Fabio Dalla Valle

Thigh-length versus below-knee compression elastic stockings for prevention of the postthrombotic syndrome in patients with proximal-venous thrombosis: a randomized trial

Although below-knee compression elastic stockings (CES) are effective for the prevention of the postthrombotic syndrome (PTS), a substantial number of patients with deep venous thrombosis still develop PTS. In the present open-label, randomized clinical trial, we compared thigh-length with below-knee CES for the prevention of PTS. A total of 267 patients with the first episode of proximal deep venous thrombosis were randomized to wear either thigh-length or below-knee CES for 2 years. After 3, 6, 12, 18, 24, and 36 months, they were assessed for PTS manifestations according to the Villalta scale. PTS developed in 44 (32.6%) of the 135 patients randomized to thigh-length CES and in 47 (35.6%) of the 132 allocated to below-knee CES, for an adjusted hazard ratio of 0.93 (95% confidence interval, 0.62-1.41). Severe PTS developed in 3 patients in each group. CES-related side effects developed in 55 (40.7%) of the 135 patients allocated to thigh-length CES and in 36 (27.3%) of those randomized to the below-knee group (P = .017), and led to premature discontinuation of their use in 29 (21.5%) and 18 (13.6%) patients, respectively. We conclude that thigh-length CES do not offer a better protection against PTS than below-knee CES and are less well tolerated.

Recurrent thromboembolism and major bleeding during oral anticoagulant therapy in patients with solid cancer: findings from the RIETE registry

Following an episode of venous thromboembolism (VTE), the risk of recurrent VTE and major bleeding complications during oral anticoagulant therapy with vitamin K antagonists (VKA) in cancer patients exceeds that observed in patients free from malignancy.[1][1]–[3][2] According to the results of

Prevalence of heart diseases in patients with pulmonary embolism with and without peripheral venous thrombosis: Findings from a cross-sectional survey

BACKGROUND In up to 80% of patients with pulmonary embolism (PE) no peripheral symptomatic thrombosis can be identified. Whether the heart may represent a source of PE is unknown. METHODS We conducted a cross-sectional survey of patients who were 60 years or older and were discharged from the hospitals of Veneto region, Italy between 2000 and 2006 with the diagnosis of PE. We compared the prevalence of several acute and chronic heart diseases in patients discharged with the diagnosis of PE alone with that of patients with co-occurring symptomatic peripheral deep venous thrombosis (PE/DVT). RESULTS Out of 11,236 eligible patients, 9079 (81%) were discharged with the diagnosis of PE alone, and 2157 with that of PE/DVT. 3239 of the 9079 (35.7%) patients with isolated PE, and 666 of the 2157 (30.9%) with PE/DVT had at least one heart disease. The adjusted odds ratio (OR) for having at least one heart disease in patients with isolated PE as compared to those with PE/DVT was 1.26 (95% CI, 1.13-1.40). The heart diseases that significantly contributed to the study results were all-cause cardiomyopathies (adjusted OR, 2.31; 95% CI, 1.37-3.89), all-cause heart failure (1.82; 1.45-2.27), coronary heart disease (1.28; 1.08-1.52), and atrial fibrillation or flutter (1.28; 1.08-1.51). CONCLUSIONS There is an association between isolated PE and a number of heart diseases. The results of our survey generate the hypothesis that in older patients several heart diseases may directly account for the development of PE. Prospective studies are needed to confirm this hypothesis.

Circulating microparticles in umbilical cord blood in normal pregnancy and pregnancy with preeclampsia

INTRODUCTION Placenta microthrombi being one of the prevalent recurrent histological findings in women with preeclampsia (PE), it is reasonable to think that the study of coagulation alterations in cord blood could be more informative than that observed in maternal blood. The aim of the present study was to measure different subtypes of microparticles (MP) plasma levels in the maternal peripheral blood at labour and in the venous cord blood of pregnant women with PE compared to those in a group of women without PE. MATERIALS AND METHODS Thirty-two pregnant women in labour, 16 with and 16 without PE, were enrolled. Blood samples were collected immediately after delivery from cord blood and from maternal peripheral blood. Total, cellular-derived and tissue factor- bearing MP were analyzed using flow-cytometry. Procoagulant activity of MP was assessed using the STA® Procoag PPL assay. RESULTS Total MP, platelet activated-derived (P-Selectin+), leukocyte-derived and TF+MP were higher in pregnancies complicated by PE as compared with normotensive women (p<0.05). Platelet-derived MP (CD61+) levels were lower in PE than in healthy women and no difference was found in endothelial-derived MP levels between the two groups. The PPL clotting time was significantly shorter in PE compared with controls. When only venous cord blood was analysed, all MP detected were significantly higher in PE than in healthy normotensive women (p<0.05). CONCLUSIONS MP are very likely involved in the hypercoagulable and pro-inflammatory intravascular reactions during PE. Prospective studies in a larger population are needed to define the clinical meaning of MP measurement in the PE setting.

Potential Role of Thrombelastography in the Monitoring of Acquired Factor VIII Inhibitor Hemophilia A: Report on a 78-year-old Woman With Life-threatening Bleedings:

A 78-year-old woman was admitted to our hospital because of syncope associated with hematomas in both legs. Acquired hemophilia A (AHA) with a low antifactor VIII antibodies activity was diagnosed. Whole blood (WB) thrombelastographic profile depicted a hypocoagulable state. During hospitalization, the patient experienced life-threatening bleedings in the neck and in the right thigh. FVIII concentrates and rFVIIa was safe and effective in controlling acute hemorrhagic symptoms. Immunosuppressive therapy was used successfully to eradicate the inhibitor. At discharge, FVIII inhibitor was absent and thrombelastogram showed a normal profile. Our report confirms that AHA is a heterogeneous condition in terms of risk of bleeding. Even though the criteria for the diagnosis of AHA is quite well defined, a laboratory test useful to predict the bleeding risk and monitor the response to treatment is lacking. ROTEM profile appears to be correlated with the response to treatment and with the eradication of the inhibitor.

What are the pharmacotherapy options for treating venous thromboembolism in cancer patients

Introduction: Venous thromboembolism (VTE) is a frequent complication in patients with malignancies. The treatment of VTE disorders in cancer patients remains a difficult clinical task. Areas covered: Current evidence on the most appropriate initial and long-term treatment of cancer patients with VTE was addressed, as was the management of recurrent VTE despite anticoagulation, the management of incidentally detected isolated pulmonary embolism (PE), the potential role of the novel direct oral anticoagulants and the impact of low-molecular-weight heparin (LMWH) on cancer evolution. Expert opinion: LMWHs are the cornerstone of VTE treatment in cancer patients. The intensity and duration of treatment are dependent on several factors that need to be individually evaluated. The novel oral anticoagulants should be investigated more carefully before being routinely implemented in the treatment of cancer-associated VTE. Incidentally detected isolated sub-segmental PE is unlikely to require systematic full-dose anticoagulation. Evidence favoring an impact of LMWH on survival in cancer patients is weak.

Factor VIIa-antithrombin complex: a possible new biomarker for activated coagulation

Abstract The activation of the extrinsic coagulation pathway occurs after endothelial injury when the tissue factor (TF), a transmembrane protein located outside the vasculature, binds factor VII (FVII) or activated FVII (FVIIa). Once formed, the TF-VIIa complex activates both factor IX and X and initiates the coagulation process. The TF-VIIa complex is inhibited by both TF pathway inhibitor (TFPI) and antithrombin (AT). The interaction between TF-VIIa and AT induces FVIIa-AT complex formation, which is released into the plasma. Because AT reacts with FVIIa only when it is bound to TF, the circulating levels of FVIIa-AT reflect the degree of exposure of TF to blood. Preliminary clinical studies have shown higher plasma levels of FVIIa-AT complex both in patients with a prior arterial or venous thrombotic event. Increased plasma levels of FVIIa-AT have also been reported in a number of other prothrombotic conditions – antiphospholipid antibodies, solid and hematological malignancies, pre-eclampsia (PE), obesity and cardiac surgery. However, most of the studies published so far are retrospective and with a limited sample size. Larger prospective clinical studies are needed to confirm these findings and to assess the prognostic role of this possible new biomarker for activated coagulation.

On-treatment platelet reactivity in peripheral and coronary blood in patients undergoing primary PCI for ST-segment elevation myocardial infarction (STEMI)

Abstract Dual antiplatelet therapy is recommended in patients undergoing primary percutaneous coronary intervention (p-PCI) for ST-segment elevation myocardial infarction (STEMI). Pre-analytical variables may influence platelet function analysis results. Our aim was to evaluate the on-treatment platelet reactivity in peripheral artery vs coronary blood in patients with STEMI. We enrolled one hundred and nine patients who consecutively underwent p-PCI at Cardiology Unit of Padua University Hospital between June 2014 and June 2015. Before the procedure, all patients received intravenous aspirin 250 mg and either of the thienopyridines; clopidogrel 600 mg, prasugrel 60 mg or ticagrelor 180 mg. ASPI-test and ADP-test using multiple electrode aggregometry (MEA) were performed in samples collected from both a peripheral artery and the culprit coronary artery. ‘Low responders’ were patients with an ASPI-test or ADP-test value greater than or equal to a pre-established normal range. No significant differences were observed in ASPI-test values between peripheral (19 (median) [3–49 (10–90 percentiles)] U) vs coronary (12 [1–40] U, p = .06) blood and in ADP-test (40 [14–82] U vs 33 [7–79] U, p =.68) blood. In peripheral blood, fifteen (14%) patients were ‘low aspirin’ and forty-one (38%) ‘low thienopyridines’ responders. The prevalence of ‘low clopidogrel’ responders was higher (45%) than prasugrel (36%) and ticagrelor (33%). Similar results were observed in coronary blood. In patients undergoing p-PCI for STEMI, MEA platelet function observed in coronary arteries was consistent with peripheral artery blood’s independently of the antiplatelet drug used. The clinical significance of peripheral and coronary on-aspirin/thienopyridines platelet reactivity needs further clarification.

Factor V Leiden paradox and the occurrence of distal vein thrombosis in a large cohort of thrombotic patients

In 1996, it was first described that Factor V Leiden (FVL) seems to be a stronger risk factor for deep vein thrombosis (DVT) than for pulmonary embolism (PE) [1] and this effect has been repeatedly reported, hence the so-called FVL paradox [2–8]. Despite evidence that the FVL paradox does not seem to affect carriers of prothrombin mutation (PTM) [5,7,8], there is not definitive data on whether it is involved in other thrombophilia defects. Finally, only one large-scale study excluded the presence of the paradox in carriers of double heterozygosity for FVL and PTM [9]. Our purposewas to present an overview of the clinical manifestations of venous thromboembolism (VTE) in our cohort of FVL and PTM carriers with a separate risk assessment for DVT and PE, with a focus on isolated distal DVT in heterozygous FVL patients compared to homozygous FVL, PTM carriers, double heterozygotes and FVL pseudohomozygotes. We enrolled consecutive inand outpatients referred to the Thrombotic Unit of the Padua University Hospital between January 2005 and September 2016 with a confirmed diagnosis of a first episode of VTE who gave a written informed consent. Cases were homozygous or heterozygous FVL and/or PTM carriers, while controls were VTE patients without thrombophilic defects. Part of this cohort has been previously described [10]. Carriers of other thrombophilic defects, subjects younger than 18, and patients with previous VTE were excluded. Detailed information about family history, exposure to exogenous risk factors for thrombosis and VTE clinical presentation were collected. Medical reports were also carefully reviewed to evaluate the symptoms and signs of the VTE event at the time of diagnosis and to confirm imaging results. Clinical data were collected prior to laboratory information. Patients were screened for activated protein C resistance (APCr), FVL, prothrombin G20210A, and hereditary deficiencies of antithrombin, protein C and protein S, as previously described [10]. FVL and PTM were detected by the GeneXpert HemosIL® Factor V and Factor II assay (Cepheid, Sunnyvale, CA, USA). DVT was confirmed by complete compression ultrasound of both legs, and PE was confirmed by high probability ventilation/perfusion lung scanning or/and pulmonary computed tomography. We considered calf vein thrombosis as distal and thrombosis in popliteal vein or above as proximal. Previously enrolled patients were excluded if the medical reports relating to VTE presentation (e.g. lack of whole leg ultrasound, lack of pulmonary scans and/or suspicions of PE) were not thorough. VTE was defined as provoked if it occurred within three months after exposure to exogenous risk factors including surgery, immobilization for more than seven days, trauma, pregnancy/puerperium, use of oral contraceptives or hormonal