The impact of exercise-induced core body temperature elevations on coagulation responses.

OBJECTIVES: Exercise induces changes in haemostatic parameters and core body temperature (CBT). We aimed to assess whether exercise-induced elevations in CBT induce pro-thrombotic changes in a dose-dependent manner. DESIGN: Observational study. METHODS: CBT and haemostatic responses were measured in 62 participants of a 15-km road race at baseline and immediately after finishing. As haemostasis assays are routinely performed at 37°C, we corrected the assay temperature for the individual's actual CBT at baseline and finish in a subgroup of n=25. RESULTS: All subjects (44±11 years, 69% male) completed the race at a speed of 12.1±1.8km/h. CBT increased significantly from 37.6±0.4°C to 39.4±0.8°C (p<0.001). Post-exercise, haemostatic activity was increased, as expressed by accelerated thrombin generation and an attenuated plasmin response. Synchronizing assay temperature to the subjects' actual CBT resulted in additional differences and stronger acceleration of thrombin generation parameters. CONCLUSIONS: This study demonstrates that exercise induces a prothrombotic state, which might be partially dependent on the magnitude of the exercise-induced CBT rise. Synchronizing the assay temperature to approximate the subject's CBT is essential to obtain more accurate insight in the haemostatic balance during thermoregulatory challenging situations. Finally, this study shows that short-lasting exposure to a CBT of 41.2°C does not result in clinical symptoms of severe coagulation. We therefore hypothesize that prolonged exposure to a high CBT or an individual-specific CBT threshold needs to be exceeded before derailment of the haemostatic balance occurs

The impact of exercise-induced core body temperature elevations on coagulation responses.

Item does not contain fulltextOBJECTIVES: Exercise induces changes in haemostatic parameters and core body temperature (CBT). We aimed to assess whether exercise-induced elevations in CBT induce pro-thrombotic changes in a dose-dependent manner. DESIGN: Observational study. METHODS: CBT and haemostatic responses were measured in 62 participants of a 15-km road race at baseline and immediately after finishing. As haemostasis assays are routinely performed at 37 degrees C, we corrected the assay temperature for the individual's actual CBT at baseline and finish in a subgroup of n=25. RESULTS: All subjects (44+/-11 years, 69% male) completed the race at a speed of 12.1+/-1.8km/h. CBT increased significantly from 37.6+/-0.4 degrees C to 39.4+/-0.8 degrees C (p<0.001). Post-exercise, haemostatic activity was increased, as expressed by accelerated thrombin generation and an attenuated plasmin response. Synchronizing assay temperature to the subjects' actual CBT resulted in additional differences and stronger acceleration of thrombin generation parameters. CONCLUSIONS: This study demonstrates that exercise induces a prothrombotic state, which might be partially dependent on the magnitude of the exercise-induced CBT rise. Synchronizing the assay temperature to approximate the subject's CBT is essential to obtain more accurate insight in the haemostatic balance during thermoregulatory challenging situations. Finally, this study shows that short-lasting exposure to a CBT of 41.2 degrees C does not result in clinical symptoms of severe coagulation. We therefore hypothesize that prolonged exposure to a high CBT or an individual-specific CBT threshold needs to be exceeded before derailment of the haemostatic balance occurs.1 februari 201

Alterations in markers of coagulation and fibrinolysis in patients with Paroxysmal Nocturnal Hemoglobinuria before and during treatment with eculizumab

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Combining factor VIII levels and thrombin/plasmin generation: A population pharmacokinetic-pharmacodynamic model for patients with haemophilia A

AIMS: Prophylactic treatment of haemophilia A patients with factor VIII (FVIII) concentrate focuses on maintaining a minimal trough FVIII activity level to prevent bleeding. However, due to differences in bleeding tendency, the pharmacokinetic (PK)-guided dosing approach may be suboptimal. An alternative approach could be the addition of haemostatic pharmacodynamic (PD) parameters, reflecting a patient's unique haemostatic balance. Our aim was to develop a population PK/PD model, based on FVIII activity levels and Nijmegen Haemostasis Assay (NHA) patterns, a global haemostatic assay that measures thrombin/plasmin generation simultaneously. METHODS: PK/PD measurements were collected from 30 patients treated with standard half-life FVIII concentrate. The relationship between FVIII activity levels and the thrombin/plasmin generation parameters (thrombin potential, thrombin peak height and plasmin peak height), were described by sigmoidal E(max) functions. RESULTS: The obtained EC(50) value was smallest for the normalized thrombin potential (11.6 IU/dL), followed by normalized thrombin peak height (56.6 IU/dL) and normalized plasmin peak height (593 IU/dL), demonstrating that normalized thrombin potential showed 50% of the maximal effect at lower FVIII activity levels. Substantial inter-individual variability in the PD parameters, such as EC(50) of thrombin potential (86.9%) was observed, indicating that, despite similar FVIII activity levels, haemostatic capacity varies significantly between patients. CONCLUSION: These data suggest that dosing based on patients' individual PK/PD parameters may be beneficial over dosing solely on individual PK parameters. This model could be used as proof-of-principle to examine the application of PK/PD-guided dosing. However, the relation between the PD parameters and bleeding has to be better defined

Platelet CD34 expression and alpha/delta-granule abnormalities in GFI1B- and RUNX1-related familial bleeding disorders

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Platelet CD34 expression in a patient with a partial deletion of transcription factor subunit CBFB

Contains fulltext : 220459.pdf (Publisher’s version ) (Open Access