1) Therapeutic phlebotomy is used to lower red blood cell mass and blood viscosity in patients with secondary polycythemia due to conditions like COPD. 2) Studies have shown that phlebotomy can improve symptoms, cerebral blood flow, and exercise tolerance in polycythemic COPD patients by reducing blood viscosity. 3) The benefits of phlebotomy are thought to be due to improved cardiac function and oxygen delivery resulting from decreased peripheral vascular resistance and improved myocardial perfusion with reduced blood viscosity.

1. ROLE OF
PHLEBOTOMY IN
COPD
Dr Shami Kumar
PG 2Y, Deptt of Internal Medicine, SKIMS

2. POLYCYTHEMIA
Polycythemia is a laboratory finding in which there is an increased number of
red blood cells (RBC), along with an accompanying increase in the
concentration of hemoglobin in the peripheral blood.

3. Laboratory parameters —
●HCT – The HCT is expressed as the percent of a blood sample occupied by intact
RBC. Polycythemia in the adult patient is considered to be present when the HCT is
>48 in women or >49 percent in men.
●HGB – HGB is expressed in grams per 100 mL of whole blood or in grams per
liter of whole blood. Polycythemia in the adult is considered to be present when the
HGB is >16.0 g/dL (>160 g/L) in women or >16.5 g/dL (>165 g/L) in men.
●RBC count – The RBC count is expressed as the number of RBC per microL or
liter of whole blood. The normal RBC count is approximately 5 x 106 cells per
microL or 5 x 1012 cells per L.

4. Polycythemia may be due to a myriad of causes. The polycythemias can
be classified as relative and absolute.
Relative polycythemia is a disorder in which the patient characteristically
has a modest elevation of the hematocrit level without an elevated RBC
mass but rather because of contraction of the plasma volume.
The absolute polycythemias are accompanied by an actual increase in
the circulating RBC mass.

6. Classification of the Absolute
Erythrocytosis.
Acquired
EPO-mediated
Hypoxia-driven
Central hypoxic process
• Chronic lung disease
• Right-to-left cardiopulmonary vascular
shunts
• Carbon monoxide poisoning
• Smoker’s erythrocytosis
• Hypoventilation syndromes including sleep
apnoea (high-altitude habitat)
Local renal hypoxia
• Renal artery stenosis
• End-stage renal disease
• Hydronephrosis
• Renal cysts (polycystic kidney disease)
Pathologic EPO production
Tumours (Hypoxia independent)
Hepatocellular carcinoma
Renal cell cancer
Cerebellar haemangioblastoma
Parathyroid carcinoma/adenomas
Uterine leiomyomas
Pheochromocytoma
Meningioma
Exogenous EPO
Drug associated
Treatment with androgen preparations
Postrenal transplant erythrocytosis
Idiopathic erythrocytosis

7. Secondary Polycythemia
Secondary Polycythemia: Polycythemia can be secondary to increased
erythropoietin production either indirectly via response to chronic hypoxia, as in
lung or cardiac disease, in smokers, at high altitudes, and in carbon monoxide
poisoning; or directly due to pathological increase in erythropoietin, as seen
with impaired renal perfusion (i.e. renal artery stenosis) or erythropoietin
producing tumors. Polycythemia can also occur after kidney transplantation
and in response to other therapeutic interventions (e.g. testosterone). Elevated
hematocrit may lead to increased blood volume and viscosity, resulting in
headache, hypertension, visual disturbances, lethargy, weakness and
thromboembolic events.
Treatment is therefore intended to lower the RBC mass and viscosity.
Decisions regarding treatment should be made on an individual basis.

8. Pathophysiology of Secondary Polycythemia
(Hypoxia-Driven)

9. Polycythemias of Pulmonary Disease
Patients of pulmonary disease frequently have arterial hypoxemia, leading to increased
production of EPO and polycythemia. Excessive EPO production occurs when the PaO2
is sustained below 67 mmHg as a result of severely impaired pulmonary mechanics.
Moderate elevations of hematocrit have been estimated to occur in 20% of patients with
COPD. Polycythemia in this setting can contribute to pulmonary hypertension, pulmonary
endothelial Cell dysfunction, reduced cerebral blood flow, hyperuricemia, gout, and an
increased risk of venous thromboembolic disease

10. Therapeutic phlebotomy, the removal of whole blood, is used for several indicated
diseases to lower either red blood cell mass, blood viscosity, and/or reduce overall
iron burden in non-anemic patients. Whether therapeutic phlebotomy affects
morbidity or mortality has never been evaluated in large unequivocal randomized
controlled trials. As a consequence, absolute standardized indications for each
disease are unavailable and specific regimens are individually tailored to patients’
needs.
In patients with erythrocytosis, phlebotomy results in iron restricted erythropoiesis
and decreased RBC mass which decreases the blood viscosity, improving cardiac
hemodynamics and oxygen delivery, and decreases the risk of thrombosis. The
same goals can also be accomplished by using erythrocytapheresis which removes
the equivalent of two units of RBCs without removing platelets or plasma while
Replacing lost volume with saline.
Therapeutic phlebotomy

11. Benefit of limited venesection in patients with HPD was demonstrated by Weisse et al
(1975), who showed that reducing the Hct to 0.50–0.52 led to an improvement in exercise
tolerance, but a further staged reduction to Hct of 0.45 did not give additional benefit.
Numerous other non-controlled patient series have also suggested that control of the Hct
reduces pulmonary vascular resistance (Segel & Bishop, 1966; Harrison et al, 1973;
Weisse et al, 1975; Harrison & Stokes, 1982), improving cerebral blood flow and
psychometric testing (Menon et al, 1981; Wedzicha et al, 1983) as well as subjectively
helping confusion and headache (Wade et al, 1981)

12. Effects of Venesection on Cerebral Function in Chronic
Lung Disease
R. BORNSTEIN, D. MENON, E. YORK, B. SPROULE and C. ZAK
THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES , Nov 1980
Regional cerebral blood flow measurements and neuropsychological testing were
conducted before and after venesection on 6 patients with polycythemia secondary
to chronic obstructive pulmonary disease. Venesection resulted in lowered viscosity
and hematocrit, and an accompanying improvement in cerebral perfusion and mental
function. Blood flow was significantly increased in the left cerebral hemisphere
following phlebotomy, and there was significant improvement in sensory & mental
function. Cerebral function would appear to be related to blood flow alterations
influenced by the viscosity of the blood

13. Symptomatic and Pulmonary Response to Acute Phlebotomy in
Secondary Polycythemia
Lang M. Dayton, M.D.; R. E. McCullough; David J. Scheinhorn, M.D.; John V. Weil, MD.
CHEST, 68: 6, DECEMBER, 1975
A double-blind study of the effects of phlebotomy was carried out in 18 patients with
polycythemia secondary to severe hypoxemic lung disease. Eleven subjects under went a
single phlebotomy of 10 percent of their blood volume, and eight patients serving as controls
underwent a sham procedure. Eight of the phlebotomized subjects, but none of the controls,
reported subjective clinical improvement (P < 0.005). Subjects who noted improvement after
venesection had higher hematocrit readings than those who did not (P < 0.02). Symptomatic
relief seemed to be most dramatic in those with clinical evi dence of congestive heart failure. In
contrast to this clear cut subjective improvement, phlebotomy did not alter objective indices of
airway obstruction, lung elastic recoil, pulmonary gas exchange, or exercise tolerance in either
the phlebotomized or the control group. Thus, although phlebotomy produced subjective
benefit in the majority of patients studied, it was not associated with objective improvement in
lung function or exercise tolerance.

14. The study demonstrates that the exercise capacity of the polycythemic COPD
patient is increased post-phlebotomy. The improvement in the exercise tolerance
appears to be due to improved cardiac function as evidenced primarily by an
increased stroke volume. It was hypothesized that the improved cardiac function is
due to a reduced peripheral vascular resistance due to decreased viscosity of the
blood. Improved cardiac contractility due to better myocardial perfusion might also
contribute to the improved cardiac function.
Exercise Performance of Polycythemic Chronic Obstructive
Pulmonary Disease Patients· Effect of Phlebotomies
Kota G. Ghetty, M.D., F.G.G.E; Richard W Light, M.D., F.G.G.E; David W Stansbury; and
Norah Milne, M.D. (Chest 1990; 98:1073-77)

15. Phlebotomy for rapid weaning and extubation in COPD
patient with secondary polycythemia and respiratory failure
Swagata Tripathy, Sudhansu S. Panda
Lung India • Vol 27 • Issue 1 • Jan - Mar 2010
A recent case report of one patient demonstrated more rapid weaning from a
ventilator, with earlier extubation, in an intubated patient with chronic
obstructive pulmonary disease. Weaning and extubation were facilitated with
phlebotomy removing 10% of his blood volume.

16. • Patients with HPD who develop an erythrocytosis should be evaluated by a
respiratory physician for consideration of long-term oxygen therapy or alternative
therapy (Grade A recommendation: Evidence level 1A).
• Patients who are symptomatic of hyperviscosity or have a Hct >0.56 should have
venesection to reduce this to 0.50–0.52 (Grade B recommendation: Evidence
level III).
Recommendations: Hypoxic pulmonary disease
British Journal of Haematology, 130, 174–195 (2005)
doi:10.1111/j.1365-2141.2005.05535.x

17. Classification of grades of
recommendations
A: Requires at least one randomised controlled
trial as part of a body of literature of overall
good quality and consistency addressing
specific recommendation (evidence levels Ia,
Ib)
B: Requires the availability of well conducted
clinical studies but no randomised clinical trials
on the topic of recommendation (evidence
levels IIa, IIb, III)
C: Requires evidence obtained from expert
committee reports or opinions and/or clinical
experiences of respected authorities. Indicates
an absence of directly applicable clinical
studies of good quality (evidence
level IV)
Classification of evidence levels
IA: Evidence obtained from meta-analysis of
randomised controlled trials
IB: Evidence obtained from at least one
randomised controlled trial
IIA: Evidence obtained from at least one well-
designed controlled study without
randomisation
IIb: Evidence obtained from at least one other
type of well-designed quasi-experimental study
III: Evidence obtained from well-designed non-
experimental descriptive studies, such as
comparative studies, correlation studies and
case studies
IV: Evidence obtained from expert committee
reports or opinions and/or clinical experiences
of respected authorities
Table I. Evidence statements and grades of recommendations.

18. Currently, experts in this field recommend that phlebotomy should be restricted to
individuals with symptoms or with extreme erythrocytosis (hematocrit >65%).
Clinical data to justify these recommendations are lacking.
Chronic oxygen therapy in patients with severe COPD has resulted in relief of hypoxia
and a modest reduction in hematocrit levels.
Pharmacologic interventions, including theophylline, inhaled nitric oxide, sildenafil, or
antagonism of the renin–angiotensin pathway with losartin, may also reduce the
degree of pulmonaryhypertension or secondary erythrocytosis.

19.  Role of Limited phlebotomy
• Individuals with secondary erythrocytosis due to a response to chronic hypoxia (eg,
right-to-left cardiac shunt, chronic pulmonary disease) may have symptoms of an
increased blood volume/hyperviscosity (eg, fatigue, headache, blurred vision,
transient loss of vision, paresthesias, slow mentation) when their hematocrit rises to
65 percent or more.
•Cautious phlebotomy to reduce their hematocrit into the range of approximately 55 to
60 percent may result in relief of these symptoms, while a reduction in their
hematocrit to levels less than 55 percent range are likely to exacerbate symptoms of
their underlying hypoxic condition (eg, shortness of breath, dyspnea on exertion).
●Because such phlebotomies may be poorly tolerated, the first phlebotomy should be
limited in volume (eg, 250 mL rather than the standard 500 mL) and performed as
isovolemic phlebotomy (ie, replacement of removed blood with an equal volume of
crystalloid).