A 25 year old female with a recent history of a left upper extremity deep venous thrombosis (DVT) s/p thrombectomy presented to the emergency room with nausea and vomiting and was found to have acute kidney injury. Two weeks prior to presentation, the patient was admitted to another hospital with left upper extremity swelling and was diagnosed with an unprovoked left upper extremity DVT on Doppler ultrasound and underwent thrombectomy. She was discharged on rivaroxaban and subsequently developed nausea and vomiting after her first dose of rivaroxaban. Due to persistent nausea and vomiting throughout the week, she was switched to apixaban with little improvement in symptoms, prompting her presentation to our emergency room. In the emergency room, workup revealed a creatinine of 9.9 from a baseline normal kidney function, and hyperkalemia to 7.2 for which she underwent emergency hemodialysis. She was admitted for workup of the acute kidney injury, which ultimately revealed a plasminogen activator inhibitor (PAI-1) 4G/4G genetic polymorphism.
Discussion:
The primary function of the PAI-1 enzyme is to inhibit tPA, which results in decreased clot breakdown and a hypercoagulable state. The 4G allele is associated with increased PAI-1 plasma activity levels and results in a mild risk for venous thromboembolism. The identified 4G/4G genotype confers a significant risk for venous thromboembolism, given the two copies of the 4G allele. A lesser-known secondary effect of the PAI-1 enzyme is increased inflammation of kidney cells, which has been reported to cause acute kidney injury via a variety of mechanisms, including thrombotic microangiopathy, renal vasculitis, proliferative glomerulonephritis, and membranous nephropathy. Given our patient’s history of a left upper extremity DVT followed by acute kidney injury, with minimal risk factors for both disease processes, a likely etiology linking the two would be the PAI-1 4G/4G gene polymorphism. Ultimately, renal biopsy is needed to confirm whether any underlying renal pathology exists.
Conclusions:
For patients presenting with an unprovoked DVT and acute kidney injury, consideration of PAI-1 gene polymorphism may be warranted. Future research regarding the optimal management of patients with PAI-1 4G/4G gene polymorphism is needed.