Phospholipase A2 levels in acute chest syndrome of sickle cell disease

Abstract

Acute chest syndrome (ACS) is associated with significant morbidity and is the leading cause of death in patients with sickle cell disease (SCD). Recent reports suggest that bone marrow fat embolism can be detected in many cases of severe ACS. Secretory phospholipase A2 (sPLA2) is an important inflammatory mediator and liberates free fatty acids, which are felt to be responsible for the acute lung injury of the fat embolism syndrome. We measured SPLA2 levels in 35 SCD patients during 20 admissions for ACS, 10 admissions for vaso-occlusive crisis, and during 12 clinic visits when patients were at the steady state. Eleven non-SCD patients with pneumonia were also evaluated. To determine if there was a relationship between sPLA2 and the severity of ACS we correlated SPLA2 levels with the clinical course of the patient. In comparison with normal controls (mean = 3.1 +/- 1.1 ng/mL), the non- SCD patients with pneumonia (mean = 68.6 +/- 82.9 ng/mL) and all three SCD patient groups had an elevation of SPLA2 (steady state mean = 10.0 +/- 8.4 ng/mL; vaso-occlusive crisis mean = 23.7 +/- 40.5 ng/mL; ACS mean = 336 +/- 209 ng/mL). In patients with ACS sPLA2 levels were 100- fold greater than normal control values, 35 times greater than values in SCD patients at baseline, and five times greater than non-SCD patients with pneumonia. The degree of SPLA2 elevation in ACS correlated with three different measures of clinical severity and, in patients followed sequentially, the rise in SPLA2 coincided with the onset of ACS. The dramatic elevation of SPLA2 in patients with ACS but not in patients with vaso-occlusive crisis or non-SCD patients with pneumonia and the correlation between levels of SPLA2 and clinical severity suggest a role for SPLA2 in the diagnosis and, perhaps, in the pathophysiology of patients with ACS.

HSP70 sequestration by free α-globin promotes ineffective erythropoiesis in β-thalassaemia

“…Circulating fat globules in the plasma of affected patients cause obstruction in the microcirculation but also lead to the production of arachidonic acid and subsequent generation of eicosanoids, inflammatory mediators known to cause tissue injury (Styles et al, 1996). Removing these compounds by performing therapeutic plasma exchange (TPE) could potentially provide additional benefit.…”

Physician‐diagnosed asthma and acute chest syndrome: Associations with NOS Polymorphisms

“…4,28 Free fatty acids released by the hydrolysis of phospholipids in embolized fat can cause acute lung injury. 29 Isoenzymes of phospholipase A2 (PLA2) hydrolyze phospholipids at the sn-2 position to generate lysophospholipids and free fatty acids. 30 Both cytosolic PLA2 and secretory PLA2 (sPLA2) function to generate arachidonic acid from phospholipids in inflammatory cells.…”

“…30 Both cytosolic PLA2 and secretory PLA2 (sPLA2) function to generate arachidonic acid from phospholipids in inflammatory cells. 31,32 Plasma concentrations of secretory phospholipase (sPLA2) are elevated in ACS 29 and have been proposed as accurate markers of ACS in patients in SCD crises. 33,34 Asthma is accompanied by increased production of arachidonic acid and enhanced activity of cysLT.…”

Airway hyperreactivity is frequent in non-asthmatic children with sickle cell disease

“…6,7,19 Eicosanoids are inflammatory mediators implicated in the pathogenesis of both allergic asthma and sickle cell lung disease. [20][21][22] While eicosanoid levels have been analyzed in the exhaled breath condensate (EBC) of children with asthma, [23][24][25][26] this has not been done in children with SCD.…”