Nabajyoti Choudhury

Transfusion transmitted infections: How many more?

Transfusion transmitted infections (TTI) are a great concern of safety for patients. Since the starting of blood transfusion scientifically in the early 1940s, various transfusion associated problems have come to the forefront for the scientific community. These include TTI, alloimmunization to various blood components, issues related to cold chain maintenance, platelet refractoriness, transfusion (iron) overload, transfusion associated graft versus host diseases (GvHD), immunomodulatory effects, etc. However, TTI was first observed in the process of blood transfusion in the late 1940s. Till early 1970s, blood bank personnel were only concentrating on a few blood borne infections like syphilis and serum hepatitis by “Australia antigens”. However, the scientific community was well aware that there would be multiple agents.

A prospective study for prevalence and/or development of transfusion-transmitted infections in multiply transfused thalassemia major patients

Objective: To evaluate the rate of seropositivity to hepatitis B and C and Human Immunodeficiency Virus (HIV) infections among children with β-thalassemia major receiving multiple transfusions in Ahmedabad, India, compared with healthy controls. Materials and Methods: The study was performed during January 2007 to January 2009 on multi-transfused children suffering with β-thalassemia major registered in the Prathama Blood Centre, Ahmedabad; Jeevandeep hospital, Ahmedabad; and Red Cross Blood Centre, Ahmedabad, and investigated for the prevalence and development of transfusion-transmitted infections. Hepatitis B surface Antigen (HBsAg), anti-Hepatitis C Virus (HCV) Antibodies (Ab), and HIV Ab were checked using a fourth-generation Enzyme-Linked Immunosorbent Assay (ELISA). Positive tests were confirmed by western blots. Healthy blood donors were used for the control group. Results: Hepatitis B surface antigen, anti-HCV Ab, and HIV Ab were positive in one of 96 (1.04%; 95% Confidence Interval (CI) = 0.17–1.3), 24 of 96 (25%; 95% CI = 11.4–14.2), and one of 96 (1.04%; 95% CI = 0.12–1.3), respectively. The rate of anti-HCV Ab was significantly higher in multi-transfused children suffering with β-thalassemia major. In thalassemia patients, the rate of positive anti-HCV Ab was significantly higher than that for positive HBsAg (P<0.001) and HIV Ab (P<0.001). Conclusion: It is concluded that HCV is the current major problem in multi-transfused children with thalassemia major and more careful pretransfusion screening of blood for anti-HCV must be introduced in blood centers.

Blood transfusion in borderless South Asia.

One third of the world’s population lives in South Asia which is more than 1.7 billion. This region has one of the most populated countries, India, with a population of about 1.2 billion as well as smaller countries like Bhutan where population is about 0.7 million. There is a strong diversity in terms of population, culture, religion, economy and social structures. If we go by segregation of countries made by the World Health Organization (WHO), majority of the countries in south Asia falls under South East Asian Regional Offi ce (SEARO). This region has eleven countries i.e. Bangladesh, Bhutan, DPR Korea, India, Indonesia, Maldives, Myanmar, Nepal, Thailand, Timor-Leste, Sri Lanka. However, for this discussion, we will include Pakistan which is our immediate neighbor. As per WHO classifi cation, it falls under Eastern Mediterranean region. In subsequent discussions, few fi gures may exclude data from Pakistan as it was compiled on SEARO data. The whole region is one of the most populous regions of the world but global disease burden is disproportionate to the population. There is very heavy disease burden of maternal and child mortality/ morbidity, infectious diseases like malaria, tuberculosis (including drug resistance strain), HIV, other neglected topic diseases and also newly emerging diseases like SARS and pandemic infl uenza. However, positive growth in the health sector in last two decades in these countries is very encouraging. One of the main reasons is emerging economy and external intervention in the health sector.

Need to change present regulatory framework for blood banks in India.

There is continuous debate among blood bank personnel whether blood bank should come under the purview of the regulatory authority overseeing Food and Drug Administration (FDA). We, blood bankers (per se transfusion medicine specialists), want to justify this fact that it should be out of FDA purview because blood is not a drug but liquid tissue. This is a true statement. However, we should remember that all blood and blood components have medicinal values. For example, we expect a rise of 1 g% of hemoglobin after transfusion of every unit of whole blood or red blood cell. That is why blood banks will come under the regulatory purview of FDA for years to come as per specific regulation decided by the law of the land. We can see the same law applicable in many countries in the world to regulate blood bank industry.

Serial follow-up of repeat voluntary blood donors reactive for anti-HCV ELISA

Background: Voluntary non-remunerated repeat blood donors are perceived to be safer than the first time blood donors. This study was planned for follow-up of previous hepatitis C virus (HCV) test results of anti-HCV enzyme-linked immunosorbent assay (ELISA) reactive repeat blood donors. The aim was to suggest a protocol for re-entry of the blood donors who are confirmed HCV negative by nucleic acid test (NAT) and recombinant immunoblot assay (RIBA). A group of repeat voluntary donors were followed retrospectively who became reactive on a cross sectional study and showed HCV reactivity while donating blood regularly. Material and Methods: A total of 51,023 voluntary non remunerated blood donors were screened for anti-HCV ELISA routinely. If anybody showed positivity, they were tested by two ELISA kits (screening and confirmatory) and then confirmed infection status by NAT and or RIBA. The previous HCV test results of repeat donors reactive by anti-HCV ELISA were looked back from the records. Data of donors who were repeat reactive with single ELISA kit (in the present study) were analyzed separately from those reactive with two ELISA kits (in the present study). Results: In this study, 140 (0.27%) donors who were reactive by anti HCV ELISA were included. Out of them, 35 were repeat voluntary donors and 16 (11.43%) were reactive with single ELISA kit. All 16 donors were reactive by single ELISA kit occasionally in previous donations. Their present ELISA positive donations were negative for HCV NAT and RIBA. A total of 19 (13.57%) donors were reactive with two ELISA kits. In their previous donations, the donors who were reactive even once with two ELISA kits were consistently reactive by the same two ELISA kits in their next donations also. Conclusion: Donor sample reactive by only single ELISA kit may not be considered as infectious for disposal as they were negative by NAT and or RIBA. One time ELISA positivity was found probably due to ELISA kit specificity and sensitivity. Donors reactive with two ELISA kit should be discarded as there is a high positivity with NAT/ RIBA. However, donors reactive by two ELISA kits and negative by NAT and RIBA should be followed up and may not be deferred permanently.

Serological study on parvovirus B19 infection in multitransfused thalassemia major patients and its transmission through donor units.

Background: Human parvovirus B19 (B19) virus is a newly recognized agent for transfusion transmitted diseases. Beta-thalassemia major patients receive a hypertransfusion regimen, hence, are prone to acquire B19 infection; moreover, B19 escapes viral inactivation methods and donor units are not tested for B19, but there are just a couple of studies globally and none from the Asian continent. Hence, a study was designed to find the frequency of B19 infection and its transmission in multitransfused thalassemia patients. Materials and Methods: Ninety multitransfused beta-thalassemia major (thalassemia) patients, 32 controls (age, sex matched) without any history of transfusion were enrolled. Besides the donor units were tested in B19 un-infected patients. B19 specific IgG and IgM antibodies in the sera were analyzed by ELISA (in-house), using B19 VPI and VP2 recombinant and purified antigens; additionally HBsAg and anti-HIV and anti-HCV antibodies were tested for coexisting infections. Results: Seventy-three (81%) thalassemia patients tested positive for anti-B19 IgG antibodies as compared to seven (21%) in the controls group (P < 0.01), while anti-B19 IgM antibodies were detected in 37 (41.1%) compared to two (6.2%) in the controls (P < 0.01). Mean age of the thalassemia patient was eight years (range 2 – 18 years) and B19 infection was highest in the six-to-ten year range. Seropositivity increased with the number of transfusions. Two of the four HBsAg positive and five of the seven anti-HCV IgM antibody-positive patients also had anti-B19 IgM. After a six-month follow-up, four (25%) of the 16 seronegative patients seroconverted and anti-B19 IgM antibodies were detected in their donor units. Conclusions: Most of multitransfused thalassemics were B19 seropositive or had anti-B19 IgM; in the remaining uninfected group, B19 got transmitted through infected / IgM-positive donor units.

True positivity of anti-Hepatitis C Virus Enzyme-linked immunosorbent assay reactive blood donors: A prospective study done in western India

Background: A significant number of safe donations are removed from the blood supply, because of the reactive anti-HCV screening test results. This study aimed to assess if the HCV (Hepatitis C Virus) seropositive donors were confirmed positive or not. Materials and Methods: More than 68,000 blood donors’ samples were routinely screened and 140 samples were found to be anti-HCV ELISA reactive. These 140 samples were tested by NAT. The NAT negative samples were tested by RIBA. Analysis of samples reactive in single ELISA kit vs. two ELISA kits was done. Results: Out of 140 anti-HCV ELISA reactive samples, a total of 16 (11.43%) were positive by NAT. The results of 124 RIBA showed 6 (4.84%) positive, 92 (74.19%) negative, and 26 (20.97%) indeterminate results. None of the sample which was reactive in only single ELISA kit was positive by NAT or RIBA. Conclusion: Only a minority of blood donors with repeatedly reactive anti-HCV screening test is positive by confirmatory testing, but all these blood units are discarded as per existing legal provisions in India. Efforts should be made to retain these donors and also donor units.

Analysis of efforts to maintain safe donor in main donor pool after completion of temporary deferral period

Background: Voluntary blood donation is not satisfactory all over India. In India, about 55% of donation is through voluntary non-remunerated blood donors (VNRBD). However, about one third already motivated blood donors are deferred due to stringent screening criteria, either temporarily or permanently. The temporarily deferred donors could be a good source of blood donation after deferral period. Aims: The present study is carried out to know retrieval of blood donors those who are deferred temporarily. Design: The present study is carried out in the Regional Blood Transfusion Centre of Western India. All donors screened as per the guideline and deferred donors are categorized as temporary and permanently deferred donors. Materials and Methods: From temporarily deferred donors, reason for deferral is considered. As per reason of deferral, time duration for recalling the donor is defined. Based on this, donor is called back to donate again. Statistical Analysis: Chi-square test is applied. Result: A total of 33% donors were deferred either temporarily or permanently. In the repeat donors (5.32%) deferral rate was significantly higher than first time (1.32%) donors. Significant female preponderance was observed (15.05% vs 2.51%). Majority of temporarily deferred donors were less than 40 years of age (80.80%), graduate (82.90%), from low income group (62.90%) and profession was service (48.10%). Conclusion: Low hemoglobin (78.30%) was the most common reason of temporary deferral, both in first time and repeat donors (71.00%). Efforts to increase the hemoglobin in the repeat donors will improve the donor retention and overall blood safety can be increased.

Visual detection of hemolysis in a blood bag before issue

Hemolysis may occur in a red blood cell (RBC) unit during blood collection, transportation, preservation and or different stages of handling in the blood bank. Visual detection of hemolysis of a unit is possible usually by observing the color of the supernatant plasma. It is a good practice to observe the color of the plasma just before issue to avoid any inadvertent serious transfusion of a hemolysed blood unit. However, practically it is difficult once the stationary blood unit is disturbed or there is no time to centrifuge every unit of cross-matched blood to observe the plasma color.

Deferral pattern in voluntary blood donors on basis of low hemoglobin and effect of application of digital hemoglobinometer on this pattern

Background: One of the responsibilities of blood center is to provide safety to blood donors. It is mandatory to screen a blood donor for hemoglobin (Hb) or hematocrit which should not be less than 12.5 g/dl or 38% Hct. Most commonly applied method for hemoglobin estimation is copper sulphate method, but this method has chances of false acceptance as well as false deferral. In order to avoid this chance of error, digital hemoglobinometer is used. This study was planned to analyze effect of application of digital hemoglobinometer for detection of Hb on donors, who are deferred by copper sulphate method. Materials and Methods: Total 35,339 voluntary non renumareted altruistic donors were included in this study between the periods of September 2005 to July 2006. Total deferred donors were 8622 (24.39%) and donors deferred due to hemoglobin by copper sulphate method were 4391 (50.92%). Digital hemoglobinometer was applied on 3163 deferred donors (72.03%). Results of digital hemoglobinometer were validated by known controls. Result: Digital hemoglobinometer was applied on 3163 donors who were deferred by copper sulphate method. Out of this, donors accepted by digital hemoglobinometer were 1196 (37.01%). Total repeat donors were 629 (52.50%) and first time were 567 (47.40%). Male donors were 891 (74.44%) and females were 305 (25.50%). Donors deferred with digital hemoglobinometer were 2135, out of them 1097 (51.14%) were repeat, 1038 (48.38%) were first time, 1349 (60.79%) were male, 786 (34.47%) donors were female donors. Range of hemoglobin in deferred donors was 7.0 to 12.4 and in accepted donors 12.5 to 16.4. Conclusion: By the application of digital hemoglobinometer 37.81% donors were found hemoglobin >12.5 which were deferred with copper sulphate method and unnecessary deferral of donors can be reduced to a great extent. In country like India, where blood supply is always less than the requirement, this new technique may be helpful to increase donor population but cost benefit ratio should be analyzed.