Disseminated intravascular coagulation in association with pig-to-primate pulmonary xenotransplantation.
BACKGROUND
Profound coagulopathy has been proposed as a barrier to xenotransplantation. Disseminated intravascular coagulation (DIC) has been observed with the rejection of renal and bone marrow xenografts but has not yet been described in pulmonary xenografts.


METHODS
This study examined the coagulation parameters in five baboons that received pulmonary xenografts and one baboon that was exposed to porcine lung during an extracorporeal perfusion. Platelet counts, prothrombin times (PT), and levels of fibrinogen, D-dimers, and thrombin-antithrombin III complex (TAT) were analyzed. In addition, serum levels of plasminogen activator inhibitor-1 (PAI-1), thrombomodulin (TM), tissue plasminogen activator (tPA), and tissue factor (TF) were determined.


RESULTS
Hyperacute pulmonary xenograft dysfunction, which occurred within 0-9 hr of graft reperfusion, was associated with clinically evident DIC. This coagulopathy was characterized by thrombocytopenia, decreased fibrinogen levels, elevations in PT, and increases in D-dimers and TAT. Furthermore, transient increases in PAI-1, increases in TM, and increases in tPA were observed in the serum of some but not all recipients. None of the baboons demonstrated measurable increases in soluble TF.


CONCLUSIONS
Although DIC in renal or bone marrow xenotransplantation develops over a period of days, DIC associated with hyperacute pulmonary xenograft dysfunction develops within hours of graft reperfusion. Thus, the DIC in pulmonary xenotransplantation may represent a unique and/or accelerated version of the coagulopathy observed with renal and bone marrow xenotransplantation.
Gaca
Jeffrey G
JG
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Lesher
Aaron
A
Aksoy
Olcay
O
Gonzalez-Stawinski
Gonzalo V
GV
Platt
Jeffrey L
JL
Lawson
Jeffrey H
JH
Parker
William
W
Davis
R Duane
RD
D000818:Animals; D000990:Antithrombin III / Q000032:analysis; D001777:Blood Coagulation; D004211:Disseminated Intravascular Coagulation / Q000209:etiology*; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D016040:Lung Transplantation / Q000009:adverse effects*; D010215:Papio; D010447:Peptide Hydrolases / Q000032:analysis; D010976:Platelet Count; D011517:Prothrombin Time; D013552:Swine; D014183:Transplantation, Heterologous / Q000009:adverse effects
D005338:Fibrin Fibrinogen Degradation Products; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D000990:Antithrombin III; D005340:Fibrinogen; D010447:Peptide Hydrolases