Upper extremity deep vein thrombosis (UEDVT) is an

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1 Update Article Upper Extremity Deep Vein Thrombosis S Malhotra*, VPS Punia** Abstract Upper extremity deep vein thrombosis (UEDVT) is a rare thrombotic disorder (1-4% or all DVT), but it has a potential for considerable morbidity in the form of pulmonary embolism, persistent upper extremity pain and swelling, superior vena cava syndrome and loss of vascular access. Newer noninvasive methods such as duplex ultrasound and magnetic resonance angiography facilitate early diagnosis. Early catheter directed thrombolysis followed by anticoagulation prevent long-term sequalae. INTRODUCTION Upper extremity deep vein thrombosis (UEDVT) is an increasingly important clinical entity with potential for considerable morbidity. Pulmonary embolism (PE) is present in upto one-third of patients with UEDVT. 1 When compared with the lower extremities, the venous pathways of the upper extremities are less likely to develop thrombus because of increased flow, gravitation effects and the absence of stasis. There are fewer valves in the upper extremities, and no counterpart to the soleal veins in the lower extremities is found. 2 The exact incidence of deep venous thrombosis of the upper extremities is unknown. A prevalence of two cases per 1000 hospital admissions 3 has been reported in a recent series. UEDVT accounts for approximately 2% of all cases of deep vein thrombosis. Originally described by Paget in 1875 and Van Schroetter in 1884, it was long felt to be a disorder associated with either trauma or spontaneous thrombogenesis occurring after streneous exercise or profound hyperabduction of the arm. Recently there is increasing incidence directly related to use of central venous catheters for cancer chemotherapy, bone marrow transplantation, dialysis and parenteral nutrition. 4 Pathogenesis Upper extremity deep vein thrombosis (UEDVT) most commonly refers to thrombosis of the axillary and/or subclavian veins. It can be classified as primary or secondary on the basis of pathogenesis (Table 1). Primary Thrombosis Primary UEDVT is a rare disorder (2 per person per year)..5 This term refers to effort thrombosis which is also *Specialist; ** Sr. Specialist, Department of Medicine, VMMC and Safdarjang Hospital, New Delhi Received : ; Revised : ; Re-revised : ; Accepted : Table 1: Causes of upper extremity DVT I Primary A. Traumatic * Effort thrombosis * Blood vessel injury B. Increased distal venous pressure *` Cervical ribs * Long transverse processes of cervical spine * Musculofascial bands of subclavius muscle and costoclavicular ligament * Clavicular or 1st rib anomalies D. Hypercoagulable state * Antiphospholipid antibodies * Factor V Leiden * Antithrombin III deficiency * Protein C & S deficiency * Prothrombin gene mutation * Hyperhomocystinemia * Pregnancy and oral contraceptive use II Secondary A. Central venous catheters B. Malignant disease * Lymphoma/Leukaemia * Pancreas cancer * Breast cancer * Chest disorders lung, pleura and oesophagus * Gastrointestinal tract C. Pacemakers D. Intravenous Drug Abuse III Idiopathic may be associated with occult cancer known as Paget Schroetter syndrome and includes patients with idiopathic UEDVT. Patients with Paget Schroetter syndrome develop spontaneous UEDVT usually in the dominant arm with physical activities such as rowing, wrestling, weight lifting and painting which involve abduction or hyperabduction of the upper extremity. The pathogenesis 6 involves a combination of exertion causing microtrauma of the vessel intima with activation of the coagulation cascade with cessation of venous flow from a reflex valsalva maneuver. JAPI VOL. 52 MARCH

2 Thoracic outlet obstruction refers to compression of subclavian vein at its point of exit at the thoracic inlet. This intermittent positional extrinsic vein compression can be produced 7 by cervical ribs, long transverse process of the cervical spine, musculofascial bands and clavicular or first rib anomalies. In contrast to Paget Schroetter syndrome, idiopathic UEDVT may have no known trigger or obvious underlying disease. In one study, 8 one-fourth of patients were associated with occult cancer and developed lung cancer or lymphoma within one year of follow up. The prevalence of hypercoagulable states in patients with UEDVT is uncertain. The yield of these tests is highest in those with idiopathic disease, a positive family history and recurrent DVT or pregnancy loss. A recent study 9 has shown that presence of lupus anticoagulant or anticardiolipin antibodies (27%) was the most frequent finding. The other abnormalities that have been found include factor V leiden, prothrombin gene mutation, hyperhomocystinaemia and rarely deficiency of protein C, protein S and antithrombin- III. Secondary Thrombosis Secondary UEDVT accounts for most cases of thrombosis. Majority of patients (33-60%) of UEDVT are asymptomatic and only fewer than 3% patients on central venous catheters and pacemakers develop clinically evident UEDVT. Malignant disease was present in 63% of patients with known DVT of the upper extremities in a recent series. 5 The incidence of DVT increased in those cancer patients who had central venous catheters. Catheter-induced vessel wall damage and impedance of blood flow through veins may be the predisposing cause in such cases. 11 Those patients who had implanted permanent pacemakers 12 with prior use of temporary pacemakers and low left ventricular ejection fractions (less than 40%) had a much higher incidence of venous thrombosis. Symptomas and Signs Axillary or subclavian vein thrombosis may be completely asymptomatic or patients complain of vague shoulder or neck discomfort and arm oedema. If thrombosis causes obstruction of superior vena cava, patients complain of facial oedema, head fullness, blurred vision, vertigo and dyspnea. Patients with thoracic outlet obstruction usually have pain that radiates into the fourth and fifth digits via the medial arm and forearm. Adson test is done in which the examiner extends the patients, arm on the affected side while the patient extends the neck and rotates the head towards the same side. The test is positive if there is weakening of the radial pulse with deep inspiration which suggests compression of the subclavian artery. Physical examination may reveal fever due to thrombosis, underlying septic infection or presence of malignancy. A high index of suspicion in those with arm and hand oedema and dilated cutaneous veins over the chest or upper arm, can clinch the diagnosis. The signs and symptoms (Table 2) of Table 2 : Signs and symptoms of UEDVT Symptoms Signs 1. Axillary or * Shoulder or neck * Supraclavicular fullness subclavian vein discomfort * Palpable cord thrombosis * Arm or hand * Arm or hand oedema oedema * Cyanosed extremity * Dilated vein * Jugular vein distention 2. Throacic outlet * Pain rediating * Brachial plexus syndrome to arm/forearm tenderness * Hand weakness * Arm or hand atrophy * Positive Adson test UEDVT are, however, non-specific and have to be differentiated 13 from lymphoedema, neoplasms, muscle injury and superficial vein thrombosis. DIAGNOSIS 1. Duplex Ultrasound : This is the initial imaging test of choice for diagnosing UEDVT because this is a non-invasive and reproducible technique with high sensitivity and specificity for assessment of cephalic, axillary and subclavian veins. But since jugular vein is best assessed by compression ultrasonography and brachiocephalic vein is visible only on venography and magnetic resonance angiography, this modality cannot be used. Non-compressibility 14 of venous segment, intraluminal thrombus and flow abnormality are sufficient for the diagnosis of DVT of the upper extremities. 2. Contrast Venography : This procedure involves injection of 30 ml contrast in the antecubital vein or distal arm vein of the affected extremity and subsequently digital subtraction images of the brachial, axillary, subclavian and superior caval veins are obtained at a rate of one frame per second. Although venography demonstrates the venous anatomy very well, technical difficulty can occur in cannulating the vein in an oedematous arm. The various reactions produced by iodinated contrast agents circumvent its routine use in clinical practice. Hence venography should be used only if suspicion for clot remains high despite a negative ultrasound. 3. Magnetic Resonance Angiography : This is an accurate, noninvasive method for detecting thromhus in the central thoracic veins such as SVC and brachiocephalic vein. This method correlates extremely well with venography 16 and provides complete evaluation of central collaterals and blood flow. 4. CT Scan : Although this method has injection of contrast 13 and requires injection of contrast agent, it has the ability to detect central thrombus especially in brachiocephalic vein thrombosis. It can also detect the presence of extrinsic vessel compression. COMPLICATIONS AND PROGNOSIS Recent studies have shown that complications of deep JAPI VOL. 52 MARCH 2004

3 venous thrombosis of upper extremity occur frequently. 13 Pulmonary embolism (8-36%) is most often asymptomatic. Acute presentation is more often seen in a setting of catheter related DVT with underlying malignancy compared to those with effort related thrombosis of the subclavian veins. Sometimes recurrent thromboembolism can present with pulmonary hypertension and right heart failure and may be fatal. In some cases catheter removal and fibrinolytic therapy may predispose to breakup of fibrin emboli and cause pulmonary embolism. Post-thrombotic syndrome (upto 50% cases) caused by venous hypertension can vary from mild oedema with little discomfort to severe limb swelling associated with pain and ulceration. Recurrent thrombosis (2-15%) after cessation of anticoagulation treatment is most frequent in Paget Schroetter syndrome and a recent series 18 has shown that the recurrence rate can be markedly reduced by early use (less than 7 days) of catheter directed thrombolysis together with first rib resection. The other reported complications (Table 3) are rare but loss of vascular access can be a practical problem since it prevents administration of essential medication and nutrition. Table 3 : Reported complications of UEDVT 1. Chronic venous insufficiency * Pain * Swelling 2. Venous gangrene 3. Superior vena cava syndrome 4. Catheter infection 5. Acute pulmonary embolism 6. Recurrent pulmonary embolization * Pulmonary hypertension * Right sided heart failure 7. Thoracic duct obstruction * Chylous pleural effusion * Chylous pericardial effusion 8. Brachial plexopathy The case fatality rate for untreated UEDVT can be as high as 10%, a rate similar to that seen with pulmonary embolism originating from the lower extremities. TREATMENT There is no consensus on treatment of UEDVT because of difficulty in obtaining adequate number of patients for a good prospective study. Firstly only diagnosis and initiation of treatment before the thrombus becomes organized is vital to the successful outcome of treatment. Secondly 19 because the underlying cause of primary UEDVT is usually an anatomic abnormality, surgical decompression of the subclavian vein is essential to prevent recurrent thrombosis. Hence a multidisciplinary treatment strategy including both medical and surgical management is needed. The various treatment modalities (Table 4) available have to be individualized in each patient. The symptomatic management includes anterior elevation of the affected Table 4 : Treatment options for UEDVT Limb elevation Graduated compression arm sleeve Anticoagulation * Unfractionated heparin as bridge to warfarin * Low molecular weight heparin as bridge to wafarin * Low molecular weight heparin as monotherapy Catheter directed thrombolysis Suction thrombectomy Vein stenting Surgical thrombectomy Thoracic outlet decompression * Surgery * Physical therapy Superior vena cava filter extremity, best rest and heat. In cases of secondary UEDVT, removal or correction of the predisposing cause (central catheter, infection, IV drug abuse) is important. Anticoagulation Anticoagulation is the mainstay of therapy. It facilitates the patency of venous collaterals and retards the propagation of the thrombus, although clot lysis is affected very little. Typically, unfractionated heparin is used as a bridge to warfarin therapy. Low molecular weight heparin as a bridge may be safe and effective for out-patient treatment and for reducing the duration of hospitalization. A recent meta analysis 20 has shown low molecular weight heparin and unfractionated heparin to be equivalent with respect to efficacy and major bleeding but low molecular weight heparin was associated with a 25% reduction in relative risk of death in venous thromboembolism compared to unfractionated heparin. Warfarin therapy should be continued for at least 6 months and probably longer in those with coagulation abnormality with a goal INR of 2.0 to 3.0. Patients who have received only symptomatic treatment and no anticoagulation have a high incidence of recurrent symptoms and long term disability from chronic venous hypertension in the upper limbs. Thrombolysis In the upper limbs, lytic therapy restores early venous patency, minimizes damage to vessel endothelium and reduces risk of post-thrombotic syndrome which is characterised by chronic arm aching and swelling. Catheter directed thrombolysis with recombinant tissue plaminogen activator (rtpa) 13 as a continuous infusion of 1-2 mg/hour for at least 8 hours or reteplase at a dose 21 of 1.0 unit/hour, in a recent study, have been able to achieve thrombolytic success in 92% of patients on follow up serial venography. The best candidates for thrombolysis are young healthy patients with primary UEDVT presenting within the first week after thrombosis, patients with symptomatic SVC syndrome and those who require insertion of mandatory central venous catheter. JAPI VOL. 52 MARCH

4 Suction Thrombectomy Percutaneous mechanical thrombectomy with devices such as the angiojet 21 is often used in combination with thrombolytics. This procedure can rapidly extract large quantities of thrombus, within 5 days after initial occlusion and thereby reduce the dose and duration of thrombolytic therapy. Surgery The importance of eradicating vein compression in patients with primary UEDVT has been shown to significantly reduce the risk of recurrent thrombosis and long term mobidity. After successful thrombolysis repeat venography of patients is preformed with the shoulder in an abducted position. Those patient showing venous compression on venography should have surgical resection of part of the first rib or clavicle 13 and lysis of dense adhesions around the subclavian veins. Angioplasty and Vein Stenting Those patients with residual stricture after surgery and thrombolytic therapy require balloon venoplasty and stenting (52% in a recent study) to ensure maintenance of patency. 18 Surgical Thrombectomy This procedure restores venous patency but is invasive, carries the risk of general anaesthesia and may be complicated by pneumothorax and brachial plexus damage. Hence this technique should be reserved for refractory cases or who have an infected thrombus as a cause of bacteraemia. 18 Physical Therapy A structured programme 13 to loosen muscles around the subclavian vein, weight loss in the obese and non-steroidal anti-inflammatory drugs may obviate the need for surgery. Those with neurological symptoms require several months of physical therapy before improvement is noted. Superior Vena Cava Filters Patients in whom anticoagulation is contraindicated, has failed or created complications, those who are poor surgical risk and those who are at risk for pulmonary embolism can benefit. CONCLUSION In primary effort thrombosis of subclavian veins, most investigators favour using thrombolytic therapy for patients presenting within first 7 days of venous thrombosis. This is followed by heparin therapy as a bridge to warfarin therapy till patient reaches on INR of Subsequently resection of first rib or clavicle is done to reduce the recurrences. Catheter associated subclavian vein thrombosis (secondary) is best prevented by giving low dose warfarin (1 mg) beginning three days before catheter placement. Since these patients have significant co-morbidity, thrombolytics should be used very cautiously. Surgery is reserved for patients with recurrent vein thrombosis despite lytic therapy and endoluminal stent placement should be used in those with residual stricture after balloon venoplasty. REFERENCES 1. Prandoni P, Polistena I, Bernardi E, et al. Upper extremity deep vein thrombosis. Risk factors, diagnosis and complication. Arch Intern Med 1997;157: Hill SE, Berry RE. Subclavian vein thrombosis: A continuing challenge. Surg 1990;108: Kroger K, Schelo C, Gocke C, et al. Colour Doppler sonographic diagnosis of upper limb venous thrombosis. Clin Sci (London) 1998;94: Hurattas MC, Wright DJ, Fenton AH, et al. Changing concepts of deep venous thrombosis of the upper extremity. Report of a series and review of the literature. Surgery 1988;104: Lindblad B, Tengborn L, Bergqvist D. Deep vein thrombosis of the axillary subclavian veins: epidemiologic data, effects of different types of treatment and late sequelae. Eur J Vasc Surg 1988;2: Zell L, Kindermann W, Marschall R, et al. Paget Schroetter syndrome in sports activities: case study and literature review. Angiology 2001;52: Parziale JR, Akelman E Weiss AP, et al. Throacic outlet syndrome. Am J Orthop 2000;29: Girolami A, Prandoni P, Zanon E, et al. Venous thrombosis of upper limbs are more frequently associated with occult cancer as compared with those of lower limbs. Blood Coag Fibrinol 1999;10: Leebeek RW, Standhouders NA, Van Stein D. Coagulation abnormalities in deep venous thrombosis of the upper extremity. Am J Haematol 2001;67: Henk-Jan Baarslag, Edwin JR. Prospective study of colour Duplex ultrasonography compared with contrast venography in patients suspected of having DVT of upper extremities. Ann Intern Med 2002;136: Luciani A, Clement O, Halimi P, et al. Catheter related upper extremity deep venous thrombosis in cancer patients: a prospective study based on Doppler US. Radiology 2001;344: Da Costa SS, Scalabrini NA, Costa R, et al. 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5 America 2001;19: Dolovich LR, Ginsberg JS, Douketis JD, et al. A meta analvsis comparing low molecular weight heparin with unfractionated heparin in the treatment of venous thromboembolism. Arch Intern Med 2000;161: Castaneda R, Li R, Young K, et al. Catheter directed thrombolysis in deep venous thrombosis with use of reteplase. Immediate results and complications from a pilot study. J Vasc Intern Radiol 2002;13: Kasirajan K, Gray B, Ouriel K. Percutaneous angiojet thrombectomy in the management of extensive deep venous thrombosis. J Vasc Intern Radiol 2001;12: Obituary Dr. PJ Geevarghese Dr. PJ Geevarghese, eminent diabetologist of international reputation and one of the pioneers of diabetes research in India passed away on at the age of 78 following subarachnoid haemorrhage. He was the President, Kerala Diabetes Foundation and executive patron of RSSDI (Research Society for Study of Diabetes in India). He was formerly Director and Professor of Medicine at Medical College, Kottayam and during his long tenure in Government service has graced almost all the then medical colleges in Kerala. In addition he has been visiting Professor at foreign university schools of New York, Marseilles and California. He has done a lot of research work on Pancreatic Diabetes which won international recognition and has authored many monographs like Pancreatic Diabetes (1968), Calcific Paancreatitis and Diabetes in Tropics (1992), A Handbook for Diabetics (8 editions) and Recent Progress in Clinical Diabetes (2002). A spiritual book Holy Trinity and the Apostolic Church was also written by him. After retirement he was practising as Consultant Diabetologist at St. Mary s Diabetes Centre and Krishna Nursing Home in Cochin. During his long and fruitful career, Prof. Geevarghese has been President, Scientific Section, Diabetic Association of India and Indian Society of Pancreatology. He has received a number of awards like Boehringer-Knoll Award, Silver Jubilee Oration Award by Trivandrum Medical College, and the Lifetime Dedication to Diabetes Care award by Novo-Nordisk. R Sajith Kumar Secretary, API Kerala Announcement Second Madras Diabetes Research Foundation (MDRF) - American Diabetes Association (ADA), Postgraduate Course on Diabetes, at Chennai, India, September The second MDRF- ADA Postgraduate Course on Diabetes will be held from 24th to 26th September 2004 at Chennai, India. The meeting will be hosted by the Madras Diabetes Research Foundation, Chennai. For further details contact : Prof V Mohan, MD, Ph D, D Sc, Madras Diabetes Research Foundation, No. 4 Conran Smith Road, Gopalapuram, Chennai , India. Phone : (91 44) , , , Fax : (91 44) , mvdsc@vsnl.com Also visit our website at for details regarding registration charges etc. JAPI VOL. 52 MARCH