Home therapy for Acute DVT in the leg! Is it safe in all countries?

Home therapy for DVT is convenient and it gives freedom with safety to treat the patients coming in the out patient clinic without admission in to the hospitals and additional burden hospital beds and expenditure to the family.

In patients with DVT, home treatment was associated with a better outcome than treatment in the hospital. Current guidelines of antithrombotic therapy recommend initial treatment of patients with acute deep venous thrombosis (DVT) with low-molecular-weight heparin (LMWH), fondaparinux, or unfractionated heparin (UFH) over no such initial therapy.¹ A number of studies comparing LMWH administered at home (without hospital admission or after early discharge) with UFH in the hospital suggested that home therapy may be associated with improved outcome and better quality of life.^{2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12} Hence, in DVT patients with adequate home circumstances, current guidelines recommend that most patients with DVT be initially treated at home rather than in the hospital.¹ However, many physicians are still concerned about the safety of home therapy because even with adequate anticoagulation, some patients may present with symptomatic pulmonary embolism (PE), recurrent DVT, major bleeding complications, or even death.

The RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry is an ongoing, international (Spain, France, Italy, Israel, Germany, Switzerland, Republic of Macedonia, and Brazil), multicenter, prospective registry of consecutive patients presenting with symptomatic acute venous thromboembolism (VTE). It started in Spain in 2001, and some years later, the database was translated into English to expand the Registry to other countries, with the aim to help physicians worldwide select the most appropriate therapy for their patients. Data from this registry have been used to evaluate outcomes after acute VTE, such as the frequency of recurrent VTE, major bleeding, and mortality, and risk factors for these outcomes.^{13, 14,15 and 16} The current analysis compared the outcome of outpatients with acute DVT of the lower limbs within the first week of anticoagulation according to initial therapy at home or in the hospital.

References

1. C. Kearon, E.A. Akl, A.J. Comerota, P. Prandoni, H. Bounameaux, S.Z. Goldhaber et al. American College of Chest Physicians. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest, 141 (Suppl) (2012), pp. e419S–e494S

2. M. Bakker, P.J. Dekker, E.A. Knot, P.F. van Bergen, J.J. Jonker Home treatment for deep venous thrombosis with low-molecular-weight heparinLancet, 2 (1988), p. 1142

3. M. Levine, M. Gent, J. Hirsh, J. Leclerc, D. Anderson, J. Weitz et al.A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med, 334 (1996), pp. 677–681

4.M.M. Koopman, P. Prandoni, F. Piovella, P.A. Ockelford, D.P. Brandjes, J. van der Meer et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The TASMAN Study Group N Engl J Med, 334 (1996), pp. 682–687

5. I.G. Schraibman, A.A. Milne, E.M. Royle Home versus in-patient treatment for deep vein thrombosisCochrane Database Syst Rev, 2 (2001), p. CD003076

6. R. Othieno, M. Abu Affan, E. Okpo Home versus in-patient treatment for deep vein thrombosisCochrane Database Syst Rev, 3 (2007), p. CD003076

7. W. Ageno, R. Grimwood, S. Limbiati, F. Dentali, L. Steidl, P.S. Wells Home-treatment of deep vein thrombosis in patients with cancer Haematologica, 90 (2005), pp. 220–224

8. S. Siragusa, C. Arcara, A. Malato, R. Anastasio, M.R. Valerio, F. Fulfaro et al. Home therapy for deep vein thrombosis and pulmonary embolism in cancer patients Ann Oncol, 16 (Suppl 4) (2005), pp. 136–139

9. S.R. Kahn, V. Springmann, S. Schulman, J. Martineau, J.A. Stewart, N. Komari et al. Management and adherence to VTE treatment guidelines in a national prospective cohort study in the Canadian outpatient setting. The Recovery Study. Thromb Haemost, 108 (2012), pp. 493–498

10. M. Winter, D. Keeling, F. Sharpen, H. Cohen, P. Vallance, Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology Procedures for the outpatient management of patients with deep venous thrombosis. Clin Lab Haematol, 27 (2005), pp. 61–66

11. V. Snow, A. Qaseem, P. Barry, E.R. Hornbake, J.E. Rodnick, T. Tobolic, American College of Physicians; American Academy of Family Physicians Panel on Deep Venous Thrombosis/Pulmonary Embolism et al. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians Ann Intern Med, 146 (2007), pp. 204–210

12. J.D. Douketis. Treatment of deep vein thrombosis. What factors determine appropriate treatment?Can Fam Physician, 51 (2005), pp. 217–223

Oncolytic viruses

Oncolytic viruses are providing an interesting approach to treat cancers:

Some time back in the past, we postulated that the virus may cause the some types of cancers. But today we are postulating that viruses can be used to cure the cancers. Cancers tend to grow at the expense of the normal tissues and so are the viruses when they invade the body. Now, there are attempts to engineer the viruses to do the jobs favorable for the humans beings and that seems to be good. Some have engineered viruses to cure multiple myeloma and others are using the virus loaded stem cells to treat tumors. Recently herpes virus loaded stem cells are used to treat brain tumor (in mice) such as glioblastoma multiforme which is a difficult tumor to treat.  It said that “Further preclinical work will be needed to use the herpes-loaded stem cells for breast, lung and skin cancer tumours that metastasize to the brain. Shah predicts the approach will enter clinical trials within the next two to three years”.

What is CaVenT study?

Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial.

209 patients were randomly assigned to treatment groups (108 control, 101 CDT). At completion of 24 months' follow-up, data for clinical status were available for 189 patients (90%; 99 control, 90 CDT). At 24 months, 37 (41·1%, 95% CI 31·5—51·4) patients allocated additional CDT presented with PTS compared with 55 (55·6%, 95% CI 45·7—65·0) in the control group (p=0·047). The difference in PTS corresponds to an absolute risk reduction of 14·4% (95% CI 0·2—27·9), and the number needed to treat was 7 (95% CI 4—502). Iliofemoral patency after 6 months was reported in 58 patients (65·9%, 95% CI 55·5—75·0) on CDT versus 45 (47·4%, 37·6—57·3) on control (p=0·012). 20 bleeding complications related to CDT included three major and five clinically relevant bleeds.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61753-4/abstract

from University of Oslo.

Longterm outcomes after catheter directed thrombolysis in DVT

What is CaVenT study?

Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. 209 patients were randomly assigned to treatment groups (108 control, 101 CDT). At completion of 24 months' follow-up, data for clinical status were available for 189 patients (90%; 99 control, 90 CDT). At 24 months, 37 (41·1%, 95% CI 31·5—51·4) patients allocated additional CDT presented with PTS compared with 55 (55·6%, 95% CI 45·7—65·0) in the control group (p=0·047). The difference in PTS corresponds to an absolute risk reduction of 14·4% (95% CI 0·2—27·9), and the number needed to treat was 7 (95% CI 4—502). Iliofemoral patency after 6 months was reported in 58 patients (65·9%, 95% CI 55·5—75·0) on CDT versus 45 (47·4%, 37·6—57·3) on control (p=0·012). 20 bleeding complications related to CDT included three major and five clinically relevant bleeds.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61753-4/abstract

from University of Oslo.

Transplantation of an allogeneic vein bioengineered with autologous stem cells

Vein segments are harvested and used for bypassing the arterial occlusions and these vein grafts have good long term patency. But when a vein has to be bypassed then we do not have an ideal graft available to us. In the recent past a 9 cm segment of allogeneic donor iliac vein was decellularised and subsequently recellularised with endothelial and smooth muscle cells differentiated from stem cells obtained from the bone marrow of the recipient. Such a graft may not require suppression for life time by sweedish team of doctors.

After one year a second stem-cell populated vein graft was used for relieving the compression of first graft graft and  to lengthen the previous graft which was used for replacing the portal vein in a patient with extra hepatic portal vein obstruction. With restored portal circulation the patient has substantially improved physical and mental function and growth. The patient has no anti-endothelial cell antibodies and is receiving no immunosuppressive drugs. An acellularised deceased donor vein graft recellularised with autologous stem cells can be considered for patients in need of vascular vein shunts without the need for immunosuppression.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60633-3/fulltext#article_upsell

Robert B. Rutherford 29 July 1931–22 November 2013

Bob Rutherford, for more than three decades, was arguably the best known and most respected vascular surgeon in the world. His textbook, VASCULAR SURGERY, has been “the textbook” and remains the premier source of information in the field since it first appeared in 1976. Since then, Rutherford's text gained in authority and respect as it went through its subsequent eight editions, just as vascular surgery grew and morphed into the defined specialty it is today. In 1996, Bob received an Honorary Fellowship from the Royal College of Surgeons and he delivered the prestigious Lister Lecture in Glasgow, Scotland. In 2005, Bob received the singular honor of the SVS Lifetime Achievement Award and, in 2006, he received the Julius H. Jacobson II Physician Excellence Award from the Vascular Disease Foundation for his exceptional leadership and contributions to vascular disease education and management.

Buerger's Disease - is still unresolved in Asian countries?

More than 100 years back the first paper on Buerger's disease was published. In many countries the disease prevalence is significantly reduced. But in the developing and poor countries where childhood smoking is uncontrolled this disease seems to be persistent. The disease is surprisingly less common in urban population and in those who have gone to proper schooling! probably this means these children are protected from the risk of childhood smoking. There are reports mentioning that autoimmunity plays an important role. The initial enthusiasm to do surgeries faded away slowly as the results are universally not satisfactory. Now, a new concept directed towards cell therapies (stem cells) renewed the interest in detecting the patients who can be benefited by them. Here is a report on endothelial progenitor cells and TAO.

Reduced circulating endothelial progenitor cells in thromboangiitis obliterans (Buerger’s disease)

Hyung Sub Park1 Kyung Hee Cho1 Koung Li Kim2 Duk-Kyung Kim2Taeseung Lee1
Taeseung Lee Department of Surgery Seoul National University Bundang Hospital Seoul National University College of Medicine 173-82 Gumi-ro, Bundang-gu, Seongnam-si Gyeonggi-do 463-707 Korea Email: tslee@snubh.org

Abstract

To determine the role of endothelial progenitor cells (EPCs) in the pathogenesis of thromboangiitis obliterans (TAO), EPC numbers and colony-forming units, migratory function and tubular structure formation in vitro were compared between 13 young male TAO patients and two age-matched healthy control groups: 11 smokers and 12 non-smokers. TAO patients had significantly lower numbers of EPCs and EPC colonies compared to both non-smokers [190 (97.0–229) vs 528 (380–556), p < 0.001 for EPCs and 0.80 (0.53–1.00) vs 2.80 (2.08–4.00) per mm2, p = 0.001 for EPC colonies] and smokers [190 (97.0–229) vs 272 (229–326), p = 0.012 for EPCs and 0.80 (0.53–1.00) vs 2.80 (1.80–3.93) per mm2, p = 0.001 for EPC colonies]. However, there were no significant differences in migratory function or tube formation between the three groups. These results suggest that TAO patients have an intrinsic decrease in EPCs not entirely associated with smoking, which may be the cause of endothelial dysfunction seen in TAO patients leading to the development of this disease at early ages.

How specific are venous symptoms for diagnosis of chronic venous disease?

I feel this is very important to know this fact, before we confirm and treat CVI patients based on only few symptoms. The recently introduced Endovenous ablative therapies are offered to lot of patients due to the safety and ease with which these procedures are performed. It would be useful to base our interventions with adequate supportive clinical features after exclude the other possible conditions. If we take these precautions there will be more satisfaction and improvement therapeutic effectiveness.

Pinjala R K
13th Jan 2014

Fruit juice - may be better to avoid concentrated juices!

Some of us like Fruit juices and believe they are safe. But are they safe?

Dear NIMS Doctor,

Fruits and fruit juices are considered to be safe and good for the health by many of us. Some of us take whole fruit while some prefer to take the readymade fruit juices. Now there are alerts to avoid the fruit juices and recommendations are in favour of whole fruit intake. If one would still like to take juices it is better to dilute them adequately.

Fruit juice should be removed from the recommended list of five-a-day portions of fruit or vegetables in the U.K. as it contained as much sugar as many soft drinks, an adviser to the government on obesity has said. Susan Jebb, head of diet and obesity research at the Medical Research Council’s Human Nutrition Research unit in Cambridge, said she did not see juice as a healthy option.

“I would support taking it out of the five-a-day guidance,” she said. “Fruit juice isn’t the same as intact fruit and it has got as much sugar as many classical sugar drinks. It is also absorbed very fast so by the time it gets to your stomach your body doesn’t know whether it’s Coca-Cola or orange juice, frankly,” she told Sunday Times.

“I have to say it is a relatively easy thing to give up. Swap it and have a piece of real fruit. If you are going to drink it, you should dilute it,” she said.

Ms. Jebb said she had herself stopped drinking orange juice and advised others to do so, or at least drink it diluted.

The paper quoted her as saying she would support a wider tax on sugar-heavy drinks.

Ms. Jebb works closely with the U.K. government on diet and obesity issues, and leads the government’s so-called health responsibility deal, which oversees voluntary pledges by the food and drink industry to improve public health. Her comments follow a similar warning in September by two U.S. scientists, Barry Popkin and George Bray, who exposed the health risks of fructose corn syrup in soft drinks in 2004.

Popkin, a professor of nutrition at the University of North Carolina, told the Guardian that fruit juices and fruit smoothies were “the new danger”.

“Think of eating one orange or two and getting filled. Now think of drinking a smoothie with six oranges and two hours later it does not affect how much you eat. The entire literature shows that we feel full from drinking beverages like smoothies but it does not affect our overall food intake, whereas eating an orange does,” he said. “So pulped-up smoothies do nothing good for us but do give us the same amount of sugar as four to six oranges or a large coke. It is deceiving,” Mr. Popkin said.

Smoking prevalence among Indian men decreased from 33.8 percent to 23 percent (1980-2012) !

A new research from the Institute for Health Metrics and Evaluation (IHME) at the University of Washington has revealed that India has made progress in reducing the prevalence of daily smoking among men.Smoking is the third top risk for health loss in India, leading to nearly one million deaths each year in the country. Between 1980 and 2012, smoking prevalence among Indian men decreased from 33.8 percent to 23 percent.

According to the research India has more female smokers  over 12.1 million  than any country except the United States. In 2012, female smoking prevalence was 3.2 percent, which is virtually unchanged since 1980. "Smoking rates remain dangerously high for men and there is more work to be done to drive these rates lower," Dr. Srinath Reddy, President of the Public Health Foundation of India, said in response to the findings. "The high number of female smokers in India is also troubling," he said.These developments in India have taken place against an increasingly complex global backdrop.Trends in age standardized tobacco use vary greatly by country and gender, with places such as Mexico and Canada seeing rapid declines while others, such as Russia and China, seeing increases since 2006.Male smokers continue to outnumber female smokers and, since 1980, the global rate of decline in female smoking prevalence was consistently faster than in men.The study is published in the Journal of the American Medical Association.

Can we manage TIA patients safely in outpatient clinics?

Can lower risk patients presenting with transient ischemic attack be safely managed as outpatients? This is a question we need to answer during these days, where one would like to avoid hospitalization expenditure

A paper published by an Australian author said in conclusion, medical assessment, expedited investigation with immediate commencement of secondary prevention and outpatient neurology review may be a reasonable alternative to admission for low risk patients presenting to the Emergency Department with TIA.

Stroke is second only to ischemic heart disease as a leading cause of disease burden in Australia. Stroke places considerable strain on the public health system in Australia (length of stay averages 8 days and outcomes range from returning home to nursing home placement to death). There is a paucity of data regarding the best approach to care provision following a transient ischemic attack (TIA) in the Australian setting. The risk of stroke following a TIA is as high as 5–10% in the first 7 days depending on the population and clinical setting examined, with the lowest risks observed in the context of emergent management. Higher rates have been reported among high risk populations in the absence of protocol driven initiation of secondary prevention.

TIA represent a window of opportunity for effective secondary stroke prevention.7 Review in a daily (as opposed to weekly) TIA  clinic with no appointment necessary and immediate commencement of therapy has demonstrated an 80% reduction in risk of recurrent cerebrovascular accident within 90 days (10.3% versus 2.1%) in the EXPRESS study with demonstrated cost-savings in terms of bed days, acute costs, and 6 month disability.8 Risk reduction with early intervention is also supported by results of the SOSTIA study and other approaches, all of which involve immediate commencement of anti platelet therapy.

External validation studies have yielded inconsistent results with regard to predictability of the age, blood pressure, clinical features, duration of symptoms and diabetes (ABCD2) score at determining risk of stroke recurrence, thus, its clinical utility remains unclear. Two recent large population based studies have again raised questions about the clinical utility of the ABCD2 score. It is likely that the optimal approach to risk stratification incorporates the results of diffusion-weighted imaging (as examined by the more recently devised ABCD2–I and ABCD3–I scores) and early carotid imaging (as assessed by the ABCD3–I score), although prompt cerebral MRI may not be possible in many practice settings.

Stroke is a major cause for loss of life, limbs and speech in India, with the Indian Council of Medical Research estimating that in 2004, there were 9.3 lakh cases of stroke and 6.4 lakh deaths due to stroke in India, most of the people being less than 45 years old. Experts say that if deaths as well as disability are counted together, then India lost 63 lakh of disability-adjusted life years in 2004.WHO estimates suggest that by 2050, 80% stroke cases in the world would occur in low and middle income countries mainly India and China. Those with high blood pressure, diabetes, high blood fat (cholesterol) are specially at risk. The most important of these risk factors is high BP. In India, more than 16% of people above 20 years of age suffer from high BP. Fifty per cent of those with high BP are not even aware of it. Of those who are aware, only 50% take measures to control it, and of those who take these measures, only 50% are adequately controlled. "Thus, only 12.5% of patients with high BP are adequately controlled".  In the absence of high risk factors (low risk patients) one may consider the outpatient clinic protocol based therapies in India also!!

Cervical rib and thromboembolic stroke

Middle aged, overweight woman was admitted with critical ischemia in the right upper limb. She was symptomatic for more than a month. In our clinic (tertiary care hospital) it is uncommon to see patients with history shorter than 1 week. She required trans brachial thrombectomy (in emergency) and removal of the cervical rib (elective) and subclavian artery thrombectomy. The vertebral artery was close to the scalenous anticus muscle. Yet the thrombus in the subclavian artery rarely goes to the vertebral artery to cause the thromboembolic stroke. But we never came across such a patient in the last 25 years in our practice. It is possible that the neurologist treating the stroke patient may miss cervical rib,  if the patient has not been specifically examined and evaluated.

I came across a paper – where this information was published, I thought it will be useful to you, if you are looking for this type of information.

Thoracic outlet syndrome occurs due to compression of the neurovascular structures as they exit the thorax. Subclavian arterial compression is usually due to a cervical rib, and is rarely associated with thromboembolic stroke. The mechanism of cerebral embolization associated with the thoracic outlet syndrome is poorly understood, but may be due to retrograde propagation of thrombus or transient retrograde flow within the subclavian artery exacerbated by arm abduction. We report an illustrative patient and review the clinical features, imaging findings and management of stroke associated with thoracic outlet syndrome.

J Clin Neurosci. 2013 Oct 4. pii: S0967-5868(13)00514-6. doi: 10.1016/j.jocn.2013.07.030. [Epub ahead of print] Thromboembolic stroke associated with thoracic outlet syndrome. Meumann EM, Chuen J, Fitt G, Perchyonok Y, Pond F, Dewey HM.

$25 billion is spent annually in the United States treating chronic skin wounds related mostly to poor blood circulation?

The research review team, led by investigators at the Johns Hopkins Evidence-Based Practice Center and the Johns Hopkins Wound Healing Center, noted than an estimated $25 billion is spent annually in the United States treating chronic skin wounds related mostly to poor blood circulation, disorders known as venous ulcers. Their prevalence is rising along with rates of diabetes and obesity, and the review was undertaken in an effort to inform physicians about the treatment options.
Probably we should take them ( tiny and giant ulcerations)  more seriously and every effort should be made to prevent them and heal them early. - Pinjala R K

Inelastic compression therapy - Is it superior to elastic compression therapies?

Inelastic versus elastic leg compression in chronic venous insufficiency – what are the effects on venous hemodynamics

In the venous disease of the lower limbs, compression therapy is considered as an important component of the treatment. There are many ways to deliver the compression therapy to the legs in the venous disease patients.  Compression therapy can treat venous stasis, venous hypertension, and venous edema. Different methods of compression therapy have been described periodically over the last 2,000 years. In addition to static compression, specialized compression pumps have been developed to treat resistant edema. A technique of massage called manual lymphatic drainage has emerged to treat primary and secondary lymphedema. Objectives of compression therapy are to reduce the swollen limb to minimum size, maintain that size, and allow the patient to participate in the care of his limb whenever possible. Reduction therapy is achieved by limb elevation, compression pumps as necessary, and compression wraps. Maintenance therapy largely consists of compression wraps or compression stockings. Nonelastic devices have found a place in treating severe lymphedema but it should be emphasized that periodic follow-up must be done during maintenance therapy so that adjunctive maintenance measures can be added as needed. In tropical countries under humid conditions people find it difficult to tolerate the compression therapies unlike those living in the cold countries. People (farmers) working in the wet fields refuse to wear the compression bandages. We need to need monitor the compression therapy measures at regular intervals and make sure that the people regularly apply them.

A brief history of compression

Descriptions of limb compression therapy are found in the Corpus Hippocraticum (450-350 BC). Because the Greeks believed that “all wounds, especially those of the lower limbs, contradict standing, sitting or walking,” they used compression to counter the adverse effects of gravity and upright posture. Guy de Chauliac, a French anatomist and surgeon, published the first mention of compression therapy for varicose veins in Chirurgica magna (1363), a leading reference textbook for almost four centuries. Giovanni Michele Savonarola (1440) formalized “conservative treatment” for varicose veins. His Practica describes how bandages should be started at the distal part of the limb and worked upward to the proximal portion. Savonarola’s successor at Padua University was Fabricio d’Aquapendente (1537-1619), who further refined these bandaging methods. The first description of laced stockings (made from dog leather) can be found in his De chirurgicis operationibus. (Contrary to popular belief, this is not the reason why “going barefoot” came to be known as “airing out your dogs”). William Harvey’s 17^th century description of the circulation of blood led to an understanding of the physiological rationale for limb compression. By the latter 18^th century, Johann Christian Anton Theden (1714-1797) was postulating that compression “reduces somewhat the flow of humours, stimulates the activity of the skin over the suffering areas and increases the returning flow of humours.”The use of sponges under a compression device (to apply additional pressure over specific areas) was introduced by E. Home and others (1797). The need for a bandage that could be applied by the patient led H.A. Martin in Boston to develop a clothless bandage made of pure rubber, which could be placed directly atop the skin and held in place by another bandage. Thomas Baynton advocated adhesive bandages and promoted their use after they became commercially available toward the end of the 19^th century. The zinc oxide paste dressing, introduced by P.G. Unna in 1885, is still in use today. Ready-to-use zinc oxide bandages came onto the market after the First World War (Varicosan, Glauco, Weicosana, others). Modern elastic stockings were born on October 26, 1948 when William Brown, of Middlesex, England, submitted a patent for compression hose.

The first compression pumps were introduced in 1902 when Hofmeister proposed a treatment for arm edema in which the limb was placed within a metal cylinder filled with mercury. In 1917, Hartel used an air-filled tube for the same purpose. Hammersfahr (1931) published his treatment of venous stasis using an air cushion that filled and emptied rhythmically. Karl Linser developed a massage boot that utilized an air-filled chamber in which the pressure varied as the subject walked.

Manual lymphatic drainage has been used to remove extremity edema for more than 50 years. The original technique used soft massage to stimulate lymphatic vessels and propel fluid through their channels. Because 20% or more of patients with chronic venous insufficiency also have a component of lymphedema, manual lymphatic drainage may have a role in a compression therapy program for chronic venous insufficiency.

Nonelastic devices. The Circaid® (see Fig) provides rigid nondistensible resistance to the limb. It can be applied over a compression stocking for additional compression.

Topical compression therapy provides a means to treat or prevent these adverse effects. Limb compression (1) alters the tissue pressure gradient, which reduces edema formation and increases edema resorption; (2) reduces the caliber of the veins and increases venous flow velocity; (3) reduces orthostatic reflux, residual volume, and ambulatory venous pressure (in part, by re-recruiting venous valves and reducing reflux in the perforating vessels); and (4) improves the effectiveness of the muscle pump.

Mayberry et al (1991) - In 16 patients with CVI – compression therapy affect was studied on – femoral, popliteal vein velocities (duplex scan), reflux and ambulatory venous pressures direct measurement. Although stocking produced substantial superficial vein, they produced only modest increases in the popliteal vein velocity and no significant improvement in deep venous hemodynamics. These authors analysed another 8 studies (previous) and said the differences in the findings were due to consistencies in the study designs.

R K Spence et al (1996 -JVS) found that inelastic compression (see fig Circaid) has a significant effect on deep venous hemodynamics by decreasing venous reflux and calf muscle pump function better than compression stockings. They concluded that initially the superficial reflux should be adequately treated with stockings. Those with extensive clinical symptoms caused by abnormal deep venous hemodynamics and primary calf muscle pump dysfunction may benefit more from the inelastic compression. 

Carotid intima media thickness (DCCT/EDIC) long term followup

The Diabetes Control and Complications Trial (DCCT) has documented the profound beneficial effects of intensive diabetes therapy (INT) compared with conventional therapy (CON) on the development and progression of microvascular and neuropathic complications during the DCCT, mediated by the separation of HbA_1c levels between the two treatment groups. In addition, the further separation of these outcomes during the Epidemiology of Diabetes Interventions and Complications (EDIC) study, despite the disappearance of the differences in HbA_1c seen in the DCCT (metabolic memory), has been described. The long-term benefits of INT versus CON are almost completely explained by the differences between the two groups in the mean level of HbA_1c during the mean of 6.5 years of treatment in the DCCT .

They assessed carotid IMT by ultrasonography at EDIC years 1, 6, and 12 . At year 1, the results were largely within the age-matched, nondiabetic range with no difference between the DCCT INT and CON groups. Carotid ultrasonography was again repeated during EDIC year 6. During the ∼5 year period between the two measurements, IMT increased within both groups, significantly more so in the former CON than INT group (Fig. 1). Ultrasonography was again conducted during year 12 (12). IMT increased even more in both groups, consistent with the recognized effects of aging. The magnitude of the increase between EDIC years 6 and 12 was slightly greater in the former INT than in the CON group, but the mean IMT remained significantly less at 12 years in the former INT group.

NETs and Deep vein thrombosis

Deep vein thrombosis (DVT) is a major health problem that requires improved prophylaxis and treatment.Inflammatory conditions such as infection, cancer, and autoimmune diseases are risk factors for DVT. We and othershave recently shown that extracellular DNA fibers produced in inflammation and known as neutrophil extracellulartraps (NETs) contribute to experimental DVT. NETs stimulate thrombus formation and coagulation and are abundant inthrombi in animal models of DVT. It appears that, in addition to fibrin and von Willebrand factor, NETs represent a third

thrombus scaffold. Here, we review how NETs stimulate thrombosis and discuss known and potential interactions ofNETs with endothelium, platelets, red blood cells, and coagulation factors and how NETs could influence thrombolysis.It was proposed that drugs that inhibit NET formation or facilitate NET degradation may prevent or treat DVT. 

Deep vein thrombosis (DVT) is a debilitating disease that may be complicated by pulmonary embolism (PE). Together DVT and PE are designated as venous thromboembolism. In the United States, venous thromboembolism develops in an estimated 900000 patients each year, and PE is responsible for ≈300000 deaths, which exceeds the mortality from myocardial infarction or stroke.DVT complications, in addition to PE, include post thrombotic syndrome caused by chronic venous stasis even in the absence of active thrombosis

NETs are produced to allow neutrophils to trap and disarm microbes in the extracellular environment. NETs are scaffolds of intact chromatin fibers with antimicrobial proteins, ideal to retain large quantities of microbes. Therefore, some pathogenic bacteria have evolved to express an extracellular deoxyribonuclease (DNase), which dismantles NETs and promotes virulence. Extracellular traps are formed in humans, animals, and even plants, indicating that NETs provide an evolutionary conserved protective mechanism. 

NETs formation is not restricted to neutrophils, and different cell types use different cellular mechanisms to release extracellular trap. One mechanism used by human neutrophils is NETosis. NETosis is a multistep cell death program . On activation, certain enzymes translocate from the granules to the nucleus. Histones are degraded by neutrophil elastase (NE) and citrullinated by peptidylarginine deiminase 4 to unwind chromatin. Further hallmarks are the breakdown of granular and nuclear membranes and cytolysis as the final step in NETosis.

Implications of NETs in Thrombolysis -To degrade and solubilize thrombi to restore blood flow, fibrin  and VWF as the main scaffolds need to be proteolytically fragmented by the proteases plasmin and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13,  respectively. NETs are newly recognized third scaffolds that need to be undone during thrombolysis (Figure 1C). NETs were seen to colocalize with fibrin in clots 15 and with VWF in venous thrombi. In vitro, we could show that NETs provide a scaffold for blood clots that is resistant to tPA-induced thrombolysis. We incubated recalcified blood with neutrophils which were prestimulated to release NETs. As shown in  Figure 3, after filtration, blood clots appeared in control samples and tPA- or DNase-treated blood but not in blood treated with the combination of tPA and DNase. Immunostainings revealed that in the presence of tPA, blood clots lacked fibrin and were held together by a scaffold  of extracellular DNA (Figure 3B). DNase1 is the predominant nuclease in plasma. Interestingly, the plasminogen system cooperates with DNase1 during chromatin degradation. DNase1 has only limited activity to degrade chromatin because it preferentially degrades protein-free DNA. Plasminogen, activated by either tPA or urokinase-type plasminogen activator, degrades histones and therefore allows for degradation of DNA by DNase1. Monocytes/macrophages may also support the DNA degradation because their lysosomes contain DNase2, which is important for the removal of apoptotic cells (Figure 1C). NETs and fibrin degradation by plasmin and DNase could result in the simultaneous release of DNA and fibrin fragments.  In baboon DVT, plasma DNA increases with similar kinetics to the fibrin degradation product D-dimers. Recently, in collaboration with Thomas Wakefield’s group, we found increased levels of DNA in plasma from patients with DVT compared with healthy controls and symptomatic patients who did not have DVT. Here also, plasma DNA con-centrations correlated with D-dimers (unpublished data; Diaz and Fuchs, 2012). Therefore, it is plausible that circulating DNA may reflect the degradation of NETs within a thrombus.NETs may also promote thrombolysis. In vitro studies have shown that NE and cathepsin G can degrade fibrin, and these proteases are present on NETs and could enhance fibrinolysis in DVT. In addition, NETs may also recruit plasminogen from the plasma. Histone H2B can serve as a receptor for plasminogen on the surface of human monocytes/macrophages and perhaps could do so in NETs.

hepPTFE AVGs failed to improve patency or decrease secondary interventions compared to standard PTFE grafts used as Arteriovenous grafts for dialysis

Vascular occlusions in the lower limbs require a bypass operation. A conduit is needed for the bypass operation. Autogenous vein graft from the contralateral limb or ipsilateral limb is considered as an ideal conduit for the bypass operations. But it is not available or inadequate in 20-30% of the patients requiring bypass operation. Then one has to use the synthetic vascular graft in the absence of autogenous vein graft. The synthetic vascular grafts are modified over a period of time to improve the patency and reduce the recurrent thrombosis and also reduce the need for reinterventions. Porous dacron grafts need preclotting and that is not needed in the PTFE grafts. The kinking and rotation of the synthetic grafts in the long subcutaneous tunnels is avoided  by external support (rings/spirals). In a similar way there were many attempts to make the inner surface of the graft less thrombogenic and heparin bonding (coating) was one of them. These grafts have initially shown better results in the literature and they are available in the market. But there were not many papers to establish the indications and evaluating the long term results. Now these vascular grafts are also used for creating AV fistula for  patients requiring hemodialysis and known as arterio-venous grafts. The long term patency of the A-Vgrafts without re-interventions is a boon for the patients. It was hoped that the heparin bonding to the internal luminal surface of the Arterio-Venous grafts may prevent the thrombosis.

Recently a paper is published saying that Heparin Bonding Does Not Improve Patency of Polytetrafluoroethylene Arterio-Venous Grafts by Matthew TA et al (Feb 2013). A total of 223 patients had 265 grafts placed. Of these, 62 (23%) were hepPTFE grafts. The average age was 66 ± 15 years in the hepPTFE group and 59 ± 17 years in the non–heparin-bonded control group (PTFE; P < 0.01). Of the hepPTFE group, 39% were men, 81% were African American, 63% were diabetic, and 81% had a tunneled catheter at the time of access placement. Of the PTFE group, 35% were men, 85% were African American, 56% were diabetic, and 83% had a tunneled catheter. HepPTFE grafts failed to improve rates of primary, assisted primary, or secondary patency based on univariate analysis (hazard ratio [HR]: 1.37 [95% confidence interval {CI}: 0.99–1.88]; HR: 1.39 [95% CI: 0.98–1.96]; and HR: 1.20 [95% CI: 0.73–1.96], respectively). The number of secondary interventions was similar in the 2 groups (1.1 interventions per person-year of follow-up PTFE versus 1.4 hepPTFE; P = 0.13). A multivariable model including age, diabetes, peripheral artery disease, tobacco use, previous access placement, and tunneled catheter found that the HR for hepPTFE was not significantly different than PTFE in primary, assisted primary, or secondary patency (HR: 1.32 [95% CI: 0.91–1.90]; HR: 1.35 [95% CI: 0.91–1.99]; and HR: 1.15 [95% CI: 0.62–2.16], respectively.
This probably indicates that the intraluminal thrombosis of Arterio-Venous Grafts (AVGs) in the patients undergoing Dialysis is dependent on many other factors other than less thrombogenisity of the intraluminal surface of the grafts.

A 15-fold increase in rates of mortality due to cardiovascular disease and coronary heart disease among subjects with large-vessel peripheral arterial disease !!! do you believe?

Peripheral arterial disease (PAD) is a widespread vascular disorder that has been addressed for over a century and continues to affect a large portion of the modernized world. Both symptomatic and asymptomatic PAD affects 4.3% of the U.S. population aged ≥40 years of age1 and is recognized as a chronic atherosclerotic progression of lower-extremity arterial obstruction, which eventually leads to limb-threatening ischemia. PAD is functionally defined as an occlusive disease that generates a resting ankle–brachial index (ABI) of ≤0.90,2 although an ABI of between 0.9 and 1 is considered borderline and may introduce diagnostic subjectivity. PAD is strongly associated with terminal coronary artery disease for patients both with and without a significant cardiovascular history.3 As defined by a history of cardiovascular events or interventions (abdominal aortic aneurysms, transient ischemic attacks, stroke, carotid endarterectomy, history of angina, myocardial infarction, coronary angioplasty, and/or coronary artery bypass graft surgery), general cardiovascular disease has been associated with 70% of patients with PAD, rendering its diagnosis a significant indication for pan-vascular risk.4 Thus, the timely detection of PAD permits treatment of the diseased limb and preemptive management of cardiovascular risks.5 Preliminary PAD screenings have evolved into routine, noninvasive vascular laboratory studies, which reduce the risks, time, and costs associated with angiography. 

In a 10 years followup study published in Annals of vascular surgery in 1992 it was found that  - Twenty-one of the 34 men (61.8 percent) and 11 of the 33 women (33.3 percent) with large-vessel peripheral arterial disease died during follow-up, as compared with 31 of the 183 men (16.9 percent) and 26 of the 225 women (11.6 percent) without evidence of peripheral arterial disease. After multivariate adjustment for age, sex, and other risk factors for cardiovascular disease, the relative risk of dying among subjects with large-vessel peripheral arterial disease as compared with those with no evidence of such disease was 3.1 (95 percent confidence interval, 1.9 to 4.9) for deaths from all causes, 5.9 (95 percent confidence interval, 3.0 to 11.4) for all deaths from cardiovascular disease, and 6.6 (95 percent confidence interval, 2.9 to 14.9) for deaths from coronary heart disease. The relative risk of death from causes other than cardiovascular disease was not significantly increased among the subjects with large-vessel peripheral arterial disease. After the exclusion of subjects who had a history of cardiovascular disease at base line, the relative risks among those with large-vessel peripheral arterial disease remained significantly elevated. Additional analyses revealed a 15-fold increase in rates of mortality due to cardiovascular disease and coronary heart disease among subjects with large-vessel peripheral arterial disease that was both severe and symptomatic.

1. Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999–2000. Circulation. 2004;110:738–743
2. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45(Suppl. S):S5–67
3. Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med. 1992;326:381–386
4. Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001;286:1317–1324
5. Verhaeghe R. Prophylactic antiplatelet therapy in peripheral arterial disease. Drugs. 1991;42((Suppl. 5)):51–57

We should check the ABI in all patients at risk of peripheral arterial disease!

International ABI awareness as the next step in the PAD campaign

Coronary artery disease, cerebrovascular disease are well known in the society as the cause for heart attack (MI) and brain attack (stroke). Peripheral artery disease is the third most common manifestation of the atherosclerosis and one can lose lower limb if the critical ischemia is precipitated by other factors. The awareness of peripheral vascular disease is not adequate enough among the people in our society or general practioners to avoid complications and toe or limb loss in India and many other countries.

Peripheral artery disease (PAD) is common, underdiagnosed, and undertreated. Owing to the systemic nature of atherosclerosis, PAD patients are at risk for polyvascular disease. For example, 63% of patients with PAD have concomitant symptomatic cerebrovascular or coronary disease. Accordingly, PAD patients are at significantly increased risk for myocardial infarction, stroke, and vascular death over a 5-year period compared to age-matched cohorts.  

The ankle–brachial index (ABI) is the preferred initial test for PAD screening and diagnosis. It is relatively inexpensive, sensitive, and specific. Current guidelines provide clear recommendations on the indications for ABI testing. However, these guidelines may not have been fully implemented among practitioners.

In our practice we rarely see patients getting referred based on the ABI recorded in the clinics. The clinicians ask for Colour Doppler study (both legs costing Rs 2000 to 3000) and then send them with a report saying diffuse peripheral vascular disease in the diabetic and smoking population. Then we are doing the ankle brachial index in our clinic to classify degree of ischemia. One should practice checking the ankle brachial index routinely in patients with suspected peripheral arterial disease.

In a survey conducted in Australia, it was found that strikingly low 6% of GPs were aware of evidence-based guidelines on PAD screening, and only 5% were aware of guidelines on PAD diagnosis. The majority of GPs (58%) never perform ABIs. Most notably, 70% of the respondents choose arterial duplex (which is more costly and time-consuming) as the initial diagnostic tool in a patient with a history and physical exam consistent with PAD; younger GPs were more likely to choose the ABI. I think we are no better than the GPs in Australia in the evaluation of Peripheral vascular disease in the community.

The most common ‘moderate to major’ barriers to PAD screening and testing were (1) equipment availability, (2) time constraints, (3) lack of training and skills, and (4) staff availability. The time constraint barrier is not surprising, given that the time for an ABI could approach the 15-minute length of a typical primary care office visit. Other studies have also identified limited reimbursement and time as primary barriers to widespread use of the ABI in primary care practices.

I think, by increasing the awareness and improving staff ability more and more GPs will make an attempt to record the ABI in their practice and follow their patients for the CV events and extend better protection measures to avoid the amputations.