Adverse drug reactions from - anticoagulants

Reactions by class

Dominant reaction across all classes is bleeding - the therapeutic effect taken too far, not a true idiosyncratic reaction
Class-specific additional reactions
- Warfarin: skin necrosis (protein C/S deficiency), purple toe syndrome, teratogenicity
- Heparin: heparin-induced thrombocytopenia (HIT) - immune, paradoxically prothrombotic
- DOACs: fewer interactions/monitoring needs, but renal clearance-dependent accumulation risk

HIT: more common with unfractionated heparin than LMWH; typically day 5-10 of exposure (earlier with prior heparin exposure)
Warfarin skin necrosis: rare, occurs in first days of therapy, esp. with protein C or S deficiency and large loading doses without heparin cover

Warfarin skin necrosis: protein C has a shorter half-life than other vitamin K-dependent factors -> transient procoagulant state in the first 24-72h before full anticoagulant effect established -> microvascular thrombosis, esp. in protein C/S deficiency
HIT: antibodies to platelet factor 4 (PF4)-heparin complex -> platelet activation -> thrombocytopenia with paradoxical thrombosis (arterial and venous)
DOAC accumulation: renal (dabigatran mostly renal; factor Xa inhibitors partly renal) -> levels rise disproportionately as GFR falls

Bleeding - clinical + coagulation studies (INR for warfarin; anti-Xa levels for DOACs/LMWH if needed, not routinely required)
HIT: 4Ts score (Thrombocytopenia, Timing, Thrombosis, oTher causes excluded) -> if intermediate/high probability, send PF4/heparin antibody assay +/- functional assay (serotonin release)
- Platelet count typically falls 30-50% from baseline, may not drop below 150
Warfarin skin necrosis - clinical (painful erythematous/purpuric plaques progressing to necrosis, typically fatty areas - breast, thigh, buttock)

Stop the agent; vitamin K + Prothrombinex-VF for warfarin; idarucizumab for dabigatran; andexanet alfa or PCC for factor Xa inhibitors; protamine for heparin
Reversal only for life-threatening or major bleeding, or before urgent surgery - not for minor bleeding

Stop all heparin immediately (including flushes), do not give platelets prophylactically
Start a non-heparin anticoagulant (e.g. fondaparinux, DTI) - do not simply switch to warfarin alone acutely (transient protein C/S depletion risks venous limb gangrene)

Stop warfarin, reverse with vitamin K, cover with heparin/LMWH, restart warfarin later at low dose with heparin overlap if still needed

Warfarin - drug/food/alcohol interactions (INR instability), teratogenicity (embryopathy in first trimester)
HIT - inc risk of arterial thrombosis (limb ischaemia), DVT/PE, adrenal haemorrhage
DOACs - accumulation in AKI/CKD, drug interactions via P-glycoprotein/CYP3A4

Bleeding risk is ongoing for the duration of therapy - balance against thrombotic indication throughout
HIT antibodies typically clear over weeks-months; thrombotic risk persists while antibodies present
Warfarin skin necrosis - can be extensive, occasionally requires debridement/grafting if not caught early

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