Hemodilution and Oxygen Transport Capacity 

Borst et al. (1999) examined blood viscosity reduction by repeated phlebotomies with substitution of 6% HES (molecular weight 40,000) and asked whether this improved pulmonary hemodynamics and oxygen uptake. The authors reported that mean pulmonary artery pressure decreased from 30 to 22 mmHg, and arterial oxygen partial pressure increased from 63.2 to 71.8 mmHg at rest. Pulmonary vascular resistance fell from 345 to 194 dyne•s•cm-5. The patients’ peak exercise capacity increased from 9.2 kJ before the study to 13.5 kJ at the end of the study. The researchers’ findings suggest that a prolonged improvement of pulmonary microcirculation by reducing blood viscosity may improve pulmonary gas exchange, hemodynamics, and exercise tolerance in patients with severe chronic obstructive pulmonary disease and pulmonary hypertension. 

Hemodilution for Leg Pain 

In patients with leg pain, which is caused by reduced blood flow to the lower limbs as a result of PAD, the healthcare provider aims to increase blood flow. The mechanism of increased perfusion results from a chain of events starting from reduced blood viscosity, reduced peripheral vascular resistance, increased venous return, and eventually increased cardiac output. The opposing effect of reduced oxygen content of blood is compensated for by the increased perfusion and increased oxygen extraction of tissue, rendering a net increase in oxygen availability due to hemodilution. 

Basic hemodynamics demonstrates that blood viscosity is related inversely to blood flow in the legs. Dormandy (1987) reported that the percentage of change in calf blood flow was two to three times greater than the percentage of change in blood viscosity due to the non-Newtonian characteristics of whole blood. Other studies have found a 10% to 25% increase in the mean blood flow values of patients with leg pain (Di Perri 1979, Forconi et al.1979). Hemodilution has shown potential in treating peripheral ischemia, and the beneficial results can be attributed to the fact that hemodilution alters blood viscosity in patients with peripheral artery disease. 

Patients suffering from arteriopathy of the lower limb were isovolumic hemodiluted with albumin and albumindextran solutions (Stoltz et al. 1999). When their hematocrits were lowered to 35%, the relief in pain occurred quickly, and ulcer healing and treadmill performance also improved. The optimum hematocrit for such hemodilution treatment with HES was reported to be 40% to 41% (Höffkes et al. 1991). The optimum hematocrit for oxygen delivery is probably lower (Birchard 1997, Kameneva et al. 2000, Laks et al. 1974, Messmer et al. 1972, Snyder 1971, Sunder-Plassman et al. 1971). 

Hemodilution for Stroke and Cognitive Dysfunction 

Isovolumic hemodilution has been used to improve blood flow to the brain and treat cerebral ischemia. Since hemodilution decreases hematocrit, it substantially increases cerebral blood flow (Dormandy 1987). The reduction in hematocrit decreases blood viscosity, which also reduces the injury caused by blood flow against the arteries. Thus, the benefit of hemodilution in treating cerebral ischemia can be attributed to an alteration in whole blood viscosity. 

Strand et al. (1984) treated the early phase of ischemic stroke by combining blood removal of 250 to 650 mL during the first 2 days with administration of low-molecular weight dextran 40. In these patients, 85% had improved neurologic scores over the first 10 days compared with 64% of matched controls. Furthermore, these patients with acute stroke had improved overall clinical outcomes for three months after hemodilution.

Goslinga et al. (1992) assessed the significance of high hematocrit and dehydration in 300 patients in the acute phase of ischemic stroke. The hemodilution group had blood withdrawn and received 20% long-lasting albumin plus crystalloids; the control group received rehydration with crystalloids. The groups were stratified by hematocrit: normal (<0.45) and high (>0.45). Two-thirds of the patients in each group (hemodilution treatment and rehydration control) had normal hematocrit. Measured by mortality rate and independent functioning at home, at three months, the normal-hematocrit hemodilution group had significantly better outcomes than the normal-hematocrit rehydration group. Interestingly, the high-hematocrit rehydration group had significantly better results than the normal-hematocrit hemodilution group. The results of hemodilution were specifically called a viscosity effect. Noting that both reducing viscosity and optimizing circulating volume must be considered in hemodilution therapy, the authors recommend customizing the hemodilution regimen for each patient. 

Hemodilution in Polycythemia 

Bertinieri et al. (1998) studied the effects of acute changes in blood viscosity on blood pressure after isovolumic hemodilution in 22 patients (10 normotensive and 12 hypertensive) with polycythemia. Clinic and 24-hour ambulatory blood pressures were taken before hemodilution and 7 to 10 days afterward, as were hematocrit, plasma renin activity, plasma endothelin-1, right atrial diameter (echocardiography), and blood viscosity. Hematocrit was significantly reduced in normotensive and hypertensive patients and in the combined group. Blood viscosity, clinic blood pressure, and ambulatory blood pressure were significantly reduced in hypertensive patients and the combined group. 

Fujioka (1989) conducted a study measuring whole blood viscosity in 10 patients with polycythemia vera and 129 normal controls. The author reported that phlebotomy and fluid infusion therapy were valuable in most patients because the viscosity was decreased at once to the normal level. 

Sources: 

Holsworth RE, Cho YI. “Hyperviscosity Syndrome: A Nutritionally-Modifiable Cardiovascular Risk Factor.” Advancing Medicine with Food and Nutrients, Second Edition. Ed. Ingrid Kohlstadt. Boca Raton: CRC Press. 2012. 

Kensey KR, Cho YI. The Origin of Atherosclerosis: What Really Initiates the Inflammatory Process, Second Edition. Summersville: SegMedica, 2007. 

References: 

Borst MM, Leschke M, König U, Worth H. Repetitive hemodilution in chronic obstructive pulmonary disease and pulmonary hypertension: effects on pulmonary hemodynamics, gas exchange, and exercise capacity. Respiration 1999;66:225-232. 

Dormandy JA. Cardiovascular disease. In: Chien S, Dormandy J, Ernst E, Matrai A, eds. Clinical Hemorheology: Applications in Cardiovascular and Hematological Disease, Diabetes, Surgery and Gynecology. Boston: Martinus Nijhoff, 1987:179-181. 

Di Perri T. Rheological factors in circulatory disorders. Angiology 1979;30:480-486. 

Forconi S, Guerrini M, Ravelli P, et al. Arterial and venous blood viscosity in ischemic lower limbs in patients affected by peripheral obliterative arterial disease. J Cardiovasc Surg (Torino) 1979;20:379-384. 

Stoltz JF, Singh M, Riha P, eds. Therapeutic applications. In: Hemorheology in Practice. Amsterdam: IOS Press, 1999:120-121.

Höffkes HG, Saeger-Lorenz K, Ehrly AM. Optimal hematocrit in patients with intermittent claudication. Exercise induced muscle tissue oxygenation pressure after stepwise isovolemic hemodilution. Acta Medica Austriaca 1991;8(suppl1):16-19. 

Kameneva MV, Watach MJ, Borovetz HS. Gender difference in oxygen delivery index: potential link to development of cardiovascular diseases. Appl Cardiopulm Pathophysiol 2000;9:382-387. 

Laks H, Pilon RN, Klövekorn WP, et al. Acute hemodilution: its effect on hemodynamics and oxygen transport in anesthetized man. Ann Surg 1974;180:103-109. 

Messmer K, Lewis DH, Sunder-Plassmann L, et al. Acute normovolemic hemodilution. Changes of central hemodynamics and microcirculatory flow in skeletal muscle. Eur Surg Res 1972;4:55-70. 

Snyder GK. Influence of temperature and hematocrit on blood viscosity. Am J Physiol 1971;220:1667-1672. 

Strand T, Asplund K, Eriksson S, et al. A randomized controlled trial of hemodilution therapy in acute ischemic stroke. Stroke 1984;15:980-989. 

Goslinga H, Eijzenbach V, Heuvelmans JH, et al. Custom-tailored hemodilution with albumin and crystalloids in acute ischemic stroke. Stroke 1992;23:181-188. 

Bertinieri G, Parati G, Ulian L, et al. Hemodilution reduces clinic and ambulatory blood pressure in polycythemic patients. Hypertension 1998;31:848-853. 

Fujioka S. Rheological study on vascular occlusion and cellular hyperviscosity syndrome in polycythemia vera. Nippon Ketsueki Gakkai Zasshi 1989;52:688-695.