Response to anticoagulation in chronic thromboembolic pulmonary hypertension

Abstract

Abstract Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by fibrotic thrombus in the pulmonary arteries, likely originating from pulmonary embolism. Inadequate anticoagulation is one of the suspected mechanisms of disease in CTEPH. The aim of our study was to assess phenprocoumon dosing and genetic polymorphisms of vitamin K epoxide reductase complex subunit 1 (VKORC 1) that are known to affect the dose required to reach therapeutic range. Methods The ratio of mean weekly phenprocoumon dose in relation to mean INR levels was assessed in CTEPH patients on phenoprocoumon oral anticoagulation for at least 6 months, compared with PAH patients. VKORC 1 (–1639, –3730) single nucleotide polymorphisms (SNPs) were determined by polymerase chain reaction (PCR). Results In 225 patients (167 CTEPH, 58 PAH) mean treatment duration was 51.7±44.7 months, and mean age was 62.9±13.87 years (49.7% female). Median weekly dose of phenprocoumon was 10.5 mg (IQR 9.0–16.5) for PAH vs. 14.25 mg (IQR 10.5–18.0) in the CTEPH cohort (p=0.016). Although median INR was not significantly different among the two groups (2.28 vs. 2.40 in the PAH vs. CTEPH, respectively, p=0.084), achieving the mentioned INR require significantly higher weekly doses in the CTEPH group. While distribution of VKORC1 variants was according to the Hardy Weinberg equilibrium, patients with CTEPH and VKORC1 –1639 GG homozygous wild type required significantly higher phenprocoumon doses compared with VKORC1 –1639 AA homozygous mutants (P<0.001). Conclusion CTEPH patients require more vitamin K antagonists in relation to INR levels than PAH patients. Unmet phenprocoumon dosing requirements may be one mechanism of disease in CTEPH. Funding Acknowledgement Type of funding sources: None.