Major bleeding on warfarin — reversal, resuscitation and investigation of underlying cause

Diagnosis: life-threatening warfarin-associated intracerebral haemorrhage (ICH) with supratherapeutic INR. The ICH is the most feared complication of warfarin — case fatality doubles compared to non-anticoagulated ICH. Time-critical reversal is the single most important intervention.^[1]

Immediate resuscitation (ABCDE):

• Airway — GCS 10 and vomiting → risk of aspiration; prepare for intubation (rapid sequence) and ventilate to normocapnia.
• Breathing — high-flow oxygen to target SpO2 94-98%.
• Circulation — IV access (two large-bore cannulae), crossmatch, check FBC, coagulation, fibrinogen, U&E; treat the hypertension (SBP over 140 is associated with haematoma expansion) — IV labetalol or nicardipine to SBP 130-140.
• Disability — GCS, pupils, glucose; neuroprotection (head up 30 degrees, normoglycaemia, normothermia).
• Exposure / escalation — ICU; activate major haemorrhage protocol; alert neurosurgery (evacuation/decompression).^[1]

Reversal strategy (do NOT wait for further INR):

• STOP warfarin immediately.^[1]
• Vitamin K (phytomenadione) 10 mg IV slow over 10 minutes — restores hepatic synthesis of carboxylated factors over 6-12 h, lasting 7-14 days.
• Four-factor prothrombin complex concentrate (PCC) 25-50 IU/kg IV immediately — replaces factors II, VII, IX, X within minutes; faster, smaller volume and lower infection risk than FFP. Always given WITH vitamin K because PCC factors decay (half-life 6-8 h) while vitamin K synthesises new ones.
• Fresh frozen plasma (15 mL/kg) is an alternative only if PCC unavailable.
• Recheck INR at 30 minutes post-PCC — confirm reversal to under 1.5.
• Avoid platelet transfusion (no indication here; platelets normal) — reserved for thrombocytopenia or antiplatelet therapy with active bleeding.^[1]

Neurosurgical management:

• Urgent neurosurgical referral — evacuation of superficial lobar haematomas over 30 mL with midline shift is generally beneficial; deep basal ganglia bleeds managed conservatively unless life-threatening mass effect.
• ICP monitoring and osmotherapy (mannitol 0.5 g/kg or hypertonic saline) if signs of raised ICP.
• Seizure prophylaxis — not routine; treat if seizures occur.

Investigations to identify the cause of the supratherapeutic INR and the bleed:

• Detailed drug history — newly added CYP2C9 inhibitors (macrolides, metronidazole, fluconazole, amiodarone, statins, SSRIs, NSAIDs, herbal products — St John's wort is an INDUCER, lowers INR; antibiotics like ciprofloxacin or co-trimoxazole raise INR).
• Adherence and dosing error — inadvertent double dosing.
• Dietary change — reduced vitamin K intake (less leafy greens).
• Acute illness — infection, heart failure, dehydration (reduced warfarin clearance).
• Liver disease / biliary obstruction — check LFTs, albumin; reduced factor synthesis.
• Thyroid dysfunction — hyperthyroidism raises INR sensitivity.
• Occult malignancy — ICH caused by metastasis (lung, melanoma, renal, choriocarcinoma), amyloid angiopathy (elderly with lobar bleeds), or AV malformation — contrast MRI/MRA once stable; the haemorrhage itself may be the first presentation of an underlying lesion.
• Drug history — antiplatelet or NSAID addition.

Disposition and follow-up:

• ICU admission for airway/ventilation and neuro-monitoring.
• Restart anticoagulation? — after ICH, the risk of stroke without anticoagulation in AF must be balanced; restart at 7-14 days post-ICH in most cases, considering bleed control and stroke risk. Switch to a DOAC (apixaban preferred) — half the ICH risk of warfarin in AF (ARISTOTLE).^[8]