Ex vivo evaluation of 4 different viscoelastic assays for detecting moderate to severe coagulopathy during liver transplantation.

Prolonged prothrombin time (PT) and its ratio are routinely used for the assessment of candidates for liver transplantation (LT), but intraoperative coagulation management of transfusion is hindered by its long turnaround time. Abnormal reaction time (R time) on thromboelastography (TEG) or clotting time (CT) of rotational thromboelastometry (ROTEM) are presumably an alternative, but there is a paucity of clinical data on abnormal R time/CT values compared to PT during LT. After receiving institutional review board approval and informed consent, we obtained blood samples from 36 LT patients for international normalized ratio (INR), factor (F) X level, and viscoelastic tests (EXTEM/INTEM and kaolin/rapid TEG) at baseline and 30 minutes after graft reperfusion. Receiver operating characteristic (ROC) curves were calculated for INR > 1.5 and viscoelastic R time/CT thresholds to assess the ability to diagnose FX deficiency at the moderate (<50%) or severe (<35%) level. The FX deficiency data were calculated using cutoff values of INR (>1.5) and abnormal R time/CT for TEG and ROTEM. Tissue factor (TF)-activated INR and EXTEM-CT performed well in diagnosing FX below 50%, but rapid TEG with combined TF and kaolin activators failed. Improved performance of INTEM-CT in diagnosing FX below 35% underlies multifactorial deficiency involving both intrinsic and common pathways. In conclusion, the differences among different viscoelastic tests and clinical situations should be carefully considered when they are used to guide transfusion during LT.

Anti-Xa e antitrombínicos específicos nas síndromes isquêmicas miocárdicas instáveis com e sem supradesnível do segmento ST / Factor Xa inhibitors and selective antithrombin agents in acute coronary syndromes

As síndromes isquêmicas miocárdicas instáveis incluem um amplo espectro de manifestações da doença coronária, variando de angina instável e infarto do miocárdio sem supradesnível do segmento ST até infarto do miocárdio com dupradesnível do seguimento ST. O mecanismo fisiopatológico subjacente envolve a combinação de aterosclerose e um evento trombótico. O tratamento com heparina não fracionada ou de baixo peso molecular tem demonstrado ser eficaz e seguro nesses pacientes. Entretanto, uma limitação inerente a essas medicações é a ausência de efeito na trombina ligada ao coágulo. Novos anticoagulantes foram desenvolvidos, tendo como alvo as duas formas de trombina - livre e aquela aderida ao coágulo (inibidores diretos da trombina) - bem como outros componentes individuais da cascata de coagulação (inibidores diretos ou indiretos do fator Xa). Esses agentes anticoagulantes demonstraram resultados promissores em estudos pré-clínicos e foram avaliados em ensaios de síndromes isquêmicas agudas em grande escala. Esta revisão discute a eficácia e a segurança desses novos agentes quando comparados com os regimes que utilizam heparina como anticoagulantes de escolha.

Acute coronary syndromes include a broad spectrum of coronary artery disease ranging from unstable angina, non-ST-segment elevation myocardial infarction to ST-segment elevation myocardial infarction. The underlying pathophysiological mechanism involves a combination of atherosclerosis and a thrombotic event. Treatment with unfractionated heparin or low-molecular-weight heparin has shown to be effective and safe in these patients. However, a common limitation of these medications is the lack of effect on clot-bound thrombin. Novel anticoagulants targeted for both the free and clot-bound forms of thrombin (direct thrombin inhibitors), or other individual components of the coagulation cascade (direct or indirect factor Xa inhibitors). These anticoagulants have shown promising results in preclinical testing and have been evaluated in large-scale clinical acute coronary syndrome trials. This review discusses the efficacy and safety of these novel agents compared with heparin-based anticoagulants.

Effects of isoflavones on the coagulation and fibrinolytic system of postmenopausal women.

OBJECTIVE: We evaluated the effects of soy isoflavone supplementation on hemostasis in healthy postmenopausal women. METHODS: In this double-blinded, placebo-controlled study, 47 postmenopausal women 47-66 y of age received 40 mg of soy isoflavone (n = 25) or 40 mg of casein placebo (n = 22) once a day for 6 mo. Levels of factors VII and X, fibrinogen, thrombin-antithrombin complex, prothrombin fragments 1 plus 2, antithrombin, protein C, total and free protein S, plasminogen, plasminogen activator inhibitor-1, and D-dimers were measured at baseline and 6 mo. Urinary isoflavone concentrations (genistein and daidzein) were measured as a marker of compliance and absorption using high-performance liquid chromatography. Baseline characteristics were compared by unpaired Student's t test. Within-group changes and comparison between the isoflavone and casein placebo groups were determined by a mixed effects model. RESULTS: The levels of hemostatic variables did not change significantly throughout the study in the isoflavone group; however, the isoflavone group showed a statistically significant reduction in plasma concentration of prothrombin fragments 1 plus 2; both groups showed a statistically significant reduction in antithrombin, protein C, and free protein S levels. A significant increase in D-dimers was observed only in the isoflavone group. Plasminogen activator inhibitor-1 levels increased significantly in the placebo group. However, these changes were not statistically different between groups. CONCLUSION: The results of the present study do not support a biologically significant estrogenic effect of soy isoflavone on coagulation and fibrinolysis in postmenopausal women. However, further research will be necessary to definitively assess the safety and efficacy of isoflavone.

[Effects of the administration of vitamin K on the activity of Factor II, VII and X in healthy newborns]. / Efecto de la administración de la vitamin K sobre la actividad de los factores II, VII y X en neonatos sanos.

The study was designed to know the effect of oral vitamin K (VK) treatment, on clotting factors II-VII-IX-X and the protein induced by VK absence from factor II (PIVCA II) on full term infants. Seventy healthy newborns were studied and each was randomly placed in one of two groups: Group A, newborns that received human milk and milk formula (mixed feeding)and group B, newborns that were exclusively breast fed. These groups were also divided in two subgroups: I received 2mg of VK1 orally and II (control) did not receive VK. Clotting activity of the coagulation factors and PIVCA II was determined from blood plasma obtained immediately after birth and 48 hours after VK administration. Basal activity of the factors analyzed was similar in all groups with values ranging from 25% to 40%. After 48 hours a significant increase in all factors studied and a decrease of PIVKA II was observed in those children who received oral VK. The results suggest that oral VK effectively increases VK dependent factors and prevents the risk of hemorrhagic disease in the newborn, with the advantage of being less traumatic and less risky to the infant than intramuscular VK.

Blood coagulation changes in homocystinuria: effects of pyridoxine and other specific therapy.

The aim of this study was to investigate the blood coagulation changes in three patients with homocystinuria, in baseline condition and during therapy. At baseline, antithrombin III activity and factor VII levels were reduced in all three patients; antithrombin III protein and protein C antigen were also slightly lowered in one patient, and factor X in another. beta-Thromboglobulin, a measure of platelet activation, was increased in one case. During pyridoxine treatment, antithrombin III activity was rapidly restored to normal; factor VII increased and beta-thromboglobulin decreased. These data suggest that, in addition to platelet activation, abnormalities of blood clotting, and particularly reduction of antithrombin III, may play a role in the thrombotic tendency associated with homocystinuria. The nature of these clotting alterations is still uncertain, but their improvement during active metabolic treatment suggests that the defect in amino acid transsulfuration of homocystinuria may directly affect synthesis or activity of some liver-dependent clotting factors.

Alterations of the blood coagulation system after accidental human inoculation by Bothrops jararaca venom.

Blood coagulation studies carried out on 78 patients up to 30 h after they were bitten by Bothrops jararaca snakes demonstrated clotting defects in 37 patients which included afibrinogenemia, reduced levels of prothrombin, of factors V and VIII, thrombocytopenia and activation of the fibrinolytic system. Factor IX and X levels were within normal range for all patients. These in vitro data suggest that the disseminated intravascular clotting observed in vivo following envenomation may be triggered by the intravascular release of patient thrombin by snake venom enzymes.

Coagulation and fibrinolytic factors in the first week of life in healthy infants.

Coagulation and fibrinolytic factors were determined daily in 74 healthy term and preterm infants to obtain a reference standard. A gestational age dependency was determined for antithrombin III, factor II, and plasminogen. The mean concentrations of antithrombin III and factor II in preterm infants increased to term values within the first week of life. Factor X levels declined independent of vitamin K administration. The values for the fibrinolytic system (alpha 2-antiplasmin and plasminogen) remained stable.

Actividad procoagulante y comportamiento tromboelastográfico en pacientes ateroscleróticos / Procoagulating activity and thromboelastographic behavior in atherosclerotic patients

Con los objetivos de determinar los niveles de los factores I, V y X de la coagulación sanguínea y algunos indicadores tromboelastográficos en una muestra de pacientes con aterosclerosis en los miembros inferiores, y comparar los resultados con los obtenidos en una muestra de controles para saber si están significativamente alterados en favor de un estado de hipercoagulabilidad evocador de trombosis incipiente, se realiza un estudio en una muestra de pacientes ateroscleróticos compuesta de 14 hombres (edad promedio 69,5 años) y en una muestra de controles senecentes (60-74 años) compuesta de 11 hombres (edad promedio 69,5 años) y 15 mujeres (edad promedio 71 años), considerados sanos desde el punto de vista angiológico clínico. En ambas muestras, se dosificaron los factores I, V y X y se hallaron indicadores tromboelastográficos de sangre total; en plasma pobre en plaquetas. Se comprobó que no existía diferencia significativa en los niveles de los factores I y X en los indicadores tromboelastográficos entre ateroscleróticos y controles, mientras que los pacientes manifestaran niveles de factor V significativamente más bajos que los controles estudiados

Prothrombin complex concentrate (Konyne) in the treatment of hemophilic patients with factor VIII inhibitors.

Two prothrombin complex concentrates, Auto-Factor IX and Proplex, have been reported to be effective in controlling bleeding in hemophilic patients with factor VIII inhibitors. A third PCC, Konyne, was used to treat 64 bleeding episodes (130 infusions) in five hemophilic patients with factor VIII inhibitors. Prompt control of bleeding was observed in each instance with doses of 15 to 100 units of factor IX/kg; no complications were encountered. Konyne resulted in in vivo and in vitro shortening of the partial thromboplastin time of patients with factor VIII inhibitors, but the mechanism of action is unknown. If further studies confirm the efficacy and safety of PCC in the treatment of such patients, its use for this purpose could lead to significant saving of factor VIII concentrates.