Upper extremity deep vein thrombosis - The venous thromboembolism Cinderella?

Abstract

When referring to venous thromboembolism (VTE), one tends to think of lower limb deep vein thrombosis (DVT) and pulmonary embolism (PE). A rarer and poorly understood form of DVT occurs in the upper extremity (UEDVT). With UEDVT being a cause of significant morbidity and mortality and its prevalence said to be increasing at a concerning rate, should the scientific community be paying more attention to the VTE Cinderella? Historically rare with an annual incidence of 2 per 100,000 persons, the medical inpatients and thrombosis study reports UEDVT to now complicate approximately 14 per 100,000 hospital admissions. Whether this is a true representation of the changing epidemiology of UEDVT is unclear due to the study’s low statistical power. What we can be certain of, however, is that secondary UEDVT is becoming increasingly prevalent, which cannot be ignored. UEDVT is classified as primary (namely idiopathic, Paget-Schroetter syndrome or thoracic outlet obstruction secondary to a first rib) or, more frequently, secondary to central and peripheral venous catheter insertion, pacemaker insertion or malignancy. Anatomically, UEDVT most commonly involves the subclavian (18–67%) or axillary (5–25%) vein. Unlike previously reported, UEDVT is far from being a benign self-limiting condition. Post-thrombotic syndrome (PTS) complicates up to 44% of UEDVT, with patients suffering ipsilateral upper limb swelling, pain and, in severe cases, ulceration. Symptomatic PE occurs in up to 33% of patients, and UEDVT recurs in as many as 8% of patients per year. Despite the reduction in patients’ quality of life through loss of work productivity and symptom chronicity, UEDVT has generated relatively little research attention. Reference to UEDVT is sparse in current VTE guidelines. Likewise, a pre-test clinical probability algorithm combining symptoms, diagnostic biochemical markers and imaging is lacking. The National Institute of Health and Care Excellence makes no reference to UEDVT in their VTE guidelines and quality standards. The British Journal of Haematology (BJH) and the American College of Chest Physicians (ACCP) however have. This in part may reflect the lack of robust evidence in the form of randomised controlled trials to base recommendations upon. Although, surely any attempt to standardise clinical practice and promote patient safety is better than none? The ACCP advocate the use of compression ultrasound for the initial investigation of UEDVT. In cases where a high index of clinical suspicion for UEDVT remains despite a negative ultrasound scan, contrast venography is recommended. The BJH, on the other hand, states no preference regarding which of the two imaging modalities is used. This is despite compression ultrasound and contrast venography differing in terms of patient safety and accessibility, with the former being non-invasive and inexpensive. The discrepancy in recommendation may reflect the contrasting level of supporting evidence used, with the BJH ascribing it as level 1B evidence compared to 2C evidence used by the ACCP. Given that both guidelines were published in the same year, one would assume that both societies had access to the same available data. We are therefore left with the uncertainty of whether the difference in specificity and sensitivity of compression ultrasound and venography is of any clinical significance in diagnosing UEDVT. The paucity of high-quality randomised controlled trials also hinders the management of UEDVT. Anticoagulation, whether it is heparin of a non-specified form or fondaparinux, followed by warfarin, is the preferred treatment. Duration of anticoagulation is arbitrary with the BJH stating no optimal duration, and the ACCP stating it to be aetiology dependent (continuation of anticoagulation for as long as the central venous catheter remains in situ, otherwise