Relative/secondary polycythemia-sleep apnea/altitude
Date: Mon, 19 May 1997 01:04:07 -0400
From: Norm Freeburg <nfreeburg@CYBERUS.CA>
Subject: sleep apnea polycythemia, beta blockers,
HCT - coronary disease
Bob, Joel, Helen, et al.,
Sleep apnea, in the journal articles I've seen anyway, is associated with
relative or apparent polycythemia and not polycythemia vera. (Normal blood
gas levels - arterial oxygen saturation- is part of the P.vera diagnosis.)
HOWEVER, it's very interesting, Bob, that your hematologist has suggested
oxygen to you (and mentioned another patient) since you ARE (I think if I
remember correctly?) from Colorado?? (Denver area??) One of the articles
that has a lengthy section on sleep apnea is the chapter on "Relative
Polycythemia" in the PVSG text, POLYCYTHEMIA VERA AND THE
MYELOPROLIFERATIVE DISORDERS, publ. in 1995 by Saunders. The section
mentions a study of 7 Denver polycythemic patients who all had hematocrit
normalized after nocturnal oxygen therapy & weight loss. And only 1 of the
7 was established as relative polcyythemia by lowered plasma volume; the
other 6 were considered to have an elevated red cell mass, but did NOT fit
P. vera criteria.
To define "relative polcythemia" - this is a raised hematocrit because the
plasma volume is lowered (not because there are actually more red cells -
since hematocrit is the percent of the red cells in the blood plasma).
However, some sources still list as "relative polcythemia" even if the
plasma volume is normal (or only slightly decreased) and the red cell mass
is high-normal. Individuals in this group would not fit the P.vera criteria
and might fit criteria for "relative" polcythemia. (Such as smoking,
obesity, hypertension, alcohol consumption.) Other sources would make a
distinction and call this "apparent polycythemia" - where the plasma volume
is not apparently lowered, but P.vera criteria is not met.
Absolute erythrocytosis (polcythemia) would be the raised hematocrit
caused by an elevated red cell mass. This might be P. vera or it might be
secondary caused usually by a raised erythropoietin level. (And some of the
secondary causes overlap with the causes of relative polcythemia - smoking,
high altitude, sleep apnea, cardio-pulmonary disease, tumors, etc.) The
terms "true" or "benign" erythrocytosis can be used for absolute
polcythemia that does NOT meet P. vera criteria. In some cases, sources
use "true" or "benign" even if there is a secondary cause; in other cases
"true" or "benign" are reserved for those cases that are absolute
(increased red cell mass), but no known secondary cause yet not meeting P.
vera criteria.
So what's the significance of all this? Well, the good news is that
benign or true erythrocytosis (if it stays "true" or "benign") does NOT
(say Najean, PVSG articles, etc.) progress to spent phase/MF.
In the case of the Denver residents who were said to have apparent sleep
apnea-induced polcyythemia - 1 was said to be "relative"; the other 6 were
said to be "true", but still not P. vera.
I hope I'm not being TOO terribly confusing - I guess what I might be
wondering in particular for you, Bob, is if your hematologist thinks you
might fit more into the relative/apparent or even the benign erythrocytosis
category (since you do live at a high altitude). At any rate that WAS the
rationale in the study of the 7 Denver polycythemic patients. (Now getting
a red cell mass is apparently also tricky with smokers, obesity,etc.) The
thrombotic risks may still exist in these other polycythemias, but the risk
to spent/MF should not be there. Some of the more definite indicators of
actual P. vera (but not usually a benign or true erythrocytosis) would be
the abnormal bone marrow biopsy, positive endogenous erythroid colonies (or
more recently BFU-E colonies), and erythropoietin levels (more likely low
in P.vera though this can overlap). And another thought in respect to
relative/apparent or secondary polcythemia is that, though phlebotomy is
still used; some do not recommend that same hematocrit level (of under 45%
for example) since, if oxygen-depravity is the cause, then phlebotomizing
to iron-deficiency so that oxygen-carrying capacity of the blood is greatly
reduced, is counterproductive.
On the other hand, if P.vera is definitely established (by biopsy, EEC
test, etc.) and someone has purposely been phlebotomized to iron-deficiency
(mean corpuscular hemoglobin greatly reduced); well, I'm just not sure how
that would work with oxygen administered. (Perhaps someone out there can
help!!!) Norm, for example, with very low MCV and MCH can not carry as
much oxygen to the cells (doesn't have the iron necessary to bind with the
oxygen, or whatever, though he still DOES have an elevated number of red
blood cells). If his blood began to carry more oxygen, if I understand
correctly, his iron levels would need to be increased, and that would be
counterproductive to what the phlebotomies are supposed to be doing. (Of
course, Norm is actually on IFN so we hope that his MCV/MCH CAN normalize.)
On the other hand, if sleep apnea, high-altitude, obesity, etc., are
causing oxygen-deprivation, then oxygen-administration would fit. UNLESS,
the theory is that the oxygen being administered is being carried directly
by the plasma (watery portion of the blood which usually oxygen doesn't
dissolve in very well). (???)
Robert,
I noticed in the same article (as mentioned above) that beta blockers are
not recommended for patients with relative polcythemia. (The entire article
is on relative polycythemia; it has a considerable section on hypertension
- not sure when it correlates to P. vera, I really haven't studied it
thoroughly.) Anyway, the statement on beta blockers: "On the other hand,
beta blockers such as propranolol, which appear to produce sensitivity to
ANPs and decrease plasma volume and increase hematocrit..not be agents of
choice for hypertensive patients with relative polycythemia."
Dan L.,
As per your comments wondering about whether (or why) hematocrit isn't
routinely kept down with coronary risk (at least, I think, this was your
comment) - in the same article mentioned above they go into GREAT lengths
about this. They mention several studies that address this question.
Although there is some disagreement (or the typical "further studies
necessary or in progress"), the article states: "..these studies do not
generally confirm the hypothesis that relatively minor increases in
hematocrit play a significant role in the expression of coronary artery
disease." HOWEVER, they come to the opposite conclusion in the matter of
cerebrovascular disease (strokes). And they list a number of studies here.
Best to all,
Ruth