Intrinsic pathway–dependent activated clotting time is not reliable for monitoring anticoagulation during cardiopulmonary bypass in neonates

Abstract

The conventional activated clotting time (ACT) stimulated by celite is often prolonged during neonatal or pediatric cardiopulmonary bypass operations. 1'2 This prolonged ACT may lead to insufficient use of heparin during bypass and result in serious consequences such as intravascular coagulation after the operation. 3 Dilution of the clotting factors because of high-degree hemodilution during bypass is often blamed for the prolongation of ACT, 2' 4 but it is still unknown whether the total clotting capacity in the circulating blood is similarly affected by the extreme hemodilution. Because the celite ACT is a clotting test dependent on the intrinsic pathway, we postulate that it is the intrinsic pathway (rather than the extrinsic and the common pathways) that fails to respond properly under highdegree hemodilution during neonatal bypass operations. As a first step, we studied the in vitro effect of dilution on celite ACT by using heparinized blood taken from 10 adults having coronary artery bypass. The samples were taken after a 300 IU/kg dose of bovine heparin was given before the start of bypass. These patients received no drugs known to affect clotting and had a normal clotting profile before the operation. Blood samples were diluted in the laboratory to 25%, 50%, and 75% with saline solution or were left undiluted as control samples. Three different types of stimuli were used to initiate clotting: celite (final concentration 3 mg/ml) stimulating clotting through the intrinsic pathway, rabbit brain thromboplast in (final concentration 4 mg/ml) through the extrinsic pathway, and high-dose thrombin (final concentration 9 U/ml) through the common pathway. All measurements were performed with a Hemochron 8000 machine (International Technidyne Co., Edison, N.J.). An ACT longer than 1000 seconds was stopped and recorded as 1000 seconds. In blood samples stimulated by celite, ACT was prolonged significantly when the blood was diluted to 75% compared with the ACT of control samples (p < 0.01), whereas in samples stimulated by thromboplast in no significant change was observed. Furthermore, in blood samples stimulated by thrombin a significant reduction of ACT was found in proport ion to the dilution of blood (p < 0.01, Table I). These results