Changes in blood coagulation and fibrinolysis associated with maximal exercise and physical conditioning in women taking low dose oral contraceptives

Hilberg, Thomas; Nowacki, P. E.; Müller‐Berghaus, Gert; Gabriel, Holger

doi:10.1016/s1440-2440(00)80005-5

Cited by 23 publications

(14 citation statements)

References 27 publications

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“…The fluctuations in presence of interacting surfaces and molecular partners of FVIII, depending on the individual physiological condition may partly explain the varying recorded activities, associated with these substitution changes. It has been shown, e.g., that aerobic exercise would increase FVIII activity [39]. Since the severity of HA phenotype is defined also by clinical criteria, other risk factors such as modifier genes, mainly prothrombotic factors could account for the observed phenotypic diversity (reviewed in [29]).…”

Section: Resultsmentioning

confidence: 99%

Combined homology modelling and evolutionary significance evaluation of missense mutations in blood clotting factor VIII to highlight aspects of structure and function

Markoff¹,

Gerke²,

Bogdanova³

2009

Haemophilia

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Most small lesions in the factor VIII (FVIII) gene that cause haemophilia A (HA) are single nucleotide substitutions resulting in amino acid replacing (missense) mutations and leading to various phenotypes, ranging from mild to severe. We took a combined approach of homology modelling and quantitative evaluation of evolutionary significance of amino acid replacing alterations using the Grantham Matrix Score (GMS) to assess their structural effects and significance of pathological expression. Comparative homology models of all amino acid substitutions summarized in the FVIII mutations database plus these identified and reported lately by us or by our collaborators were evaluated. Altogether 640 amino acid replacing mutations were scored for potential distant or local conformation changes, influence on the molecular stability and predicted contact residues, using available FVIII domain models. The average propensity to substitute amino acid residues by mutation was found comparable to the overall probability of de novo mutations. Missense changes reported with various HA phenotypes were all confirmed significant using GMS. The fraction of these, comprising residues apparently involved in intermolecular interactions, exceeds the average proportion of such residues for FVIII. Predicted contact residues changed through mutation were visualized on the surface of FVIII domains and their possible functional implications were verified from the literature and are discussed considering available structural information. Our predictive modelling adds on the current view of domain interface molecular contacts. This structural insight could aid in part to the design of engineered FVIII constructs for therapy, to possibly enhance their stability and prolong circulating lifetime.

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Section: Resultsmentioning

confidence: 99%

Combined homology modelling and evolutionary significance evaluation of missense mutations in blood clotting factor VIII to highlight aspects of structure and function

Markoff¹,

Gerke²,

Bogdanova³

2009

Haemophilia

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“…It is well known that vascular alterations and other diseases, as well as lipid levels, body mass index, the fitness level itself, and the type of exercise, its length and intensity, all influence coagulation and fibrinolysis. 16,[23][24][25][26] Many of these confounders could be eliminated by the study design used.…”

Section: Discussionmentioning

confidence: 99%

Coagulation and Fibrinolysis are in Balance After Moderate Exercise in Middle-aged Participants

Menzel

Hilberg

2008

Clin Appl Thromb Hemost

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Increased age is associated with a higher risk of thrombotic events. The aim of this study was to investigate the age-related changes in hemostasis before and after moderate exercise controlled by individual anaerobic threshold as recommended for rehabilitation training. In this study, 24 young (25 + 1 years) and 24 middle-aged healthy nonsmokers (48 + 1 years) underwent an individualized exercise test with 80% of individual anaerobic threshold (young individuals: 127 + 6 W; middle-aged individuals: 128 + 5 W; values are expressed as mean + standard error of mean) for 60 minutes. The blood samples were collected before and after the exercise. The age-related higher (P .05) levels could be detected in factors II, VII, VIII, IX, XI, XII, prothrombin fragment 1þ2, in tissue plasminogen activator antigen and activity, as well as in plasminogen. The relative exercise-induced increases in these parameters were similar in both groups, although beginning at a higher level for those in the middle-aged group. A statistically enhanced increase after exercise in the middle-aged group could be shown in prothrombin fragment 1þ2 (young individuals: 98 + 6 to 102 + 6 pmol/L; middle-aged individuals: 138 + 7 to 156 + 8 pmol/L) and in thrombin-antithrombin complex (young individuals: 2.2 + 0.1 to 3.1 + 0.2 mg/L; middle-aged individuals: 2.4 + 0.3 to 3.9 + 0.6 mg/L); the latter only showing a tendency. The data show the age-related changes with a rise in blood coagulation and fibrinolysis in a healthy middle-aged group compared with younger participants. Moderate exercise leads to comparably relative increases in hemostatic parameters but starting at higher levels. However, the exercise-induced thrombin generation (prothrombin fragment 1þ2) is enhanced in the middle-aged participants in comparison with younger participants, but may be compensated by a sufficient fibrinolysis, and therefore the hemostatic system remains in balance.

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“…59,85 Other studies have found improvements in hemostatic markers, including PT, FVIII, prothrombin F1 þ 2, and VWF in subjects between 50 and 75 years old but not in a younger population. 122,123 Gender Most studies examining the hemostatic effects of training included only male subjects. The response of peripheral blood cell counts and D-dimer levels to a single bout of exercise appear the same in both genders, whereas the postexercise clotting times decreased more in males than females.…”

Section: Agementioning

confidence: 99%

Effects of Repeated Bouts of Exercise on the Hemostatic System

Vorm

Huskens

Kicken

et al. 2018

Semin Thromb Hemost

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Physical activity is beneficial for health, for example, by lowering the risk of cardiovascular events. However, vigorous exercise is associated with the occurrence of thromboembolic events and sudden cardiac death, in particular in untrained individuals. Whereas acute exercise is known to cause a hypercoagulable state, repeated exposure to (strenuous) exercise by means of training may actually condition the hemostatic response to exercise. To date, the effects of exercise training on blood coagulability and the underlying mechanisms have yet to be fully discerned. In this review, the authors provide an overview of existing literature on how training programs and training status influence hemostasis in healthy individuals. Furthermore, they present data of a pilot study in which we studied the effects of repetitive submaximal intensity cycling on procoagulant and anticoagulant processes. It is known that factor VIII (FVIII) and von Willebrand factor (VWF) increase after exercise, but we found that this increase in FVIII and VWF (antigen, propeptide, and VWF in active conformation) was smaller on each of three subsequent days, suggesting either adaptation of endothelial activation or exhaustion of endothelial VWF supplies. With respect to thrombin generation, elevated FVIII significantly increased the thrombin generation peak but not the endogenous thrombin potential. In contrast, platelet activation in terms of P-selectin expression after stimulation with protease-activated receptor-1 and glycoprotein VI agonists decreased after exercise and did not recover, indicating exhaustion of the platelet response to repetitive exercise.

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Changes in blood coagulation and fibrinolysis associated with maximal exercise and physical conditioning in women taking low dose oral contraceptives

Cited by 23 publications

References 27 publications

Combined homology modelling and evolutionary significance evaluation of missense mutations in blood clotting factor VIII to highlight aspects of structure and function

Combined homology modelling and evolutionary significance evaluation of missense mutations in blood clotting factor VIII to highlight aspects of structure and function

Coagulation and Fibrinolysis are in Balance After Moderate Exercise in Middle-aged Participants

Effects of Repeated Bouts of Exercise on the Hemostatic System

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