European Journal of Cardiovascular Medicine

Antiphospholipid syndrome (APS) is a multisystem autoimmune disorder characterized by the persistent presence of antiphospholipid antibodies (APLA) in individuals with arterial or venous thrombosis and/or pregnancy complications. The estimated incidence of APS in the United States is 2.1 per 100,000 individuals, with a prevalence of 50 per 100,000. In contrast, Europe reports a lower incidence of 1.1 per 100,000, while South Korea records an incidence of 0.75 per 100,000 and a prevalence of 6.19 per 100,000 [1]. APS can be primary, occurring without an associated autoimmune disease, or secondary, often linked to systemic lupus erythematosus (SLE) in approximately 40% of cases. Genetic predisposition, particularly certain HLA alleles (HLA-DR7, DR4, DRw53, DQw7, and C4 null alleles), contributes to APS development. Various infections, especially viral, such as Borrelia burgdorferi, Coxiella burnetii, hepatitis C, HIV, COVID-19, and Epstein-Barr virus (EBV), have been associated with APLA production. A meta-analysis found nearly 50% of COVID-19 patients had positive APS markers, primarily lupus anticoagulant, though without an increased thrombotic risk. Additionally, drugs like chlorpromazine, procainamide, quinidine, and phenytoin can induce APLA formation, while transient APLA positivity may occur, necessitating confirmation with two positive antibody tests at least 12 weeks apart for an APS diagnosis [2].

Based on clinical manifestations, APS is classified into thrombotic, obstetric, and catastrophic APS. Thrombotic APS involves arterial or venous thrombosis, with deep vein thrombosis (DVT) being the most frequent presentation. Obstetric APS is diagnosed in patients with pregnancy-related complications such as fetal loss beyond 10 weeks, severe preeclampsia requiring preterm delivery, placental insufficiency, or multiple early pregnancy losses, along with persistent APLA positivity. Catastrophic APS, though rare, is a life-threatening variant involving widespread thrombosis affecting multiple organs at both microvascular and macrovascular levels [3]. APLA alone, without clinical thrombotic or obstetric manifestations, is insufficient to diagnose APS.

Herein, we present a case of APS in a young female, a known case of APS with near complete occlusion of the middle and distal third of left subclavian artery and proximal axillary artery on anticoagulation, antiplatelet and immunosuppressant presenting with uvula thrombosis.

A 14-year-old female, diagnosed with thrombotic antiphospholipid syndrome (APS), presented with a five-day history of blood-tinged saliva. There were no accompanying symptoms such as sore throat, difficulty in swallowing, foreign body sensation, cough, cold, vomiting, fever, or history of trauma to the throat. The patient had been on a stable medication regimen for the past five months, which included aspirin (75 mg once daily), acenocoumarol (2 mg once daily), methotrexate (10 mg once weekly), prednisolone (10 mg once daily), and atorvastatin (10 mg once daily). She had no significant comorbidities, being non-obese, normotensive, and a non-smoker, with no history of diabetes or metabolic syndrome. A notable family history included a younger sibling diagnosed with sickle cell disease. Given the lack of common causes for oral bleeding, including infection, trauma, or systemic conditions such as thrombocytopenia, an underlying microvascular complication of APS was suspected.

Clinical Examination and Management

On examination, the oral cavity appeared healthy except for a reddish discoloration at the tip of the uvula, without active bleeding or ulceration. There were no signs of laryngo-pharyngeal inflammation, swelling, or structural abnormalities. Given her ongoing anticoagulation therapy, antiplatelet and anticoagulant medications were temporarily withheld to prevent further bleeding. The patient was started on dexamethasone to reduce any potential inflammatory response and was given a prophylactic course of amoxicillin-clavulanic acid to mitigate any secondary infection risk.

Laboratory investigations revealed prolonged coagulation parameters, with a prothrombin time (PT) of 27.4 seconds (control: 11.4 seconds) and an international normalized ratio (INR) of 2.60, suggesting an increased bleeding tendency. The activated partial thromboplastin time (APTT) was mildly prolonged at 40.5 seconds (control: 22-34 seconds), while fibrinogen levels were within the normal range (284 mg/dL; normal: 200-400 mg/dL). D-dimer levels were 0.310 mg/L (normal: 0.16-0.39 mg/L), indicating no significant evidence of widespread thrombotic activity. Complement levels were also within the normal range (C3: 146 mg/dL, normal: 84-168; C4: 32 mg/dL, normal: 13-44). A chest X-ray was unremarkable, ruling out any pulmonary or systemic vascular involvement.

Despite conservative management, the blood-tinged saliva persisted for another seven days, without any significant progression or worsening of symptoms. The uvular discoloration remained unchanged, and there was no evidence of further thrombosis or necrosis. Given the stable clinical status, the patient was discharged with instructions to resume her previous medication regimen while remaining under close follow-up for any new or worsening symptoms.

Thrombotic APS is characterized by hypercoagulability due to the presence of antiphospholipid antibodies (aPL), which interfere with natural anticoagulant mechanisms [4]. Initially, it was believed that the primary mechanism of thrombosis in APS was due to direct inhibition of anticoagulant proteins such as protein C, protein S, and antithrombin. However, later studies have highlighted that aPL can induce procoagulant and proinflammatory effects through cellular activation and complement system dysregulation, leading to both venous and arterial thrombosis [5].

Uvular thrombosis is an extremely rare presentation of APS. In the literature, there have been reports of uvular thrombosis occurring in association with Catastrophic APS (CAPS) [3], a life-threatening form of APS characterized by widespread microvascular thrombosis and multiorgan failure. Additionally, cases of post-traumatic uvular necrosis have been described, although these are often linked to direct mechanical injury rather than a thrombotic process [6,7]. The absence of any trauma or infection in this patient suggests that the uvular discoloration and persistent minor bleeding were likely due to microvascular involvement in APS rather than an external insult.

Microvascular APS predominantly affects small blood vessels, leading to severe complications such as diffuse alveolar hemorrhage, aPL-nephropathy, livedoid vasculopathy, cardiac microthrombosis, and adrenal hemorrhage or infarction [6]. While these manifestations are well-documented, isolated uvular involvement is rare and may serve as an early indicator of systemic microvascular complications. There is emerging evidence suggesting that patients with microvascular APS have a higher risk of progression to CAPS, though this has not been extensively studied [8]. Therefore, recognizing and closely monitoring such atypical presentations is crucial for early intervention and prevention of severe thrombotic events.

Uvular thrombosis is a rare but important manifestation of APS that may indicate underlying microvascular involvement. In patients with APS, particularly those on anticoagulant therapy, clinicians should be vigilant for atypical presentations such as blood-tinged saliva, as they could signal localized microthrombosis or an impending systemic thrombotic event. While isolated uvular thrombosis may not be immediately life-threatening, it warrants close observation and careful assessment to rule out the potential for progression to CAPS. Early recognition, appropriate management, and long-term monitoring are essential to preventing severe complications in APS patients.

Conflict of interest: Nil

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