The Question

A patient repeatedly presents to the hospital with an elevated hemoglobin that then falls precipitously by the following day.

Shown here are two of several similar admissions in the same patient. In one episode, the hemoglobin fell from 18.8 g/dL on arrival to 13.3 g/dL nine hours later.

What is the most likely explanation?

• Therapeutic phlebotomy
• Acute hemolysis
• IV fluids
• Laboratory artifact

Poll Results

We posed this question on Twitter.

The majority answer was IV fluids, which is correct.

At first glance, such a large change in hemoglobin may seem surprising. But the explanation is not a matter of intuition or clinical experience. It follows directly from basic physiology and a simple quantitative calculation.

Working Through the Calculation

Assumptions

For the calculations below we assume:

• Initial hemoglobin: 18.8 g/dL
• Blood volume when euvolemic: ≈5 L
• Severe dehydration contracts blood volume to ≈4 L (~20% contraction)
• Normal saline: ~25% remains intravascular
• Therapeutic phlebotomy: ~0.5 L whole blood per unit
• RBC mass remains constant unless blood is removed or destroyed

Simple Calculation Method

Convert hemoglobin to g/L for consistency with blood volume.

19 g/dL ≈ 190 g/L

Initial RBC mass proxy:$$Hb \times BV = 190 \times 5 = 950$$Hb × BV=190 ×5 = 950

After phlebotomy of x L

• RBC mass decreases by 190 × x
• blood volume decreases by x

After normal saline of y L

• blood volume increases by 0.25 × y
• RBC mass unchanged

$$Hb_{new} \approx \frac{\text{new RBC mass}}{\text{new blood volume}}$$

The same approach can be applied to other scenarios. The table below summarizes the expected hemoglobin values under several common clinical conditions.

Summary of estimated hemoglobin values

Scenario	Starting BV	Blood removed	NS given	Net intravascular change	Expected Hb
IV fluids only (euvolemic)	5 L	0	2 L	+0.5 L*	~17.3
IV fluids correcting dehydration**	4 L	0	4 L	+1.0 L	~15.2
Phlebotomy (1 unit) immediate***	5 L	0.5 L	0	−0.5 L	~18.8
Phlebotomy after plasma refill****	5 L	0.5 L	0	~0	~16.9
Phlebotomy + 1 L NS	5 L	0.5 L	1 L	−0.25 L	~18.0

* Normal saline: approximately 25% remains in the intravascular space, with the remainder distributing to the interstitial compartment.
** Dehydration scenario: starting blood volume of 4 L represents ~20% plasma volume contraction, consistent with severe dehydration.
*** Therapeutic phlebotomy removes whole blood, so both RBC mass and plasma volume decrease initially, resulting in little immediate change in hemoglobin concentration.
**** Plasma refill: over several hours after phlebotomy, interstitial fluid shifts into the intravascular space, restoring plasma volume while RBC mass remains reduced.

Evaluating the possible explanations

The calculations lead to the following conclusions.

Mechanism	Physiologic change required	Approximate quantity
IV fluids (euvolemic)	~40% plasma expansion	~8 L saline
IV fluids correcting dehydration	Restoration of contracted plasma volume	~2–4 L IV fluid
Therapeutic phlebotomy	Removal of ~30% RBC mass	~1.4–1.6 L blood (~3 units)
Acute hemolysis	Destruction of ~30% RBC mass	Would cause severe illness
Laboratory artifact	No physiologic change	Possible but unlikely here

Approximate quantities are derived from the calculations above and assume a euvolemic blood volume of ~5 L unless otherwise stated.

Why Phlebotomy Cannot Explain the Observation

Therapeutic phlebotomy removes whole blood, not just red cells.

This means both:

• RBC mass decreases
• plasma volume decreases

Because numerator and denominator fall together, hemoglobin concentration changes very little immediately after phlebotomy.

Even with plasma redistribution or IV fluids afterward, achieving a drop from 18.8 → 13.3 g/dL would require removing an implausibly large amount of blood and replacing that volume with plasma.

What About Hemolysis or Laboratory Error?

Hemolysis severe enough to reduce hemoglobin by ~30% within hours would typically produce clear clinical signs of acute illness.

Laboratory artifact is always possible, but in this case it was unlikely: the same pattern occurred during two separate hospital admissions.

The Clinical Context

This patient was a 60-year-old man with cyclical vomiting who repeatedly presented with:

• Hemoglobin ~19 g/dL on arrival
• Rapid fall to ~13 g/dL after rehydration

Severe dehydration produced hemoconcentration (high hemoglobin despite unchanged RBC mass), and IV fluids restored plasma volume, leading to rapid normalization of hemoglobin.

Take-Home Message

Rapid changes in hemoglobin concentration are rarely mysterious.

When red cell mass remains constant, hemoglobin simply reflects plasma volume.

With a few physiologic assumptions and a short calculation, the answer becomes clear.

Clinical reasoning grounded in quantitative physiology often beats intuition.