RESUMO
BACKGROUND: Heparin therapy and prophylaxis may be accompanied by bleeding and thrombotic complications due to individual responses to treatment. Dosage control based on standard laboratory assays poorly reflects the effect of the therapy. The aim of our work was to compare the heparin sensitivity of new thrombodynamics (TD) assay with sensitivity of other standard and global coagulation tests available to date. STUDY POPULATION AND METHODS: A total of 296 patients with high risk of venous thromboembolism (deep vein thrombosis (DVT), early postoperative period, hemoblastosis) were enrolled in the study. We used a case-crossover design to evaluate the sensitivity of new thrombodynamics assay (TD) to the hemostatic state before and after unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) therapy/prophylaxis and to compare it with the activated partial thromboplastin time (APTT), anti-Xa activity test, thrombin generation test (TGT) and thromboelastography (TEG). A receiver operating characteristic (ROC) curve analysis was used to evaluate changes before and after heparin prophylaxis and therapy. Blood was sampled before heparin injection, at the time of maximal blood heparin concentration and before the next injection. RESULTS: Hypercoagulation before the start of heparin treatment was detected by TD, TGT and TEG but not by APTT. The area under the ROC curve (AUC) was maximal for TD and anti-Xa, intermediate for TGT and TEG and minimal for APTT. CONCLUSIONS: These results indicate that TD has a high sensitivity to the effects of UFH and LMWH after both prophylactic and therapeutic regimes and may be used for heparin monitoring.
Assuntos
Anticoagulantes , Monitoramento de Medicamentos/métodos , Heparina , Trombose Venosa/prevenção & controle , Adulto , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/farmacocinética , Estudos Transversais , Feminino , Heparina/administração & dosagem , Heparina/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Tromboelastografia , Trombose Venosa/sangueRESUMO
The actual coagulation status may be reliably measured using only highly sensitive global functional tests; however, they are not numerous and all of them have disadvantages. Thrombodynamics (TD), a novel global coagulation test, is sensitive to hypo- and hypercoagulable states. The main properties of this test were investigated, and its capabilities for hemostasis analysis were verified through pharmacodynamic monitoring of the most widely used anticoagulants, heparins. The anticoagulant effects in the plasma of donors (n = 20) and patients after hip replacement (n = 20) spiked with unfractionated heparin or enoxaparin were measured in vitro to eliminate the influence of pharmacokinetic factors. Sensitivity for heparins was compared for activated partial thromboplastin time, thrombin generation tests and TD. TD was shown to reliably characterize the pharmacodynamics of any heparin in the entire range of its prophylactic and therapeutic concentrations. Inter-individual variability for the anticoagulant action of heparins was also calculated using the TD data. This variability did not differ between the investigated groups and did not exceed 12% and 20% for the stationary clot growth rate in the presence of unfractionated heparin and enoxaparin, respectively. That finding was in accordance with the values determined earlier using the thrombin generation test. The study results showed that TD has advantages over the other global methods of coagulation analysis. These advantages are good standardization, high reproducibility, independence of the parameter values from patient age and gender, and a narrower parameter distribution in a normal population. These results indicate that TD is a promising universal assessment method that improves the quality of hemostasis analysis because it more reliably detects deviations from the parameters' reference values.
Assuntos
Anticoagulantes/farmacologia , Testes de Coagulação Sanguínea/métodos , Coagulação Sanguínea/efeitos dos fármacos , Heparina/farmacologia , Trombina/metabolismo , Adolescente , Adulto , Idoso , Testes de Coagulação Sanguínea/instrumentação , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto JovemRESUMO
INTRODUCTION: The incidence of venous thromboembolism (VTE) after cesarean section is up to 0.6%, and the widespread use of cesarean section draws attention to this group. The dosage and duration of low-molecular-weight heparin (LMWH) prophylaxis after delivery is estimated by anamnestic risk-scales; however, the predictive potency for an individual patient's risk can be low. Laboratory hemostasis assays are expected to solve this problem. The aim of this study was to estimate the potency of tests to reflect the coagulation state of patients receiving LMWH in the early postpartum period. MATERIALS AND METHODS: We conducted an observational study on 97 women undergoing cesarean section. Standard coagulation tests (Fg, APTT, prothrombin, D-dimer), an anti-Xa assay, rotation thromboelastometry and thrombodynamics/thrombodynamics-4D were performed. Coagulation assay parameters were compared in groups formed in the presence or absence of LMWH to estimate the laboratory assays' sensitivity to anticoagulation. RESULTS: Coagulation assays revealed hypercoagulation after delivery and a tendency toward normalization of coagulation during early postpartum. The thromboprophylaxis results revealed a higher percentage of coagulation parameters within the normal range in the LMWH group. CONCLUSION: This research is potentially beneficial for the application of thrombodynamics and thrombodynamics-4D in monitoring coagulation among patients with high VTE risk who receive thromboprophylaxis with heparin.
Assuntos
Testes de Coagulação Sanguínea/estatística & dados numéricos , Cesárea/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Período Pós-Parto/sangue , Tromboembolia Venosa/prevenção & controle , Adulto , Anticoagulantes/uso terapêutico , Procedimentos Cirúrgicos Eletivos , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Gravidez , Tromboembolia Venosa/etiologia , Adulto JovemRESUMO
Pregnancy is associated with a significant procoagulant shift in the hemostatic system balance as well as other metabolic changes. Pregnancy can thereby provoke manifestation of otherwise dormant disorders of hemostasis (e.g., thrombophilia), or even cause new, pregnancy-specific disorders (e.g., HELLP syndrome). Application and interpretation of laboratory assays of hemostasis in pregnancy is particularly challenging, because normal physiological ranges are no longer applicable, and because the most dangerous and complex changes are not detected by classic routine coagulation/platelet assays. New global assays of coagulation and of platelet-dependent hemostasis appear to be promising in this respect, but are still far from clinical practice and rarely appear in current patient management guidelines. These global assays require a high level of research to identify their relationship to clinically significant outcomes. Here, we review the state-of-the-art knowledge of the molecular changes in the hemostatic system in normal pregnancy and during pregnancy-related complications (preeclampsia, thrombotic microangiopathies, antiphospholipid syndrome, etc.). We also discuss the sensitivity of various classic and innovative assays to these pregnancy-associated changes, and describe current and potential future applications of these assays in meeting specific clinical needs.
Assuntos
Hemostasia , Complicações na Gravidez/sangue , Testes de Coagulação Sanguínea/métodos , Feminino , Humanos , Testes de Função Plaquetária/métodos , GravidezRESUMO
This review is focused on the epidemiology of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), associated with pregnancy. Superficial vein thrombosis, a less hazardous and less studied type of thrombosis in pregnant women, is beyond the scope of this review. This study discusses the VTE incidence rate in women from developed countries for both antepartum and postpartum periods and for subpopulations of women affected by additional risk factors, such as thrombophilias, circulatory diseases, preeclampsia of varying degrees of severity, and Caesarean section. To minimize bias due to historical changes in medical and obstetric practices, lifestyle, diet, etc., this review is generally limited to relatively recent studies, i.e., those that cover the last 35 years. The absolute risk or incidence rate was used to ascertain risk of VTE associated with pregnancy. For the studies where the direct incidence rates of VTE were not reported, we calculated an estimate of the observed but not reported absolute incidence rates using the data presented in respective articles.