Thromboelastography (TEG) has been used increasingly as an intraoperative hemostasis monitoring device. Low-molecular-weight heparins are given increasingly to reduce the development of antibodies against the heparin-platelet factor 4 complex, and heparinoids are given to patients who have developed the antibody. We studied the effect of unfractionated heparin, a low-molecular-weight heparin (enoxaparin sodium [Lovenox]), and a heparinoid (danaparoid sodium [Orgaran]) on blood clotting assayed with TEG (TEG clotting) in vitro and the efficacy of protamine sulfate and heparinase for reversing the effect. Heparin, enoxaparin, and danaparoid all caused a dose-dependent inhibition of TEG clotting of normal blood. Concentrations of enoxaparin and danaparoid that totally inhibited TEG clotting only minimally prolonged the activated partial thromboplastin time. While inhibition of TEG clotting by heparin and enoxaparin was reversed by protamine sulfate and heparinase, inhibition by danaparoid was reversed only by heparinase. Abnormal TEG clotting was observed in patients receiving enoxaparin whose plasma level of the drug was more than 0.1 antiXa U/mL. However, the degree of TEG abnormality did not always coincide with plasma levels of the drug.

We have investigated platelet morphology and function in human maternal-newborn pairs. Fibrinogen concentration and factor-VIII activity in plasma were also determined. Our results showed that, compared to maternal platelets, neonatal platelets were poorly responsive to adenosine diphosphate, adrenaline and collagen. Uptake of labelled serotonin by neonatal and maternal platelets was the same, but release of the radioactivity was reduced in the former. Phagocytic activity of neonatal platelets, demonstrated with latex particles, was similar to that of maternal platelets. Although the ultrastructure of neonatal platelets approximated that of maternal platelets, immature appearing platelets were occasionally found in the neonatal samples. An unanticipated finding was that platelet aggregation induced by ristocetin was more vigorous in neonatal than in maternal platelet-rich plasma samples. Furthermore, neonal -lasma, which had lower fibrinogen and factor-VIII content than maternal plasma, facilitated maternal platelet aggregation by ristocetin and showed a greater ability than maternal plasma to promote ristocetin-induced aggregation of platelets of a patient with von Willebrand's disease. These results indicate that the plasma of neonates contains large quantities of the ristocetin-dependent platelet aggregation factor (RAF), probably more than is in maternal plasma, despite the higher levels of factor-VIII procoagulant activity in the latter. Thus, in the newborn, there is a clear dissociation between factor-VIII clotting activity and the RAF activity.

Hematin is clinically useful in the treatment of acute intermittent porphyria. Recently, hematin-induced coagulopathy has been reported, and a patient we treated bled during hematin therapy. On 3 separate occasions, infusions of hematin (4 mg/kg) induced thrombocytopenia, prolongation of the prothrombin time, partial thromboplastin time. Reptilase time, and apparent decreases in fibrinogen and increases in fibrin(ogen) degradation products (FDP). However, fibrinogen assayed by heat precipitation was unchanged, the protamine paracoagulation test was negative, there was no red blood cell fragmentation, and plasminogen and antithrombin III remained normal, excluding the presence of disseminated intravascular coagulation. Furthermore, premedication with heparin, 5000 U i.v., failed to prevent the lengthening of the Reptilase time and exacerbated the thrombocytopenia. In vitro studies revealed that hematin, 0.1 mg/ml, aggregated platelets and induced the release of 14C-serotonin and adenosine triphosphate (ATP). Hematin also aggregated washed or gel-filtered platelets but had no effect on formalin-fixed platelets. Aggregation was inhibited by aspirin (0.12 mg/ml), adenosine triphosphate, and apyrase, suggesting that hematin aggregated platelets by inducing adenosine diphosphate (ADP) release. Hematin (0.07 mg/ml) progressively inactivated thrombin and 0.1 mg/ml prolonged the Reptilase time. Thus, hematin is unique in that it both induces platelet aggregation and inhibits coagulation.

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