Coagulation/fibrinolysis abnormality and vascular endothelial damage in the pathogenesis of thrombocytopenic multiple organ failure.
OBJECTIVE
Until recently, attention has been directed to disseminated intravascular coagulation as a cause of multiple organ failure (MOF). On the other hand, it has now become clear that humoral mediators play important roles in the pathogenesis of MOF. Therefore, we performed the present study in patients with thrombocytopenic MOF to investigate the relationship between various humoral mediators and vascular endothelial damage reported to be triggered by such humoral mediators in the pathogenesis of MOF.


METHODS
A retrospective clinical study.


METHODS
Intensive care unit of a university hospital.


METHODS
The study included 18 thrombocytopenic patients whose conditions progressed to septic MOF (MOF group) and 20 others who did not progress to MOF (non-MOF group). The MOF group and non-MOF group were also presented with infection and with platelet counts of <100,000/mm3.


RESULTS
The MOF group had fibrinolysis abnormality, as indicated by increased plasminogen activator inhibitor-1 level. On the other hand, the MOF group had increased polymorphonuclear elastase and polymorphonuclear-mediated fibrinogen degradation product levels with consequent prolonged elevation of thrombomodulin. In addition, both polymorphonuclear elastase and polymorphonuclear-fibrinogen degradation products were significantly positively correlated with thrombomodulin in the MOF group, but no such positive correlation was observed between interleukin-6 or plasminogen activator inhibitor-1 and thrombomodulin. In the non-MOF group, on the other hand, thrombomodulin exhibited no significant positive correlation with polymorphonuclear elastase, polymorphonuclear-fibrinogen degradation products, interleukin-6, or plasminogen activator inhibitor-1.


CONCLUSIONS
Our study provided evidence that vascular endothelial damage was the primary cause of organ failures in patients with thrombocytopenic MOF and that humoral mediators played a major role in the development of vascular endothelial damage in such patients. These results suggest that it is important to treat thrombocytopenic MOF as a condition of vascular endothelial damage, with weight placed on countermeasures against disorders of humoral mediators.
Ueno
Hirokazu
H
Department of Emergency and Critical Care Medicine, Chiba University School of Medicine, Japan. h-ueno@umin.ac.jp
Hirasawa
Hiroyuki
H
Oda
Shigeto
S
Shiga
Hidetoshi
H
Nakanishi
Kazuya
K
Matsuda
Kenichi
K
D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005342:Fibrinolysis; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D019272:Leukocyte Elastase / Q000097:blood; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D010976:Platelet Count; D012189:Retrospective Studies; D018805:Sepsis / Q000150:complications; D013921:Thrombocytopenia / Q000097:blood / Q000150:complications*; D018180:Thrombomodulin / Q000097:blood
D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D010972:Platelet Activating Factor; D018180:Thrombomodulin; D019272:Leukocyte Elastase