Postoperative Bleeding after CABG - does Individualized Heparin Management Save Blood?

Objectives: To compare routine activated clotting time (ACT) based hemostasis management to individualized heparin management (IHM) in terms of postoperative bleeding, platelet function, and coagulation markers.

Methods: 120 CABG patients (≥ 3 distal anastomoses) were enrolled in a prospective trial and were randomized for hemostasis management (ACT versus IHM). With a target ACT of 400 second conventional hemostasis management antagonized heparin with protamine in a ratio of 1:>0.8, whereas in IHM protamine dosages were calculated from residual heparin concentrations. Hemostasis was analyzed immediately post-OP by thrombelastometry, aPTT, INR, and a range of coagulation markers.

Results: A total of 112 patients (ACT: 56, IHM: 56) were included. Median heparin dosages were equivalent in both groups, whereas IHM patients received significantly less protamine. INR did not differ significantly, but aPTT values were significantly higher in HM patients. INTEM clotting times were elevated in IHM patients, whereas HEPTEM clotting times did not differ. Most coagulation markers (antithrombin III, d-dimers, fibrinogen, factors II/V/VIII/X, tissue factor pathway inhibitor, platelet counts) did not differ between groups, whereas thrombin-antithrombin complexes (TATs) were higher in ACT patients (29.69 [15.14–42.19] versus 18.50 [12.14–29.22] µg/l, p = 0.005), indicating recovered coagulation capacities. TATs correlated significantly with protamine doses (p = 0.022). Blood losses were slightly but significantly higher in IHM patients within the first 12 hour which balanced at 24 hour and which did not lead to more blood transfusions (40 PRBC in 15 patients versus 44/17, p = 0.926).

parameters	ACT	IHM	p
[Perioperative parameters (median[1st qu.-3rd qu])].
total heparin (IU/kg)	435.8 [411.7–505.1]	418.5 [346.9–590.5]	0.581
protamin (IU/kg)	355.3 [348.2–392.8]	233.4 [181.7–307.7]	< 0.0001
protamine/total heparin	0.852 [0.760–0.909]	0.521 [0.463–0.582]	< 0.0001
aPTT (s)	37.0 [33.0–40.0]	50.5 [40.0–60.0]	< 0.0001
INR	1.30 [1.30–1.40]	1.35 [1.30–1.40]	0.717
INTEM-CT (s)	201 [191–216]	215 [192–236.8]	0.040
HEPTEM-CT (s)	186 [175.5–207.3]	192 [173.8–202.0]	0.249
blood loss within 12 hour post-OP (ml)	345 [230.0–482.5]	420 [337.5–605.0]	0.004
blood loss within 24 hour post-OP (ml)	665 [487.5–900.0]	750 [580.0–920.0]	0.112

Conclusions: IHM patients did not benefit from allegedly reduced coagulation factor activation mainly because heparin dosages were unexpectedly identical in both groups. On the contrary, postoperative parameters indicated an incomplete heparin antagonization in IHM patients.