You Make the Call: Could hormonal contraceptives contribute to a renal infarction in a 23-year-old?

This month, Joel Bennett, MD, discusses anticoagulation options for a young patient with a renal infarction and patent foramen ovale.

And don’t forget to check out next month’s clinical dilemma – send in your responses for a chance to win an ASH Clinical News-themed prize!

I have a 23-year-old female patient with no past medical history who was diagnosed with a renal infarction while on a vaginal ring contraceptive. She was also diagnosed with a patent foramen ovale (PFO) and has planned for the closure of the PFO. Currently, she is on intravenous heparin. Does anticoagulation need to be continued after PFO closure, and if so, for how long? Could the vaginal ring contraceptive, which contains estradiol, have contributed to the infarction?

This patient poses three interesting dilemmas.

First, the question of whether the contraceptive could have contributed to the infarction is the easiest to address. The prescribing information for the vaginal ring, which is a combined hormonal contraceptive (CHC), states that in studies “required or sponsored by regulatory agencies, users had a risk of venous thromboembolism (VTE) similar to combined oral contraceptives (COCs).” However, the renal infarction the patient suffered is an arterial event. The prescribing information states that “use of CHCs also increases the risk of arterial thrombosis such as strokes and myocardial infarctions.” Based on the prescribing information, as well as a 2013 report by Sidney et al. in Contraception regarding the risks of VTE and other cardiovascular events in CHC users,¹ I conclude that the answer is likely yes.

Second, the assumption is that because a PFO was detected and the patient had a CHC in place, her renal infarction was due to a paradoxical embolus. Given that a PFO can be detected in about 25% of people, is it certain that this is the case? Although many women take COCs and a substantial percentage of these women would be predicted to have a PFO as well, the number of reports of isolated renal infarctions due to paradoxical emboli is sparse. However, that’s not to say a paradoxical embolus could not be the etiology for the renal infarction in this patient.

Recent reports regarding the efficacy of closing PFOs raise additional questions about this patient.² For example, how big was the patient’s PFO? Was there any evidence of VTE, cardiac thrombi, or cardiac arrhythmia following prolonged monitoring? Did the patient have any concurrent diseases, particularly a collagen-vascular disease like systemic lupus erythematosus? Was there evidence for renal artery fibromuscular hyperplasia or dissection? If none of these factors were present, then the renal infarction was truly “cryptogenic,” and a paradoxical embolus remains a possibility.

The third and most vexing dilemma is whether the patient’s PFO should be closed. There are a multitude of reports concerning closure of a PFO after a cryptogenic stroke, but I would assume they would also apply to cryptogenic renal infarcts. Closing the PFO and anticoagulants/antiplatelet agents seem to have about the same outcome,2 so the issue here is the size of the PFO.³

My suggestion is that if the PFO is sizable, then closing it makes sense. Further, since the patient could have had a paradoxical embolus from a VTE provoked by the CHC, I would give her a three-month course of anticoagulation. If the PFO is small, I would be inclined to place the patient on low-dose aspirin but would not object to using a direct oral anticoagulant instead, assuming she does not have antiphospholipid antibodies.

References

1. Sidney S, Cheetham TC, Connell FA, et al. Recent combined hormonal contraceptives (CHCs) and the risk of thromboembolism and other cardiovascular events in new users. Contraception. 2013;87:93-100.
2. Saver JL. Clinical practice. Cryptogenic stroke. N Engl J Med. 2016;374:2065-74.
3. Ropper AH. Tipping point for patent foramen ovale closure. N Engl J Med. 2017;377:1093-5.

How did readers respond? Check out You Make the Call – Readers’ Response.

I have an 85-year-old male patient with a history of ulcerative colitis on disease-modifying antirheumatic drug therapy who presented with an iliofemoral deep vein thrombosis (DVT) with phlegmasia cerulea dolens. He required urgent catheter-directed thrombolysis with a venous stent placement and is on full-dose oral apixaban 5 mg twice daily, with baby aspirin. He was not immobile preceding the DVT, and his only risk factor appears to be the inflammatory disease. He has normal renal and hepatic function. I was considering changing him to lower-dose of apixaban 2.5 mg twice daily now that he is stable. I realize the AMPLIFY-EXT trial was open only to patients who had less severe presentations and there was equipoise between continuing versus stopping anticoagulation. Can we extrapolate those results to this setting where likely indefinite anticoagulation is indicated?

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