JJ

1. Prof Yasser M. Abdelhamid MD
Professor of Nephrology
Cairo University

2. Definitions
• Apharesis: Extracorporial procedure in
which blood separator technology is used
to remove abnormal blood cells and
constituents.
• Plasma Exchange: Isolation of plasma from
the donor, and replacement with a proper
solution (subsequent removal of large
molecular weight substance).

3. Definitions
• Plasmapheresis A procedure in which blood of the
patient or the donor is passed through a medical
device which separates plasma from other
components of blood and the plasma is removed
(i.e., less than 15% of total plasma volume) without
the use of colloid replacement solution.
• High-volume plasma exchange (HVP): Exchange of
15% of ideal body weight (representing 8–12 L);
patient plasma at a rate of 1–2 L / hour with
replacement in equivalent volume.

4. • A) Techniqual Considerations
• B) Clinical Indications
• C) conditions

5. • A)Techniqual Considerations
• B) Clinical Indications
• C) conditions

6. Principles
o Removal of a pathogenic molecular target
through removal of 1-1.5 of estimated plasma
volume each procedure.
o Volume of each procedure reflects a patient
parameter
o Number of session and frequency is
determined by type and severity of the
disease

7. Modalities
• Therapeutic plasma exchange (TPE).
• Other apharesis modalities:
• Double filtration plasmapharesis .
• Immunoadsorption columns ( IgG).
• LDL apharesis (LDL).
• Erythrocytapheresis, Leukocytapheresis
and Thrombocytapheresis.

8. Plasma Exchange (Centrifuge)

9. Plasma Exchange (Membrane)

10. Other Techniques
Immunoadsorption

14. Substance Removed
At At least one of the following conditions must be
present for TPE to be a rational therapeutic
choice:
 Sufficiently large (mol wt greater than 15,000 kd),
 Sufficiently long half-life,
 Acutely toxic and
 Resistant to conventional therapy.

15. Myeloma cast nephropathy
Free kappa or lambda light chain
Cryoglobulinemia :Cryglobulins
TTP
Autoantibody reactive with the ADAMTS13
enzyme
Anti-GBM
Antibody against noncollagenous (NC1)
domains of a3 and a5 chains of collagen type IV

16. ANCA + GN:
ANCA
Catastrophic antiphospholipid syndrome
Anticardiolipin and antibeta-2-glycoprotein
autoantibodies
Antibody mediated TX rejection
Alloantibody reactive with HLA antigen(s)
FSGS
Permeability factor

17. How Many Sessions?
• Depends upon substance to be removed;
A) Intra or extravscular.
B) Rebound or not.
C) Sudden termination?

18. How Many Sessions?• IgM (intravascular): One or two sessions.
• IgG (extravscular): multiple sessions due to
rebound increase (48 h) due to;
0
10
20
30
40
50
60
70
80
90
100
0 2 4 6 8 10 12

19. How Many Sessions?
• IgM (intravascular): One or two sessions.
• IgG (extravscular): multiple sessions due to
rebound increase (48 h) due to;
Lymphatic drainage,
Reproduction.

20. • General recommendation of The American
Association of Blood Banks for conditions
requiring plasmapheresis states that;
• one exchange be performed every
second or third day,
• Each exchange consisting of 1 to 1.5
plasma volumes.

21. How Many Sessions?
 Usually 5-7 exchange over 7-10 days.
 Gradual withdrawal;
 TTP.
 Anti-GBM antibodies.

22. o Cessation of TPE after several procedures
can result in pretreatment or even higher
levels of IgG, especially if the patient is not
on immunosuppressive therapy.
o Intensive regimen involving several TPE
procedures and the institution of
immunosuppressive therapy is required to
significantly reduce IgG levels.

23. A. Concomitant Treatment (Immunosuppression).
B. Treating Early (anti-GBM).

24. PlasmaVolume
Related to Hematocrite
0.07 X weight(Kg) X (1- Hct)
35 ml/Kg(Normal Hct)
40 ml/Kg (Low Hct)

25. Replacement Solution
Albumin
Albumin + Saline (50 – 50 %)
Fresh frozen plasma, cryoprcipitate (TTP).

26. DisadvantagesAdvantagesSolution
• Expensive
• No coagulation factors
• No immunoglobulin
• No risk of infection
• Room Temperature
• No Allergy
• No need for ABO
• Depletes mediators
Albumin
• Blood born infection
• Allergy
• ABO Incompatibility
• Frozen
• Citrate load
• Coagulation factors
• Beneficial factors
(immunoglobulin,
complement)
FFP

27. FFP is specifically indicated in;
 Replace deficient plasma factors in TTP.
 Pre-existing defect in haemostatic system.
 After 2nd -3rd session (depletion of clotting factors).
 Catastrophic antiphospholipid syndrome (CAPS).
 Pulmonary–renal syndrome with active lung
hemorrhage.
 Membranoproliferative GN (MPGN) type II with
factor H deficiency.

28. Why Spaced Sessions?
• Single session; fall in fibrinogen (80%) ,
prolongation of PTT (100%), Fall of prothrombin
(50-70%).
• Thrombocytopenia
• Risk of bleeding.
• Increase is biphasic; rapid initial increase (4h),
slower increase (4-24h).
• Complete recovery by 48h.

29. Laboratory Evaluation
• CBC,
• Immunoglobulin levels,
• Coagulation profile.
• Electrolyte studies should be performed.
• For a patient undergoing therapeutic
cytapheresis, the appropriate cell count
determines the adequacy of response.

30. • A) Techniqual Considerations
• B) Clinical Indications

31. American Society for Apheresis 2016 indication
categories for therapeutic apheresis
Disorders for which
apheresis is accepted as
first-line therapy, either
as primary stand-alone
treatment or in
conjunction with other
modes of treatment.
Disorders for which apheresis
is accepted as second-line
therapy, either as a stand-
alone treatment or in
conjunction with other modes
of treatment.
Disorders for which the
optimum role of
apheresis therapy is not
established. Decision
making should be
individualized
Disorders for which
published evidence
demonstrates or
suggests apheresis to
be ineffective or
harmful.
Category I
Category II
Category III
Category IV

32.  Goodpasture’s syndrome (Anti-GB): DX
independency, alveolar hemorrhage.
 TTP.
 Wilson disease, fulminant.
 Hyperviscosity in monoclonal
gammopathies.
 Chronic inflammatory demyelinating
polyneuropathy.
 Myasthenia gravis.
 Guillian-Barre syndrome.
Category I

33. • Lambert-Eaton myasthenic syndrome
• Multiple sclerosis (unresponsive to steroids)
• RBC alloimmunization in pregnancy
• Mushroom poisoning
• Acute disseminated encephalomyelitis
• HUS(atypical, due to cf mutations)
• Autoimmune hemolytic anemia (life-threatening cold
agglutinin disease)
• Systemic lupus erythematosus (severe)
• Myeloma cast nephropathy
Category II

34. o Post-transfusion purpura
o Autoimmune hemolytic anemia (warm
autoimmune hemolytic anemia)
o Hypertriglyceridemic pancreatitis.
o Thyroid storm
Category III

35. o Stiff person syndrome.
o Hemolytic uremic syndrome (typical diarrhea-
associated).
o Systemic lupus erythematosus (nephritis).
o Immune thrombocytopenia.
Category IV

37. • A) Techniqual Considerations
• B) Clinical Indications
• C) conditions

38. Thrombotic thrombocytopenic
Purpura
• With the use of FFP to replenish ADAMTS13 and
removing of antibodies (44-65% of patients have
a detectable level of inhibitor).
• Gradual withdrawal after improvement.
• Will tolerated in pregnancy induced cases and
should be done (George, Curr Opin Hematol, 2003).
• In HELLP with failure of recovery of
thrombocytopenia by 5th day post partum (Eckford et
al, J Obstet Gynaecol, 1998).

39. Waldenstrom’s and Type I Cryoglobulin
Renal Diseases
• Depletion of IgM with infrequent exchanges.
• Intravascular, non rebound.

40. Anti- GBM Disease
• Improves renal recovery, decreases ESRD,
rapid resolution of hemoptysis in DAH.
• Early ,Scr <5.7mg/dl not on DX.
• Otherwise,…..Only in cases of DAH.

41. Anti- GBM Disease
• Daily or every other day for minimum of 2 wks
or antibody levels are undetectable.
• Replace with FFP in cases of DAH during last
portion of exchange.
• In recurrent Alport’s syndrome post renal TX
(Diaz et al, Arch Pathol Lab Med, 1994).

42. Pauci-Immune RPGN and ANCA
Associated Disease
• TPE should be considered in Severe renal disease,
Scr >5.7 mg/dl, dialysis dependency or alveolar
hemorrhage (Szczepiorkowski, J Clin Apher, 2010)
• Typical regimen includes a 1–1.5 plasma volume
exchange, with 5% albumin for replacement, with
1–2 l of FFP if pulmonary hemorrhage is present
• Consider daily TPE in fulminant cases or in
presence of DAH, then every 2–3 days for a total of
six to nine procedures.

43. Meyloma Cast Nephropathy
• High level of circulating IgG.
• In cases of acute presentation
• Early, intensively for 5 days then every other
day.
• Monitored by immunoglobulin level.

44. • Daily for 3-5 days (clinical assessment) with
FFP replacement.
• IVIG instead of TPE (Asherson et al, Lupus, 2003).
• Recommended in pregnancy associated cases.
(Erkan et al, Rheumatology (Oxford), 2008)
Catastrophic Antiphospholipid
Syndrome

45. Systemic Lupus Erythrematosis
• No benefits of addition of TPE to standard
treatment (Lewis et al, N Engl J Med, 1992- Wallace et al, J Clin Apher,
1998).
• Could be considered in RPGN or lung
hemorrhage. (Pagnoux et al, Transfus Apher Sci, 2007)

46. Published guidelines are lacking.
Reports of plasma exchange for pregnant
patients are largely limited to isolated cases in
which patients with autoimmune type disease
with failed other treatment modalities.
(Cox et al, Journal of Clinical Apheresis,2017)
Pregnany

47. Case Reports
 TTP (Fyfe-Brown et al, AJP Rep 2013)
 Antiphospholipid syndrome
(Mayer-Pickel et al, Case Rep Obstet Gynecol 2015)
 Rh alloimmunization and pregnancy
(Houston et al, Transfusion Apheresis Sci 2015)
 Severe lupus (Chen Y-JA et al, Lupus 2014)
 Relapsing MS (Cox et al, Journal of Clinical Apheresis, 2017)

48. • Consensus manuscripts and publications also
largely omit recommendations beyond stating
that TPE is generally considered safe in
pregnant patients
Pre-term delivery?????????

49. • Left Lateral Decubitus Position
– Minimize inferior vena cava compression.
• Adjustment of Plasma Volume.
- Increase calculated plasma volume by 50% at the
start of the 2nd trimester.
• Prevention of hypocalcemia
– Administration of calcium gluconate (starting
dose 1 g)
Precautions

50. • Fibrinogen levels.
– Consider the lower limit of normal fibrinogen to be 50% higher
than the lower limit for non-pregnant individuals
– Postpone procedures or modify replacement fluid to include
FFP.
• Obstetrics Consultation.
• Determination of Rh Status and Rh Ig Re-administration.
- Plasma exchange may reduce Rh-Ig levels below recommended
levels. Re-administration of Rh-Ig may be considered after
cessation of plasma exchange
Precautions

51. CONCLUSION

52. CONCLUSION
• Therapeutic apharesis are extracorporial
modalities that can remove abnormal
pathogenic molecules.
 Don't hesitate if it is clearly indicated,
 Don’t rush other wise.

54. Hazards
• It is safe during pregnancy and has even saved
patients during fulminant crises. As the etiology
of preterm delivery is unknown, plasmapheresis
is (or may be) associated with preterm delivery.
Other complications can occur from hypovolemic
reactions or allergies. Large hormone shifts may
cause preterm delivery.
• Therapeutic apheresis in pregnancy: General
considerations and current practice

55. Hormonal Change in PE
• insulin, cortisol and sex hormones that are rapidly cleared
from the circulation and re-secreted again if needed
• T4 has an especially prolonged half-life time of around 7
days, a small fraction of free hormone (free thyroxine (fT4)
around 0.03%) and a quite stable plasma level throughout
the day
• PE removes these binding proteins resulting in major
changes of the total hormone pool (TT4)
• shift from bound to freely available thyroid hormone, the
pituitary-thyroid axis is thought to compensate for a PE-
induced reduction in TT4 in a physiological condition