Ulla Wartiovaara-Kautto

Antithrombin reduces pulmonary hypertension during reperfusion after cardiopulmonary bypass in a pig

Background:  Antithrombin (AT) may alleviate many cardiopulmonary bypass (CPB) and ischemia‐reperfusion (I/R)‐related adverse effects. Using a porcine model of clinical cardiac surgery on CPB, we tested the effects of supplementary AT on myocardial and lung I/R injury.

The procoagulant effects of factor V Leiden may be balanced against decreased levels of factor V and do not reflect in vivo thrombin formation in newborns

Thrombin regulation in newborns remains incompletely understood. We studied tissue factor-initiated thrombin formation in cord plasma in vitro, and the effects of Factor V(Leiden) (FVL) heterozygosity on thrombin regulation both in vitro and in vivo in newborns. Pregnant women with known thrombophilia (n=27) were enrolled in the study. Cord blood and venous blood at the age of 14 days were collected from 11 FVL heterozygous newborns (FVL-positive) and from 16 FVL-negative newborns. Prothrombin fragment F1 +2 and coagulation factors were measured. Tissue factor-initiated thrombin formation was studied in cord platelet-poor plasma (PPP) of FVL-negative and -positive newborns, and in both PPP and platelet-rich plasma (PRP) of healthy controls. The endogenous thrombin potential (ETP) in cord PPP or PRP was approximately 60% of that in adult plasma, while thrombin formation started approximately 55% and approximately 40% earlier in cord PPP and PRP, respectively. Further, in FVL-positive newborns thrombin formation started significantly earlier than in FVL-negative newborns. Exogenous activated protein C (APC) decreased ETP significantly more in cord than in adult PRP. In FVL-negative cord plasma 5 nM APC decreased ETP by 17.4+/-3.5% (mean+/-SEM) compared with only 3.5+/-3.8% in FVL-positive cord plasma (p=0.01). FVL-positive newborns showed similar levels of F1 +2 but significantly decreased levels of factorV compared with FVL-negative newborns both in cord plasma (FV 0.82+/-0.07 U/ml vs. 0.98+/- 0.05 U/ml, p=0.03) and at the age of two weeks (FV 1.15+/-0.04 U/ml vs. 1.32+/- 0.05 U/ml, p=0.03). In conclusion, newborn plasma showed more rapid thrombin formation and enhanced sensitivity to APC compared with adult plasma. FVL conveyed APC resistance and a procoagulant effect in newborn plasma. Lack of elevated F1+2 levels in FVL-positive infants, however, suggested the existence of balancing mechanisms; one could be the observed lower level of factor V in FVL heterozygous newborns.

Thrombin Generation in vitro and in vivo, and Disturbed Tissue Factor Regulation in Patients with Acute Pancreatitis

Background: Being a central link between inflammation and coagulation, tissue factor (TF) and its inhibitor (TFPI) might be associated with the severity of acute pancreatitis (AP) and the development of organ failure (OF). Methods: The study comprises 9 severe AP patients with OF and 24 reference patients (11 mild AP and 13 severe AP without OF). Plasma samples were collected on admission. TF-induced thrombin generation in plasma samples was studied using the thrombogram method. In vivo thrombin generation was estimated by prothrombin fragment F1+2. Free and total TFPI levels were measured. To evaluate coagulation status the activated partial thromboplastin time, prothrombin time, platelet count, D-dimer, fibrinogen, antithrombin (AT) 3 and protein C (PC) were determined. Results: There was no significant difference in F1+2 levels between the patient groups. Patients with severe AP tended to show low platelet counts, PC and AT3 levels, and high D-dimer levels. In 11 patients the standard TF stimulation did not trigger thrombin generation in the thrombogram. All deaths occurred in these patients. Free TFPI levels and free/total TFPI ratios were significantly higher in these patients and in non-survivors. Conclusion: Failure of TF-initiated thrombin generation in the thrombogram assay explained by high levels of circulating free TFPI may be associated with OF and mortality in AP.

Thrombin regulation in neonates undergoing cardiopulmonary bypass

Satu Långström1, Paula Rautiainen2, Leena Mildh2, Kaija Peltola2, Ulla Wartiovaara-Kautto3, Markku Heikinheimo1,4, Jari Petäjä1,5 1Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland; 2Department of Anesthesia and Intensive Care, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland; 3Helsinki University Central Hospital Laboratory Services (HUSLAB), Department of Clinical Chemistry, Laboratory of Hematology, University of Helsinki, Finland; 4Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA; 5Department of Pediatrics, Jorvi Hospital, University of Helsinki, Espoo, Finland

Fresh frozen plasma does not reduce in vivo thrombin formation after neonatal cardiopulmonary bypass surgery.

Fresh frozen plasma does not reduce in vivo thrombin formation after neonatal cardiopulmonary bypass surgery -

Exchange transfusion activates coagulation and alters the coagulation profile in newborn infants

Exchange transfusion (ET) with adult blood is a standard procedure for neonates with severe hyperbilirubinemia. How ET affects newborn coagulation system remains, however, largely unknown. Thus, we prospectively evaluated the effect of ET on thrombin formation and coagulation profile in 18 newborns (22 ETs). Prothrombin fragment F1+2 and thrombin-antithrombin complexes increased considerably during ET while platelets were significantly reduced. Protein C increased less (p < 0.001) and factor VIIIc more (p < 0.001) than expected based on their levels in the infused blood. Further, in vitro thrombin generation initiated by 5 pM tissue factor was analysed. Before the first ET, newborn endogenous thrombin potential (ETP) and thrombin peak remained at approximately 60% of adult control plasma levels, but the lag time to thrombin burst in newborn plasma was approximately 45% shorter than the lag time in adult plasma. At the end of the first ET, the thrombin burst still started approximately 35% earlier in newborn than adult plasma, whereas ETP and thrombin peak were increased to > 90% of adult levels. ETP and peak remained elevated at adult levels until the beginning of the second ET. APC-induced reductions in newborn ETP remained unaltered throughout the first ET. The reductions of ETP by APC were less pronounced in newborn than adult plasma (p < 0.0001). We conclude that ET is associated with multiple procoagulant changes and increased in vivo thrombin formation. This ET-induced procoagulant challenge may be of clinical significance in sick newborns already prone to bleeding and thrombotic complications.

Contents Vol. 11, 2011

99 43rd European Pancreatic Club (EPC) Meeting June 22–25, 2011, Magdeburg, Germany Guest Editor: Halangk, W. (Magdeburg) (available online only) 276 Erratum 277 IAP Society News 278 EPC Society News No. 3