Behaviour of the Contact Phase of Blood Coagulation in the Adult Respiratory Distress Syndrome (ARDS)

Abstract

SummaryIn order to assess the role of the kallikrein-kinin (K-K) system in the pathogenesis of the adult respiratory distress syndrome (ARDS) we have prospectively determined coagulation contact phase, blood gas and hemodynamic parameters in patients with ARDS at 0, 36 and 72 h from diagnosis.Compared to normal values, significantly lower mean levels of factor XII (71.4 ± 9.8%, p <0.0005), prekallikrein (PPK) (52 ± 5.7%, p <0.0005), high molecular weight kininogen (HMWK) (73 ± 2%, p <0.0005) and α2-macroglobulin (α2-M) (51 ± 7.1%, p <0.0005) were found in ARDS patients.The functional kallikrein inhibitory activity (KKI) and Cr esterase inhibitor antigenic (CIINH) were significantly higher in these patients (113.2 ± 5, p <0.005 and 124.7 ± 7.6, p <0.0005 respectively) compared with normal values during the entire study period.The KKI/CIINH ratio decreased significantly in our ARDS patients at 0, 36 and 72 h (p <0.025; p <0.05 and p <0.005 respectively).We found a significant correlation between PPK levels and oxigenation index (r = 0.69, p <0.001), PPK and the static thoracic compliance values (r = 0.64, p <0.001). There was also a significant correlation between PPK levels and Qs/Qt (r = -0.89, p <0.001). ARDS patients that survived presented a stability in the PPK values in successive tests. Nevertheless non-survivors showed a progressive decrease in PPK levels during the follow-up period.Our results suggest that the plasma kallikrein system becomes activated during ARDS and that this activation might increase the lung vessels’ permeability. In addition, PPK levels are in our opinion a useful prognostic parameter in predicting the outcome of ARDS patients.

Endotoxin-induced pulmonary dysfunction is prevented by C1-esterase inhibitor.

“…This decrease could not be attributed to hemodilution in that the hematocrit increased moderately during the experiment and the increase was similar in both groups (data not shown). Previous studies by us and others have shown that, in ARDS patients, the plasma levels of HK, factor XII, and PK were decreased suggesting an activation of the kallikrein-kinin system (29,30). In our study (29), the decrease in PK levels correlated with the severity of the pulmonary dysfunction; conversely, in patients with pulmonary dysfunction due to cardiogenic pulmonary edema without ARDS, the plasma levels of PK, factor XII, and high molecular weight kininogen were not decreased.…”

“…Previous studies by us and others have shown that, in ARDS patients, the plasma levels of HK, factor XII, and PK were decreased suggesting an activation of the kallikrein-kinin system (29,30). In our study (29), the decrease in PK levels correlated with the severity of the pulmonary dysfunction; conversely, in patients with pulmonary dysfunction due to cardiogenic pulmonary edema without ARDS, the plasma levels of PK, factor XII, and high molecular weight kininogen were not decreased. Thus, it appears that in ARDS the activation ofthe contact system is not a direct consequence of the pulmonary edema (3 1 ).…”

“…In a previous report, we observed decreased plasma levels of prekallikrein (PK) in patients with ARDS (29); this finding was considered a result ofthe activation ofthe contact phase of blood coagulation (29,30). In these patients, the decrease in plasma PK levels correlated with the degree ofpulmonary dysfunction.…”

Haemocompatibility of paediatric membrane oxygenators with heparin-coated surfaces

“…The usual postperfusion syndromes can then appear, with their escalating possibilities, even continuing to sepsis, ARDS or MOF. [5][6][7][8]23 In light of this relationship, the value of improving the artificial materials' biocompatibility as a means to controlling these syndromes has long been recognized. As the first heparin-coated oxygenators became available in the last half of the 1980s, many research groups examined the oxygenators' biocompatibility in in vitro systems, animal models, and later, in patient studies.…”

“…This syndrome can lead to systemic inflammatory response syndrome (SIRS), acute lung failure (ARDS, adult respiratory distress syndrome), sepsis and multi-organ failure (MOF). [5][6][7][8][9] The incomplete haemocompatibility of the perfusion systems used during ECC plays a significant role in these changes. Therefore, in paediatric cardiac surgery, minimization of the CPB-mediated activation mechanisms caused by the interactions of the blood with the artificial surfaces are of prime importance.…”