SCIENTIFIC SUBCOMMITTEE SESSION
7 July 2007 Palexpo, Geneva, Switzerland
Disseminated Intravascular Coagulation (DIC)
Chair: C.-H. Toh (UK)
Co-Chairs: N. Key (USA), J.D. Nielsen (Denmark), K. Okajima (Japan), H. Wada (Japan)
Theme: From Scoring System to Patient Care
CH Toh presented an overview of work from this subcommittee and referred to the Communication from 2001 (Thromb Haemost 2001; 86: 1327) as a key reference point with development of the diagnostic criteria. The first phase of this work culminated with this year’s SSC Communication (J Thromb Haemost 2007; 5: 604). As the past 5 years’ work has primarily concentrated on the DIC of sepsis, the next phase of activities will include further diagnostic refinement especially into the DIC of trauma and obstetric disorders as these are likely to have pathogenic differences to sepsis. Emphasis would continue to be about Prognostication and Pathogenesis.
J Thachil highlighted the unique properties of the uteroplacental system whose procoagulant potential is set at a higher level than in other vascular systems and therefore prone to perturbation. The main causes of DIC are pre-eclampsia and post partum haemorrhage. The former has an inflammatory component albeit at significantly lower levels than those seen in sepsis. Evidence was also presented that the DIC of obstetrics mainly represents overspill of uteroplacental site coagulation activation rather than a systemic state of events. As such, delivery of the placenta usually leads to resolution of the DIC.
D de Prost from hôpital Louis Mourier, Colombes, France evaluated the usefulness of fibrinogen level in the management of PPH. She presented data showing that a low level of fibrinogen during labour can predict the later occurrence of PPH; moreover, in declared PPH, a low level of fibrinogen is an independent predictor of the severity of haemorrhage. These results suggest that the fibrinogen level can be used to guide the management of PPH and monitor coagulopathy. The interest of using a point of care device to shorten the delay for getting the laboratory result should be evaluated.
Uri Martinowitz considered coagulopathy in trauma as a distinct entity whose pathogenesis was about localised endothelial damage and clot formation rather than the diffuse process in sepsis, albeit fairly similar coagulation abnormalities. Concern was expressed that as DIC-sepsis management is increasingly about the value of anticoagulant treatment that haematologists might mistake this to be treatment in DIC trauma.
Bertil Bouillon with his experience as a trauma surgeon, presented coagulopathy as a clinical problem in the trauma population. The current concept is of primary and secondary injury with coagulopathy contributing to the latter. Data was presented of how coagulopathy contributes to an adverse outcome. A new classification concept of bleeding and coagulopathy in severe trauma was proposed as was a concept for diagnostics and treatment.
Markus Huber-Lang presented an educational lecture on the interaction between coagulation and complement pathways. This adds to our knowledge of thrombin ubiquity and may well have potential in early recognition of maladaptive host responses to injury.
Marcel Levi highlighted the value of the ISTH DIC score as the strongest predictor of mortality in multivariate analysis of sepsis trials. In addition, present evidence indicates that a dministration of recombinant human activated protein C should be considered in the DIC of sepsis but it increases the risk of major bleeding. Interestingly, analysis of the Kybersept trial of high dose antithrombin concentrate in severe sepsis showed the subgroup of patients that had DIC and that did not receive heparin showed a remarkable survival benefit, but this finding requires prospective validation . As regards heparin, a recent large trial in patients with severe sepsis which is in press has shown a non-significant benefit of low molecular weight heparin on 28 day mortality and underscores the importance of not stopping heparin in patients with DIC and abnormal coagulation parameters.
Hideo Wada found the level of thrombin-antithrombin complexes to be similar in DIC sub-groups but other parameters such as protein C and antithrombin levels were not always the same suggesting that disease specificity affected the functional consequence of thrombin generation. He also presented data that antithrombin levels below 70% had value when incorporated into the DIC scoring system.
B. Jilma informed us that only limited methodologies exist that can be used in human volunteers to mimic the physiologic alterations observed in critically ill patients. the coagulation response to experimental endotoxemia is self-limited, and the consumption of coagulation factors and natural anticoagulant is relatively modest. Similarly, the use of endotoxin is not necessarily reflecting the pathophysiology of microorganisms other than Gram negative bacteria. Thus, while experimental endotoxemia presents a well standardized translational tool for the development of novel anticoagulants, precautions are necessary in the extrapolation of data to septic patients with DIC.
Hidehiko Saito concluded the session with promising study results of using recombinant soluble thrombomodulin ART-123 in DIC from infection and malignancies. The molecule has a long half-life of 20 hours but does not appear to have bleeding complications. Current results show no effect on mortality but quicker resolution of DIC.
CH Toh concluded this well-attended session whose numbers were consistently above 300. There was broad agreement without dissenting comments on adopting the presented plan of activities for the future. Laboratory standardisation will continue on various fronts as will continued refinement to the DIC score for disease-specific relevance. Collaboration will continue with SSCs of Fibrinolysis and Haemostasis in Malignancy respectively on the issue of D-dimer; with SSC on Vascular Biology over measuring microparticles and SSC on Control of Anticoagulation over the issue of PT/INR.