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Venous Thromboembolism and Blood Rheology

Deep vein thrombosis (DVT) is a blood clot that develops and adheres within deep veins, typically in the legs. A dislodged DVT that mobilizes can result in blockage of pulmonary arterial circulation, causing pulmonary embolism (PE), a potentially deadly condition. Together, DVT and PE are conditions that constitute venous thromboembolism (VTE), a disease which is responsible for nearly 1% of total hospitalizations in the United States and between 100,000 to 180,000 deaths annually.1,2

Traditional risk factors for VTE include advanced age, history of previous VTE, immobility, recent trauma and/or surgery, inherited thrombophilias, cancer, pregnancy, estrogen-containing oral contraceptives, and known cardiovascular risk factors such as hypertension and cigarette smoking.3 However, about 30 to 50% of VTE cases have no known predispositions.4

Central to the development of venous thromboses is Virchow’s triad of endothelial injury, hypercoagulability, and stasis of blood flow. This triad is well-known to physicians and has provided support for the role of blood viscosity in the development of blood clots within the venous system.

The tendency of red blood cells (RBCs) to aggregate contributes significantly to blood viscosity, especially in areas of low shear, such as venous valve pockets, where blood flow is slow and venous thrombi are most likely to develop. A study by French hematologist Chabanel showed that RBC aggregation was significantly higher in 54 patients with leg vein thrombosis having no known predispositions when compared to age-matched controls (p < 0.05).5 Prolonged sitting has also been shown to induce localized stasis and elevated viscosity within the venous system of the legs without affecting systemic blood flow.6  Compression stockings, often worn by those at risk for DVT, were shown to significantly reduce abnormalities in RBC aggregation (p < 0.05).5 These garments compress limbs and increase blood flow by restoring normal vascular permeability, providing the force necessary to overcome the attraction of red blood cells, and improving venous return, thus reducing stasis.

Hematocrit plays an important role both in elevated blood viscosity and in hemostasis. The Tromso study prospectively followed 26,108 adults in Norway for a median of 12.5 years to determine an association between hematocrit and VTE risk. After controlling for age, BMI, and smoking, each 5% increase in hematocrit was associated with a 25% higher risk of total VTE incidence (HR 1.25; 95% CI: 1.08–1.44) and 37% higher risk of unprovoked VTE (HR 1.37; 95% CI: 1.10–1.71).7

A separate prospective study conducted by a team of Swiss researchers at the University Hospital Zurich evaluated blood viscosity in patients with acute DVT, 6 weeks post-DVT, and 1 year post-DVT. During the acute phase, high-shear blood viscosity was significantly elevated compared to controls [(5.78; 95% CI: 5.61–5.87) vs. (5.59; 95% CI: 5.27–5.9)] mPa s, (p < 0.01).8 This increase was explained by elevations in fibrinogen, plasma viscosity, and erythrocyte aggregation, even though hematocrit was reduced. After one year, viscosity showed a constant decrease and returned to normal in patients with transient risk factors. However, patients with persistent DVT risk factors had significantly higher levels of plasma viscosity, fibrinogen, and RBC aggregation vs. subjects with transient risk factors (all p < 0.01). It is possible that adverse blood flow may causally explain the increased risk of DVT recurrence in patients with persistent risk factors. 

If blood viscosity plays a central role in the pathogenesis of VTE, it follows that the mainstays of treatment and prevention of these disorders should have viscosity-lowering effects. Indeed, heparin, low-molecular weight heparin, compression stockings, and exercise have been shown to reduce blood viscosity and improve blood flow.5,9-13 Monitoring blood viscosity may help identify thrombogenic risk in individuals who are otherwise absent of traditional risk factors for VTE.  

1.  Heit JA. The epidemiology of venous thromboembolism in the community. Arteriosclerosis, thrombosis, and vascular biology. 2008;28(3):370-372.

2.  Goldhaber SZ. Deep Venous Thrombosis and Pulmonary Thromboembolism. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill Education; 2015.

3.  Goldhaber SZ. Venous thromboembolism: epidemiology and magnitude of the problem. Best practice & research. Clinical haematology. 2012;25(3):235-242.

4.  White RH. The epidemiology of venous thromboembolism. Circulation. 2003;107(23 Suppl 1):I4-8.

5.  Chabanel A, Horellou MH, Conard J, Samama MM. Red blood cell aggregability in patients with a history of leg vein thrombosis: influence of post-thrombotic treatment. British journal of haematology. 1994;88(1):174-179.

6.  Hitosugi M, Niwa M, Takatsu A. Rheologic changes in venous blood during prolonged sitting. Thromb Res. 2000;100(5):409-412.

7.  Braekkan SK, Mathiesen EB, Njolstad I, Wilsgaard T, Hansen JB. Hematocrit and risk of venous thromboembolism in a general population. The Tromso study. Haematologica. 2010;95(2):270-275.

8.  Alt E, Banyai S, Banyai M, Koppensteiner R.. Thrombosis research. 2002;107(3-4):101-107.

9.  Ruggiero HA, Castellanos H, Caprissi LF, Caprissi ES. Heparin effect on blood viscosity. Clin Cardiol. 1982;5(3):215-218.

10.  Erdi A, Thomas DP, Kakkar VV, Lane DA. Effect of low-dose subcutaneous heparin on whole-blood viscosity. Lancet. 1976;2(7981):342-344.

11.  Calabrò A, Piarulli F, Milan D, Rossi A, Coscetti G, Crepaldi G. Clinical assessment of low molecular weight heparin effects in peripheral vascular disease. Angiology. 1993;44(3):188-195.

12.  Coppola L, Grassia A, Coppola A, et al. Effects of a moderate-intensity aerobic program on blood viscosity, platelet aggregation and fibrinolytic balance in young and middle-aged sedentary subjects. Blood Coagul Fibrinolysis. 2004;15(1):31-37.

13.  Lowe GD. Virchow's triad revisited: abnormal flow. Pathophysiol Haemost Thromb. 2003;33(5-6):455-457.

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