Therapeutic phlebotomy recent updates

1. Journal Presentation
Dr.Manikandan.N
Junior Resident 2nd Year
Department of Transfusion Medicine,
M.G.M Medical college
MODERATOR
Dr.Nidhi Sharma,
Assistant Professor,
Department of Transfusion Medicine,
M.G.M Medical college

2. Murugesan, Mohandoss; Das, Soumya1,; Shastry,
Shamee2. Effect of Therapeutic Phlebotomy on
Plasma Volume in Polycythemia Patients. Global
Journal of Transfusion Medicine 3(2):p 117-120,
Jul–Dec 2018. | DOI:
10.4103/GJTM.GJTM_27_18

3. Editorial Board
Editor -in Chief
Dr. C. Shivaram
Consultant and Head-Transfusion Medicine
Manipal Hospital Bangalore, India
Ph: +9180 25024224/ 25024357
Mobile: +919845375432 editor-in-chief @aatmweb.org;
shivaram@manipalhospitals.com
Editors
Dr. Sunil B. Rajadhyaksha
Prof. and Head, Dept. of Transfusion Medicine
Tata Memorial Hospital, Mumbai, India.
Tel: +91-22-24127096
Fax: +91-22-24146937
Email: dtmtata@gmail.com; sunilrajadhyaksha@gmail.com
Dr. Gajendra Gupta
Consultant –Department of Pathology and Transfusion
Medicine
SDM Hospital and Research Centre, Jaipur, India.
Ph: +91 9929607025/01412574189
Email: guptagajendra@yahoo.com
Editorial Co-ordinator
Dr. Vijith Gunasekara
Director (Laboratory Services)
(Director/Member, Board of Management-SLF/SLFI and SLSPC)
Ministry of Health, Sri Lanka.
Mob: +94777316540; Dir: +94112673135; Fax: +94112673138
vijithg@gmail.com
Associate Editors
Dr. Amit Agarwal
Consultant-Transfusion Medicine
Fortis Escort Heart Institute,
New Delhi, India
Phone: 0-8527312555
Email: dr.agrawalamit@gmail.com
Dr Ambuja K.
Specialist-Transfusion Medicine
Manipal Hospital Transfusion Services
Bangalore , India
Ph: 9611107110
E-Mail : ambuja.k@manipalhospitals.com

4. Volume 3 Issue 2
Received:
July, 2018.
Accepted:
August, 2018

5. Discussion
01 04
02
03
Polycythemia
Journal
05
Therapeutic
Phlebotomy[TP]
Polycythemia Vera
Other indications of
TP

6. Polycythemia
01

7. Polycythemia/Erythrocytosis
Polycythaemia or
erythrocytosis
an increase in the red blood cell mass.
[Hemoglobin (Hb) >16.5 g/dL(men) and >16g/dL(women)OR Hematocrit (Hct) >49%
in men and Hct > 48% in women ]
Absolute polycythaemia increase in the number of red blood cells
Relative polycythaemia
Decrease in the plasma volume
Excessive Alcohol intake and use of diuretics
Apparent polycythaemia/
Gaisbock’s Syndrome
Relative polycythaemia
Associated with Hypertension , Obese persons
Primary Polycythemia Normal/Low Erythropoietin level Eg; POLYCYTHEMIA VERA
Secondary Polycythemia Due to increased EPO production from cortical peritubular interstitial Fibroblasts

8. HARRISON
2Oth edition

9. Causes Of Secondary Erythrocytosis

10. Polycythemia
Vera
02

11. • Capable of Transforming into
Each other due to JAK2
Mutation
• Indolent and Slow
• Natural History in Decades

12. THROMBOSIS
Arterial>Venous>Microvascular
• Headache
• Tinnitus
• Vertigo
• Pruritis [AQUAGENIC]
• Bleeding/Epistaxis
• Erythromelalgia
SYMPTOMS

14. Polycythaemia Vera Study Group

15. WHO 2008 Criteria

16. Diagnostic Criteria
Major Criteria
1) Hemoglobin (Hb) >16.5 g/dL(men) and >16g/dL(women)
OR
Hematocrit (Hct) >49% in men and Hct > 48% in women
2) Bone marrow biopsy showing hypercellularity for age with
trilineage growth (panmyelosis) including prominent erythroid,
granulocytic, and megakaryocytic proliferation with pleomorphic,
mature megakaryocytes (differences in size)
3) Presence of JAK2V617F or other functionally similar mutation
such as JAK2 exon 12 mutation
Minor Criterion
Subnormal serum erythropoietin level[4 to 26 milliunits per liter
(mU/mL).
WHO 2016 Criteria
Diagnosis requires the presence
of all three major criteria or the
first two
major criteria and minor criterion

18. Microcytic Erythrocytosis
Beta Thalassemia Trait
Hypoxic Erythrocytosis
Polycythaemia Vera
 Hb 19.5
 Haemotocrit 59%
 MCV 70[78-94]
 MCH 27[26-32]
 MCHC 32[ 32-36]
 RDW 17[11-14]
 Total Count 12000 cells
 Platelet Count 5,67,000cells
Typical CBC Of Polycythemia Patient

20. Therapeutic
Phelobotomy
03

21. What do see first when requisition has
been sent?
How much Volume to be removed?
Whether to use Replacement fluid post
procedure?

22. PROCEDURE
1. Proper consent
2. AMOUNT: 350ml/450ml of blood
3. Once a week until desired HCT is
achieved
4. Small volume of plasma removed by
phelobotomy does not need replacement
5. Oral Liquid intake before and after
phlebotomy is recommended
RATIONALE
1. As the body is compensating for blood loss
through blood plasma with a short amount of
time, yet requires several weeks to produce new
RBC’s, HCT can be temporarily reduced using
this treatment
2. Induce a state of iron deficiency that prevents
accelerated expansion of red cell mass
Therapeutic phlebotomy

23. Other
Indications
04

24. Hereditary Hemochromatosis

26. • Primary mode of iron reduction
• Phlebotomy therapy should be started
in all patients whose serum ferritin
level is elevated and should not be
withheld from the elderly on the basis
of age or from iron-loaded patients
who have not developed clinical
symptoms
• One phlebotomy per week (1 unit or 7
mL/kg of whole blood not to exceed
550 mL per phlebotomy) until the
serum ferritin is below 50 ng/ml
• Annually remove 3–4 units of blood to
maintain the ferritin between 50 and
100 ng/mL

27. CONTRAINDICATIONS
Chronic Transfusion Dependent
Anaemia
Unstable Hemodynamic Status
Iron Chelation

30. SYMPTOMS
IMPROVED
• Malaise
• Weakness
• Fatigability,
• Skin
pigmentation,
• Cardiac
function
• Liver
transaminase
elevation
NO
IMPROVEMENT
• Diabetes,
• Cirrhosis,
• Arthropathy,
• Pituitary dysfunction
• Hypogonadism

31. Donation Of Phlebotomized blood
RATIONALE
Transmission of siderophilic
infections such as Yersinia
enterocolitica,other blood-
borne pathogens, and
potential toxicity from non-
transferrin-bound iron (NTBI)
Current RBC storage
practices, including
maintaining donated blood at
temperatures <10°C,
have been shown to minimize
the risk of transmission of
bacterial infection
Iron readily undergoes oxidation–reduction reactions that can generate tissue
toxicity
In most humans, the majority of iron is bound to transferrin , but in patients
with HH, the amount of absorbed iron frequently exceeds the binding capacity
of such molecules and can therefore form free complexes with
potential cytotoxic effects

32. Porphyria Cutanea Tarda
• Therapeutic phlebotomy has long been considered the
treatment of choice
• Hydroxychloroquine is the alternative treatment if
phlebotomies cannot be tolerated
• According to Rocchi et al., 450 mL of whole blood should
be removed during each phlebotomy session, with sessions
repeated every 2 weeks until the haemoglobin level is
below 11 g/dL or until the serum ferritin level is below 20
ng/mL, which is close to the lower limit of normal.
• Most patients require 6 months to achieve remission but
clinical improvement may be noted during the third month
after starting phlebotomy.
Hydroxychloroquine was found to be
superior to phlebotomy in decreasing
porphyrin production; however, liver
disease was
more severe in the
hydroxychloroquine group.

33. Secondary Erythrocytosis
• Altitude,
• Smoking,
• Renal cell carcinoma,
• Hepatocellular carcinoma,
• Adrenal adenoma,
• von Hippel-Lindau disease
• Cushing's syndrome and
• Phaeochromocytoma
• Patients with hypogonadism on
testosterone therapy
• Athletes on anabolic steroids
PHLEBOTOMY NOT DONE

34. BENEFITS IN CHRONIC OBSTRUCTIVE
PULMONARY DISEASE
POST RENAL TRANSPLANT
PATIENTS

35. Isovolemic
phlebotomy
 Moderate symptoms of
hyperviscosity (i.e.,
headache, , visual
disturbance, tinnitus,
dizziness, etc.)
 Withdrawal of up to a
unit of whole blood,
replaced by 750–1000
mL of isotonic saline

36. Journal
Presentation
05
Effect of Therapeutic Phlebotomy on Plasma Volume in
Polycythemia Patient

37. To determine the plasma volume
changes in polycythemia patients
undergoing Therapeutic
Phlebotomy[TP]
AIM

38. Materials and Methods
Patient’s Criteria
a prospective study on
patients with
polycythemia who
underwent TP from
September 2013
to July 2014
Written Informed
Consent
Clinical details and
Physical examination
of patients
Investigations
• CBC
• JAK2 mutation
• Erythropoietin levels
• ABG analysis

39. Phlebotomy Study
• Changes in peripheral blood volume during the
phlebotomy were estimated on the basis of the Hb
concentration measured at two-time points during the
whole process
• At the end of the phlebotomy, a blood sample was
taken with a clamp applied to the tubing, considering
it to be the Hb at the end of the phlebotomy.

40. Estimation of blood volume
Pre collection &
Post collection blood
volume
Pre phlebotomy&
Post phlebotomy
BV1&
BV2
Ogawa’s equation,
0.168H3 + 0.050W + 0.444 for adult males
0.250H3 + 0.0625W −0.66 for adult females
Height (m)
Weight (kg)
Hb1&
Hb2
PV1&
PV2
Pre collection &Post collection
plasma volume
[1 − Hct × BV]

41. RESULTS
134 Patients
236 events of
TP procedures

44. Results

45. Results
Positive correlation between mean drop in Hb and
Hct in procedures with positive plasma volume
expansion (P < 0.01).

46. DISCUSSION
MAJOR GOAL
Reduce the
red cell mass
only 47%
episodes of
TP (Group A)
had a change
in plasma
volume
mean increase
in plasma
volume was
1.14 ± 1.6
mL/kg
Symptomatic
improvements
were noted in
60% of the
patients
immediately
after TP
procedure
A progressive
reduction in
hematocrit (1.7
± 2.6 %)
and
hemoglobin
(0.78 ± 0.5
g/dL)

47. LIMITATION
• 55% of patients underwent only one TP procedure
• Only 4.8% of patients reached the target HCTwithin the study
period
• TP though commonly performed for reducing red cell mass in
polycythemia had poor compliance from patients, resulting in
failure to achieve the desired level

48. CONCLUSION
TP in addition to a direct reduction
in total blood volume, plasma volume expansion is a
relatively immediate effect making TP at once both
corrective and protective.
Recommend proper education and communication
during the subsequent follow-up of the patients after
consultation with the team of a hematologist.

49. REFERENCES
1. Assi TB, Baz E. Current applications of therapeutic phlebotomy. Blood Transfusion
2014;12 Suppl 1:s75-83
2. Spivak JL. Polycythemia vera: Myths, mechanisms, and management. Blood
2002;100:4272-90.
3. Thiele J, Kvasnicka HM, Orazi A, et al. The international consensus classification of
myeloid neoplasms and acute leukemias: myeloproliferative neoplasms. Am J
Hematol. 2023;98:166-179
4. Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of
myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and
genomic data. Blood. 2022;140:1200- 1228
5. Rossi’s Principles Of Transfusion Medicine 6th Edition [278-285]
6. Harrison’s Priciple of Internal medicine 21st edition

50. THANK YOU