20 Venous Disorders by Urvi Trivedi

SECTION 20

Venous Disorders 188.

Anatomy, Physiology & Classification of Varicose Veins Ravul Jindal, Bhanupriya Wadhawan, Piyush Chaudhary

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189.

Incidence and Prevalence of Venous Disease in India Pinjala Ramakrishna

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190.

Medical Treatment of Varicose Veins Ajay K Khanna, Soumya Khanna

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191.

Endovenous Ablation Therapy for Varicose Veins Shoaib F Padaria

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192.

Over View of Management of Acute Deep Vein Thrombosis Vimalin Samuel, Edwin Stephen

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193.

Pulmonary Embolism Harinder Singh Bedi

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194. Catheter directed Thrombolysis in Deep Vein Thrombosis ( DVT), Technique and Results Over Last Decade DB Dekiwadia

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Anatomy, Physiology & Classification of Varicose Veins Ravul Jindal, Bhanupriya Wadhawan, Piyush Chaudhary

Varicose veins are dilated, tortuous, elongated superficial veins that are usually seen in the legs. It can occur in any age group but most common in mid- twenties. It is a progressive disease. It is more common in females than males.

ANATOMY

All veins in the body are either part of the superficial venous system or the deep venous system. The principal superficial veins of the lower extremity are the small saphenous vein (SSV), which usually runs from ankle to knee and the great saphenous vein (GSV), which usually runs from ankle to groin1 (Figure 1). Superficial collecting veins deliver their blood into the great and small saphenous veins, which deliver most of their blood into the deep system. Superficial veins are also connected to a variable number of perforating veins (PV) that pass through openings in the deep fascia to join deep veins of the calf or thigh either directly or through smaller plexus of smaller veins2,3 (Figure 2). All venous blood is eventually received by the deep venous system on its way back to the right atrium of the heart. The principal deep venous trunk of the leg is called the popliteal vein from below the knee until it passes upward into the distal thigh, where it is called the femoral vein (FV) for the remainder of its course in the thigh. This is the largest and longest deep vein of the lower extremity.

also functions as a reservoir to hold extra blood. You could say that the venous system is almost magical in its function when you are told that the entire cardiac output volume of 5–10 L/min is received into periphery venous system for eventual delivery back to the heart and lungs.

PATHOANATOMY

The veins have one-way valves to prevent them from backward flow. The correct functioning of the venous system depends on a complex series of valves. It has been known that varicose veins in the legs are caused by weakening of the veins and valves in the great saphenous veins and/or small saphenous veins. When the valves in these malfunction, blood begins to collect in the legs resulting in the buildup of pressure. The veins become enlarged and knotted and are visible near the surface of the skin as a varicose vein (Figure 3a and b). Major valves which dysfunctions in the caution of varicose vein are saphenofemoral junction (SFJ) and saphenopopliteal junction (SPJ). The termination point of the GSV into the common femoral vein, located proximally at the groin, is called the Saphenofemoral junction. The terminal valve of the GSV is located within the junction itself. In most cases, at least one additional sub terminal valve is present within the first few centimeters of the GSV. Most patients have

Unlike arteries with thick walls, most veins are very thin and easily distendable, so the peripheral venous system Femoral Vein

Popliteal Vein

Long Saphenous Vein

Short Saphenous Vein

Tributaries of LSV

Fig. 1: Showing superficial and deep venous system

Fig. 2: Showing perforating veins

VF=femoral vein GSV=Great saphenous vein SSV=Supra-saphenic valve TV=Terminal valve PTV=Pre-terminal valve

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Fig. 3a: Showing normal veins and diseased veins A

Deep veins Iliac vein

Venous insuﬁciency Common femoral vein

Superﬁcial veins

Great saphenous vein Normal vein Open valve

Popliteal vein

Normal valve opens to allow blood ﬂow toward heart

Normal vein Closed valve

Normal valve closes to prevent reverse of blood ﬂow

Varicose vein Damaged/nonfunctional valve

Incompetent valve Vein wall thinned and bulging Abnormal blood ﬂow backward down leg

Damaged nonfunctional valve cannot close properly and blood ﬂow is impaired

Normal blood ﬂow back to heart

Deep vein

Superﬁcial vein

Perforating vein Fascia layer

Deep vein Perforating veins

Superﬁcial veins

Incompetent perforating valve causing abnormal blood ﬂow

Normal perforating valve and normal blood ﬂow

Fig. 3b: Showing normal veins and diseased veins a single sub terminal valve that can be readily identified approximately 1 cm distal to the junctional valve.

PATHOPHYSIOLOGY

The pathophysiology behind their formation is complicated and involves the concept of ambulatory venous hypertension. In healthy veins, the flow of venous blood is through the superficial system into the deep system and up the leg and toward the heart. One-way venous valves are found in both systems and the perforating veins. Incompetence in any of these valves can lead to a disruption in the unidirectional flow of blood toward the heart and result in ambulatory venous hypertension (AVH). 6 Incompetence in the superficial venous system alone usually results from failure at valves located at the SFJ and SPJ. The gravitational weight of the column of blood along the length of the vein creates hydrostatic pressure, which is worse at the more distal aspect of the length of vein. Reflux at or near the SFJ does not always come through the terminal valve of the GSV, nor does it always involve the entire trunk of the GSV. Reflux can enter the GSV below the sub terminal valve or even immediately below the junction, passing through a failed sub terminal valve

Fig. 4: Showing terminal and preterminal valve to mimic true SFJ incompetence. Reflux can also pass directly into any of the other veins that join the GSV at that level, or it may pass a few centimeters along the GSV and then abandon the GSV for another branch vessel. Incompetence of the perforating veins leads to hydrodynamic pressure. The calf pump mechanism helps to empty the deep venous system, but if perforating vein valves fail, then the pressure generated in the deep venous system by the calf pump mechanism are transmitted into the superficial system via the incompetent perforating veins. Once venous hypertension is present, the venous dysfunction continues to worsen through a vicious circle. Pooled blood and venous hypertension leads to venous dilatation, which then causes greater valvular insufficiency. Over time, with more local dilatation, other adjacent valves sequentially fail, and after a series of valves has failed, the entire superficial venous system is incompetent. This can then cause subsequent perforator and deep venous valvular dysfunction. The clinical findings of varicose veins, reticular veins, and telangiectasias are due to the hypertension in the superficial venous system that spreads to collateral veins and tributary veins, causing dilated tortuous structures. Treatment modalities are geared towards correcting the superficial venous hypertension. In contrast to the superficial veins, the deep veins do not become excessively distended. They can withstand the increased pressure because of their construction and the confining fascia.

THE CLASSIFICATION OF VENOUS DISEASE

Venous disease of the legs can be classified according to the severity, cause, site and specific abnormality using the CEAP classification. The elements of the CEAP classification are:

• Clinical severity

a. Pigmentation or Eczema b. Lipodermatosclerosis or athrophie blanche

• Etiology or cause

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• Anatomy • Pathophysiology For the initial assessment of a patient, the clinical severity is the most important and can be made by simple observation and does not need special tests. There are seven grades of increasing clinical severity 3,4,5: Description

No evidence of venous disease. Skin pigmentation in the gaiter area (lipodermatosclerosis)

C5 Superficial spider veins (reticular veins) only

A healed venous ulcer

C2 C6

Simple varicose veins only An open venous ulcer The majority of patients referred to the vascular surgical clinic have grade 2 diseases (simple varicose veins).

Ankle edema of venous origin (not foot edema)

Patients with C3-6 disease are demonstrating increase severity of chronic venous insufficiency, and all have a functional abnormality of the venous system. These patients are most at risk of chronic ulceration and require specialized tests such as venous duplex and ambulatory venous pressure measurement to diagnose and characterize the underlying venous abnormality. If we correct the venous abnormality in the disease process then the risk of complications associated with the venous disease are much lower.

CHAPTER 188

Grade

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clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum.Society for Vascular Surgery; American Venous Forum. J Vasc Surg 2011; 53(5 Suppl):2S-48S.

REFERENCES

Souroullas P, Barnes R, Smith G, Nandhra S, Carradice D, Chetter I.The classic saphenofemoral junction and its anatomical variations. Phlebology 2016 Feb

Goldman MP, Fronek A. Anatomy and pathophysiology of varicose veins. J Dermatol Surg Oncol 1989; 15:138-45.

Rabe E, Pannier F. Clinical, aetiological, anatomical and pathological classification (CEAP): gold standard and limits. Phlebology 2012; 27 Suppl 1:114-8.

Gloviczki P, Comerota AJ, Dalsing MC, Eklof BG, Gillespie DL, Gloviczki ML, Lohr JM, McLafferty RB, Meissner MH, Murad MH, Padberg FT, Pappas PJ, Passman MA, Raffetto JD, Vasquez MA, Wakefield TW; The care of patients with varicose veins and associated chronic venous diseases:

Vasquez MA, Rabe E, McLafferty RB, Shortell CK, Marston WA, Gillespie D, Meissner MH, Rutherford RB; Revision of the venous clinical severity score: venous outcomes consensus statement: special communication of the American Venous Forum Ad Hoc Outcomes Working Group.American Venous Forum Ad Hoc Outcomes Working Group. J Vasc Surg 2010; 52:1387-96.

Yetkin E, Ileri M. Dilating venous disease: Pathophysiology and a systematic aspect to different vascular territories. Med Hypotheses 2016; 91:73-6.

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Incidence and Prevalence of Venous Disease in India

Cardiac problems, arterial and venous problems are common in the modern world which are grouped under non-communicable disease. Acute venous thromboembolism (VTE) is known to be the 3rd most common cause of death. Chronic venous disorders can be post-thrombotic or non-thrombotic. The chronic venous disorders are known to be associated increased morbidity and significant economic loss to the society. In our modern society the people develop multiple risk factors which increase the incidence of deep vein thrombosis (acute, chronic), pulmonary embolism, varicose veins, leg edema, Lipodermatosclerosis (LDS) and venous ulceration (Figure 1). Some studies have shown gender differences in the incidence of venous problems. Brand FN et al (1988) in the Framingham study found that the incidence of varicose veins is higher among women than men with no clear age differences.1 Women with varicose veins were more often obese (p <.01), had lower levels of physical activity (p <.001) and higher systolic blood pressure (p <.001), and were older at menopause (p <.001). Women who reported spending eight or more hours in an average day in sedentary activities (sitting or standing) also had a significantly higher incidence of varicose veins than those who spent four or fewer hours a day in such activities (p <.05). For men, varicose veins coexisted with lower levels of physical activity (p <.05) and higher smoking rates (p <.05). While men and women with varicose veins had a higher incidence of atherosclerotic cardiovascular disease than Rthose without varicose veins, only the excess risk Pinjala K September 2016 of coronary heart disease in women was statistically

Fig. 1: Types of Venous disease

Pinjala Ramakrishna

significant (p <.05). However, this finding was not significant after controlling for body mass and systolic blood pressure. These results suggest that increased physical activity and weight control may help prevent varicose veins among adults at high risk, and reduce the overall risk of atherosclerotic cardiovascular disease as well. In an Indian epidemiological study, S L Malhotra (1972) reported the prevalence of varicose veins among railway men of identical socio-economic status and doing identical work in the Indian railways. He showed that the prevalence was 25.08% among South Indian employees and 6.8% among the North Indian employees. While men and women with varicose veins had a higher incidence of atherosclerotic cardiovascular disease than those without varicose veins, only the excess risk of coronary heart disease in women was statistically significant (p <.05). However, this finding was not significant after controlling for body mass and systolic blood pressure. These results suggest that increased physical activity and weight control may help prevent varicose veins among adults at high risk, and reduce the overall risk of atherosclerotic cardiovascular disease as well. He said that While constipation, body weight, smoking, posture and tight undergarments do not appear to contribute to the causation of varicose veins, the role of heredity could not be examined in this study. Since such differences are known to be diet related, this study suggested that, in the prevalence of varicose veins, patterns of diet and eating may play an important part. Therefore, there would seem to be hope that this disease may be prevented.2 The risk factors for venous thromboembolism are commonly prevalent in the hospitalized patients admitted into the acute ward beds. In the ENDORSE study (2008), A large proportion of hospitalized patients were found to be at risk for VTE, but there was a low rate of appropriate prophylaxis. It was said that there is a need for rationale for the use of hospital-wide strategies to assess patients’ VTE risk and to implement measures that ensure that at-risk patients receive appropriate prophylaxis. 68 183 patients were enrolled; 30 827 (45%) were categorized as surgical, and 37 356 (55%) as medical. On the basis of ACCP criteria, 35 329 (51·8%; 95% CI 51·4–52·2; betweencountry range 35·6–72·6) patients were judged to be at risk for VTE, including 19 842 (64·4%; 63·8–64·9; 44·1–80·2) surgical patients and 15 487 (41·5%; 41·0–42·0; 21·1–71·2) medical patients. Of the surgical patients at risk, 11 613 (58·5%; 57·8–59·2; 0·2–92·1) received ACCP-recommended

872

VTE prophylaxis, compared with 6119 (39·5%; 38·7–40·3; 3·1–70·4) at-risk medical patients.3

VENOUS DISORDERS

In Subset data of ENDORSE, it was found out despite a similar proportion of at-risk hospitalized patients in India and other participating countries, there was major underutilization of prophylaxis in India. It necessitates increasing awareness about VTE risk and ensuring appropriate thromboprophylaxis Results: In India, we recruited 2058 patients (1110 surgical, 948 medical) from 10 randomly selected hospitals in India between August 2006 and January 2007. According to the ACCP criteria, 1104 (53.6%) patients [surgical 680 (61.3%), medical 424 (44.7%)] were at-risk for VTE. Chronic pulmonary disease/heart failure and complete immobilization were the most common risk factors before and during hospitalization, respectively. In India, 16.3 per cent surgical and 19.1 per cent medical at-risk patients received ACCP recommended thromboprophylaxis. Interpretation & conclusions: Despite a similar proportion of at-risk hospitalized patients in India and other participating countries, there was major underutilization of prophylaxis in India. It necessitates increasing awareness about VTE risk and ensuring appropriate thrombo-prophylaxis.4 Varicose veins are part of the spectrum of chronic venous disease and include spider telangiectasias, reticular veins, and true varicosities. Approximately 23% of US adults have varicose veins.5 If spider telangiectasias and reticular veins are also considered, the prevalence increases to 80% of men and 85% of women.6 Generally more common in women and older adults, varicose veins affect 22 million women and 11 million men between the ages of 40 to 80 years. 1 of these, 2 million men and women will develop symptoms and signs of chronic venous insufficiency, including venous ulceration. The sheer prevalence of varicose veins and the substantial cost of treating late complications such as chronic venous ulcers contribute to a high burden on health care resources.2 Chronic venous ulcerations result in the loss of 2 million workdays and cost an estimated $3 billion per year to treat in the United States.7 Even varicose veins alone, without more advanced signs of chronic venous insufficiency, result in important reductions in quality of life.8 In United Kingdom, assessment and treatment of varicose veins comprises a significant part of the surgical workload. In the UK, National Health Service waiting lists suggest that there is still considerable unmet need. In India too, assessment and treatment of venous diseases in an unmet need. Callam MJ (1994) analyzed all the published data on the epidemiology of varicose veins, paying particular regard to the differing epidemiological terminology, populations sampled, assessment methods and varicose

vein definitions, which account for much of the variation in literature reports. Half of the adult population have minor stigmata of venous disease (women 50-55 per cent; men 40-50 per cent) but fewer than half of these will have visible varicose veins (women 20-25 per cent; men 10-15 per cent). The data suggest that female sex, increased age, pregnancy, geographical site and race are risk factors for varicose veins; there is no hard evidence that family history or occupation are factors. Obesity does not appear to carry any excess risk. Accurate prevalence data allow provision of appropriate resources or at least aid rational debate if demand is greater than the resources available.9 In India, the importance of identifying and treating the venous disease is getting better with increased use of ultrasound and doppler assessment, endovenous therapies, adequate anticoagulation, compression therapies, thrombo-prophylactic measures and venous ulcer care. However more epidemiological studies are needed to assess the incidence and natural course of the venous disease in different populations and effect of various treatments on the natural course of venous diseases, so it is accepted that this is an unmet need.

REFERENCES

Brand FN, Dannenberg AL, Abbott RD, Kannel WB. The epidemiology of varicose veins: the Framingham Study. Am J Prev Med 1988; 4:96-101.

S. L. MALHOTRA. An Epidemiological Study of Varicose Veins in Indian Railroad Workers from the South and North of India, with Special Reference to the Causation and Prevention of Varicose Veins. Int J Epid 1972; 1:177–183.

Alexander T Cohen, MD for the ENDORSE Investigators. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. The Lancet 2008; 371:387–394.

4. Ramakrishna Pinjala on behalf of all ENDORSEIndia investigators*- Venous thromboembolism risk & prophylaxis in the acute hospital care setting (ENDORSE), a multinational cross-sectional study: Results from the Indian subset data. Indian J Med Res 2012; 136:60-67. 5. Hamdan A. Management of varicose veins and venous insufficiency. JAMA 2012; 308:2612–2621. 6.

Bergan JJ, Schmid-Schönbein GW, Smith PD, Nicolaides AN, Boisseau MR, Eklof B. Chronic venous disease. N Engl J Med 2006; 355:488–498.

7. McGuckin M, Waterman R, Brooks J, Cherry G, Porten L, Hurley S, Kerstein MD. Validation of venous leg ulcer guidelines in the United States and United Kingdom. Am J Surg 2002; 183:132–137. 8.

Shepherd AC, Gohel MS, Lim CS, Davies AH. A study to compare disease-specific quality of life with clinical anatomical and hemodynamic assessments in patients with varicose veins. J Vasc Surg 2011; 53:374–382.

Callam MJ.Epidemiology of varicose veins. Br J Surg 1994; 81:167-73.

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Medical Treatment of Varicose Veins

Risk factors for varicose veins include increased intraabdominal pressure as chronic cough, constipation, family history of venous disease, female sex, obesity, older age, pregnancy, and prolonged standing. The exact pathophysiology is debated, but it involves a genetic predisposition, incompetent valves, weakened vascular walls, and increased intravenous pressure. A heavy, achy feeling; itching or burning; and worsening with prolonged standing are usual symptoms of varicose veins. Potential complications include infection, leg ulcers, stasis changes, and thrombosis. Some conservative treatment options are avoidance of prolonged standing and straining, elevation of the affected leg, exercise, external compression, loosening of restrictive clothing, medical therapy, modification of cardiovascular risk factors, reduction of peripheral edema, and weight loss. More aggressive treatments include external laser treatment, injection sclerotherapy, endovenous interventions, and surgery. Comparative treatment outcome data are limited. There is little evidence to preferentially support any single treatment modality. Choice of therapy is affected by symptoms, patient preference, cost, potential for iatrogenic complications, available medical resources, insurance reimbursement, and physician training. Lifestyle changes include avoiding standing or sitting for long periods without taking a break. When sitting, avoid crossing your legs. Keep legs raised when sitting, resting, or sleeping. Do physical activities to get legs moving and improve muscle tone. In overweight or obese, try to lose weight. This will improve blood flow and ease the pressure on veins. Avoid wearing tight clothes, especially those that are tight around waist, groin and legs. Avoid wearing high heels for long periods. Lower heeled shoes can help tone calf muscles. External compression devices (e.g., bandages, support stockings, intermittent pneumatic compression devices) have been recommended as initial therapy for varicose veins. Typical recommendations include wearing 20 to 30 mm Hg elastic compression stockings with a gradient of decreasing pressure from the distal to proximal extremity. Inelastic, elastic, intermittent pneumatic is the standard of care and is associated with a decreased rate of ulcer recurrence. Although compression therapy is of proven benefit, the effect of intermittent pneumatic therapy is less evident. It reduces oedema and pain, improves venous circulation and enhances ulcer healing. Lifelong maintenance of compression therapy after ulcer healing reduces the rate of recurrence. However, in the presence

Ajay K Khanna, Soumya Khanna

of eczematous dermatitis, obesity, pain and discharging ulcer, strict adherence to the regime of compression therapy becomes cumbersome. Clinically significant arterial insufficiency and heart failure are contraindications to compression therapy. Elastic compression sustains pressure during both ambulation and rest. In ulcerations, a pressure of around 35â&#x20AC;&#x201C;40 mmHg is necessary. In the absence of ulcer, a pressure between 25 and 30 mmHg may suffice. Elastic bandages or stockings may be used. The latter is more useful as it provides a graded pressure from below upwards, highest being at the ankle. It should be taken off at night and changed usually after 6 months as pressure is reduced by regular washing. Multilayered elastic bandages have proved to be more effective than single layered ones, but require skilled application and frequent change in the presence of discharge.

DRUGS

Pentoxifylline (400 mg three-times daily) has been shown to be of additive beneficial effect to compression. It acts by action on leucocyte metabolism, inhibition of platelet aggregation, reduction in viscosity of blood and consequent improvement in microcirculation. But its effect as monotherapy has not been shown to be cost effective. Micronised purified flavanoid fraction-Daflon 500 mg and prostaglandin E1 analogue-are used due to their action on leucocyte metabolism. These drugs are most effective when used in conjunction with compression. Aspirin (300 mg daily) is effective when used with compression therapy. It acts by reducing platelet adhesion. Antibiotics are used in case of suspected cellulitis, and its routine use is not recommended. Oral zinc, despite having an anti-inflammatory effect, has not been shown to be useful. Various ayurvedic preparations have been used as. Apple Cider Vinegar, Olive Oil, Cayenne Pepper, Garlic, Butcherâ&#x20AC;&#x2122;s Broom, , Hawthorn berries, blueberries, blackcurrants, blackberries, horse chestnut, Gotu kola, Bromelain has been tried. Other drugs as levamisole, doxycycline, hydroxyethylrutosides, calcium dobesilate has also been tied with variable results. Laser machines that deliver various wavelengths of light through the skin and into the blood vessels are available to treat varicose veins. The light is absorbed in the vessels by hemoglobin, leading to thermocoagulation. Types of lasers include pulsed dye, long pulsed, variable pulsed, neodyxiumdoped yttrium aluminum garnet (Nd:YAG), and alexandrite lasers. Potentially, any small, straight vein branch is amenable to external laser ablation. However, laser therapy has typically been used on

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telangiectasias and smaller vessels rather than on larger veins. Long-pulsed lasers have been shown to completely clear veins with diameters less than 0.5 mm. For veins with diameters of 0.5 to 1.0 mm, improvement but not clearance is achieved. Sclerotherapy involves injecting superficial veins with a substance that causes them to collapse permanently. The substance displaces the blood and reacts with the vascular endothelium, sealing and scarring the vein. A variety of products are used, including hyperosmotic solutions (e.g., hypertonic saline), detergent solutions (e.g., sodium tetradecyl sulphate/polidaconol), and corrosive agents (e.g., glycerin). Injections typically work better on small (1 to 3 mm) and medium (3 to 5 mm) veins; however, a precise diameter used to make treatment decisions is lacking. Although sclerotherapy is a clinically effective and cost-effective treatment for smaller varicose veins, concerns about the development of deep venous

thrombosis and visual disturbances, and the recurrence of varicosities have been noted.

CONCLUSION

Varicose veins are treated with lifestyle changes and medical procedures. The goals of treatment are to relieve symptoms, prevent complications, and improve appearance. Lifestyle changes often are the first treatment for varicose veins. These changes can prevent varicose veins from getting worse, reduce pain, and delay other varicose veins from forming. Compression stockings create gentle pressure up the leg. This pressure keeps blood from pooling and decreases swelling in the legs. Many of the patients with varicose veins will require active intervention in form of Surgery, Endovenous ablations etc. and medical treatment may be adjunct to that.

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Endovenous Ablation Therapy for Varicose Veins

Varicose veins is an extremely common medical condition affecting about 6 to 7 % of the entire population. In the past two decades, various non surgical treatment methods have evolved, which effectively close the refluxing veins without resorting to any surgical incisions. With continuous refinement in techniques and evolvement of technology, these endovenous techniques have currently become the first choice of treatment in varicose veins. Thermal ablation is a method whereby heat energy is used to close the veins. In laser thermal ablation, a thin laser fiber is introduced percutaneously into the refluxing vein under ultrasound guidance. Currently the favoured laser wavelength is 1470 nano microns, and a radial tipped laser fiber is used. Dilute tumescent anesthetic is then injected under ultrasound guidance around the vein. As the laser is fired, thermal energy is generated, which caused thermal damage to the endothelium of the vein, causing its immediate closure. The fiber is gradually pulled back though the vein, achieving complete closure of the vein along its length. The patient is immediately

Shoaib F Padaria

mobilized, and most patients can resume their normal duties within 24 to 48 hours. Compression garments are usually prescribed, to be worn during daytime for upto a month. Radiofrequency is another technique whereby thermal energy is generated. The delivery element of the Radiofrequency catheter is about 7 cm long, and thermal energy is delivered in a circumferential manner. Multiple segments of the vein are closed sequentially by delivering thermal energy. The results of radiofrequency ablation are similar to those achieved by laser treatment. Foam sclerotherapy is a technique whereby a sclerosant solution is converted into foam, and injected into the refluxing varicose viens under ultrasound guidance. The most commonly used sclerosants are polidocanol and sodium tetradecyl sulphate. This relatively simple technique gives fairly good immediate results, although the long term results of closure are inferior to those of thermal ablation.

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Over View of Management of Acute Deep Vein Thrombosis

Deep vein thrombosis (DVT) and pulmonary embolism are the two main manifestations of venous thrombo embolism (VTE). It is well established that anti coagulation with vitamin K antagonist (VKA) is the main stay of treatment for DVT,after intial treatment with unfractioned heparin [UFH] or low molecular weight heparin [LMWH]. However, in the light of emerging drugs like newer oral anti coagulants (NOACS) and new surgical options like catheter directed thrombolysis (CDT), the therapeutic options have broadened. NOMENCLATURE — For the purposes of discussion in this topic, the following terms apply: Unprovoked DVT – implies no identifiable provoking event for DVT is evident. Provoked DVT – caused by a known event, ie; major surgery > 30 minutes, hospitalization or immobility ≥ 3 days, caesarian section), transient minor risk factors (minor surgery < 30 minutes, hospitalization < 3 days, pregnancy, estrogen therapy, reduced mobility ≥ 3 days) or persistent risk factors. Persistent risk factors include reversible conditions (eg, curable malignancy, inflammatory bowel disease that resolves) and irreversible conditions such as inheritable thrombophilias, chronic heart failure, and metastatic end-stage malignancy. Proximal DVT – Located in the popliteal, femoral and iliac veins. Distal DVT – No proximal component, is located below the knee and involves the calf veins.

INTRODUCTION

The earliest case of DVT was described by Sushruta in his book Sushruta Samhita around 600–900 BC. In 1856, German physician and pathologist Rudolf Virchow published what is referred to as Virchow’s triad, the three major causes of thrombosis. The triad provides the theoretical framework for the current explanation of venous thrombosis. The true incidence of VTE in India is underreported. In a retrospective study in CMC Vellore from (1996-2005) to determine the incidence of VTE among hospitalized patients andshowed an overall incidence of confirmed DVTs to be 17.46per 10,000 admissions with 64% being non surgical non traumapatients. PE was diagnosed in 14.9% of the study patients. Mortality in those with confirmed PE was 13.5%.

Vimalin Samuel, Edwin Stephen

SIGNS, SYMPTOMS AND PHYSICAL EXAMINATION

Classic symptoms of DVT include swelling, pain, and erythema of the involved extremity. There may not necessarily be a correlation between the location of symptoms and the site of thrombosis. A complete history includes age, surgical procedures, hospitalization, trauma, pregnancy, heart failure, and immobility, use of oral contraceptives or hormone replacement therapy as well as their obstetric history in women. The presence of recurrent fetal loss in the second or third trimester suggests the possible presence of an inherited thrombophilia or antiphospholipid antibodies. Collagen-vascular disease, myeloproliferative disease, atherosclerotic disease, or nephrotic syndrome and the use of drugs which can induce antiphospholipid antibodies such as hydralazine, procainamide, and phenothiazines must be ruled out. The patient should also be questioned about a past history of cancer. Other findings that may suggest an underlying malignancy are constitutional symptoms such as loss of appetite, weight loss, fatigue, pain, hematochezia, hemoptysis, and hematuria. A positive family history of VTE is particularly important, since a well documented history of VTE in one or more first-degree relatives under age 50 suggests the presence of a hereditary defect and/or an increased susceptibility for venous thromboembolic disease. The Wells criteria can be used for diagnosis of a DVT if the clinical suspicion is high. Physical examination may reveal a palpable cord (reflecting a thrombosed vein), calf or thigh pain, unilateral edema or swelling with a difference in calf diameters, warmth, tenderness, erythema,and/or superficial venous dilation. The peripheral pulses must be documented to rule out venous gangrene and prevent compression related complications. The initial laboratory evaluation in patients with venous thrombosis should include a complete blood count and platelet count, coagulation studies (eg, prothrombin time, activated partial thromboplastin time), renal and liver function tests, urinalysis, chest x-ray and ECG.

DIAGNOSIS OF DVT

A positive noninvasive study with a compression ultrasound in patients with a first episode of DVT usually establishes the diagnosis, with a positive predictive value for compression ultrasonography of 94%. If the initial study is negative and the clinical suspicion of DVT is high, a repeat study should be obtained on day 5 to 7.

DVT- MANAGEMENT Renal failure — IV UFH is the preferred anticoagulant in those with severe renal failure.

LOWER LIMB EDEMA SUSPECT DVT – VENOUS DUPLEX , PULSES POSITIVE [ UN / Provoked ]

NEGATIVE 100iu UFH /Kg IV stat [ max 5000iu] CELLULITIS FILARIAL FRACTURE

LMWH

-Clexane [ 1 mg /kg b.d ] -Fragmin [ 175u/kg ] -Fraxiparine

1000iu /hr infusion APTT – 4hours <60 yr [ 70-90] >60 yr [ 50-70]

Hemodynamic instability — IV UFH is the preferred anticoagulant in those who are hemodynamically unstable since thrombolysis, interventional procedure, or surgery may need to be considered in this population. Extensive clot burden — IV UFH is the preferred anticoagulant for those patients with extensive DVT or with phlegmasia cerulea dolens, or those with massive or submassive PE which is based upon an anticipated need for a procedural or surgical intervention.

Obesity or poor subcutaneous absorption — There is no preferred agent in patients who are obese. However, Fig. 1: DVT-Management therapeutic anticoagulation can be assured with IV UFH. Dosing requirements for LMWH are different for each LMWH product. Treatment with LMW heparin, fondaparinux, or unfractionated heparin should be continued D-dimer level <500 ng/mL by ELISA or a negative IV UFHformay also be an alternative to subcutaneous LMW at least 3 days and oral anticoagulation with a vitamin K antagonist should be overlapped with when subcutaneous absorption is potentially SimpliRED assay in conjunction with a low clinical heparin LMWH, fondaparinux, or UFH for at least 3 days. poor probability (ie, Wells score) or other negative noninvasive THROMBOLYSIS [ < 21days ]

Warfarin should be initiated simultaneously with the heparin, at an initial oral dose of tests may be useful in excluding DVT, without the need Heparin-induced thrombocytopenia — For patients approximately 5 mg/day. In elderly patients and in those at high risk of bleeding or who are for ultrasound testing with VTE and a diagnosis of heparin-induced undernourished, debilitated, or have heart failure or liver disease, the starting dose should be thrombocytopenia (HIT), anticoagulation with heparin, reduced. The heparin product can be discontinued Oral TREATMENT OF DVT (FIGURE 1) on day 3 if the INR is therapeutic.including UFH and LMW heparin, is contraindicated. anticoagulation with a vitamin K antagonist should prolong the INR to a target range between The primary objectives for treatment of a DVT include Anticoagulation with a non-heparin anticoagulant (eg, 2.0 to 3.0. Dabigatran, fondaparinux) should be administered. 1. Prevent further clot extension For patients receiving UFH, ACCP Guidelines suggest that platelet counts be obtained regularly to monitor2. for thePrevent development of thrombocytopenia. stopped useif of thrombolytic agents, surgical thrombectomy, pulmonary embolismThe heparin product should beThe any one of the following occurs: a precipitous or sustained fall in the platelet count, or a platelet or percutaneous mechanical thrombectomy in the 3. Reduce the risk of the patient developing a chronic treatment of DVT must be individualized. Patients with count <100,000/microL. venous Malignancy — For patientsinsufficiency with malignancy and VTE, LMWH is the preferred anticoagulant massive iliofemoral thrombosis (ie, phlegmasia cerulea for long-term use. dolens), and who are also at low risk to bleed, are the 4. Reduce the risk of recurrence of DVT

Dosing requirements for LMWH are different for each LMWH product. Treatment with LMW heparin, fondaparinux, or unfractionated heparin should be continued for at least 3 days and oral anticoagulation with a vitamin K antagonist should be overlapped with LMWH, fondaparinux, or UFH for at least 3 days. Warfarin should be initiated simultaneously with the heparin, at an initial oral dose of approximately 5 mg/ day. In elderly patients and in those at high risk of bleeding or who are undernourished, debilitated, or have heart failure or liver disease, the starting dose should be reduced. The heparin product can be discontinued on day 3 if the INR is therapeutic. Oral anticoagulation with a vitamin K antagonist should prolong the INR to a target range between 2.0 to 3.0. For patients receiving UFH, ACCP guidelines suggest that platelet counts be obtained regularly to monitor for the development of thrombocytopenia. The heparin product should be stopped if any one of the following occurs: a precipitous or sustained fall in the platelet count, or a platelet count <100,000/microL. Malignancy — For patients with malignancy and VTE, LMWH is the preferred anticoagulant for long-term use. Pregnancy — LMWH is the preferred agent for long-term anticoagulation in pregnant women with acute VTE.

most appropriate candidates for such treatment.

Inferior vena caval filter placement is recommended when there is a contraindication to, or a failure of, anticoagulant therapy in an individual with, or at high risk for, proximal vein thrombosis or PE. It is also recommended in patients with recurrent thromboembolism despite adequate anticoagulation. Despite prior concerns regarding the potential for embolization, early ambulation is safe in patients with acute DVT and should be encouraged as soon as is feasible. Class 2 compression stockings should be started after anticoagulant therapy, within two weeks of the diagnosis, and continued for an year. The minimal requirements for outpatient treatment for patients with DVT include 1.

The patient is ambulatory, stable and with normal vital signs.

There is a low risk of bleeding.

Normal renal function.

There is a system in place for administration of heparin, appropriate monitoring and surveillance.

NEWER/NOVEL ORAL ANTI COAGULANTS

For most non-pregnant patients who do not have severe renal insufficiency (eg, creatinine clearance [CrCl <30mL/ minute) or active cancer, we suggest the direct oral

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Warfarin /Acitrome/NOACS + Grade II compression stockings below knee

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anti coagulants, rivaroxaban, apixaban, edoxaban, or dabigatran, rather than warfarin and suggest warfarin rather than LMW heparin. While rivaroxaban and apixaban can be administered as monotherapy, edoxaban and dabigatran are preferably administered following a five day course of heparin. However treatment with newer anti coagulants is expensive and may place a large financial burden on the patient.

VENOUS DISORDERS

Typical initial doses in those with normal renal function are: ●

Rivaroxaban - 15 mg by mouth twice daily for three weeks followed by 20 mg once daily

●

Apixaban - 10 mg twice daily for seven days followed by 5 mg twice daily

●

Edoxaban - 60 mg once daily

●

Dabigatran - 150 mg twice daily

DURATION OF THERAPY

Most patients with a first episode of DVT (provoked or unprovoked) should receive anticoagulation for a minimum of three months. Extending anticoagulation beyond three months is NOT routinely considered in patients who have a provoked DVT with the following: transient risk factors, assuming the risk factor is no longer present (eg, surgery, cessation of hormonal therapy), isolated distal DVT, sub segmental or incidental pulmonary embolism (PE), or those in whom the risk of bleeding is considered to be high. Patients who should be considered as candidates for indefinite anticoagulation are recurrent VTE and diagnosed thrombophilia.

SUMMARY AND RECOMMENDATIONS

Anti - coagulation is the main stay of treatment of DVT. CDT is reserved for select patients in centres with the expertise to perform the procedure.

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Pulmonary Embolism Harinder Singh Bedi

Pulmonary embolism (PE) and deep vein thrombosis (DVT) together constitute one of the “big three” cardiovascular diseases, the other two being myocardial infraction (MI) and stroke. Venous thrombombolism (VTE) encompasses PE and DVT and causes more than 100,000 deaths annually in the United States. The in-hospital case fatality rate for patients who present with hemodynamic instability is approximately 30%, 10-fold higher than for patients who are haemodynamically stable. Advances in diagnostic therapeutic and preventive strategies along with a better understanding of pathophysiology have helped us in improving results of therapy.

PE can elicit a complex cardiopulmonary response that includes increased pulmonary vascular resistance due to vascular obstruction, neurohumoral agents, or pulmonary artery baroreceptors; impaired gas exchange caused by increased alveolar dead space from vascular obstruction and hypoxemia from alveolar hypoventilation and right to left shunting as well as impaired carbon monoxide transfer caused by loss of gas exchange surface ; increased airway resistance due to bronchoconstriction and decreased pulmonary compliance due to lung hemorrhage and loss of surfactant.

Availability of new oral anticoagulant such as rivaroxaban allows the management of PE and DVT without any parenteral anticoagulant for a majority of patients. For patients requiring advanced therapy new invasive tools such as ultrasound facilitated and catheterassisted thrombolysis with low dose tissue plasminogen activator therapy promise a lower rate of hemorrhagic complications than that associated with traditional systemically administered thrombolysis.

As obstruction increases pulmonary artery pressure rises. Further increase in pulmonary vascular resistance and pulmonary hypertension result from secretion of vasoconstrictors such as serotonin,reflex pulmonary artery vasoconstriction and hypoxemia. The overloaded right ventricle releases cardiac biomarkers such as pro-B type natriuretic peptide (pro-BNP), brain natriuretic peptide (BNP) and troponin, all of which portend an increased likehood of adverse clinical outcome.

AETIOLOGY

The sudden rise in pulmonary artery pressure abruptly increases right ventricular after load with consequent elevation of right ventricular wall tension followed by right ventricular dilation and dysfunction. As the right ventricle dilates the interventricular septum shifts towards the left leading to underfilling and decreased left ventricular diastolic distensibility. With hampered filling of the left ventricle systemic cardiac output and systolic arterial pressure both decline impairing coronary perfusion and producing myocardial ischemia. Elevated right ventricular wall tension after massive PE reduces right coronary artery flow and increases right ventricular myocardial oxygen demand causing ischemia. Perpetuation of this cycle can lead to right ventricular infarction circulatory collapse and death.

Stasis,hypercoagulabilty and endothelial injury (Virchow’s triad) activate the pathophysiology cascade leading to VTE (Figure 1). Venous thrombic contain fibrin, red blood cells, platelets and neutrophils. From the leg these clots migrate to the lungs and produce a PE.

CARDIOPULMONARY DYNAMICS

CLASSIFICATION AND RISK STRATIFICATION OF PULMONARY EMBOLISM

Fig. 1: Virchow's triad

Classification of acute PE is based on assessing clinical markers, markers of RV dysfunction and markers of myocardial injury. The classification assists with prognostication and clinical management. Because PE manifests with a wide spectrum of acuity ranging from mild to severe; rapid and accurate risk stratification is of paramount importance. Low risk patients have an excellent prognosis with intensive anticoagulation. High risk patients may require intensive hemodynamic

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and respiratory support with inotropes or mechanical ventilation, whereas the PE itself is managed with advanced therapy such as systemic thrombolysis, pharmacomechanical catheter assisted therapy,vena cava filter placement, or surgical embolectomy.

VENOUS DISORDERS

The three key components for risk stratification are given in Table 1. PE is divided into 3 categories: massive, sub-massive and low risk. Massive PE accounts for 5% to 10% of cases. Submassive PE is more common, occurring in approximately 20% to 25% of patients. Low risk PE constitutes the majority of PE cases-approximately 70%.

MASSIVE PULMONARY EMBOLISM

Patients with massive PE present with cardiogenic shock. Associated renal insufficiency,hepatic dysfunction and altered mentation are common findings. Thrombosis is widespread affecting at least half of the pulmonary arterial vasculature. Clot typically is present bilaterally, sometimes as a “saddle” PE. Dyspnea usually is the most prominent symptom; chest pain is unusual,transient

Table 1: Components for risk stratification in PE Clinical markers

Shock Hypotensiona

Markers of RV dysfunction

RV dilatation, hypokinesis or pressure overload on echocardiography RV dilatation on spiral computed tomography BNP or NT-proBNP elevation Elevated right heart pressure

Markers of

Cardiac troponin T or I positive

myocardial injury BNP = brain natriuretic peptide; NT-proBNP = N-terminal proBNP; RV = right ventricle; aDefined as a systolic blood pressure <90 mmHg or a pressure drop of ≥ 40 mmHg for > 15 min if not caused by new-onset arrhythmia, hypovolemia or sepsis.

cyanosis is common, and systemic arterial hypotension requiring inotropes occurs frequently. The mortality risk markers and treatment options are given in Table 2.

SUBMASSIVE PULMONARY EMBOLISM

Patients with submassive PE present with moderate or severe right ventricular hypokinesia as well as elevations in troponin, pro-BNP, or BNP but they maintain normal systemic arterial pressure. Usually one third or more of the pulmonary artery vasculature is obstructed in these patients. Most survive but may require escalation of therapy with pressure support or mechanical ventilation.

LOW RISK PULMONARY EMBOLISM

Those patients designated as having low risk PE exhibit no markers of an adverse prognosis. They present with normal systemic arterial pressure, no cardiac biomarkers release, and normal right ventricular function. They often prove to have an anatomically small PE and appear clinically stable. Adequate anticoagulation results in an excellent clinical outcome.

PULMONARY INFARCTION

Pulmonary infraction is characterized by pleurtitic chest pain that may be unremitting or may wax and wane. Occasionally it is accompanied by hemoptysis. The embolus usually lodges in the peripheral pulmonary arterial tree, near the pleura. Tissue infraction usually occurs 3 to 7 days after embolism. Signs and symptoms often include fever,leukocytosis, elevated erythrocyte sedimentation rate and radiologic evidence of infraction.

LOWER- EXTREMITY DVT AND THE RELATIONSHIP BETWEEN DVT AND PE

In DVT - the more proximal the thrombus is within the deep leg veins, the more likely it is to embolize and cause acute PE. When venous thrombi detach from their sites of formation, they travel through the right atrium and right ventricle and then enter the pulmonary arterial circulation. An extremely large embolus may lodge at the bifurcation of the pulmonary artery, forming a saddle embolus. In many patients with large PEs ultrasonographic evidence

Table 2: Risk markers of mortality and treatment of PE Risk Markers PE-related early Mortality Risk

CLINICAL (shock or hypotension)

RV dysfunction

Myocardial injury

High >15%



(+)a

Intermediate 3-15%



Low <1%



Non High

Potential treatment implications Thrombolysis or embolectomy Hospital admission Early discharge or home treatment

In the presence of shock or hypotension it is not necessary to confirm RV dysfunction/injury to classify as high risk of PE-related early mortality. PE = pulmonary embolism; RV = right ventricle.

PE should be suspected when there is evidence of

Table 3: Wells Criteria for DVT Probability Clinical Characteristic

Score 1

Paralysis, paresis, or recent plaster immobilization of the lower extremities

Recently bedridden >3 days or major surgery within 12 weeks requiring general or regional anesthesia

Localized tenderness along the distribution of the deep venous system

Entire leg swollen

Calf swelling 3 cm larger than asymptomatic side (measured 10 cm below tibial tuberosity)

Pitting edema confined to the symptomatic leg Collateral superficial veins (nonvaricose)

Alternative diagnosis at least as likely as deep venous thrombosis

-2

of DVT is lacking probably because the clot has already embolized to the lungs.

EPIDEMIOLOGY

Clinical risk factors

Risk factors for VTE include advancing age, cancer, previous VTE, venous insufficiency, pregnancy, trauma, major surgery, frailty and immobility.

Hypercoagulable States

Classically the pathogenesis of PE has been dichotomized as caused by either inherited (Primary) or acquired (secondary) risk factors. A combination of thrombohillia and acquired risk factors, however usually precipitate thrombosis. The two most common identified genetic causes of thrombophilia are factor V Leiden and the prothrombin gene mutation.

Diagnosis

One of the greatest challenges in diagnosis PE is that it can masquerade as other illness, thereby confounding the diagnostic workup. The most useful approach is a clinical assessment of likehood, based on presenting symptoms and signs, in conjunction with judicious diagnostic testing. A normal plasma D-dimer level usually can rule out PE. When PE is strongly suspected, a D-Dimer need not be obtained; in most cases with high clinical suspicion, it is appropriate to proceed directly to chest computed tomography(CT) imaging.

Clinical Presentation

Dyspnea is the most frequent symptom, and tachypnea is the most frequent sign of PE. Severe dyspnea, syncope or cyanosis portends a major life threatening PE, in which the clinical picture often is devoid of chest pain. Paradoxically severe pleurtitic pain often signifies that the embolism is small and not life threatening and located in the distal pulmonary arterial system, near the pleural lining.

venous thrombosis or predisposing VTE risk factors;

acute cor pulmonale ( acute right ventricular failure), with features such as distended neck veins, right sided S3 gallop, right ventricular heave tachycardia, or tachypnea; especially if

echocardiographic findings of right ventricular dilation and hypokinesia or electrocardiographic evidence of acute cor pulmonale manifested by a new S1Q3T3 pattern, new right bundle branch block or right ventricular ischemia manifested by inferior T wave inversion or T wave inversion in leads V1 through V4.

Clinical decision rules can stratify patients into groups with high clinical likehood or non-high clinical likehood of PE, using a set of seven bedside assessment questions known as the Wells Criteria (Table 3). Pretest probability score- low≤ 0, moderate if 1–2, and high if ≥ 3. If both the legs are symptomatic score the more severe leg

Differential Diagnosis

DD includes - Aortic dissection, Cardiac tamponade, MI, corpulmonale, TR, acute exacerbation of COPD, pneumonia In critically ill patients one must have a low threshold for entertaining PE esp in the setting of risk factors such as malignancy, recent surgery, central lines or prior VTE/ DVT

Lab testing and Bedside Tools 1.

D-Dimer – 95% sensitive for VTE - but also elevated in malignancy, infection, surgery, MI

Hypoxia: highly sensitive but poorly specific

ECG: tachycardia, S1 Q3 T3 pattern, low voltage, RBBB, P pulmonale. Helps to rule out acute MI and acute pericarditis

IMAGING METHODS

Chest Radiography

A near normal radiographic appearance in the setting of severe respiratory comprise is highly suggestive of massive PE. Major chest radiographic abnormalities are uncommon. Focal oligemia indicates massive central embolic occlusion. A peripheral wedge shaped density above the diaphragam (Hampton hump) – arrow in Fig 1 - usually indicates pulmonary infarction.

Lung Scanning

Pulmonary radionuclide perfusion scintigraphy (lung scanning) uses radiolabedled aggregates of albumin or microspheres that lodge in the pulmonary microvasculature. Patients with large PE often have multiple perfusion defects. Three principal indications for obtaining a lung scan are :

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Active cancer (treatment ongoing, within previous 6 months, or palliative)

881

VENOUS DISORDERS

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Fig. 1: Chest X-ray and CT showing a peripheral pulmonary infarct (arrow)

Fig. 2 : CT scan showing a large saddle pulmonary embolus (PE) •

renal insufficiency

•

anaphylaxis occurring in reaction to intravenous contrast agent

•

pregnancy (lower radiation exposure to the fetus).

Chest computed Tomography (Figures 2 & 3)

Chest CT has supplanted pulmonary radionuclide perfusion scintigraphy as the initial imaging test in most patients with suspected PE, allowing ready visualization of massive PE and confirmation of surgical or catheter accessibility to the centrally located thrombus. The chest CT scan also can detect other pulmonary diseases that manifest in conjunction with PE or explain a clinical presentation that mimics PE. These diseases include dissection aorta,pneumonia, atelectasis, pneumothorax, and pleural effusion.

Echocardiography

Echocardiography findings are normal in approximately one half of unselected patients with acute PE, so echocardiography is not recommended as a routine diagnostic test for PE. Echocardiography is however a rapid practical and sensitive technique for detection of right ventricular overload among patients with established and large PE. Moderate or severe right ventricular

Fig. 3: Large pulmonary embolus (PE) in right pulmonary artery hypokinesis, persistent pulmonary hypertension, patent foramen ovalen and free floating thrombus in the right atrium or right ventricle are factors associated with high risk of death or recurrent thromboembolism. Echocardiography also can help identify illness that may mimic PE, such as MI and pericardial disease.

Venous Duplex Ultrasonography

The primary diagnostic criterion for DVT on ultrasound imaging is loss of vein compressibility. At least one half of the patients with PE have no imaging evidence of DVT. Therefore if the level of clinical suspicion of PE is moderate or high, patients even without evidence of DVT should undergo further investigation for PE.

Magnetic resonance imaging

Gadolinium enhanced magnetic resonance angiography (MRA) is far less sensitive than CT for the detection of PE but unlike chest CT or catheter based pulmonary angiography, MRA does not require ionizing radiation or injection of an iodinated contrast agent. Pulmonary MRA also can asses right ventricular size and function.

Invasive Pulmonary Angiography

Invasive pulmonary angiography formerly was the reference standard for the diagnosis of PE, but it is now rarely performed as a diagnostic test. Use of this modality is routine however when interventions such as pharmacomechanical catheter assisted therapy are planned.

Contrast Venography

Overall strategy: An Integrated Diagnostic Approach

Suspected PE can be investigated with a wide array of diagnostic tests. The first step in an integrated diagnostic strategy is a directed history and physical examination to assess the clinical likehood for acute PE. The findings of non-high clinical probability is followed by D-dimer testing. A normal D-dimer assay usually rules out PE. If the D- dimer is elevated chest CT usually provides the definitive diagnosis or exclusion of PE.

THERAPY

Anticoagulation therapy for acute pulmonary embolism: Parenteral Anticoagulation

Unfractionated Heparin

Anticoagulation is the cornerstone of treatment for PE. It prevents additional thrombus formation and permits endogenous fibrinolytic mechanisms to lyse at least some of the clot that has already formed. Heparin does not directly dissolve thrombus. For patients with average bleeding risk, UFH should be started with an intravenous bolus of 80 units/kg, followed by a continuous infusion at 18 units/kg/hr. The aPTT should be targeted between 1.5 and 2.5 times the control value. The therapeutic range commonly is 60 to 80 seconds. The short half life of UFH is advantageous for patients who may require subsequent insertion of an inferior vena cava filter systemic thrombolysis, catheter directed pharmacomechanical therapy, or surgical embolectomy.

Low Molecular Weight Heparin

Low molecular weight heparin (LMWH) has greater bioavailability with a more predictable dose response and a longer half life compared with UFH. These features permit weight based LMWH dosing without laboratory tests, because no dose adjustment is needed in most instances. LMVH has revolutionized the management of DVT and has shortened treatment from a mandatory minimum 5 day hospitalization with intravenous UFH to either an overnight stay or outpatient therapy for most patients.

Warfarin Anticoagulation

Warfarin is a vitamin K antagonist. The full anticoagulant effect of warfarin becomes evident after 5 to 7 days. For

883

Warfarin Overlap with Heparin

Overlapping warfarin for at least 5 days with an immediately effective parenteral heparin (UFH, LMWH) allows quick onset of therapy and counteracts the procoagulant effect of unopposed warfarin.

Novel Oral AntiCoagulants NOAC

Novel oral anticoagulants have a rapid onset of action and provide systemic levels of anticoagulation within several hours of ingestion. They are prescribed in fixed doses without laboratory coagulation monitoring and have minimal drug-drug or drug-food interactions. These agents have a short half life, so when they are stopped for an invasive diagnostic or surgical procedure no bridging is needed. They are noninferior to warfarin for efficacy and are equivalent, or in some cases superior to warfarin for safety.

Oral monotherapy with Rivaroxaban for Acute Deep vein Thrombosis or Acute Pulmonary Embolism

In November 2012, the FDA approved rivaroxaban a direct inhibitor of activated factor x, as oral monotherapy for acute DVT and acute PE. This approval changes the fundamental approach to the treatment of VTE. Completely oral therapy with rivaroxaban is a prudent option for patient with DVT or PE at low or moderate risk for adverse events using a 3 weeks loading dose of 15 mg twice daily, followed by 20 mg once daily thereafter. For most patients the traditional approach using initial parenteral anticoagulation as a bridge to warfarin will no longer be necessary. Home treatment of acute PE will be facilitated. In the EINSTEIN â&#x20AC;&#x201C;PE trial 4833, patient with acute symptomatic PE were treated with either rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg once daily, or with standard therapy using enoxaparin as a bridge to an adjusted dose vitamin K antagonist, usually warfarin. The principal efficacy outcome of symptomatic recurrent venous thromboembolism occurred in 2.1% receving rivaroxaban and 1.8% receving standard therapy achieving statistical noninferiority for rivaroxaban. Rivaroxaban had superior safety. Major bleeding rates were 1.1% for rivaroxaban verus 2.2% for enoxaparin bridging to warfarin (P=0.003). As summarized in the American College of Chest Physicians (ACCP) 2012 Guidelines, â&#x20AC;&#x153;for acute DVT or PE we recommended initial parenteral anticoagulation or anticoagulation with rivaroxaban.

Selection of an Optimal Anticoagulant for extended duration Anticoagulation

The choices for extended-duration anticoagulation have broadened with a wide array of options including warfarin, LMWH, aspirin rivaroxaban, dabigatran and apixaban now available. Standard intensity anticoagulation with warfarin is the conventional time honored approach with a target INR range of 2.0 to 3.0.

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Although contrast phlebography was once the reference standard for DVT diagnosis, venograms are rarely obtained now for diagnostic purpose. Venography is the first step, however for evaluation of patients with large femoral or iliofemoral DVT who will undergo invasive pharmacomechanical catheter-directed therapy.

patients with VTE, the usual target INR is between 2.0 and 3.0.

VENOUS DISORDERS

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Table 4: Advanced therapy for PE Technique

Description

Thrombolysis

Catheter in main PA. bolus of thrombolytic followed

Table 5: Contraindications to thrombolysis Comments

No reduced risk of blccdmg documented No evidence of benefit of by infusion Often combined catheter-directed with mechanical lysis over fragmentation to systemic unless combined with increase surface fragmentation area of thrombus exposed to thrombolytic

Fragmentation

Breaking up targe central clot with catheter device: device rotated by operator Fragments migrate distally Often combined with local thrombolysis

Embolectomy

Balloon angioplasty

Percutaneous thrombectomy

Improved rccanalization wim thrombolytics Example: Cook Europe rotatable pigtail catheter

Catheter directed to thrombus and manual suction used to remove thrombus

Examples: Greenfield embolceiomy device

Compression of embolus Often combined with local thromboryso

Results in partial fragmentation of embolus Difficult to tell if thrombolytic explains hemodynamic benefits when combined Examples: Wallstent, Giancurco Z stents

Clot pulverized and removed via catheter by rotation of device or hydrodynam* vortex

Examples: Amplatz thrombectomy device, the Hydrolizcr. Aspirex

Advanced therapy (In addition to anticoagulation ) for acute pulmonary embolism

American Heart Association (AHA) and ACCP guideline recommend advanced therapy for patients with massive

Absolute Contraindications

Relative Contraindications

Major trauma, surgery, head trauma within 3 weeks

Cancer

Prior hemorrhagic stroke

Age > 75-80 Transient ischemic attack within 6 months

Ischemic stroke within prior 6 months

Oral anticoagulant therapy

Central nervous system neoplasm

Noncomprcssiblc punctures

Gastrointestinal bleeding within one month

Traumatic resuscitation

Active bleeding

Advanced liver disease

Refractory hypertension Infective endocarditis Active peptic ulcer Pregnancy or within one week postpartum

PE and for patients with submassive PE at the unstable end of the spectrum. These advanced therapy options include full dose systemic thrombolysis, pharmacomechanical catheter directed therapy (usually with low dose thrombolysis), surgical embolectomy, and inferior vena cava filter placement (Table 4).

Systemic Thrombolysis Administered Through a Peripheral Vein

The FDA has approved alteplase for massive PE in a dose of 100mg delivered as a continuous infusion over 2 hours, without concomitant heparin. Unlike that for MI effective use of thrombolysis for PE shows a wide â&#x20AC;?timewindow â&#x20AC;&#x153;of benefit. Patients who receive thrombolysis up to 14 days after onset of new symptoms or signs can derive benefit, probably because of the effects on the bronchial collateral circulation. Patients being considered for thrombolysis require screening for contraindications (Table 5). Intracranial hemorrhage is the most feared and severe complication.

Advances in pharmacomechanical Catheter Directed Therapy including Thrombolysis

The 1% or greater rate of intracranial hemorrhage in patients with PE receving systemic thrombolysis has dampened enthusiasm for this potential life saving therapy. Pharmacomechanical catheter directed reperfusion, however holds the promise of good efficacy with lower rates of major bleeding owing to lower doses of thrombolytic agent. The typical dose of tissue plasminogen activator (tPA) in a pharmacomechanical catheter based procedure for example is 25 mg or less-compared with 100 mg or systemic administration. Interventional mechanical techniques usually performed on conjunction with low dose thrombolysis include mechanical fragmentation and aspiration of thrombus through standard pulmonary artery catheter,

885

clot pulverization with a rotating basket catheter, rheolytic thrombectomy and pigtail rotational catheter embolectomy. Successful catheter embolectomy rapidly restores normal blood pressure and decrease hypoxemia. Low intensity ultrasound facilitated fibrinolysis is a novel approach. Ultrasound disaggregates fibrin strands increase clot permeability, and disperses infused fibrinolytic drug into the through acoustic microstreaming effects.

Surgical Embolectomy

Emergency surgical embolectomy has reemerged for the management of patients with massive PE and systemic arterial hypotension or submassive PE with severe right ventricular dysfunction in whom contraindications preclude thrombolysis. This procedure also is suitable for patients with acute PE who require surgical excision of a right Atrial thrombus or closure of a patent foramen ovale. Surgical embolectomy also can be used as resuce therapy for patients in whom PE is refractory to thrombolysis. Result are best when patients undergo surgery before they become pressor dependent and before the onset of cardiogenic shock and multisystem organ failure. The surgery is done under hypothermic cardio-pulmonary bypass. The heart is arrested, the pulmonary artery opened and the clots carefully and completely removed â&#x20AC;&#x201C; Figure 4. With better methods of myocardial preservation and timely surgery the results are good.

Inferior Vena Cava Filters

The AHA supports the use of inferior vena cava filters for patients with (1) contraindication to anticoagulation ;(2) recurrent PE despite therapeutic levels of anticoagulation

Fig. 5: Filter (F) in IVC and (3) very poor cardiopulmonary reserve including patients with massive PE. For patients with a temporary contraindication to anticoagulation, placement of a nonpermanent, retrievable filter is appropriate (Figure 5). Retrievable filters can be left in place for weeks to months or can remain permanently, if necessary.

CONCLUSION

PE remains a diagnostic and therapeutic challenge. With advances in understanding of the disease process, a high index of suspicion and quicker and better imaging techniques and therapeutic modalities the results of therapy and likely to get better.

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Fig. 4: Clots removed from the pulmonary artery in 2 different patients. RA = right atrium, LPAS = left pulmonary artery, RPA = right pulmonary artery

C H A P T E R

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Catheter directed Thrombolysis in Deep Vein Thrombosis ( DVT), Technique and Results Over Last Decade DB Dekiwadia

ABSTRACT

DVT is recognized clinically by painful edema of the leg, tender calf thigh and iliac fossa. Vascular Ultrasonographyis diagnostic. Untreated DVT may result in pulmonary embolism (PE), pulmonary hypertension or Post thrombotic syndrome. In CATHETER DIRECTED THROMBOLYSIS a Tissue Plasminogen Activator (TPA). (Urokinase, or r-tpa) is directly delivered in the thrombus and most effective clot lyses is achieved. A retrospective analysis of 243 CASES OF DVT, treated with Urokinase was done. This included 150 males and 93 females. Age of 18 to 80 years. Duration of symptoms 1 week to 4 months. 168 cases with post procedure warfarin and 75 of Rivaroxaban. USG guided puncture of Popliteal vein or PTV was done to place the sheath Through sheath and a multihole catheter thrombolysis done usimgh urokinase 250000units/hr. Check fluoroscopy & catheter repositioning as needed. Adjuvant I/V heparin. Procedure terminated at complete resolution or a max. of 1 million unit infusion. Post procedure oral anticoagulant was given with INR set at 2.50.

Since January 2015 till date: Post procedure rivaroxaban initially 15 mg/day for1 month and thenafter 10 mg/day for two months. This was to help resolve small thrombotic load and prevention os VT. After 3 mnths 75 mg/ day aspirin anti platelet regimn was started to last for 1 year and review at one year. A check usg vein study after 3 months and at 6 months.

RESULTS

Complete Resolution: 206 Cases, Partial Resolution 33 Cases Re-thrombosis: 2 Cases. No Result: 2 cases

FOLLOW UP

8 YRS. Post thrombotic syndrome five, secondary varicose veins: 02

CONCLUSION

TPA delivered intrathrombus gives optimum results in DVT, preserves valves and prevents post thrombotic syndrome. Recent addition of rivaroxaban and omission of warfarin has changed the need to perform INR and the socio economic burden to the patient.