Idiopathic pulmonary vein thrombosis treated with apixaban

Abstract Pulmonary vein thrombosis (PVT) is a rare clinical finding that is potentially fatal and with an unknown incidence rate as known cases exist predominantly in case reports. We present the case of a 58‐year‐old female who reported sudden onset of chest pain, shortness of breath, and dyspnoea on exertion. A computed tomography (CT) pulmonary angiogram was negative for evidence of pulmonary embolism; however, it did demonstrate the evidence of thrombosis of the right lower lobe segmental pulmonary vein. She had no identifiable aetiologies for her PVT; therefore, she was diagnosed with idiopathic PVT and was treated successfully with apixaban. This case represents the 14th incidence of idiopathic PVT in the current body of medical literature and the first case of successful treatment with apixaban.


Introduction
Pulmonary vein thrombosis (PVT) is a rare and lifethreatening condition commonly associated with interventional thoracic procedures such as thoracic surgery and radiofrequency catheter ablation for atrial fibrillation. Idiopathic PVT is exceedingly rare with an unknown incidence rate as it has only been reported in case reports. We present a case of idiopathic PVT which represents the 14th identified case within the current body of medical literature and the first ever case successfully treated with apixaban.

Case Report
We present a 53-year-old female with a past medical history significant for right breast cancer, status-post lumpectomy followed by completion of six rounds of chemotherapy (Taxotere [Sanofi-Aventis, France], Herceptin [Genentech, USA], and carboplatin) and 36 rounds of radiation six years prior and currently in remission, hypertension, and bilateral lower extremity varicose veins, status-post phlebectomy 14 years prior complicated by a post-operative right lower extremity deep vein thrombosis treated successfully with three months of Coumadin (Bristol Myers Squibb, USA). She presented to the hospital with complaints of sudden onset sharp, constant, and nonradiating substernal chest pain while eating dinner with her husband at home. Her symptoms were not associated with nausea, diaphoresis, haemoptysis, palpitations, or syncope. She denied any symptoms suggestive of acid reflux; however, she did endorse shortness of breath and dyspnoea on exertion. There were no provoking factors. She denied any recent history of recent immobilization, trauma, calf/leg pain or swelling, long car rides, or air travel. There was no surgical history of prior lobectomies, lung transplants, or atrial fibrillation ablations. Her family history is negative for blood dyscrasias or blood clots and her social history is negative for tobacco or illicit drug use. She has no active cancer disease.
Her initial investigations in the emergency department demonstrated completely unremarkable parameters in regards to her complete blood count, complete metabolic panel, prothrombin time, troponin-I, D-dimer, and electrocardiogram. Her physical examination was unrevealing. The chest radiograph did not demonstrate evidence of acute disease. A computed tomography (CT) pulmonary angiogram was performed which did not demonstrate evidence of pulmonary arterial embolism; however, there was evidence of significant thrombosis of a right lower lobe segmental pulmonary vein without an obvious visualizable aetiology ( Fig. 1). Her transthoracic echocardiogram demonstrated normal left ventricular systolic function without evidence of right heart strain or elevated right ventricular systolic pressure. There was no evidence of mitral stenosis and no presence intra-atrial or ventricular thrombus formation. A hypercoagulable workup, consisting of anticardiolipin IgG/M, lupus anticoagulant, and proteins C and S, was performed and found to be negative. No identifiable source was determined to be the underlying culprit; therefore, her pulmonary vein thrombus was determined to be idiopathic in nature.
The rest of her hospital course was unremarkable after the initiation of intravenous therapeutic anticoagulation via unfractionated heparin. She was discharged home with instructions to continue apixaban for three months followed by re-evaluation in the outpatient setting. During her follow-up visit in our outpatient pulmonary clinic, she was found to be in good health with complete resolution of all prior presenting symptoms and normoxic on ambient air. A follow-up CT scan was offered to evaluate for resolution of the thrombus; however, due to the risk of further radiation, the patient declined.

Discussion
PVT is a rare clinical condition with an unknown incidence rate as majority of our current understanding stems from case reports. Due to the non-specific nature of its presentation, it presents a diagnostic challenge. Patients may demonstrate evidence of dyspnoea, pleuritic chest pain, cough, or haemoptysis which may lead to the misdiagnosis of a pulmonary embolism. Clinically, there is no difference in patient presentation of PVT in a provoked scenario and idiopathic [1]. The rare occurrence of identified cases in the current literature could be explained by the extensive collateral venous network within the pulmonary circulation, although, if left untreated, it could potentially result in interstitial pulmonary oedema, right ventricular failure, and pulmonary infarction [1,2]. Dyspnoea from PVT is not always conducive to an abnormal resting echocardiogram as demonstrated by prior reported cases in Table 1. Such a large pulmonary vein thrombus can cause a reduction in total pulmonary vascular volume with associated decrements of left atrial volume and cardiac output to meet exercise demands [15,16]. This may be more evident with a more invasive exercise right heart catheterization.
Identified causes of PVT are usually associated with manipulation of the pulmonary veins during lung transplantation or lobectomy, radiofrequency ablation for atrial fibrillation, sclerosing mediastinitis, pulmonary malignancy, atrial myxoma, congenital pulmonary vein narrowing, or mitral stenosis [17]. In a review of five cases of idiopathic PVT, four cases were found to have normal D-dimer levels in addition to 17 of 23 cases of PVT with an identifiable cause, suggesting that D-dimer does not appear to be correlated with the presence of a PVT [13].
There is no gold standard for the diagnosis of PVT. Diagnosis is often made with the use of a combination of multiple imaging modalities such as transoesophageal echocardiogram, cardiac gated magnetic resonance imaging, pulmonary angiogram, or CT pulmonary angiogram [14]. CT scans that are typically meant to evaluate the pulmonary arterial anatomy may be misleading due to the poor opacification and mixing artefact in the pulmonary vein, potentially mimicking thrombus and left atrial masses. Utilizing longer scan delays allows for better evaluation of both pulmonary veins and left atrium [1]. Although our patient did not receive a repeat CT scan to demonstrate resolution, citing risk of radiation, it is not standard of practice to do so if the patient's symptoms have resolved as clot resolution occurs in as little as three weeks with anticoagulant treatment [18].
To date, there have been no randomized control trials evaluating treatments for PVT; however, multiple case reports have demonstrated success with the use of warfarin, rivaroxaban, and dabigatran [13,14]. Our case is rare in that it represents the 14th case (Table 1) of a reported idiopathic PVT and the first reported treated successfully with apixaban.

Disclosure Statement
Appropriate written informed consent was obtained for publication of this case report and accompanying images.