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Primary deep vein thrombosis in an upper limb : a retrospective study with an emphasis on the pathogenesis and late sequelae

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posted on 2024-09-02, 18:58 authored by Thomas Arnhjort

Background: Upper extremity deep vein thrombosis (UEDVT) is an uncommon disease with an incidence of 1–11% of all deep vein thrombosis. UEDVT can be classified into two groups, primary and secondary UEDVT. Primary UEDVT includes idiopathic and effort-related UEDVT. Secondary UEDVT is caused by central venous devices, trauma, and cancer. This thesis is focused on primary UEDVT.

Aim: This project emerged from a clinical question when we started to review our guidelines for deep vein thrombosis at the Emergency Department at Södersjukhuset, Stockholm. The overall aim of this thesis was to increase the level of knowledge concerning primary UEDTV.

Patients: Thirty-one patients (23 females, 8 males) with primary UEDVT were enrolled for Papers I. For paper II there was thirty-two patients (23 females and 9 males) included. Fifteen of these patients agreed to participate in the third study, the MRI Study, in which a control group of 15 healthy volunteers was also included. The fourth paper is a retrospective case-control study based on data from the Swedish National Patient Register (NPR) and comprises 25 patients with primary UEDVT.

Methods: In Paper I, the patients were evaluated using interviews, clinical examinations, computerized strain-gauge plethysmography, and color duplex ultrasound (CDU) imaging. The degree of postthrombotic syndrome (PTS) was rated according to the Villalta score. For the second paper, the Villalta score was supplemented with the DASH test (Disability of the arm shoulder and hand). The visual analog scale (VAS) was used to estimate pain and disability. An arm exercise capacity test was performed to evaluate working capacity. Blood samples were taken for analyses of factor V Leiden and common coagulation factors. In Paper III, the subclavian region (the costoclavicular distance) and vessel area of the subclavian vein were examined using magnetic resonance imaging (MRI). The MRI was performed with the arms in two positions: alongside and elevated. PTS and disability were quantified with the Villalta and DASH scores. The 25 patients in the fourth paper were matched on an individual basis with 474 controls (patients with acute appendicitis) in relation to sex, age at the index point, and the year of the index point. Comorbidity was described as the number of unique ICD codes (diagnoses) registered in the NPR from the index point to the end of year 2011.

Results: Paper I. The rate of venous emptying was significantly lower in the arms with DVTs than in the contralateral arms. Fifty-eight percent had a residual thrombus and seventy-five percent of the patients had some morphologic abnormality in the thrombotic vein. There was no statistically significant relationship between the plethysmographic and duplex findings. No significant difference in the relationship between the postthrombotic syndrome score and duplex findings or venous emptying was evident. Paper II. None of the patients developed malignancies, pulmonary embolism, or recurrent UEDVT. Twenty-eight percent of the patients had mild to moderate PTS according to the scoring instruments. The prevalence of thrombophilia was 40%; the most frequent disorders were the mutation of the gene for factor V Leiden (19%) and elevated fibrinogen (22%). Paper III. The costoclavicular distance was significantly narrower in the patients than in the controls with the arms alongside the body, but there was a significant difference only in the left arm with the arms elevated. Area of the subclavian vein: on comparing the patients’ non-thrombotic arm with that of the controls, there was a significant difference only with the arms in the supine position. Measurements of disability: there was a high correlation between DASH, the Villalta score, and VAS, but there was no correlation between the MRI measurements and the patients’ symptoms. Paper IV. The 25 cases and 474 controls, 48% male and 52% female, had a mean age at the index point of 48 years (range, 20–80, SD 17.5). The mean follow-up time was 8 years (range, 5.7–9). There was no significant difference between patients and controls regarding the frequency of reported unique ICD codes in the NPR when all ICD codes were analyzed together, but there was a significant difference for codes related to symptoms from the blood and blood-forming organs, the endocrine and metabolic systems, disease of the nervous and circulatory systems, and skin and musculoskeletal systems. There was no difference in ICD codes relating to malignancies. The cases had a significantly higher number of healthcare contacts.

Conclusions: ∙ Primary UEDVT is a rather benign disease with a low rate of recurrences, but with a non-negligible proportion of the postthrombotic syndrome. ∙ Fifty-eight percent had a residual thrombus. Seventy-five percent of the patients had some morphologic abnormality in the thrombotic vein, which was detectable with CDU. The rate of venous emptying was significantly lower in the arms with DVTs than in the contralateral arms. ∙ There was no correlation between PTS and plethysmography findings, area of the subclavian vein, and morphologic abnormalities detected by CDU. ∙ The frequency of coagulation disorders was about 40%; the most common disorders in our study population were mutations of factor V Leiden. ∙ There seemed to be some influence regarding the anatomy of the thoracic outlet and the development of both effort-related and idiopathic UEDVT. ∙ The rate of malignancies seems to be in line with that of the general population. ∙ It is extremely important to validate data from the National Patient Register with the medical records especially when there is no unique ICD-code.

List of scientific papers

I. Hemodynamic and morphologic evaluation of sequelae of primary upper extremity deep venous thrombosis treated with anticoagulation. Persson LM, Arnhjort T, Lärfars G, Rosfors S. J Vasc Surg. 2006 Jun;43(6):1230-5; discussion 1235.
https://doi.org/10.1016/j.jvs.2006.02.045

II. Primary deep vein thrombosis in the upper limb: A retrospective study with emphasis on pathogenesis and late sequelae. Arnhjort T, Persson LM, Rosfors S, Ludwigs U, Lärfars G. Eur J Intern Med. 2007 Jul; 18(4):304-8.
https://doi.org/10.1016/j.ejim.2006.12.005

III. The importance of the costoclavicular space in upper limb primary deep vein thrombosis, a study with magnetic resonance imaging (MRI) technique enhanced by a blood pool agent. Arnhjort T, Nordberg J, Delle M, Borgis CJ, Rosfors S, Lärfars G. Eur J Intern Med. 2014 Jul; 25(6):545-9.
https://doi.org/10.1016/j.ejim.2014.05.005

IV. Primary upper extremity deep venous thrombosis and comorbidity: A population-based nationwide study in Sweden. Arnhjort T, Lärfars G, Adami J, Järnbert-Pettersson H. [Submitted]

History

Defence date

2016-12-16

Department

  • Department of Clinical Science and Education, Södersjukhuset

Publisher/Institution

Karolinska Institutet

Main supervisor

Lärfars, Gerd

Publication year

2016

Thesis type

  • Doctoral thesis

ISBN

978-91-7676-324-7

Number of supporting papers

4

Language

  • eng

Original publication date

2016-11-04

Author name in thesis

Arnhjort, Thomas

Original department name

Department of Clinical Science and Education, Södersjukhuset

Place of publication

Stockholm

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