First description of atrial fibrillation and congenital thrombotic thrombocytopenic purpura treated by left atrial appendage occlusion

Abstract Given an increased risk of both thrombosis and bleeding, thrombotic thrombocytopenic purpura (TTP) presents a unique challenge when anticoagulation is required for comorbid disease, particularly in the setting of major bleeding events. We present for the first time a patient with TTP and atrial fibrillation, presenting with recurrent stroke, but unable to tolerate anticoagulation due to prior intra‐cerebral hemorrhage. To address both issues concomitantly, we describe the successful application of a novel management approach to facilitate left atrial appendage occlusion, there by offering a non‐pharmacologic means of stroke prevention without added bleeding risk.


INTRODUCTION
Systemic anticoagulation (SAC) has long been the standard approach to thromboembolic (TE) stroke prevention in atrial fibrillation (AF). In patients with bleeding disorders, alternative approaches have been lacking, leaving patients to choose between heightened bleeding risk, or remaining unprotected from TE risk. Thrombotic thrombocytopenic purpura (TTP) presents a unique management conundrum when combined with AF. A thrombotic microangiopathy characterized by systemic microvascular platelet aggregation due to failure in degradation of von Willebrand factor (vWF) [1,15], TTP can predispose patients to both thrombosis and hemorrhage due to marked thrombocytopeniaa relative contraindication to SAC. In this instance, the patient presented with vision changes and expressive aphasia. Brain magnetic resonance imaging (MRI) and magnetic resonance angiography of the head/neck were unremarkable for acute insult and symptoms were attributed to TIA. Neuro-vascular and Hematology services met to discuss preventative strategies. As long-term anticoagulation was still felt to pose a high bleeding risk, the patient was referred to our Neuro-cardiac service seeking nonpharmacologic means to prevent stroke. LAAO was proposed if the patient could tolerate a short period of SAC. Hematology agreed to Apixaban use if the platelet count remained above 50,000/µl. However, given prior ICH, the patient elected discharge with plans to discuss in the outpatient setting. Unfortunately, he presented soon thereafter for sudden onset aphasia/dysarthria and asymmetric extremity weakness.
He was ineligible for tissue plasminogen activator due to a platelet count of less than 100,000/µl. Brain MRI demonstrated a new infarct.

DISCUSSION
Advances in understanding congenital TTP have yielded a dramatic effect on prognosis. While untreated mortality is nearly 90%, the use of therapies such as plasma exchange has improved survival by nearly 85% [7,8]. There remains a paucity of literature describing the management of congenital TTP patients with concomitant AF. The presence of thrombocytopenia poses a treatment dilemma due to the increased risk of both thromboembolism and bleeding events [9,10].
Current AF guidelines offer little insight into the ideal management of patients on SAC with concomitant thrombocytopenia, although prospective studies have shown an increased incidence of mortality in this population [11]. This increased risk perhaps explains why patients with thrombocytopenia were largely excluded from previous randomized controlled trials (RTCs) evaluating the role of SAC in the prevention of TE stroke [12,13]. Percutaneous LAAO has emerged as an alternative to long-term SAC with similar efficacy in TE stroke prevention, but with a large reduction in bleeding risk. It is based on the observation that most thrombi, when seen by echocardiography in patients with nonvalvular AF, are located in the LAA [2]. days, SAC can be discontinued, as seen in our patient, with continued long-term low-dose antiplatelet therapy [3].
To our knowledge, this is the first reported case of a patient with TTP and AF successfully treated with LAAO for the prevention of TE stroke.
We also applied a novel, tailored process by which this patient could be successfully treated, with contingencies incorporated to allow for clinical variability. While there are limited small retrospective studies showing that LAAO may be an efficacious and safe option for patients with thrombocytopenia, there is still a need for larger trials assessing the long-term implications of LAAO in AF patients with concurrent thrombocytopenia [14].

FUNDING INFORMATION
The authors received no specific funding for this work.

DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no new data were created or analyzed in this study.