The trends in venous thromboembolism occurrence and prevention after minimally invasive varicose vein surgery.

OBJECTIVES: To assess the trends of VTE occurrence and prevention in varicose vein surgery. METHOD: The registry-based CAPSIVS trial (NCT03041805) analysis includes results in 1878 lower limbs. The primary outcome is a 28-day symptomatic or asymptomatic DVT revealed with duplex ultrasound. RESULTS: Any DVT, including EHIT, was observed in 3.4%, while symptomatic in 0.5%. Prophylactic anticoagulation was administrated in 20.4% with LMWH (13.2%) or DOAC (7.1%) for patients with higher VTE risk but did not reduce the events rate. With propensity score matching DOACs were superior to LMWHs (1.5% vs 9.8%). Duration of anticoagulation was essential: the lowest incidence (4.2%) was associated with prophylaxis for up to 7 days, while a single LMWH injection resulted in a DVT rate of 8.8%. With individual VTE history, any anticoagulation duration appeared insufficient. CONCLUSIONS: Prophylactic anticoagulation after varicose vein surgery should be based on the individual VTE risk and provided for ≥7-30 days.

Neutrophils Mediate Pulmonary Artery Thrombosis In Situ.

Pulmonary embolism is a life-threatening condition, which can result in respiratory insufficiency and death. Blood clots occluding branches of the pulmonary artery (PA) are traditionally considered to originate from thrombi in deep veins (usually in legs). However, growing evidence suggests that occlusion of the vessels in the lungs can develop without preceding deep vein thrombosis (DVT). In this work, we used an inferior vena cava (IVC) complete ligation model of DVT in Wistar rats to explore the possibility and mechanisms of PA thrombosis under the conditions where all routes of thrombotic mass migration from peripheral veins are blocked. We demonstrate that rats both with normal and reduced neutrophil counts developed thrombi in the IVC, although, neutropenia caused a substantial decrease in thrombus size and a shift from fresh fibrin toward mature fibrin and connective tissue inside the thrombus. Massive fibrin deposition was found in the PA branches in the majority of DVT rats with normal neutrophil counts, but in none of the neutropenic animals. Neutrophil ablation also abolished macroscopic signs of lung damage. Altogether, the results demonstrate that thrombi in the lung vasculature can form in situ by mechanisms that require local neutrophil recruitment taking place in the DVT setting.

Rivaroxaban for the prevention of venous thromboembolism after radiofrequency ablation of saphenous veins concomitant with miniphlebectomy, sclerotherapy, or no treatment of varicose tributaries.

OBJECTIVE: To assess the efficacy and safety of once-daily 10 mg rivaroxaban for venous thromboembolism prophylaxis after ClosureFast radiofrequency ablation (RFA) of saphenous veins. METHOD: The medical records of patients, who had a Caprini score of ≥3, underwent RFA, received prophylactic rivaroxaban for five days, and completed follow up at one month were reviewed for efficacy (a combination of endovenous heat-induced thrombosis [EHIT] grade of 2-4, any symptomatic or asymptomatic deep vein thrombosis [DVT], and symptomatic pulmonary embolism [PE]) and safety (a combination of major and clinically relevant non-major [CRNM] bleeding) outcomes. RESULTS: The results of RFA for 248 great saphenous and 24 small saphenous veins with the concomitant miniphlebectomy (63.8%) and sclerotherapy (16.5%) were analyzed. The primary efficacy outcome occurred in 5 of 218 (2.3%; 95%CI, 1.0-5.3%) patients: three EHITs and two symptomatic DVTs. The CRNM bleeding was reported in two patients (0.9%; 95% CI, 0.2-3.3%). No difference was observed in comparison with 79 similar patients who received 40 mg of subcutaneous enoxaparin during the same time period. CONCLUSION: Once-daily 10 mg rivaroxaban is suitable for VTE prophylaxis after RFA of saphenous veins.

Prolonged prothrombin time as an early prognostic indicator of severe acute respiratory distress syndrome in patients with COVID-19 related pneumonia.

BACKGROUND: Clinical observations demonstrated that COVID-19 related pneumonia is often accompanied by hematological and coagulation abnormalities including lymphopenia, thrombocytopenia, and prolonged prothrombin time. The evaluation of laboratory findings including coagulation and inflammation parameters may represent a promising approach for early determination of COVID-19 severity. METHODS AND MATERIALS: In the present study, we aimed to identify laboratory parameters present upon admission in patients with COVID-19 related viral pneumonia and associated with an early in-hospital development of refractory respiratory failure or severe acute respiratory distress syndrome requiring treatment in an intensive care unit. We investigated differences in the C-reactive protein (CRP) and fibrinogen levels, prothrombin time (PT) and international normalized ratio (INR) between COVID-19 patients who had been transferred to an ICU within two weeks after admission (n = 82) and COVID-19 patients with stable course of the disease (n = 74). RESULTS: Multiple comparisons showed statistically significantly prolonged PT on admission in ICU-transferred COVID-19 patients (14.15 sec, median, CI 95% 13.4 ÷ 14.9) compared to the stable COVID-19 patients (13.25 sec, median, CI 95% 12.9 ÷ 13.6) (p-value = .0005). CRP levels upon admission were statistically significantly higher in ICU-transferred COVID-19 patients (132 mg/L, median, CI95% 113 ÷ 159) compared to the stable COVID-19 patients (51 mg/L, median, CI95% 33 ÷ 72) (p-value < .0001). On-admission fibrinogen and INR levels did not statistically significantly differ between ICU-transferred COVID-19 patients and stable COVID-19 patients. CONCLUSION: We suggest that CRP and PT levels present on admission in COVID-19 patients may be used as early prognostic markers of severe pneumonia requiring transfer to ICU.

Intermittent Pneumatic Compression in Addition to Standard Prophylaxis of Postoperative Venous Thromboembolism in Extremely High-risk Patients (IPC SUPER): A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of adjunctive IPC to standard prophylaxis of postoperative VTE in patients at extremely high-risk. SUMMARY OF BACKGROUND DATA: The standard prophylaxis for postoperative VTE is insufficient in extremely high-risk patients. It is unclear whether an adjunctive use of IPC would result in a lower incidence of postoperative venous thrombosis. METHODS: We randomly assigned patients who underwent major surgery and had a Caprini score of ≥11 to receive either IPC in addition to standard prophylaxis with anti-embolic stockings (pressure of 18-21 mm Hg at the ankle) and low-molecular-weight heparin (IPC group) or standard prophylaxis alone (control group). The primary outcome was an asymptomatic venous thrombosis of the lower limbs, as detected by duplex ultrasound scan performed before inclusion and every 3-5 days after surgery. RESULTS: A total of 407 patients underwent randomization, of which 204 were assigned to the IPC group and 203 to the control group. The primary outcome occurred in 1 (0.5%) patient in the IPC group and 34 (16.7%) patients in the control group [relative risk, 0.03, 95% confidential interval (CI): 0.01-0.21]. Pulmonary embolism occurred in none of the 204 patients in the IPC group and in 5 (2.5%) patients in the control group (relative risk, 0.09; 95% CI, 0.01-1.63), and postoperative death occurred in 6 (2.9%) patients in the IPC group and 10 (4.9%) in the control group (relative risk, 0.50; 95% CI, 0.50-1.60). CONCLUSIONS: Among patients with a Caprini score of ≥11 who received standard prophylaxis for VTE, adjunctive IPC resulted in a significantly lower incidence of asymptomatic venous thrombosis.

Pulmonary Artery Thrombosis: A Diagnosis That Strives for Its Independence.

According to a widespread theory, thrombotic masses are not formed in the pulmonary artery (PA) but result from migration of blood clots from the venous system. This concept has prevailed in clinical practice for more than a century. However, a new technologic era has brought forth more diagnostic possibilities, and it has been shown that thrombotic masses in the PA could, in many cases, be found without any obvious source of emboli. Chronic obstructive pulmonary disease, asthma, sickle cell anemia, emergency and elective surgery, viral pneumonia, and other conditions could be complicated by PA thrombosis development without concomitant deep vein thrombosis (DVT). Different pathologies have different causes for local PA thrombotic process. As evidenced by experimental results and clinical observations, endothelial and platelet activation are the crucial mechanisms of this process. Endothelial dysfunction can impair antithrombotic function of the arterial wall through downregulation of endothelial nitric oxide synthase (eNOS) or via stimulation of adhesion receptor expression. Hypoxia, proinflammatory cytokines, or genetic mutations may underlie the procoagulant phenotype of the PA endothelium. Both endotheliocytes and platelets could be activated by protease mediated receptor (PAR)- and receptors for advanced glycation end (RAGE)-dependent mechanisms. Hypoxia, in particular induced by high altitudes, could play a role in thrombotic complications as a trigger of platelet activity. In this review, we discuss potential mechanisms of PA thrombosis in situ.

The frequency and clinical significance of nontarget superficial and deep vein occlusion after physician compounded foam sclerotherapy of varicose tributaries.

OBJECTIVE: To evaluate the incidence and clinical relevance of silent nontarget occlusion (NTO) of superficial and deep veins occurring after ultrasound-guided foam sclerotherapy (UGFS) that can be detected by serial duplex ultrasound scan (DUS). METHODS: This retrospective analysis evaluated the medical records of patients treated with UGFS at a private clinic in Moscow, Russia from 2015 to 2017. All patients underwent serial DUS at 1 to 2 weeks and 1, 3, 6, and 12 months after UGFS. RESULTS: During the observation period, 268 patients were treated with UGFS, using physician compounded polidocanol foam 257 lower limbs of 196 patients (73%) with varicose veins who underwent DUS at 1 to 2 weeks after the last session of UGFS (inclusion time-point): 139 women and 57 men (mean age: 44.2 ± 12.2 years) with the following CEAP clinical class distribution: C2, 74.0%; C3, 20.0%; C4, 4.5%; and C5, 1.5%. NTO at the inclusion time-point occurred in 60 limbs (23.3%) of 57 patients (28.5%) and was symptomatic only in three limbs (1.2%). Most occlusions were localized in the untreated great saphenous vein trunk (n = 28) and the calf muscle veins (n = 23). Overall, 72%, 44%, 29%, and 10% of all limbs and 77%, 45%, 28%, and 12% of limbs with NTO were followed up by DUS at 1, 3, 6, and 12 months, respectively. There were no cases of thrombus progression or symptomatic venous thromboembolism (VTE). At six months, no deep vein occlusions persisted. CONCLUSIONS: The frequency of nontarget vein occlusion after UGFS revealed by serial DUS may be as high as 23.3%. These occlusions tend to resolve within six months and are not associated with symptomatic VTE.

Utilization of the Caprini score in conjunction with thrombodynamic testing reduces the number of unpredicted postoperative venous thromboembolism events in patients with colorectal cancer.

BACKGROUND: The thrombodynamic test (TD) is a novel global test of hemostasis that allows to study the spatial-temporal characteristics of a clot formation in real time under conditions close to natural ones and demonstrates high sensitivity to detect the state of hypercoagulation. The main paraments of the test are the velocity of clot growth, clot's size, and clot density. The objective of this study was to compare the classic Caprini 2005 score and its modified version in association with the results of TD. The goal is to predict postoperative venous thromboembolism (VTE) in surgical patients undergoing surgery for colorectal cancer. METHODS: This was a prospective observational clinical study involving 80 patients (33 men and 47 women; mean age, 73.9 ± 7.2 years) who underwent major (79 cases) or minor (1 case) surgery for colorectal cancer. Patients were at high risk for postoperative VTE (ie, a mean Caprini score of 9.9 ± 2.0) and received combined prophylaxis (ie, antiembolic compression stockings and enoxaparin 40 mg once daily) until discharge. Enoxaparin was administered at a fixed time of blood sampling for the TD test. Duplex ultrasound scan was performed to detect postoperative vein thrombosis before and 5 to 7 days after surgery. RESULTS: Postoperative vein thrombosis was found in 21 of 80 patients (26.3%; 95% confidence interval, 17.9%-36.8%). Regression analysis and receiver operating characteristic (ROC) curve showed that Caprini scores significantly predicted VTE (P < .0001; area under the curve [AUC] = 0.839 ± 0.045). Analysis of ROC curve coordinates showed that a cutoff point of 11 scores had a sensitivity of 76.2% and a specificity of 74.6%. The results of the TD test showed significant hypercoagulation despite enoxaparin administration in patients with VTE. Regression analysis and ROC curves demonstrated that the following TD parameters had the greatest predictability for postoperative DVT: initial velocity of clot growth (Vin) and clot size (CS) measured at 12 hours after enoxaparin administration (AUC, 0.697 ± 0.063 and AUC, 0.790 ± 0.059, respectively), as well as Vin and CS measured 24 hours after the enoxaparin injection (S = 0.847 ± 0.059 and S = 0.803 ± 0.069, respectively). The cutoff points for VTE prediction at 12 and 24 hours seemed to be a Vin of greater than 62.5 and greater than 64.5 µm/minute (normal range, 35-56 µm/minute) as well as a CS of greater than 1351.5 and greater than 1333.5 µm (normal range, 800-1200 µm), respectively. Identified thresholds for TD parameters have been integrated into Caprini scores under the item "other congenital or acquired thrombophilia." The total Caprini scores were recalculated in patients where one or all TD parameters had exceeded the cutoff followed by reanalysis of the ROC curves. The best predictability was found for Caprini scores considering the elevation of all four TD parameters (AUC, 0.924 ± 0.029) with increased cutoff to a score of 12 with a sensitivity of 85.7% and a specificity of 81.4%. The use of cutoffs for the original and modified scores could be used to calculate the number of patients that were under cutoff but developed with VTE: 10.2% and 5.9%, respectively. CONCLUSIONS: Integrating TD parameters into the Caprini score increases the ability to predict postoperative VTE.

Rivaroxaban in the treatment of upper extremity deep vein thrombosis: A single-center experience and review of the literature.

INTRODUCTION: Direct oral anticoagulants (DOACs) have become widely used to treat patients with venous thromboembolism (VTE), but evidence about their use in the treatment of upper extremity deep vein thrombosis (UEDVT) is lacking. OBJECTIVES: To assess rivaroxaban's efficacy and safety in the treatment of UEDVT. PATIENTS/METHODS: This was a single-center prospective observational study involving patients with their first UEDVT episode confirmed by duplex ultrasound scan. All patients initially received low-molecular-weight heparin for 1 to 2 days and then were switched to rivaroxaban for 3-6 months. The primary endpoint was any symptomatic episode of recurrent VTE. RESULTS: Thirty patients were included in the study, and all patients were followed for 6 months. There were no episodes of recurrent symptomatic venous thromboembolism or asymptomatic UEDVT. No episode of major bleeding was observed. Clinically relevant non-major bleeding occurred in two patients (6.7%, 95% confidence interval [CI]: 1.9-21.4%) with uterine bleeding and large skin hemorrhage. Minor bleeding was observed in two patients (6.7%, 95% CI: 1.9-21.4%) presenting with nasal and gingival bleeding. Recanalization of the upper extremity deep veins was observed in all affected limbs at three months, and it persisted up to 6 months. The signs of upper limb post-thrombotic syndrome (PTS) were found in four patients (13.4%; 95% CI: 5.4-29.8%), and the mean modified Villalta score was 2.1 ±â€¯1.9. CONCLUSION: Treatment of UEDVT with rivaroxaban, preceded by one to two days of LMWH, seems to be safe and effective.

Electrical calf muscle stimulation in patients with post-thrombotic syndrome and residual venous obstruction after anticoagulation therapy.

BACKGROUND: The aim of this study was to assess the impact of electrical calf muscle stimulation (EMS) on clinical and ultrasound outcomes in patients with post-thrombotic syndrome (PTS) and residual venous obstruction (RVO). METHODS: This was a prospective, comparative, non-randomized clinical trial involving patients who had completed a standard 6-month course of anticoagulation therapy for a first episode of unprovoked femoro-popliteal DVT and had signs of RVO in the affected veins and PTS as shown by a Villalta Score of >5. A blinded outcome assessor performed the ultrasound evaluations. A total of 60 patients in the age range from 40 to 86 years (mean 58.5±11.4) consisting of 38 men and 22 women were enrolled. They were divided into two groups of 30 participants each. Both groups (experimental and control) were treated by active walking, below-knee graduated compression stockings, and micronized purified flavonoid fraction. In the experimental group, EMS with «Veinoplus VI¼ device (three applications for 30 min every day) was also used. The patients were followed for 12 months with monthly DUS to reveal recurrent DVT and changes in RVO. The clinical criteria for treatment efficacy included changes in Villalta, VCSS and CIVIQ-20 scores. RESULTS: Recurrent DVT was found in seven of 30 patients in the control group and in zero of 30 patients in the experimental group (23.3% versus 0%, P=0.01). Through the follow-up period the degree of RVO decreased in all affected veins in both groups (P<0.01). The most significant changes were found in the popliteal vein; 60.8% decreased to 28.8% in the experimental group and 50.9% to 27.3% in the control group (P<0.01) with significant differences between the groups (P<0.01). VCSS, Villalta and CIVIQ-20 scores also significantly decreased in both groups (P<0.01). In the group with EMS, changes in the current parameters were more intensive (P<0.01). CONCLUSIONS: There is an ongoing process of deep vein recanalization during the 12 months after anticoagulant therapy cessation. Use of EMS in PTS treatment allows for reduction of recurrent DVT rates, increase the speed of deep vein recanalization and leads to additional improvement in the clinical PTS outcomes.

Validation of the Caprini risk assessment model for venous thromboembolism in high-risk surgical patients in the background of standard prophylaxis.

OBJECTIVE: We used the Caprini venous thromboembolism risk assessment score to prospectively evaluate if there was a correlation between the Caprini scores and the incidence of postoperative deep vein thrombosis (DVT) in high-risk surgical patients. A second objective was to determine whether patients at extremely high risk need a more effective prophylactic regimen. METHODS: This prospective multicenter observational study involved 140 high-risk patients who underwent abdominal (48%) or cranial and/or spinal (52%) surgery. All patients were assessed using the Caprini model and had a mean score of 9.5 ± 2.7 (range, 5-15). Our standard prophylaxis for venous thromboembolism consisted of above-knee graduated compression stockings with 18 to 21 mm Hg pressure and subcutaneous low-dose unfractionated heparin three times per day, starting on the first or second through the fifth postoperative day depending on the risk of bleeding. We performed a duplex ultrasound examination at baseline during the first 12 to 24 hours after surgery and then every 3 to 5 days until discharge to assess the lower limb venous system up to the inferior vena cava. The end point of the study was ultrasound verification of fresh DVT or pulmonary embolism (PE). Verification of PE was made in all cases of DVT using echocardiography, lung scintigraphy, combined single-photon emission computed tomography and X-ray computed tomography, or autopsy. RESULTS: Fresh postoperative DVT was found in 39 patients (28%). The incidence of DVT was 2% in patients with a Caprini score of 5 to 8, 26% in patients with scores of 9 to 11, and 65% in patients with scores of 12 to 15 (P for trend < .01). The risk for DVT was increased 18.7-fold for patients with scores of 9 to 11 and 98.4-fold for scores of 12 to 15 compared with patients with scores of 5 to 8. The area under the receiver operating characteristic curve was 0.87 (95% confidence interval, 0.81-0.94) and a Caprini score of 11 was the cutoff point that provided the highest sensitivity combined with highest specificity. In the 77 patients with a score of <11, DVT occurred in 2 patients (3%). In contrast, in the 63 patients with a score of ≥ 11, DVT occurred in 37 patients (59%; P < .01). PE was found in 13 patients (9%) and confirmed with autopsy. In all cases, verified fresh DVT was the source of embolism. CONCLUSIONS: There was a significant correlation between Caprini scores and the incidence of postoperative DVT in high-risk surgical patients. A Caprini score of ≥ 11 can identify a subgroup of patients at extremely high risk. These patients need a more effective prophylactic regimen.