A centralized hemovigilance program to assure patient safety and to promote public health has been launched for the first time in India on Dec 10, 2012 in 60 medical colleges in the first phase along with a well-structured program for monitoring adverse reactions associated with blood transfusion and blood product administration. National Institute of Biologicals (NIB) will be the National Coordinating Centre for Hemovigilance. This program will be implemented under overall ambit of Pharmacovigilance Program of India (PvPI), which is being coordinated by Indian Pharmacopoeia Commission (IPC). All medical colleges of the country will be enrolled in this program by the year 2016 in order to have a National Centre of Excellence for Hemovigilance at NIB, which will act as a global knowledge platform.
Hemovigilance; India; Medical colleges; Transfusion Reaction Reporting Form
Background and Objectives:
Different methods of platelet concentrate preparations leave behind certain number of residual leukocytes, accounting for most of the febrile nonhemolytic transfusion reactions, especially in multitransfused patients. Various inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 are generated during storage and have been implicated for these adverse effects. We have studied the levels of these cytokines and their correlation with leucocyte contents in platelet concentrates prepared by three different methods.
Study Design and Methods:
Five pools of platelet rich plasma platelet concentrates (PRP-PC) and buffy-coat platelet concentrates (BC-PC) each were prepared and divided into two halves. One half of the pool was leucofiltered (LF), whereas the other half was stored as such. Ten apheresis units were also included in the study. All the platelet concentrates were assessed for leucocyte load and cytokine content (IL-1β, IL-6, and TNF-α) on different days of storage (0, 3, and 5) using Nageotte chamber and commercially available immunoassays respectively.
There was a statistically significant rise in cytokine levels (IL-1β, IL-6, and TNF-α) in nonleucofiltered (NLF) random donor platelet concentrates (RDPs) (PRP-PC and BC-PC) during storage (day 3 and 5) whereas LF RDP concentrates (PRP-PC and BC-PC) and apheresis platelet concentrates (AP-PC) did not show any significant rise in cytokine levels (on day 3 and 5) over the baseline values at day 0.
This data suggests that although AP-PCs are superior to PRP-PC (NLF) and BC-PC (NLF) in terms of in vitro quality control parameters and cytokine generation during storage, BC-PC mode of platelet preparation followed by leucofiltration is the best method to store platelets and minimise the cytokine accumulation. This strategy is best suited for transfusion in multitransfused hematooncologic patients, who cannot afford single donor apheresis platelets.
Cytokines; leucocytes; platelet concentrate
This study was designed to perform serial assessment of alterations in platelet (PLT) count, morphology and biochemical markers of PLT activation during storage of platelet concentrates (PCs) and to correlate morphological changes with these activation markers.
Materials and Methods:
Our study included the platelet-rich plasma (PRP)-PC and buffy coat reduced PC (BC-PC) prepared from whole blood (WB) donations and the apheresis platelets (AP-PC). Routinely evaluated in vitro PLT parameters were followed. Morphology score (MS) was performed using the light microscopy, glucose and lactate concentration and soluble P-selectin (sP-selectin) level were determined using commercial kits.
The fall in mean pH from day 0 to the last day of storage was significant (P < 0.001) in all the groups. Glucose utilization was less in PRP-PC prepared from WB donations at Blood Donation Centre [PRP-PC (BDC)] when compared to PRP-PC prepared from WB donations at mobile blood drives [PRP-PC (M)] and BC-PC. Lactate accumulation was almost similar in these groups on day 3 of storage, but it was significantly lower in the AP-PC (67.54 mg/dl) except on day 5. The deterioration in MS (out of 200) was similar for PRP-PC and BC-PC on day 3 (145/144 and 145 respectively), whereas the AP-PC had a score of 161 and 147 on days 4 and 5 respectively. sP-selectin level was significantly higher in PRP-PC (BDC) in comparison to BC-PC (P = 0.001) from day 1 to day 3 and in AP-PC it was not so high (P = 0.067) even on day 5. A negative correlation existed between the MS and sP-selectin level on all days of storage within each group of PC (r = −0.351; P < 0.001) and a positive correlation was found between the MS and pH from day 0 to day 3 (r = 0.680; P = 0.004).
The AP-PCs are superior to the BC-PC and PRP-PC with respect to in vitro quality control parameters, morphological changes and biochemical markers of PLT activation. The PRP-PCs prepared from WB donations at outstation exhibiting more rapid changes should be utilized earlier for transfusion.
Biochemical markers; morphology score; platelet concentrate; storage
This study was designed to determine the prevalence and assess the risk factors responsible for platelet transfusion refractoriness in hemato-oncological patients.
Materials and Methods:
The study included 30 patients. Twelve were clinically diagnosed as aplastic anemia and the 18 were of acute myeloid leukemia. A prospective 3 months follow-up was planned to monitor the response of platelet transfusion therapy, based on their posttransfusion corrected count increment at 1st and 24th h. Based on the observations, patients were categorized into refractory and nonrefractory groups. Common nonimmunological causes such as fever, sepsis, bleeding, disseminated intravascular coagulation, chemotherapy, splenomegaly, ABO mismatch, and antithymocyte globulin therapy were monitored. Among the immunological causes, presence of antihuman leukocyte antigen (HLA) class I antibodies and platelet glycoprotein antibodies in patient's serum were monitored.
During the study period, 17 (56.66%) patients did not show desired platelet count increment. Transfusion requirements of refractory group for both red cell and platelet product were significantly higher (P < 0.05) in comparison to nonrefractory group. Among immunological causes, anti HLA class I antibodies (P < 0.013), antihuman platelet antigen-5b antibodies (P < 0.033) were significantly associated with refractoriness. Among nonimmunological causes, bleeding (P < 0.019, odd ratio 8.7), fever (P < 0.08, odd ratio 5.2), and infection (P < 0.07, odd ratio 5.4) were found to associated with refractoriness.
Platelet refractoriness should be suspected in multitransfused patients not showing expected increment in platelet counts and thoroughly investigated to frame further guidelines in order to ensure proper management of these kind of patients.
Alloimmunization; acute myeloid leukaemia; aplastic anemia; multitransfused; platelet transfusion; refractoriness
Most anti-N antibodies are naturally occurring, IgM antibodies, and not active above 25°C and are not clinically significant but IgG anti- N has also been described. Immune anti-N resulting from multiple transfusions does occur & has been implicated as the cause of hemolytic transfusion reactions and mild hemolytic disease of fetus and newborn. Anti- N reacting at room temperature can be a cause for ABO blood group discrepancy
Anti-N antibody; naturally occurring anti-N; warm reacting antibody
The development of anti-red blood cell antibodies (both allo-and autoantibodies) remains a major problem in thalassemia major patients. We studied the frequency of red blood cell (RBC) alloimmunization and autoimmunization among thalassemia patients who received regular transfusions at our center and analyzed the factors, which may be responsible for development of these antibodies.
Materials and Methods:
The study was carried out on 319 multiply transfused patients with β-thalassemia major registered with thalassemia clinic at our institute. Clinical and transfusion records of all the patients were examined for age of patients, age at initiation of transfusion therapy, total number of blood units transfused, transfusion interval, status of splenectomy or other interventions. Alloantibody screening and identification was done using three cell and 11 cell panel (Diapanel, Bio-rad, Switzerland) respectively. To detect autoantibodies, autocontrol was carried out using polyspecific coombs (IgG + C3d) gel cards.
Eighteen patients out of total 319 patients (5.64%) developed alloantibodies and 90 (28.2%) developed autoantibodies. Nine out of 18 patients with alloantibodies also had autoantibodies. Age at first transfusion was significantly higher in alloimmunized than non-immunized patients (P = 0.042). Out of 23 alloantibodies, 52.17% belonged to Rh blood group system (Anti-E = 17%, Anti D = 13%, Anti-C = 13%, Anti-Cw = 9%), 35% belonged to Kell blood group system, 9% of Kidd and 4% of Xg blood group system.
Alloimmunization was detected in 5.64% of multitransfused thalassemia patients. Rh and Kell blood group system antibodies accounted for more than 80% of alloantibodies. This study re-emphasizes the need for RBC antigen typing before first transfusion and issue of antigen matched blood (at least for Rh and Kell antigen). Early institution of transfusion therapy after diagnosis is another means of decreasing alloimmunization.
Alloimmunization; autoimmunization; thalassemia major; transfusion
The percentage of HIV cases attributable to blood transfusion has decreased significantly in the last decade. The newer 4th generation Enzyme linked immunosorbent assay (ELISA) has been shown to have increased sensitivity compared to 3rd generation ELISA.
To estimate the seroprevalence of HIV among blood donors using 4th generation ELISA assay and to compare it with the 3rd generation ELISA.
Materials and Methods:
This prospective study involved 10,200 blood donors- 6,800 were voluntary donors (3400-students and 3400-non students) and 3400 were replacement donors. All blood units were tested with 3rd as well as 4th generation ELISA. All samples found reactive or in grey zone with either 3rd or 4th generation ELISA were retested by Western blot (WB).
The seroprevalence of HIV was estimated to be 1.37/1000 donations (0.14%) with 3rd generation ELISA compared to 3.62/1000 donations (0.36%) with 4th generation ELISA (p>0.05). The seroprevalence of HIV among voluntary donors was estimated to be 1.32/1000 donations (0.13%) with 3rd generation ELISA and 3.67/1000 donations (0.36%) with 4th generation ELISA. The prevalence of HIV among replacement donors was 1.47/1000 donations (0.15%) with 3rd generation ELISA and 3.52/1000 donations (0.35%) with 4th generation ELISA.
4th generation HIV ELISA detects a higher number of seroreactive donors compared to 3rd generation ELISA. However, larger studies are required with confirmatory tests for both 3rd and 4th generation ELISA for making any policy changes.
Enzyme linked immunosorbent assay; Human immunodeficiency virus; window period; transfusion associated HIV/AIDS; blood donors
Lack of awareness and community motivation, compounded with fragmented blood transfusion services in our country, Often leads to shortage of blood. Donor recruitment and retention are essential for ensuring adequate blood supply. However, adverse events (AEs) in donors have a negative impact on donor return.
Aims and Objectives:
The present study was aimed to assess the frequency of AEs in whole blood donors and analyze the predisposing factors for AEs.
Material and Methods:
The study was conducted on allogeneic whole blood donors over a period of 14 months, i.e., from January 2002 to February 2003. A total of 37,896 donors were monitored for any AEs: 22587 (59.6%) were voluntary donors (VD) and 15,309 (40.4%) were replacement donors (RD).
Overall reaction rate was 2.5% with vasovagal reactions constituting 63.5% and hematomas 35.0% of all reactions. Vasovagal reactions showed a significant association with young age, lower weight, first time donation status, female gender, and nature of blood donation camps. Amongst male donors, RDs had more reactions (P=0.03) than VDs. Majority of donors (85%) with vasovagal reactions admitted to some fear or anxiety prior to donation. Hematoma formation occurred significantly more when less trained staff performed phlebotomy.
Donor safety is an essential prerequisite to increase voluntary blood donation. AE analysis helps in identifying the blood donors at risk of donor reactions and adopting appropriate donor motivational strategies, pre-donation counseling, and care during and after donation.
Adverse events; donors; vasovagal reactions
This study was designed to analyze the incidence and spectrum of adverse effects of blood transfusion so as to initiate measures to minimize risks and improve overall transfusion safety in the institute.
Materials and Methods:
During the period from July 2002 to July 2003 all the adverse events related to transfusion of blood and blood components in various clinical specialties were recorded. They were analyzed and classified on the basis of their clinical features and laboratory tests. Attempt was also made to study the predisposing risk factors.
During the study period 56,503 blood and blood components were issued to 29,720 patients. A total of 105 adverse reactions due to transfusion were observed during the study period. A majority of the adverse reactions was observed in hemato-oncology patients 43% (n = 45) and in presensitized patient groups 63% (n = 66). FNHTR 41% (n = 43) and allergic reactions 34% (n = 36) were the most common of all types of adverse transfusion reactions, followed by AcHTR 8.56% (n = 9). Majority of these AcHTR were due to unmonitored storage of blood in the refrigerator of wards resulting in hemolysis due to thermal injury. Less frequently observed reactions were anaphylactoid reactions (n = 4), bacterial sepsis (n = 4), hypervolemia (n = 2), hypocalcemia (n = 2), TRALI (n = 1), DHTR (n = 1), and TAGvHD (n = 1).
Analysis of transfusion-related adverse outcomes is essential for improving safety. Factors such as improvement of blood storage conditions outside the blood bank, improvement in cross-matching techniques, careful donor screening, adherence to good manufacturing practices while component preparation, bedside monitoring of transfusion, and documentation of adverse events will help in reducing transfusion-related morbidity and mortality.
Hemovigilance; transfusion reaction; adverse events of transfusion; haemolytic transfusion reaction; risk associated with transfusion
Removal of leucocytes from various blood products has been shown to minimize Febrile nonhemolytic transfusion reactions, HLA alloimmunization, platelet refractoriness in multitransfused patients and prevention of transmission of leukotropic viruses such as EBV and CMV. Rapidly growing size of hemato-oncological patients in our country requiring multiple transfusion of blood and components during the course of their management pose a great challenge to transfusion services to provide them red cell and platelet antigen matched products in alloimmunized subjects. Thus removal of leucocytes below a certain threshold, ≤ 5 × 106 in a blood component certainly helps in prevention of alloimmunization and associated risks in these patients. Currently the best Leucoreduction can be achieved with the help of 3rd and 4th generation leukofilters, both in laboratory and patient bed side, and state of the art apheresis devices. The present article briefly reviews the current literature for pros and cons of leucofilteration and its scope of implementation in the cost constrained settings.
Blood component; developing countries; leukoreduced component
Platelet rich plasma-platelet concentrate (PRP-PC), buffy coat poor-platelet concentrate (BC-PC), and apheresis-PC were prepared and their quality parameters were assessed.
In this study, the following platelet products were prepared: from random donor platelets (i) platelet rich plasma - platelet concentrate (PRP-PC), and (ii) buffy coat poor-platelet concentrate (BC-PC) and (iii) single donor platelets (apheresis-PC) by different methods. Their quality was assessed using the following parameters: swirling, volume of the platelet concentrate, platelet count, WBC count and pH.
A total of 146 platelet concentrates (64 of PRP-PC, 62 of BC-PC and 20 of apheresis-PC) were enrolled in this study. The mean volume of PRP-PC, BC-PC and apheresis-PC was 62.30±22.68 ml, 68.81±22.95 ml and 214.05±9.91 ml and ranged from 22-135 ml, 32-133 ml and 200-251 ml respectively. The mean platelet count of PRP-PC, BC-PC and apheresis-PC was 7.6±2.97 × 1010/unit, 7.3±2.98 × 1010/unit and 4.13±1.32 × 1011/unit and ranged from 3.2 –16.2 × 1010/unit, 0.6-16.4 × 1010/unit and 1.22-8.9 × 1011/unit respectively. The mean WBC count in PRP-PC (n = 10), BC-PC (n = 10) and apheresis-PC (n = 6) units was 4.05±0.48 × 107/unit, 2.08±0.39 × 107/unit and 4.8±0.8 × 106/unit and ranged from 3.4 -4.77 × 107/unit, 1.6-2.7 × 107/unit and 3.2 – 5.2 × 106/unit respectively. A total of 26 units were analyzed for pH changes. Out of these units, 10 each were PRP-PC and BC-PC and 6 units were apheresis-PC. Their mean pH was 6.7±0.26 (mean±SD) and ranged from 6.5 – 7.0 and no difference was observed among all three types of platelet concentrate.
PRP-PC and BC-PC units were comparable in terms of swirling, platelet count per unit and pH. As expected, we found WBC contamination to be less in BC-PC than PRP-PC units. Variation in volume was more in BC-PC than PRP-PC units and this suggests that further standardization is required for preparation of BC-PC. As compared to the above two platelet concentrates, all the units of apheresis-PC fulfilled the desired quality control criteria of volume. Apheresis-PC units showed better swirling and platelet count than PRP-PCs and BC-PCs. All the platelet concentrates units had pH well above the recommended norm.
Corrected count increment; buffy coat poor-platelet concentrate; percentage recovery; platelet concentrate; platelet rich plasma-platelet concentrate; random donor platelet; single donor platelets