# Clinical characteristics and prognostic factors of Clostridium perfringens infection complicated by massive intravascular hemolysis in patients with hematologic diseases: a retrospective case series study

## TL;DR

This study examines Clostridium perfringens infections causing severe hemolysis in patients with blood disorders, highlighting altered mental status as a key risk factor and the need for urgent treatment.

## Contribution

The study identifies altered mental status as an independent risk factor for mortality in Clostridium perfringens-associated massive intravascular hemolysis in hematologic patients.

## Key findings

- Altered mental status was an independent risk factor for mortality (OR = 14.03).
- The overall mortality rate was 73.9% with a median survival of 13.5 hours among non-survivors.
- A 'double-hit' model involving α-toxin and θ-toxin was proposed to explain the pathogenic cascade.

## Abstract

Clostridium perfringens (CP), an anaerobic Gram-positive bacterium, is commonly associated with food poisoning and gas gangrene. In rare instances, it can cause fatal massive intravascular hemolysis (MIH), a condition associated with exceedingly high mortality that poses a serious clinical challenge. A retrospective analysis was performed using a fatal case of T-lymphoblastic lymphoma/leukemia complicated by CP-associated acute hemolysis treated at our center in November 2024 and case reports of CP-associated MIH in hematologic patients from January 1987 to September 2025. A total of 23 eligible cases from our institution and published literature were included. The cohort consisted of 60.8% (n = 14) male patients, with a mean age of 45.87 ± 17.94 years. All patients presented with fever, hematuria was observed in 69.5% of patients, shock in 78.2%, and altered mental status (AMS) in 60.8%. The overall mortality rate was 73.9%, with a median survival time of 13.5 (6, 24) hours among non-survivors. AMS was identified as an independent risk factor for mortality (OR = 14.03, 95% CI: 1.19–165.08, p = 0.036). The pathogenic cascade, conceptualized as a “double-hit” model, is triggered by the synergistic action of α-toxin and θ-toxin. Together, they induce fulminant intravascular hemolysis and a systemic inflammatory response, culminating in organ injury. Although no specific therapeutics are available, immediate empirical combination antibiotic therapy (such as penicillin with clindamycin) is paramount. Adjunctive measures, including intensive care support and toxin removal strategies, are essential components of care. This study emphasizes the severity of CP-MIH in hematologic patients and identifies AMS as a key prognostic marker, underscoring the need for early intervention and further research into rapid diagnostics and targeted treatments.