Marije ten Wolde

Biomarkers in pulmonary embolism.

Purpose of review Controversy exists about the precise role of thrombolytic therapy in normotensive patients with pulmonary embolism. To resolve this controversy two major questions must be addressed. First, can a subgroup of normotensive pulmonary embolism patients with a high risk for adverse outcomes, such as in-hospital mortality or early recurrent venous thromboembolism, be identified? Second, is there convincing evidence that the benefits of more aggressive therapy counterbalance its risks? Troponin I and T as well as brain natriuretic peptide (BNP) have recently been introduced as promising tools in the risk assessment of patients with pulmonary embolism. Recent findings The studies in series of patients with pulmonary embolism showed prevalences of elevated cardiac biomarkers of 16 to 84%. Positive predictive values for in-hospital mortality varied from 6 to 44%, whereas negative predictive values for uneventful outcome were above 93% in all studies. Summary Although a correlation between elevated biomarkers and in-hospital mortality in pulmonary embolism patients is present in most of the studies, the positive predictive value appears to be insufficient to extend the indication for thrombolytic therapy to all patients with elevated biomarkers. Future research is necessary to show whether combining different biomarkers with echocardiography is more useful.

Frequency of the TAFI – 438 G/A and factor XIIIA Val34Leu polymorphisms in patients with objectively proven pulmonary embolism

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are considered to be two forms of the same disease, however it is not fully understood what determines their clinical presentation. Proteins encoded by the FXIIIA and TAFI genes are involved in stabilizing the fibrin clot and in making it more lysis resistant. The FXIIIA 34Leu and TAFI -438A alleles might protect against DVT. Information on such an association with PE is either contradictory or missing. We hypothesized that both polymorphisms might influence the formation and fate of emboli and accordingly the risk of PE. We determined the frequencies of both polymorphisms in patients with objectively demonstrated PE. The frequency of FXIIIA Leu34Leu in PE patients and non-PE patients was 4.5% and 8.8%, [OR 0.5 (95% CI: 0.1 to 1.9)], respectively. For -438 A/A TAFI genotype the frequency was 1.5% and 8.1% [OR 0.1 (95% CI: 0.02 to 1.1)], respectively.

Pulmonary embolism as a first clinical sign of occult malignancy: A prospective follow-up study

Pulmonary embolism as a first clinical sign of occult malignancy: A prospective follow-up study -

Lower prevalence of subsegmental pulmonary embolism after application of the YEARS diagnostic algorithm

The rate of identified isolated subsegmental pulmonary embolism (ssPE) has doubled with advances in computed tomography pulmonary angiography (CTPA) technology, but its clinical relevance is debated. The YEARS diagnostic algorithm was shown to safely reduce the number of required CTPAs in the diagnostic management of PE. We hypothesized that the higher threshold for performing CTPA in YEARS was associated with a lower prevalence of ssPE compared to the conventional diagnostic algorithm. We compared 2291 consecutive patients with suspected PE managed according to YEARS to 3306 consecutive control patients managed according to the Wells score for the prevalence of isolated ssPE. In the YEARS cohort, 52% were managed without CTPA, 12% had pulmonary embolism (PE) of which 10% were isolated ssPE, and the 3‐month diagnostic failure rate was 0·35%. In the control cohort, 32% were managed without CTPA, 20% had PE of which 16% were isolated ssPE, and the 3‐month failure rate was 0·73%. The isolated ssPE prevalence was significantly lower in YEARS (absolute difference 6·2% (95% confidence interval [CI] 1·4–10), Odds Ratio 0·58 (95% CI 0·37–0·90). In conclusion, YEARS is associated with a lower prevalence of isolated ssPE, due to reduction in CTPAs by the higher D‐dimer threshold. This was however not associated with a higher risk of recurrent VTE during follow‐up.

Residual vein occlusion in relation to immediate compression and postthrombotic syndrome in deep vein thrombosis

Thus far, the association between residual vein occlusion and immediate compression therapy and postthrombotic syndrome is undetermined. Therefore, we investigated whether compression therapy immediately after diagnosis of deep vein thrombosis affects the occurrence of residual vein obstruction (RVO), and whether the presence of RVO is associated with postthrombotic syndrome and recurrent venous thromboembolism. In a prespecified substudy within the IDEAL (individualized duration of elastic compression therapy against long-term duration of therapy for prevention of postthrombotic syndrome) deep vein thrombosis (DVT) study, 592 adult patients from 10 academic and nonacademic centers across The Netherlands, with objectively confirmed proximal DVT of the leg, received no compression or acute compression within 24 hours of diagnosis of DVT with either multilayer bandaging or compression hosiery (pressure, 35 mm Hg). Presence of RVO and recurrent venous thromboembolism was confirmed with compression ultrasonography and incidence of postthrombotic syndrome as a Villalta score of at least 5 at 6 and 24 months. The average time from diagnosis until assessment of RVO was 5.3 (standard deviation, 1.9) months. A significantly lower percentage of patients who did receive compression therapy immediately after DVT had RVO (46.3% vs 66.7%; odds ratio, 0.46; 95% confidence interval, 0.27-0.80; P = .005). Postthrombotic syndrome was less prevalent in patients without RVO (46.0% vs 54.0%; odds ratio, 0.65; 95% confidence interval, 0.46-0.92; P = .013). Recurrent venous thrombosis showed no significant association with RVO. Immediate compression should therefore be offered to all patients with acute DVT of the leg, irrespective of severity of complaints. This study was registered at ClinicalTrials.gov (NCT01429714) and the Dutch Trial registry in November 2010 (NTR2597).

Toll-like receptor 9 gene expression in the post-thrombotic syndrome, residual thrombosis and recurrent deep venous thrombosis: A case-control study

OBJECTIVE Animal models suggest that toll-like receptor 9 (TLR9) promotes thrombus resolution after acute deep venous thrombosis (DVT). We hypothesized that TLR9 expression is lower in patients with post-thrombotic syndrome (PTS) and investigated the role of TLR9 in residual thrombosis (RT) and recurrence. METHODS Patients with a history of DVT with PTS (cases, n=30) and without PTS after minimal 24 months follow-up (controls, n=30) were selected. Healthy individuals (HI, n=29) without DVT were included as reference. TLR9 mRNA expression in leukocytes was determined by qPCR and normalized to the housekeeping succinate dehydrogenase subunit A gene using the ΔCt method. Sub analyses were performed to explore the TLR9 expression in patients with and without RT and multiple DVT episodes. RESULTS The median TLR9 expression was 0.45 (interquartile range 0.31 to 0.93), 0.39 (0.25 to 0.69) and 0.62 (0.32 to 0.75) in cases, controls and HI respectively (p=0.61). The median TLR9 expression was 0.39 (0.26 to 0.51) in patients with RT compared to 0.55 (0.30 to 0.86, p=0.13) in those without. The median TLR9 expression was significantly lower in patients who had one DVT compared to patients with recurrent DVT, 0.37 (0.23 to 0.63) versus 0.55 (0.43 to 0.96) respectively (p<0.01). CONCLUSION No significant difference in TLR9 expression was found between cases, controls and HI. However TLR9 expression seems lower in individuals with DVT and RT, albeit not significant. Interestingly, TLR9 might play a role in recurrent DVT, as the TLR9 expression was significantly higher in patients with recurrent DVT.