Robert Flaumenhaft, MD, PhD
Dr. Flaumenhaft indicated no relevant conflicts of interest.
Echtler K, Stark K, Lorenz M, et al. Platelets contribute to postnatal occlusion of the ductus arteriosus. Nat Med. 2010;16:75-82.
The role of platelets in host defense is well established. They limit blood loss, stimulate inflammation, and respond to invading microbes. Platelets are also known to contribute to vascular intergrity and participate in angiogenesis and wound healing. Less well-studied is the role that platelets play in normal development. Recent studies indicate that platelets serve a role in the formation of the lymphatic system. Echtler et al. now demonstrate that platelets are crucial for permanent closure and remodeling of the ductus arteriosus following birth, providing a striking example of how platelets may contribute to normal development.
In the fetus, the ductus arteriosus shunts blood from the placenta to the aorta, bypassing the nonventilated lungs. Following birth, the ductus arteriosus closes, enabling perfusion of the newly ventilated lungs. The ductus arteriosus is subsequently remodeled into a fibrous band by mechanisms that are incompletely understood. Working in the Massberg laboratory in Munich, Echtler et al. found histological evidence of platelet accumulation within the lumen of the ductus arteriosus of newborn mice evaluated directly after birth. Intravital microscopy of newborn pups 20 minutes after birth demonstrated substantial adhesion of platelets at the ductus arteriosus, but not in the adjacent aorta. Using closure angiography, they demonstrated that mice deficient in the platelet fibrinogen receptor integrin áIIb, mice infused with an antibody to the collagen receptor GPVI, or congenitally thrombocytopenic mice demonstrated a high incidence of persistent patency of the ductus arteriosus. The thrombocytopenic mice with persistent patency demonstrated pulmonary hypertension and right ventricular remodeling. To assess the relevance of their results to the human process, the investigators evaluated specimens from newborns undergoing cardiac surgery for congenital heart disease. They demonstrated exposure of the adhesion protein von Willebrand factor and fibrinogen as well as platelet accumulation in the lumen of the ductus arteriosus. They also performed a retrospective analysis of premature infants that demonstrated thrombocytopenia as a major risk factor for patency of the ductus arteriosus.
|Click image to enlarge
Persistence of a patent ductus arteriosus is a major cause of morbidity and mortality in preterm infants. The incidence is approximately 0.2 percent. However, in babies < 1,500 g, the incidence is > 30 percent. The model presented in this paper suggests that an initial contraction of the ductus arteriosus and subsequent platelet-mediated sealing are required for permanent closure. This model accounts for the observation that thrombocytopenia is associated with failed closure of patent ductus arteriosus by indomethacin, which stimulates constriction of the vessel but not sealing. These observations provide substantial evidence for platelet closure of the ductus arteriosus in mice and premature infants. The role of platelets in closure of the ductus arteriosus in mature newborns remains less clear, as hypoxia alone may stimulate sufficient remodeling. Nonetheless, these studies provide an important and unexpected role of platelets in the development of the heart.
back to top