Year in review in Intensive Care Medicine 2009: II. Neurology, cardiovascular, experimental, pharmacology and sedation, communication and teaching

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Danaparoid cross-reactivity with heparin-induced thrombocytopenia antibodies: report of 12 cases.

PURPOSE: Danaparoid is a safe and effective drug for the treatment of heparin-induced thrombocytopenia (HIT). We describe an uncommon complication: danaparoid cross-reactivity with HIT antibodies. DESIGN AND SETTING: A retrospective observational multicenter study on HIT was conducted in France. In this study concerning HIT patients treated with lepirudin, 12 patients were treated with lepirudin because danaparoid cross-reacted with the heparin-dependent antibodies. RESULTS: Three groups of situations can be separated. In a first group, four patients received a short course of danaparoid until their initial functional HIT assay showed a cross-reactivity between danaparoid and HIT antibodies. One patient presented a fatal thrombotic complication but the relationship between this thrombotic complication and danaparoid cross-reactivity cannot be certain. In a second group, four patients received for 4 days at least a danaparoid treatment while the initial functional test did not show any danaparoid cross-reactivity. During danaparoid treatment, no significant increase of platelet count was observed and two patients presented a fatal thrombotic complication. In a third group, cross-reactivity between danaparoid and HIT antibodies was not checked before danaparoid therapy. During danaparoid treatment, no significant increase of platelet count was observed and the four patients developed a venous thromboembolic complication. CONCLUSION: Absence of any increase in platelet count after 3 to 5 days of danaparoid therapy and/or the occurrence of a new thrombotic event should lead to danaparoid cross-reactivity suspicion. However, before attributing thrombotic complications to danaparoid cross-reactivity, it is crucial to verify that the patients received the recommended danaparoid dosage regimen

Thrombin generation and heparin-induced thrombocytopenia.

International audienceBACKGROUND: Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin therapy. IgG antibodies targeting the platelet factor 4-heparin complex activate platelets and generate microparticles with procoagulant activity. OBJECTIVES: To determine whether the thrombin generation assay is capable of detecting procoagulant activity induced by patient platelet-poor plasma (PPP) in donor platelet-rich plasma (PRP). PATIENTS AND METHODS: We explored two groups of patients; group 1 (n = 23): patients with a positive clinical and biological diagnosis of HIT; group 2 (n = 25): patients with a negative clinical and biological diagnosis of HIT. Mixtures of donor PRP and patient PPP (1:1) were incubated either with unfractionated heparin 0.2 U mL(-1) or with physiological saline. Thrombin generation was assessed by calibrated thrombinography. The effect of heparin on the mixtures was evaluated according to the ratio of the values with and without heparin (wH/woH) of the five thrombogram parameters. RESULTS: With low heparin concentrations, plasma of group 1 activates donor platelets and generates procoagulant activity. A set of three ratios outside the cut-off values corresponds to the 'HIT thrombogram profile', characterized by a highly specific aspect of the thrombogram wH in relation to the thrombogram woH. None of the group 2 patients presented a HIT thrombogram profile. The results of thrombinography correlate well with the results of the platelet aggregation test. CONCLUSION: Our studies illustrate the central paradox of HIT, namely enhancement of thrombin generation in the presence of heparin. The HIT thrombogram profile as it is defined in this study can detect the procoagulant activity of HIT IgG antibodies

Clustering of Thrombin Generation Test Data Using a Reduced Mathematical Model of Blood Coagulation

Correct interpretation of the data from integral laboratory tests, including Thrombin Generation Test (TGT), requires biochemistry-based mathematical models of blood coagulation. The purpose of this study is to describe the experimental TGT data from healthy donors and hemophilia A (HA) and B (HB) patients. We derive a simplified ODE model and apply it to analyze the TGT data from healthy donors and HA/HB patients with in vitro added tissue factor pathway inhibitor (TFPI) antibody. This model allows the characterization of hemophilia patients in the space of three most important model parameters. The proposed approach may provide a new quantitative tool for the analysis of experimental TGT. Also, it gives a reduced model of coagulation verified against clinical data to be used in future theoretical large-scale modeling of thrombosis in flow. © 2019, Springer Nature B.V

Danaparoid cross-reactivity with heparin-induced thrombocytopenia antibodies: report of 12 cases.

PURPOSE: Danaparoid is a safe and effective drug for the treatment of heparin-induced thrombocytopenia (HIT). We describe an uncommon complication: danaparoid cross-reactivity with HIT antibodies. DESIGN AND SETTING: A retrospective observational multicenter study on HIT was conducted in France. In this study concerning HIT patients treated with lepirudin, 12 patients were treated with lepirudin because danaparoid cross-reacted with the heparin-dependent antibodies. RESULTS: Three groups of situations can be separated. In a first group, four patients received a short course of danaparoid until their initial functional HIT assay showed a cross-reactivity between danaparoid and HIT antibodies. One patient presented a fatal thrombotic complication but the relationship between this thrombotic complication and danaparoid cross-reactivity cannot be certain. In a second group, four patients received for 4 days at least a danaparoid treatment while the initial functional test did not show any danaparoid cross-reactivity. During danaparoid treatment, no significant increase of platelet count was observed and two patients presented a fatal thrombotic complication. In a third group, cross-reactivity between danaparoid and HIT antibodies was not checked before danaparoid therapy. During danaparoid treatment, no significant increase of platelet count was observed and the four patients developed a venous thromboembolic complication. CONCLUSION: Absence of any increase in platelet count after 3 to 5 days of danaparoid therapy and/or the occurrence of a new thrombotic event should lead to danaparoid cross-reactivity suspicion. However, before attributing thrombotic complications to danaparoid cross-reactivity, it is crucial to verify that the patients received the recommended danaparoid dosage regimen

Patient-Specific Modelling of Blood Coagulation

Blood coagulation represents one of the most studied processes in biomedical modelling. However, clinical applications of this modelling remain limited because of the complexity of this process and because of large inter-patient variation of the concentrations of blood factors, kinetic constants and physiological conditions. Determination of some of these patients-specific parameters is experimentally possible, but it would be related to excessive time and material costs impossible in clinical practice. We propose in this work a methodological approach to patient-specific modelling of blood coagulation. It begins with conventional thrombin generation tests allowing the determination of parameters of a reduced kinetic model. Next, this model is used to study spatial distributions of blood factors and blood coagulation in flow, and to evaluate the results of medical treatment of blood coagulation disorders. © 2021, The Author(s), under exclusive licence to Society for Mathematical Biology