Year : 2016 | Volume : 4 | Issue : 4 | Page : 208 - 210  

Original Articles
Adverse events associated with apheresis procedures: incidence and relative frequency

Sujatha P 1, Sreenivasa Murthy K 2, Kruthika S Margam 3

1 Professor, Department of Pathology, Malla Reddy Institute of Medical Sciences, Hyderabad

2 Dhanvantari Blood Bank, Kakinada

3 MBBS Scholar, Gandhi Medical College, Secunderabad

Corresponding Author:

Dr. Sujatha P



Background: Apheresis procedures [plateletpheresis, plasmapheresis, peripheral blood stem cell collection] are usually well tolerated. Occasionally Adverse Events (AEs) of variable severity may occur during or after the procedure. AEs that occur in Donor/ Patients are divided into local reactions and systemic reactions.

Objective: To study adverse events associated with apheresis procedures.

Methods: A total of 768 plateletpheresis were performed on Haemonetics MCS + cell separator in one of the major blood banks whose annual blood collection was between 8000 and 10000 units.

Results: 21 AEs were reported. Out of which the rate of vascular injury (VI) citrate reaction (CR) and presyncopal/syncopal (PS/S) in plateletpheresis were 1.56% (12/768), 0.91 % (7/768) and 0.26 % (2/786) respectively.

Conclusion: Apheresis procedures performed on cell -separators are safe with low incidence of significant AE Apheresis procedures are usually well tolerated. However adverse events (AE) of variable severity may occur during or after the procedure. AEs that occur can be divided into local reactions and systemic.

Key words: adverse events, citrate reaction, vascular injury


Local reactions are usually hematomas due to extravasations of blood from the vein, caused by the in correct placement of the needle during the venipuncture. Pain hyperemia and swelling may develop at the site of the extravasations. Local phlebitis and thrombophlebitis is rare. 1

Systemic reactions are mainly vasovagal reactions that can be triggered by the pain of the venipuncture, or by the anxiety of undergoing the donation. These are characterized by the pallor, sweating, dizziness, nausea, hypotension, bradycardia and syncope. Citrate toxicity occurs because of the use of Acid-Citrate- Dextrose (ACD) in apheresis. 2


A total of 768 (254 in 2012, 248 in 2013 and 266 in 2014) apheresis procedures were performed during three year period in a major blood bank. A single needle intermittent type of cell separator, MCS + (HAEMONETICS) was used. All donations were collected using a 16 gauge needle inserted into a vein in the ante-cubital fossa, with all the aseptic precaution.

Donors were selected as per the set criteria for single donor platelet (SDP) preparation according to AABB guidelines:

  • Weight: >50 kg
  • Age: 18 to 60 years
  • Gap: At least three months from last donation/ three days from last plateletpheresis
  • Hemoglobin >12.5 gm/dl
  • Platelet count > 150 x 103 /l
  • Absence of any illness
  • No consumption of non- steroidal anti-inflammatory drugs for last seven days. Negative test for HIV, Hepatitis B, Hepatitis C, Syphilis and Malaria.

All adverse events were recorded by the staff. The adverse events occurring during or after were classified as vascular injuries (VI) citrate reaction (CR) presyncopal/syncopal (PS/S) and PS + CR (Table 1)


A total of 768 procedures of three year study period were analyzed. All AEs were divided into mild/moderate to severe reaction (Table 2). 22 AE were reported to the total 768 plateletpheresis procedures. The rate of Vascular Injuries (VI) Citrate Reaction (CR) and Presyncopal/Syncopal (PS/S) were 1.56% (12/768), 0.91 % (7/768), and 0.39 % (3/768) respectively VI, CR, and PS/S were mostly of mild intensity no severe adverse reaction were observed during the study period.


Total Number of Procedures each year





Total Adverse Events
























12 (1.56%)

7 (0.91%)

3 (0.39%)



Out of 12 VI (Pain/ Bruising/ hematoma) 8 occurred during procedure and 4 after the plateletpheresis. All 7 CR were mild /moderate (circumoral paraesthesia/ tingling and numbness). No severe reaction (tetany) was reported. 3 PS/S were noted. But no combined case of PS + CR was reported.


Modern blood transfusion advocates optimal use of every blood donation by way of blood component preparation. The development of plastic blood collection bags, integral tubing, high speed refrigerated centrifuge, deep freezers, and cell separator machines have made blood component preparation easier and practical.

The adverse events during the process of plateletpheresis have been broadly divided into: 3, 4, and 5

  • Venipuncture related
  • Syncope/faintness/sweating
  • Citrate reaction

The increased percentage of hematoma using MCS + HAEMONETICS equipment could be as a result of the fact that the same vein in one arm is used for inflow and return of the blood resulting in trauma and hematoma formation.

Citrate reaction (CR): Citrate is used as the primary anticoagulant in donor apheresis procedures. The anticoagulant effect of citrate is due to chelation of calcium ions. The non-availability of calcium ions hinders the coagulation cascade. Normally citrate is quickly metabolized in the body, but if the amount of citrate infused exceeds the body’s ability to metabolize it then the donor may feel numbness or tingling sensation around the mouth, shivering light headedness, twitching and tremors. In addition, some patients experience nausea and vomiting. In severe cases the symptoms may progress to carpopedal spasm, tetany and seizure. In our study Citrate Reactions were mild.

The treatment for citrate reaction is simple. The rate of infusion of returning component is reduced. And exogenous calcium supplementation is given to the donor. In our study we gave 1 gm of calcium carbonate orally. The administration of oral calcium carbonate and its effects on Citrate toxicity have examined by Bolan et al 2 These authors found that administration of calcium carbonate was associated with significant reduction in the severity of par aesthesia

In our study the vasovagal reaction (syncopal/ faintness/ sweating) occurred in the form of sweating. This can be attributed to apprehension. Tomita et al 3 noted that hypocalcaemia may be involved in the onset of vasovagal reactions in apheresis donors.

Hypovolemia and vasovagal reaction are treated similarly. The procedure should be temporarily paused and fluid infusion should be started. If the reaction is due to hypovolemia the blood pressure should increase and the pulse rate should decrease in response to intervention. Additional treatment for vasovagal reactions includes placing the donor in Trendelenburg position.

The overall rate of acute adverse reactions, among the healthy donors undergoing plateletpheresis procedures in our study was 2.86% This is similar to McLeod et al 1 multi – institutional study ( 2.18 %.) Frequency of VI, CR AND PS/S in plateletpheresis was 1.6%, 1% and 0.09% respectively. Our study findings were also similar; 1.56%, < 1% and 0.39%. Frequency of PS/S was 0.83% in a study done by Tomita et al 3 which is more in comparison to our study (0.39%). Frequencies of these AEs studied by other authors are almost equal to the results seen in our study.

Overall apheresis donation performed on cell separators are safe and have acute reaction rates less than those seen in whole blood donation. The acute adverse effects of donation are relatively mild and easily treated. However recent evidence suggests that repeated apheresis donation may produce long term adverse effects in donors such as bone demineralization and cataract formation. 6, 7 Additional researches are needed to ascertain the risks of long –term apheresis donation.

Table 1: Definition and Predominant Symptoms of Types of Donor AEs



Predominant Symptoms


Vascular Injury (VI)

Bruising or Hematoma at venipuncture site, maybe with Pain, Tingling or Bruising Sensation


Citrate Reaction (CR)

Tingling, Burning Sensation, Muscle Cramps, Tetany or Seizures


Presyncopal/Syncopal (PS/S)

Pallor, Hypotension, Weakness, Syncopal Attack, Light Headedness, Tachy/Brady cardia


Presyncopal and Citrate Reaction(PS + CR)

Both symptoms are present


Table 2: Adverse Events Associated with Apheresis Procedures


Mild to Moderate




Fasting with or without fall injury


Nausea /Vomiting

Muscle Cramps


Pain, Burning Sensation, Tingling during or Post Donation

Seizures, Tetany


Twitching Movements

Laryngeal/Tongue Edema



Pain, Burning Sensation, Tingling Persistent for >48 hrs and requiring Consultation by Physician


Any Mild Symptom ( pallor, diaphoresis, light headedness, feeling of warmth, nausea ) lasting > 10 min

Any Moderate Symptom lasting >5 min


  1. McLeod BC, Price TH, Owen H et al. Frequency of Immediate Adverse Effects Associated with Aphaeresis Donation. Transfusion 1998;38:938-43
  2. Bolan CD, Greer SE, Cecco SA et al. Comprehensive Analysis of Citrate Effects During Platelet Apheresis in Normal Donors. Transfusion 2001;41:1165-71
  3. Tomita T, Takayanagi M, Kiwada K et al. Vasovagal Reactions in Apheresis Donors. Transfusion 2002;42:1561-6
  4. Brecher ME, Leger RM. AABB Technical Manual 15th, Bethesda. American Association of Blood banks 2005
  5. Winters JL, Complications of Donor Apheresis. J Clin Apher 2006;21:132-41
  6. Despotis GJ, Goodnough LT, Dynis M et al. Adverse Events in Platelets Aphaeresis Donors; A Multi Variate Analysis in a Hospital Based Program. Vox Sang 1999;77(1):24-32.
  7. Philip J, Sarkar RS, Pathak A. Adverse Events Associated with Aphaeresis Procedures. Incidence and Relative frequency. Asian J Transfusion 2013;7:37-41


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