Haptoglobin 1 allele predicts higher serum haptoglobin concentration and lower multiorgan failure risk in sickle cell disease

Abstract

Haptoglobin (HP) is an acute phase protein and the main scavenger of cell-free hemoglobin. When haptoglobin is depleted, as observed in hemolytic conditions such as sickle cell disease (SCD), cell-free hemoglobin can lead to acute organ damage. The impact of the HP 1-1, 2-1, and 2-2 isoforms on HP and cell-free hemoglobin concentrations and SCD-related complications is unclear. In a longitudinal cohort of SCD patients, the HP 1 allele was associated with higher HP and lower cell-free hemoglobin concentrations at a routine clinic visit as well as during hospitalization for a vaso-occlusive episode (VOE) or acute chest syndrome. With a median follow up of 6.8 years, acute chest syndrome occurred in 42% (n=163) and multiorgan failure in 14% (n=53) of 391 SCD patients with a minimum follow-up of six months. The HP 1 allele was independently associated with lower risk of developing multiorgan failure during acute chest syndrome (additive model HR 0.5; P<0.001). Future studies assessing the regulation of HP concentrations and ability to bind cell-free hemoglobin according to HP genotype may help to identify SCD patients at high risk for multiorgan failure and to guide interventions, such as rapid initiation of exchange transfusion or HP replacement therapy.

Predictors and clinical complications associated with antiphospholipid antibodies in sickle cell disease

“…Vaso‐occlusive episodes were defined as pain episodes requiring medical attention (acute care center, emergency room visit, or inpatient hospitalization). Organ failure was defined as previously described [ 5 ]. Multiorgan failure was defined as the involvement of three organ systems simultaneously or within less than a week, and probable catastrophic antiphospholipid antibody syndrome (CAPS) was defined according to the international consensus statement as multiorgan failure in the presence of elevated aPL levels [ 6 ].…”

Sickle Cell Disease and CKD: An Update

“…A genetic variant in HP leads to three genotypes, HP 1-1, 2-1, and 2-2, that may differ by induction of HP or scavenging efficiency for cell-free Hb [99]. In a cohort of SCD patients, the HP 1 allele was associated with higher HP concentrations and lower cell-free Hb-to-HP ratios in circulation during hospitalizations for vaso-occlusive episodes or acute chest syndrome [100]. In this study, the HP 1 allele was associated with a lower risk of AKI during hospitalizations for acute chest syndrome.…”