Can increases in warfarin (International Normalized Ratio (INR) anticoagulant) cause rashes?

Warfarin Can Cause Various Types of Skin Rashes

Yes, increases in warfarin dosage or elevated INR levels can cause various types of skin rashes, including potentially serious conditions like warfarin-induced skin necrosis.

Types of Warfarin-Related Skin Reactions

• Warfarin can cause several types of skin reactions, including urticarial rashes, erythematous lesions (due to delayed type 4 hypersensitivity reactions), and skin necrosis (often due to vasculitis) 1
• The true incidence of skin reactions caused by warfarin is unknown, but they are considered relatively uncommon adverse effects 1
• In rare cases (0.01% to 0.1% of patients), warfarin can cause a serious condition called warfarin-induced skin necrosis 1, 2

Warfarin-Induced Skin Necrosis

• Warfarin-induced skin necrosis typically occurs 3-6 days after initiation of therapy in 93% of cases, but has been reported as late as 18 months after starting treatment 1
• The condition is diagnosed clinically, with rash usually appearing over fatty areas, most commonly the breasts, followed by the thighs and buttocks 1
• It is more common in middle-aged, perimenopausal women with venous thromboembolism 1
• Pathophysiology may involve large loading doses of warfarin, thrombosis of superficial dermal capillaries, and inherited protein C and S deficiencies 1

Leukocytoclastic Vasculitis

• Leukocytoclastic vasculitis (LV) is another type of skin reaction that can occur with warfarin use 3
• This is primarily a cutaneous small vessel vasculitis, though systemic involvement may be encountered 3
• LV can be a late-onset adverse reaction, developing after receiving warfarin for several years 3
• Skin lesions typically resolve after warfarin is discontinued, and rechallenge with warfarin can lead to recurrence of the lesions 3

Risk Factors and Management

• Protein C and protein S deficiency have been associated with warfarin-induced skin necrosis 1
• Treatment involves discontinuation of warfarin and replenishing vitamin K-dependent factors 1
• Severe cases may require debridement, grafting, or amputation as needed for skin necrosis 1
• For patients who develop skin reactions but still require anticoagulation, heparin should be considered as an alternative for long-term treatment of thromboembolic disease 1

Monitoring and Prevention

• More frequent INR monitoring is essential in patients showing sensitivity to warfarin, initially daily until stabilized 4
• When INR becomes excessively elevated (>5.0) due to warfarin sensitivity, temporary discontinuation of warfarin is recommended until INR falls to safer levels 4
• For patients showing extreme sensitivity to warfarin, initial doses should be lower (0.5-2mg daily) rather than the standard 5mg daily 4
• Overlooking drug interactions that may further increase warfarin sensitivity in already sensitive individuals can lead to dangerous INR elevations and potentially increase the risk of adverse effects including skin reactions 4

Clinical Implications

• If a patient on warfarin develops a rash, particularly after a dose increase or with an elevated INR, the medication should be considered as a potential cause 1, 3
• Prompt recognition and management of warfarin-induced skin reactions is essential to prevent progression to more serious complications 1
• Alternative anticoagulation options should be considered for patients who develop significant skin reactions to warfarin 1