Apparent Polycythaemia

T. C. P e a r s o n

S U M M A R Y. Patients with apparent polycythaemia are characterised by a raised packed cell

volume (PCV; males above 0.51, females above 0.48) but normal red cell mass (RCM; less than 25%
greater than predicted). Prediction and interpretation of RCM and PV should be based on height and
weight, sincg the use of body weight alone is misleading. Patients with PCV values up to 0.60 may
have apparent polycythaemia but only 18% have a reduced PV (relative polycythaemia). Therefore,
the most common cause of the raised PCV is a change in RCM and[or PV within their normal ranges.
The clinical associations and possible causes for the R C M [ P V changes include male sex, obesity,
dehydration, diuretics, smoking, hypertension, alcohol, arterial oxygen desaturation, renal disease
and increased catecholamine levels. Retrospective studies of patients with apparent polycythaemia and
information from other groups of polycythaemic patients suggest an increased risk of vascular
occlusion, although other factors, such as hypertension and smoking, are also involved. Proposed
management includes modification of possible underlying causes and examination for risk factors for
vascular occlusion. In patients with PCV levels chronically above 0.54 venesection should be used, but
patients with PCV values below this level should only be venesected if they are considered to be at risk
of vascular occlusion. The suggested target value for PCV for venesected patients is 0.45 or below.

Investigation of patients with a raised packed cell
volume (PCV) reveals that although some have an
increased red cell mass (RCM), an absolute polycy-
thaemia, there are a significant number who do not.
It is the latter group of patients, those with a raised
PCV but normal RCM, that are the subject of this
review. A variety of descriptive titles have been
proposed for these patients and include Geisbtck's
syndrome, 1 stress polycythaemia, 2 relative polycy-
thaemia, 3 apparent polycythaemia, 4 pseudo-polycy-
thaemia 5 and spurious polycythaemia. 6 RCM and
PV measurements were not available to Geisbtck
and hence his group of patients cannot be defined by
modern criteria. Stress polycythaemia was introduced
by Lawrence and Berlin (1952) 2 since they considered
that their small group of patients were under
Professor T. C. Pearson, Department of Haematology, St T h o m a s '
Hospital, Lambeth Palace Road, London SE1 7EH, U K .
emotional stress. This certainly does not apply to all
patients. Thus stress polycythaemia is not an appro-
priate descriptive title. However, the relative merit of
the other terms could be argued. Accepting this
uncertainty, the present paper will describe all patients
with a raised PCV but normal RCM as having
apparent polycythaemia and use relative polycythae-
mia for the sub-group with a significant reduction in
PV.
Since a raised PCV and normal RCM are essential
for the definition of patients with apparent polycy-
thaemia, these measurements will be examined first.
Raised PCV
A number of physiological factors have been shown
to alter the PCV level including posture, time of day,
exercise and food intake. To provide comparable
PCV values, it has been proposed that blood samples

Blood Revtews (1991) 5, 205-213

© 1991LongrnanGroup UK Ltd
206 APPARENT POLYCYTHAEMIA
should be taken in the morning with no or minimal
venous occlusion from the patient who is fasting or
had a light breakfast and has been sitting for 30 min. v
While these conditions might seem over elaborate, it
is essential that some precautions to achieve standard-
isation are undertaken. In practice, minimal venous
occlusion is the most important. For blood samples
with normal red cell indices, electronic cell counters
give virtually identical results for PCV as the micro-
haematocrit method. 8 However, since the micro-
haematocrit is the primary standard for PCV
measurement then this method should be preferred
in the initial evaluation of these patients. In the
continuing management, an electronic cell counter
may be used for PCV measurement as long as it is
appreciated that some instruments under-estimate the
PCV at reduced mean corpuscular haemoglobin va-
lues. In this situation, the micro-haematocrit should
be used. 8
There has been some variation in the proposed
upper limits for normal PCV. Taking into account
recent reference texts, previous publications and the
fact that post-menopausal females have higher PCV
values than younger women, upper limits for the
definition of apparent polycythaemia of 0.51 for
males and 0.48 for females would seem justified.9'1°'11
Before considering investigating patients further it is
a wise precaution to make PCV measurements on at
least two occasions, lz
Normal R C M and PV
There are established and reliable techniques for
measuring both RCM and PV. 13 Despite clear dem-
onstrations that results and normal values expressed
in terms of total body weight alone lack precision,14'15
many laboratories still interpret RCM and PV data
using ml/kg expressions. The inaccuracy is particu-
larly demonstrable in obese individuals, since adipose
tissue is relatively avascular and does not contribute
proportionately to the blood volume. This has par-
ticular relevance to apparent polycythaemia, since a
significant proportion of patients are above their ideal
body mass index. 16 The best correlation is between
lean body mass and RCM. lr'18 Unfortunately, the
measurement of lean body mass cannot be regarded
as a practical routine procedure. 13 Thus, at present,
the most appropriate method of RCM and PV predic-
tion and interpretation is to use formulae based on
height and weight. The published formulae have been
compared. 19 Although derived from totally different
sources, the formula proposed by Hurley (1975) 2o
and that based on the work ofNadler et al (1962), 15'2~
give closely similar mean values for both males and
females for each height/weight combination. The
proposed normal range for each prediction is _+25%
of the mean value. Therefore, individuals with elev-
ated PCV values but with a measured RCM less than
25% above their mean normal predicted value can
be regarded as fulfilling the criteria of apparent
polycythaemia.
The interpretation of measured PV values is rather
more difficult. The use of ml/kg expressions has the
same intrinsic error as for RCM data. However, while
recognizing the obesity of their patient population, a
large number of authors have concluded, based on
ml/kg expressions, that the cause for the raised PCV
in apparent polycythaemia was a reduced PV. This
has been compounded by the use of a normal range 2z
that is undoubtedly too high. Comparison of various
proposed formulae for normal mean PV based on
height and weight show that they do not closely
agree.19 However, they are a significant improvement
on mt/kg interpretations, although at the present time
the relative accuracy of the different formulae cannot
be stated. Using one of the proposed formulae and
taking an arbitrary lower normal PV value of 12.5%
below the predicted mean normal value, the incidence
of absolute polycythaemia (raised RCM), apparent
polycythaemia (normal RCM and PV) and relative
polycythaemia (normal RCM, low PV) in males with
raised PCV values are shown in the Table. This shows
that, as expected, the incidence of absolute polycy-
thaemia increases as the PCV increases and at a PCV
o f 0.60 and above an increased RCM is found in all
patients. Reflecting the increasing incidence of absol-
ute polycythaemia, apparent polycythaemia is less
frequently observed as the PCV rises. However, a
low PV, as defined above, is not the explanation for
the raised PCV in the majority of patients since
relative polycythaemia was found in only 18% of
male patients with PCV values between 0.500 and
0.599. 23 A similar incidence of reduced PV was found
in an earlier study. 6 Thus the most common finding
in patients with elevated PCV and without absolute
polycythaemia is a change in RCM and PV within
their normal ranges but with the summated effect
producing an increase in PCV.
Mechanisms
Some individuals must, by definition, represent the
upper end of the normal distribution for PCV and
their measured RCM and PV fall within the normal
range. 6 However, this probably does not apply to the
majority with apparent polycythaemia and not to
those with relative polycythaemia. A number of
different associations have been identified and causa-
tive factors proposed. In patients with relative poly-
cythaemia, it would be reasonable to seek a specific
cause for the reduction in PV. In apparent polycythae-
mia, both RCM and PV are within the normal range.
However, the RCM range is wide and it is possible
that some pathological increase in a patient's RCM
may occur without the measured RCM being greater
than 25% above their mean predicted value so that
a diagnosis of absolute polycythaemia would be
appropriate. Similarly, all patients who have absolute
polycythaemia must have passed through a phase
when their RCM was above their own normal value
but not exceeding the upper limit of normal. These

Table 1 Results and interpretations of RCM and PV measurements in 188 males with PCV
values above 0.50.
Number
Venous of Absolute
PCV patients polycythaemia
0.500-0.519 57 17.5%
0.520-0.539 39 20.5%
0.540-0.559 38 55.3%
0.560 0.579 17 64.7%
0.580-0.599 11 90.9%
> 0.600 26 100%
The PCV values were recorded after the patient had been recumbent for 30 min. This typically
reduces the 'sitting' PCV by approximately 0.02. Data taken from Pearson et al, 1984.23
considerations and the fact that the accuracy of R C M
measurement is probably in the order of + 5 % 24
suggests that all the possible causes of an absolute
polycythaemia must be considered in patients with
apparent polycythaemia. Increases in RCM, even
within the normal range, may provoke homeostatic
mechanisms of blood volume control leading to some
reduction in PV. In addition, many of the proposed
causative factors o f apparent polycythaemia increase
the R C M and reduce PV independently and it is the
interplay of these two changes that lead to the
increased PCV. These factors and other associations
will now be considered. In the majority of patients
more than one possible causative factor is present a6
and m a n y of the factors are inter-related.
Age and Sex
Marked male predominance is a feature of all studies
of apparent and relative polycythaemia, z'6'x6'2s-27
The reason for this has not been established, but it
could reflect the fact that the normal female PCV is
lower than that of males and marginally elevated
PCV values in females are not so frequently investi-
gated. At PCV values above 0.50, the majority (80%)
of females have an absolute polycythaemia. 19 The
age at diagnosis is rather variable, but the mean age
tends to be rather lower than that for primary prolifer-
ative polycythaemia. 1'16'z6
Obesity
Earlier studies emphasized the high incidence of
obesity in patients with raised PCV but normal
RCM. 2 The possible reason for this based on ml/kg
R C M expressions has already been discussed. How-
ever, a recent study 16 showed a higher frequency of
obesity in patients with apparent polycythaemia than
in an age-matched population. Obesity could produce
its effect by causing arterial hypoxaemia due to
hypoventilation in the recumbent position and at
night. 28-3° However, hypertension is more c o m m o n
in obese individuals 31 and hypertension is a relatively
c o m m o n finding in patients with apparent polycy-
thaemia.
BLOOD REVIEWS 207
Apparent Relative
polycythaemia polycythaemia
65% 17.5%
51.3% 28.2%
36.8% 7.9%
11.8% 23.5%
- 9.1%
- -
Fluid Loss and Diuretics
There are a number of causes of acute PV reduction,
such as increased fluid loss, reduced fluid intake,
increase in capillary leakage (e.g. septicaemia). The
use of diuretics at high doses may produce a signifi-
cant PV reduction and PCV increase. The more
interesting question is the effect of chronic tow dose
diuretic therapy. Such treatment with thiazides has
been shown to lead to an approximate 5% reduction
in PV, 31 which would be sufficient to increase the
PCV by 0.02-0.03. In a small number of patients,
this increase might take the PCV above the upper
limit of normal. Another mechanism for fluid loss
has been proposed by the study of 2 patients with
relative polycythaemia and considered to be under
emotional stress, These patients showed reduced noc-
turnal anti-diuretic hormone activity with nocturnal
water loss. 33
Smoking
In studies of apparent and relative polycythaemia,
smoking emerges as a major factor. There are twice
as m a n y smokers in these patients compared with the
population at large. 16 Smokers have higher PCV
values than non-smokers, usually by 0 . 0 2 - 0 . 0 3 . 34'35
However, in some individuals more significant
increases in PCV occur and the PCV is clearly
elevated. 36'37 While some have an absolute polycy-
thaemia, the majority have an apparent polycythae-
mia with a few having a significantly reduced PV
volume. The reason for the particularly raised PCV
values in some smokers is strictly due to excessive
smoking. However, more commonly, smoking is an
additional factor in patients with, for example, lung
disease, sleep apnoea syndromes and obesity. 28'38
Smoking affects the PCV by increasing the R C M and
may also reduce the PV. The principal effect is to
reduce the arterial oxygen content by increasing the
carbon monoxide content of the blood from the non-
smoker level of less than 2.5% to values up to 10%
and occasionally more. 36-39 It should be noted that
m a n y pieces of equipment designed to measure the
oxygen saturation of blood do not allow for the
208 APPARENTPOLYCYTHAEMIA
carbon monoxide content, which must be separately
assessed and subtracted from the measured oxygen
saturation. In addition to reducing the oxygen satu-
ration, the presence of carbon monoxyhaemoglobin
shifts the oxygen dissociation curve to the left and
alters its shape, further compromising tissue oxygen
delivery and stimulating erythropoiesis via the renal
sensor. ~°-42 The effect of smoking on PV is less
clearly established. Some reduction in PV may occur
as a result of a homeostatic mechanism to maintain
a normal blood volume at increased RCM levels. 36
Alternatively, it has been shown that smoking signifi-
cantly increases venous tone 43 and possibly increases
capillary permeability. 44
Hypertension
Hypertension has been associated with apparent poly-
cythaemia in many studies. 6"16'25-27'45'46 In surveys
of hypertensive patients it has been shown that the
PCV is higher than in the non-hypertensive popu-
lation, but the PCV usually remains within the normal
r a n g e s However, since hypertension may produce
both an increase in the RCM and reduction in PV,
it is not surprising to find that in the occasional
patient, hypertension leads to a PCV above normal.
Patients with hypertension and raised PCV levels are
more likely to have renal arterial disease. ~8 The
resulting renal ischaemia might lead to increased
erythropoietin secretion. 49 In addition, another mech-
anism which could lead to erythropoietic stimulation
is the observed high incidence of sleep apnoea in
hypertensive patients. 5° PV studies in hypertension
have revealed variable results. 5~ In some patients
there is evidence of a reduced PV 52 and studies in
man and spontaneously hypertensive rats have shown
increased venous tone with a reduction in blood
volume in the venous capacitance vessels. 53-56 In
addition, an altered red cell distribution with a re-
duced body:venous haematocrit ratio has been ob-
served in some untreated hypertensive patients with
raised PCV values. 27
Cardiovascular Disease
Apart from hypertension, the incidence of cardiovas-
cular disease and/or complications at presentation
has been noted in a number of studies of apparent
polycythaemia. 6'16'26'27'57 The incidence has varied
but has been recorded in up to one third of patients. 16
It has not been established whether the incidence is
greater than in an age and sex-matched normal
population since in the published studies the chosen
control population has not strictly been normal. 6'26
The question whether a raised PCV value is a risk
factor for vascular occlusion is discussed below.
Alcohol
Chronic alcohol abuse has been proposed to be more
common in patients with apparent polycythaemia.
However, the incidence is only marginally greater
than in the normal population. 16'z6 Acute abuse of
alcohol inhibits the release of anti-diuretic hormone 58
with a reduction in PV and rise in PCV. Only a
limited number of cases of relative polycythaemia
improving with the cessation of alcohol have been
described. 59'6° While the effect of alcohol may be
principally on the PV, there are theoretical reasons
for an indirect enhancement of erythropoiesis. These
include the depression of respiration by alcohol, 61
increasing the degree of nocturnal arterial oxygen
desaturation in some patients and precipitating sleep
apnoea in snorers. 62 In addition, the liver dysfunc-
tion, which is often observed in alcoholics, may lead
to hepatic erythropoietin elaboration or altered er-
ythropoietin metabolism. 63-65
Arterial Oxygen Desaturation
Daytime arterial oxygen desaturation is an obvious
cause for an absolute (secondary) polycythaemia. Not
so well recognized is that intermittent arterial oxygen
desaturation occuring during sleep, may be sufficient
to stimulate erythropoiesis and produce an increase
in RCM. 66 In some patients, arterial oxygen desatu-
ration may be associated with a raised PCV but
normal RCM. A retrospective study of 34 patients
with apparent or relative polycythaemia showed that
15% had a reduced arterial oxygen saturation. 16 This
led to a prospective study of 16 further patients, 67
which demonstrated that 2 patients with relative and
2 patients with apparent polycythaemia had daytime
and/or nocturnal arterial oxygen desaturation. Only
these patients showed a reduced arterial oxygen satu-
ration during the day in the supine position suggesting
that this was a useful screening procedure for noctur-
nal desaturation. It is not clear why some patients
respond to the daytime and/or nocturnal hypoxic
stimulus other than by a dominant stimulatory effect
on erythropoiesis. It could be that the length and/or
degree of arterial oxygen desaturation is an in-
sufficient stimulus to erythropoiesis or that in some
patients PV reduction is partly or mainly involved.
There is good evidence that acute arterial hypoxaemia
produces sympathetic nervous system stimulation,
increases plasma catecholamine levels and venous
tone and reduces P V . 44'68-73 In some patients these
effects may come into play on a chronic basis. In
addition, patients with arterial oxygen desaturation
due to obstructive sleep apnoea have been shown to
have bursts of release of atrial natriuretic peptide,
which may partly explain their observed increased
diuresis during sleep.74
Renal Disease
Various types of renal pathology, for example renal
tumours, cystic disease and hydronephrosis, are well
established as causes of secondary polycythaemia. In
some patients with elevated PCV levels, the RCM is

not increased sufficiently to meet the definition of an
absolute polycythaemia. This has been illustrated in
patients with raised PCV levels and diffuse parenchy-
mal disease of the kidney. 75 In the patients with
raised PCV values following renal transplantation an
increase in RCM and/or a reduction in PV have been
demonstrated. 76-79
Stress and Catecholamines
Some of the factors already discussed, for example
arterial oxygen desaturation and smoking may pro-
duce some of their blood volume effects via sympath-
etic nervous stimulation or catecholamine secretion
from the adrenal medulla. There is evidence that
acute mental stress will marginally increase the
PCV. 8° Chronic mental stress may have a similar
effect but this has not been shown consistently. 81-s3
Mental and physical stress stimulate the autonomic
nervous system and increase catechotamine pro-
duction. 84 Infusion of adrenaline and noradrenaline
leads to an increase in venous tone with reduction in
venous capacitance, a reduction in PV and an increase
in P C V . 85"86 In general, the PCV changes have been
modest. However, in patients with phaeochromocy-
toma, a raised PCV is occasionally observed. In these
patients, although an increased RCM has been ob-
served in ~ome, more commonly a reduced PV is
found. 87-89 The reduced blood volume can lead to
circulatory instability at the time of surgical removal
of these tumours. 87 Similarly, a patient with a Guill-
ain-Barr6 syndrome has been described in whom
there was an increase in PCV due to PV reduction
and marked sympathetic nervous system and renin-
angiotensin activation. 9°
Vascular Occlusive Risk
The most important question in the management of
these patients is whether the raised PCV increases the
risk of vascular occlusion. There is no prospective
study of untreated patients. However, two limited
retrospective studies have been published. Burge et
al (1975) 25 reported that in a group of 23 patients
followed-up for a mean of 4 years the mortality was
six times greater than expected for a sex and age-
matched population. Four of the observed 6 deaths
were due to vascular occlusion and 2 other patients
had thromboses in the follow-up period. Weinreb and
Shih (1975) 26 described 47 patients followed for up
to 12 years. The incidence of thromboembolic compli-
cations was 30%. In patients with predominantly a
reduced PV, 35% had had a major vascular occlusive
event within 5 years of presentation. Further analysis
suggested that the major risk factor for death was
hypertension. These authors 26 concluded that it was
this that needed treatment rather than the elevated
PCV, although Burge et al (1975) 2s proposed that
the PCV should be reduced. These observations sug-
gest some controversy. However, there is good evi-
BLOOD REVIEWS 209
dence to propose that a raised PCV is a risk factor
for vascular occlusion. 9t
Experiments in animals have shown that the PCV
is directly related to peripheral resistance but inversely
related to cardiac output. Systemic oxygen transport
is maximal at normal PCV values and falls at elevated
PCV levels. Hypervolaemia reduces peripheral vascu-
lar resistance and increases cardiac output and al-
though the systemic oxygen transport is still reduced
at high compared with normal PCV, hypervolaemia
mitigates against the effect. 92 While most patients
with primary and secondary polycythaemia are hyper-
votaemic, patients with apparent polycythaemia have
a normal or reduced blood volume. Thus, the general
circulatory changes of hypervolaemia do not come
into play and therefore in these patients, a local
vascular occlusive event might have a worse outcome
than in hypervolaemic polycythaemic patients. Obser-
vation in man with arterial 93 and venous 94 occlusions
and experiments using carotid artery occlusion in
animals 95-97 have shown larger areas of local ischae-
mia or non-perfusion at high compared with normal
PCV values. Cerebral blood flow measurements in
primary polycythaemia have shown an inverse corre-
lation with P C V . 98 Similar findings have been shown
in patients with apparent potycythaemia whether
predominantly due to high normal RCM or low
P V . 99 The observed PCV/cerebral blood flow re-
lationship has been explained by the increase in
arterial oxygen content that occurs with increasing
PCV and that the adjustments of cerebral blood flow
occur to maintain a constant cerebral oxygen trans-
port. 1°° These findings suggest that the increased
blood viscosity at high PCV levels is not the major
factor limiting cerebral blood flow. However, a study
of cerebral oxygen transport in 20 patients with
elevated PCV and without evidence of arterial oxygen
desaturation revealed an increase in oxygen transport
in half of the patients following venesection to reduce
the PCV to normal. 1°1 This finding might explain the
improvement in cerebral ischaemic symptoms which
occasionally accompanies PCV reduction in these
patients. 1°2 In addition, reduced cerebral blood flow
might predispose to cerebral thrombosis, which has
been specifically observed in primary proliferative
polycythaemia, 1°3-~°5 idiopathic erythrocyto-
sis 1°7'1°s and occasionally been recorded in patients
with apparent polycythaemia.25'26'x°9
Further evidence linking increased PCV level with
thrombotic risk can be demonstrated in observations
of patients with primary proliferative polycythae-
mia 1°3"11° and this risk can be reduced by PCV
reduction. 1°4 It could be argued that quantitative or
qualitative platelet changes in primary proliferative
polycythaemia play a part in increasing the vascular
occlusive risk. However, a fall in thrombotic compli-
cations with PCV reduction has been observed in
patients with idiopathic erythrocytosis9'a°6'1°7 who
by definition do not have platelet changes. Similarly
patients with secondary renal polycythaemia have
210 APPARENTPOLYCYTHAEMIA
also been shown to be at risk of thrombosis. 76'77 In
addition, post-mortem studies in the normal popu-
lation have shown a higher incidence of myocar-
dial, ~ t and cerebral ~2 thrombosis at high compared
with low normal PCV values.
Proposed Management
In the evaluation of these patients, it is important to
consider two aspects. First, the presence of causes
for the alterations in RCM and/or PV that might be
responsible for the increase in P C V - - a l b e i t accepting
that a small percentage of the normal population will
have PCV values above the defined upper limit;
second, the risk of vascular occlusion.
In some patients there is an obvious cause for the
elevated PCV, such as dehydration or high doses of
diuretic therapy. In these patients, the treatment is
straight forward. However, in the majority of patients
no single cause can be established and often manage-
ment rests with, for example, the control of obesity,
cigarette smoking, alcohol intake and/or hyperten-
sion. The reversibility of the effects of smoking on
PCV, RCM and PV has been demonstrated. 36'H3
However, simple reduction in the number of cigarettes
smoked, is not necessarily effective in reducing carbon
monoxyhaemoglobin levels, since subjects respond by
inhaling more deeply. 113 In a small number of hyper-
tensive patients with apparent polycythaemia, re-
duction of the elevated PCV has been achieved by
treatment of the hypertension with methyldopa, gu-
anethidine or propanolol. 17'1~4 Conversely, treatment
of hypertension by diuretic therapy may effectively
control blood pressure but with a reduction in PV. 5°
Thus the choice of hypotensive agent in these patients
needs to be carefully considered.
Observation of the PCV values within the first few
months of presentation has shown that the PCV falls
to within the normal range in up to one third of
patients. 16'z5 Although there are occasionally situ-
ations, such as sudden thrombotic events, ischaemic
symptoms or very high PCV values, when immediate
intervention to lower the PCV is indicated, in general,
decisions relating to PCV reduction should not be
made until some time has elapsed and attention given
to the possible causative factors.
In patients with a permanently raised PCV, a
decision must be made whether to institute treatment
to lower the PCV. This decision should be based on
the PCV level and the risk of vascular occlusion. In
all cases, the long-term implications once PCV re-
duction is deemed necessary for treatment should be
considered. The simplest method for long term PCV
reduction is venesection. The infusion of dextran has
been shown to last for only a very short period but
does reduce the PCV and increase the PV and cerebral
blood flow, while oral fludrocortisone therapy was
shown to be ineffective, in patients with relative
polycythaemia. 1~5 Blood volume studies performed
in these patients before and after PCV reduction by
venesection have shown that in the majority the RCM
falls, the PV increases while the blood volume remains
unchanged. 116 This suggests that in these patients
PCV and RCM reduction by venesection can modify
the mechanisms controlling PV.
In patients with PCV values of 0.54 and above,
venesection should be used to reduce the PCV. The
choice of this PCV level is to some extent arbitrary
but it equates to approximately three standard devi-
ations above the mean normal. Thus normal individ-
uals at the extreme end of the distribution for PCV
will not be regarded as abnormal and treated. In
patients with raised PCV values but less than 0.54
an arbitrary judgement must be made of the vascular
occlusive risk, such as previous evidence of throm-
bosis and the presence of cardio-vascular disease. It
is accepted that it is difficult to precisely quantitate
this risk in some patients but venesection is proposed
for those patients considered to be at greatest risk.
In untreated patients, it is important to assess the
blood count at intervals, for example 3-monthly, to
check that there is no further rise in PCV and that
no underlying disease or factor emerges.
The method and volume of venesection deserve
some comment. Venesection of 450 mls of blood
without volume replacement is satisfactory, even in
patients with a history of ischaemic heart disease
and/or receiving treatment for hypertension. 117 How-
ever, in patients with a recent history of thrombosis
or current ischaemic symptoms, isovolaemic venesec-
tion with saline replacement is a reasonable pre-
caution. In addition, since some of these patients,
particularly in the relative polycythaemia sub-group,
have a reduced blood volume, the initial venesection
should be limited to 250 300 mls with an increase in
volume at subsequent procedures up to the normal
450 ml amount. The frequency of venesection should
be assessed by the clinical situation.
The target value for the PCV if venesection is
instituted has not been established. By analogy with
the incidence of vascular occlusion during treatment
in primary proliferative polycythaemia and idiopathic
erythrocytosis, the incidence of vascular occlusion
found at post-mortem in the normal population and
the cerebral blood flow findings in patients with raised
PCV values, x18 a target PCV of 0.45 or below is
proposed. While this might appear a rather rigorous
approach, it formulates a clear-cut treatment decision
rather than the policy that is used for treatment of
these patients in some centres of an occasional ven-
esection without defining precise treatment end-
points. Ideally a randomized prospective study is
required to establish whether venesection reduces the
incidence of vascular occlusion in these patients. Such
a study was instituted t~9 but unfortunately later had
to be abandoned since insufficient patients were re-
cruited within the first few years. Thus for the time
being treatment proposals must be argued, as in this
paper, on the current published evidence.

Acknowledgement
The author gratefully acknowledges Dr M. Messinezy for her
helpful and constructive criticism of the original manuscript.
References
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