Chronic thromboembolic pulmonary hypertension (CTPH) is associated with considerable morbidity and mortality. Its incidence after pulmonary embolism and associated risk factors are not well documented. We conducted a prospective, long-term, follow-up study to assess the incidence of symptomatic CTPH in consecutive patients with an acute episode of pulmonary embolism but without prior venous thromboembolism. Patients with unexplained persistent dyspnea during follow-up underwent transthoracic echocardiography and, if supportive findings were present, ventilation–perfusion lung scanning and pulmonary angiography. CTPH was considered to be present if systolic and mean pulmonary-artery pressures exceeded 40 mm Hg and 25 mm Hg, respectively; pulmonary-capillary wedge pressure was normal; and there was angiographic evidence of disease. The cumulative incidence of symptomatic CTPH was 1.0 percent (95 percent confidence interval, 0.0 to 2.4) at six months, 3.1 percent (95 percent confidence interval, 0.7 to 5.5) at one year, and 3.8 percent (95 percent confidence interval, 1.1 to 6.5) at two years. No cases occurred after two years among the patients with more than two years of follow-up data. The following increased the risk of CTPH: a previous pulmonary embolism (odds ratio, 19.0), younger age (odds ratio, 1.79 per decade), a larger perfusion defect (odds ratio, 2.22 per decile decrement in perfusion), and idiopathic pulmonary embolism at presentation (odds ratio, 5.70). CTPH is a relatively common, serious complication of pulmonary embolism. Diagnostic and therapeutic strategies for the early identification and prevention of CTPH are needed.

Summary. One of the conclusions of the subcommittee meeting on Lupus Anticoagulant/Phospholipid dependent antibodies, held in Geneva on 2007, was the need to update the guidelines on Lupus Anticoagulant (LA) detection. Particular emphasis was given to several aspects discussed in this official communication. A new paragraph is dedicated to the patient selection, and aims to minimize inappropriate requests for LA testing. Modalities for blood collection and processing are fully delineated and the choice of tests is limited to dRVVT and a sensitive aPTT. Calculation of cut‐off values for each diagnostic step are clearly stated. A final paragraph reports the interpretation of the results in general and in particular situations.

Rivaroxaban is an effective and safe alternative to warfarin in patients with atrial fibrillation and venous thromboembolism. We tested the efficacy and safety of rivaroxaban compared with warfarin in high-risk patients with thrombotic antiphospholipid syndrome. This is a randomized open-label multicenter noninferiority study with blinded end point adjudication. Rivaroxaban, 20 mg once daily (15 mg once daily based on kidney function) was compared with warfarin (international normalized ratio target 2.5) for the prevention of thromboembolic events, major bleeding, and vascular death in patients with antiphospholipid syndrome. Only high-risk patients triple positive for lupus anticoagulant, anti-cardiolipin, and anti–β2-glycoprotein I antibodies of the same isotype (triple positivity) were included in the study. The trial was terminated prematurely after the enrollment of 120 patients (59 randomized to rivaroxaban and 61 to warfarin) because of an excess of events among patients in the rivaroxaban arm. Mean follow-up was 569 days. There were 11 (19%) events in the rivaroxaban group, and 2 (3%) events in the warfarin group. Thromboembolic events occurred in 7 (12%) patients randomized to rivaroxaban (4 ischemic stroke and 3 myocardial infarction), whereas no event was recorded in those randomized to warfarin. Major bleeding occurred in 6 patients: 4 (7%) in the rivaroxaban group and 2 (3%) in the warfarin group. No death was reported. The use of rivaroxaban in high-risk patients with antiphospholipid syndrome was associated with an increased rate of events compared with warfarin, thus showing no benefit and excess risk. This trial was registered at www.clinicaltrials.gov as #NCT02157272. Publisher9s Note: There is a Blood Commentary on this article in this issue. Key Points Direct anticoagulants are currently used in patients with thromboembolism, irrespective of the presence of antiphospholipid antibodies. This trial shows an increased rate of events with rivaroxaban compared with warfarin in patients with antiphospholipid syndrome. Visual Abstract

Background and Objectives While it has long been recognized that patients with acute unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) have a higher risk of recurrent venous thromboembolism (VTE) than that of patients with secondary thrombosis, whether other clinical parameters can help predict the development of recurrent events is controversial. The aim of this investigation was to assess the rate of recurrent VTE after withdrawal of vitamin K antagonists, and to identify clinical parameters associated with a higher likelihood of recurrence. Design and Methods We followed, up to a maximum of 10 years, 1626 consecutive patients who had discontinued anticoagulation after a first episode of clinically symptomatic proximal DVT and/or PE. All patients with clinically suspected recurrent VTE underwent objective tests to confirm or rule out the clinical suspicion. Results After a median follow-up of 50 months, 373 patients (22.9%) had had recurrent episodes of VTE. The cumulative incidence of recurrent VTE was 11.0% (95% CI, 9.5–12.5) after 1 year, 19.6% (17.5–21.7) after 3 years, 29.1% (26.3–31.9) after 5 years, and 39.9% (35.4–44.4) after 10 years. The adjusted hazard ratio for recurrent VTE was 2.30 (95% CI, 1.82–2.90) in patients whose first VTE was unprovoked, 2.02 (1.52–2.69) in those with thrombophilia, 1.44 (1.03–2.03) in those presenting with primary DVT, 1.39 (1.08–1.80) for patients who received a shorter (up to 6 months) duration of anticoagulation, and 1.14 (1.06–1.12) for every 10-year increase of age. When the analysis was confined to patients with unprovoked VTE the results did not change. Interpretation and Conclusions Besides unprovoked presentation, other factors independently associated with a statistically significant increased risk of recurrent VTE are thrombophilia, clinical presentation with primary DVT, shorter duration of anticoagulation, and increasing age.

See also Galli M. The antiphospholipid triangle. This issue, pp 234–6. Summary. Background: The characteristics and the clinical course of antiphospholipid syndrome (APS) in high‐risk patients that are positive for all three recommended tests that detect the presence of antiphospholipid (aPL) antibodies have not been described. Methods: This retrospective analysis of prospectively collected data examined patients referred to Italian Thrombosis Centers that were diagnosed with definite APS and tested positive for aPL [lupus anticoagulant (LA), anti‐cardiolipin (aCL), and anti‐β2‐glycoprotein I (β2GPI) antibodies]. Laboratory data were confirmed in a central reference laboratory. Results: One hundred and sixty patients were enrolled in this cohort study. The qualifying events at diagnosis were venous thromboembolism (76 cases; 47.5%), arterial thromboembolism (69 cases; 43.1%) and pregnancy morbidity (11 cases; 9.7%). The remaining four patients (2.5%) suffered from catastrophic APS. The cumulative incidence of thromboembolic events in the follow‐up period was 12.2% (95%CI, 9.6–14.8) after 1 year, 26.1% (95%CI, 22.3–29.9) after 5 years and 44.2% (95%CI, 38.6–49.8) after 10 years. This was significantly higher in those patients not taking oral anticoagulants as compared with those on treatment (HR=2.4 95%CI 1.3–4.1; P < 0.003). Major bleeding associated with oral anticoagulant therapy was low (0.8% patient/years). Ten patients died (seven were cardiovascular deaths). Conclusions: Patients with APS and triple positivity for aPL are at high risk of developing future thromboembolic events. Recurrence remains frequent despite the use of oral anticoagulants, which significantly reduces the risk of thromboembolism.