A European consensus statement on the use of four-factor prothrombin complex concentrate for cardiac and non-cardiac surgical patients.

Modern four-factor prothrombin complex concentrate was designed originally for rapid targeted replacement of the coagulation factors II, VII, IX and X. Dosing strategies for the approved indication of vitamin K antagonist-related bleeding vary greatly. They include INR and bodyweight-related protocols as well as fixed dose regimens. Particularly in the massively bleeding trauma and cardiac surgery patient, four-factor prothrombin complex concentrate is used increasingly for haemostatic resuscitation. Members of the Transfusion and Haemostasis Subcommittee of the European Association of Cardiothoracic Anaesthesiology performed a systematic literature review on four-factor prothrombin complex concentrate. The available evidence has been summarised for dosing, efficacy, drug safety and monitoring strategies in different scenarios. Whereas there is evidence for the efficacy of four-factor prothrombin concentrate for a variety of bleeding scenarios, convincing safety data are clearly missing. In the massively bleeding patient with coagulopathy, our group recommends the administration of an initial bolus of 25 IU.kg-1 . This applies for: the acute reversal of vitamin K antagonist therapy; haemostatic resuscitation, particularly in trauma; and the reversal of direct oral anticoagulants when no specific antidote is available. In patients with a high risk for thromboembolic complications, e.g. cardiac surgery, the administration of an initial half-dose bolus (12.5 IU.kg-1 ) should be considered. A second bolus may be indicated if coagulopathy and microvascular bleeding persists and other reasons for bleeding are largely ruled out. Tissue-factor-activated, factor VII-dependent and heparin insensitive point-of-care tests may be used for peri-operative monitoring and guiding of prothrombin complex concentrate therapy.

A large-scale study on the effect of age at first calving, dam parity, and birth and calving month on first-lactation milk yield in Holstein Friesian dairy cattle.

Milk yield during first lactation is an important economical trait. Age at first calving (AFC) is considered an important predictor of subsequent milk yield. In addition, both season of birth, as well as season of calving, have been shown to influence milk production, with conflicting results. Finally, higher parity of the dam has been associated with a lower performance of the offspring. The aim of the present study was to assess the effect of the above-mentioned factors based on a large-scale study and to rank the most important determinants for first-lactation milk yield. Data on 3,810,678 Holstein Friesian heifers, born in Belgium and the Netherlands between 2000 and 2015, were provided by Cooperative CRV and CRV BV (Arnhem, the Netherlands) and consisted of birth dates, calving dates, and first-lactation productions. In addition, herd, sire, and dam information was provided. Linear regression models were built with herd-calving year and sire as random effects and 305-d energy-corrected milk (ECM) yield during first lactation as outcome variable. Birth month, calving month, parity of the dam, and AFC were included as fixed effects in the model and a dominance analysis was performed to rank the associated factors according to importance. Results revealed AFC to be the most important factor (R2 = 0.047), with an increase in ECM up to an age of 33 mo. Calving month was a more important predictor than birth month (R2 = 0.010 vs. R2 = 0.002, respectively), with the highest first-lactation production in heifers calving in October to December, and the lowest in heifers calving in June and July. Birth month had a limited effect on first-lactation milk yield (R2 = 0.002), potentially masked by rearing strategies during early life. Finally, parity of the dam ≥3 was associated with a reduced ECM of the offspring (R2 = 0.002). In conclusion, our results show AFC to be an important determinant of milk yield during first lactation. In addition, seasonal patterns in milk production are seen, which should be further explored to identify the underlying mechanism.

The role of fibrinogen and fibrinogen concentrate in cardiac surgery: an international consensus statement from the Haemostasis and Transfusion Scientific Subcommittee of the European Association of Cardiothoracic Anaesthesiology.

To date, data regarding the efficacy and safety of administering fibrinogen concentrate in cardiac surgery are limited. Studies are limited by their low sample size and large heterogeneity with regard to the patient population, by the timing of fibrinogen concentrate administration, and by the definition of transfusion trigger and target levels. Assessment of fibrinogen activity using viscoelastic point-of-care testing shortly before or after weaning from cardiopulmonary bypass in patients and procedures with a high risk of bleeding appears to be a rational strategy. In contrast, the use of Clauss fibrinogen test for determination of plasma fibrinogen level can no longer be recommended without restrictions due to its long turnaround time, high inter-assay variability and interference with high heparin levels and fibrin degradation products. Administration of fibrinogen concentrate for maintaining physiological fibrinogen activity in the case of microvascular post-cardiopulmonary bypass bleeding appears to be indicated. The available evidence does not suggest aiming for supranormal levels, however. Use of cryoprecipitate as an alternative to fibrinogen concentrate might be considered to increase plasma fibrinogen levels. Although conclusive evidence is lacking, fibrinogen concentrate does not seem to increase adverse outcomes (i.e., thromboembolic events). Large prospective multi-centre studies are needed to better define the optimal perioperative monitoring tool, transfusion trigger and target levels for fibrinogen replacement in cardiac surgery.

Anticoagulant and side-effects of protamine in cardiac surgery: a narrative review.

Neutralisation of systemic anticoagulation with heparin in cardiac surgery with cardiopulmonary bypass requires protamine administration. If adequately dosed, protamine neutralises heparin and reduces the risk of postoperative bleeding. However, as its anticoagulant properties are particularly exerted in the absence of heparin, overdosing of protamine may contribute to bleeding and increased transfusion requirements. This narrative review describes the mechanisms underlying the anticoagulant properties and side-effects of protamine, and the impact of protamine dosing on the activated clotting time and point-of-care viscoelastic test results, and explains the distinct protamine dosing strategies in relation to haemostatic activation and postoperative bleeding. The available evidence suggests that protamine dosing should not exceed a protamine-to-heparin ratio of 1:1. In particular, protamine-to-heparin dosing ratios >1 are associated with more postoperative 12 h blood loss. The optimal protamine-to-heparin ratio in cardiac surgery has, however, not yet been elaborated, and may vary between 0.6 and 1.0 based on the initial heparin dose.

Validation of a point-of-care prothrombin time test after cardiopulmonary bypass in cardiac surgery.

Point-of-care coagulation monitoring can be used for the guidance of haemostasis management. However, the influence of time on point-of-care prothrombin time testing following protamine administration after cardiopulmonary bypass has not been investigated. Bland-Altman and error grid analysis were used to analyse the level of agreement between prothrombin time measurements from point-of-care and laboratory tests before cardiopulmonary bypass, and then 3 min, 6 min and 10 min after protamine administration. Prothrombin times were expressed as International Normalised Ratios. While the point-of-care and laboratory prothrombin time measurements showed a high level of agreement before bypass, this agreement deteriorated following protamine administration to a mean (SD) bias of -0.22 (0.13) [limits of agreement 0.48-0.04]. Error grid analysis revealed that 35 (70%) of the paired values showed a clinically relevant discrepancy in international normalised ratio. At 3 min, 6 min and 10 min after cardiopulmonary bypass there is a clinical unacceptable discrepancy between the point-of-care and laboratory measurement of prothrombin time.

Researching 100 t cows: An innovative approach to identify intrinsic cows factors associated with a high lifetime milk production.

Longevity is an important trait both from an economic and social perspective. Modern dairy cows are criticized for their short productive lifespan: only a minority of animals survives to a fourth lactation, implying that most cows are culled before reaching their maximal potential. In contrast, the population of 100 t cows (HT), reaching the threshold of 100,000 kg lifetime milk yield, is growing rapidly. As these cows combine a long lifespan with high functionality, a better understanding of their intrinsic characteristics might help us to improve the overall lifespan and lifetime production in dairy cows. The aim of the present research was to compare HT with their less-producing herd mates in order to identify intrinsic cow factors associated with longevity and high lifetime production. Therefore, we matched 26,248 HT with 691,597 herd mates, born in the same year in the same herd. Data were provided by Coöperatie rundveeverbetering (CRV) and contained birth dates, calving dates, milk yield and dam information. In addition, scores for conformation traits based on classifications in the first lactation and breeding values (for milk yield, fertility, udder health and claw health) were provided. Multivariable conditional logistic regression models were built to identify factors associated with reaching a lifetime milk yield of 100,000 kg. Results revealed cows born in September and born out of heifers to have the highest odds to become a HT. When cows received a score ≥ 83 (population average 80) for udder and feet & legs conformation, they had higher odds of reaching the 100,000 kg threshold. While a greater body condition and larger rump angle increased the odds of becoming a HT, this was decreased in cows with a large body depth. Finally, breeding values for milk yield, fertility, udder health and claw health were positively associated with the likelihood of reaching a lifetime milk yield of 100,000 kg. In conclusion, to increase lifetime milk yield in dairy herds, farmers should select heifers with high scores for conformation traits like udder and feet & legs and high breeding values for milk yield, fertility and udder health. Furthermore, our data suggest that being born in September out of a heifer potentially contributes to reaching a high lifetime milk yield.