Red blood cell count, hematocrit, and hemoglobin concentrations are regularly measured in clinical practice and changes in hematocrit or hemoglobin concentrations are most commonly used to assess the degree of hemoconcentration.1 A relative change in hematocrit refers to a change in blood volume and is reflected by the change in blood concentrations of hemoglobin and red blood cell count.2–4 However, the relative change of hematocrit is not a direct measure of changes in plasma volume or plasma concentrations.5 This is especially important in hemodialysis where large changes in intravascular volume occur and where concentrations of various plasma components such as albumin or hepatitis C virus RNA concentrations need to be corrected for hemoconcentration.6
The discrepancy is probably best demonstrated by the following example: assume 1 L of blood at a hematocrit of 50% and the baseline plasma volume of 500 ml. When 100 ml of plasma water is removed, the plasma volume falls by 20% (100 ml plasma water/500 ml plasma) but the reduction in blood volume is only 10% (100/1,000). Therefore, the change in plasma concentration using a smaller reference volume, i.e., plasma volume, when calculating the relative change as a percentage must be much larger (twice as large in this case) than the corresponding change in blood concentration.
The hemoconcentration hH of a blood component such as red blood cells induced by changes in plasma water volume is given as
where H is the hematocrit (the volume of red blood cells per volume of blood, given in percent), and where indices 0 and 1 refer to the condition before and after dialysis, respectively.
On the other hand, the hemoconcentration hp of a plasma component such as the hepatitis C virus RNA concentration given per volume of plasma is given as
showing that hp ≤ hH when H0 (and H1) > 0 (see Appendix). In case of ultrafiltration-induced hemoconcentration where H1 > H0 it follows from Equation 2 that hp > hH demonstrating that the effect on plasma volume exceeds the effect on blood volume. In hemodialysis where the relative change in hematocrit is in the range of 15%7 (hH = 1.15; Equation 1) and sometimes even more, the discrepancy between hp and hH can be substantial (Figure 1).
To account for the effect of hemoconcentration the concentration of a plasma component P1 after an intervention (e.g., a postdialysis concentration) has to be divided by the degree of hemoconcentration hp according to
Any significant deviation of P′1 from initial plasma concentration P0 then indicates an effect not merely explained by hemoconcentration (or hemodilution), but also by other mechanisms (e.g., clearance through the dialysis membrane in hemodialysis patients). Failure to correct for hp with ultrafiltration-induced hemoconcentration (where H1 > H0, and where hp > hH) therefore leads to a systematic overestimation of P′1.
The issue of identifying the proper reference volume is akin to the discrepancy between plasma and plasma water concentrations. Thus, if a concentration is given per unit blood volume, hemoconcentration has to be calculated for a blood component (hH). If a concentration is given per unit plasma volume, hemoconcentration has to be calculated for a plasma component (hp).
The correction for effects of hemoconcentration (or hemodilution) according to Equation 3 is valid under the assumption of a constant red blood cell volume such as in the absence of hemorrhage or blood infusions, as well as in the absence of osmotic fluid shifts between plasma and red blood cells.8 These conditions are usually met during hemodialysis performed under isotonic (isonatremic) conditions and where blood loss is minimized. It is further assumed that the distribution of red blood cells between different parts of the circulation remains constant. If this is not the case the proper assessment of hemoconcentration requires additional measurements beyond the possibility of everyday clinical practice.
In conclusion, when fluid volume is removed from (or added to) the plasma volume during an intervention such as hemodialysis, the change in concentration of a plasma component is much larger than the concomitant hematocrit change. Thus, to correctly assess whether the change of a plasma component resulted from the volume change or from other aspects of the intervention, the plasma concentration has to be divided by the hemoconcentration for the plasma compartment hp as described earlier and not by the hemoconcentration for the blood compartment, as it is frequently done.
For a plasma component not removed from the plasma by ultrafiltration, mass balance requires that
where P is the plasma concentration, Vp is the plasma volume, and indices 0 and 1 refer to conditions at baseline and after the volume change, respectively. Plasma volume is given as
where Vb is blood volume, and H is hematocrit (in percent). Substituting Vp0 and Vp1 in Equation 4 by Equation 5 under consideration of the proper indices gives a ratio for the protein concentrations after the volume shift relative to the volume concentration at baseline:
The ratio P1/P0 describes the hemoconcentration (hemodilution) of a plasma component and is termed hp. The balance of red blood cell volume requires that
where hH is the hemoconcentration of a blood component. Insertion of Equation 7 into Equation 6 provides a relationship to relate the hemoconcentration hp to the baseline hematocrit and the hematocrit change:
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