Sevuparin Does Not Reduce Duration of Vaso-Occlusive Crisis in Patients with Sickle Cell Disease

sickle cell disease in bloodstream
Sickle cell anaemia. Artwork showing normal red blood cells (round), and red blood cells affected by sickle cell anaemia (crescent shaped). This is a disease in which the red blood cells contain an abnormal form of haemoglobin (bloods oxygen-carrying pigment) that causes the blood cells to become sickle-shaped, rather than round. Sickle cells cannot move through small blood vessels as easily as normal cells and so can cause blockages (right). This prevents oxygen from reaching the tissues, causing severe pain and organ damage.
In this study, the researchers tested whether sevuparin could shorten vaso-occlusive crisis duration in hospitalized patients with sickle cell disease.

The non-anticoagulant heparinoid sevuparin did not reduce the duration of vaso-occlusive crisis in hospitalized patients with sickle cell disease, according to a study published in The Lancet Haematology.

Patients were randomly assigned to receive either sevuparin (18 mg/kg/day) or placebo intravenously. The primary endpoint was time to crisis resolution, which was defined as freedom from parental opioid use and readiness for discharge.

Participants had a median age of 22.2 (range, 12 to 33) years, had a diagnosis of sickle cell disease, were receiving a stable dose of hydroxyurea, and were hospitalized with vaso-occlusive crisis for parenteral opioid analgesia with a projected stay of more than 48 hours. The sevuparin and placebo groups included 69 and 75 patients, respectively, of which 58 and 69 fulfilled the criteria for the primary endpoint.

The median time to crisis resolution was 100.4 hours (95% CI, 85.5-116.8) for sevuparin compared with 86.4 hours (95% CI, 70.6-95.1) for placebo. No significant differences were noted between groups (hazard ratio, 0.89; 95% CI, 0.6-1.3; P =.55). No significant differences were found in key secondary efficacy endpoints, such as mean change in pain severity from baseline until resolution and median time to a 30% reduction in pain.

Sevuparin was well-tolerated by the participants and no notable differences in the numbers of treatment-emergent adverse events between study groups were observed. The most common adverse events reported overall were pyrexia, constipation, and hemoglobin decrease. A single patient in the placebo group died after a hyperhemolytic episode due to alloimmunization, and no patients died in the treatment group.

The study had several limitations. Readiness to discharge was judged by the patient or physician, leading to subjectivity in the primary endpoint. The actual onset time of the crisis compared with start of treatment in the study meant the opportunity for treating in the early phase when antiadhesive mechanisms may be more effective was potentially missed. Future studies should investigate early administration, according to investigators.

Researchers concluded, “The findings in this study suggest that anti-adhesive strategies antagonising selectins such as non-anticoagulant heparinoids are not beneficial when administered in the context of an already established vaso-occlusive crisis.” They added that this indicates “strategies to treat vaso-occlusive crises in sickle cell disease might differ from strategies to prevent this complication.”

Disclosure: This research was supported by Modus Therapeutics. Please see the original reference for a full list of disclosures.


Biemond BJ, Tombak A, Kilinc Y, et al. Sevuparin for the treatment of acute pain crisis in patients with sickle cell disease: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Haematol. 2021;8(5):e334-e343. doi:10.1016/S2352-3026(21)00053-3