What causes bloody sclera in a patient, considering potential underlying conditions such as trauma, infection, inflammation, hypertension, diabetes, bleeding disorders, and anticoagulant (e.g. warfarin or aspirin) use?

Bloody Sclera: Causes and Clinical Approach

Direct Answer

Bloody sclera (subconjunctival hemorrhage or scleral bleeding) is most commonly caused by trauma, but can also result from hypertension, bleeding disorders, anticoagulant use (warfarin, aspirin, DOACs), infection (particularly post-surgical), or inflammatory conditions like scleritis. 1

Trauma-Related Causes

Trauma is the leading cause of bloody sclera and must be ruled out first. 1

• Blunt or penetrating ocular trauma directly damages scleral vessels, causing hemorrhage that can range from minor subconjunctival bleeding to severe intraocular hemorrhage 1
• Surgical trauma including cataract surgery, pterygium excision, or trabeculectomy can lead to infectious scleritis with scleral hemorrhage—9 of 12 cases in one series had preceding surgical or accidental trauma 2
• Traumatic coagulopathy develops in approximately one-third of major trauma patients, significantly increasing bleeding risk 1

Anticoagulant and Antiplatelet Medications

Anticoagulants substantially increase the risk of ocular bleeding and should be assessed immediately. 1

• Warfarin increases bleeding risk, particularly when INR is supratherapeutic—check INR immediately and consider reversal with 4-factor PCC (25-50 IU/kg) plus vitamin K (5-10 mg IV) if bleeding is severe 3
• Direct oral anticoagulants (DOACs) including rivaroxaban, apixaban (factor Xa inhibitors) and dabigatran (factor IIa inhibitor) increase major bleeding risk 1.6-3.6 per year 1
  • For dabigatran: administer idarucizumab 5g IV (two 2.5g boluses) 1
  • For rivaroxaban/apixaban: administer andexanet alfa (400-800mg bolus followed by infusion) 1
• Aspirin and NSAIDs increase bleeding risk through platelet inhibition 1

Hypertension and Vascular Factors

Hypertension is a major risk factor for bloody sclera, though acute blood pressure lowering is NOT routinely recommended. 1

• Hypertension increases risk of retinal vein occlusions (which can present with scleral hemorrhage) and is associated with branch retinal vein occlusion through arterial-venous crossing changes 1
• Do NOT routinely lower blood pressure acutely in patients with bloody sclera, as excessive reduction may cause renal, cerebral, or coronary ischemia 1
• Monitor blood pressure but base treatment decisions on bleeding severity, patient comorbidities, and risks of blood pressure reduction 1

Bleeding Disorders and Coagulopathy

Inherited and acquired bleeding disorders must be considered, especially in younger patients or those with recurrent episodes. 1

• Inherited conditions including factor V Leiden mutation, prothrombin gene mutation, protein S/C deficiency, and antithrombin deficiency increase thrombotic risk but paradoxically can be associated with bleeding complications 1
• Acquired coagulopathy from liver disease, chronic kidney disease, or disseminated intravascular coagulation 1
• Approximately 58% of patients with retinal vein occlusion (which can cause bloody sclera) under age 50 have a nontraditional risk factor on systemic evaluation 1

Infectious Scleritis

Infection must be ruled out in any case of bloody sclera with preceding trauma or surgery. 2

• Pseudomonas, Klebsiella, and Nocardia are common causative organisms, often presenting with multifocal scleral abscesses 2
• History of small-incision cataract surgery, pterygium surgery, or trabeculectomy increases risk 2
• Poor visual acuity at presentation predicts worse visual outcome (P=0.005), and aggressive surgical intervention improves anatomical but not visual outcomes 2

Inflammatory/Autoimmune Scleritis

Noninfectious scleritis causes scleral inflammation and hemorrhage, often associated with systemic autoimmune disease. 4, 5, 6, 7

• Rheumatoid arthritis is the most common systemic association with scleritis 4, 7
• Granulomatosis with polyangiitis is the most common vasculitis causing scleritis 7
• Necrotizing scleritis represents the most severe form, destroying scleral structural components through macrophage and T-lymphocyte infiltration 5
• Spondyloarthropathies and systemic lupus erythematosus also increase risk 1, 4

Diabetes and Metabolic Factors

Diabetes increases risk of retinal vascular complications that can present with bloody sclera. 1

• Diabetes is a risk factor for retinal vein occlusions, which affect approximately 0.5% of the population aged 30+ years 1
• Diabetic patients have 2.5-3.5 times higher incidence of ischemic stroke and increased peripheral vascular disease 1

Critical Pitfalls to Avoid

• Never assume benign subconjunctival hemorrhage without ruling out trauma, infection, or severe coagulopathy 1, 2
• Do not delay reversal of anticoagulation in severe bleeding—administer specific reversal agents immediately without waiting for laboratory results 3
• Do not aggressively lower blood pressure in acute bloody sclera, as this may cause end-organ ischemia 1
• Always obtain surgical history—post-operative infectious scleritis can rapidly destroy the globe 2