Can apixaban (Apixaban) cause drug-induced leukocytoclastic vasculitis after two years of treatment?

From the Guidelines

Yes, drug-induced leukocytoclastic vasculitis (LCV) is possible after two years on apixaban, though it is rare. Apixaban (Eliquis), a direct oral anticoagulant, has been associated with cutaneous vasculitis in a small number of case reports, even after prolonged use 1. The delayed onset doesn't rule out a drug reaction, as some medications can trigger hypersensitivity reactions after extended periods of exposure.

Key Considerations

• If LCV is suspected while on apixaban, a thorough evaluation is necessary, including skin biopsy to confirm the diagnosis and laboratory tests to exclude other causes of vasculitis.
• Management typically involves discontinuation of the suspected drug under medical supervision and switching to an alternative anticoagulant if needed, as suggested by guidelines for anticoagulant therapy 1.
• Temporary corticosteroids may be prescribed to manage inflammation.
• The mechanism likely involves immune complex formation and deposition in blood vessel walls, leading to neutrophil infiltration and vessel damage.
• The temporal relationship between drug exposure and symptom onset, improvement after drug discontinuation, and exclusion of other causes would support the diagnosis of apixaban-induced LCV.

Clinical Guidance

• Clinicians should be vigilant about the potential for drug-induced LCV in patients on long-term apixaban therapy, particularly if they present with cutaneous symptoms suggestive of vasculitis.
• The use of direct oral anticoagulants, including apixaban, for primary thromboprophylaxis in ambulatory cancer patients has been guided by studies such as CASSINI and AVERT 1, but these do not directly address the risk of LCV.
• Given the potential for rare but serious adverse effects like LCV, the decision to continue or discontinue apixaban should be made on a case-by-case basis, considering the individual patient's risk factors and the availability of alternative anticoagulant therapies.

From the Research

Drug-Induced Leukocytoclastic Vasculitis

• Leukocytoclastic vasculitis is a rare adverse event that can be caused by various medications, including anticoagulants like warfarin 2 and apixaban 3, 4.
• The condition is characterized by inflammation of small blood vessels, which can lead to skin lesions, palpable purpura, and other symptoms.
• Drug-induced leukocytoclastic vasculitis can occur at any time during treatment, but it is often reported to occur within weeks or months after starting the medication 5, 6.

Apixaban-Induced Leukocytoclastic Vasculitis

• There have been reported cases of apixaban-induced leukocytoclastic vasculitis, including a case of a 74-year-old woman who developed the condition after 23 days of apixaban therapy 3.
• Another case reported a 95-year-old male who developed leukocytoclastic vasculitis after 12 days of apixaban treatment 4.
• These cases suggest that apixaban can cause leukocytoclastic vasculitis, although the exact mechanism is unknown.

Time Frame for Development of Leukocytoclastic Vasculitis

• While most cases of drug-induced leukocytoclastic vasculitis occur within weeks or months after starting the medication, it is possible for the condition to develop after a longer period of treatment.
• However, there is limited evidence to suggest that leukocytoclastic vasculitis can occur after two years of apixaban treatment.
• Further research is needed to determine the likelihood of developing leukocytoclastic vasculitis after long-term apixaban use.