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Joanna M Heal

Publications and source records attributed to Joanna M Heal.

10 recordsLinked to original sources
PubMed2006

Soluble CD40 ligand accumulates in stored blood components, primes neutrophils through CD40, and is a potential cofactor in the development of transfusion-related acute lung injury.

Transfusion-related acute lung injury (TRALI) is a form of posttransfusion acute pulmonary insufficiency that has been linked to the infusion of biologic response modifiers (BRMs), including antileukocyte antibodies and lipids. Soluble CD40 ligand (sCD40L) is a platelet-derived proinflammatory mediator that accumulates during platelet storage. We hypothesized that human polymorpho-nuclear leukocytes (PMNs) express CD40, CD40 ligation rapidly primes PMNs, and sCD40L induces PMN-mediated cytotoxicity of human pulmonary microvascular endothelial cells (HMVECs). Levels of sCD40L were measured in blood components and in platelet concentrates (PCs) implicated in TRALI or control PCs that did not elicit a transfusion reaction. All blood components contained higher levels of sCD40L than fresh plasma, with apheresis PCs evidencing the highest concentration of sCD40L followed by PCs from whole blood, whole blood, and packed red blood cells (PRBCs). PCs implicated in TRALI reactions contained significantly higher sCD40L levels than control PCs. PMNs express functional CD40 on the plasma membrane, and recombinant sCD40L (10 ng/mL-1 mug/mL) rapidly (5 minutes) primed the PMN oxidase. Soluble CD40L promoted PMN-mediated cytotoxicity of HMVECs as the second event in a 2-event in vitro model of TRALI. We concluded that sCD40L, which accumulates during blood component storage, has the capacity to activate adherent PMNs, causing endothelial damage and possibly TRALI in predisposed patients.

CD40 Antigens↗
PubMed2006

An association of soluble CD40 ligand (CD154) with adverse reactions to platelet transfusions.

BACKGROUND: Removal of stored supernatant abrogates most transfusion reactions to leukoreduced platelets (PLTs), suggesting that PLT-derived soluble mediators are involved. PLTs are the primary source of soluble CD40 ligand (sCD40L). Engagement of the receptor for CD40L induces synthesis of proinflammatory mediators including interleukin (IL)-6, IL-8, and monocyte chemotactic protein-1 (MCP-1). STUDY DESIGN AND METHODS: Supernatants from poststorage leukoreduced PLT concentrates were assayed for white cell- (IL-6, IL-8, MCP-1) and PLT-derived (sCD40L, RANTES) inflammatory mediators. These levels were correlated with clinical outcomes. RESULTS: Of 534 transfusions, there were 12 reported (2.2%) and 2 unreported reactions (0.4%)--10 febrile and 4 allergic. Transfusions with reactions had significantly higher levels of IL-6 (2.3-fold higher; p = 0.005), IL-8 (2.2-fold higher; p = 0.001), MCP-1 (2.6-fold higher; p = 0.002), and sCD40L (1.24-fold higher; p = 0.015), but not RANTES. (1.14-fold higher; p = 0.22). The vast majority (>93%) of patients transfused with mediator levels in the highest quintile had no reactions. When levels of all five mediators were summed, the reaction rates in the first through fifth quintiles increased from 1 to 7 percent (p = 0.027). All but one reaction occurred in patients with hematologic malignancies (13 reactions/380 transfusions; 3.4%; p = 0.04 vs. other diagnoses). CONCLUSIONS: These are the first data demonstrating that a PLT-derived mediator, sCD40L, is associated with adverse transfusion events. Existing clinical factors, for example, inflammation or leukopenia, may influence whether infused mediators cause reactions.

Adult↗
PubMed2005

Decreased sepsis related to indwelling venous access devices coincident with implementation of universal leukoreduction of blood transfusions.

BACKGROUND: Randomized trials and animal models demonstrate that leukoreduction of transfusions can reduce the risk of post-operative infections. We performed a retrospective study of sepsis related to indwelling venous access devices (line related infections) before and after the July 2000 implementation of universal leukoreduction. METHODS: Line related infection data were collected from hospital infection control records for an 18-month period before and after July 2000. Transfusion histories were obtained from transfusion service records. RESULTS: Line related infections decreased in number from 150 to 98 (-35%) in transfused patients after implementation of universal leukoreduction, whereas line related infections increased from 41 to 45 (+10%) in nontransfused patients (p = 0.04). This corresponded to a decrease from 5.3 to 3.3 infections/10,000 patient days in transfused patients (p = 0.002). The infection rate remained stable in nontransfused patients at 1.5 infections/10,000 patient days both pre- and postimplementation of universal leukoreduction. Quantitatively similar decreases (33-45%) were seen in transfused surgical, medical and pediatric patients. CONCLUSIONS: A substantial and statistically significant decrease in line related infections occurred coincident with implementation of universal leukoreduction. These improved outcomes were observed in transfused but not nontransfused patients, across all clinical services, suggesting a causal relationship with universal leukoreduction.

Adolescent↗
PubMed2004

A randomized trial of washed red blood cell and platelet transfusions in adult acute leukemia [ISRCTN76536440].

BACKGROUND: Platelet transfusion is universally employed in acute leukemia. Platelet concentrate supernatants contain high concentrations of biologic mediators that might impair immunity. We investigated whether washed platelet and red cell transfusions could improve clinical outcomes in adult patients with acute leukemia. METHODS: A pilot randomized trial of washed, leukoreduced ABO identical transfusions versus leukoreduced ABO identical transfusions was conducted in 43 adult patients with acute myeloid or lymphoid leukemia during 1991-94. Primary endpoints to be evaluated were platelet transfusion refractoriness, infectious and bleeding complications and overall survival. RESULTS: There were no significant differences in infectious or major bleeding complications and only one patient required HLA matched platelet transfusions. Minor bleeding was more frequent in the washed, leukoreduced arm of the study. Confirmed transfusion reactions were more frequent in the leukoreduced arm of the study. Overall survival was superior in the washed arm of the study (40% versus 22% at 5 years), but this difference was not statistically significant (p = 0.36). A planned subset analysis of those </=50 years of age found that those in the washed, leukoreduced arm (n = 12) had a 75% survival at five years compared with 30% in the leukoreduced arm (n = 10) (p = 0.037) CONCLUSION: This study provides the first evidence concerning the safety and efficacy of washed platelets, and also raises the possibility of improved survival. We speculate that transfusion of stored red cell and platelet supernatant may compromise treatment, particularly in younger patients with curable disease. Larger trials will be needed to assess this hypothesis.

Journal Article↗
PubMed2003

WBC reduction of RBC transfusions is associated with a decreased incidence of RBC alloimmunization.

BACKGROUND: Allogeneic transfusion stimulates Th2 (humoral) immunity. A hypothesis was developed that WBC reduction, by reducing the Th2 stimulus associated with transfusions, might reduce RBC alloimmunization. STUDY DESIGN AND METHODS: The first retrospective cohort study involved determining the prevalence of newly detected alloimmunization in transfused patients with acute myeloid leukemia (AML) in our hospital in the period before WBC reduction and after its introduction for this particular group of patients. The second study involved determining the incidence of newly detected RBC alloimmunization in all transfused hospital patients during three annual periods with WBC-reduction prevalences ranging from 0 to 100 percent. RESULTS: The alloimmunization prevalence rate in AML patients was 8.2 percent in those receiving non-WBC-reduced RBCs and platelets (n=195) and 2.8 percent in those receiving only WBC-reduced components (n=215) (p=0.016). In all patients, the alloimmunization incidence rate decreased from 3.47 per 1000 antibody screens in 1987 (no WBC reduction) to 2.97 per 1000 in 1999 (40% of transfusions WBC-reduced) to 2.38 per 1000 in 2001 (100% of transfusions WBC-reduced) (p=0.0298). A decrease in alloimmunization was observed in both males and females, with the decrease more clearly evident in males. CONCLUSION: These preliminary data support the hypothesis that WBC reduction may be associated with a reduced frequency of RBC alloimmunization. These findings require confirmation and further investigation.

Blood Component Removal↗
PubMed2002

Leukocyte-reduced transfusions in cardiac surgery results of an implementation trial.

An implementation trial of leukocyte-reduced transfusions in cardiac surgery (primary coronary artery bypass graft and valve replacement) was performed from July to December 1998; comparisons were made with data from the same period in 1997. Patients from both periods were similar in important preoperative and intraoperative variables (age, sex, weight, number of units of RBCs transfused, ejection fraction). The mean total number of complications was statistically significantly decreasedfrom 0.26 complications per patient in the non-leukocyte-reduced to 0.19 in the leukocyte-reduced recipients. Overall, the mean +/- ISD costs of care per patient decreasedfrom 1997 ($27,615 +/- $33,973) to 1998 ($27,038 +/- $24,107). Mean costs decreased $1,700 per patient for recipients of leukocyte-reduced blood in 1998 compared with recipients of non-leukocyte-reduced blood in 1997 Mean costs increased $4,000 per patient in patients who did not receive transfusions in 1998 compared with 1997. Hospitalization costs decreased when leukocyte-reduced transfusions were implemented for patients undergoing cardiac surgery in our institution. Implementation of leukocyte reduction may be cost neutral or cost saving in at least some settings.

Adjuvants, Immunologic↗