Changes in protein C, factor VII and endothelial markers after autologous bone marrow transplantation: possible implications in the pathogenesis of veno-occlusive disease.
In a recent prospective study of allogenic bone marrow transplantation we reported that decreases in factor VII and protein C were predictive markers for high risk of veno-occlusive disease (VOD). In order to determine the relative involvement of endothelial and hepatocyte injury in the genesis of VOD, 34 consecutive patients undergoing autologous bone marrow transplantation (BMT) were studied. Conditioning was performed by chemotherapy alone or associated with total body irradiation (TBI). Protein C and factor VII, the endothelial markers Von Willebrand factor (vWF and t-PA, fibrinogen and fibronectin were measured weekly before and after BMT. Protein C and factor VII were within the normal range before BMT, decreased significantly on day 7 to 73 and 64% respectively (p < .01) and then returned to normal values. Fibrinogen increased to 7 g/l (p < .001) on day 7 but then returned to normal levels. Fibronectin was abnormally high (p < .001) before BMT and decreased thereafter, while vWF increased (p < 0.001) for three consecutive weeks. t-PA was low (p < 0.001) before conditioning but increased thereafter. These results demonstrate the presence of endothelial lesions before BMT and acute hepatic and endothelial lesions after conditioning. Although VOD was never observed in our patients, this complication could well arise from preexisting vascular lesions due to previous chemotherapy and/or from acute hepatocytic injury, which could also be of endothelial origin, after conditioning.
Bazarbachi
A
A
Institut d'Hématologie, Hôpital Saint-Louis, Paris, France.
Scrobohaci
M L
ML
Gisselbrecht
C
C
Marolleau
J P
JP
Mansi
A
A
Brice
P
P
Gorra
P
P
Drouet
L
L
D015415:Biomarkers / Q000097:blood; D001779:Blood Coagulation Factors / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000737:chemistry*; D005167:Factor VII / Q000378:metabolism*; D005353:Fibronectins / Q000097:blood; D006504:Hepatic Veno-Occlusive Disease / Q000097:blood / Q000209:etiology*; D006801:Humans; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism; D014182:Transplantation, Autologous
D015415:Biomarkers; D001779:Blood Coagulation Factors; D005353:Fibronectins; D011486:Protein C; D012709:Serum Albumin; D005167:Factor VII