Care of Adults and Infants with Pulmonary DisordersHigher dose of warfarin for patients with pulmonary embolism complicated by obstructive sleep apnea hypopnea syndrome
Introduction
The overall prevalence of obstructive sleep apnea hypopnea syndrome (OSAHS) in the general population is between 1.2%–4.5% in females and 3.1%–7.5% in males.1 However, the under-recognition of OSAHS among patients admitted for coronary heart disease is astonishingly high. For example, it was reported that the prevalence of OSAHS among acute coronary syndrome patients was 69%, with 34% of them having severe OSAHS (apnea–hypopnea index (AHI) > 30).2 In our previous study, the concomitant prevalence of OSAHS and PE was very high. Also, the patients with PE complicated by OSAHS had a significantly younger mean age of onset of disease and a higher incidence of obesity and diabetes than patients without OSAHS. Aggressive treatment was needed for them because of more lung segment involvement and lower partial pressure of oxygen in arterial blood.3 OSAHS may cause a pathologic prothrombotic state which could possibly promote the development of venous thromboembolic disease.4, 5, 6, 7, 8 The potential association between OSAHS and PE has already been discovered by several studies.9, 10, 11 Obesity, which is closely related to the occurrence of OSAHS and has a significant effect on its severity, may also aggravate the prothrombotic state and increase the risk of thrombosis.12
PE is thought to account for 5%–10% of deaths in hospitalized patients.13 If untreated, approximately one third of those who survive an initial PE die of a future embolic episode. Anticoagulant treatment plays a pivotal role in the management of patients with PE. Warfarin, still the most commonly used anticoagulation agent, should be initiated during the early phase of treatment with heparin, and the dose of warfarin should be adjusted to achieve an optimal international normalized ratio (INR). The anticoagulant effectiveness of warfarin is associated with non-genetic factors (including sex, age, and body weight) and genetic factors.14, 15
However, according to our knowledge, no data are available on the coagulation of patients who have PE complicated by OSAHS. Generally, OSAHS patients tend to have higher weight and more risks of hypercoagulation due to factors such as sedentary behavior, increased hematocrit (HCT) levels,16 slower blood viscosity,17 and increased platelet activity,18 all of which tend to permit more aggressive anticoagulation. We tested the hypothesis that having untreated OSHAS would be associated with the need for a higher dose of warfarin to achieve a therapeutic INR.
Section snippets
Study subjects
This prospective study was performed between June 2012 and May 2013. Ninety-seven identified patients with PE were recruited consecutively. The inclusion criteria were patients who have been diagnosed of PE and agreeing to participate in the study. Exclusion criteria were: 1. Patients unable or unwilling to participate or to provide consent; 2. Patients younger than 18 or older than 80, and pregnant women; 3. Patients diagnosed with malignant tumor, connective tissue disease, and heart failure
Clinical characteristics
As shown in Table 1, OSAHS group versus non-OSAHS group had more male patients, with a much higher body mass index (BMI), body weight, and triglyceride level. For the patients in our study, 78.13% of OSAHS patients had hypertension, while the incidence was 55.39% for non-OSAHS patients. Although arterial PO2 was similar for the two groups, the OSAHS group had a much higher arterial PCO2 compared to the arterial PCO2 of the non-OSAHS. There was no significant difference between the two groups in
Discussion
According to our knowledge, this is the first study to verify that OSAHS constitutes an independent factor for high warfarin dose when PE is present and treated without thrombolysis. OSAHS, a prothrombotic risk factor,20 was detected among patients who have PE at strikingly high rates.10, 11 Screening of OSAHS may affect the treatment strategies of patients with PE.
Similar to others, we found that body weight was significantly associated with warfarin dosage; obese patients required higher
Study limitations
Several shortcomings should be mentioned in our study. First and foremost, when the dose of warfarin was compared between OSAHS and non-OSAHS patients, weight, one of the most important influential factors, was adjusted. However, it was very hard to adjust for other potential factors concomitant with overweight, such as hypertension, diabetes, hyperlipemia, hyperuricemia, reduced physical exercise, etc, which made deviation almost inevitable. Secondly, a few people with AHI ≥5 events/hour, but
Conclusions
To treat PE, the OSAHS group required a comparatively higher dose of warfarin to achieve an INR of 2.0–3.0. This difference still exists after adjusting for weight and achieved INR value. The more severe the OSAHS was, the higher the dose of warfarin that was possibly needed. OSAHS patients had relatively high hypercoagulation states, but hypercoagulation was not an important reason for a higher warfarin dose for them. Many genetic and non-genetic factors may determine warfarin dose.
Acknowledgment
This study is supported by Beijing Project of Science and Technology (Z101107050210044).
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Obstructive sleep apnea and venous thromboembolism: Overview of an emerging relationship
2020, Sleep Medicine ReviewsCitation Excerpt :Besides, as previously discussed, there is evidence that OSA is associated with a hypercoagulation state [10,12,64,65]. As a matter of fact, patients with PE and OSA required higher warfarin doses to achieve a therapeutic international normalized ratio than subjects without OSA [66], and patients with PE and OSA had higher rates of elevated D-dimer levels after discontinuing oral anticoagulation than patients without OSA [46]. There are two longitudinal studies that investigated whether OSA was associated with an increased risk of recurrent PE after discontinuation of oral anticoagulation [26,67].
OSA Is a Risk Factor for Recurrent VTE
2016, ChestUsefulness of the SAME-TT<inf>2</inf>R<inf>2</inf> score to predict anticoagulation control on VKA in patients with atrial fibrillation and obstructive sleep apnea
2016, International Journal of CardiologyPrevalence of pulmonary embolism in patients with obstructive sleep apnea and chronic obstructive pulmonary disease: The overlap syndrome
2019, Heart and LungCitation Excerpt :Our retrospective data suggested that OS, a pathologic state with concomitant COPD and OSA, is associated with PE prevalence among patients referred for sleep tests, mostly for suspicion of nocturnal disordered breathing. The current finding is consistent with previous studies demonstrating contribution of OSA2-6 and COPD11,12 to thrombogenesis respectively, and proves that OS is more closely associated with PE prevalence than isolated OSA. As a common clinical syndrome, OS needs medical concerns not only from traditional cardiovascular profile but also from the aspect of pulmonary circulation.