Hematomas after coughing: a case description of vascular Ehlers-Danlos syndrome

Introduction

Ehlers-Danlos syndrome (EDS) is a genetically inherited connective tissue disease characterized by excessive skin elasticity, hyperactive joints, and increased tissue fragility. EDS encompasses several subtypes, one of which is vascular Ehlers-Danlos syndrome (vEDS) (1,2). It is an autosomal dominant genetic disease caused by mutations in the type III procollagen gene, most commonly in the COL3A1 gene (2-5). Due to the defect in the vessel wall caused by abnormal collagen, patients with vEDS are prone to bleeding due to increased vascular fragility. Usually, petechiae, bruises, purpura, or menorrhagia are seen in the primary hemostasis defects; hematomas in vEDS likely stem from the extreme fragility of blood vessels, rather than a conventional primary or secondary hemostatic defect. Here, we report a rare case of a young male who presented with multiple hematomas following minimal trauma from coughing and was ultimately diagnosed with vEDS.

Case presentation

A 25-year-old male patient came to our hospital with a 20-day history of coughing, followed by swelling in the right chest wall and upper left abdominal wall after severe coughing episodes. He had a history of easy bruising following minor trauma since childhood, lung bullae, recurrent pneumothorax, and a left calf hematoma confirmed by surgical exploration (probably for diagnosis rather than treatment) 15 years ago. He denied any familial history of bleeding disorders or concurrent use of anticoagulants or anti-thrombotic medications. Ultrasonography examination revealed hypoechoic areas within the muscle layers at the right posterior axillary line (7.7 cm × 6.0 cm × 3.7 cm) and upper left abdomen (8.6 cm × 8.1 cm × 3.9 cm), with irregular shapes and poorly defined borders, consistent with hematomas (Figure 1). His complete blood count (CBC) parameters showed: white blood cell (WBC) 10.88×10⁹/L [reference range, (3.5–9.5)×10⁹/L], hemoglobin (HGB) 147 g/L (reference range, 120–160 g/L), and platelet (PLT) 482×10⁹/L (reference range, 100–350×10⁹/L). A qualitative Factor XIII test was negative, and von Willebrand factor (vWF) antigen levels were 88.7% (normal: 50–150%). PLT aggregation induced by 10 µM adenosine diphosphate (ADP) was reduced to 65% (normal: 71–88%), whereas aggregation in response to 2 µg/mL collagen was 79% (normal: 70–94%). Aggregation with 1.2 mg/mL ristocetin was 22% (normal: 87–102%), and no aggregation was observed at 0.5 mg/mL ristocetin (normal: 0–0%). Additional tests, including blood immunofixation electrophoresis and free light chain testing were unremarkable. The International Society on Thrombosis and Hemostasis Bleeding Assessment Tool (ISTH-BAT) was used to assess the patient’s bleeding history, yielding a score of 2, with spontaneous muscle hematoma being the contributing factor. Physical examination revealed excessive movement in the patient’s distal interphalangeal joints (Figure 2). Given his history of hypermobility, recurrent pneumothorax, and easy bruising, EDS was suspected. Genetic testing revealed a heterozygous mutation in the COL3A1 gene [c.3149G>A (p.Gly1050Asp)], confirming the diagnosis of vEDS. The patient was advised to avoid excessive physical exertion, monitor lung function changes, and manage heart rate as well as blood pressure to minimize vascular damage.

Figure 1 Hematomas at the muscle layer in the right posterior axillary line (7.7 cm × 6.0 cm × 3.7 cm) and upper left abdomen (8.6 cm × 8.1 cm × 3.9 cm).

Figure 2 Excessive movement of the patient’s distal interphalangeal joints.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was provided by the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

vEDS represents approximately 4% of all EDS cases, with an estimated prevalence ranging from 1:50,000 to 1:200,000 individuals (6). Since type III collagen mainly exists in tissues such as blood vessel walls, gastrointestinal tract, and uterus (3), the reduction or heterogeneity of this protein leads to pathological changes of the walls in the above parts and causes clinical symptoms (7). The diagnosis of vEDS depends on spontaneous rupture of blood essels/organs, hypermobility of small joints, characteristic facial features, and genetic testing (2,3). COL3A1 gene sequencing and deletion/duplication mutation detection is highly sensitive and have important diagnostic value.

Primary hemostasis relies on blood vessel wall contraction and PLT aggregation, but it is usually manifested as petechia, purpura, or heavy menstrual bleeding; hematomas are rare. In vEDS, however, the extreme fragility of blood vessels predisposes patients to spontaneous vessel rupture. The fragility of the tissue and the tendency of the hemorrhaged blood to spread may also present in vEDS patients. Therefore, hematomas could occur. Vascular complications of vEDS are often seen as aneurysms or dissections. A study of 142 patients with vEDS found that 68 (48%) had an aneurysm and/or vascular dissection (8). Another cohort of 180 patients showed that 72 patients (40%) had a total of 165 vascular events, among whom 75 (45.45%) had vascular dissection and 61 (36.96%) had aneurysm (9). In most patients, easy bruising is the predominant clinical manifestation, with only a few cases reporting hematoma (10-13).

This case underscores the importance of considering EDS in patients with hematomas, particularly when accompanied by features such as joint hypermobility, translucent skin, poor wound healing, easy bruising, excessive skin elasticity, and spontaneous pneumothorax. EDS patients may also have PLT dysfunction, which may further aggravate the bleeding manifestations (14).

Conclusions

We described a case of vEDS in which the primary clinical manifestation was the development of multiple hematomas following coughing. Clinicians should be vigilant in considering rare conditions such as vEDS in patients with hematomas, especially when associated with characteristic features of connective tissue disorders. Early recognition and genetic diagnosis are essential for appropriate management and patient care.

Acknowledgments

We thank the patient and his family for their trust in this study.

Footnote

Funding: This work was supported by the National High Level Hospital Clinical Research Funding (grant No. 2022-PUMCH-A-021 to L.Z.) and CAMS Innovation Fund for Medical Sciences (ClFMS) (grant No. 2023-I2M-C&T-B-045 to L.Z.).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-2080/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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