|Year : 2018 | Volume
| Issue : 1 | Page : 30-33
Machine and man individualities in apheresis adverse events
Sudipta Sekhar Das, Subrata Sen, Ritam Chakrabarty
Department of Transfusion Medicine, Apollo Gleneagles Hospitals, Calcutta, West Bengal, India
|Date of Web Publication||5-Apr-2018|
Dr. Sudipta Sekhar Das
Department of Transfusion Medicine, Apollo Gleneagles Hospitals, Calcutta, West Bengal
Source of Support: None, Conflict of Interest: None
Background: Adverse events due to plateletpheresis are not unheard of, citrate-related reactions being the most common. Most of these events are mild and self-limiting. The current study describes adverse events in plateletpheresis using modern apheresis systems. Materials and Methods: The prospective study included 1455 plateletpheresis procedures from July 2013 to April 2016. Procedures were performed on Amicus, Trima Accel and Cobe spectra cell separators. The endpoint of each procedure was a yield of 3 × 1011 platelets (PLTs) per unit. Donor adverse reaction if any was managed, reported, and documented. Results: The median age of donors was 31 years with male-to-female ratio of 13:1. The median body surface area and body mass index were 1.64 m2 and 22.4 kg/m2, respectively. The mean PLT count of donors was 199.8 × 103/uL with a mean hemoglobin value of 13.6 g/dl. ACD infusion was significantly more in the Cobe (P < 0.01). Donation time was least with the Trima compared to Amicus (P < 0.01) and Cobe (P < 0.001). Total whole blood volume processed was higher in Cobe (P < 0.01). Paresthesia due to citrate toxicity was the most common adverse reaction (65.3%), and vascular injury was observed in only five donors. Adverse reaction was significantly more with the Cobe (P < 0.01). The overall incidence of adverse reaction was 3.4%. Conclusion: Serious adverse events were not observed. The modern-generation apheresis machines are more donor-friendly and cause less adverse reactions compared to the older versions. Good donor screening, optimized donor physiognomic and hematological values, and skilled operator are the key factors to reaction reduction by apheresis.
Keywords: Adverse events, cell separator, citrate reaction, plateletpheresis, vascular injury
|How to cite this article:|
Das SS, Sen S, Chakrabarty R. Machine and man individualities in apheresis adverse events. Glob J Transfus Med 2018;3:30-3
| Introduction|| |
Although plateletpheresis procedures are considered safe, adverse events related to these procedures have been discussed elaborately in the literature., Donors suffer a mild reaction rarely requiring any medical intervention. Apheresis procedures are commonly associated with citrate-related reactions and comprise 30%–40% of all reactions. These reactions are generally transient and self-limiting. Other adverse events include hematoma, pain or swelling at the phlebotomy site, peripheral neuropathy, blood loss, hypertension, and allergic reactions. Serious adverse events due to plateletpheresis such as severe vasovagal reactions, nonvasovagal hypotension, neuropathy, syncope, angina, or myocardial ischemia are rare and comprise only 0.16%–0.24% of all reactions.,,,, The possible effects of apheresis on a donor or a patient can be classified as “physiological effects” and “adverse effects”. The easily reversible physiological effects such as mild paresthesias and lightheadedness due to citrate infusion are an expected phenomenon that has trivial deviations from baseline physiology. Adverse effects due to apheresis are those that are unusual and clinically troublesome occurrences. Frequency of apheresis donor reactions varies from study to study, and the authors have also observed that “almost all” their donors experienced some form of physiological or adverse effects during or after the donation.,,,
The current study describes adverse events in plateletpheresis using modern apheresis systems.
| Materials and Methods|| |
Donors and procedures
This was a prospective study that included 1455 plateletpheresis procedures performed on eligible donors from July 2013 to April 2016. All procedures were performed by the same apheresis team after taking informed consent. No prophylactic calcium supplementation was administered to any donors. A total of 561 procedures were performed on Amicus cell separator (version 3.21, Fenwal Healthcare Corporation, Deerfield, IL, USA), 679 on Trima Accel cell separator (version 5.1, Terumo BCT, Lakewood, USA), and 215 using the Cobe spectra cell separator (version 7.0 LRS turbo, Terumo BCT, Lakewood, USA). All these procedures were performed following the departmental standard operating procedure using closed-system apheresis kits and acid citrate dextrose (ACD) - A anticoagulant in the proportion of 1:10–1:12. The endpoint of each procedure was based on the target yield of 3 × 1011 platelets (PLTs) per unit. Procedure summary including donor and plateletpheresis details, patient details, donor reaction if any, reaction management, and quality of product obtained was recorded in the departmental procedure register.
As a part of the screening process, predonation hematological values of all donors, such as PLTs, hemoglobin (Hb), hematocrit, and white blood cell count, were measured using a routinely calibrated automated cell counter (Beckman Coulter Inc, California, USA).
Reporting and documenting donor reactions
Procedure details were explained to the donors and all were directed to report any form of discomfort or uneasiness immediately to the apheresis team. Donors were also observed for any specific significant reactions.
Any donor reaction, physiologic or adverse, was reported accordingly, and details of each reaction including its management were documented and notified to medical officer in charge of apheresis section.
Statistical analysis was performed using the SPSS statistical package (IBM, SPSS, Version 14, USA). All results were calculated as mean ± standard deviation, and “P” < 0.05 was considered statistically significant.
| Results|| |
The median age of plateletpheresis donors was 31 years with a male-to-female ratio of 13:1. The median body surface area and body mass index were calculated to be 1.64 m 2 and 22.4 kg/m 2, respectively. The mean preapheresis PLT count of the donor population was 199.8 × 103/uL with a mean Hb value of 13.6 g/dl [Table 1].
|Table 1: Donor demography, hematological values & procedural factors in plateletpheresis (n=1455)|
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[Table 1] also describes the procedure-related factors in plateletpheresis. ACD infusion was significantly more in the Cobe (351 ml) compared to Amicus (269.7 ml) or Trima (290 ml; P < 0.01). Donation time was least with the Trima (63.3 min) and the value was significantly lower compared to Amicus (69.3 min; P < 0.01) and Cobe (77.3 min; P < 0.001). Total whole blood volume processed was higher in Cobe (3557.3 ml) compared to the other two machines (P< 0.01). [Table 2] depicts the adverse reaction during or after plateletpheresis. Where paresthesia due to citrate toxicity was the most common adverse reaction (32/49, 65.3%), vascular injury was observed in only five donors. Adverse reaction was significantly more with the Cobe (5.6%) compared to Amicus (3.6%) and Trima (2.5%; P < 0.01). In the present study, the overall incidence of adverse reaction in plateletpheresis was 3.4%.
| Discussion|| |
Data with regard to donor adverse effects in plateletpheresis vary from center to center despite using the modern apheresis instruments. Donor demographic and physiological profiles probably play important roles in determining such adverse effects.,, We observed that factors such as low normal PLT counts, average donor built, and average total blood volume necessitate high blood volume processing and high donor anticoagulant infusion to achieve the target yield of 3 × 1011 PLTs per unit. All these may contribute to donor adverse effects in plateletpheresis significantly. None of the 105 female donors had any adverse event despite being first-time donors and mean weight of 52 kg. This may be attributed to high PLT count (mean: 266 × 103/uL) demonstrated in our female donors, which reduced the donation time (57.9 min vs. 69.3 min, P < 0.001) and anticoagulant utilization (249 ml vs. 291 ml, P < 0.01) significantly.
Where a total of 4497 healthy donors were screened for eligible plateletpheresis, 1957 (43%) donors were selected. Most of the male donors were deferred due to low PLT count and poor venous access. The most common cause of female deferral was anemia. Female donors could withstand procedure well compared to male donors. ACD infusion was significantly more in the Cobe machine compared to Amicus or Trima (P< 0.01). Donation time was least with the Trima machine and the value was significantly lower compared to Amicus (P< 0.01) and Cobe (P< 0.001). Total whole blood volume processed was higher in the Cobe compared to the other two machines (P< 0.01). Similar observation was depicted by Tendulkar and Rajadhyaksha where total blood volume processed and donation time were higher in the Cobe compared to Amicus. While anticoagulant usage was higher with the Cobe in the current study, Tendulkar andRajadhyaksha observed a low anticoagulant use with the Cobe compared to Amicus. In another study by Keklik et al., the Trima and Amicus were comparable with regard to all parameters, except PLT yield and collection efficiency which was better with the Trima compared to Amicus.
The present study observed paresthesia or perioral tingling sensation due to hypocalcemia as the most common adverse reaction, and this was observed in 32 donors which constituted 65.3% of the total adverse reactions. Other reactions included nausea and flushing (14.3%), vasovagal episodes (12.2%), and vascular injury such as hematoma or arm pain (10.2%). None of the donors with citrate-related reactions needed intravenous therapy and were managed with oral elemental calcium in a dose of 1–1.5 g. Adverse reactions were observed more with Cobe, and this can be attributed to processing of significantly high whole blood volume and infusion of increased ACD with long donation time. To prevent future paresthesia and citrate toxicity due to hypocalcemia, we started prophylactic 1 g chewable oral elemental calcium before all plateletpheresis procedures since August 2016. Of the 197 PLT donations from August 2016 to November 2016, citrate toxicity in the form of perioral tingling was observed in 1 healthy donor. This definitely suggests the therapeutic benefit of prophylactic calcium supplement before plateletpheresis.
In context to Indian studies, Philip et al. observed 85 adverse reactions in 3120 plateletpheresis procedures with majority (52, 61%) complaining of vascular injury. Citrate reactions were observed in 30 donors. In contrast, the current study witnessed more citrate-related reactions than vasovagal reactions or vascular injury. However, majority of vascular injury can be prevented by good vein selection and skilled phlebotomist. Donor inattentiveness, excessive arm movement, or high return rate in a case of thin vein may cause vascular injury. In a multicentric study by McLeod et al., 2.18% of plateletpheresis donors suffered acute adverse reaction; most of the reactions were associated with the Hemonetics cell separator.
While volume of ACD-A usage varies with cell separators, the modern separators have been observed to utilize less anticoagulant compared to the older machines. Moreover, extracorporeal volume in modern machines is much lower than the older machine which controls the volume of blood returned to the donor, thereby enhancing adequate blood dilution throughout total extracellular fluid of the donor. Second, the body gets sufficient time to metabolize infused citrate and release the bound calcium. Despite modernization and equipment optimization, citrate-related reactions are the most common adverse events in plateletpheresis. These are due to donor individuality and variable biological and physiological donor characteristics. Das et al. depicted that hypocalcemia-like symptoms may be caused by hypomagnesemia and the authors observed significant lowering of ionized magnesium after plateletpheresis. Such situation at times may be misdiagnosed and calcium supplementation becomes unfruitful. Crocco et al. concluded that 0.3% of their whole blood and apheresis donors were complicated by adverse events; most of these reactions were mild and did not necessitate hospitalization. They reported citrate toxicity and vasovagal reactions in 189 (0.38%) and 124 (0.24%) apheresis donors, respectively. In the contrary, Leanes et al. observed that 53% of the adverse reactions were vascular injury followed by vasovagal (23.7%), lipemia (10.3%), and citrate reactions (5%). In the present study, most reactions were mild, except one low-weight (54 kg) male donor who needed help from the emergency team for prolonged vasovagal symptoms and nausea. Of 15,763 plateletpheresis procedures performed by Yuan et al. using the Trima Accel cell separator, 59 (0.37%) donors suffered adverse reactions, the most common reaction being presyncopal or syncopal episode (32.2%). Winters in a review concluded that by large, the most common apheresis-specific reaction is hypocalcemia due to citrate anticoagulation which is usually mild but at times has potential for injuring the donor severely.
| Conclusions|| |
We concluded that modern-generation apheresis machines are more donor-friendly and cause less adverse reactions compared to the older versions. In addition, good donor screening, optimized donor physiognomic and hematological values, and skilled operator are the key factors to reaction reduction by apheresis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]