Red Cell Exchange as Adjunctive Therapy for Babesiosis: Is it Really Effective?
Tannous T, Cheves TA, Sweeney JD
Transfusion medicine reviews. 2021
Human babesiosis is a parasitic disease prevalent in the Northeastern and Midwestern United States (US). Treatment with antibiotics is the standard of care but red cell exchange (RCE) has been used as an adjunctive treatment in more severe disease. Data for the efficacy of RCE in the treatment of babesiosis has been based on case reports and case series. An English language literature search was conducted for cases of babesiosis treated with RCE since 1980 and relevant laboratory and clinical outcome data were extracted. Similar data were obtained on severe cases of babesiosis referred for RCE in our hospitals in the time period 2000 to 2020. Fifty reports including forty-one individual case reports and nine case series were retrieved. There were 108 patients that underwent RCE with an overall mortality rate of 20%. Some patients had more than one RCE. The patients varied in the level of anemia and evidence of compromise of renal or pulmonary function. The pre-RCE level of parasitemia varied between 1.7% to 85% with the vast majority >10%. The post-RCE level of parasitemia varied between 1% to 10%. Since 2000, 32 patients were referred for RCE in our hospitals and RCE was performed on 23 of 32. There were more patients treated with RCE in the second decade as compared to the first decade, 19 versus 4 respectively. The overall mortality was 22% similar to the national data. Comparing the cohort treated with RCE to the 9 patients who were treated only with antibiotics, there were similar levels of parasitemia and laboratory parameters. The overall number of days needed to achieve a parasite count <1% was similar between the two cohorts and mortality for the antibiotics only cohort was 0%. More than 40 years after the first reported case of RCE in severe babesiosis it cannot be concluded that this adjunctive therapy favorably influences the clinical outcome. Since there is largely equipoise, a registry of severe patients treated with or without RCE could identify a benefit or otherwise.
The effect of blood storage age on treatment of lactic acidosis by transfusion in children with severe malarial anaemia: a pilot, randomized, controlled trial
Dhabangi A, Mworozi E, Lubega IR, Cserti-Gazdewich CM, Maganda A, Dzik WH
Malaria Journal. 2013;12:55
BACKGROUND Severe malarial anaemia requiring blood transfusion is a life-threatening condition affecting millions of children in sub-Saharan Africa. Up to 40% of children with severe malarial anaemia have associated lactic acidosis. Lactic acidosis in these children is strongly associated with fatal outcomes and is corrected by blood transfusion. However, it is not known whether the storage age of blood for transfusion affects resolution of lactic acidosis. The objective of this pilot study was to evaluate the effect of blood storage age on resolution of lactic acidosis in children with severe malarial anaemia and demonstrate feasibility of conducting a large trial. METHODS Children aged six to 59 months admitted to Acute Care Unit of Mulago Hospital (Kampala, Uganda) with severe malarial anaemia (haemoglobin<=5g/dL) and lactic acidosis (blood lactate >=5mmol/L), were randomly assigned to receive either blood of short storage age (one to 10 days) or long storage age (21-35days) by gravity infusion. Seventy-four patients were enrolled and randomized to two equal-sized study arms. Physiological measurements, including blood lactate, oxygen saturation, haemoglobin, and vital signs, were taken at baseline, during and after transfusion. The primary outcome variable was the proportion of children whose lactic acidosis resolved by four hours after transfusion. RESULTS Thirty-four of 37 (92%) of the children in the short storage treatment arm compared to 30/37 (81%) in the long storage arm achieved a blood lactate <5mmol/L by four hours post transfusion (p value=0.308). The mean time to lactic acidosis resolution was 2.65hours (95% CI; 2.25-3.05) in the short storage arm, compared to 3.35hours (95% CI; 2.60-4.10) in the long storage arm (p value=0.264). CONCLUSION Pilot data suggest that among children with severe malarial anaemia and lactic acidosis transfused with packed red blood cells, the storage age of blood does not affect resolution of lactic acidosis. The results support a larger and well-powered study which is under way. TRIAL REGISTRATION clinicaltrials.gov NCT01580111.
Absence of activation of CMV by blood transfusion to HIV-infected, CMV-seropositive patients
Drew WL, Chou S, Mohr BA, Assmann SF, Miner RC, Laycock ME, Busch MP, Viral Activation Transfusion Study Group
BACKGROUND The Viral Activation Transfusion Study (VATS) afforded an opportunity to determine whether blood transfusions, and in particular exogenous WBCs, activateCMV replication in HIV-infected, CMV-seropositive patients, and whether such patients can be superinfected by additional strains of CMV transmitted via blood transfusions. STUDY DESIGN AND METHODS A total of 531 patients were randomized to receive either WBC-reduced (WBCR) or non-WBC-reduced (NWBCR) RBC units. Plasma CMV PCR assays were performed before transfusion and weekly after transfusion for 4 weeks. NWBCR cases with evidence of possible reactivation and/or superinfection were further studied for donor viremia by DNA PCR of frozen retention segments and new genotype acquisition using gB envelope sequence analysis of pre- and posttransfusion recipient specimens. RESULTS VATS patients received a median of two RBC units during their initial transfusion. Whether positive or negative for CMV DNA at baseline, there were no significant treatment-arm differences in the percentage of patients who had positive qualitative CMV PCR or increases in CMV viral load at follow-up. Of 50 recipients randomized to NWBCR RBC and meeting criteria for possible CMV superinfection, 25 had sufficient CMV DNA load in a baseline and one or more viremic follow-up sample to permit comparison of gB genotypes. Only two recipients showed genotype shifts. Of 125 WBC pellets prepared from the seropositive units transfused into these 50 cases, only 1 tested weakly PCR positive for CMV DNA (insufficient copy number for genotyping). CONCLUSION There was no evidence of activationof CMV by blood transfusion. Among the NWBCR RBC recipients, there was little evidence of possible transmission of new CMV strains. Hence, the current policy for transfusion support of HIV-infected patients, which allows transfusion of CMV-antibody-positive blood to CMV-seropositive patients, is appropriate.
The transfusion trigger and number of units transfused in patients with HIV: associations with disease stage and functional status
Kennedy MS, Kalish LA, Mohandas K, Gernsheimer T, Townsend-McCall D, Viral Activation Transfusion Study Group
BACKGROUND The influence of quality of life (QOL), physical functioning, and HIV disease stage on the transfusion trigger and the number of units transfused was investigated. STUDY DESIGN AND METHODS The Viral Activation Transfusion Study, a randomized, double-blind study at 11 participating sites, enrolled HIV-positive patients with anemia who required RBC transfusion; 428 patients were included in the analysis of the first transfusion. The QOL scores, Perceived Health Index, Karnofsky score, CD4+ cell count, HIV viral load, and site were analyzed for relationships with the Hb level and the number of units transfused. RESULTS The transfusion trigger was lower in patients with higher levels of Karnofsky score, Perceived Health Index, CD4+ cell count, and a number of QOL scales. Both the Hb trigger and the number of units transfused had a significant site variation. Males were transfused at a significantly lower Hb level than females. In multivariate analysis, the CD4+ cell count remained significant, but the Karnofsky score or the Perceived Health Index did not. The number of RBC units transfused was associated with the Hb level, CD4+ cell counts, and Karnofsky scores in unadjusted analysis but with only Hb in adjusted analysis. CONCLUSIONS In this group of HIV+ patients, lower CD4+ cell counts prompted transfusion at higher Hb levels. However, after controlling for the Hb level, the number of units transfused was associated with only the Hb level. The HIV stage appears to influence the decision to transfuse at a particular Hb level but not to influence the number of RBC units transfused. The functional status does not appear to influence the decision to transfuse.
Signs and symptoms associated with the transfusion of WBC-reduced RBCs and non-WBC-reduced RBCs in patients with anemia and HIV infection: results from the Viral Activation Transfusion Study
Lane TA, Gernsheimer T, Mohandas K, Assmann SF
BACKGROUND RBC transfusion is associated with fever and other reactions in some patients. The Viral Activation Transfusion Study randomly assigned patients to receive either unmodified or WBC-reduced RBCs and thus offered an opportunity to assess the effect of WBC-reduced RBCs on the incidence of transfusion reactions prospectively. STUDY DESIGN AND METHODS This prospective, randomized, double-blind, multicenter study compared prestorage WBC-reduced RBCs to unmodified RBCs in HIV-infected, CMV-seropositive, and transfusion-naive persons who required transfusions for anemia. Primary endpoints were survival and change in the plasma HIV RNA level at 7 days after transfusion. The incidence of transfusion reactions was prospectively evaluated. RESULTS The two groups had similar baseline characteristics and study endpoints; 3864 RBC units (median storage age, 9 days) were administered to 531 patients during 1745 transfusions. The most frequent signs reported were elevated temperature and hypotension. Subjects who reported fever within the week prior to transfusion were more likely to have an elevation in temperature associated with transfusion. The administration of RBCs that were less than 10 days old was associated with a marginal increase in the incidence of transfusion-associated temperature elevation among recipients of unmodified RBCs, but not among recipients of WBC-reduced RBCs. Caregivers reported fewer instances of both elevated temperature and hypotension than were identified by review of transfusion records. CONCLUSIONS The incidence of elevated temperature and hypotension associated with transfusion in this population was unexpectedly high. Use of WBC-reduced RBCs had no effect on the overall rates of elevated temperature or hypotension associated with transfusion of RBCs. The occurrence of a pre-existing fever was associated with a higher frequency of transfusion-associated elevated temperature.
Leukocyte-reduced red blood cell transfusions in patients with anemia and human immunodeficiency virus infection: the Viral Activation Transfusion Study: a randomized controlled trial
Collier AC, Kalish LA, Busch MP, Gernsheimer T, Assmann SF, Lane TA, Asmuth DM, Lederman MM, Murphy EL, Kumar P, et al
CONTEXT Allogeneic blood transfusions have immunomodulatory effects and have been associated with activation of human immunodeficiency virus (HIV) and cytomegalovirus (CMV) in vitro and of HIV in small pilot studies. Retrospective studies suggest that transfusions adversely affect the clinical course of HIV. Data in selected non-HIV-infected patients requiring blood transfusion have suggested clinical benefit with leukocyte-reduced red blood cells (RBCs). OBJECTIVE To compare the effects of leukoreduced and unmodified RBC transfusions on survival, complications of acquired immunodeficiency syndrome, and relevant laboratory markers in HIV-infected patients. DESIGN AND SETTING Double-blind randomized controlled trial conducted in 11 US academic medical centers from July 1995 through June 1999, with a median follow-up of 12 months (24 months in survivors). PATIENTS A total of 531 persons infected with HIV and CMV, aged 14 years or older, who required transfusions for anemia; 259 received leukoreduced transfusions and 262 received unmodified transfusions (10 did not receive the planned transfusion). MAIN OUTCOME MEASURES Survival and change in plasma HIV RNA level 7 days after transfusion, compared by type of transfusion. RESULTS At entry, the groups were similar in demographic, clinical, and relevant laboratory characteristics. A total of 3864 RBC units were transfused. Two hundred eighty-nine deaths occurred (151 with leukoreduced transfusion; 138 with unmodified transfusion); median survival was 13.0 and 20.5 months, respectively (relative hazard [RH], 1.20; 95% confidence interval [CI], 0.95-1.51; log-rank P =.12). Analyses adjusted for prognostic factors suggested possible worse survival with leukoreduction (RH, 1.35; 95% CI, 1.06-1.72). There was no difference in time to new opportunistic event/death or frequency of transfusion reactions. No changes in plasma HIV RNA level were seen in either group at days 7, 14, 21, or 28, even in patients not taking antiretroviral drugs. There were no differences in trends between groups in CMV DNA, CD4 cell counts, activated (CD38% or human leukocyte antigen-DR) CD8 cell counts, or plasma cytokine levels. CONCLUSIONS We found no evidence of HIV, CMV, or cytokine activation following blood transfusion in patients with advanced HIV infection. Leukoreduction provided no clinical benefit in these patients. These data demonstrate the importance of conducting controlled studies of effects of leukoreduction in different patient populations, since smaller studies in other patient populations have suggested leukoreduction may be beneficial.
Number of RBC units and rate of transfusionto anemic HIV-positive patients assigned to receive WBC-reduced or non-WBC-reduced RBCs: the Viral Activation Transfusion Study experience
Brecher ME, Triulzi DJ, Assmann SF, Viral Activation Transfusion Study
BACKGROUND It is known that the use of filtration to reduce WBCs in RBC units is associated with a 6- to 15-percent loss of RBCs. It is not known if the use of such WBC-reduced RBCs results in an increased need for RBC units or in the transfusion of more units per year to patients with anemia. STUDY DESIGN AND METHODS In the multicenter Viral Activation Transfusion Study (VATS), anemic HIV-positive patients were randomly assigned to receive either WBC-reduced or non-WBC-reduced RBCs. The number of RBC units transfused per patient and the rate of RBC use were studied. All RBC units given after the enrollment transfusion were counted, until the end of follow-up or the occurrence of bleeding (receiving >5 RBCs within 2 consecutive days). RESULTS As expected, the WBC-reduced RBC units in VATS were lighter in weight than the non-WBC-reduced units (median weight: WBC-reduced, 300 g; non-WBC-reduced, 330 g; p<0.0001). After the enrollment transfusion, 258 WBC-reduced arm patients received 1279 units of RBCs (average, 5.0 units/patient, median, 2 units) while 262 patients in the non-WBC-reduced arm received 1111 RBCs (4.2 units/patient; median, 2 units). The number of units transfused for anemia was slightly greater in the WBC-reduced arm, but the difference was not significant (p = 0.41). Similarly, the rate of RBC use was somewhat higher in the WBC-reduced arm, but the difference was not significant (p = 0.14). The median was 2.3 units per patient per year of follow-up in the WBC-reduced arm; the median in the non-WBC-reduced arm was 1.2 units. CONCLUSION This study confirms that WBC-reduced RBC units are significantly lighter in weight than non-WBC-reduced RBCs. However, in the setting of a large, randomized, blinded study of transfusion for anemia, the smaller size of the WBC-reduced RBC units had no significant effect on the number of RBC units transfused or on the rate at which RBC units were used. In this study, the frequency of blood transfusion may have had a greater relationship to the frequency of routine, scheduled appointments or transfusion orders for a specified Hb trigger than to the actual Hb content of the unit.
WBC reduction in RBC concentrates by prestorage filtration: multicenter experience
Yomtovian R, Gernsheimer T, Assmann SF, Mohandas K, Lee TH, Kalish LA, Busch MP, Viral Activation Transfusion Study Group
BACKGROUND As universal leukocyte (WBC) reduction (ULR) is being considered as a new standard, few data are available on the performance of WBC-reduction filtration in routine practice. The performance of WBC-reduction in RBCs, using varied filtration practices, in meeting the current FDA requirement (<5 x 10(6)), Council of Europe (EC) recommendation, the proposed FDA requirement (<1 x 10(6)), and a more stringent proposal (<5 x 10(5)) for residual WBCs per RBC unit was assessed and compared. STUDY DESIGN AND METHODS Participating facilities were the 11 sites of the Viral Activation Transfusion Study (VATS), a prospective study of the impact of transfusion with and without WBC-reduction on survival and HIV viral load in HIV-1-infected patients. Patients randomly assigned to undergo WBC reduction were required to receive RBCs < or =14 days old that had undergone prestorage (within 72 hours of collection) WBC-reduction filtration by a method devised to achieve a postfiltration WBC count of <5 x 10(6). Residual WBC quantitation was performed by PCR in the central VATS laboratory by using frozen WBC-reduced RBC samples obtained at issue for transfusion. RESULTS A total of 1869 WBC-reduced RBC units were studied. Filtration practices varied within and between sites. There were significant differences in mean residual WBC counts at the 11 sites (p<0.001). Among the WBC-reduced RBC units, 0.8 percent exceeded 5 x 10(6) WBCs per unit, 8.3 percent exceeded 1 x 10(6) WBCs per unit, and 14.3 percent exceeded 5 x 10(5) WBCs per unit. CONCLUSION Residual WBCs in WBC-reduced RBC units vary within and between sites. WBC reduction was successful, in that over 99 percent and 91 percent of VATS WBC-reduced RBC units met US and EC thresholds, respectively. However, the small but measurable failure rate indicates that not every unit will meet these guidelines.
Blood transfusion for treating malarial anaemia
Meremikwu M, Smith HJ
Cochrane Database of Systematic Reviews. 1999;((4):):CD001475.
BACKGROUND Blood transfusion is used in patients with severe malarial anaemia, but risks adverse reactions, transmission of disease, and is complicated to organise in developing countries. OBJECTIVES This review evaluates the effects of routine blood transfusion for severe anaemia on death and adverse outcomes in malarious areas. SEARCH STRATEGY We searched the Cochrane Infectious Diseases Group Specialized Register (July 2006), CENTRAL (The Cochrane Library Issue 3, 2006), MEDLINE (1966 to July 2006), EMBASE (1980 to July 2006), LILACS (July 2006), and reference lists of relevant articles. We contacted researchers and organizations working in the field. SELECTION CRITERIA Randomised and quasi-randomised trials of blood transfusion compared with conservative management in malaria-associated severe anaemia. DATA COLLECTION AND ANALYSIS Trials were identified and data extracted by a single reviewer (MM) and checked by a second (HS). Inclusion criteria were applied and data were extracted independently by both reviewers. MAIN RESULTS Two randomised trials of 230 children were included. In the transfusion group, there was a non-signficant tendency towards fewer deaths (RR 0.41, 95% CI 0.06 to 2.70), but a trend towards more severe adverse events (RR 8.60, 95% CI 1.11 to 66.43). In one trial by Bojang (1997a) respiratory distress was less common and hospital stay was shorter in the transfusion group (WMD 1.88 days, 95% CI 2.41 to 1.35). Subsequent need for urgent blood transfusion was less common in the transfusion group (RR 0.12, 95% CI 0.02 to 0.68). Day 28 packed cell volume was less in the transfusion group (WMD -1.34, 95% CI -2.57 to -0.11). There was no information on HIV or Hepatitis B virus transmission. AUTHORS' CONCLUSIONS There is insufficient data to be sure whether routinely giving blood to clinically stable children with severe anaemia in endemic malarious areas reduces death, or results in higher haematocrit measured at one month.
Impact of transfusion on viral load in human immunodeficiency virus infection
Seminars in Hematology. 1997;34((3, Suppl 2):):27-33.
Recent research has shown that anemia and transfusion are associated with accelerated mortality in patients with human immunodeficiency virus type 1 (HIV-1) infection. It appears that blood transfusions may directly accelerate HIV-1 disease progression through activation of HIV-1 expression and/or transfusion related immunosuppression. In vitro and in vivo evidence suggests that immunization with common recall antigens (eg, tetanus toxoid) can significantly increase plasma HIV viremia, as well as the in vitro susceptibility of peripheral blood mononuclear cells to acute infection. Allogeneic leukocytes also present an antigenic challenge to HIV-infected mononuclear cells, which may cause them to proliferate and increase viral production. In vitro incubation of HIV-infected mononuclear cells with allogeneic blood components (mainly leukocytes) results in increased viral replication. Whether the effects of transfusion on HIV viral load are due to a reduced immune response and/or activation of the virus itself remains to be determined. An ongoing study is evaluating the effects of depleting leukocytes from blood prior to transfusion in HIV-infected patients. Patients are randomized to receive standard of leukocyte-depleted red blood cell (RBC) transfusions and the effect of transfusion on HIV replication is measured. Preliminary data suggest that leukocyte depletion prior to RBC transfusion does not alter viral replication compared with standard packed RBC transfusions.