Background

Hyperhemolysis syndrome (HHS) is a rare, potentially fatal transfusion complication seen in

patients with sickle cell disease (SCD), characterized by the destruction of both donor and

recipient red blood cells, leading to a paradoxical drop in hemoglobin. Eculizumab, a

monoclonal antibody targeting the terminal complement protein C5, has shown promise in

controlling complement-mediated hemolysis. We aim to investigate outcomes with

Eculizumab in patients with HHS.

Methods

Following PRISMA guidelines, a comprehensive literature search was

conducted on PubMed, Cochrane, Google Scholar, and ClinicalTrials.gov, and 11 original

studies reporting outcomes in HHS patients treated with Eculizumab were included for

analysis and review. Pooled proportions with 95% confidence intervals were calculated

using the DerSimonian–Laird estimator and analyzed with the ‘meta’ package in R (version

4.16-2). Demographic, clinical, genetic, and treatment-related data were extracted and

analyzed descriptively.

Results

A total of 11 reports reporting outcomes in 14 patients were included for analysis. The

median age was 25 years (range, 9-42), and 71% (n = 10) were female. Most patients had an

SS genotype (n = 10/14, 71%). HHS was acute in 50% (n = 7) of the cases. Reported triggers

included transfusions (n = 10, 71%), infections (n = 3, 14%), and surgery (n = 1, 7%).

Common pre-treatments included steroids (n = 9/14, 64%), intravenous immunoglobulins

(IVIG) (n = 9/14, 64%), and Rituximab (n = 5/14, 36%). The median hemoglobin (Hb) level

before treatment with Eculizumab was 4.2 g/dL (range, 2.4-9.0 g/dL). The dose of

Eculizumab ranged from 600 mg to 1200 mg; patients required from 1 to 8 infusions. The

pooled rates for patients who required admission to the intensive care unit (ICU) and

mechanical ventilation were 27% (95% CI: 0.0-0.73, I2 = 30.2, p = 0.1676) and13% (95%CI:

0.00-0.49, I2 = 0.0%, p = 0.7527), respectively. The pooled rate of HHS resolution was 93%

(95% CI: 0.62-1.00, I2 = 0.00%, p = 0.947). The pooled rates for HHS recurrence and

mortality were 0% (95% CI: 0.00-0.25, I2 = 0.00%, p = 1.00) and 7% (95% CI: 0.00-0.38, I2

= 0.00%, p = 0.947), respectively. The pooled rate for overall survival (OS) at the last follow-

up was 93% (95%CI: 0.59-1.00, I2 = 0.0%, p = 0.9149). The pooled rates of fever,

hypotension, and thrombosis were 14% (95% CI: 0.00-0.48, I2 = 0.0%, p = 0.9348), 7%

(95% CI: 0.00-0.38, I2 = 0.0%, p = 0.9471), and 0% (95% CI: 0.00-0.18, I2 = 0.0%, p = 1.00)

respectively, whereas the pooled rate for anaphylaxis was 0% (95% CI: 0.00-0.18, I2 =

0.0%, p = 1.00).

Conclusion

Eculizumab was associated with the complete resolution of HHS in the majority of cases,

with a low recurrence rate and an excellent survival rate at follow-up. However, there is a

lack of high-quality data and larger, prospective registries and clinical trials are urgently

needed to validate these findings, define optimal patient selection, timing, and dosing.

This content is only available as a PDF.
2025
Sign in via your Institution