Microcirculatory disorders in sepsis and transplantation: therapy with natural coagulatory inhibitors antithrombin and activated protein C.
OBJECTIVE
Modern technologies allow visualization of microcirculatory disorders. This review describes how the coagulatory inhibitors antithrombin and activated protein C (APC) can improve microcirculation in sepsis and transplantation.


RESULTS
The effects of antithrombin and APC on microcirculatory disorders in ischemia reperfusion and experimental sepsis have been reported recently. In addition, antithrombin has recently been clinically used to reduce graft pancreatitis after pancreas-kidney transplantation, and to improve kidney perfusion. It was demonstrated that septic capillary perfusion failure as well as leukocyte-endothelial cell interactions can be reversed by high-dose prophylactic antithrombin application. APC was also highly effective in this context. Thus, APC could improve microcirculatory blood flow in septic patients as recently measured by in-vivo orthogonal polarization spectral imaging techniques. For antithrombin, comparable measurements in humans are currently not available.


CONCLUSIONS
Microcirculatory dysfunction plays a key role in the development of organ dysfunction in septic patients and after solid organ transplantation. The exogenous application of coagulatory inhibitors may provide a new important strategy for prevention and treatment of microcirculatory disorders. This mode of action may be the reason why coagulatory inhibitors could improve mortality in septic patients without directly influencing inflammatory mediator concentrations.
Hoffmann
Johannes N
JN
Department of Surgery, Klinikum Grosshadern, University of Munich, Germany. johannes.hoffmann@med.uni-muenchen.de
Fertmann
Jan M
JM
Jauch
K W
KW
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D000991:Antithrombins / Q000494:pharmacology*; D006801:Humans; D008833:Microcirculation / Q000187:drug effects*; D023421:Models, Animal; D016377:Organ Transplantation / Q000009:adverse effects*; D011486:Protein C / Q000494:pharmacology*; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control
D000925:Anticoagulants; D000991:Antithrombins; D011486:Protein C