Treatment of deep vein thrombosis with rivaroxaban and its potential to prevent the post-thrombotic syndrome.

BACKGROUND: The study was initiated following the observation of complete recanalization of thrombus in subjects with DVT treated with rivaroxaban after 1-2 weeks. The aim of this observational retrospective study was to evaluate clinically and by means of echo color Duplex, the fibrinolytic effect of rivaroxaban in patients with recent and previous DVT. To accomplish this two populations of patients were evaluated. METHODS: Group 1 was comprised of 31 patients (ranging in age 52-73 years) with popliteal-femoral DVT (12 months ago) treated with standard anticoagulant therapy. In these patients, we found a complete superficial femoral recanalization and partial recanalization of the popliteal vein (30% of residual thrombus). The patients had normal creatinine clearance and liver function. The patients were switched from warfarin to rivaroxaban due to a lack of compliance with warfarin therapy. Group 2 was comprised of 22 patients (ranging in age 65-82 years) with previous popliteal-femoral DVT and documented complete common femoral veins recanalization who presented with a recent superficial femoral vein re-thrombosis (1 week before). The patients had normal creatinine clearance and liver function. The patients switched from warfarin to rivaroxaban due to a lack of compliance with warfarin therapy. RESULTS: In group 1, all patients exhibited the complete recanalization of the popliteal veins after 4 weeks of rivaroxaban therapy. In group 2, all patients exhibited the complete recanalization of the popliteal veins after 4 weeks, and the complete recanalization of the acute re-thrombosis of the superficial femoral veins after 2 weeks of rivaroxaban therapy. No adverse events for both groups were observed. CONCLUSIONS: Our results suggest that rivaroxaban could have a pro-fibrinolytic effect not only on recent thrombus but also on organized thrombus that results in a complete recanalization of affected veins. It is proposed that this lytic effect will preserve venous valve structure and lead to a reduction of incidence of post-thrombotic syndrome in rivaroxaban treated patients.

Neuromuscular electrical stimulation reduces sludge in the popliteal vein.

BACKGROUND: The common peroneal nerve stimulator (CPNS) is a UK-approved device for reducing venous thromboembolism (VTE) risk. It resembles a wrist watch and is placed over the common peroneal nerve, discharging electricity at a rate of 1 impulse/s. It has been presumed that as blood flow slows, erythrocytes aggregate into ultrasound-detectable echogenic particles, described as venous sludge. The aim of the study was to determine whether the CPNS reduces venous sludge by using an ultrasound-derived gray-scale (0-255) venous sludge index (VSI). METHODS: Twenty-five healthy volunteers had their right popliteal vein video recorded using B-mode ultrasound at 22 frames/s in longitudinal and transverse views, standing and lying. This was performed first with the CPNS off and then with the CPNS on. The CPNS impulse intensity used was set from 1 to 7 for each individual, and the level was sufficient to cause an outward jerking movement of the foot. A single frame of the possible 154 frames, lasting 7 seconds, was selected using a random number generator for the image analysis. The "brightness" of the erythrocyte aggregates (pixels) within a circular sampling area was quantified using the VSI. The brighter the sample, the greater the sludge. RESULTS: Values are expressed as median (interquartile range). On standing with the device off, there was a significantly higher VSI (P < .0005) compared with lying (longitudinal view, 27.7 [18.8-41.4] vs 11.7 [5.5-17.5]; transverse view, 20.7 [13.6-32.2] vs 11.4 [6.3-15.9]). Activation of the CPNS significantly reduced all the VSI values (P < .0005) shown (longitudinal view, 2 [1.1-3.2] and 1.5 [0.5-3.1]; transverse view, 1.1 [0.6-2.7] and 0.8 [0.5-2.1]). CONCLUSIONS: The CPNS device significantly reduces venous sludge within the popliteal vein irrespective of whether the subject is standing or lying down or of the longitudinal or transverse position of the ultrasound transducer. The principal mode of action of the device in the claim that it may reduce venous thromboembolism risk may be through a reduction of venous sludge. However, the relationship between erythrocyte aggregation, venous stasis, and venous thromboembolism risk requires more investigation.

Comparative lower limb hemodynamics using neuromuscular electrical stimulation (NMES) versus intermittent pneumatic compression (IPC).

Deep Vein Thrombosis (DVT) is a life threatening condition and a serious concern among hospitalised patients, with death occurring in approximately 6% of cases. Intermittent pneumatic compression (IPC) is commonly used for DVT prevention, however suffers from low compliance and issues of usability and portability. Neuromuscular electrical stimulation (NMES) has been shown to improve lower limb hemodynamics but direct comparison with IPC in terms of hemodynamics is rare but very important to determine the potential effectiveness of NMES in DVT prevention.Lower limb IPC was compared to calf NMES, in 30 healthy volunteers (18-23 years). Each intervention was carried out on each leg, on the popliteal vein measured using Doppler ultrasound. All interventions produced significantly greater haemodynamic responses compared to baseline. Calf-IPC and NMES produced significant increases in venous blood velocity (cm/s) and volume of blood ejected per cycle (1 cycle of NMES expels 23.22 ml compared to the baseline ejected volume of 2.52 ml, measured over 1 s (p < 0.001 versues baseline).Improving lower limb hemodynamics is vital in preventing DVT. NMES resulted in larger ejected volumes compared to IPC (x3 greater than foot-IPC and x1.7 greater than calf-IPC) more effectively emptying the veins and soleal sinuses. This is an important finding as DVT occurs predominantly in the soleal sinuses. NMES is silent and portable and thus does not suffer many of the issues associated with IPC. This work supports the potential widespread application of NMES in hospital and home settings where the risk of DVT formation is high.

Novel treatment techniques for recanalization of femoral-popliteal deep venous occlusion from chronic thrombosis.

Patients with postthrombotic syndrome due to previous femoral-popliteal deep venous thrombosis often experience lifestyle-limiting lower-extremity pain and swelling. Conservative treatment options include compression stockings and lymphedema massage, but in many cases these treatments only temporarily and partially improve symptoms. Ultrasound and venography in patients with postthrombotic syndrome often show only partial recanalization of the femoral vein with significant collateral vein formation. These abnormal veins are insufficient for adequate venous drainage from the lower extremity as evidenced by the patient's continued symptoms. Recanalization of the occluded or partially occluded femoral vein using prolonged venoplasty, with or without chemical thrombolysis, combined with optimizing anticoagulation and conservative treatment measures, results in lasting improvement in symptoms for a high percentage of patients.

Haemodynamic performance of neuromuscular electrical stimulation (NMES) during recovery from total hip arthroplasty.

BACKGROUND: Patients post total hip arthroplasty (THA) remain at high risk of developing Deep Vein Thrombosis (DVT) during the recovery period following surgery despite the availability of effective pharmacological and mechanical prophylactic methods. The use of calf muscle neuromuscular electrical stimulation (NMES) during the hospitalised recovery period on this patient group may be effective at preventing DVT. However, the haemodynamic effectiveness and comfort characteristics of NMES in post-THA patients immediately following surgery have yet to be established. METHODS: The popliteal veins of 11 patients, who had undergone unilateral total hip replacement surgery on the day previous to the study, were measured using Doppler ultrasound during a 4 hour neuromuscular electrical stimulation (NMES) session of the calf muscles. The effect of calf muscle NMES on peak venous velocity, mean venous velocity and volume flow were compared to resting values. Comfort was assessed using a 100mm non-hatched visual analogue scale taken before application of NMES, once NMES was initiated and before NMES was withdrawn. RESULTS: In the operated limb NMES produced increases in peak venous velocity of 99% compared to resting. Mean velocity increased by 178% compared to resting and volume flow increased by 159% compared to resting. In the un-operated limb, peak venous velocity increased by 288%, mean velocity increased by 354% and volume flow increased by 614% compared to basal flow (p<0.05 in all cases). There were no significant differences observed between the VAS scores taken before the application of NMES, once NMES was initiated and before NMES was withdrawn (p=.211). CONCLUSIONS: NMES produces a beneficial hemodynamic response in patients in the early post-operative period following orthopaedic surgery. This patient group found extended periods of calf-muscle NMES tolerable. TRIAL REGISTRATION: ClinicalTrials.gov NCT01785251.

Venous flow dynamics during spinal block in normotensive and hypertensive elderly patients: a duplex ultrasonographic study.

BACKGROUND: Spinal block induces hyperkinetic change in lower extremity blood flow. We compared the venous flow dynamic responses to spinal block in normotensive and hypertensive elderly patients. METHODS: Following spinal block using 10 mg 0.5% (w/v) bupivacaine, we measured changes in blood pressure, heart rate, and venous flow dynamics of the popliteal vein by duplex ultrasonography in 20 normotensive (NBP group) and 18 hypertensive (HIBP group) patients. RESULTS: Spinal block caused significant decreases in blood pressure in both groups; similar rates of hypotension were observed. At baseline, peak velocity, time-averaged maximum velocity, and time-averaged mean velocity were higher in the HIBP than in the NBP group. During spinal block, peak velocity increased in both groups, and the between-group differences were no longer significant. At baseline, volume flow in the two groups was similar and increased by 141.5% in the NBP and 131.7% in the HIBP group during spinal block. CONCLUSIONS: Blood pressure and flow dynamics in the popliteal vein showed similar changes during spinal anaesthesia in elderly patients taking antihypertensive medication and normotensive patients, despite differences in baseline values.

The efficacy of a new stimulation technology to increase venous flow and prevent venous stasis.

OBJECTIVES: Electrical stimulation of calf muscles has been shown to be effective in prevention of DVT. The aim was to determine: (a) dependence of venous blood velocity and ejected volume on the rates of stimulated calf contractions: (b) clinical factors affecting efficacy in healthy individuals. METHODS: The maximum intensity stimulus tolerated was applied to calves of 24 volunteers. In popliteal veins, peak systolic velocities (PSV), ejected volume per individual stimulus (stroke volume SV) and ejected total volume flow per minute (TVF) of expelled blood were determined using ultrasound. Stimulation rates from 2 to 120 beats per minute (bpm) were applied. RESULTS: Mean baseline popliteal PSV was 10 cm/s. For stimulation rates between 2 and 8 bpm, the PSV was 10 times higher and reached 96-105 cm/s. Stroke volume (SV) per individual stimulus decreased in a similar fashion. With increasing rates of stimulation the TVF increased by a factor of 12 times (from 20 ml/min to 240 ml/min). CONCLUSION: Electrical stimulation is an effective method of activating the calf muscle pump. Enhancements of popliteal blood velocity and volume flow are key factors in the prevention of venous stasis and DVT. Further studies are justified to determine the stimulation rates in those with a compromised venous system.

Electrical foot stimulation: a potential new method of deep venous thrombosis prophylaxis.

The purpose of this study was to compare venous blood flow velocity of intermittent pneumatic compression to electrical stimulation of the foot. A prospective randomized controlled study of 40 healthy volunteers was conducted. Subjects were seated for 4 hours during which they received electrical stimulation of the sole of the foot or intermittent pneumatic compression of the foot... Short-term electrical foot stimulation is at least as effective as foot intermittent pneumatic compression in increasing popliteal and femoral blood flow velocity. [corrected] Popliteal and femoral venous blood flow velocities were measured via Doppler ultrasonography. Blood flow velocity in the nonstimulated or noncompressed lower extremity served as a simultaneous control. For both the femoral and popliteal veins, the electrical foot stimulation group exhibited a greater increase in blood flow velocity than the intermittent pneumatic compression group. Electrical foot stimulation was noninferior relative to standard intermittent pneumatic compression. Specifically, this result of a greater increase in blood flow velocity is achieved at time = 120 minutes for the femoral vein (t = 2.70; p = .005) and time = 120 (t = 2.75; p = .004) and 240 (t = 2.27; p = .014) minutes for the popliteal vein. Short-term electrical foot stimulation is at least as effective as knee-high intermittent pneumatic compression in increasing popliteal and femoral blood flow velocity. Electrical foot stimulation has the potential to be an effective method of deep venous thrombosis prophylaxis.

Prevention of venous stasis in the lower limb by transcutaneous electrical nerve stimulation.

OBJECTIVES: This study aims to investigate the effects of thromboprophylactic transcutaneous electrical nerve stimulation (TpTENS) of the peroneal nerve on venous blood flow in the limbs of volunteers. TpTENS might be considered for use in preventing venous stasis during surgical treatment. METHODS: In 10 volunteers, peak venous velocity (PV) and flow volume (FV) in the popliteal vein were measured using duplex ultrasonography during calf-muscle stimulation. The effects of TpTENS of the peroneal nerve were compared with those of other mechanical methods, including electrical muscle stimulation, intermittent pneumatic compression, active ankle motion and calf squeeze, used to prevent venous stasis and achieve thromboprophylaxis. RESULTS: TpTENS had similar effects on popliteal vein blood flow in comparison with other established methods of thromboprophylaxis. The PV increased its basal flow by 3.9 times (p < 0.01) and FV by 2.7 times (p < 0.01), respectively, compared with baseline values. CONCLUSIONS: TpTENS is as effective as other electrical and mechanical methods of calf-muscle pump activation in achieving acceleration of venous flow in the lower limb.

Different outcome of six homozygotes for prothrombin A20210A gene variant.

Prothrombin G20210A gene variant (FII G20210A) is a risk factor for venous thrombotic disease while conflicting results have been reported for the risk of arterial thrombotic events. However, vascular episodes were absent in up to 40% of the 67 homozygotes for the G20210A described so far, which indicates that the clinical expression depends on additional risk/trigger factors. We describe six homozygotes for the G20210A variant, among which the first pair of siblings (cases n. 3 and 4) reported so far that displayed a strongly heterogeneous clinical outcome. Case 1, a female of 27 years, developed a full thrombosis of common femoral, superficial and popliteal veins. She assumed oral contraceptives in the last two years. Case n. 2, 34 years old, suffered of recurrent pregnancy loss in absence of any causative alteration. Cases n. 3 and n. 5 experienced arterial thrombotic disease, i.e., juvenile myocardial infarction (40 years old) and stroke (48 years old), respectively, in absence of other risk factors. Finally, cases n. 4 and 6 identified as homozygotes for the FII G20210A variant being consanguineous of symptomatic subjects bearing the variant, did not experience any episode of venous nor arterial disease. Both of them have chronic liver disease with an impairement of the prothrombin time INR. Thus, homozygotes for the G20210A are at risk for arterial (in addition to venous) thromobotic events; chronic liver disease might modulate this risk.

Prevention of venous thrombosis and thrombophlebitis in long-haul flights with pycnogenol.

The aim of this study was to evaluate the occurrence of deep venous thrombosis (DVT) and superficial vein thrombosis (SVT) and its prophylaxis with an oral anti-edema and antithrombotic agent (Pycnogenol, Horphag, Research Management SA, Geneva, Switzerland) in long-haul flights, in subjects at moderate to high-risk of DVT and SVT. The study pre-included 244 pre-selected subjects; 211 were included (33 were excluded for several reasons due to logistic problems) and 198 completed the study; 13 subjects were lost for follow-up at the end of the flight, all for non-medical problems (i.e., for difficult connections). All subjects were scanned within 90 minutes before the flight and within 2 hours after disembarking. Subjects were supplemented with 100 mg Pycnogenol per capsule. Treatment subjects received two capsules between 2 and 3 hours before flights with 250 mL of water; two capsules were taken 6 hours later with 250 mL of water and one capsule the next day. The control group received comparable placebo at the same intervals. The flight duration was on average 8 hours and 15 minutes (SD 55 min) (range, 7.45-12.33). In the control group there were five thrombotic events (one DVT and four superficial thromboses) while only nonthrombotic, localized phlebitis was observed in the Pycnogenol group (5.15% vs. no events; p<0.025). The ITT (intention to treat) analysis detects 13 failures in the control group (eight lost to follow up + five thrombotic events) of 105 subjects (12.4%) vs. five failures (4.7%; all lost, no thrombotic events) in the treatment group (p<0.025). No unwanted effects were observed. In conclusion, this study indicates that Pycnogenol treatment was effective in decreasing the number of thrombotic events (DVT and SVT) in moderate-to-high risk subjects, during long-haul flights.

Subcutaneous radionuclide venography. An effective method for diagnosis of deep venous thrombosis.

Traditional acupuncture points K-3 are physiologically tender points located halfway between the Achilles tendon and the medial malleolus. Recently, the authors developed a new method of radionuclide venography of the lower limbs, namely subcutaneous radionuclide venography (SC-RNV), by subcutaneous injection of Tc-99m pertechnetate at these points. The authors applied this method in a patient with suspected deep vein thrombosis of both lower limbs. For comparison, ascending radionuclide venography by intravenous injection (IV-RNV) of Tc-99m MAA and color Doppler ultrasound were also done. The SC-RNV showed partial obstruction of right popliteal vein and complete obstruction of the left popliteal vein with prominent collateral flows. These results were compatible with the findings of color Doppler ultrasound. However, the IV-RNV showed small narrowing with patency of the left popliteal vein, and normal flow on the right. This suggests that the results of SC-RNV may be different from that of IV-RNV. The benefits of SC-RNV in the detection of deep vein thrombosis are described.