency Medicine Consult (780 page)

• Thorough history:
  
  • Many chief complaints are complicated by anticoagulation.
    
    • Reason for anticoagulation, recent dose changes, compliance, recent INR testing, other prescriptions, over the counter, and alternative medicines
      
    • Subtle changes in mental status, recent “minor falls,” or bleeding
      
• Check for vital sign abnormalities:
  
  • Early hemorrhagic shock
    
  • Hypertension and bradycardia may be secondary to Cushing response in ICH.
    
  • Cardiac meds often mask important changes in vital signs.
    
• Examine carefully for:
  
  • Pallor, contusions, abrasions, ecchymosis, palpable pulses in affected extremity and skin lesions
    
  • Check stool for blood.
    

• PT/PTT/INR:
  
  • Significant bleeding may occur even in INR therapeutic range.
    
  • PTT also elevated with toxicity
    
  • Elevations will be delayed in overdose
    
• CBC:
  
  • Initial HCT inaccurate measure of acute rapid bleeding
    
  • Platelets:
    
    • Aspirin and ADP inhibitors/Plavix result in normal platelet levels but qualitative deficits.
      
• Electrolytes, BUN, creatinine, LFTs, and glucose:
  
  • Elevated BUN may indicate blood in GI tract.
    
  • Coingestants if intentional ingestion
    
• Type and cross-match
  

• Low threshold for CT imaging to detect occult but life-threatening bleeding:
  
• Head CT:
  
  • Minor mechanisms of blunt head trauma without loss of consciousness
    
  • Detect ICH prior to symptom onset
    
• Abdominal CT:
  
  • Blunt abdominal trauma without significant tenderness
    
  • Retroperitoneal hemorrhage
    
  • Solid organ or visceral injury
    

• All causes of bleeding:
  
  • GI, retroperitoneal, CNS, and traumatic
    
• Skin lesions—hemorrhagic skin disorders:
  
  • Hemostatic deficits such as platelet disorders
    
  • Vascular purpuras including glucocorticoid use, vitamin C deficiency, purpura fulimnans, disseminated intravascular coagulation, Henoch–Schönlein purpura, protein C deficiency
    

TREATMENT

• ABCs
  
• Treat hypotension with 2 large-bore IV lines and 0.9% NS infusion.
  
• Cardiac and pulse oximetry monitoring
  

• Establish central IV access for hypotension not responsive to initial fluid bolus:
  
  • Compressible sites only
    
• Replace lost blood as soon as possible
  
  • Initiate with O-negative blood until type-specific blood available.
    
  • 10 mL/kg bolus in children
    

• Specific management depends on the INR, presence of bleeding, reason for anticoagulation, and reliability of patient:
  
  • INR <5 without bleeding:
    
    • Lower or omit next dose.
      
    • Recheck INR in 24 hr.
      
  • INR ≥5–<9 without bleeding:
    
    • Omit next 1 or 2 doses or omit 1 dose and give 1–2.5 mg PO vitamin K.
      
    • If at increased risk for bleeding or pre-op, then administer vitamin K 1–5 mg PO, INR will be lowered in 24 hr.
      
    • Recheck INR in 24 hr.
      
  • INR ≥9 without significant bleeding:
    
    • Hold warfarin and give vitamin K 2.5–5 mg PO; INR will be substantially lowered in 24–48 hr
      
  • INR >20 with minor bleeding or life-threatening bleeding regardless of INR:
    
    • Hold Warfarin
      
    • Vitamin K 10 mg by slow IV infusion
      
    • Fresh frozen plasma (FFP) or prothrombin complex concentrate (PCC) depending on volume status and availability
      
    • PCC shows faster INR reversal and hemostasis; however, no clear benefit has been shown in patient outcome
      
    • PCC preferred in cases of ICH, volume overload, or massive bleeding.
      
• In the setting of controlled bleeding, maintain the INR at the lower level of therapeutic efficacy:
  
  • 1.5–2 for atrial fibrillation
    
  • 2–2.5 with mechanical heart valves
    
• Starting reversal agents before transferring patient leads to better outcomes
  

• Vitamin K1 phytonadione:
  
  • Side effects:
    
    • Anaphylaxis with IV >> IM or PO
      
    • SC absorption unpredictable
      
    • IM administration may result in hematoma formation.
      
    • Breakthrough thromboembolism with complete correction, prolonged risk if high dose vitamin K
      
  • 10 mg IV infusion over 10–30 min is recommended for life-threatening active bleeding with effects beginning in 1–2 hr
    
• FFP:
  
  • Traditionally 3–4 U of FFP (1 L) are given to control continued bleeding in the short term without excessive risk of thromboembolism.
    
  • Additional units may be necessary
    
  • Follow serial INR closely
    
  • Patient response is variable and may not correlate with correction of the INR.
    
  • Side effects:
    
    • Fluid overload
      
    • Virus transmission-rare
      
    • Transfusion-related acute lung injury (TRALI) – rare
      
• PCC:
  
  • Long shelf life and easy reconstitution into a highly concentrated volume (20 mL vs. 1 L of FFP per dose)
    
  • Rapid reversal without volume overload
    
  • Side effects:
    
    • Thrombosis
      
    • Less virus transmission than FFP
      
  • Multiple studies show more rapid reversal of INR, reduction bleeding compared to FFP
    
  • Relationship to patient outcome has not been demonstrated
    
  • 4-factor PCC
    (Kcentra) is a fractionation product of FFP containing equal amounts of factors II, VII, IX, and X:
    
    • FDA approved in 2013, not widely available
      
    • For patients with an INR of 2–3.9, administer 25 U/kg, 4–5.9, 35 U/kg, and >6, 50 U/kg
      
  • 3-factor PCC
    (Bebulin-VH, Profilnide-SD) contains very little factor VIIa:
    
    • Some use in combination with VIIa or VIIa alone depending on availability
      
    • 50 U/kg PCC and 1–2 mg FVIIa has been suggested
      
    • Consider FFP supplementation of FVIIa unavailable
      
    • More widely available in US
      
    • Warfarin reversal is off label use
      

FOLLOW-UP

• Active GI, retroperitoneal, or CNS bleeding
  
• Anticoagulated trauma patient with evidence of active bleeding requires:
  
  • Reversal of anticoagulation and blood replacement
    
  • Early surgical consultation for operative intervention
    
  • Transport to a level 1–trauma center after initial stabilization for definitive care.
    
• Skin necrosis and limb gangrene requires admission for anticoagulation with alternative agents in consultation with a hematologist.
  
• Subtheraputic patient may require adequate anticoagulation with inpatient heparin or low molecular weight heparin to prevent a breakthrough thromboembolism:
  
  • Outpatient Lovenox therapy followed by increased warfarin with close follow-up prevents unnecessary hospitalization
    

• Asymptomatic reliable patient with a supratherapeutic INR after consideration of:
  
  • Indication for anticoagulation, reason for supratherapeutic level, underlying comorbidities, overall risk of bleeding, fall risk, social situation, reliability, and availability of follow-up
    
• Asymptomatic anticoagulated patient with minor trauma, therapeutic INR, stable hemoglobin, normal imaging studies, and reliable caretakers, can be discharged with close follow-up.
  

• Patient should follow up with primary care physician or specialist within 24–48 hr of discharge for INR check and further warfarin adjustments.
  
• Psychiatric referral for intentional overdose
  

Educate patient on monitoring for signs and symptoms of excessive bleeding and/or new thrombotic event.

• Maintain a low threshold for imaging trauma patients on warfarin
  
• No vitamin K for an INR <5 without bleeding
  
• Vitamin K1 IV may result in fatal anaphylaxis:
  
  • Use only in patients with INR >20 with minor bleeding, or patients with life-threatening bleeding
    
    • Administer PO for everyone else.
      
• For rapid reversal, FFP is still considered a 1st-line agent
  
• 4-factor PCC, or 3-factor PCC/FVIIa should be used in patients with ICH, volume overload, or massive bleed
  

• Ansell J, Hirsh 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;133:160S–198S.
  
• Denas G, Marzot F, Offelli P, et al. Effectiveness and safety of a management protocol to correct over-anticoagulation with oral vitamin K: A retrospective study of 1,043 cases.
  J Thromb Thrombolysis
  . 2009;27(3):340–347.
  
• Garcia, DA, Crowther MA. Reversal of warfarin: Case-based practice recommendations.
  Circulation
  . 2012;125:2944–2947.
  
• Sarode R, Matevosyan K, Bhagat R, et al. Rapid warfarin reversal: A 3-factor prothrombin complex concentrate and recombinant factor VIIa cocktail for intracerebral hemorrhage.
  J Neurosurg.
  2012;116:491–497.
  

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