Anticoagulation in patients with pulmonary arterial hypertension: An update on current knowledge

Abstract

Pulmonary hypertension is a severe clinical condition characterized by molecular and anatomic changes in pulmonary circulation. It is associated with increased pulmonary vascular resistance, which leads to right-sided heart failure if left untreated and, ultimately, death. Treatment of patients with pulmonary arterial hypertension (PAH) involves a complex strategy that takes into consideration disease severity, general and supportive measures, and combination drug regimens. Abnormalities of blood coagulation factors, anti-thrombotic factors, and the fibrinolytic system may contribute to a prothrombotic state in patients with idiopathic PAH. These physiologic changes, in concert with the presence of non-specific risk factors for venous thromboembolism such as heart failure and immobility, are thought to be the basis for oral anticoagulation in PAH. Several observational studies provide helpful information in favor of anticoagulation use in idiopathic PAH but not in other pulmonary hypertension etiologies. Guideline recommendations are based on the lack of prospective comparative trials in this regard. For that reason, large differences exist in the use of anticoagulants in different countries and centers. More studies should be carried out to clarify the risks and the potential benefits of anticoagulant use in a heterogeneous population of patients who are already at considerable life risk.

Idiopathic Pulmonary Arterial Hypertension in Children: A Review

“…Antipyretics should be administered for temperature elevations greater than 38°C (100.4°F) to minimize the consequences of increased metabolic demands on an already compromised cardio-respiratory system. Antitussive medications are also important in children with PAH, as cough can increase intrathoracic pressure, decreasing systemic venous return and cardiac output leading to syncope; this has been described as vasovagal insufficiency in patients with PAH [120]. Antitussive medications are also important in children with PH after episodes of hemoptysis, to prevent further bleeding.…”

“…Consideration of chronic anticoagulation in children with PAH is based on studies in adults with IPAH. Warfarin has been shown to be associated with improved survival in adult patients [120]. Warfarin may be considered in children with IPAH, patients with low cardiac output, those with a long-term indwelling catheter and those with hypercoagulable states.…”

Where do we go from here? Reappraising the data on anticoagulation in pulmonary arterial hypertension

“…Alternatively, this area of clinical uncertainty would be well suited for a randomized registry study (64), an attractive, economic avenue that has not been successfully employed in PAH as of yet (65). While not without consequences (9,33), anticoagulation retains a place in treatment algorithms, prompting urgent reconciliation of this therapeutic dilemma in PAH. …”

“…Overall, the data favored anticoagulation, with a 31% reduction in mortality described in a meta-analysis and systematic reviewalthough with concern for publication bias (10,20). In line with this finding, international guidelines continue to recommend use of anticoagulation in idiopathic pulmonary artery hypertension (iPAH) but recognize the scarcity of supportive trials (9,21,22). Guidance for anticoagulation in connective tissue disease-associated PAH (CTD-PAH) remains even more elusive (14).…”

“…There is strong pathophysiologic rationale for this type of therapy, as numerous studies have identified in situ thrombosis and a pro-coagulant milieu in PAH (3)(4)(5)(6)(7)(8)(9). Unfortunately, a paucity of randomized controlled studies has left practicing clinicians relying on a handful of observational investigations to guide practice patterns (1,2,10,11).…”