[Use of heparin and platelet GPIIbIIIa inhibitor tirofiban for cardiac surgery in patients for suspicion of heparin-induced thrombocytopenia]. / Chirurgie cardiaque effectuée avec une association héparine non fractionnée et inhibiteur des récepteurs GPIIbIIIa plaquettaire (tirofiban) pour suspicion de TIH.

In a patient with heparin-induced thrombocytopenia few antithrombotic alternate treatments are proposed for cardiac surgery with or without cardiopulmonary bypass: danaparoid, lepirudine or powerful antiplatelet agent. Recently, the platelet GPIIbIIIa antagonist tirofiban (Aggrastat) was tested in humans. We reported two cases of patients operated upon for cardiac surgery with unfractionnated heparin (UFH) and tirofiban. The first patient underwent an off-pump coronary artery bypass graft and the second one a mitral valvular replacement under cardiopulmonary bypass. Tirofiban was associated with UFH and aprotinine. Postoperative bleeding was in the normal range for the two types of surgeries and haemodynamic tolerance was good. These two case reports support the possibility of secure cardiac surgery under efficient platelet inhibition with tirofiban. The management of cardiac surgery with tirofiban without monitoring of platelet aggregation appeared to be more simple than with the other alternate antithrombotic agents.

High incidence of anti-heparin/platelet factor 4 antibodies after cardiopulmonary bypass surgery.

Fifty-one patients undergoing cardiopulmonary bypass (CPB) were studied on day 0 and day 8 for heparin-induced thrombocytopenia (HIT). The platelet aggregation test (PAT) and tests for anti-heparin-platelet factor 4 (anti-H.PF4), anti-IL8 and anti-neutrophil activating peptide 2 (anti-NAP2) antibodies (Ab) were performed by ELISA. On day 8, 27% of patients were positive for anti-H.PF4Ab. None of these results were found to influence thrombotic complications or platelet counts after CPB. Our results suggest that IgG to H.PF4 may be considered a risk factor, but that additional factors must be required for HIT to develop. We conclude that assays based on platelet activation would be more appropriate for the diagnosis of HIT after CPB.

Postoperative hemostasis and fibrinolysis in patients undergoing cardiopulmonary bypass with or without aprotinin therapy.

Intra- and postoperative blood loss during open heart surgery is reduced by approximately 50% when aprotinin, a potent inhibitor for plasmin and kallikrein, is administered during surgery. But whether aprotinin increases the risk of thrombotic complications remains controversial. The aim of this study was to evaluate the effects of aprotinin administration on coagulation and fibrinolysis during and after cardiopulmonary bypass (CPB). Thirty patients undergoing CPB were randomly assigned to two comparable groups for a double-blind study (16 patients receiving high-dose aprotinin, 14 patients receiving placebo). Patients' plasma levels of ATM (thrombin-induced modified antithrombin III), FbDP (fibrin degradation products, D-Dimers), t-PA (tissue-type plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) were measured at regular intervals. In both groups, ATM level increased during surgery (from less than 30 to 90-110 ng/ml) and returned to normal 24 h after surgery and remained unchanged thereafter. Aprotinin reduced this increase in ATM levels (p = 0.02 at 30 min after the start of CPB). The FbDP generated during surgery was greatly reduced in the aprotinin group (945 ng/ml) in comparison with the placebo group (1889 ng/ml, p = 0.004). After surgery, FbDP levels decreased in both groups with nadirs at 2nd day (placebo group: 940 ng/ml and aprotinin group: 865 ng/ml) indicating a hypofibrinolytic period. Then, the FbDP level in both groups started to increase up to the 9th day, in an identical manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemostasis in patients undergoing extracorporeal circulation: the effect of aprotinin (Trasylol).

The administration of aprotinin during extracorporeal circulation (ECC) reduces blood loss. To explore the mechanism of this effect, a placebo-controlled double-blind study was performed in 20 patients (10 were administered with a high dose of aprotinin, 10 with placebo) undergoing a primary, elective operation of coronary artery bypass grafting (CABG) with ECC. Biological tests were performed at 4 different time points during the operation. A marked reduction in the placebo group of ristocetin-induced platelet agglutination (binding of von Willebrand factor [vWF] to platelet glycoprotein [GP] Ib) was shown during ECC and at the end of surgery, but not in the aprotinin group. This abnormality is not related to the hydrolysis of vWF or GP Ib, since washed platelets were resuspended in pooled normal plasma which provided a constant amount of vWF in this test and since the plasma concentration of the fragment of GP Ib (glycocalicin) did not correlate with this abnormality. Despite a high concentration of heparin (5-7 IU/ml) in patient's plasma during bypass, activation of blood coagulation in both groups was evidenced by an increase in ATm (thrombin-modified antithrombin III) level. The level of ATm in the placebo group reached a maximum at the end of ECC during rewarming, while in the aprotinin group, ATm level at this time point was significantly lower than in the control group. In comparison to the placebo group, the generation of the fibrin degradation products (DDE complexes) was inhibited by aprotinin during ECC, but the level of DDE complexes in the aprotinin group was slightly elevated after ECC, although much less than in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Temperature dependence of plasmin-induced activation or inhibition of human platelets.

It is known that at 37 degrees C plasmin may have two opposite effects on platelets: at high concentrations (greater than 1.5 caseinolytic units [CU]/mL), plasmin activates platelets; at lower concentrations (0.1 to 1.0 CU/mL) it inhibits platelet activation induced by thrombin, collagen, or calcium ionophore A23187. In this study, we report that when lowering the incubation temperature to 22 degrees C, plasmin at low concentrations (0.1 to 0.5 CU/mL) fully activated platelets. When platelets were treated with 0.2 CU/mL of plasmin, lowering the incubation temperature from 37 degrees C to 22 degrees C resulted in an increase in the expression of fibrinogen receptors, in platelet release and aggregation. Thromboxane A2 was not generated by plasmin treatment at either temperature. Ultrastructural studies showed that platelets responded to low-dose plasmin at 37 degrees C by forming pseudopods, centralizing granules without fibrinogen release, whereas at 22 degrees C the same dose of plasmin caused platelet degranulation with the appearance of alpha-granule fibrinogen within the lumen of the surface connected canalicular system. In addition, at 22 degrees C plasmin at doses insufficient to induce platelet aggregation potentiated platelet response to thrombin. Thus, we suggest that plasmin may initiate both activating and inhibitory processes within platelets and that the change of temperature could influence this balance. These results may be of clinical relevance, because the fibrinolytic system was found activated during cardiopulmonary bypass in which the temperature of patient's blood circulation was reduced. This temperature-dependent behavior is also an interesting model for a further study on platelet response to serine proteinases.