In Vivo Evaluation of a New Therapeutic Plasma Exchange (TPE) Procedure
Snyder, Edward L.1; Winters, Jeffrey L.2; Burgstaler, Edwin A.2; Balogun, Rasheed A.3; Gottschall, Jerome4; Lee, Wanda5; Bodnar, Jason5; Houghton, Jaime R.5
1. School of Medicine, Yale University, New Haven, CT, United States., 2. Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States.
3. Renal Unit & Extracorporeal Therapies, University of Virginia Health System, Charlottesville, VA, United States., 4. BloodCenter of Wisconsin, Milwaukee, WI, United States.
5. Fenwal, Inc., Lake Zurich, IL, United States.
Background
Results (cont’d)
A new protocol was developed that enables the AMICUS
separator (Fenwal) to perform Therapeutic Plasma
Exchange (TPE) using centrifugal technology. This study
compared the efficacy and safety of the AMICUS
separator in patients with the existing COBE Spectra.
This was a randomized, non-blinded, paired study,
conducted at four sites with 30 evaluable patients. All
patients completed consecutive TPE procedures consisting
of one AMICUS (Test) and one Spectra (Control). Patient
diagnoses (N) were as follows: Multiple Sclerosis (11);
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (4); Hyperviscosity Syndrome (3); Renal Transplantation [antibody mediated rejection or desensitization] (2);
Myasthenia Gravis (2); Recurrent Focal Segmental
Glomerulosclerosis (2); Thrombotic Thrombocytopenic
Purpura (2); Lambert-Eaton Syndrome (1); Pemphigus
Vulgaris (1); Neuromyelitis Optica (1); and Myeloma Cast
Nephropathy (1).
Figure 1. PLASMA COLLECTION EFFICIENCY
p < 0.025
90
80
PERCENT
Materials & Methods
Results (cont’d)
70
81.9+7.6
60
75.2+6.3
AMICUS
50
40
Spectra
30
20
Paired comparisons with the student t-test were used
(Instat Version 3.0, GraphPad Software, Inc., San Diego, CA
USA). P-value <0.025* was considered significantly
different for the PCE and p <0.05 was used for all other
parameters.
*FDA requirement
Results
The AMICUS mean PCE (Figure 1) was 81.9 ± 7.6% (range:
68-96%) and the mean Spectra PCE was 75.2 ± 6.3%
(range: 61-88%). Amicus was statistically superior to
Spectra in PCE. The average fluid balance accuracy for
AMICUS was significantly higher (p <0.05), 99.8 ± 0.2%
compared to 98.8 ± 1.8% for Spectra. The average patient
blood volume (AMICUS 5,329 ± 1,039 ml vs. Spectra 5,314
± 1,030 ml), pre-procedure Plt, and hematocrit (Table I)
were not significantly different.
Plt (AMICUS 4.7 + 6.2 x1010 vs. Spectra 4.7 + 5.5 x1010)
and pHb (AMICUS 20 + 25 mg vs. Spectra 30 + 79 mg) in
the waste plasma were minimal for both devices and
were not significantly different. As expected, TPE using
either device had non-significant effects on peripheral plt
count and HCT. There was no evidence of activation of
coagulation as assessed by fibrinogen, d-dimer and prothrombin fragment 1.2 (PT1.2) or complement C3a or C5a
with either device (Table I). There were no serious
adverse events; 4 patients each in Test and Control
reported a total of 12 minor to moderate AE’s routinely
seen with TPE (Table II).
10
0
Figure 2. VOLUMES PROCESSED AND REMOVED
p < 0.05
p < 0.05
N.S.
Plasma volumes exchanged, types of replacement fluid,
and fluid balance were determined by the prescribing
physician and were based on medical need. Replacement
fluids included albumin, plasma protein fraction, fresh
frozen plasma, and plasma, cryoprecipitate reduced.
The primary outcome measure, plasma collection
efficiency (PCE), was evaluated first for non-inferiority at a
margin of 15% and then superiority to the PCE for the
Spectra. Secondary outcome measures included: platelet
content (Plt) and plasma hemoglobin (pHb) in the waste
plasma; patient coagulation factors and evidence of
complement activation; machine fluid balance accuracy
and reported adverse events.
The whole blood processed (corrected for anticoagulant)
and plasma volumes processed were significantly less for
AMICUS than Spectra (Figure 2), but the plasma volume
removed was statistically equivalent at a margin of 2.6%.
Anticoagulant (AC) used (AMICUS 577 + 164 ml vs.
Spectra 598 + 144 ml) and anticoagulant returned to the
patient (AMICUS 126 + 86 ml vs. Spectra 144 + 53 ml)
were less for AMICUS than Spectra, but this was not
significant.
Table II. ADVERSE EVENTS
Infiltration
Nausea
Chills
Headache
Rigors
Paresthesia
Fatigue
Dizzy/Light-Headed
Table I. PERIPHERAL BLOOD VALUES
AMICUS
Parameter
Pre
Platelet Count
(x103/µL)*
Post
223 ± 81 197 ± 81
Spectra
Day 1
Post
Pre
225 ± 82
225 ± 81
Post
Day 1
Post
Total AE’s Reported
AMICUS
0
1
1
1
1
2
0
1
-7
Spectra
1
0
0
0
0
2
1
-1
5
Severity
Mild
Moderate
Mild
Moderate
Mild
Mild
Mild
Moderate-Test
Mild – Control
198 ± 83 219 ± 88
Hematocrit (%)*
36 ± 5
34 ± 7
37 ± 7
36 ± 6
35 ± 6
37 ± 6
Conclusions
WBC Count
(x103/µL)*
8±4
9±5
9±4
8±4
9±6
9±4
Hemoglobin (g/dL)*
12 ± 2
12 ± 2
12 ± 2
12 ± 2
12 ± 2
12 ± 2
MPV (fL)**
9±2
9±1
9±1
9±1
9±1
9±1
Fibrinogen
(mg/dL)***
231 ± 94
94 ± 43
162 ± 52
250 ± 85
99 ± 46
156 ± 48
The AMICUS plasma collection efficiency was statistically
superior to the PCE for Spectra. Fluid balance accuracy
was also statistically higher for AMICUS compared to the
Spectra. Significantly less whole blood and plasma were
processed for an equivalent plasma volume removed
with AMICUS compared to the Spectra resulting in less,
although not significantly different AC volume returned
to the patient. There were no significant changes in
peripheral blood counts or laboratory evidence of
coagulation or complement activation with either device.
There were no serious adverse events and only a small
number of reactions commonly experienced with TPE
were reported.
D-Dimer (ng/mL)*** 408 ± 397 259 ± 366 422 ± 579 467 ± 652 211 ± 234 374 ± 482
PT 1.2 (pmol/L)*** 276 ± 174 200 ± 385 234 ± 161 277 ± 178 156 ± 120 230 ± 121
Complement C3a
(ng/mL)***
Complement C5a
(ng/mL)***
911 ± 595 470 ± 290 748 ± 562 1059 ± 642 468 ± 229 690 ± 416
17 ± 6
8±4
15 ± 5
18 ± 5
8±4
15 ± 6
*N=30 (Day1 Post: N=29), **N=21 (Day1 Post: N=20), ***N=29
AABB Annual Meeting & CTTXPO 2011. San Diego, October 22-25