Hydration does not prevent orthostatic hypercoagulability

Summary

Prolonged standing activates the coagulation cascade by the activation of endothelial cells, and probably the haemoconcentration effect contributes to this "orthostatic hypercoagulability". It was the objective of this study to assess whether rehydration (haemodilution) prevents or attenuates orthostatic induced thrombin formation. Twelve healthy young subjects were studied during two separate visits. Haematocrit (Hct), total plasma protein, coagulation profile tests, including endothelial activation related factors, and protein C global pathway were studied at rest supine, and while standing at 15 and 30 minutes (min). During the second visit the study was repeated after intravenous 1.5 liter 0.9% saline. While in supine posture, intravenous rehydration resulted in Hct reduction of 14.2 ± 2% (haemodilution), a decrease of 11.5 ± 1.3% in total protein, as well as a significant dilutional effect on most of the coagulation parameters. Still standing for 30 min, with and without rehydration caused a comparable increase in tissue factor by 49.83 ± 13.6%, and 35.34 ± 8.55% (p>0.05), respectively and in von Willebrand factor (vWF) 9.5 ± 2.4% and 13.59 ± 2.17% (p>0.05), respectively. At 30 min standing, after intravenous rehydration, factor V and VIII activities, and fibrinogen rose by 22 ± 1.9%, 31.2 ± 6.2%, 9.15 ± 2.64%, (p<0.002 for all), respectively. Prothrombin fragments 1+2 elevated by 84.84 ± 15.3% (p<0.001). Comparable results were obtained with and without the rehydration. Additionally, protein C assay results decreased by 19.4 ±1.7% and 17.5 ± 2.6%, with and without fluids (p<0.05 for both). In healthy subjects, intravenous prophylactic rehydration with normal saline resulted in a haemodilution of all the coagulation parameters, but did neither attenuate nor prevent the orthostatic hypercoagulability.

Keywords

Orthostatic hypercoagulability - prolonged standing - tissue factor - hydration

^* Equal contribution.

• References

• 1 Hinghofer-Szalkay H, Moser M. Fluid and protein shifts after postural changes in humans. Am J Physiol 1986; 250: H68-H75.
• 2 Persson PB. Modulation of cardiovascular control mechanisms and their interaction. Physiol Rev 1996; 76: 193-244.
• 3 Bassenge E. Endothelial function in different organs. Prog Cardiovasc Dis 1996; 39: 209-228.
• 4 Felmeden DC, Lip GY. Endothelial function and its assessment. Expert Opin Investig Drugs 2005; 14: 1319-1336.
• 5 Dielis AW, Smid M, Spronk HM. et al. The prothrombotic paradox of hypertension: role of the renin-angiotensin and kallikrein-kinin systems. Hypertension 2005; 46: 1236-1242.
• 6 Lin MC, Almus-Jacobs F, Chen HH. et al. Shear stress induction of the tissue factor gene. J Clin Invest 1997; 99: 737-744.
• 7 Chong BH, Lee SH. Management of thromboembolism in hematologic malignancies. Semin Thromb Hemost 2007; 33: 435-448.
• 8 Rosenberg RD, Aird WC. Vascular-bed--specific hemostasis and hypercoagulable states. N Engl J Med 1999; 340: 1555-1564.
• 9 Edelsberg J, Hagiwara M, Taneja C. et al. Risk of venous thromboembolism among hospitalized medically ill patients. Am J Health Syst Pharm 2006; 63: S16-S22.
• 10 Lee AY. Epidemiology and management of venous thromboembolism in patients with cancer. Thromb Res 2003; 110: 167-172.
• 11 Masoud M, Sarig G, Brenner B. et al. Orthostatic hypercoagulability: a novel physiological mechanism to activate the coagulation system. Hypertension 2008; 51: 1545-1551.
• 12 Dati F, Hafner G, Erbes H. et al. ProC Global: the first functional screening assay for the complete protein C pathway. Clin Chem 1997; 43: 1719-1723.
• 13 Kraus M, Noah M, Fickenscher K. The PCAT--a simple screening assay for assessing the functionality of the protein C anticoagulant pathway. Thromb Res 1995; 79: 217-222.
• 14 Hagan RD, Diaz FJ, Horvath SM. Plasma volume changes with movement to supine and standing positions. J Appl Physiol 1978; 45: 414-417.
• 15 Osterud B, Bjorklid E. Sources of tissue factor. Semin Thromb Hemost 2006; 32: 11-23.
• 16 Mazzolai L, Silacci P, Bouzourene K. et al. Tissue factor activity is upregulated in human endothelial cells exposed to oscillatory shear stress. Thromb Haemost 2002; 87: 1062-1068.
• 17 Ovanesov MV, Ananyeva NM, Panteleev MA. et al. Initiation and propagation of coagulation from tissue factor-bearing cell monolayers to plasma: initiator cells do not regulate spatial growth rate. J Thromb Haemost 2005; 3: 321-331.
• 18 Panteleev MA, Ovanesov MV, Kireev DA. et al. Spatial propagation and localization of blood coagulation are regulated by intrinsic and protein C pathways, respectively. Biophys J 2006; 90: 1489-1500.
• 19 Galbusera M, Zoja C, Donadelli R. et al. Fluid shear stress modulates von Wille-brand factor release from human vascular endothelium. Blood 1997; 90: 1558-1564.
• 20 Hoffman M, Monroe III DM. A cell-based model of hemostasis. Thromb Haemost 2001; 85: 958-965.
• 21 Toulon P, Adda R, Perez P. Sensitivity of the ProC global assay for protein C pathway abnormalities. clinical experience in 899 unselected patients with venous thromboembolism. Thromb Res 2001; 104: 93-103.
• 22 Juhan-Vague I, Alessi MC, Raccah D. et al. Daytime fluctuations of plasminogen activator inhibitor 1 (PAI-1) in populations with high PAI-1 levels. Thromb Haemost 1992; 67: 76-82.
• 23 Kapiotis S, Jilma B, Quehenberger P. et al. Morning hypercoagulability and hypofibrinolysis. Diurnal variations in circulating activated factor VII, prothrombin fragment F1+2, and plasmin-plasmin inhibitor complex. Circulation 1997; 96: 19-21.
• 24 Sarig G, Aberbach I, Schliamser L. et al. Evaluation of ProCGlobal assay in women with a history of venous thromboembolism on hormonal therapy. Thromb Haemost 2006; 96: 573-583.
• 25 Schreijer AJ, Cannegieter SC, Caramella M. et al. Fluid loss does not explain coagulation activation during air travel. Thromb Haemost 2008; 99: 1053-1059.