The platelet function defect of cardiopulmonary bypass [see comments]

Abstract

The use of cardiopulmonary bypass (CPB) during cardiac surgery is associated with a hemostatic defect, the hallmark of which is a markedly prolonged bleeding time. However, the nature of the putative platelet function defect is controversial. In this study, blood was analyzed at 10 time points before, during, and after CPB. We used a whole-blood flow cytometric assay to study platelet surface glycoproteins in (1) peripheral blood, (2) peripheral blood activated in vitro by either phorbol myristate acetate, the thromboxane (TX)A2 analog U46619, or a combination of adenosine diphosphate and epinephrine, and (3) the blood emerging from a bleeding-time wound (shed blood). Activation-dependent changes were detected by monoclonal antibodies directed against the glycoprotein (GP)Ib-IX and GPIIb-IIIa complexes and P-selectin. In addition, we measured plasma glycocalicin (a proteolytic fragment of GPIb) and shed-blood TXB2 (a stable breakdown product of TXA2). In shed blood emerging from a bleeding-time wound, the usual time-dependent increase in platelet surface P-selectin was absent during CPB, but returned to normal within 2 hours. This abnormality paralleled both the CPB-induced prolongation of the bleeding time and a CPB-induced marked reduction in shed-blood TXB2 generation. In contrast, there was no loss of platelet reactivity to in vitro agonists during or after CPB. In peripheral blood, platelet surface P-selectin was negligible at every time point, demonstrating that CPB resulted in a minimal number of circulating degranulated platelets. CPB did not change the platelet surface expression of GPIb in peripheral blood, as determined by the platelet binding of a panel of monoclonal antibodies, ristocetin-induced binding of von Willebrand factor, and a lack of increase in plasma glycocalicin. CPB did not change the platelet surface expression of the GPIIb-IIIa complex in peripheral blood, as determined by the platelet binding of fibrinogen and a panel of monoclonal antibodies. In summary, CPB resulted in (1) markedly deficient platelet reactivity in response to an in vivo wound, (2) normal platelet reactivity in vitro, (3) no loss of the platelet surface GPIb-IX and GPIIb-IIIa complexes, and (4) a minimal number of circulating degranulated platelets. These data suggest that the “platelet function defect” of CPB is not a defect intrinsic to the platelet, but is an extrinsic defect such as an in vivo lack of availability of platelet agonists. The near universal use of heparin during CPB is likely to contribute substantially to this defect via its inhibition of thrombin, the preeminent platelet activator.

Nitric oxide diffusion across membrane lungs protects platelets during simulated extracorporeal circulation

“…CPB causes prolongation of bleeding time and reduced agglutination, secretion and aggregation [13][14][15][16]. Flow cytometric analysis of different platelet receptors reveales no uniform pictures, decreased [13,17,18], unchanged [19] or increased [20] GPIb expression, decreased [18] or unchanged [13,19] GPIIb-IIIa expression, and increased [13] or unchanged [18,19] numbers of activated circulating platelets having been found during ECC. The reasons for these different findings are not clear, but they may be due to different experimental conditions (e.g.…”

“…shear stress) or the presence of different subpopulations of circulating platelets. Others have postulated that the platelet functional defect is not an intrinsic defect of the platelet but an extrinsic effect due to lack of availability of platelet agonists caused by heparin-induced inhibition of thrombin [19]. However, there is considerable evidence that not only GPIb but also GPIIb-IIIa is involved in platelet-surface interactions [21].…”

Recent Advances on Plasmin Inhibitors for the Treatment of Fibrinolysis‐Related Disorders

“…175 Aprotinin is known to interfere with heparin binding to platelets and appears to reduce peri-and postoperative blood loss resulting from heparin usage. 176,177 Despite the many advantageous effects of aprotinin, results from the BART clinical trial led to suspension of aprotinin's clinical use in May 2008. 178,179 This large multicenter study found that even though the risk of bleeding was lowest in the aprotinin group for patients undergoing high-risk cardiac surgery in comparison to TXA and EACA groups, mortality was significantly higher, which led to early termination of the trial.…”

Thrombelastography/thromboelastometry

“…Another cause of coagulopathy is the trauma associated with the extracorporeal circuit resulting in cellular damage. This leads to a decrease in platelet number and function (Kestin et al, 1993) and activation of inflammatory systems. Platelet function is further impaired as a result of hypothermia (Valeri et al, 1987).…”