NYU Langone Health clinicians utilized expertise and knowledge of the medical literature to avoid surgery and successfully treat a patient with antiphospholipid syndrome, whose left-brain stroke had been triggered by a large thrombotic valvular vegetation.

Informed Testing Reveals a Diagnosis of Nonbacterial Thrombotic Endocarditis

A 36-year-old man living in New York City who had been previously diagnosed with primary antiphospholipid syndrome (PAPS) and rejected first-line treatment with warfarin was treated with rivaroxaban due to personal preference. His medical history included a prior deep vein thrombosis as well as hypertension and asthma. The patient presented to the Ronald O. Perelman Center for Emergency Services, located within NYU Langone’s Tisch Hospital, with a left-brain stroke characterized by aphasia in March 2018. A brain MRI revealed evidence of multiple cerebral emboli, and a transthoracic echocardiogram demonstrated a large, 2.7-cm vegetation on his aortic valve.

H. Michael Belmont, MD, professor of medicine and co-director of NYU Langone’s Lupus Center, says several aspects of the case influenced how the medical team responded. Test results revealed a triple-positive antiphospholipid (aPL) antibody profile, which is associated with a high risk for arterial and venous thrombotic antiphospholipid syndrome (APS) as well as non-criteria manifestations of APS, which includes cardiac valvulopathy. Dr. Belmont notes that the lupus anticoagulant (LAC) test result could have been a false positive given the patient’s use of rivaroxaban, a Factor Xa inhibitor, at the time of the test. Assay for antiphosphatidylserine-prothrombin can be useful in this circumstance as the presence of this aPL associates with a true LAC but is insensitive to anticoagulation.

Based on the patient’s negative blood cultures and lack of fever or leukocytosis, as well as prior PAPS, Dr. Belmont made a clinical diagnosis of nonbacterial thrombotic endocarditis or marantic endocarditis.

Analysis of Valvular Vegetation Points to Heparin Therapy in Lieu of Surgery

The existing medical literature, relying principally on acute or chronic bacterial endocarditis, argues that a vegetation in excess of 1 cm, with evidence of clinical embolization, should be surgically managed with a thrombectomy or aortic valve replacement. However, based on confidence that the vegetation was neither infectious nor inflammatory, with no clinical or serological systemic lupus erythematosus (SLE) to suggest a Libman-Sacks valvular lesion, the rheumatology team recommended that surgery be deferred and the patient instead be treated with a continuous therapeutic heparin infusion.

That decision not only spared the patient from major cardiovascular surgery but also resulted in a rapid and complete response of his marantic endocarditis. “In a series of 3 echocardiograms over 10 days, the large vegetation completely disappeared,” Dr. Belmont says. The patient subsequently agreed to warfarin anticoagulation therapy with a target international normalized ratio (INR) of 3.

Anticoagulation Therapy for Valvular Vegetation Is Backed by Clinical Trials and Case Reports

According to Dr. Belmont, several published case reports had previously demonstrated the efficacy of anticoagulation therapy in treating valvular vegetations in APS, typically with a longer time course than what doctors observed here. The patient’s positive outcome also reinforced a growing consensus that rivaroxaban is not the drug of choice for PAPS, he notes. Two recent randomized, open-label studies, in fact, strongly suggest that rivaroxaban is less effective than warfarin in preventing recurrent thrombotic events in APS.

In a trial of 190 adult patients in Spain diagnosed with thrombotic APS, those taking rivaroxaban had a significantly increased risk of recurrent thrombosis, including stroke, throughout a 3-year period, thrombosis occurred in 11.6 percent of those taking rivaroxaban and in 6.3 percent of those on warfarin (Ordi-Ros et al., 2019). Clinicians in Italy terminated a second trial prematurely after enrolling 120 high-risk patients because of an excess number of thromboembolic events and major bleeding among patients in the trial’s rivaroxaban arm—events occurred in 19 percent of those taking rivaroxaban, compared with 3 percent of those on warfarin (Pengo et al., 2018).

Despite Risks, Warfarin-Based Treatment Leads to Patient’s Full Recovery

Warfarin still requires careful monitoring for adverse events such as excessive bleeding. The patient was readmitted to the Ronald O. Perelman Center for Emergency Services in September 2019 with a supratherapeutic INR of 7 after experiencing 2 weeks of abdominal pain and was diagnosed with a hemoperitoneum. The bleeding resolved with judicious use of vitamin K and prothrombin complex concentrate, and the patient resumed a heparin drip bridge to a lower dose of warfarin.

PAPS can be complicated by large cardiac valvular vegetations, which can serve as the source of cerebral embolization. But in contrast to infectious endocarditis, this can rapidly respond to medical therapy with anticoagulation, thereby sparing the patient the risks associated with surgery.

“The patient has made a full recovery,” Dr. Belmont says, “but he will require indefinite warfarin treatment until and unless an alternative option for anticoagulation proves to have a comparable efficacy and isn’t accompanied by an increased risk of bleeding.” Follow-up visits have confirmed that the patient is clinically well, and repeat echocardiograms have shown continued resolution of his thrombotic vegetation.

References

Ordi-Ros J … Cortés-Hernández J. Rivaroxaban versus vitamin K antagonist in antiphospholipid syndrome: A randomized noninferiority trial. Ann Intern Med. 2019. DOI.

Pengo V … Banzato A. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. 2018. DOI.