Extracorporeal circulation in sheep with normal bleeding time using a surface heparinized circuit.

Bleeding due to systemic heparinization represents the major side effect of extracorporeal respiratory support. In the present animal study, a surface heparinized system (Carmeda Biological Active Surface) was applied to assess the feasibility of prolonged perfusion at low circulating heparin levels. Eight sheep divided into two groups: group A (5 animals) and group B (3 animals) underwent venovenous bypass using a heparin coated surface circuit. The following protocol was used: a) 24 hours at high heparin dose (30 to 100 U/kg/hr with an ACT [activated coagulation time] three to four times normal); b) 24 hours at low heparin dose (3 to 8 U/kg/hr with an ACT within the normal range); c) 24 hours at high heparin dose. Group B animals also received fresh frozen sheep plasma (14 ml/kg/day). During Period b, the clotting times were within baseline range. The bleeding time showed a dramatic decrease after change from a to b (27.9 +/- 3 minutes vs. 10.2 +/- 5.6 minutes). There was a negative relationship between antithrombin III (AT III) and thrombin coagulase time (TC); the latter is considered to be an aspecific indicator of circulating fibrin(ogen) degradation products. Maintaining AT III over 70%, TC changes were only minor. The use of the bioactive heparin surface allowed the performance of a 24 hour bypass, with normal coagulation times, at low circulating heparin levels.

Physiopathology and management of coagulation during long-term extracorporeal respiratory assistance.

Thrombohemorrhagic risk is one of the main limiting factors in extracorporeal circulation. We describe here our experience in managing some life-threatening hematological complications in 58 patients with acute respiratory failure treated with long-term extracorporeal assistance. These patients were studied by clinical and laboratory means to assess questions related to heparin monitoring, coagulation complications and bleeding incidence. We found that two clotting tests, activated partial thromboplastin time (APTT) and activated clotting time (ACT) can be easily used to assess the safety of anticoagulant treatment (therapeutic ranges: APTT from 55 to 95 sec and ACT from 170 to 220 sec). A certain degree of coagulation activation, despite heparin, was indicated by the constant finding of thrombin-antithrombin complexes, while fibrinolytic activation, measured as plasminogen activator activity, was confined to the time of bypass connection and was of no clinical consequence. Platelet function was always impaired without relation to the platelet loss. Disseminated intravascular coagulation (DIC) (13 episodes) and severe bleeding (11 episodes) were major complications. DIC was corrected with a good outcome for 8 of 13 patients, while severe bleeding was correlated with a poor outcome in 8 of the 11 patients, probably because of the severity of the underlying disease.

Fibrinolytic response in normal subjects to venous occlusion and DDAVP infusion.

A set of fibrinolytic parameters was measured in 40 healthy subjects before and after a venous occlusion (VO) test lasting 10 min. After VO, plasma levels of tissue-type plasminogen activator (t-PA) antigen increased in all subjects, t-PA activity increased only in 25 subjects who were considered responders and remained unchanged in 15 (non-responders). High levels of plasminogen activator inhibitor (PAI) in the non-responder group explain this discrepancy. The non-responders had basal levels of PAI activity and t-PA antigen higher than responders (p less than 0.0001) and their basal levels of t-PA activity were lower (p less than 0.001). DDAVP infusion elicited good responses in 7 of 9 non-responders to VO with a fall of PAI activity to 0. Our data indicate that a high proportion of healthy subjects do not have a fibrinolytic response after VO, that a lack of fibrinolytic response to VO is due to high plasma levels of PAI and that DDAVP infusion appear to be more selective than VO for detecting non-responders.