Pulmonary platelet thrombi and vascular pathology in acute chest syndrome in patients with sickle cell disease.
A growing body of evidence suggests a role for platelets in sickle cell disease (SCD). Despite the proinflammatory, occlusive nature of platelets, a role for platelets in acute chest syndrome (ACS), however, remains understudied. To provide evidence and potentially describe contributory factors for a putative link between ACS and platelets, we performed an autopsy study of 20 SCD cases-10 of whom died from ACS and 10 whose deaths were not ACS-related. Pulmonary histopathology and case history were collected. We discovered that disseminated pulmonary platelet thrombi were present in 3 out of 10 of cases with ACS, but none of the matched cases without ACS. Those cases with detected thrombi were associated with significant deposition of endothelial vWF and detection of large vWF aggregates adhered to endothelium. Potential clinical risk factors were younger age and higher platelet count at presentation. However, we also noted a sharp and significant decline in platelet count prior to death in each case with platelet thrombi in the lungs. In this study, neither hydroxyurea use nor perimortem transfusion was associated with platelet thrombi. Surprisingly, in all cases, there was profound pulmonary artery remodeling with both thrombotic and proliferative pulmonary plexiform lesions. The severity of remodeling was not associated with a severe history of ACS, or hydroxyurea use, but was inversely correlated with age. We thus provide evidence of undocumented presence of platelet thrombi in cases of fatal ACS and describe clinical correlates. We also provide novel correlates of pulmonary remodeling in SCD.
Vascular Biology Center, Georgia Regents University, Augusta, Georgia.
Ciprian B
CB
Anea
Department of Emergency Medicine, Georgia Regents University, Augusta, Georgia.
Matthew
M
Lyon
Vascular Biology Center, Georgia Regents University, Augusta, Georgia.
Itia A
IA
Lee
Vascular Biology Center, Georgia Regents University, Augusta, Georgia.|Department of Medicine, Division of Pulmonary/Critical Care, Georgia Regents University, Augusta, GA.
Joyce N
JN
Gonzales
Vascular Biology Center, Georgia Regents University, Augusta, Georgia.
Amidat
A
Adeyemi
Department of Pathology, Georgia Regents University, Augusta, Georgia.
Greer
G
Falls
Department of Medicine, Division of Hematology/Oncology, Augusta, Georgia.
Abdullah
A
Kutlar
Vascular Biology Center, Georgia Regents University, Augusta, Georgia.
Julia E
JE
Brittain
D056586:Acute Chest Syndrome / Q000097:blood / Q000473:pathology*; D000755:Anemia, Sickle Cell / Q000097:blood / Q000473:pathology; D001344:Autopsy; D001792:Blood Platelets / Q000473:pathology*; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000473:pathology*; D015539:Platelet Activation; D010976:Platelet Count; D011651:Pulmonary Artery / Q000473:pathology*; D011655:Pulmonary Embolism / Q000473:pathology*; D066253:Vascular Remodeling