Distal Deep Venous Thrombosis Research Articles

Thrombosis Tendency After Splenectomy in a Danish Family With Hemoglobin Volga, and a Literature Review

Hemoglobin (Hb) Volga is a rare, unstable β-chain hemoglobin variant (β27 Ala→Asp), causing chronic hemolytic anemia. This study presents two members of a Danish family, splenectomized due to Hb Volga at and with multiple thrombotic events. The proband was diagnosed with Hb Volga 9 years old and splenectomy was performed as a part of treatment. Throughout his life, he experienced multiple superficial thrombophlebitis, two episodes of distal deep venous thrombosis (DVT) on lower extremities (age 32 and 33) and a transient ischemic attack (TIA) presented as amaurosis fugax (age 51). Thrombophilia investigation was normal. The proband’s son was diagnosed with Hb Volga and underwent splenectomy at the age of 6. Despite anticoagulation therapy, he suffered from multiple venous thromboembolic events in his youth and died of chronic pulmonary embolism (PE)/pulmonary hypertension combined with infection. Given the observed propensity for multiple thromboses in these two patients, a literature review was conducted investigating reported occurrence of thrombotic events in individuals with Hb Volga. Currently 25 cases of Hb Volga are reported worldwide. The clinical symptoms primarily described are related to hemolytic anemia. Splenectomy is reported in 15 patients. Thromboses have previously been reported in only three patients who were also splenectomized. These cases involved DVT and PE, myocardial infarction, and an unspecified thrombotic event. The proband represents the first reported Hb Volga case with both venous and arterial thrombotic disorders. The exact mechanism underlying thrombotic tendency in patients with Hb Volga remains unknown, but it is probably associated with splenectomy.

Risk assessment scales to predict risk of lower extremity deep vein thrombosis among multiple trauma patients: a prospective cohort study

BackgroundDeep vein thrombosis (DVT) is a common complication in orthopedic patients. Previous studies have focused on major orthopedic surgery.There are few studies with multiple trauma. We aimed to describe the prevalence of DVT and compare the predictive power of the different risk assessment scales in patients with multiple trauma.MethodsThis prospective cohort study involved multiple trauma patients admitted to our hospital between October 2021 and December 2022. Data were prospectively collected for thrombotic risk assessments using the Risk Assessment Profile for thromboembolism(RAPT), the DVT risk assessment score (DRAS), and the Trauma Embolic Scoring System (TESS), respectively. The receiver operation characteristic (ROC) curve and the area under the curve (AUC) were evaluated to compare the predictive power. The whole leg duplex ultrasound of both lower extremities Doppler ultrasound was used to determine DVT incidence.ResultsA total of 210 patients were included, and the incidence of DVT was 26.19%. Distal DVT accounted for 87.27%; postoperative DVT, 72.73%; and bilateral lower extremity thrombosis, 30.91%. There were significant differences in age, education degree, pelvic fracture, surgery, ISS, D-dimer level, length of hospital stay and ICU stay between the thrombosis group and the non-thrombosis group. The AUCs for RAPT, DRAS, and TESS were 0.737, 0.710, and 0.683, respectively. There were no significant differences between the three ROC curves.ConclusionsThe incidence of DVT was relatively high during hospitalization. We prospectively validated the tests to predict risk of DVT among patients with multiple trauma to help trauma surgeons in the clinical administration of DVT prophylaxis.

Incidence and Risk Factors for Thrombosis in Cancer Patients with COVID-19

Introduction: Cancer is a leading cause of morbidity and mortality in the United States, and cancer patients infected with COVID-19 are at increased risk of death. Given that cancer and COVID-19 are both risk factors for thrombosis, it has been hypothesized that cancer patients with COVID-19 may be at greater risk for thromboembolic events than patients with COVID-19 alone. This risk could necessitate the need for more vigilant thrombosis prophylaxis. However, studies investigating risk factors for thromboembolic events in this population are limited with mixed results. We aimed to determine the incidence and risk factors for thromboembolic events in patients with cancer and COVID-19. Methods: We performed a retrospective cohort review of all cancer patients hospitalized with COVID-19 at our institution between January 1, 2021 and April 1, 2023. Patients over the age of 18 who had previously been diagnosed with cancer, received treatment within the prior 6 months, and had been hospitalized due to COVID-19 were included in the study. We assessed whether patients had experienced a thromboembolic event during their hospital stay, which included thrombosis of the extracorporeal circuit, distal or proximal lower extremity deep venous thrombosis (DVT), upper extremity DVT, pulmonary embolism, superficial thrombophlebitis, ischemic stroke, or other arterial event. Information regarding comorbidities and clinical course was extracted from the patient's record. Descriptive analysis was performed, and association between qualitative variables was studied with the Chi-squared test and the Fisher Exact test, when appropriate. For quantitative variables, the t-test or the Mann-Whitney U test was performed. Multivariate logistic regression was used to assess variables predictive of thromboembolic events. Results: 456 patients with cancer and COVID-19 were included in the study. The median age was 69 years (IQR 62 - 78) and 55% of patients were male. The majority (85%) of patients were White. Most patients had either lung (19%) or bone marrow (17%) cancer, and 196 (43%) had received chemotherapy in the 6 months prior to hospitalization. 37 patients (8.1%) had thromboembolic events during their hospital stay. Age, race, receipt of chemotherapy, and history of hypertension, heart disease, obesity, and stroke were not predictive of thromboembolic events. Patients with thromboembolic events experienced significantly longer lengths of hospital stay than those without thromboembolic events (9 days vs 12 days, p<0.05). Conclusion: Thromboembolic events affect many cancer patients with COVID-19 and may complicate their treatment course during hospitalization. Patients who experienced a thromboembolic event had prolonged hospital stays, which may lead to increased financial and emotional burden in this patient population. Evidence-based strategies for preventing thrombosis, including pharmacologic and mechanical methods, should be emphasized in hospitalized cancer patients with COVID-19, which may decrease thrombotic complications. Further, methods of secondary thrombosis prophylaxis, such as early detection with screening methods or treatment of subclinical methods, should be encouraged. Future studies should promote risk classification in this patient population and optimal prophylaxis paradigms.

Guideline Compliance and Indications for Inferior Vena Cava Filter Placement at a Quaternary Care Medical Center.

This study investigated physician compliance with indications for inferior vena cava (IVC) filter placement according to the 2012 American College of Chest Physicians (ACCP) and the 2011 Society of Interventional Radiology (SIR) guidelines. A retrospective medical record review of 231 retrievable IVC filters placed between August 15, 2016, and December 28, 2017, at a large urban academic medical center. Guideline compliance to the 2012 ACCP and the 2011 SIR guidelines, and indications for IVC filter placements were assessed through an adjudication protocol. Filter retrieval and complication rates were also examined. Compliance to guidelines was low (60.2% for ACCP; 74.0% for SIR), especially for non-intensive care unit (ICU) patients (ICU 74.6% vs non-ICU 54.8%, p=0.007 for ACCP; ICU 82.5% vs non-ICU 70.8%, p=0.092 for SIR). After adjudication, 8.2% (19/231) of filters were considered non-indicated but reasonable, 17.7% (41/231) non-indicated and unreasonable, and 13.9% (32/231) SIR-indicated but not ACCP-indicated. The most common indication was venous thromboembolism with contraindication to anticoagulation. The most common reasons for non-compliance were distal deep venous thrombosis with contraindication to anticoagulation (19/60, 31.6%) and clot burden (19/60, 31.6%). One-year filter retrieval and 90-day complication rates were 32.0% (74/231) and 6.1% (14/231), respectively. Compliance to established guidelines was low. Reasons for non-compliance included limitations or discrepancies in guidelines, as well as non-evidence-based filter placements. Despite increasing utilization of inferior vena cava (IVC) filters, guideline compliance for IVC filter placement among providers is unclear. The results of this study indicate that physician compliance to established guidelines is poor, especially in non-intensive-care-unit patients. Noncompliance stems from non-evidence-based filter placement as well as differences and limitations in guidelines. Avoiding non-indicated IVC filter placement and consolidation of guidelines may significantly improve guideline compliance. The critical insights gained from this study can help promote judicious use of IVC filters and highlight the role of venous thromboembolism experts in navigating complex cases and nuances of guidelines.

Nomogram for predicting pulmonary embolism in gynecologic inpatients with isolated distal deep venous thrombosis.

To investigate the incidence of isolated distal deep venous thrombosis (IDDVT) concurrent with pulmonary embolism (PE) in gynecologic inpatients, analyze the risk factors for IDDVT with PE, and establish a nomogram model for IDDVT patients with PE. A total of 260 patients were diagnosed with IDDVT between December 2017 and November 2020. The incidence of PE in these patients was determined using computed tomography pulmonary angiography. Logistic regression analysis was used to identify the related risk factors. On this basis, nomogram risk prediction models were established. Among 260 patients with IDDVT, 106 (40.8%) had concurrent PE, of whom 74 (28.5%) experienced silent PE. Univariate logistic analysis demonstrated statistical significance for body mass index (BMI; P = 0.044), glucocorticoid therapy (P = 0.009), hypertension (P < 0.001), and diabetes (P < 0.001). Multivariate logistic analysis revealed that these were independent risk factors for IDDVT with PE that retained statistical significance. A nomogram based on these factors was constructed to predict PE in patients with IDDVT. Its receiver operating characteristic (ROC) showed an area under the curve of 0.710 (95% confidence interval 0.642-0.779), with prediction sensitivity of 64.2% and prediction specificity of 76.6%. In the present study, a high prevalence of PE was found in gynecologic inpatients with IDDVT. Glucocorticoid therapy, hypertension, diabetes, and BMI were independent risk factors for IDDVT patients with PE. Taking these risk factors into account, a nomogram risk prediction model was developed to help facilitate early detection of concurrent PE.

Radiofrequency ablation as a method of choice for the treatment of lower extremity varicose veins disease

The aim of the work is to improve the radiofrequency ablation (RFA) protocol in order to minimize disease recurrence and to improve the life quality of patients with lower extremity varicose veins disease (LEVVD).&#x0D; Materials and methods. An open-label, prospective study of the effectiveness of a modified RFA protocol for the treatment of 210 consecutive patients with clinical grade C2-C6 of LEVVD was conducted. The effectiveness and safety of the procedure were evaluated by the anatomical success of vein obliteration, the dynamics of the severity of venous pathology according to the VCSS scale, quality of life indicators determined using the AVVQ-UA questionnaire, and development of postoperative complications.&#x0D; Results. Sonographic control was conducted in the first 48 hours, 7 days and 1 month after the RFA procedure and recorded 100 % occlusion of the great saphenous vein, obtaining the effect of “radiofrequency crossectomy” in the jugular area. After 6 months and 1 year of follow-up, 208 (99.1 %) patients experienced vein occlusion and 2 (0.9 %) patients had partial vein occlusion within 1 cm of the sapheno-femoral junction without pathological reflux. After 2 years the partial occlusion was diagnosed in 4 (1.9 %) patients.&#x0D; During the first 2 weeks after treatment, 64 (30.5 %) patients reported complications, which didn’t require treatment. However, in 2 (0.9 %) cases asymptomatic distal DVT and in 1 (0.5 %) EHIT II were diagnosed. Anticoagulant therapy was prescribed. Regression of clinical symptoms with a statistically significant difference in the VCSS score (p &lt; 0.001) was observed 6 months after RFA. The application of the proposed RFA protocol made it possible to statistically significantly improve the quality of life indicators 1 month after treatment by 3.36 ± 0.81 (р &lt; 0.001) with further positive dynamics.&#x0D; Conclusions. The application of the proposed RFA protocol in patients with LEVVD has a good safety profile, allows to minimize disease recurrences, performing the effect of “radiofrequency crossectomy”, and has a positive effect on the regression of clinical symptoms and quality of life indicators.

Clonal haematopoiesis of indeterminate potential in patients with venous thromboembolism.

Over the last decade, the concept of Clonal haematopoiesis of undetermined potential (CHIP) has emerged. Low frequency somatic mutations in hematopoietic cells can occur with age and might allow formation of clones in individuals with no characterized haematological pathology. These CHIP mutations are associated with an increased risk of cancer or atherothrombosis, and their prevalence are more and more studied in pathologies with an inflammatory component. In our study, we analysed, by next generation sequencing, the prevalence of CHIP mutation in 94 patients with deep venous thrombosis (DVT), distinguishing two clinical phenotypes: provoked distal and non-provoked proximal DVTs. We show that there is no difference in CHIP prevalence between these two groups, nor with a matched-aged control group. The number of mutation per patients and the affected genes remain also the same between the three groups. Consequently and despite the relative small number of patients in each cohort, it seems that CHIP is not a strong concern in venous thromboembolism.

Systematic Review and Meta-Analysis of the Pooled Rate of Post-Thrombotic Syndrome After Isolated Distal Deep Venous Thrombosis

Systematic Review and Meta-Analysis of the Pooled Rate of Post-Thrombotic Syndrome After Isolated Distal Deep Venous Thrombosis

Incidence and Clinical Features of Venous Thromboembolism in Inpatients with Mental Illness.

We investigated the incidence and clinical features of venous thromboembolism (VTE) in inpatients with mental illnesses. We retrospectively analyzed records of inpatients with mental illnesses and confirmed VTE at The First Hospital of Hebei Medical University between August 2018 and July 2022. We recorded demographic characteristics, psychosis-related conditions, and thrombus distribution. Among 12939 patients diagnosed with mental illness, 156 (1.21%) presented with VTE at the first visit or during the disease course. Crude VTE incidence varied significantly across mental illnesses, being highest in patients with organic mental disorders (5.20%), followed by emotional disorders (1.10%), and others (P < 0.001). Distal and proximal deep venous thromboses (DVT) occurred in 79.17% and 20.84% of patients, respectively. The Hamilton Depression Scale (HAMD) score was higher in patients with proximal DVT than in those with distal DVT (P < 0.001). On multivariate analysis, the HAMD score (odds ratio [OR] 1.173, confidence interval [CI] 1.100-1.251, P＜0.001) was a risk factor and the Hamilton Anxiety Scale (HAMA) (OR 0.862, CI 0.796-0.934, P＜0.001), a protective factor against DVT progression. VTE is not rare in patients with mental illnesses and is most commonly associated with organic mental disorders. Psychosis-related DVT typically shows a significantly high incidence of distal DVT. Prevention and early treatment in patients with severe depression and distal DVT can prevent DVT aggravation.

Evaluation of the relationship between monocyte to high-density lipoprotein cholesterol ratio and thrombus burden in patients with deep vein thrombosis

The purpose of this study was to evaluate monocyte count and high-density lipoprotein cholesterol levels and their ratio (monocyte/high-density lipoprotein ratio) in patients with deep venous thrombosis as well as to determine whether this ratio at the time of diagnosis can be an indicator of thrombus burden in terms of thrombus location in deep venous thrombosis. We retrospectively analyzed the patient's diagnosis of deep venous thrombosis confirmed with venous Doppler ultrasound, using a database query for outpatients between 2018 and 2022. Of 378 patients included, blood count results at the time of diagnosis were available for 356. We recruited 300 age- and sex-matched patients with appropriate blood counts, without a diagnosis of deep venous thrombosis, as the control group, by querying the outpatient clinic database. The monocyte/high-density lipoprotein ratio was computed from the ratio of monocyte count to high-density lipoprotein-C. Patients were categorized based on the level of thrombus and the number of vein segments involved as evidenced by Doppler ultrasound findings. The serum level of monocyte/high-density lipoprotein ratio was significantly higher in the patient group compared to the control group (p<0.01). Patients with proximal deep venous thrombosis had a higher mean monocyte/high-density lipoprotein ratio (19.6±5.1 vs. 17.1±5.5; p<0.01) than patients with distal deep venous thrombosis. Monocyte/high-density lipoprotein ratio increased with the number of vein segments involved (p<0.01). Monocyte/high-density lipoprotein ratio is significantly elevated in patients with deep venous thrombosis when compared to the control group. Monocyte/high-density lipoprotein ratio levels were correlated with disease burden reflected by thrombus location and the number of vein segments involved in deep venous thrombosis patients.

Risk factors of venous thromboembolism after incisional ventral hernia repair.

The problem of venous thromboembolic events (VTE) after incisional hernia repair remains relevant. According to the literature the frequency of VTE ranges from 0.2 to 4.2%. The data on risk factors of VTE in this cohort of patients are scarce. Aim of our study is to find frequency and risk factors for VTE development in patients who underwent surgery for incisional ventral hernia. There were 240 patients enrolled in our retrospective study. We included patients, who were operated for incisional hernia in Saveljev University Surgery Clinic from January 2018 to December 2019. Compression duplex ultrasound of lower extremity veins was performed within median 3days (min 1day, max 7days) after surgery for all participants. The primary endpoint was the occurrence of the VTE event, including deep venous thrombosis (DVT) and pulmonary embolism (PE). VTE was detected in 19 patients, which accounted for 7.9% in analyzed cohort. All patients received standard pharmacological prophylaxis. There were 3 (1.3%) proximal, 16 (6.7%) distal DVT, in one patient (0.4%) distal thrombosis was complicated by symptomatic pulmonary embolism. In multivariate Cox proportional hazard model was found that component separation (HR 3.99, 95% CI 1.14-14.0, p = 0.03), duration of operation in hours (HR 1.67. 95% CI 1.13-2.5, p = 0.011) and body mass index (HR 1.13, 95% CI 1.02-1.2, p = 0.02) were statistically significant risk factors. The incidence of postoperative VTE in patients after incisional hernia repair is high with a predominant distal DVT as a thrombotic event. Component separation, duration of operation and body mass index are statistically significant factors of VTE in patients undergoing surgery for incisional hernia.

Abstract 14686: Prevalence and Predictors of Normotensive Shock in Intermediate-Risk Pulmonary Embolism

Introduction: In patients presenting with pulmonary embolism (PE) and shock/hypotension (high-risk PE), immediate thrombolytic therapy or mechanical thrombectomy is recommended. However, the prevalence and predictors of normotensive shock in patients with intermediate-risk PE are not well defined. Methods: PE patients undergoing mechanical thrombectomy with the FlowTriever System (Inari Medical) were enrolled in the FLASH Registry. Patients were included in this analysis if they were intermediate-risk per ESC guidelines (i.e., normotensive) and had cardiac index (CI) measured pre- and post-thrombectomy. Invasive hemodynamics were measured pre- and post-thrombectomy and compared using paired data. Patients were grouped into those with normotensive shock (CI ≤ 2.2 l/min/m 2 ) or without shock (CI &gt; 2.2 l/min/m 2 ). Multiple logistic regression was used to identify baseline predictors of normotensive shock. Safety outcomes through 30 days were recorded. Results: Out of 384 intermediate-risk PE patients, more than one-third (131, 34.1%) were in normotensive shock at baseline. The shock group had significantly lower BMI, higher RV/LV ratio, and higher rates of moderately/severely reduced RV function and concomitant DVT (Table). Significant predictors of shock included tachycardia, distal concomitant DVT, moderately/severely reduced RV function, and saddle PE. The normotensive shock group showed significant on-table improvement in CI and mean PA pressure post-thrombectomy (Figure). Safety profiles were not significantly different between groups, with similarly low rates of major adverse events and mortality through 30 days (Table). Conclusion Although identified as intermediate-risk, over one-third of patients had normotensive shock, suggesting they may be at risk of hemodynamic deterioration despite appearing stable. Treatment with mechanical thrombectomy improved patient hemodynamics on the table, with low rates of mortality in both groups.

Case Report OCLC Number/Unique Identifier: Unusual Thrombosis Despite Anticoagulation

Background: Pulmonary Embolism (PE) is a life-threatening condition with annual incidence ranging from 39 to 115 cases per 100,000 population [1]. Along with many other causes, neoplasia is one of the highest risk factors for pancreatic, lung, gastric, cerebral and haematological cancer [2]. Patients with neoplasia often have venous thromboembolism (VTE) during the course of the disease, but occasionally neoplasia is diagnosed as secondary to VTE. Case Presentation: A 55-year-old man known with high blood pressure and dyslipidaemia is diagnosed with bilateral distal Deep Venous Thrombosis (DVT) and treated with a factor Xa inhibitor. Two months later he is admitted for fatigue, dry cough, unwanted weight loss of approximately 5kg for a month and progressive exertion dyspnea. The echocardiographic examination reveals dilated right chambers with thrombus in the Right Ventricle (RV). The suspicion of pulmonary embolism it was confirmed on thoracic contrast CT examination. Large bilateral mediastinal adenopathies and a right lung nodule were also visualised on lung CT scan. The patient was treated with unfractionated heparin, slow-acting nitrate, aspirin, calcium blocker, with the disappearance of the thrombus from the right ventricle. Bronchoscopy showed a lesion near the right main bronchus. The diagnosis of pulmonary adenocarcinoma is confirmed histopathologically on the sample obtained at bronchoscopy and from the mediastinal lymph node obtained at mediastinoscopy. The patient was referred to the oncology service for specialised treatment. Conclusion: VTE under anticoagulant treatment should always raise some suspicions and other causes should be sought. Undiagnosed neoplasms , drug resistance or drug interactions, thrombophilias are some of the causes that should be suspected in case of thrombosis under therapeutic anticoagulant.

Combined oral contraceptive-associated venous thromboembolism revealing an antiphospholipid syndrome: International retrospective study of outcomes.

IntroductionLimitations in the data used to define thromboprophylaxis for patients with antiphospholipid antibodies (aPLAbs) and thrombosis include uncertainties after an initial provoked venous thromboembolic event (VTE). We aimed to study such cases associated with combined oral contraceptive (COC) intake. MethodsWe retrospectively analysed thrombotic outcomes after a first COC-associated VTE and positive aPLAbs, with a low risk HERDOO2 score, on low-dose aspirin (LDA) secondary thromboprophylaxis, seen from 2010 to 2021 in 3 tertiary referral centres, one in France and 2 in Russia. Data from 264 patients (distal deep vein thrombosis DVT: 62.9 %), cumulating in 1327.7 patient-years of observation, were collected. ResultsThere were 22 cases of thrombosis: 16 distal DVTs, 3 proximal, 1 pulmonary embolism (PE) and 2 transient ischemic attacks. Recurrence rate was 1.66 per 100 patient-years (p-y; 95 % CI: 0.96–2.33). No major bleeding occurred. Risk factors affecting recurrence-free survival were the time between first COC intake and VTE (p < 0.0001; the shortest, the lower), proximal DVT (p = 0.021), active smoking (p = 0.039), an associated systemic disease (p = 0.043) and circulating monocyte counts (p = 0.001). ConclusionsWe observed a low risk of recurrence which was modulated by classical risk factors for VTE. These observational data may provide clues for future randomized controlled trials.

Hospitalized patients with isolated distal deep vein thrombosis: anticoagulation therapy or not?

BackgroundIsolated distal deep vein thrombosis (IDDVT), a disease frequently detected in hospitalized patients, can progress to proximal deep vein thrombosis (PDVT) and pulmonary embolism (PE). Here, we evaluated the effects of anticoagulation in hospitalized IDDVT patients.MethodsWe conducted a retrospective study in our hospital and enrolled hospitalized IDDVT patients diagnosed by compression ultrasonography (CUS) from January to December 2020. Participants were divided into anticoagulation (AC) and non-anticoagulation (non-AC) groups. After propensity score matching (PSM), multivariate Cox regression analyses were performed to assess whether anticoagulation was associated with PDVT/PE, and all-cause mortality.ResultsA total of 426 IDDVT inpatients with CUS follow-up were screened from 1502 distal DVT patients and finally enrolled. The median age was 67 years with 51.4% males and 15.5% cancer patients. The median follow-up was 11.6 months. There were 288 and 138 patients treated with or without anticoagulants, respectively. Patients in the non-AC group had less body mass index and more comorbidities. Patients in the AC group were treated with rivaroxaban or dabigatran (52.1%), low molecular weight heparin (42.7%), and warfarin (5.2%). The PSM generated 111 pairs of well-matched IDDVT patients with or without anticoagulation. The Kaplan–Meier analysis demonstrated that neither the incidence of PDVT/PE (5.4% vs. 2.7%, log-rank p = 0.313) nor all-cause mortality (27.9% vs. 18.9%, log-rank p = 0.098) was significant different between groups. Anticoagulation was not associated with PDVT/PE and all-cause mortality in the multivariable Cox regression analyses using the matched cohorts. The main risk factors for all-cause mortality were age, malignancy history, BMI, sepsis, heart failure, and white blood cell (WBC) count.ConclusionsIn hospitalized IDDVT patients, the thrombosis extension rate to PDVT/PE was low. Anticoagulation did not reduce the incidence of thrombosis extension of IDDVT and was not associated with all-cause mortality.

Incident thrombus location and predicting risk of recurrent venous thromboembolism

BackgroundUnderstanding venous thromboembolism (VTE) recurrence risk is central to determining the appropriate treatment course. Whether this risk varies after discontinuing anticoagulation or overall by type of incident event (pulmonary embolism [PE] vs deep vein thrombosis [DVT]) and by the detailed location of the DVT needs further clarification. MethodsIn this population‐based inception cohort of incident VTE cases with follow‐up by electronic health record review, incident DVT was categorized as distal, popliteal, or iliofemoral. We used the Fine‐Gray regression model to describe the predictive association of the thrombus location with the risk of recurrence before death. ResultsAmong 2766 participants with an incident event from 2002 to 2010, 1713 (62%) ceased anticoagulation and were followed for recurrent events; 301 events were observed during the 4.5 years of follow‐up. Relative to participants with an incident thrombus in an iliofemoral location and no PE, those with a thrombus in a popliteal location and no PE had a similar risk of recurrence (adjusted subdistribution hazard ratio [aSHR], 0.82 [95% confidence interval (CI), 0.57–1.19]), while those with a thrombus in a distal location and no PE and those with a thrombus that included a PE had lower risk of recurrence: aSHR, 0.34 (95% CI, 0.20‐0.57); and aSHR, 0.58 (95% CI 0.45‐0.76), respectively. ConclusionsThe findings of this population‐based inception cohort confirm that the risk of recurrent VTE after discontinuing anticoagulants is similar after iliofemoral and popliteal DVT but is lower after distal DVT. Recurrence may be lower after PE than proximal DVT.

Incidence, timing, location, risk factors, and nomogram of lower extremity deep venous thrombosis after acutecarbon monoxide poisoning.

Data on lower extremity deep venous thrombosis (DVT) following acute carbon monoxide (CO) poisoning are lacking. This study aimed to identify the incidence rate, timing, locations, risk factors, and nomogram of lower extremity DVT after acute CO poisoning. A total of 203 patients with acute CO poisoning from October 2019 to April 2021 were included in this retrospective study. Multivariate logistic regression analysis was performed to identify the independent risk factors associated with lower extremity DVT. Nomogram was drawn and area under the curve (AUC) was calculated to predict lower extremity DVT. Overall, 14.3% (29/203) had lower extremity DVT, with incidence rates of 2.5% (5/203) for proximal DVT and 11.8% (24/203) for distal DVT. The lower extremity DVTs involved intermuscular vein in 28 patients, popliteal vein in 5 patients, and posterior tibial vein in 3 patients. The mean time from end of exposure to diagnosis of lower extremity DVT was 1.24days. Among 29 lower extremity DVT cases, 6 (23.1%) DVT cases had thrombolysis. Multivariate logistic regression analysis revealed that long coma duration (P < 0.001) and high D-dimer levels (P < 0.001) were significantly associated with lower extremity DVT. The discrimination of nomogram was good with AUC of 0.93 (95% CI, 0.89-0.98). Clinicians should be aware of and concerned with lower extremity DVT after acute CO poisoning, especially in patientswith long coma duration and high D-dimer levels.

Increased Prevalence of Elevated D-Dimer Levels in Patients on Direct Oral Anticoagulants: Results of a Large Retrospective Study.

Elevated D-dimer levels during anticoagulant therapy with vitamin K antagonists (VKA) are associated with an increased risk of thrombosis. It has been hypothesized that elevated D-dimer levels in patients receiving direct oral anticoagulants (DOACs) also indicate an increased risk of thrombosis recurrence, but data on the distribution of D-dimer levels in patients with VTE on DOACs are sparse. In the present study we retrospectively analyzed D-dimer levels in patients taking DOACs after first or recurrent venous thrombosis (n = 1,716, 1,126 thereof rivaroxaban, 481 apixaban, 62 edoxaban, and 47 dabigatran). Patients on VKA (n = 402) served as control group. Thrombotic events in the study population were categorized into distal deep venous thrombosis (DVT, n = 552 patients), distal DVT with pulmonary embolism (PE, n = 166), proximal DVT (n = 685), proximal DVT with PE (n = 462), PE without DVT (n = 522), DVT of the upper extremity (n = 78), cerebral venous sinus thrombosis (CVST, n = 48), and other venous thrombosis (n = 74). In VKA users a median D-dimer level of 0.20 mg/l was observed. In patients on DOACs D-dimer levels were significantly higher, with 0.26 mg/l for rivaroxaban, 0.31 mg/l for apixaban (P < 10−16 each), 0.24 mg/l for edoxaban (P = 2 × 10−5), and 0.25 mg/l for dabigatran (P = 4 × 10−4). These differences in comparison to patients on VKA treatment could not be explained by the patients' age, sex, body mass index, and type of thrombosis as these characteristics did not differ significantly between cohorts. Moreover, the prevalence of D-dimer levels above age-adjusted cut-offs [≥0.50 mg/l in ≤50-year-old patients, ≥(age × 0.01) mg/l in >50-year-old patients] was higher in patients on rivaroxaban (13.9%, RR 1.74, 95% CI 1.21–2.50), apixaban (17.0%, RR 2.14, 95% CI 1.45–3.15) and dabigatran (23.4%, RR 2.94, 95% CI 1.59–5.44) than in patients on VKA (8.0%). In patients on edoxaban D-dimer levels above the reference range were observed in 14.5%, but no statistical significance was reached in comparison to the VKA cohort. In conclusion, the obtained data suggest, that the type of oral anticoagulant should be considered in the clinical assessment of D-dimer levels in thrombosis patients. Further studies are warranted to evaluate a potential association between elevated D-dimer levels and thrombosis risk in patients on DOACs.

Incidence and Outcomes Associated with 6,841 Isolated Distal Deep Vein Thromboses in Patients with 13 Common Cancers.

The epidemiology of isolated distal deep venous thrombosis (iDDVT) among cancer patients is not well described, particularly the incidence of recurrent venous thromboembolism (rVTE) and effect on mortality by cancer type. The cumulative incidence (CI) of iDDVT was determined for patients with 13 common cancers between 2005 and 2017 using the California Cancer Registry linked to the California Patient Discharge and Emergency Department Utilization datasets. The CI of rVTE was calculated and association of incident cancer-associated thrombosis (CT) location with rVTE was determined using Cox proportional hazards regression models. The association of incident CT location with overall and cancer-specific mortality was determined using Cox models, stratified by cancer site, and adjusted for individual characteristics. Among 942,109 cancer patients, CT occurred in 62,003 (6.6%): of these, 6,841 (11.0%) were iDDVT. Compared with more proximal sites of CT, iDDVT was associated with similar risk for rVTE. IDDVT was associated with increased mortality across all cancer types when compared with patients without CT (hazard ratio: 1.56-4.60). The effect of iDDVT on mortality was similar to that of proximal DVT (pDVT) for most cancers except lung, colorectal, bladder, uterine, brain, and myeloma, where iDDVT was associated with a lesser association with mortality. iDDVT represented 11% of CT. The risk of rVTE after iDDVT was similar to other sites of CT and rVTE occurred in more proximal locations after an incident iDDVT. IDDVT was associated with increased mortality and this effect was similar to that of pulmonary embolism or pDVT for most cancer types.

Pathogenesis of Two Faces of DVT: New Identity of Venous Thromboembolism as Combined Micro-Macrothrombosis via Unifying Mechanism Based on "Two-Path Unifying Theory" of Hemostasis and "Two-Activation Theory of the Endothelium".

Simple SummaryDVT is an intravascular blood clotting disorder that can be a life-threatening disease, particularly if it occurs in critically ill patients. Typically, distal DVT develops following a vascular injury associated with incidental trauma commonly involving lower extremities, which is transient and benign condition localized in the lower legs as solitary lesion. However, proximal/central DVT (i.e., venous thromboembolism) typically occurs in association with critical illnesses such as sepsis, diabetes, hypertension, cancer, autoimmune disease and others in the hospitalized patient, especially in the ICU. Recognition of different pathogenesis between distal DVT and proximal/central DVT is critically important because the prognosis is poorer in VTE. Its therapeutic approach should be different from distal DVT. The aim of this review is to identify the pathogenesis of two different types of DVT based on in vivo hemostatic mechanisms, which can explain their distinct phenotypes by clinical characteristics, laboratory data and imaging findings. An appropriate preventive measure can be put into the practice to avoid the onset of VTE. Additionally, should VTE be developed, proper and rational therapeutic regimen based on its pathogenesis can be designed for clinical trials to improve the outcome.Venous thrombosis includes deep venous thrombosis (DVT), venous thromboembolism (VTE), venous microthrombosis and others. Still, the pathogenesis of each venous thrombosis is not clearly established. Currently, isolated distal DVT and multiple proximal/central DVT are considered to be the same macrothrombotic disease affecting the venous system but with varying degree of clinical expression related to its localization and severity. The genesis of two phenotypes of DVT differing in clinical features and prognostic outcome can be identified by their unique hemostatic mechanisms. Two recently proposed hemostatic theories in vivo have clearly defined the character between “microthrombi” and “macrothrombus” in the vascular system. Phenotypic expression of thrombosis depends upon two major variables: (1) depth of vascular wall damage and (2) extent of the injury affecting the vascular tree system. Vascular wall injury limited to endothelial cells (ECs) in sepsis produces “disseminated” microthrombi, but intravascular injury due to trauma extending from ECs to subendothelial tissue (SET) produces “local” macrothrombus. Pathogen-induced sepsis activates the complement system leading to generalized endotheliopathy, which releases ultra large von Willebrand factor (ULVWF) multimers from ECs and promotes ULVWF path of hemostasis. In the venous system, the activated ULVWF path initiates microthrombogenesis to form platelet-ULVWF complexes, which become “microthrombi strings” that produce venous endotheliopathy-associated vascular microthrombotic disease (vEA-VMTD) and immune thrombocytopenic purpura (ITP)-like syndrome. In the arterial system, endotheliopathy produces arterial EA-VMTD (aEA-VMTD) with “life-threatening” thrombotic thrombocytopenic purpura (TTP)-like syndrome. Typically, vEA-VMTD is “silent” unless complicated by additional local venous vascular injury. A local venous vessel trauma without sepsis produces localized macrothrombosis due to activated ULVWF and tissue factor (TF) paths from damaged ECs and SET, which causes distal DVT with good prognosis. However, if a septic patient with “silent” vEA-VMTD is complicated by additional vascular injury from in-hospital vascular accesses, “venous combined micro-macrothrombosis” may develop as VTE via the unifying mechanism of the “two-path unifying theory” of hemostasis. This paradigm shifting pathogenetic difference between distal DVT and proximal/central DVT calls for a reassessment of current therapeutic approaches.