A. Rosenkranz

Calibrated automated thrombin generation in normal uncomplicated pregnancy

Pregnancy is associated with substantial changes in the haemostatic system and a six-fold higher incidence of venous thromboembolism. Conventional global tests, such as prothrombin time and activated partial thromboplastin time, do not definitely detect this hypercoagulable condition. We investigated whether the changes in haemostatic system during pregnancy are reflected in the calibrated automated thrombography (CAT). Thrombin generation was measured in platelet-poor plasma (PPP) of 150 healthy pregnant women without any pregnancy associated diseases by means of CAT. In addition, prothrombin (FII), antithrombin (AT), protein S, protein C, tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex (TAT), and prothrombin fragments 1+2 (F1+2) were measured. Endogenous thrombin potential (ETP) and peak of thrombin generation increased significantly with gestational weeks, while lag time and time to peak remained unchanged. A significant increase of PAI-1, TFPI, F1+2 and TAT as well as a significant decrease of free protein S, protein S antigen, and protein S activity was observed. Levels of AT and protein C remained stable during pregnancy. Division of population in trimester of pregnancy and analysis of differences between the trimesters showed rather similar results. Our study shows that endogenous thrombin potential does increase with duration of normal uncomplicated pregnancy. Whether parameters of continuous thrombin generation will correlate with thrombembolic disease remains to be shown.

Phospholipid content, expression and support of thrombin generation of neonatal platelets

Aim: Newborns have, despite low clotting factors and poor in vitro platelet function, a well functioning haemostasis. We investigated whether phospholipids (PL) in neonatal platelets differ from those in adult platelets in their exposure on the platelet surface, and their effect on thrombin generation.

Thrombin generation before and after multicomponent blood collection

BACKGROUND: Apheresis technology has made tremendous progress up to the development of automated blood component collection, which offers increased efficiency in donor blood use, but the concern about the contact of donor blood with artificial surfaces remains. Activation of the hemostatic system is a major issue in this context and is controversial. The aim of this study was to estimate the effect of apheresis on continuous thrombin generation (TG), representing a new tool to examine the overall function of the plasmatic clotting system.

Monocytes Enhance rVIIa Induced Thrombin Generation in Absence of Platelets and Microparticles

Recombinant activated factor VII (rVIIa) was developed for the treatment of bleeding episodes in patients suffering from hemophilia with inhibitors. Its use is also established in non hemophilia patients with acquired antibodies against factor VIII [1, 2, 3]. In factor deficiency where no specific factor concentrates are available, such as V, VII and XI, use of rVIIa is also a therapeutic option. In clinical studies a beneficial effect of rVIIa in therapy of intra cerebral hemorrhage is reported [4]. There are studies in progress that rVIIa might be beneficial in trauma therapy [5, 6]. First studies in liver failure are also promising [7, 8]. Good results are reported in case studies with rVIIa as an alternative to platelet transfusion in preventing or controlling bleeding, including surgical bleeding, in patients with Glanzmann Thrombasthenia [9]. Results are not so consistent in thrombocytopenia [10, 12, 31, 32].

Thrombin Generation in Pregnancy

A well functioning hemostasis depends on the well-balanced interaction between many procoagulatory and inhibiting factors of the coagulation and the fibrinolytic system. During normal pregnancy this balance is shifted towards a state of hypercoagulability [1], which is more marked around term and in the immediate post partum period [2].

Pediatric patients with congenital heart disease: thrombin generation measured by calibrated automated thrombography.

The aim of this study was to investigate the possible suitability of the calibrated automated thrombography to determine the coagulation status of pediatric patients with congenital heart disease. Thrombin generation was measured in 60 patients with congenital heart disease using the calibrated automated thrombography and compared to data using standard coagulation parameters such as prothrombin, antithrombin, tissue factor pathway inhibitor, prothrombin fragment 1.2 (F 1.2), and activated partial thromboplastin time. A significant positive correlation was observed between prothrombin and the endogenous thrombin potential (P < 0.01; r = 0.295) as well as between prothrombin and peak height (P < 0.01; r = 0.581). A significant negative correlation was seen between tissue factor pathway inhibitor and endogenous thrombin potential (P < 0.01; r = −0.480) and between tissue factor pathway inhibitor and peak height (P < 0.01; r = −0.234). No statistically significant correlation was found between antithrombin and parameters of continuous thrombin generation. Significant correlation was seen neither between activated partial thromboplastin time and F1.2 nor between activated partial thromboplastin time and prothrombin. The data presented here indicate that calibrated automated thrombography measurements determine thrombin generation more accurately and therefore reflect better the coagulation status of pediatric patients with congenital heart disease then standard global coagulation assays such as activated partial thromboplastin time.