Subclinical Venous Thromboembolism Research Articles

Subclinical venous thromboembolism after pulmonary resection for lung cancer: an observational study

BackgroundSubclinical venous thromboembolism is a hidden pathology which may present with catastrophic consequences if not diagnosed at an early stage. This study was undertaken to estimate the occurrence and associated risk factors of subclinical deep vein thrombosis after lung resection for lung cancer patients. A prospective observational cohort study was performed in a tertiary cardiothoracic surgery center. One hundred fifty patients who underwent different types of lung resection for lung cancer were enrolled. Caprini’s risk score was assessed in all patients. All patients received prophylactic stockings and anticoagulants. On the 5th postoperative day, a duplex venous ultrasound of bilateral lower limbs was performed on every asymptomatic patient.ResultsOut of 150 patients enrolled in the study, 147 patients completed the study. Four patients (2.72%) developed subclinical deep vein thrombosis. The patients were divided into 2 groups: group 1 (n = 143) post-lung resection and no DVT and group 2 (n = 4) with post-lung resection subclinical DVT. No patient developed postoperative clinical DVT. The incidence was found to be highest in the group of individuals who had a longer stay in the ICU (odds ratio 37.9) (p = 0.04). Among the various pathologies, the incidence was higher in patients who received preoperative chemotherapy (odds ratio 21.9) (p = 0.001). One patient in the subclinical DVT group (25%) died, while no mortality was observed in the no DVT group.ConclusionsThe incidence of subclinical deep vein thrombosis is low in the postoperative period among patients undergoing lung resection for lung cancer if appropriate prophylactic measures are applied. However, patients receiving preoperative chemotherapy and those with longer periods of immobilization are at a higher risk of developing postoperative DVT despite anticoagulant prophylaxis. Due to the sample size and design limitations, the mentioned risk factors could be associated with DVT not a cause of DVT. It might be justified to screen these high-risk groups to detect subclinical DVT to allow for post-discharge prophylaxis.

Post-discharge Thromboembolic Events in COVID-19 Patients: A Review on the Necessity for Prophylaxis.

Coronavirus disease 2019 (COVID-19) affects the respiratory system of patients and is characterized by pneumonia with hypoxemia. Hospitalized patients and particularly those admitted to intensive care unit (ICU) may encounter a cascade of coagulopathies, which may lead to macrovessel thrombotic events such as pulmonary embolism (PE), deep vein thrombosis (DVT), or arterial thromboembolism (ATE). These events can result in serious life-threatening diseases including cerebrovascular stroke and myocardial infarction. Despite all available information about the incidence, prevention, and treatment of venous thromboembolism (VTE) among hospitalized patients, few data are available on the incidence of both symptomatic and subclinical VTE after discharge. Therefore, there is no precise suggestion or guideline for prophylaxis against VTE in post-discharge period, and some controversies exist over the current guidelines. In the present study, we aimed to review and summarize available literature upon incidence, prevention, diagnosis, and therapeutic approaches for VTE in COVID-19 patients. Also, the pathogenic mechanisms of VTE in infected individuals with COVID-19 were discussed.

D-Dimer Combined with Fibrinogen Predicts the Risk of Venous Thrombosis in Fracture Patients.

Objective While D-dimer can successfully diagnose venous thrombosis due to its excellent negative predictive value (NPV), it cannot be used to detect venous thromboembolism (VTE) because of its low positive predictive value (PPV). This study aims to investigate if a combination of using D-dimer and fibrinogen can improve PPV in the VTE diagnosis. Methods We retrospectively analyzed various data including D-dimer, fibrinogen, C-reactive protein, ultrasound, and others collected from 10775 traumatic fracture patients and categorized them into two groups of VTE and non-VTE. By comparing the difference between the two groups, we employ multiple logistic regression to find risk factors that are useful to detect VTE. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic yield of using fibrinogen, D-dimer, and their combination, respectively. Also, these data were classified into quartiles by patient age. We perform the same analysis on the quartiles and find if the patient's age has an impact on diagnosing VTE. Results The univariate analysis demonstrated that five factors of age, D-dimer, fibrinogen, C-reactive protein, and high-density lipoprotein cholesterol were significant to predict VTE. ROC showed that D-dimer was more useful than fibrinogen for the diagnosis of VTE, while the area under the curve (AUC) was 0.7296 for D-dimer and 0.5209 for fibrinogen. The cutoff point of D-dimer and fibrinogen was 424.89 ng/ml and 3.543 g/L, respectively. The specificity of fibrinogen was 0.777 which was better than D-dimer, while the sensitivity of fibrinogen was lower than that of D-dimer. Both PPV and NPV were similar in D-dimer and fibrinogen. The PPV of combining D-dimer and fibrinogen in ages Q3 (60 < age ≤ 70) and Q4 (age > 70) was better than using either D-dimer or fibrinogen. Conclusions Fibrinogen is a promising strategy for the diagnosis of subclinical VTE and postoperative VTE. In particular, a combination of D-dimer and fibrinogen can improve the PPV to successfully diagnose VTE in traumatic fracture patients who are more than 60 years old. Levels of Evidence. This assay is a diagnostic test at level II.

The Evaluation of Fibrin-Related Markers for Diagnosing or Predicting Acute or Subclinical Venous Thromboembolism in Patients Undergoing Major Orthopedic Surgery.

The cutoff values of fibrin-related markers (FRMs) diagnosing or predicting the occurrence of a venous thromboembolism (VTE) were evaluated. Fibrin-related markers such as fibrin monomer complex (FMC), D-dimer, and fibrinogen and fibrin degradation products (FDPs) before surgery were measured in 326 patients undergoing orthopedic surgery to diagnose subclinical VTE or predict postoperative VTE. Although the FMC, D-dimer, and FDP levels were all useful for the diagnosis of acute VTE, the FDP level was not useful for diagnosing subclinical VTE or predicting postoperative VTE. The results of several D-dimer assays closely correlated with other D-dimer assays. There were various cutoff ranges for diagnosing or predicting VTE. Some D-dimer assays were useful for diagnosing low levels of D-dimer and others were useful for diagnosing moderate to high D-dimer levels. Increased D-dimer levels were useful for diagnosing acute (cutoff values: 2.0-5.9 μg/mL) or about 10% of subclinical VTE (cutoff values: 3.4-5.3 μg/mL), for predicting about 10% of postoperative VTE (cutoff values: 3.4-5.3 μg/mL), and for excluding VTE. Although increased D-dimer levels were useful for diagnosing subclinical VTE and predicting the risk of VTE, there were various cutoff values for the diagnosis or prediction of VTE.

Fibrin-related markers for diagnosing acute-, subclinical-, and pre-venous thromboembolism in patients with major orthopedic surgery.

Venous thromboembolism (VTE) is a common complication in patients who have undergone major orthopedic surgery, but there are few predictors of VTE after major orthopedic surgery treated with an anticoagulant. We measured levels of fibrin-related markers (FRMs), such as D-dimer, soluble fibrin (SF), and fibrinogen and fibrin degradation products (FDPs) in 66 patients with acute-phase VTE, and 367 patients undergoing major orthopedic surgery. Plasma FDP, D-dimer, and SF levels were significantly higher in patients with acute VTE, but only FDP and D-dimer levels were significantly higher in subclinical VTE. Adequate cut-off levels of D-dimer were 2.2 μg/ml for diagnosing acute VTE and 1.5 μg/ml for diagnosing subclinical VTE. D-dimer of less than 1.9 or 0.7 μg/ml ruled out acute VTE or subclinical VTE. D-dimer of more than 1.3 μg/ml preoperatively showed a moderate risk for postoperative VTE. Measurement of FRMs is useful for evaluating the risk of subclinical or postoperative VTE in patients with major orthopedic surgery. In particular, FDP is the most valuable marker for diagnosing acute VTE, whereas D-dimer is the most valuable for diagnosing subclinical VTE or predicting VTE.

Silent venous thromboembolism before treatment in endometrial cancer and the risk factors

Venous thromboembolism (VTE) often occurs after surgery and can even occur before surgery in patients with gynaecological malignancies. We investigated the incidence of VTE before treatment of endometrial cancer and associated risk factors. Plasma D-dimer (DD) levels before initial treatment were examined in 171 consecutive patients with endometrial cancer. Venous ultrasound imaging (VUI) of the lower extremities was performed in patients with DD ⩾1.5 μg ml−1, as the negative predictive value of DD for VTE is extremely high. For patients with deep vein thrombosis (DVT), pulmonary scintigraphy was performed to ascertain the presence of pulmonary thromboembolism (PTE). Risk factors for VTE were analysed using univariate and multivariate analyses for 171 patients. Of these, 37 patients (21.6%) showed DD ⩾1.5 μg ml−1, 17 (9.9%) displayed DVT by VUI and 8 (4.7%) showed PTE on pulmonary scintigraphy. All patients with VTE were asymptomatic. Univariate analysis for various risk factors revealed older age, non-endometrioid histology and several variables of advanced disease as significantly associated with VTE before treatment. Obesity, smoking and diabetes mellitus were not risk factors. Multivariate analysis confirmed extrauterine spread and non-endometrioid histology as independently and significantly associated with risk of VTE. These data suggest that silent or subclinical VTE occurs before treatment in at least around 10% of patients with endometrial cancer. Risk factors for VTE before treatment might not be identical to those after starting treatment.

High incidence of silent venous thromboembolism before treatment in ovarian cancer

Venous thromboembolism (VTE) such as deep-vein thrombosis (DVT) and pulmonary thromboembolism (PTE) often occurs after surgery and rarely occurs even before surgery in patients with ovarian cancer. It is well known that levels of plasma D-dimer (DD) before treatment in most ovarian cancer patients are increased. This study therefore examined whether increased levels of DD are associated with presence of VTE before treatment of ovarian cancer. Between November 2004 and March 2007, DD levels prior to initial treatment were measured in 72 consecutive patients with presumed epithelial ovarian cancer (final diagnosis: epithelial ovarian cancer, n=60; and epithelial ovarian borderline malignancy, n=12). Venous ultrasound imaging (VUI) of the lower extremity was conducted for all patients except for two patients in whom DVT was detected by pelvic computed tomography (CT). When DVT was found, pulmonary scintigraphy was subsequently performed to ascertain presence of PTE. D-dimer levels were above the cut-off value (0.5 μg ml−1) in 65 of 72 patients (90.2%). Venous ultrasound imaging or CT revealed DVT in 18 of 72 patients (25.0%) and pulmonary scintigraphy found PTE in 8 patients (11.1%). All patients with VTE were asymptomatic when VTE was found. D-dimer levels were associated with incidence of VTE (0–1.4 μg ml−1; 0 of 26 (0%), 1.5–7.4 μg ml−1; 9 of 30 (30%) and ⩾7.5 μg ml−1; 9 of 16 (56.3%), P for trend=0.0003). However, even if 1.5 μg ml−1 was used as a cut-off value, this had low specificity and positive predictive value (47.2, 38.3%), though it had high sensitivity and negative predictive value (100, 100%). Therefore, ovarian cancer patients with DD level ⩾1.5 μg ml−1 should be examined using VUI to detect silent DVT. Patients with VTE underwent preventive managements including anticoagulant therapy before initial treatment, chemotherapy or surgery, and after surgery. There was no clinical onset of postoperative VTE in all 72 patients. Measurement of DD levels and subsequent ultrasonography revealed that silent or subclinical VTE frequently occurs before surgery in ovarian cancer. The usefulness of preoperative assessment of VTE needs further confirmation in randomised controlled trials.

The Risk of Venous Thromboembolism Following Hospitalization in Medical Patients without Cancer.

Background: Heparin therapy is recommended for prevention of venous thromboembolism (VTE) in hospitalized medical patients. This recommendation is based on studies demonstrating the efficacy of heparin in preventing surrogate endpoints such as positive venograms or vascular ultrasounds in patients without symptoms or signs of VTE. The efficacy of low-dose heparin prophylaxis in preventing clinical VTE in hospitalized general medical patients remains uncertain. Short-term studies suggest that up to 15% of such patients experience subclinical thrombosis during or shortly after hospital admission.Objective: To quantify the incidence of clinically significant events, we determined the rate of readmission for acute venous thromboembolism (VTE) in patients without cancer discharged from an medical inpatient stay.Methods: The study was performed using nation-wide DVA administrative and inpatient pharmacy databases. The source population was all male patients without a diagnosis of cancer admitted to any DVA medical service between April 1, 2002 and September 30, 2005. To qualify, the index medical admission (IMA) had to be longer than 3 days and not preceded by a surgical admission. Using ICD-9 codes for VTE and postphlebitic syndrome, subjects were categorized as follows: no history of VTE (noVTE), a history of prior VTE (pVTE) and an IMA of acute VTE (aVTE). Annualized rates of subsequent readmission for VTE were determined in each of these groups by life-table analysis and Cox proportional hazard models were used to derive hazard ratios (HR).Results: The final cohort consisted of 206,290 subjects of whom 0.36% had a subsequent readmission for VTE. The rates of VTE in the first year following IMA were 7.15%, 2.13% and 0.30% for aVTE, pVTE and noVTE groups respectively. Age adjusted Cox proportional models demonstrated a HR of 24.3 (95%CI 20.6, 28.8) for the aVTE and 7.7 (95%CI 5.9, 10.0) for the pVTE compared to the noVTE group. In the noVTE group, 25% of patients received warfarin or therapeutic heparin, 11% received only heparin prophylaxis and 64% received no anticoagulant therapy at any time during the IMA, with readmission for VTE occurred in 0.3%, 0.2% and 0.2% of patients in these subgroups respectively.Conclusions: Despite high rates of sub-clinical VTE in clinical trials enrolling patients admitted to medical services, we found that only 0.36% of patients are readmitted to hospital for VTE following discharge. An exception appears to be patients with a history of VTE who have considerably higher rates (2.13%). The rate of readmission for VTE in patients with an index admission for VTE (7.15%) is within the expected range, and consistent with other published reports. Despite the low utilization rates of heparin prophylaxis in patients without prior VTE, readmission with clinically apparent VTE is distinctly uncommon. These results support the argument claiming that prophylaxis may be unnecessary in the majority of medical patients without known malignancy or prior VTE.

Venous thromboembolism after acute stroke.

Treatment for venous thromboembolism (VTE) is highly effective in preventing morbidity and mortality, yet pulmonary embolism (PE) accounts for up to 25% of early deaths after stroke. This is because the current diagnostic paradigm is reactive rather than proactive: the clinician responds to VTE when it becomes symptomatic, in the expectation that initiation of treatment will prevent progression to more serious manifestations. This approach is flawed, because sudden death from PE is frequently unheralded and nonfatal symptomatic pulmonary emboli are often unrecognized or misdiagnosed. Morbidity and mortality from PE could be reduced either by more effective thromboprophylaxis or earlier diagnosis and treatment of established VTE. The fact that early use of short-term, low-dose, unfractionated heparin (UFH) is not associated with sustained, clinically meaningful benefit suggests that a fundamental change in the diagnostic approach to VTE is needed, one which requires a greater appreciation that clinically apparent events are merely the tip of the thromboembolism iceberg. Research into a strategy of screening for subclinical VTE in these patients is needed, with a view to identifying a subgroup at risk of progression to symptomatic and life-threatening events, in whom outcome might be improved by anticoagulation.