Abstract
Background: The LALA-Fc modification achieves immune silencing by abrogating Fc-mediated effector functions and has been regarded for more than two decades as a widely applicable safety standard. However, extreme high-altitude hypoxia can profoundly reshape immune and coagulation homeostasis, and antibody-drug safety data for the approximately 400 million people residing above 2,500 m remain absent. Case presentation: A woman in her late 60s of Tibetan ethnicity with hepatocellular carcinoma, a lifelong high-altitude resident (approximately 2,880 m), received transarterial embolization followed by ivonescimab (1,400 mg). She developed a lethal paradox: focal hepatic injury markedly repaired (ALT 763→87 U/L), meeting discharge criteria, yet she died approximately one month later with clinical features of multi-organ failure dominated by coagulopathy and microcirculatory collapse (INR 1.80; fibrinogen nadir 1.02 g/L; D-dimer peak 6.00 mg/L FEU). Lactate was 7.4 mmol/L at hemorrhagic shock, falling to 2.8 mmol/L after resuscitation; blood ammonia was only mildly elevated (74.7 μmol/L) without hepatic encephalopathy, arguing against classic liver failure. No autopsy was performed. Conclusion: To our knowledge, this sentinel case provides the first clinical evidence that LALA-Fc immune silencing may have a high-altitude contextual boundary. Antibody-drug safety for 400 million high-altitude residents warrants dedicated evaluation.