Giuliana Guazzaloca

D-dimer testing as an adjunct to ultrasonography in patients with clinically suspected deep vein thrombosis: prospective cohort study

Abstract Objective To investigate the efficacy of using a rapid plasma D-dimer test as an adjunct to compression ultrasound for diagnosing clinically suspected deep vein thrombosis. Design D-dimer concentrations were determined in all patients with a normal ultrasonogram at presentation. Repeat ultrasonography was performed 1 week later only in patients with abnormal D-dimer test results. Main outcome measure Patients with normal ultrasonograms were not treated with anticoagulants and were followed for 3 months for thromboembolic complications. Setting University research and affiliated centres. Subjects 946 patients with clinically suspected deep vein thrombosis. Results Ultrasonograms were abnormal at presentation in 260 (27.5%) patients. Of the remaining 686 patients tested for D-dimer, 88 (12.8%) had abnormal concentrations. During follow up venous thromboembolic complications occurred in one of the 598 patients who were not treated with anticoagulants and who had an initial normal ultrasonogram and D-dimer concentration, whereas thromboembolic complications occurred in two of the 83 untreated patients who had abnormal D-dimer concentrations but a normal repeat ultrasonogram. The cumulative incidence of venous thromboembolic complications during follow up was 0.4% (95% confidence interval 0% to 0.9%). The rapid plasma D-dimer test used as an adjunct to compression ultrasonography resulted in a reduction in the mean number of repeat ultrasound examinations and additional hospital visits from 0.7 to 0.1 per patient. Conclusions Testing for D-dimer as an adjunct to a normal baseline ultrasound examination decreased the number of subsequent ultrasound examinations considerably without any increased risk of venous thromboembolic complications in patients not receiving anticoagulants. The use of ultrasound and testing for D-dimer enabled treatment decisions to be made at the time of presentation in most patients.

D-dimer levels in combination with residual venous obstruction and the risk of recurrence after anticoagulation withdrawal for a first idiopathic deep vein thrombosis

We assessed the predictive value of D-dimer levels in combination with residual venous obstruction (RVO) for recurrent venous thromboembolism (VTE) in a prospective cohort of outpatients after oral anticoagulant therapy (OAT) suspension for a first episode of idiopathic proximal deep vein thrombosis of the lower limbs during a 2-year follow-up. Patients (n=400) were enrolled on the day of OAT suspension when RVO was determined by compression ultrasonography (present in 48.6% of patients). D-dimer (cut-off value: 500 ng/mL) was measured 30+/-10 days afterwards (abnormal in 56.4% of patients). The overall recurrence rate was 16.7% (67/400; 95% confidence intervals - CI -: 13-21 %). The multivariate hazard ratio (HR) for recurrence was 3.32 (95% CI: 1.78-6.75; p<0.0001) for abnormal D-dimer compared to normal D-dimer and 1.2 (95% CI:0.72-2.07; p>0.05) for RVO compared to absent RVO. The recurrence rate was 5.7% (95% CI:2-13%) and 10.4% (95% CI:6-18%), respectively, for normal D-dimer either without or with RVO, 22.9% (95% CI: 14-33%) and 25.9% (95% CI: 18-35%), respectively, for abnormal D-dimer, either without or with RVO. When compared with normal D-dimer without RVO, the multivariate HR for recurrence was similar for abnormal D-dimer either with RVO (4.76 - 95% CI:1.78-12.8) or without RVO (4.3-95%:1.56-11.88). Abnormal D-dimer at one month after OAT withdrawal is an independent risk factor for recurrent VTE, while RVO at the time of OAT withdrawal, either with normal or abnormal D-dimer after one month, does not influence the risk of recurrence.

Risks factors for highly unstable response to oral anticoagulation: a case-control study

The factors associated with persistent instability of oral anticoagulant treatment (OAT) were investigated in a case‐control study. The most unstable patients from 35 Italian anticoagulation clinics were matched with stable controls, for gender, age and OAT indication. Socio‐demographic data, medical history, dietary and life habits, cytochrome P450 CYP2C9 variants, blood cell count, liver and renal functions were investigated. An ‘Abbreviated Mental Test’ (AMT) and a questionnaire to assess patient compliance to, and comprehension of, OAT indications and mechanisms were administered. An International Normalized Ratio (INR) above 4·5 was more frequently found in cases (n = 77) than controls (n = 80) (12·3% vs. 0·4%; P < 0·0001). The odds ratio for instability was significantly higher for: people who worked versus pensioners, acenocoumarol versus warfarin, and an insufficient score in the AMT and/or in the questionnaire. Cytochrome P450 CYP2C9 variants *1/*3 or *2/*3 or *3/*3 were more frequent among cases than controls (29·9% vs.15·0%; P = 0·042). No differences were observed as regards the other variables. In conclusion, we found that high intra‐individual variability in OAT control was multifactorial, but poor OAT comprehension was prevalent.

Evolution of untreated calf deep-vein thrombosis in high risk symptomatic outpatients: the blind, prospective CALTHRO study.

The natural history of calf deep-vein thrombosis (DVT) is still uncertain and it is debated whether it warrants to be diagnosed and treated. We aimed to investigate the complication rate of untreated isolated calf DVT (ICDVT). Symptomatic outpatients were prospectively managed with serial compression ultrasonography (SCUS). Those without proximal DVT and with likely pre-test clinical probability (PCP) or altered D-dimer received immediate subsequent complete examination of calf deep veins (CCUS) by a different operator. The result of CCUS was kept blind both to the managing doctor and the patient and disclosed after three months. Primary outcome was the rate of venous thromboembolism at three months. We examined 431 subjects (196 males; median age 68.0 years) in whom five outcomes were recorded (1.2%; 95% confidence intervals [CI]: 0.4-2.7). If CCUS results had been available, outcomes would have been recorded in 3/424 patients (0.7%; 95% CI: 0.2-2.1) with two events in subjects negative at both serial and complete CUS. ICDVT was diagnosed in 65 subjects (15.3%; 95% CI: 12-19); of whom 59 remained uneventful (one was lost to follow-up). A significant higher rate of outcomes was recorded in subjects with than without ICDVT (5/64; 7.8%; 95% CI: 3-17 vs. 3/351; 0.8%; 95% CI: 0-2; p=0.003). However, after excluding two events picked at serial CUS in subjects with ICDVT, the difference became barely significant (3/64; 4.7%; 95% CI: 1-13; p=0.049). Thrombotic evolution of untreated ICDVT in high-risk subjects may be relevant. Larger studies are needed to address this issue.

D-dimer and residual vein obstruction as risk factors for recurrence during and after anticoagulation withdrawal in patients with a first episode of provoked deep-vein thrombosis

D-dimer and residual venous obstruction (RVO) have been separately shown to be risk factors for recurrent venous thromboembolism (VTE) after a first episode of unprovoked proximal deep-vein thrombosis (DVT). It was the objective of this study to assess the predictive value of D-dimer and residual vein obstruction (RVO), alone and in combination, for recurrence after provoked DVT of the lower limbs. A total of 296 consecutive patients with a first episode of symptomatic provoked proximal DVT were evaluated at a university hospital in Bologna, Italy. On the day of anticoagulation withdrawal (T0), RVO was determined by compression ultrasonography. D-dimer levels (cut-off: 500 ng/ml) were measured at T0 and after 30 ±10 days (T1). The main outcome was recurrent VTE during a two-year follow-up. D-dimer was abnormal in 11.6% (32/276) and 31% (85/276) of subjects at T0 and at T1, respectively. RVO was present in 44.8% (132/294) of patients. Recurrence rate was 5.1% (15/296; 95% confidence interval [CI]: 3-8%; 3% patient-years; 95% CI: 2-5 %). An abnormal D-dimer either at T0 or at T1 was associated with an adjusted hazard ratio (HR) for recurrence of 4.2 (95% CI:1.2-14.2; p=0.02) and 3.8 (95%CI: 1.2-12.1; p=0.02), respectively, when compared with normal D-dimer. The HR for recurrence associated with RVO was not significant, and RVO did not increase the recurrence risk associated with an abnormal D-dimer either at T0 or T1. In conclusion, an abnormal D-dimer during vitamin K antagonist (VKA) treatment or at one month after VKA withdrawal is a risk factor for recurrence in patients with provoked DVT, while RVO at the time of anticoagulation withdrawal is not.

The Wells rule and D-dimer for the diagnosis of isolated distal deep vein thrombosis

Summary.  Background:  Pretest clinical probability with the Wells rule and D‐dimer have been widely investigated for the diagnosis of symptomatic proximal deep vein thrombosis (DVT) of the lower limbs, but they have not been formally tested for symptomatic isolated distal DVT diagnosis.

The SAME-TT2R2 score predicts the quality of anticoagulation control in patients with acute VTE: A real-life inception cohort study

The SAMe-TT2R2 score has recently been proposed to predict the quality of vitamin K antagonist (VKA) anticoagulation control in patients with atrial fibrillation. We aimed at investigating whether the score is effective also in patients with venous thromboembolism (VTE). Patients included in the START-Register because started VKA therapy for a recent VTE episode and with > 3 months follow-up were analyzed. The score was calculated using the baseline patients characteristics present in the electronic database of the registry, where all INR results were also available and analysed to calculate the time in therapeutic range (TTR). A total of 1308 patients (53.4 % female, median age 68 years) were analysed. During 998 patient-years follow-up, the median TTR was 63 %. The maximum score in the patients was 4, with 70 % of them having 0-1. INR controls within range (2.0-3.0) were significantly less prevalent in patients with score ≥ 2 vs 0-1 score (58.5 ± 20 % vs 61.5 ± 19 %, respectively, p = 0.046). Patients with score ≥ 2 vs 0-1 had a highly significant lower TTR during the first 3 months of therapy (53 ± 26 % and 61 ± 26 %, respectively; p=0.0001), difference mainly due to more time spent below 2.0 INR (38 ± 28 % vs 31.3 ± 26.7 %, respectively; p=0.0001). In conclusion, the study proved, for the first time, that the SAMe-TT2R2 score is useful to predict among VTE patients those who will have good (score 0-1) or less good (score ≥ 2) VKA anticoagulation control. The score can help decision-making in everyday clinical practice, especially when choosing between VKA and non-vitamin K antagonists direct anticoagulants.

Duration of anticoagulant treatment and recurrence of venous thromboembolism in patients with and without thrombophilic abnormalities

Duration of anticoagulant treatment and recurrence of venous thromboembolism in patients with and without thrombophilic abnormalities -

The incidence of heparin-induced thrombocytopenia in patients treated with low molecular weight heparin for superficial vein thrombosis

BACKGROUND The risk of heparin induced thrombocytopenia (HIT) associated with low molecular weight heparin (LMWH) for treatment of superficial vein thrombosis (SVT) is uncertain. As a result the necessity of platelet count monitoring is unclear in this setting. AIMS To assess the risk of HIT in outpatients treated with LMWH for SVT. METHODS In a prospective single centre study we included all symptomatic outpatients in whom a real-time B-mode and color Doppler ultrasonography examination revealed SVT without DVT. Patients treated with vitamin K antagonists or fondaparinux were excluded. Patients received full dose enoxaparin for 1week followed by half therapeutic dose for 3weeks or parnaparin 8500UI aXa for 10days followed by 6400UI aXa once daily for 20days. Platelet count was performed on the day of diagnosis (D0) and 7 (D7), and 14 (D14) days afterward. Primary outcomes were the rate of thromboembolic events and of HIT during a 3-month follow-up. RESULTS 678 outpatients (age: 64.7±16.2years, male: 42.0%) were evaluated. During follow-up, 7 venous thrombo-embolic events were recorded (1.03% CI 95%: 0.50-2.11%), while no major bleeding was observed (0.0% CI 95%: 0.0-0.56%). Platelet count was 255±93×10(9)/L at D0, 245±93×10(9)/L at D7 (p=0.204 vs. D0) and 261±116×10(9)/L at D14 (p=0.405 vs. D0). No fall in platelet count>50% and no case of HIT were recorded (HR 0.0% CI 95%: 0-0.56%). CONCLUSIONS A 4-week LMWH treatment for SVT is associated with an incidence of HIT lower than 0.6% and platelet count monitoring may be omitted in this setting.

A Bridging Protocol in High-Thrombotic Risk Mechanical Valve Bearers Undergoing Surgery or Invasive Procedures

Periprocedural bridging in high-thrombotic-risk mechanical heart valve (htr-MHV) bearers has not been definitively addressed [(1–3)][1]. In a previous study [(4)][2], we assessed the effectiveness and safety of a bridging protocol with an intermediate dose of low-molecular-weight heparins (LMWHs