Clinical probability assessment and D-dimer determination in patients with suspected deep vein thrombosis, a prospective multicenter management study

Objectives

To investigate the reliability of a combined strategy of clinical assessment score followed by a local D-dimer test to exclude deep vein thrombosis. For comparison D-dimer was analysed post hoc and batchwise at a coagulation laboratory.

Design

Prospective multicenter management study.

Setting

Seven hospitals in southern Sweden.

Subjects

357 patients with a suspected first episode of deep vein thrombosis (DVT) were prospectively recruited and pre-test probability score (Wells score) was estimated by the emergency physician. If categorized as low pre-test probability, D-dimer was analysed and if negative, DVT was considered to be ruled out. The primary outcome was recurrent venous thromboembolism (VTE) during 3 months of follow up.

Results

Prevalence of DVT was 23.5% (84/357). A low pre-test probability and a negative D-dimer result at inclusion was found in 31% (110/357) of the patients of whom one (0.9%, [95% CI 0.02-4.96]) had a VTE at follow up. Sensitivity, specificity, negative predictive value and negative likelihood ratio for our local D-dimer test in the low probability group were 85.7%, 74.5%, 98.2%, and 0,19 respectively compared to 85.6%, 67,6%, 97.9% and 0,23 using batchwise analysis at a coagulation laboratory.

Conclusion

Pre-test probability score and D-dimer safely rule out DVT in about 30% of outpatients with a suspected first episode of DVT. One out of 110 patients was diagnosed with DVT during follow up. No significant difference in diagnostic performance was seen between local D-dimer test and the post hoc batch analysis with the same reagent in the low probability group.     

Comparison of high specificity with standard versions of a quantitative latex D-dimer test in the assessment of community pulmonary embolism: HaemosIL D-dimer HS and Pulmonary Embolism

Background

D-dimer assays are sensitive but have poor specificity. False positive results lead to extra imaging and hospital admissions.

Objectives

To make a pilot comparison of the diagnostic accuracy of the standard quantitative latex HemosIL D-dimer assay with a newer HemosIL D-dimer HS version designed to have improved specificity.

Patients / Methods

Consecutive patients presenting from the community to an Emergency Department that were investigated for suspected pulmonary embolism using a D-dimer test were included in the study. Standard and D-dimer HS tests were performed. Pulmonary Embolism was diagnosed on the basis of imaging studies or post-mortem at any time from presentation to 90 days thereafter.

Results

The prevalence of Pulmonary Embolism was 4.5% (18/402). The sensitivity, specificity, negative predictive value, and positive predictive value for the standard quantitative D-dimer test was 100% (81.5 - 100.0), 49.2% (44.1 - 54.3),100% (98.1 - 100.0), and 8.5% (5.1 - 13.0), respectively, and 100% (81.5 - 100.0), 58.3% (53.2 - 63.3),100% (98.4 - 100.0), and 10.1% (6.1 - 15.5), for the D-dimer HS test. There were 35 (16%) fewer ‘false positives’ using the D-dimer HS assay compared with the standard assay.

Conclusions

D-dimer HS has superior specificity to the standard quantitative D-dimer test without any loss of sensitivity. The generation of fewer false positive results should lead to less unnecessary diagnostic imaging; the use of which is associated with increased hospital admissions and length of stay. The HS assay may therefore have significant health economic benefits.     

Accuracy and usefulness of a clinical prediction rule and D-dimer testing in excluding deep vein thrombosis in cancer patients

Introduction

Deep vein thrombosis (DVT) can be safely and reliably excluded in patients with a low clinical probability and a negative D-dimer result but the accuracy and utility of such a strategy is less certain in cancer patients. We sough to compare the performance of the Wells pretest probability (PTP) model and D-dimer testing between patients with and without cancer and to examine the utility of the two PTP model classification schemes (low/moderate/high versus unlikely/likely) in excluding DVT in patients with cancer.

Materials and methods

Pooled analysis of databases from three prospective diagnostic studies evaluating consecutive outpatients with suspected DVT.

Results

A total of 2696 patients were evaluated. DVT was diagnosed in 403 (15%) patients overall and in 83 of 200 (41.5%) cancer patients. The PTP distribution and the prevalence of DVT in each PTP category were significantly different between patients with and without cancer, regardless of the classification used (p < 0.01). In patients with cancer, the negative predictive values of a low or unlikely PTP score in combination with a negative D-dimer result were 100% (95% CI 69.8%-100%) and 100% (95% CI 82.8%-96.6%), respectively. However, the specificities ranged from 46.2% (95%CI 27.1%-66.3%) to 57.1% (95%CI 41.1%-71.9%). Further testing was required in 94% of cancer patients using the low/moderate/high PTP classification and in 88% using the unlikely/likely stratification.

Conclusions

As in patients without cancer, the combination of a low or unlikely PTP with a negative D-dimer result can exclude DVT in patients with cancer. However, this strategy has limited utility because very few cancer patients present with this combination.     

Multicenter evaluation of a new quantitative highly sensitive D-dimer assay, the Hemosil® D-dimer HS 500, in patients with clinically suspected venous thromboembolism

Introduction

D-dimer testing is widely used in conjunction with clinical pretest probability (PTP) for venous thromboembolism (VTE) exclusion. We report on a multicenter evaluation of a new, automated, latex enhanced turbidimetric immunoassay [HemosIL® D-Dimer HS 500, Instrumentation Laboratory (IL)].

Materials and Methods

747 consecutive outpatients with suspected proximal deep vein thrombosis (DVT, n = 401) or pulmonary embolism (PE, n = 346) were evaluated at four university hospitals in a management study with a 3 month follow-up. Samples were tested at each center using the new D-dimer assay on an automated coagulation analyzer [ACL TOP (IL)], with clinical cut-off for VTE at 500 ng/mL (FEU).

Results

The sensitivity and negative predictive value (NPV) were 100% for all PTP subgroups (no false negative results); for both sensitivity and NPV the lower limit of the 95% CI in patients with moderate/low PTP was higher than 95%. The overall specificity was 45.1% (95%CI: 41.1-49.3%). Higher specificity value was recorded in the low PTP subgroup [49.2% (95%CI: 41.7-56.7)]. No significant differences were found between patients suspected of having DVT or PE; sensitivity and NPV were 100%. The reproducibility of the assay was good, being the total CVs% less than 10% for D-dimer concentration near the clinical cut-off.

Conclusions

The new, highly sensitive D-dimer assay proved to be accurate when used for VTE diagnostic work-up in outpatients. Based on 100% sensitivity and NPV and lower limit of the 95% CI higher than 95%, the assay can be used as a stand-alone test in patients with non high PTP.     

Diagnosis and management of venous thromboembolism: Results of a survey on current clinical practice

Background

The implementation of evidence from clinical studies into daily clinical practice is not a straightforward process. We developed a standardized questionnaire to explore clinical practice patterns in the management of VTE, in particular about the use of pre-clinical probability and D-dimer testing and on the home treatment of pulmonary embolism (PE).

Methods

The standardized questionnaire was sent to all 394 physician members of the Italian Society of Thrombosis and Haemostasis (SISET) by e-mail. The questionnaire contained three groups of questions: about general information, about the diagnostic process for both deep venous thrombosis (DVT) and PE, and about home-therapy of PE.

Results

One hundred and twenty-eight (32.5%) physicians responded the questionnaire. For DVT diagnosis 69 (54.3%) physicians answered that they always use the D-dimer test; 4 (3.1%) do never use it; whereas only 11 (8.7%) take notice of the D-dimer result before visiting the patients; 38 (29.9%) use only clinical judgment to assess pre-clinical probability of disease. For the diagnosis of PE 80 (66.1%) physicians always use the D-dimer test, whereas 3 (2.5%) do never use it; whereas 14 (11.7%) take notice of the D-dimer result before visiting the patients; 50 (41.3%) use only clinical judgment to assess pre-clinical probability. Sixty-six (59.5%) clinicians declared to treat patients with PE at home, when feasible.

Conclusion

The diagnostic approach to VTE among expert physicians appears to be heterogeneous; in particular there is no widespread use of clinical prediction rules. The majority of expert physicians appear to consider the possibility of treating at home patients with PE.     

Unprovoked proximal venous thrombosis is associated with an increased risk of asymptomatic pulmonary embolism

Introduction

Pulmonary embolism (PE) is common in patients with deep venous thrombosis (DVT). The outcome of DVT with concomitant symptomatic PE is worse than the outcome of isolated DVT. The risk factors for DVT and simultaneous asymptomatic PE have not been systematically studied yet.

Aim

To evaluate the frequency and risk factors for asymptomatic PE in patients with DVT.

Patients/methods

In 155 consecutive patients with a first episode of DVT and no PE symptoms, a ventilation-perfusion lung scan was performed. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated and concentrations of D-dimer, high-sensitivity CRP (hsCRP), tissue plasminogen activator (t-PA) and troponin were measured. Laboratory tests for thrombophilia were performed.

Results

Asymptomatic PE was present in 36% of patients. No differences in gender, age, BMI and WHR were found between the patients with and without PE. PE was more common in patients with proximal DVT than in those with distal DVT (42% vs. 17%, p < 0.01), and in patients with unprovoked DVT compared to patients with provoked DVT (51% vs. 28%, p < 0.01). The risk of silent PE was the highest in patients with unprovoked proximal DVT (OR, 6.9; 95% CI, 2.3–21.0). Patients with asymptomatic PE had significantly higher values of D-dimer, hsCRP, t-PA and troponin than patients with isolated DVT.

Conclusions

Asymptomatic PE affected more than one third of patients with a first DVT. Unprovoked proximal DVT is the most important risk factor for the occurrence of silent PE.     

The G534E-polymorphism of the gene encoding the Factor VII-activating protease is a risk factor for venous thrombosis and recurrent events

Introduction

A single nucleotide polymorphism of the factor VII activating protease (FSAP), FSAP Marburg I (rs7080536) has been identified as a risk factor for venous thrombosis, but its clinical role has so far been controversial in part due to small cohort sizes. The aim of the present case-control study was to elucidate the impact of the FSAP Marburg I polymorphism (FSAP-MI) on the development of venous thromboembolic disease (VTE) with other known sequence variations, including Factor V Leiden (rs6025) and Factor II G20210A (rs1799963).

Materials and Methods

The study included 891 patients (312 male and 579 female) with a history of deep venous thrombosis (DVT) and/or pulmonary embolism (PE) and 1283 healthy blood donors with no history of venous thromboembolic disease.

Results

We found that besides to the well-established aforementioned sequence variations of FV and Prothrombin, the FSAP Marburg I (FSAP-MI) polymorphism was significantly associated with the development of DVTs (1.65 (1.16-2.34) OR (95% CI)) and recurrent thromboembolic events (DVT and PE) (2.13 (1.35-3.36) OR (95% CI)). Comparing patients displaying one or more events FSAP-MI was still associated with the development of recurrent thromboembolic events (1.64 (1- 2.69) OR (95% CI)).

Conclusions

We conclude that FSAP Marburg-I genotyping may be used to determine the risk for thromboembolic disorders in patients with suspected thrombophilia and known DVT or PE.     

A nationwide family study of pulmonary embolism: identification of high risk families with increased risk of hospitalized and fatal pulmonary embolism

Background

Family history is an important risk factor for deep venous thrombosis. However, few studies have determined the importance of family history of pulmonary embolism (PE).

Objective

This nationwide study aimed to determine the familial risks of fatal and hospitalized PE.

Methods

The Swedish Multi-Generation Register for subjects aged 0 to 76 years old born since 1932 were linked to the Hospital Discharge Register and Cause of Death Register for the period 1964-2008. Standardized incidence ratios (SIRs) for first hospitalization or death (without previous hospitalization for PE) with a main diagnosis of PE were calculated for individuals whose parent or siblings were hospitalized with or died from PE, compared to those whose parent or siblings were not affected by PE.

Results

A total of 20,860 individuals were hospitalized for PE and 862 died due to primary fatal PE (without previous hospitalization for PE). The familial SIR for individuals with one sibling with hospitalized PE was 2.49 (95% CI 1.62-3.83). The familial SIR for siblings with two affected probands was 114.29 (95% CI 56.57-223.95). The familial SIRs for individuals with a parent or sibling hospitalized for PE were significantly increased for fatal PE (1.76; 95% CI 1.38-2.21) and hospitalized PE (2.13; 95% CI 2.04-2.23). Spouses had low overall familial risk for PE (1.09; 95% CI, 1.03-1.14).

Conclusion

The high familial risk in multiplex sibling families suggests the existence of strong genetic risk factors for PE. Familial factors and possibly genetic factors are important risk factors for primary fatal pulmonary embolism.     

Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: A meta-analysis

Introduction

The Wells clinical decision rule (CDR) and D-dimer tests can be used to exclude pulmonary embolism (PE). We performed a meta-analysis to determine the negative predictive value (NPV) of an “unlikely” CDR (≤ 4 points) combined with a normal D-dimer test and the safety of withholding anti-coagulants based on these criteria.

Methods

Prospective studies that withheld anti-coagulant treatment from patients with clinically suspected PE and an “unlikely” CDR in combination with a normal D-dimer concentration without performing further tests were searched for in Medline, Cochrane and Embase. Primary endpoints were the recurrence rate of venous thromboembolism (VTE) and PE-related mortality during 3-months follow-up.

Results

Four studies including 1660 consecutive patients were identified. The pooled incidence of VTE after initial exclusion of acute PE based on an “unlikely” CDR and normal D-dimer was 0.34% (95%CI 0.036-0.96%), resulting in a NPV of 99.7% (95%CI: 99.0-99.9%, random effects-model). The risk for PE related mortality was very low: 1/1660 patients had fatal PE (0.06%, 95%CI 0.0017-0.46%).

Conclusion

Acute PE can be safely excluded in patients with clinically suspected acute PE who have an “unlikely” probability and a negative D-dimer test and anticoagulant treatment can be withheld. There is no need for additional radiological tests in these patients to rule out PE.     

Clinical prediction of pulmonary embolism in respiratory emergencies

Introduction

The initial management of suspected pulmonary embolism (PE) is commonly done in respiratory departments, but is based on clinical prediction rules developed in other settings.

Objective

To determine the accuracy of established prediction rules for PE in patients with respiratory emergencies.

Design

A prospective study

Materials and Methods

Patients presenting to respiratory emergency department with acute symptoms and signs suggestive of PE (n = 183) and subsequently admitted to hospital were prospectively enrolled. Wells’ rule, original and revised Geneva scores, their components separately, and other common clinical parameters were recorded during admission. PE was diagnosed by perfusion lung scanning, computed tomographic pulmonary angiography, lower limb venous ultrasonography, magnetic resonance pulmonary angiography, and/or pulmonary angiography.

Results

PE was confirmed in 52 and ruled out in 131 patients. Tachycardia, atelectasis, elevated hemidiaphragm, clinical signs of deep-venous thrombosis, physician perception that PE is the likeliest diagnosis, previous thromboembolism, chest pain, and absence of chronic obstructive pulmonary disease or cough were associated with the presence of PE. These significant parameters could be combined for accurate pre-test PE prediction, with a newly devised combinatorial tool exhibiting the highest area under curve [0.92 (95% CI: 0.87-0.97)], followed by Wells’ rule [0.86 (95% CI 0.79-0.92)], the revised Geneva score [0.83 (95% CI 0.77-0.90)], and the original Geneva score [0.75 (95% CI 0.68-0.83)].

Conclusion

Wells’ rule and the revised Geneva score are more useful in diagnosing PE in respiratory emergencies. A newly devised prediction tool can be of even greater accuracy in this patient population.     

Low level of factor V is associated with development of deep-vein thrombosis in Japanese patients

Background

Factor V, having two functions (procoagulant and anticoagulant), is a key factor in blood coagulation, and low plasma levels of factor V may be a risk factor for thrombosis.

Objective

The levels of plasma factor V antigen (FV:Ag), and the phospholipid binding capability of Factor V (FV:PL-bound) were evaluated in patients with deep-vein thrombosis (DVT).

Methods

Levels of FV:Ag, and FV:PL-bound were expressed as a percentage of the normal level found in pooled plasma from control subjects. One hundred and twenty-three Japanese patients with deep-vein thrombosis (DVT) were included, with 100 age and sex-matched healthy control subjects.

Results

The FV:Ag, and FV:PL-bound values were significantly lower in DVT patients than in healthy subjects (p < 0.05 and p < 0.005, respectively). Among the 123 patients, 30 for FV:Ag (24.4%), and 32 for FV:PL (26%) had less than the arbitrary cutoff point (set at the 5th percentile of the value for FV:Ag and FV:PL-bound from healthy subjects), and the odds ratios (ORs) were 6.1 (95% confidence interval [CI], 2.3-16.5) and 6.7 (95%CI, 2.5-17.9), respectively. When patients with a deficiency of natural anticoagulants (antithrombin, protein C, and protein S) were excluded from the analysis, the ORs increased for all patients (6.6 for FV:Ag (95%CI, 2.4-18.3) and 7.4 for FV:PL-bound (95%CI, 2.7-20.3). Moreover, twenty-one (17%) of the 123 DVT patients, and 1 (1%) of 100 control subjects had values below the cutoff points for both FV:Ag and FV:PL-bound, and the OR was 21.6 (95%CI, 2.85-163.1).

Conclusions

These results suggest that low levels of factor V are associated with development of DVT, and may be a predictor for DVT.     

Dabigatran, rivaroxaban and apixaban versus enoxaparin for thomboprophylaxis after total knee or hip arthroplasty: pool-analysis of phase III randomized clinical trials

Objectives

To compare the main efficacy and safety endpoints of the pivotal randomised clinical trials (RCTs) on venous thromboembolism (VTE) prevention after total hip (THR) or knee (TKR) replacement with the new oral anticoagulants (NAs) versus enoxaparin.

Methods

A pool-analysis of 10 RCTs that included 32.144 randomised patients was performed. Efficacy outcomes were total VTE and all-cause mortality, major VTE, and proximal DVT. Safety outcomes were major bleeding, and clinically relevant (major or non-major) bleeding.

Results

Overall, a significant effect favouring NAs was found for the primary efficacy outcome (RR 0.71; 95%CI 0.56-0.90), major VTE (RR 0.59; 95%CI 0.41-0.84), and proximal DVT (RR 0.51; 95%CI 0.35-0.76). Compared to enoxaparin 40 mg QD, rivaroxaban showed superiority (RR 0.50; 95%CI 0.34-0.73), followed by apixaban (RR 0.63; 95%CI 0.36-1.01) and dabigatran (RR 1.02; 95%CI 0.86-1.20). There was significant heterogeneity among trials and subgroups analysed for these efficacy outcomes. Major bleeding (RR 1.04; 95% CI 0.74-1.46) and clinically relevant bleeding (RR 1.03; 95%CI 0.88-1.21) was similar with NAs or enoxaparin. Rivaroxaban showed a trend toward more major bleeding episodes than enoxaparin (RR 1.88; 95%CI 0.92-3.82) and apixaban showed the lowest clinically relevant bleeding risk (RR 0.81; 95%CI 0.64-1.01).

Conclusions

Overall, NAs showed more efficacy and same safety when compared to the recommended dose of enoxaparin after THR and TKR. There are little differences in efficacy and bleeding risk among NAs and the type of prophylaxis that should be analysed further.     

Has the incidence of deep vein thrombosis in patients undergoing total hip/knee arthroplasty changed over time? A systematic review of randomized controlled trials

Background

There is a perception in the orthopaedic and thromboembolism community that the incidence of deep vein thrombosis (DVT) has decreased in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA).

Objectives

To assess the incidence of DVT with warfarin thromboprophylaxis over time in patients undergoing elective TKA or THA.

Methods

The MEDLINE, EMBASE, and Cochrane Library databases were searched to October 2006, supplemented by a manual search of reference lists. Two reviewers independently extracted data on study characteristics, quality and the frequency of total, symptomatic and proximal DVT.

Results

Fourteen studies (4,423 patients) were included. Total and proximal DVT after TKA declined over time (r = − 0.75, p = 0.031; r = − 0.86, p = 0.007 respectively). Total and proximal DVT after THA did not change. The risk of developing DVT after TKA was significantly higher than after THA (OR 1.85, 95% CI 1.6 - 2.14; p < 0.0001). The risk of developing symptomatic DVT after THA was significantly higher than after TKA (OR 2.18, 95% CI 1.11 - 4.27; p = 0.012).

Conclusions

The incidence of DVT in patients undergoing elective TKA appears to have declined in patients receiving warfarin thromboprophylaxis.     

Comparison of the clinical usefulness of two quantitative D-Dimer tests in patients with a low clinical probability of pulmonary embolism

Background

Quantitative D-Dimer tests are established methods in the non-invasive diagnostic management to rule out venous thromboembolism (VTE). The diagnostic performance and the clinical efficiency different D-Dimer assays in the exclusion of pulmonary embolism (PE) have not yet been compared in a clinical outcome study.

Objective

Evaluation of the efficiency and safety of excluding the diagnosis of PE with two different quantitative D-Dimer assays in consecutive patients with clinically suspected PE.

Patients and Methods

We studied the VTE-failure rate of 2206 consecutive patients with an unlikely clinical probability in whom VIDAS or Tinaquant D-Dimer tests were performed.

Results

The prevalence of PE in 1238 patients whose D-Dimer level was analyzed with Tinaquant assay was 11%. The VIDAS assay group consisted of 968 patients with a PE prevalence of 13%. The VIDAS assay had a sensitivity of 99.2% (95%CI; 96- > 99.9%), the Tinaquant assay of 97.3% (95%CI; 93 -99%). The negative predictive value (NPV) in the Tinaquant assay group was 99.4% (95%CI 98-99.8%) in comparison to 99.7% (95%CI 99-> 99.9%) in the VIDAS assay group. During 3 month of follow-up, there were no fatal cases of PE among patients with normal D-Dimer and unlikely clinical probability in both D-Dimer assay groups. In addition, the test efficiency of Tinaquant assay was significantly higher in comparison to VIDAS assay (52% vs 42%, p < 0.001).

Conclusion

Both Tinaquant and VIDAS D-Dimer tests perform equally well in combination with an unlikely clinical probability in excluding PE. The Tinaquant test was shown to be more efficient.     

Comparison of the Wells score with the simplified revised Geneva score for assessing pretest probability of pulmonary embolism

Introduction

The Wells score is widely used in the assessment of pretest probability of pulmonary embolism (PE). The revised Geneva score is a fully standardized clinical decision rule that was recently validated and further simplified. We compared the predictive accuracy of these two scores.

Methods

Data from 339 patients clinically suspected of PE from two prospective management studies were used and combined. Pretest probability of PE was assessed prospectively by the Wells score. The simplified revised (SR) Geneva score was calculated retrospectively. The predictive accuracy of both scores was compared by area under the curve (AUC) of receiver operating characteristic (ROC) curves.

Results

The overall prevalence of PE was 19%. Prevalence of PE in the low, moderate and high pretest probability groups assessed by the Wells score and by the simplified revised Geneva score was respectively 2%(95% CI (CI) 1-6) and 4% (CI 2-10), 28% (CI 22-35) and 25% (CI 20-32), 93% (CI 70-99) and 56% (CI 27-81). The Wells score performed better than the simplified revised Geneva score in patients with a high suspicion of PE (p < 0.05). The AUC for the Wells score and the simplified revised Geneva score was 0.85 (CI: 0.81 to 0.89) and 0.76 (CI: 0.71 to 0.80) respectively. The difference between the AUCs was statistically significant (p = 0.005).

Conclusions

In our population the Wells score appeared to be more accurate than the simplified revised Geneva score. The impact of this finding in terms of patient outcomes should be investigated in a prospective study.     

Anti-prothrombin antibodies are associated with thrombosis in children

Introduction

This investigation aimed to evaluate thrombotic risk factors in children, with special reference to autoantibodies against prothrombin and protein S.

Materials and methods

We studied 57 consecutive Swedish children and adolescents referred with a radiologically confirmed acute thrombotic event. Clinical data were collected and a thrombophilia investigation was performed, including analysis of autoantibodies against protein S (anti-PS) and prothrombin (anti-PT). The anti-PS and anti-PT autoantibodies were also investigated in sera from 47 healthy controls. Detection of autoantibodies was performed by quantitative enzyme-linked immunosorbent assays.

Results

Results for anti-PT antibodies were positive in 21% (12/57) of the patients and 2.1% (1/47) of the controls (OR 12.0, 95% CI 1.7-534; p = 0.005). Seven percent (4/57) of the patients and 2.1% (1/47) of the controls were positive for anti-PS antibodies (OR 3.4, 95% CI 0.3-174; p > 0.30). The FV G1691A mutation was found in 25% (14/57), and 44% (25/57) had 2 or more prothrombotic risk factors. Sixty percent (34/57) of the thrombosis patients were female. Peaks in frequency of thromboembolic events were found in the neonatal and the adolescent periods. Fifty-three percent (30/57) had thrombosis in the lower venous system. Associated clinical conditions occurred in 91% (52/57): systemic illness in 31% (18/57), infections in 26% (15/57), and oral contraceptive use in 25% (14/57). Four percent (2/57) had no apparent clinical or prothrombotic risk factors.

Conclusions

This study suggests that anti-PT autoantibodies may be common risk factors for thrombosis in children, and it confirms the multifactorial nature of pediatric thrombosis.     

Circulating tissue factor positive microparticles in patients with acute recurrent deep venous thrombosis

Introduction

Circulating tissue factor positive microparticles (MPTF) were reported in a wide range of diseases with thrombotic tendency. Though D-dimer assay had a high negative predictive value for deep venous thrombosis (DVT) recurrence, there are currently no reliable positive predictors for recurrent DVT. We therefore quantified MPTF in patients with acute recurrent DVT to determine whether MPTF levels could be used to predict recurrent DVT.

Materials and Methods

Microparticles (MPs) were isolated from plasma of initial DVT patients (n = 25), recurrent DVT patients (n = 25) and sex- and age-matched healthy individuals (n = 25), stained with annexin V, cell-specific monoclonal antibodies (MoAbs) and a MoAb directed against tissue factor (TF), and analyzed by flow cytometry. We also determined the plasma procoagulant activity with a Human TF Chromogenic Activity Assay Kit.

Results

We found total MPTF to be elevated in recurrent DVT patients versus normal individuals (P = 0.001). The number of monocyte-derived MPTF in both initial and recurrent DVT was higher than in normal individuals (P < 0.01, respectively). The platelet and endothelial cell derived MPTF in recurrent DVT were significantly increased relative to other MPTF (P < 0.05), although there was no difference between initial DVT patients and normal individuals. We demonstrated elevated procoagulant activity of platelet-free plasma in DVT patients relative to normal individuals, and a positive correlation with MPTF.

Conclusions

The elevated MPTF could be a potentially predictor for DVT recurrence. Further studies are needed to validate its sensitivity and specificity.     

Incidence and predictive factors of symptomatic thrombosis related to peripherally inserted central catheters in chemotherapy patients

Introduction

The incidence of symptomatic catheter-related deep vein thrombosis (DVT) in cancer patients remains unclear and there is a lack of reliable data on the risk factors of PICC-related DVT.

Materials and Methods

We performed a retrospective cohort study of consecutive cancer patients who received an ultrasound guided PICC line for the administration of chemotherapy. Univariable and multivariable logistic regression analyses were performed to identify risk factors for symptomatic PICC-related DVT.

Results

In total, 340 cancer patients obtained PICC lines for the administration of chemotherapy. Of these patients, 19 (5.6%; 95% CI: 3.6-8.6) developed symptomatic PICC-related DVT. Factors previously associated with catheter-related DVT, including side of catheter placement, lumen size, tip location, need for repositioning, and number of insertion attempts, were not significant determinants in our analysis. Patients with diabetes were three times more likely to develop PICC-related DVT (OR 3.0, p = 0.039), while the presence of COPD and metastatic cancer also increased the odds (OR 3.3, p = 0.078 and OR 2.3, p = 0.083 respectively). Diabetes remained a significant risk factor after adjustment for effect of metastases and COPD (OR 3.175, p = 0.039). Further, the presence of metastases was a significant predictor (OR 3.34, p = 0.024) in our multivariable model.

Conclusions

Symptomatic PICC-related DVT are frequent in cancer patients receiving chemotherapy. Previously described factors associated with catheter-related thrombosis were not predictive of PICC-related DVT in our study. Diabetes, advanced disease and COPD appear to increase the risk of developing PICC-related DVT in chemotherapy patients.     

The impact of co-morbid conditions on family history of venous thromboembolism in Whites and Blacks

Introduction

Our objectives were to compare the magnitude of family history as a risk factor for venous thromboembolism (VTE) risk between Blacks and Whites, and to assess the impact of co-morbid conditions on familial risk for VTE.

Materials and methods

We used data from the Genetic Attributes Thrombosis Epidemiology (GATE) study, a matched case-control study which enrolled Blacks and Whites aged 18-70 years in Atlanta, Georgia. A total of 1,094 case patients with a deep vein thrombosis (DVT) or pulmonary embolism (PE) and 1,264 control patients were interviewed about their family history.

Results

Family history of VTE was a statistically significant risk factor for VTE among Blacks (odds ratio (OR) = 2.9, 95% confidence interval (CI) 2.0-4.1; P value < 0.0001) and among Whites (OR = 2.7, 95% CI 1.9-3.7; P value < 0.0001); among Blacks and Whites who were obese or had hypertension; among Blacks who had diabetes mellitus or cancer; as well as among males and females, and across all age categories. Family history of VTE increased the risk of VTE among Blacks with cancer by about 6-fold, whereas among Blacks without cancer the increased risk due to a positive family history was about 3-fold; a 2-fold relative difference. In addition, family history was a risk factor for VTE among case patients with DVT only or with PE only. The effect of family history generally was stronger among those with recurrent episodes of VTE compared with a first episode of VTE. For example, family history of any VTE was a strong risk factor among Black females with recurrent VTE compared with Black females with first VTE (OR = 3.9, 95% CI 2.0-7.5; P value < 0.0001).

Conclusion

Our study indicated that the adjusted attributable fraction for VTE was 16.9% among Blacks vs. 18.3% among Whites, and certain co-morbid conditions could further increase the risk of VTE associated with a positive family history of VTE.