Introduction
Venous thromboembolic disease of upper extremities is an unsufficiently known and, perhaps, undervalued clinical issue, which is gaining the special significance in times of the common use of transvenous intracardiac stimulation devices. It accounts for at least 1–4% of all cases of deep vein thrombosis [1] and it may lead, in rare situations, to a life-threatening pulmonary embolism [2]. The other complications include, among others, superior vena cava syndrome and post-thrombotic syndrome [2]. The incidence of venous thromboembolism associated to the implantation of heart stimulating systems, cardioverter-defibrillators or cardiac resynchronization therapy devices is being estimated on 5.5 to even 44% [3].
Therefore, it is one of the most frequent ‘after-pacemaker’ complications, although in its symptomatic form it is regarding only 1–3% of cases [1, 2]. The most common place for thrombus forming after implantation of cardiac stimulator is the proximal section of the left subclavian vein. Due to the possibility of the rapid development of effective collateral circulation, subclavian vein occlusion usually remains asymptomatic and the problem emerges in case of the need to remove, replace or upgrade a stimulation system [3, 4]. Below we present the case of symptomatic thromboembolism in the left subclavian and internal jugular vein in our patient, who was treated successfully by only three-month long low-molecule heparin therapy.
Case report
A 69-year-old female with hypertension, hypercholesterolemia, chronic venous insufficiency, diverticulosis, the history of peptic ulcers of the stomach and uterine fibroids was hospitalized at the Department of Cardiology of the Bielański Hospital in Warsaw in order to undergo an implantation of a heart pacemaker due to paroxysmal second-degree atrioventricular block with concomitant MAS (Morgagni-Adams-Stokes) syndrome. The procedure of permanent DDDR pacemaker’s implantation was performed via left subclavian vein, with no complications. One week after the discharge patient was diagnosed with acute bronchitis and treated with clarithromycin at home. After another week she was admitted to Department again with a painful left shoulder, adjoining part of the chest and arm, with accompanying swelling and excess warmth of skin, as well as with mildly increased body temperature for the last three days. According to the patient, the complaints mentioned above didn’t result from any trauma or physical activity, which she had been avoiding because of the infection. She was also reporting a single episode of dyspnea at rest and weakening without complete loss of consciousness on the day of admission. Her family history towards venous thrombosis and cancer was negative. Due to the concomitant diseases she was staying under the permanent care of a gastrologist and a gynaecologist, as well as she had undergone mammography in the previous months and the result was normal. Her physical examination revealed, above already mentioned, tenderness to palpation of submandibular region with a low-grade enlargement of local lymph nodes. In laboratory tests a raised level od d-dimers (2.32 ug/ml, at the norm to 0.5 ug/ml) paid attention; blood counts was normal (platelets count – 343 000/ul), creatinine level was 0.73 mg/dl, C-reactive protein (CRP) – 2.12 mg/l. Chest X-ray, electrocardiogram and echocardiography didn’t disclose any abnormalities. An ultrasound with doppler imaging showed the presence of thrombi in left internal jugular and subclavian vein with narrow flow channel; axillary vein and other veins of upper extremity were passable. Pulmonary embolism was excluded with angiotomography. A doppler ultrasound of lower limb deep veins was also performed and revealed no signs of thrombosis. The patient was administered subcutaneous enoxaparin in the therapeutical dose, she didn’t give her consent to adjoining the oral anticoagulant. The stimulator was controlled – there was no evidence of malfunction. The laryngologist, who was consulting the patient, after performing a neck ultrasound, established the diagnosis of the acute infection of submandibular salivary gland and recommended new antibiotic therapy (cefuroxym was initiated). In consecutive days the swelling and the pain of the left arm gradually diminished. Antithrombotic treatment was being continued for 3 months at home, first in the therapeutical dose and after that – due to the recanalization of the clotted veins and the patient’s preferences – in the maintenance dose (reduced by half). The repeat ultrasound was performed one month and three months after the beginning of treatment and showed no thrombotic changes. During this whole time the patient wasn’t reporting any of the symptoms from upper extremities. She was handed over to the Clinic of Vessel Diseases in order to be further monitored.
Discussion
By the term ‘upper limb deep vein thrombosis’ we mean the formation of thrombi in veins that are localized under the fasciae of arm and forearm. Its primary form, also called Paget-Schroetter syndrome or ’effort thrombosis’, mostly occurs in young men after the hard use of a limb and it mainly affects right side of the body (the dominant). Here the clots formation results from repetitive vein injury, caused by the bone, ligamentous or muscular structures within the canal, through which the neurovascular bundle of the arms is passing. Especially patients who have congenital or acquired (mostly posttraumatic) anatomic abnormalities within this canal are in danger to develop compressive symptoms; in these cases we are talking about different variants of so-called thoracic outlet syndrome (TOS). After the age of 50, thrombosis is mainly secondary. It constitutes up to 80% of all cases of upper limb thrombosis. The most frequent cause of the secondary form is puncturing the large veins (subclavian or jugular) in order to insert catheters for medications’ administration, parenteral nutrition or invasive haemodynamic monitoring, as well as to implant electrodes for heart stimulation [1].
The pacemaker-associated thrombosis develops in the period from a few days up to even a few years after device implantation. It is not entirely known why the same mechanisms, which to the certain point are associated with electrode’s implantation process in all patients (these are: endothelial damage, change of blood flow from laminar to turbulent and local alterations in blood components causing its transitional hypercoagulability), only in some cases lead to the development of thrombosis. It seems unusually essential to identify the factors which are supporting it. Unfortunately in spite of numerous studies, they didn’t manage to demonstrate explicit relationship with any of the investigated indicators. It seems most likely that the influence of factors below is clinically relevant: history of myocardial infarction, heart failure (especially higher NYHA classes), supraventricular arrhythmias, systemic infection, cigarettes smoking, history of thrombosis, temporary cardiac pacing before permanent implantation, venous anomalies, hormone-replacement therapy, anticoagulation therapy and number of implanted leads. The meaning of the diseases of internal medicine such as hypertension, diabetes or widely comprehended atherosclerosis is still not clear [3, 5, 6]. When it comes to the case discussed above, we assume that a few factors most probably predisposed to the development of thrombosis, which happened quite shortly (about 2 weeks) after the implantation of a cardiac stimulator. It seems most likely that the coincidence with infection (doubling the risk of vein occlusion [3, 5]) together with no anticoagulation administered (due to, for example, the absence of arrhythmia) played the crucial role. Since however the protective influence of such therapy is not fully proved [3], the discussion on applying anticoagulation as prevention both in pre- and post-implantation period remains still open, especially in the context of constantly appearing new anticoagulant drugs [4].
It stays inconclusive how to optimize the diagnostic approach as well as the treatment of already diagnosed upper limb vein thrombosis. Due to less common appearance, the present knowledge about its risk factors, prophylaxis and treatment is much more limited than the one we have in the reference to lower limb deep vein thrombosis and pulmonary embolism. The current guidelines suggest in most cases basing on the experience and patterns which were worked out for these more common kinds of venous thromboembolic disease [7].
The means used to reach the diagnosis of venous thromboembolism range from ultrasonography, computed tomography, magnetic resonance to contrast venography. Colour coded doppler ultrasound is an effective and repeatable method for imaging veins, especially when the proximal thrombosis is suspected. Among the advantages of this examination there is its noninvasiveness, availability and relatively low cost, which together with high, established on 94-100% sensitivity and specificity, makes an ultrasound the method of first choice for diagnosis and monitoring of clots’ presence in venous system [2]. That is why we based our diagnostic approach on this method. Due to the fact that venous thrombosis is not rarely the first sign of the latent cancer, in many cases it seems justified to expand the diagnostic testing by neoplasms screening for, among others, the cancers of the chest (including breast cancer) or of digestive and urogenital system. It is difficult to define the range of tests that should be run for that purpose. Basing on data of the literature, it is possible to accept that thorough medical history and physical examination (including pelvic examination in women and urologic examination in men), together with basic laboratory tests (widened if necessary by the fecal occult blood test) and chest X-ray is enough for patients with no additionally symptoms or risk factors suggesting neoplastic process. It is especially useful in the context of no explicitly proven benefits of performing wider diagnostic testing [8, 9]. In the cases where the compression syndrome is suspected, provocation tests, thoracic outlet imaging and neurophysiologic exam should be run. Thus the utility of screening for thrombophilia is controversial [10], it is mainly recommended for patients less than 40 years old, with burdening family history and with recurrent thrombosis.
As for therapy of patients with deep vein thrombosis, anticoagulant drugs, mainly low-molecule heparin, are most commonly used. It is a preferred option in most of patients, both in hospital and at home. It is recommended that it should be combined with vitamin K antagonist as soon as in the first day of treatment, and in case of inability of applying oral therapy (such as in described case) heparin alone should be continued for at least 3 months [7]. To the methods more rarely used belong: fibrinolysis (preferentially local), venous thrombectomy, as well as superior vena cava filters [1].