Plasmapheresis is a medical procedure that involves the separation and removal of plasma from whole blood. The document summarizes guidelines from the American Academy of Neurology (AAN), American Society for Apheresis (ASFA), and American Association of Blood Banks (AABB) on the use of plasmapheresis to treat various medical conditions. The guidelines categorize conditions into four categories based on the evidence for the efficacy of plasmapheresis as a treatment. Category I conditions have the strongest evidence that plasmapheresis is an effective first-line therapy. This includes Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and thrombotic thrombocytopenic purp

1. Plasmapheresis in critical care
Dr.Ahmed Balshi
Medical Consultant, MD, ABIM, SB-Med, ICU Fellow
Dr. Muhammad Asim Rana
MBBS, MRCP, MRCPS, FCCP, EDIC, SF-CCM
ICU Consultant

2. Objectives
 Terminology.
 To understanding plasmapheresis.
 Review of the (ANN) American Academy of Neurology
Recommendations.
 Review of (ASFA) The American Society for Apheresis /
(AABB) The American Association of Blood Banks)
guidelines.
 BMJ best practice recommendations.
 Case presentation.

3. TERMINOLOGY
Apheresis : An umbrella term for "taking away" a blood component.
From Roman aphairesis meaning to take away by force.
Plasmapheresis : A general term used to denote the automated,
selective removal of plasma. Plasmapheresis uses centrifugation to
separate the blood components, in contrast to dialysis, which uses
filtration to separate small molecules from the blood.
Plasma exchange (also called therapeutic plasma exchange [TPE])
Removal of patient plasma and replacement with another fluid (eg,
donor plasma, colloid, crystalloid).

4. TERMINOLOGY
Hemapheresis (also called cytapheresis) – A term used to denote
selective removal of abnormal blood cells or excessive numbers of
cells.
Dialysis – A diffusion-based treatment best suited for the removal of
fluid or small molecules (eg, uremic toxins, some drugs) from the
blood using a filter.
Plasma filtration – A technique that separates plasma from cellular
components with a highly permeable filter (plasma filter) using a
dialysis or hemofiltration machine.

5. Therapeutic
Plasma Exchange

7. Therapeutic Plasma Exchange
 The basic of (TPE) is that removal of certain pathologic substances
from the plasma will reduce further damage and may permit reversal
of the pathologic process.
 The process involves the removal of most or all of the patient’s
plasma, by passing venous blood through an extracorporeal continuous
flow centrifugation device.
 This device separates blood into its components, shunts some or all of
the plasma into a discard container, and returns most of the remaining
blood to the patient, along with a short-acting anticoagulant (usually
citrate).

13. PRESCRIPTION
 The following formula can be used to Estimate the
plasma volume in an adult:
Estimate plasma volume (in liters)
= 0.07 x weight (kg) x (1 - hematocrit)
 For most conditions in which plasmapheresis is used, it
is considered acceptable to perform 1 to 1.5 plasma
volume exchanges per procedure

15.  Technique :Plasma exchange is most commonly
performed with centrifugation devices used in blood
banking procedures. These devices also offer the
advantage of allowing selective cell removal (cytapheresis).
 Venous access : Successful execution of a therapeutic
plasma exchange (TPE) procedure requires reliable venous
access, which may be either two large durable peripheral
veins or central line.

16. Apheresis schedule
The AABB general recommendation is that one exchange be performed
every 2nd or 3rd day, each exchange consisting of 1 to 1.5 plasma
volumes, for a total of 3 to 5 procedures.
Exceptions include the following:
*In acute GBS, it may be necessary after the initial exchanges to
perform TPE one to two times a week until improvement occurs.
*In TTP, plasma exchanges should be performed daily until the platelet
count is normal for two to three consecutive days.
*Treatment for Goodpasture's syndrome (anti-GBM mediated disease) is
generally also performed on a daily basis for at least two weeks.
AABB: American Association of Blood Banks

17. Replacement fluids
Albumin, saline, or a combination of albumin and saline, are the
replacement fluids of choice for most conditions. It is generally
recommended that plasma only be used as the replacement fluids for
TTP, (TTP-HUS), or thrombotic microangiopathy (TMA).
 5% Albumin : Albumin has the advantages of lack of viral
transmission and minimal risk of anaphylactic reactions.
 Albumin-saline combination : When colloid and crystalloid solutions
are used in combination, the amount of colloid should not be <50% of
the total infused. An appropriate replacement solution would consist of
60 to 80% colloid and 20 to 40% saline .
 Plasma : Plasma can be provided in the form of FFP, plasma frozen
24 hours after collection (FP24).

18. Cytapheresis
 Cytapheresis aims to lower the leukocyte, platelet, erythrocyte count.
 The post-procedure target WBC count in hyperleukocytosis is < 100,000
 For thrombocytosis, the target platelet count is < 1,000,000
Cytapheresis of red blood cells can be done for the following:
 Removing red blood cells in patients with polycythemia or iron overload.
 Exchange transfusion to prevent or treat complications of SCD (stroke)
or for vasoocclusive pain events (sickle cell crisis). In crisis, the goal is
the removal of more than 50% of hemoglobin S, and it monitored by
measuring the Hgb concentration and percent hemoglobin S.
 Severely parasitemic conditions, such as malaria and babesiosis, in order
to promote response to pharmaceutical management.

19. Complications
 HYPOTENSION
 TRANSFUSION-RELATED ACUTE LUNG INJURY
 CITRATE-INDUCED HYPOCALCEMIA
 CITRATE-INDUCED METABOLIC ALKALOSIS
 COAGULATION ABNORMALITIES
 INFECTION
 VIRAL TRANSMISSION BY PLASMA
 ANAPHYLACTIC REACTIONS TO PLASMA
 HYPOKALEMIA
 PROBLEMS WITH VASCULAR CATHETERS
MORTALITY: 0.03 % to 0.05 %, Respiratory or Cardiac complications
were most common.

20. Evidence Based Guidelines
ANN/ASFA/AABB/BMJ

21. AAN Guideline Process
Clinical Question
Evidence
Conclusions
Recommendations
 All studies rated Class I, II, III, or IV
© 2011 AMERICAN ACADEMY OF NEUROLOGY

22. AAN Level of
Recommendations
• A = Established as effective, ineffective or harmful.
• B = Probably effective, ineffective or harmful.
• C = Possibly effective, ineffective or harmful.
• U = Data inadequate or conflicting; given current
knowledge, treatment (test, predictor) is unproven.
Note that recommendations can be positive or negative.
© 2011 AMERICAN ACADEMY OF NEUROLOGY

23.  Question 1: What is the efficacy of
plasmapheresis in the treatment of AIDP,
also known as GBS?
2011 AMERICAN ACADEMY OF NEUROLOGY

24. Conclusion:
 Plasmapheresis is established as effective for the
treatment of AIDP/GBS severe enough to impair the
ability to walk independently or severe enough to
require mechanical ventilation.
Recommendation:
 Plasmapheresis should be offered in the treatment of
AIDP/GBS severe enough to impair independent
walking or to require mechanical ventilation (Level A).
© 2011 AMERICAN ACADEMY OF NEUROLOGY

25. Conclusion:
 For milder AIDP/GBS, in which ambulation is preserved,
plasmapheresis is probably effective.
Recommendation:
 Plasmapheresis should be considered in the treatment of
milder clinical presentations of AIDP/GBS (Level B).
© IV immunoglobulin (IVIG) is an alternative treatment
used in patients with AIDP/GBS. There is insufficient
evidence to demonstrate the superiority of one
treatment over the other.
© 2011 AMERICAN ACADEMY OF NEUROLOGY

26.  Question 2: What is the efficacy of
plasmapheresis in the treatment of CIDP?
© 2011 AMERICAN ACADEMY OF NEUROLOGY

27. Conclusion:
 Plasmapheresis is established as effective in the short-term
treatment of CIDP; both studies showed the
beneficial effect is not sustained, with worsening
beginning 1 to 5 weeks after last plasmapheresis
treatment.
Recommendation:
 Plasmapheresis should be offered as a short-term
treatment for patients with CIDP (Level A).
© Steroids, IVIG, and immunosuppressants have also
been used in the treatment of CIDP.
© 2011 AMERICAN ACADEMY OF NEUROLOGY

28.  Question 3: What is the efficacy of
plasmapheresis in the treatment of MG?
© 2011 AMERICAN ACADEMY OF NEUROLOGY

29. Conclusion:
 There are inadequate data to evaluate the use of
plasmapheresis in the treatment of myasthenic crisis
or in the treatment of MG prethymectomy.
Recommendation:
 Because of the lack of randomized controlled studies
with masked outcomes, there is insufficient evidence
to support or refute the efficacy of plasmapheresis in
the treatment of myasthenic crisis (Level U) or MG
prethymectomy (Level U).
© 2011 AMERICAN ACADEMY OF NEUROLOGY

30. Clinical Context
 Despite the fact that the use of
plasmapheresis in myasthenic crisis and
MG prethymectomy receives a Level U
recommendation, plasmapheresis is still
used at many medical centers for these
indications.
© 2011 AMERICAN ACADEMY OF NEUROLOGY

31.  Question 4: What is the efficacy of
plasmapheresis in the treatment of
dysimmune neuropathies?
© 2011 AMERICAN ACADEMY OF NEUROLOGY

32. Conclusion:
 Plasmapheresis is probably effective in IgA- and IgG-monoclonal
gammopathy of undetermined significance
(MGUS)-associated polyneuropathy.
Recommendation:
 Plasmapheresis should be considered in polyneuropathy
associated with IgA and IgG MGUS (Level B).
© 2011 AMERICAN ACADEMY OF NEUROLOGY

33. Conclusion:
 Plasmapheresis is probably not effective in
polyneuropathy associated with IgM MGUS.
Recommendation:
 Plasmapheresis should not be considered in the
treatment of polyneuropathy associated with IgM
MGUS (Level B).
© 2011 AMERICAN ACADEMY OF NEUROLOGY

34.  Question 5: What is the efficacy of
plasmapheresis in the treatment of CNS
demyelinating disease (MS) ?
© 2011 AMERICAN ACADEMY OF NEUROLOGY

35. Conclusion:
 Plasmapheresis as adjunctive therapy is probably
effective for management of exacerbations in
relapsing forms of MS.
Recommendation:
 Plasmapheresis should be considered for the
adjunctive treatment of exacerbations in relapsing
forms of MS (Level B).
© 2011 AMERICAN ACADEMY OF NEUROLOGY

36. Conclusion:
 Plasmapheresis is possibly effective for acute fulminant
CNS demyelinating diseases (including MS, acute
disseminated encephalomyelitis [ADEM], neuromyelitis
optica [NMO], and transverse myelitis [TM]) that fail to
respond to high-dose corticosteroid treatment.
 Because the study included subgroups of patients with
demyelinating diseases, it is not possible to determine
if plasmapheresis is more or less effective in patients
with different demyelinating diseases.
© 2011 AMERICAN ACADEMY OF NEUROLOGY

37. Recommendation:
 Plasmapheresis may be considered in the treatment of
fulminant CNS demyelinating diseases that fail to respond
to high-dose corticosteroid treatment (Level C).
© 2011 AMERICAN ACADEMY OF NEUROLOGY

38. Conclusion:
 For chronic progressive or secondary progressive
MS, plasmapheresis is established as ineffective
based on consistent Class I evidence.
Recommendation:
 Plasmapheresis should not be offered for chronic
progressive or secondary progressive MS (Level A).
© 2011 AMERICAN ACADEMY OF NEUROLOGY

39. GENERAL THERAPEUTIC
CATEGORIES
(ASFA) / (AABB) guidelines for TPE are based on extensive literature
reviews. These guidelines are generally updated every two or three
years (last update 2013). Conditions are divided into four categories,
based on evidence of clinical efficacy of TPE reported in reviewed
literature.
Category I: Disorders for which apheresis is accepted as 1st line therapy.
Category II: Disorders for which apheresis is accepted as 2nd line therapy.
Category III: Disorders for which the optimum role of apheresis therapy
is not established.
Category IV: Disorders for which published evidence demonstrates or
suggests apheresis to be ineffective or harmful.
ASFA :The American Society for Apheresis. AABB: The American Association of Blood Banks

40. Category I Plasma exchange
 GBS as first-line stand alone therapy.
 CIDP.
 Hyperviscosity in monoclonal gammopathies.
 ANCA-associated rapidly progressive glomerulonephritis (Wegener's).
 Anti-GBM disease (Goodpasture's syndrome).
 Severe Cryoglobulinemia.
 FSGS (Recurrent in transplanted kidney).
 HUS (Atypical HUS due to autoantibody).
 TTP.
 MG (Moderate-severe ,Pre-thymectomy).
 Wilson disease, fulminant.

41. Category I
 Red blood cell exchange (ie, exchange transfusion) in
sickle cell disease for the management of acute stroke.
 Red blood cell exchange :Severe Babesiosis.
 Erythrocytapheresis: Hereditary hemochromatosis,
Polycythemia vera.
 Leukocytapheresis: Leukostasis

43. Category II Plasma exchange
 Secondary treatment for acute disseminated encephalomyelitis
after high-dose intravenous corticosteroid failure.
 Autoimmune hemolytic anemia (life-threatening cold agglutinin
disease).
 Antiphospholipid syndrome, catastrophic.
 Multiple sclerosis.
 Myeloma cast nephropathy.
 Neuromyelitis optica (Devic's syndrome), acute.
 Overdose, Venoms, and Mushroom poisoning.
 SLE, severe (eg, cerebritis, diffuse alveolar hemorrhage).

44. Category II
 Red blood cell exchange for acute chest syndrome in
sickle cell disease.
 Red blood cell exchange for severe Malaria.
 Thrombocytapheresis: Symptomatic Thrombocytosis.

46. Category III Plasma exchange
 Aplastic anemia.
 Immunoglobin A nephropathy.
 Hypertriglyceridemic pancreatitis.
 Chronic progressive Multiple sclerosis.
 Severe Pemphigus vulgaris.
 Post-transfusion purpura.
 Scleroderma (progressive systemic sclerosis).
 Sepsis with multiorgan failure.
 Thyroid storm.

47. Category III
 Erythrocytapheresis: Secondary erythrocytosis.
 Leukocytapheresis: Hyperleukocytosis , Prophylaxis.
 Lymphocytapheresis: Psoriasis .
 Thrombocytapheresis: Thrombocytosis, Prophylactic
or secondary.

48. Category IV Plasma exchange
 Active rheumatoid arthritis.
 Amyotrophic lateral sclerosis.
 Dermatomyositis, polymyositis.
 Inclusion body myositis.
 Immune thrombocytopenia, refractory.
 POEMS syndrome.

49. Guillain-Barre syndrome
● Both plasma exchange and intravenous immunoglobulin
(IVIG) have been shown to be equally efficacious. The
choice between them is often institution-dependent.
● The dose for plasma exchange is given through a
central venous catheter every other day for 7 to 14 days.

50. Chronic inflammatory demyelinating
polyradiculoneuropathy
Initial monotherapy: IVIG, corticosteroids, or plasma exchange.
 Approximately 75% to 85% of patients will respond to monotherapy with
intravenous immunoglobulin (IVIG), corticosteroids, or plasma exchange.
While there are several trials showing similar efficacy, there is no consensus
as to which is the preferred treatment, and all have been advocated as initial
therapies.
 Methylprednisolone: 1000 mg iV once daily for 3-5 days, followed by 1000 mg once weekly until clinical
response (usually 4-12 wks)
 Dexamethasone: 40 mg PO once daily for 4 days every 4 weeks for 6 months
 Prednesolone:. 0.5 to 1 mg/kg/day PO until clinical response (usually 4-12 wks)
 IV IG : 2000 mg/kg/dose iV, given as either 400 mg/kg once daily for 5 consecutive days, or 1000 mg/kg for two
consecutive days; repeat every 2-4 weeks depending on response

51. MS,acute relapse affecting
function
 1st Line :Methylprednisolone: 1000 mg iv once daily for 3 days
 2nd Line :IV IG Can be used if methylpredisolone is ineffective or
contraindicated (e.g., in patients with infection, poorly controlled
diabetes, or hypertension).
 Plasma exchange :When a patient becomes quadriplegic over days
to weeks, plasma exchange has been shown to be effective in some
patients and is used in severe cases.

52. Myasthenia gravis
 Severe disease (myasthenic crisis):
1st intubation and mechanical ventilation
plus
plasma exchange ( 1 to 1.5 plasma volume during each of 5
treatments daily or on alternate days over 2 week period) or
IVIG (400 mg/kg/day iv for 5 days).
plus
supportive care
Note :Plasma exchange has rapid response with onset usually after 2
to 3 sessions. Effects are temporary, lasting weeks.

53. Lambert-Eaton myasthenic
syndrome
 Severe respiratory or bulbar weakness
1st intubation and mechanical ventilation
plus
plasma exchange or (IVIG) .
plus
supportive care.
Note :Plasma exchange or high-dose IVIG may be used to induce
relatively rapid but transient improvement in symptoms.

54. Haemolytic uraemic syndrome
 Epidemic HUS: adults
1st Line plasma exchange.
 Sporadic and secondary HUS: not due to S. pneumoniae
1st Line plasma exchange.
 Sporadic and secondary HUS: due to S pneumoniae
1st Line antibiotic therapy.

55. Thrombotic thrombocytopenic purpura
 Acute episode
1st Line plasma exchange.
The mortality rate prior to the use of plasma
exchange was as high as 90% .

56. PLASMA EXCHANGE :
 The efficacy of plasma exchange in the treatment of TTP in adults
has been demonstrated in two trials that included 210 patients. The
results of these studies can be summarized as follows :
• Plasma exchange with fresh frozen plasma was more effective than
plasma infusion alone. At six months, the remission rate and survival
rate with these two procedures was 78 versus 31 percent (remission)
and 78 versus 50 percent (survival) . (The mortality rate is much higher
in non responders to these interventions.)
• As noted above, plasma infusion alone is less effective than plasma
exchange, and may be complicated by volume overload.
• Plasma infusion without exchange might therefore serve as
emergency treatment in those not having immediate access to
plasma exchange.

57.  In approximately 15 % of patients, twice daily plasma
exchange is required, because of either failure to respond
to the initial daily plasma exchange or exacerbation of
symptoms.
Twice daily exchange of one plasma volume is
more effective replacement therapy than
increasing the volume of a single daily exchange.
Once recovery begins, single daily plasma exchanges are
resumed.
 Relapses, defined as recurrent TTP after at least
30 days of no treatment and no evidence of TTP

60. CASE PRESENTATION
A 37 years old female C/O severe headache, fever, transient
weakness & numbness of the left upper limb for 2 days,
brought to E.R in confusional state, irritability, then she
developed two attacks of convulsion in the recovery room.
Not known to have any chronic medical illness before.
No history of recent travel.
Negative drug history.
 O/E :Confused, Irritable, Pallor, Tinge of jaundice. Febrile
38.3C After few hours, she desaturated, intubated
electively and connected to the ventilator later on.

61.  WBC 15.2 Hgb 7.23 Plt 25000
 PT 12 PTT 28.1 INR 1.11
 Retic 10% Urea 11 Creat 125.7
 T.Bili 52.3 Direct 15.3 Indirect 36.9
LDH 1740
Initial CXR: Normal
Plain CT-SCAN Brain : on admission: Normal.

62.  Peripheral Blood Film: showed leucoerythroblastic
picture, reticulocytosis, fragmented red cells, severe
thrombocytopenia.
 Coomb's test (direct, indirect): Negative.
 Malaria Film X 4: Negative.
 RF : Negative.
 ANA: Negative.
 U/S Abdomen & Pelvis: Mild hepatomegaly only.
 Bone Marrow Aspiration: Hypercellular bone marrow
with megakaryocytic and erythroid hyperplasia.

63. Hospital Course:
Patient intubated (electively) on the same day of presentation.
 Plasma Exchange requested immediately.
 FFP transfusion started as a bridge to Plasma Exchange .
 After two days, She developed Two attacks of generalized tonic
clonic convulsions, Diazepam iv given, Phenytoin started.
She transferred from recovery room to I.C.U bed 12.
 Within 10 days, her level of consciousness is improved
gradually, became responding to verbal commands.
 After Two weeks, extubated, shifted to the general ward. The
patient become fully conscious, oriented , alert but we
discovered that she is (Quadriplegic). Plasma Exchange stopped.

64. Plain CT-SCAN Brain repeated: showed multiple small infarctions
at RT.parital lobe, RT.frontal lobe and LT.parital lobe.
MRI Brain, Brain stem, Cervical spine done: showed:
High signal intense lesions at:
Rt.internal capsule, LT.internal capsule Rt.frontal white matter.
Para ventricle lesion(parital lobe). Biparital white matter.
Mild focal disc plugging.
One day before discharge:
WBC 9.6 Hgb 11.2 PLT 519
Urea 4.2 Creat 50 K+ 3.8 LDH 390
Length of hospital stay: 31 days.

65. TABLE
LAB 10/7 11/7 12/7 13/7 14/7 15/7 16/7 18/7 19/7 20/7 21/7 22/7 23/7 24/7 25/7 26/7
WBC 23.6 15.2 11.6 17.8 15.2 14.5 8.1 8.0 6.6 11.0 7.3 9.3 5.9 6.1 7.1 7.9
Hgb 8.1 9.1 8.15 8.1 7.0 9.9 8.4 8.3 7.1 10.6 10.7 10.6 9.6 9.4 9.5 10.4
PLT 20 27 24.6 42 53 12 49 65 88 113 248 183 229 317 314 472
Urea 14.8 16.8 12.7 9.2 7.1 8.2 7.5 4.7 5.3 5.9 5.8 4.5 5.0 4.7 5.2 4.8
Creat 127 135 116 99 88 67 55 49 81 64 49 63 56 54 35 45
LDH 1450 2850 1636 677 1152 1260 573 350 353 299 344 261

66. Plasma Exchange: started 07/07 D/C 23/07
TOTAL FFP : 305 units
PRBCs transfusion: B +ve
TOTAL PRBCs: 16 units
A Disintegrin-like And Metalloprotease with ThromboSpondin type1)

67.  Schedule and rate of response :
Plasma exchanges should be performed daily until the platelet
count and serum (LDH) concentration are normal for two to three
consecutive days. On average, 7 to 16 daily exchanges are required
to induce remission, but the variability is large and unpredictable,
ranging from 3 to 145 required exchanges.
The recommended volume to be exchanged is one estimated
plasma volume per procedure.
 The following formula can be used to estimate the plasma volume
in an adult :
Estimated plasma volume (in liters) =
0.07 x Weight (kg) x (1 - Hematocrit)

68. Simply:
Estimated plasma volume (in ml) =
T. Blood volume x (1 - Hematocrit)
T. Blood volume (in ml)= Female 69 X weight (kg)
Male 70 X weight (kg)
For example:
Male patient , 70 kg , Hematocrit 20%
T. Blood volume (in ml)= 70 X 70 = 4900 ML
Estimated plasma volume (in ml) =
T. Blood volume x (1 - Hematocrit)
4900 X ( 1 - 0.20 ) = 3920 ML

69. Summary
 TPE plays an important role in the treatment of several autoimmune,
neurological, hematological, renal disorders.
 TPE is not without risks and hazards (e.g., vascular access, bleeding,
allergy), which should also be considered.
 Idiopathic familial and nonfamilial thrombotic thrombocytopenic purpura
as well as the subset of the hemolytic uremic syndrome not associated
with diarrhea are clear indications for TPE using fresh frozen plasma as
replacement fluid.
 Patients with myasthenic crisis will also benefit from TPE and will
improve within 1 day.
 Acute pancreatitis as a complication of the chylomicronemia syndrome
has a poor prognosis and should be treated with TPE without any delay.