Case Author(s): David A. Hillier, M.D., Ph.D. and Jerold Wallis, M.D. , 7/1/99 . Rating: #D., #Q4

Diagnosis: Polycythemia vera

Brief history:

63 yo woman with intermittent transient ischemic attacks.

Full history/Diagnosis is available below

Diagnosis: Polycythemia vera

Full history:

63 yo woman with polycythemia, peripheral hematocrit of 75%, and symptoms of intermittent transient ischemic attacks. The patient underwent phlebotomy last evening of 430 ml.


Blood volume, 19.5 uCi Cr-51 labeled autologous red blood cells, IV.

4.2 uCi I-125 human serum albumin, IV.

6 drops SSKI.


The results (summarized in bold) are the most important for intepretation. The remainder demonstrates the calculations used in determining the result and duplicate crosschecks for ensuring validity.

Corrected hematocrit (peripheral): 10 min sample): 69%

RBC mass (ml/kg): Measured, (10 min): 73.1 (low normal: 15.2, mean: 20.3, high normal: 25.3)

Plasma vol (ml/kg): Measured, (10 min): 44.4 (low nl: 24.8, mean: 33.0, high nl: 41.3)

Whole-body hematocrit: (10 min) 62.2

Whole-body / venous hematocrit (F-cell ratio): (10 min) 0.90

Numbers used for calculations follow; you may skip to the discussion below if desired.

Blood volume examination (12/3/97):

63 yo woman, Weight: 83 Kg, BSA (sq m): 1.97

Corrected hematocrit (peripheral):

10 min sample: 69%

20 min sample: 69%

Cr-51 syringe weights (gm):

Full: 21.43

After Std: 20.32

Empty: 9.65

I-125 syringe weights (gm):

Full: 14.572

After Std: 14.12

Empty: 9.62

Counting data (all samples 2 ml):

Cr-51 Std, Cr-51 window, number 1: 45723

Cr-51 Std, Cr-51 window, number 2: 46097

Cr-51 Std, I-125 window, number 1: 782

Cr-51 Std, I-125 window, number 2: 796

I-125 Std, Cr-51 window, number 1: 524

I-125 Std, Cr-51 window, number 1: 525

I-125 Std, I-125 window, number 1: 47510

I-125 Std, I-125 window, number 2: 47314

10 min sample, Cr-51 window, number 1: 5492

10 min sample, Cr-51 window, number 2: 5395

10 min sample, I-125 window, number 1: 4210

10 min sample, I-125 window, number 1: 4141

20-min sample, Cr-51 window, number 1: 5476

20-min sample, Cr-51 window, number 2: 5446

20-min sample, I-125 window, number 1: 4206

20-min sample, Cr-51 window, number 2: 4127

Blood Bkg, Cr-51 window, number 1: 520

Blood Bkg, Cr-51 window, number 2: 491

Blood Bkg, I-125 window, number 1: 120

Blood Bkg, I-125 window, number 2: 103

Air Bkg, Cr-51 window, number 1: 501

Air Bkg, Cr-51 window, number 2: 503

Air Bkg, I-125 window, number 1: 127

Air Bkg, I-125 window, number 2: 101

Crossover factor: 0.0149

RBC mass (ml/kg):

Measured, 10 min: 73.1 (low normal: 15.2, mean: 20.3, high normal: 25.3)

Measured, 20 min: 72.8

Plasma vol (ml/kg)

Measured, 10 min: 44.4 (low nl: 24.8, mean: 33.0, high nl: 41.3)

Measured, 20 min: 44.5

Total vol of whole blood

10 min 117.5 (Mean: 53.3)

20 min 117.4

Whole-body hematocrit

10 min 62.2

20 min 62.1

Whole-body / venous hematocrit (F-cell ratio):

10 min 0.90

20 min 0.90


The blood volume examination is based on a dilution technique: volume = (quantity injected) / (concentration of diluted tracer). Red cells are labeled with Cr-51. Plasma volume is assessed with I-125 labeled human serum albumin. To assure that the only Cr-51 present is in red cells, the labeled blood is centrifuged and then washed (the plasma supernatent is removed and reconstituted with saline) prior to being reinjected. After injection of tracer intravenously, samples are withdrawn at 10 and 20 minutes post injection. Samples are measured in a well counter.

The fact that two different isotopes are being measured simultaneously creates minor measurement difficulties. Two different energy windows are set for the two isotopes, but there is some crossover of one isotope into the energy window of the other. The gamma photon energy of Cr-51 is much higher than that of I-125. Therefore, downscatter from Cr-51 will fall into the I-125 window. The degree to which this occurs can be determined by measuring the activity in the I-125 window from a Cr-51 standard of known activity. A correction cross-over factor can then be determined to compensate for this scatter. The Cr-51 activity in the blood samples is multiplied by the cross-over factor and this is then subtracted off from the measurement in the I-125 window.

The blood volume examination is complex and there are therefore many opportunities for errors and artifacts. At our institution, each sample and standard are run in duplicate to help prevent this. Contamination with another radiopharmaceutical (particularly Tc-99m) is is easily introduced (just a tiny amount on a glove that is inadvertently introduced into a sample can cause a dramatic artifactually elevated count rate). If a sample is suspected to have a spurious high count rate, the vial may be recounted after a delay (for example, 1 or 2 days later). The physical decay rate can then be used to determine if contamination was present (both Cr-51 and I-125 have much longer half-lives than Tc-99m).

If there is extravasation at the injection site, the concentration of tracer in the blood will be reduced, making the apparent volume of distribution and therefore the measured red cell mass or plasma volume appear larger than it really is. Conversely, if the measured concentration is too high, the measured red cell mass or plasma volume will be artifactually reduced. It is therefore important to inject and draw subsequent samples from different veins (preferably from different arms) to avoid residua in the line or vein from artifactually increasing the measured concentration.

The whole-body hematocrit is lower than the peripheral hematocrit. This is due to streaming effects in which plasma flows more readily through capillaries than red cells. Thus, there is relatively a higher proportion of plasma in the capillaries than in larger, peripheral vessels. The F-cell ratio is a measure of whole-body hematocrit, determined in the blood volume examination, to the measured peripheral hematocrit. This number is typically in the range of 0.9.

Albumin diffuses slowly into the extracellular space. 10% will leave the intravascular space at one hour. The error is 1 to 3% normally at 10 minutes. This error is increased if there is protein loss or if vascular permeability is increased (e.g., burn patients). One can approximately compensate for the error by obtaining two measurements (e.g., at 10 and 20 minutes). The later, 20 minute sample, will show an increase in volume of distribution and therefore an increased measured plasma volume. The correct value can be approximated by extapolating from the 20 minute measurement through the 10 minute measurement back to time 0. In practice, the degree of error is small and this extrapolation is not generally necessary.

Polycythemia vera was first described by Vaquez in 1892 as characterized by a triad of cyanosis, polycythemia and splenomegaly. It is currently believed to result from the transformation of a single stem cell by analysis of the polymorphic X-chromosome marker glucose-6-phosphate dehydrogenase. The onset is insidious and is most common in elderly patients. Symptoms include headaches, plethora, prurutis, thrombosis and GI bleeding. Thrombosis and hemorrhage are the most common complications (seen in 1/3) and manifesting in such conditions as CVA, MI, DVT / PE and Budd-Chiari. There is commonly a low partial pressure of oxygen. An absolute neutrophilia is seen in 2/3. Elevated platelets are seen in 1/2 (> 1,000,000 in 10%). The platelets do not function properly. PT and PTT are generally normal.

Diagnostic features include erythrocytosis, leukocytosis, thrombocytosis and splenomegaly. The phases of polycythemia include the plethoric phase (increased red cell mass), followed after years by the spent phase characterized by anemia and marrow fibrosis (similar to myelofibrosis).

Treatments have included phlebotomy, P-32 radiation treatment, chlorambucil and hydroxyurea. The polycythemia study group (1986) determined that the median survival for phlebotomy alone is 13.9 years, P-32 11.8 years and chlorambucil 8.9 years. Some have reported an increased incidence of leukemia with P-32 or chlorambucil therapy.

Currently, phlebotomy is considered first-line therapy. If the hematocrit is > 64%, phlebotomy is generally conducted every other day until the value drops to 55%. It is then performed as needed to maintain hematocrit at 45%. Hydroxyurea is a second-line treatment that is useful if the platelet count is greater than 1,000,000.

Differential Diagnosis List

The differential diagnosis for a high hematocrit includes polycythemia vera, idiopathic erythrocytosis, secondary polycythemia due to increased erythropoietin (due to hypoxia or renal neoplasm - platelets, neutrophils and spleen will be normal) and apparent polycythemia due to hypovolemia (with a resulting small plasma volume and normal red cell mass). The blood volume examination is used to determine the actual red cell mass (as opposed to hematocrit which yields the ratio of red cell mass to plasma volume). It can therefore be used to distinguish true polycythemia from apparent polycythemia. A true polycythemia in the setting of a low erythropoietin level is consistent with polycythemia vera.

ACR Codes and Keywords:

References and General Discussion of Blood Volume (Anatomic field:Vascular and Lymphatic Systems, Category:Neoplasm, Neoplastic-like condition)

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Case number: bv001

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