Kenichiro Aoi

Activation of the extrinsic coagulation pathway in patients with severe sepsis and septic shock

OBJECTIVES To obtain systematic information on the extrinsic coagulation pathway, as well as to investigate the time course of the coagulation abnormalities in sepsis. DESIGN Prospective observational study. SETTING General intensive care unit. PATIENTS Nineteen patients with the diagnosis of severe sepsis or septic shock and nine control patients. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Tissue factor antigen concentration (tissue factor antigen), prothrombin fragment F1+2, thrombin antithrombin III complex, fibrinopeptide A, D-dimer, and antithrombin III concentrations were measured on the day of diagnosis of severe sepsis and septic shock, and on days 1, 2, 3, and 4 after diagnosis. The concentrations of tissue factor antigen, prothrombin fragment F1+2, fibrinopeptide A, and D-dimer were significantly increased in patients with severe sepsis and septic shock compared with control subjects. However, the concentrations of thrombin antithrombin III complex showed no statistical differences between the septic patients and the control subjects. Significantly, low antithrombin III concentrations were observed in the septic patient groups compared with control subjects. With the exception of D-dimer, the concentrations of the hemostatic markers were similar between severe sepsis and septic shock patients. Significant correlations were noted between tissue factor antigen and the disseminated intravascular coagulation score (r2=.236, p< .0001) and the number of dysfunctioning organs (r2=.229, p=.035). CONCLUSIONS We systematically elucidated coagulation disorders in newly defined sepsis. The extrinsic coagulation pathway is activated in patients with severe sepsis and septic shock. In these patients, enhanced thrombin generation and activation, and fibrin formation were demonstrated when compared with the control subjects. Furthermore, the thrombin generated appears not to be fully neutralized by antithrombin III.

Therapeutic strategy of perioperative use of percutaneous cardiopulmonary bypass support (PCPS) for adult cardiac surgery

SUBJECT AND METHOD Percutaneous cardiopulmonary bypass support is beneficial for patients with circulatory collapse. However, therapeutic strategies of percutaneous cardiopulmonary bypass support for post-cardiotomy LOS have not been determined. We reviewed 9 patients undergoing cardiac surgery and treated with percutaneous cardiopulmonary bypass support to determine an adequate strategy for perioperative use of percutaneous cardiopulmonary bypass support. Patients included 8 males and 1 female with a mean age of 56.4 +/- 3.9 years. Six patients with IHD underwent CABG for 5 and CABG + MVR for 1 patient and 3 patients with valvular disease underwent AVR, AVR + MVR, and Ross operation respectively. Indication for percutaneous cardiopulmonary bypass support was post-cardiotomy LOS in 7 and preoperative cardiogenic shock in 2 patients. All patients underwent IABP associated with percutaneous cardiopulmonary bypass support. Systemic blood pressure was regulated to 100-120 mmHg by percutaneous cardiopulmonary bypass support flow and with minimum inotropic supports. RESULTS Six of 9 patients (66.7%) were weaned from percutaneous cardiopulmonary bypass support and 5 patients were discharged. Five of 6 patients (83.3%) with IHD were weaned from percutaneous cardiopulmonary bypass support compared to 1 of 3 patients (33.3%) (p = 0.134) with valvular disease. Hemodynamic conditions in patients weaned from percutaneous cardiopulmonary bypass support were markedly improved within 40 hours of the introduction of percutaneous cardiopulmonary bypass support (mean percutaneous cardiopulmonary bypass support running time: 23.9 +/- 5.5 hrs). In contrast, those unable to be weaned from percutaneous cardiopulmonary bypass support (mean percutaneous cardiopulmonary bypass support running time: 84.3 +/- 6.3 hrs) showed no improvement and developed major complications such as cerebral damage or multiorgan failure. CONCLUSIONS Perioperative use of percutaneous cardiopulmonary bypass support may be more effective for patients undergoing coronary artery surgery. Limited use of percutaneous cardiopulmonary bypass support within 48 hours may be applicable for post-cardiotomy patients.

Role of pulmonary intravascular macrophages in anti-platelet serum-induced pulmonary hypertension in sheep

It has been reported that an injection of anti-sheep platelet serum (AsPS) induces transient pulmonary hypertension in sheep, but the mechanism by which this occurs has not been well explained. To examine the hypothesis that pulmonary intravascular macrophages (PIMs) are involved in this phenomenon, we investigated the morphological features of PIMs from sheep that received three different kinds of AsPS injections. The pulmonary arterial pressure response was examined not only in sheep that have many PIMs in the lung and had received AsPS, but also in rats that reportedly have few PIMs and had received an injection of anti-rat platelet serum. The pulmonary arterial pressure responses of the two species were quite different in quality and quantity. In sheep whose pressure response was definitely positive in association with production of thromboxane in the pulmonary circulation, PIMs were found by fluorescent microscopy and electron microscopy to phagocytize aggregated platelets that bound AsPS. These results suggest that PIMs significantly contribute to AsPS-induced transient pulmonary hypertension in sheep.