1. Dr.Md.Mizanur Rahman Chowdhury
Specialist
Transfusion medicine
United hospital ltd.

2. 
 Therapeutic plasma exchange (TPE, plasmapheresis) is an
extracorporeal treatment that can be performed by
centrifugation or filtration and is designed for the removal of
plasma along with pathogenic substances, such as antibodies,
immune complexes, or large molecular weight substances from
the plasma.
Therapeutic plasma
exchange

3. 

4. 
 In TPE, using centrifugation, whole blood is pumped into a
rapidly rotating separation chamber and component separate
into layers based upon their density, plasma layer is removed
and discarded and the remaining cellular elements are mixed
with a replacement fluid and returned to the patient.
 In TPE using membrane filtration, secondary membrane
plasma fractionation can selectively remove undesired
macromolecules, which then allows for return of the processed
plasma to the patient instead of donor plasma or albumin.
Continue…

7. Advantages Disadvantages
Membrane apheresis
Fast and efficient plasmapheresis
No citrate requirements
Can be adapted for cascade filtration
Removal of substances limited by sieving coefficient of membrane
Unable to perform cytapheresis
Requires high blood flows, central venous access
Requires heparin anticoagulation, limiting use in bleeding disorders
Centrifugal devices
Capable of performing cytapheresis
No heparin requirement
More efficient removal of all plasma components
Expensive
Requires citrate anticoagulation
Loss of platelets

9. Advantages Disadvantages
Membrane apheresis
Fast and efficient plasmapheresis
No citrate requirements
Can be adapted for cascade filtration
Removal of substances limited by sieving
coefficient of membrane
Unable to perform cytapheresis
Requires high blood flows, central
venous access
Requires heparin anticoagulation,
limiting use in bleeding disorders
Centrifugal devices
Capable of performing cytapheresis
No heparin requirement
More efficient removal of all plasma
components
Expensive
Requires citrate anticoagulation
Loss of platelets
Comparisons of this methods

11. 
 The MCS+ fills the disposable centrifuge bowl with
anticoagulated whole blood.
 Sterile air is displaced from the bowl into the air bag.
 During the filling bowl phase, substitution fluid flows into the
substitution fluid bag on the weigher.
 The bowl will fill up and a cellular separation will occur.
 The plasma begins to overflow from the bowl into the waste.
How machine works..

12. 
 When the buffy coat is detected by the Bowl Optic Sensor end
of collection algorithm.
 Packed cells from the bowl and fluid from the temporary
substitution fluid bag are mixed and returned to the patient (if
substitution is enabled).
Continue..

14. 

15. 

16. 
 Total Plasma Volume (TPV) to be removed is calculated by
obtaining the total blood volume (TBV) multiplied by (100% -
Hct%)
 Total blood volume is between 5.5-7.5% of body mass for most
adults and may be estimated as 70ml/kg for males and 65
ml/kg for female . Because TBV increase with muscle mass.
 Example: Patient Wt:70 kg and Patient Hct40%
TBV: 70 kg x 70ml/kg = 4900ml
TPV: 4900 ml x (100% -40%) = 2940 ml
Plasma volume calculation

17. 
 Kaplan's equation
[0.065 x weight (kg)] x (1- Hct)
 A course of plasma exchange consist of 3-5 exchanges of 1-1.5
volumes each, with an interval of 1-2 days between procedures.
Continue..

18. 
 5% Albumin
• Most common used replacement fluid
• Dilute only with Saline
• GBS, MG, Goodpasture’s Syndrome
 Combination of saline and albumin
 FFP (Fresh Frozen Plasma)
• Used when necessary to replace clotting factors
• Typically used with TTP patients
 Cryo poor Plasma
• Cryoprecipitate has been removed
• Useful in refractory TTP patients
Replacement fluid

19. Advantage
Albumin FFP
No risk of hepatitis Coagulation factors
Stored at room temperature Immunoglobulin's ‘’ beneficial’’
factors complement
Allergic reaction are rare
No concern about ABO blood group
Depletes inflammation
Disadvantage
Expensive Risk of hepatitis, HIV transmission
No coagulation factors Allergic reaction
No immunoglobulin's Hemolytic reaction
Must be ABO compatible
Citrate load

20. 
 Citrate
 Heparin
Anticoagulant

22. 
Patho-physiological changes
in TPE

23. 
 Apheresis procedure require anticoagulation,& citrate has
become the anticoagulant of choice. It anticoagulates by
chelating calcium ion and blocking calcium dependent platelet
activation and clotting factor activation. 47% of plasma
calcium is free and, it is this free (ionized)calcium fraction that
participate in coagulation reaction and chelated by
endogenous citrate.
Calcium regulation

24. 

25. 
 Hypocalcemia most often manifests in perioral and/or
peripheral paresthesia. Sever case of hypocalcemia may cause
continuous muscle contraction if not corrected tetany,
laryngospasm grand mal seizures. Chvostek`s & Trousseau`s
sign may be positive. Infusion of Ca to the return line or with
replacement fluid may reduce incidence of citrate toxicity.
Calcium regulation
Calcium regimen Symptom (%) Author
No calcium 9.1% Mokrzycki M, kaplan A,
Am j Kidney Dis 1994
IV Ca++ gluconate 1%
Ca++ added to albumin 2.7% Kankirawatana et al.
J Clin Apheresis 2007

26. 
 Potassium decrease (minimal)(0.25meq/L with albumin and up
to 0.7meq/L with FFP
 No change in sodium and glucose
 Bicarbonate decrease 6meq/L and chloride increase 4meq/L
with albumin and this reverses with FFP (more citrate in FFP)
Electrolytes

27. 
 One plasma volume exchange:
 IgG drops to 34% of baseline
 IgA drops to 39% of baseline
 IgM drops to 31% of baseline
 Ranges from 3 days to 5 weeks to full recovery
 Most non immunoglobulin proteins recover to nearly 100% of
baseline within 48 to 72 hours after TPE.
 Administration of immunosuppressive drugs may effect the
contribution of synthesis to the recovery of immunoglobulin
after TPE.
Normal
Immunoglobulins

28. 
 When plasma is exchanged for nonplasma replacement
solution, coagulopathy resulting from dilution of coagulation
factor is a potential problem.
 Prothrombin time rise 30%
 Activated partial thromboplastin time rise 100%
 Fibrinogen levels may decrease 25%
 Plate count reduce resulting from adherence to the surfaces of
the apheresis circuit are usually modest & level quickly return
to base line.
 These changes revert toward normal within several hours
except which recovered to baseline levels after 2 to 3 days.
Coagulation status

29. Fibrinogen:
Decrease to 25% of pretreatment with single exchange of 1 PV
Decrease to 10-30% of pretreatment with consecutive daily 1 PV exchange
recover to 100% of pretreatment levels by 2-3 days
Prothrombin:
Decreased to 30% of baseline
Factor VII & factor VIII:
Decreased to 45-50% of baseline
Factor IX:
Decreased to 60% of baseline
Factor V, X, XI:
Decrease to 38% of baseline
Antithrombin:
Activity to 40%, Ag to 70%r to 100% of pretreatment levels by 2-3 days
Coagulant Proteins

30. 
 Fluid over load may be a problem for patient with cardiac or
renal impairment .In other situations , hypovolemia may be a
concern. Hemodynamic changes are more common with
intermittent flow centrifugation than with continuous flow
procurer.
Hemodynamic changes

31. 
 TPE can remove pharmacological the quantity of drug that is
removed depends on its volume of distribution(intravascular
Vs other),its half life in circulation, and weather it is
administered immediately before or during apheresis.
Dilutional effect

32. 
 As large volume of donor or patient blood circulate through an
apheresis device blood cells are intentionally or incidentally
removed. Apheresis only modest decrease in circulating blood
cell counts, which are not associated with any immediate
toxicity. Small amount of red lost in apheresis circuit which is
well tolerated except anemic patient meager production
capacity who is undergoing multiple procedures. Although
generally well tolerated, large volume leukapheresis for stem
cell collections in often result decline in hematocrit and platelet
count.
Cellular loss

33. 
 Removal of paraproteins (ie myeloma) is 50% of predicted
 Some cases can have greater removal than predicted (see last 2
reasons)
Due to:
 Increase in plasma volume (up to 1.5x greater, especially if IgG
>40g/L)
 Some myeloma patients have higher proportion of IgG in
intravascular space (56-85%)
 As remove paraprotein in TPE, plasma volume progressively
decreases
Paraproteins

34. An early study of 29 patients with multiple myeloma and acute kidney
injury included 24 patients on dialysis and an additional 5 with creatinine
concentrations higher than 5 mg/dL. The patients were randomly assigned
to one of two groups: 15 patients received plasmapheresis plus standard
therapy, and 14 patients received standard therapy alone. Of the 15 patients
who received plasmapheresis, 13 patients recovered renal function
(creatinine concentration < 2.5 mg/dL), in contrast to only 2 of the 14
receiving standard therapy. 51 However, in a study of 21 patients who were
randomly assigned to receive either plasmapheresis plus chemotherapy or
chemotherapy alone, Johnson and colleagues 52 reported no difference in
patient survival or in recovery of kidney function. The mortality rate at 6
months was 20% in each group, which increased to 60% to 80% at 12
months. In the largest study to date, 97 patients with multiple myeloma and
acute kidney injury were randomly assigned to receive either conventional
therapy alone or conventional therapy plus five to seven plasma exchanges
(5% human serum albumin) of 50 mL per kilogram of body weight for 10
days. The primary endpoint (death, dialysis, or glomerular filtration rate
<30 mL/min) occurred in 33 (56.9%) of 58 patients who received
plasmapheresis and in 27 (69.2%) of 39 control subjects. 53

35. 
Removal of circulating pathologic factors
Auto Antibodies GBS
Alloantibody antibody mediated transplant rejection
Immune complexes SLE
Cryoglobulin Cryoglobulinemia
Myeloma protein Multiple Myeloma
Prothorombotic factors Hemolytic uremic syndrome /thrombotic
thrombocytopenic purpura
lipoproteins familial hyper cholesterolemia
Protein bound toxin or drugs barbiturate poisoning
Possible mechanisms of action
of plasmapheresis

36. Effects on the immune system
Removal of complement
products
Lupus nephritis
Effect on immune regulation Transplantation
Improvement in
reticuloendothelial function
Cryoglobulinemia
Replacement of deficient plasma factors
Antithrombotic or fibrinolytic
factor
HUS/TTP Effects on the
immune system

37. 
Indications

39. 
 The American Society for Apheresis evaluates potential
indications for apheresis and categorizes them from I to IV.
 Category I (disorders for which apheresis is accepted as first-
line therapy)
 Category II (disorders for which apheresis is accepted as
second-line therapy)
 Category III (optimum role of apheresis therapy is not
established; decision-making should be individualized)
 Category IV (disorders in which published evidence
demonstrates or suggests apheresis to be ineffective or
harmful)
Indication

40. 
Hematological disorder

41. DISEASE ASFA/AABB Category
ABO-incompatible marrow transplant II
Aplastic Anaemia III
Autoimmune haemolytic anaemia III
Coagulation factor inhibitor II
cryoglobulinaemia II
HELLP syndrome NR
Hemolytic uremic syndrome III
Hyper viscocity symdrome/multiple
myeloma
II
Immmune thrombocytopenic purpura II
Platelet alloimmunization III
Post tyransfusion purpura I
Pure red cell aplesia III
Red cell alloimmunization III
Thrmbotic thmbocytopenic purpura I

42. 
Neurologic disorders

43. DISEASE ASFA/AABB Category
Guillain-Barre syndrome I
Chronic inflammatory demyelinating polyneuropathy I
Polyneuropathy with IgG/IgA monoclonal protein I
Polyneuropathy with IgM monoclonal protein II
Myasthenia gravis I
Stiff person syndrom III
Lambertr –eaton myasthenic syndrom II
Paraneoplastic neurologic syndromes III
Polymyositis or dermatomyositis III
Multple sclorosis IV
Idiopathic inflammatory demyelinating disease III
Refsum`s disease II
Sydenham`s chorea II
PANDAS(Pediatric autoimmune neuropsychiatric
disorder associated with streptococcal infection)
II

44. 
Renal disorder

45. DISEASE ASFA/AABB Category
Glomerular basement membrane antibody
disease
I
Other rapidly progressive
glomerulonephritis
II
Hemolytic uremic syndrome III
Recurrent focal and segmental
glomerulonephritis
III
Lupus nephritis IV

46. 
Rheumatic disease

47. DISEASE ASFA/AABB Category
Systemic vasculitis III
Scleroderma/progrresive systemic disease III
Systemic lupus erythrometosus NR
Antiphopholipid antibody syndrome NR
Rhematoid arthritis IV

48. 
Metabolic disorder
Solid organ transplant

49. DISEASE ASFA/AABB Category
Acute hepatic failure III
Overdose /poisoning III
Presensitizatin of donor organ
III
Transplantation across ABO barrier
III
Heart transplant rejection
III
Renal transplant rejection
IV

50. 
 The rate of adverse event during therapeutic apheresis is 4% to
5%,with the risk being slightly higher during the first
procedure.
1. Citrate-induced hypocalcemia, Metabolic alkalosis
2. Vasovagal reactions
3. Problems related to vascular access
I. Hematoma,
II. venous sclerosis
III. thrombosis
Complications

51. 
4. Allergic Reaction
5. Anaphylactic reaction to plasma
6. Drug interactions
7. Hemolysis
8. Air embolism
9. Hypotension
10. Infections
11. Coagulation abnormalities
12. Transfusion related acute lung injury
13. Hypothermia
14. Pyrogenic reaction
Continue..

52. 
 Plasmapheresis is contraindicated in the following patients:
 Patients who cannot tolerate central line placement
 Patients who are actively septic or are hemodynamically
unstable
 Patients who have allergies to fresh frozen plasma or albumin
depending on the type of plasma exchange
 Patients with heparin allergies should not receive heparin
 as an anticoagulant during plasmapheresis.
Contraindications

53. 
 Patients with hypocalcemia are at risk for worsening of their
condition because citrate is commonly used to prevent clotting
and can potentiate hypocalcemia
 Patients taking angiotensin-converting enzyme (ACE)
inhibitors are advised to stop taking the medication for at least
24 hours before starting plasmapheresis
Contraindications cont.…..

54. 
Thank you