Platelet transfusions play a central role in therapeutic regimens for patients with hematologic/oncologic diseases who develop severe thrombocytopenia either in the course of their disease or following cytostatic therapy. Like other blood components, platelet transfusions have achieved a high degree of safety as far as transmission of viral diseases is concerned. However, transfusion of platelet concentrates is accompanied by a high frequency of febrile and anaphylactoid reactions. In rare cases, recipients of platelet concentrates are threatened by severe reactions as septic complications due to bacterial contamination of platelet concentrates, transfusion-related acute lung injury and severe anaphylactic episodes.
Platelet transfusion; Transfusion reactions; Bacterial contamination of blood products; Hemolytic transfusion reactions; Febrile nonhemolytic transfusion reactions
In recent years, pulmonary transfusion reactions have gained increasing importance as serious adverse transfusion events.
Review of the literature.
Pulmonary transfusion reactions are not extremely rare and, according to hemovigilance data, important causes of transfusion-induced major morbidity and death. They can be classified as primary with predominant pulmonary injury and secondary as part of another transfusion reaction. Primary reactions include transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO) and transfusion-associated dyspnea (TAD). Secondary pulmonary reactions are often observed in the wake of hemolytic transfusion reactions, hypotensive/anaphylactic reactions, and transfusion-transmitted bacterial infections.
Knowledge and careful management of cases of pulmonary transfusion reactions are essential for correct reporting to blood services and hemovigilance systems. Careful differentiation between TRALI and TACO is important for taking adequate preventive measures.
Acute lung injury; Transfusion reaction; Transfusion risks
Background: Haptoglobin polymorphism is associated with the prevalence of infections, autoimmune diseases, cardiovascular diseases, and other disorders. Congenital haptoglobin deficiency is associated with anaphylactic transfusion reactions in anhaptoglobinaemic patients with antihaptoglobin antibody.
Aims: To investigate haptoglobin genotypic distribution (including the Hp0 allele) and associated serum haptoglobin concentrations in Koreans.
Methods: Five hundred and nine healthy Korean adults were randomly selected. Two methods were used: haptoglobin genotyping based on a polymerase chain reaction (PCR) system that exploited the structural difference of the Hp1 and Hp2 alleles, and another PCR method that detected haptoglobin gene deletion by amplification of the junctional region of the Hp0 allele. Serum haptoglobin concentrations were measured by nephelometry.
Results: The haptoglobin genotypes of 509 subjects were as follows: Hp1Hp1, 7.1%; Hp2Hp1, 37.7%; Hp2Hp2, 49.3%; Hp0Hp1, 2.2%; Hp0Hp2, 3.5%; Hp0Hp0, 0.2%. The gene frequency of Hp0 in Koreans was calculated to be 0.031. Significant differences were seen among the concentrations of each haptoglobin genotype (Kruskal-Wallis test). Hp0Hp2, but not Hp0Hp1, was associated with hypohaptoglobinaemia.
Conclusions: PCR methods for differentiating between haptoglobin genotypes, including the Hp0 allele, may be useful in a broad spectrum of basic studies and clinical examinations.
haptoglobin; genotyping; gene deletion; hypohaptoglobinemia; anhaptoglobinemia
Non-haemolytic transfusion reactions are the most common type of transfusion reaction and include transfusion-related acute lung injury, transfusion-associated circulatory overload, allergic reactions, febrile reactions, post-transfusion purpura and graft-versus- host disease. Although life-threatening anaphylaxis occurs rarely, allergic reactions occur most frequently. If possible, even mild transfusion reactions should be avoided because they add to patients' existing suffering. During the last decade, several new discoveries have been made in the field of allergic diseases and transfusion medicine. First, mast cells are not the only cells that are key players in allergic diseases, particularly in the murine immune system. Second, it has been suggested that immunologically active undigested or digested food allergens in a donor's blood may be transferred to a recipient who is allergic to these antigens, causing anaphylaxis. Third, washed platelets have been shown to be effective for preventing allergic transfusion reactions, although substantial numbers of platelets are lost during washing procedures, and platelet recovery after transfusion may not be equivalent to that with unwashed platelets. This review describes allergic transfusion reactions, including the above-mentioned points, and focusses on their incidence, pathogenesis, laboratory tests, prevention and treatment.
allergic transfusion reaction; IgE; tryptase; basophil activation test; washed platelets
In this study, we report the first Korean case of an anti-Gerbich (Ge) alloantibody to a high-incidence antigen that belongs to the Ge blood group system. The alloantibody was detected in a middle-aged Korean woman who did not have a history of transfusion. Her blood type was B+, and findings from the antibody screening test revealed 1+ reactivity in all panels except the autocontrol. The cross-matching test showed incompatible results with all 5 packed red blood cells. Additional blood type antigen and antibody tests confirmed the anti-Ge alloantibody. While rare, cases of hemolytic transfusion reaction or hemolytic disease in newborns due to anti-Ge have been recently reported in the literature. Therefore, additional further studies on alloantibodies to high-incidence antigens, including anti-Ge, are necessary in the future.
Ge; Blood group antigens; Transfusion
To receive and collate reports of death or major complications of transfusion of blood or components.
Haematologists were invited confidentially to report deaths and major complications after blood transfusion during October 1996 to September 1998.
Hospitals in United Kingdom and Ireland.
Patients who died or experienced serious complications, as defined below, associated with transfusion of red cells, platelets, fresh frozen plasma, or cryoprecipitate.
Main outcome measures
Death, “wrong” blood transfused to patient, acute and delayed transfusion reactions, transfusion related acute lung injury, transfusion associated graft versus host disease, post-transfusion purpura, and infection transmitted by transfusion. Circumstances relating to these cases and relative frequency of complications.
Over 24 months, 366 cases were reported, of which 191 (52%) were “wrong blood to patient” episodes. Analysis of these revealed multiple errors of identification, often beginning when blood was collected from the blood bank. There were 22 deaths from all causes, including three from ABO incompatibility. There were 12 infections: four bacterial (one fatal), seven viral, and one fatal case of malaria. During the second 12 months, 164/424 hospitals (39%) submitted a “nil to report” return.
Transfusion is now extremely safe, but vigilance is needed to ensure correct identification of blood and patient. Staff education should include awareness of ABO incompatibility and bacterial contamination as causes of life threatening reactions to blood.
Key messagesBlood transfusion, while extremely safe, has several potentially fatal hazardsAll staff handling blood should be aware of the importance of correct identity of sample, patient, and blood bag at all stagesResources should be directed to evaluation of methods for improving identification of patientsAcute fever or collapse during or after transfusion may be due to ABO incompatibility or bacterial contaminationMicrobiological complications of transfusion accounted for a minor component of all reports
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.
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.
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)
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.
We report a case of a pregnant woman with a complex hemoglobinopathy who developed a symptomatic anemia at 28 weeks of gestation and was treated with multiple transfusions of type-specific packed red blood cells. Shortly thereafter, she developed a fever and joint pains, along with laboratory values consistent with hemolysis. Timing suggested a delayed transfusion reaction. An extensive evaluation including red blood cell antigen identification and cross-reaction failed to reveal the cause for her hemolysis. Despite her critically low hemoglobin levels, her transfusions were withheld in an attempt to allow the patient to recover conservatively. With this strategy, her hemoglobin remained below her baseline, but her symptoms began to improve. Her laboratory values normalized, and hemolysis was no longer evident. Three weeks later, her hemoglobin levels returned back to her baseline without additional intervention. She went on to deliver a full-term male infant.
HLA antibodies have been implicated in transfusion related acute lung injury, but the probability that the transfusion of a blood component containing HLA antibodies will cause a reaction is not known. This study compared the prevalence of reactions associated with the transfusion of platelet components with and without HLA antibodies.
Study Design and Methods
This retrospective study tested 96 consecutive apheresis platelet donors for HLA class I and II antibodies. Matched-control donors without HLA antibodies were selected and records were reviewed to determine the proportion of components from each group that caused reactions. In addition, all apheresis platelet donors involved with 2 or more reactions were identified and tested for HLA Class I antibodies.
Five of the 96 donors had antibodies to Class I or Class II antigens and of these, four had components transfused. The prevalence of reactions to components from these four donors with HLA antibodies and the 12 matched control donors without antibodies was similar (3 reactions to 167 transfusions or 1.8% vs 3 to 295 or 1.0% respectively, p = 0.32). A retrospective review of the transfusion records from all platelet donors found that components from 22 caused 2 or more reactions and 3 (13.6%) had antibodies to HLA Class I antigens compared to 4.2% of the consecutively selected donors (p =0.12). None of the patients experienced transfusion related acute lung injury.
Reactions associated with transfusion of apheresis platelets containing HLA antibodies are unusual.
Transfusion associated graft versus host disease is a rare disorder usually confined to patients who are immunosuppressed. A case is described in a 77 year old woman who was presumed immunocompetent. She was transfused with one unit of blood from an individual who was homozygous for the same HLA haplotype as her. The diagnosis of transfusion associated graft versus host disease should be suspected in a patient who develops aplastic anaemia within 30 days of a transfusion of blood products. It is suggested that blood donations from first degree relatives should not be permitted, unless the donation is irradiated to prevent lymphocyte proliferation.
Anaphylaxis due to an anesthetic is one type of cardiovascular emergency that can occur during general anesthesia. Anaphylactic reactions to muscle relaxants have been documented. Barbiturates, used as sedatives, are well known to produce cutaneous reactions, but anaphylaxis after their ingestion seems to be rare. Generalized allergic reactions to thiopental sodium during anesthesia are mentioned in the product monograph for Penthothal sodium, and rare case reports of anaphylactic reactions to infused thiopental have appeared, generally in the anesthesiology literature. Documentation of the immunologic responses to thiopental sodium has been limited to the demonstration of an allergic reaction to thiopental by skin testing in some cases. This report describes a woman who, after having tolerated thiopental sodium and other general anesthetics, became sensitive to this agent and had a severe acute reaction at the time of induction of general anesthesia.
Graft-versus-host disease (GVHD) is a well-known complication of allogeneic bone marrow transplantation. Transfusion associated graft-versus-host disease (TA-GVHD) is much less common and nearly uniformly fatal complication of blood transfusion. The risk factors underlying the development of TA- GVHD are incompletely defined, but it is commonly seen in individuals with congenital or acquired immunodeficiency, transfusions from blood relatives, intrauterine transfusions and HLA-matched platelet transfusions. Diagnosis of TA-GVHD may be difficult at a time due to rarity in occurrence and overlapping clinical features with various infections and drug reactions. We describe a case of transfusion-associated GVHD that occurred after transfusion of whole blood from unrelated donor in an immunocompetent patient.
Graft versus host disease; Blood transfusion; TA-GVHD
The case of a 52 year old woman with chronic severe refractory thrombocytopenia is presented. Over a three year period, her platelet count was persistently less than 20 × 109/litre (normal range, 150–400). She required repeated hospital admission for management of bleeding and received multiple blood transfusions. She was given repeated courses of steroids, immunosuppression, immunoglobulin, and splenectomy, without success, in an attempt to stop the chronic blood loss. Eventually, she was found to be profoundly hypothyroid. On correction of her thyroid deficiency the platelet count returned to the normal range and all bleeding stopped. The platelet count remains in the normal range three years later.
hypothyroidism; thrombocytopenia; thyroxine
The intravenous use of fluorescein 10% during retinal angiography can cause severe systemic reactions including, on rare occasions, anaphylaxis. Fluorescein 2% eye drops are used extensively for clinical examination and diagnosis, but to the best of our knowledge, they have only been reported as being responsible for a systemic anaphylactic response on two previous occasions.
We report the case of a 51-year-old woman who developed an anaphylactic reaction when she was administered fluorescein sodium 2% eye drops after cataract surgery. This was the second time she had been exposed to fluorescein. She had brittle asthma and a history of anaphylaxis following exposure to a variety of drug and food allergens. She was successfully resuscitated and recovered completely over a period of two days.
Fluorescein 2% drops are universally used in general practice, ophthalmology, optometry, and casualty departments. Our case report reveals the potential for this benign eye drop to cause a life-threatening systemic reaction and emphasises the importance of considering this consequence when administering topical fluorescein 2% to a patient with a history of anaphylaxis to other allergens.
Sodium-N-chlorine-p-toluene sulfonamide, commonly known as chloramine-T, is a derivative of chlorine which is widely used as a disinfectant. For many years, chloramine-T has been described as a cause of immediate-type hypersensitivity, especially with regard to asthma and rhinitis, and as a cause of occupational dermatoses in cleaning personnel in hospitals, although no anaphylactic reaction has yet been reported. Hence, to the best of our knowledge we present the first case of anaphylaxis to chloramine-T with evidence of specific immunoglobulin E antibodies.
We describe the case of a 25-year-old Caucasian woman who was in good health and with a negative history for atopy, including no respiratory symptoms of rhinitis or asthma, and with no professional exposure to chloramine-T. She, while showering, applied a chloramine-T solution to a skin area with folliculitis on her leg, and within a few minutes developed generalized urticaria and angioedema, followed by vomiting and collapse with loss of consciousness. A skin prick test with a chloramine-T solution at 10mg/mL concentration was positive, and specific immunoglobulin E to chloramine-T was quantified at a value of 2.9 optical density as measured by the enzyme allergosorbent test technique.
The strict cause-effect relationship and the results of the skin test and the in vitro test make certain the causative role of chloramine-T in this case of anaphylaxis. This suggests that chloramine-T, based on its wide use as a disinfectant, should be considered a possible cause in anaphylaxis of unknown origin.
Leukemia is the second most malignant tumor in children. The chemotherapy induced anemia (CIA) and hemorrhage are the most popular side-effects due to the myelosuppression of chemotherapy. So far, multitransfusion is still the timely and effective measure in curing these complications. The acquisition of HIV infection and subsequent development of AIDS by component transfusion from donors at risk is well known, and prognosis of HIV infection is particularly severe in patients with leukemia.
We report two leukemic cases that were infected with HIV through transfusion. The first patient was totally transfused with 16 U RBC, 20 U platelets and 820 ml fresh frozen plasma, and later test showed that his first used FFP carried the HIV. For the second 2 U RBC, 5 U platelets and 1500 ml fresh frozen plasma were transfused to her. Late test of her used blood products showed that the fourth RBC carried the HIV. Both results were confirmed by the local Center for Disease Control (CDC). They were not transfused before the diagnosis of leukemia. Their parents were healthy with negative HIV-Ab.
Since the two leukemic patients suffered transfusion-associated HIV with poor prognosis, we must take more efforts to utilize blood products judiciously, manage blood donors, test blood samples etiologically, shorten HIV testing "window periods" and develop preventive vaccination against HIV to reduce the incidence as low as possible.
HIV; Blood Treansfusion; Leukemia; AIDS
Antibodies to IgA may cause severe anaphylactic reactions during blood transfusions. Tests for anti-IgA antibodies were carried out on six patients with IgA deficiency (five of whom also had hypogammaglobulinaemia) who had received continuous gammaglobullin treatment for chronic or recurrent infections for three to eight years. Three patients had minute amounts of IgA, and three had none (less than 0.01 microgram/ml). Only one patient had anti-IgA. Her antibody titre did not change during treatment. No patient had any untoward effects of treatment, which relieved the symptoms of infection in every case. IgA determinations should be performed by more accurate methods than radial immunodiffusion when evaluating the risks of giving gammaglobulin to patients with hypogammaglobulinaemia and IgA deficiency. Probably the stimulus provided by intramuscular gammaglobulin in such patients is insufficient for the formation of anti-IgA antibody.
We report a case of two consecutive episodes of acute hemolytic transfusion reactions (HTRs) due to multiple alloantibodies in a 34-yr-old man who suffered from avascular necrosis of left femoral head. He received five units of packed red blood cells (RBCs) during surgery. Then the transfusion of packed RBCs was required nine days after the surgery because of the unexplained drop in hemoglobin level. The transfusion of the first two units resulted in fever and brown-colored urine, but he received the transfusion of another packed RBCs the next day. He experienced even more severe symptoms during the transfusion of the first unit. We performed antibody screening test, and it showed positive results. Multiple alloantibodies including anti-E, anti-c and anti-Jkb were detected by antibody identification study. Acute HTRs due to multiple alloantibodies were diagnosed, and the supportive cares were done for 6 days. We suggest the antibody screening test should be included in the panel of pretransfusion tests for safer transfusion, and it is particularly mandatory for the patients with multiple transfusions, pregnant women, and preoperative patients.
Transfusion associated bacterial sepsis has been a significant risk of morbidity and mortality related to platelet transfusion therapy. Previously we determined the rate of septic transfusion reactions (SPTRs) to single donor platelets (SDPs) in our hospital to be 1 in 15,098 transfusions. The goal of this study was to determine if there has been a reduction in the rate of SPTRs in our hospital since the implementation of bacterial testing of SDPs.
STUDY DESIGN AND METHODS
An automated microbial detection system was implemented at our regional blood supplier in February 2004. We performed a retrospective examination of the number of SPTRs that have occurred to SDPs at our hospital since that time, using the same criteria we used prior to bacterial screening. Transfusions over a three and a half year period were examined. Clinical and laboratory data were gathered and correlated from transfusion reaction files and three independent computer documentation systems.
From 3/1/04 through 8/31/07, there were 49,625 transfusions of SDP with 1,096 transfusion reactions reported. Only one reaction detected the same organism in two of three sites, meeting the criteria we set for a SPTR. Consequently we identified our rate of SPTRs in SDPs as 1 in 49,625.
Although not statistically significant we did observe in our institution a decrease in the rate of STRs to SDPs from to with the implementation of bacterial testing.
SPTR(s) septic transfusion reaction(s); SDP(s) single donor platelet(s)
The risk of bacterial transmission by platelet transfusion has been recognised internationally as the leading residual infections transfusion risk in the last decade. We describe the clinical and logistical aspects of bacterial contamination screening of platelets introduced in Australia in early 2008. Sampling occurs at 24 h, and platelets are released to hospitals ‘negative to date’. Bacterial screening detection of initial machine-positive (IMP) and all follow-up results are notified to transfusing laboratories. Results of screening between 2008 and 2010 found a significant rate of IMP samples (1.06%) with a true-positive/indeterminate rate of 0.18%. Components were already transfused in 32.5% of cases at time of initial notification. Confirmed cases of septic transfusion reactions have declined significantly since the introduction of pre-release platelet screening, reflecting an important additional improvement in transfusion safety in Australia.
Bacterial testing; Platelets; Septic transfusion reaction
Post-transfusion purpura is a rare immunohematological disorder characterized by severe thrombocytopenia following transfusion of blood components and induced by an alloantibody against a donor platelet antigen. It occurs primarily in women sensitized by pregnancy and is most commonly caused by anti-human platelet antigen-1a antibodies. Here, we describe what we believe to be the first documented case of an African-American man who developed post-transfusion purpura due to an anti-human platelet antigen-5b alloantibody after receiving multiple blood products.
A 68-year-old African-American man initially admitted with atrial flutter was started on anticoagulation treatment, which was complicated by severe hematemesis. On days 4 and 5 of hospitalization, he received six units of packed red blood cells, and on days 4, 13 and 14 he received plasma. His platelet count began to drop on day 25 and on day 32 reached a nadir of 7 × 109/L. His platelet count increased after receiving intravenous immune globulin. An antibody with reactivity to human platelet antigen-5b was detected by a solid-phase enzyme-linked immunoassay. Our patient was homozygous for human platelet antigen-5a.
This case emphasizes the importance of including post-transfusion purpura in the differential diagnosis for both men and women with acute onset of thrombocytopenia following transfusion of blood products. The prompt recognition of this entity is crucial for initiation of the appropriate management.
Collecting, processing and dispensing blood for hemotherapy has evolved into Transfusion Medicine (TM), a newly recognized discipline. Joining my efforts to those of collaborators all over the world during this period of transformation, my scientific career spanned from the investigation of the immunogenetics of Bombay (OhOh) blood to establishing the academic TM program at the University of California, San Francisco (UCSF). The twin discoveries of class-specific antibodies against immunoglobulin A (IgA) causing anaphylactic transfusion reactions, and of anti-IgA of limited specificity defining A2m(1) as the first genetic marker of IgA led to the award of the Julliard Prize. My precocious appointment as the head of the Bombay Municipal Blood Center in India launched my academic career in 1969 as the Chief of the Blood Bank at UCSF Medical Center. Viral hepatitis, then the principal risk of transfusion, engaged me in the molecular analyses of purified hepatitis B virus (HBV) and its surface antigen (HBsAg). Consequently the first HBV vaccine, derived from infected plasma (superseded by cloned HBV-envelope protein), and hepatitis B immune globulin (HBIG) were developed for clinical trials that led to FDA-licensed biological products for prophylaxis and therapy. The advent of HIV/AIDS in the early 1980s raised renewed concern about transfusion safety and led me to push for anti-HBc blood screening for improved transfusion safety. The triennial International Symposia on Viral Hepatitis and Liver Disease (ISVHLD), which I started in 1972, continue to be the foremost forum for the contemporary assessment of hepatitis prevention and treatment. Besides viral hepatitis, I undertook multiplexed flow cytometric analyses for markers of infection by blood-borne viruses and their PCR-amplified gene products, kinetics of HIV replication in peripheral blood lymphocytes, leukocyte depletion for safer transfusion, and removal/inactivation of blood-borne viruses. The TM training and research programs I initiated at UCSF in the 1980s with NIH support enabled me to recruit new faculty members who continue to foster the worldwide advancement of transfusion safety.
Transfusion reactions; Anti-IgA; Blood; borne infections; Viral hepatitis; Transfusion safety; Passive-active immunization
Platelet Rich Plasma-Platelet concentrate (PRP-PC), Buffy Coat poor-platelet concentrate (BCPC), and Apheresis — PC were prepared and their therapeutic efficacy were assessed in thrombocytopenic patients.
Study design and methods
PRP-PC and BC-PC were prepared from whole blood and Apheresis-PC by automated cell separator. The post transfusion efficacy of transfused platelets was assessed at 1 hour and 20 hours by corrected count increment (CCI) and percentage recovery (PR).
A total of 60 patients’ (20 each for PRP-PC, BC-PC and Apheresis-PC) were enrolled in this study. Forty one patients received therapeutic and nineteen received prophylactic transfusion support. Patients with aplastic anemia 43% (25/60) and acute leukemia 38% (23/60) formed a majority of study population. Platelet dosage of patients’ received PRP-PC, BC-PC and apheresis-PC were 2.4±0.82 × 1011 (mean±SD), 2.2±0.83 × 1011 (mean±SD) and 4.14±1.82 × 1011 (mean±SD) and ranged from 1.16–4.11 × 1011, 1.04−4.20 × 1011 and 1.22−8.90 × 1011 respectively. There was significantly increase in inter-transfusion interval with Apheresis-PC than with PRP-PC and BC-PC recipients [(Mean±S.D.), 4.7±1.33 days Vs 2.7±0.82 days Vs 2.5±0.7 days respectively] (p < 0.05).
Patients transfused with apheresis-PC had received higher platelet dosage than PRP-PC and BC-PC and this difference was statistically significant (p < 0.001). The post transfusion platelet counts and increments at 1 hour and 20 hours were significantly higher with apheresis-PC than PRP-PC and BC-PC (p < 0.001). However, the corrected count increment (CCI) and percentage recovery (PR) in all three groups were comparable. There was significantly increase in inter-transfusion interval with apheresis-PC than PRPPC and BC-PC (p < 0.05).
Random donor platelets; Buffy coat poor-platelet concentrate; Platelet Rich Plasma-Platelet concentrate; Thrombocytopenic patients
Anaphylaxis is a life-threatening systemic allergic reaction with the potential for a recurrent or biphasic pattern. Despite an incidence of biphasic reaction between 5 and 20%, the molecular mechanism for the reaction is unknown. Using a murine model of penicillin V–induced systemic anaphylaxis, we show an autoregulatory cascade of biphasic anaphylactic reactions. Induction of anaphylaxis caused a rapid increase in circulating platelet-activating factor (PAF) levels. In turn, the elevated PAF contributes to the early phase of anaphylaxis as well as the subsequent activation of the nuclear factor (NF)-κB, a crucial transcription factor regulating the expression of many proinflammatory cytokines and immunoregulatory molecules. The induction of NF-κB activity is accompanied by TNF-α production, which, in turn, promotes late phase PAF synthesis. This secondary wave of PAF production leads eventually to the late phase of anaphylactic reactions. Mast cells do not appear to be required for development of the late phase anaphylaxis. Together, this work reveals the first mechanistic basis for biphasic anaphylactic reactions and provides possible therapeutic strategies for human anaphylaxis.
early anaphylaxis; biphasic anaphylaxis; mast cell; penicillin V; TNF-α
There are multiple benefits to transfusing only ABO identical blood components. Historically our institution routinely transfused ABO non-identical platelets (PLTs) and cryoprecipitate to surgical patients. In April 2005, we implemented a policy of transfusing only ABO identical components whenever feasible, regardless of outdating/logistic considerations.
Technical staff closely monitored product usage and adjusted blood center orders based on recent utilization and planned transfusions. When unable to provide ABO identical PLTs ABO compatible platelets were washed to remove incompatible plasma. Data on outdating were collected for eighteen months before and after implementation. We compared transfusion reaction and red cell alloimmunization incidence for four years preceding (2001–2004) and subsequent (2006–2009) to implementation.
In the year following implementation, only 11 of 410 surgical patients received ABO non-identical platelets (2.7%). There was a 5.6% increase in outdating of platelets. Transfusing ABO identical components was associated with significant reductions in febrile (−46%; 8.0 to 4.3 per 10,000 components; p<0.0001) and allergic transfusion reactions (−23%; from 7.0 to 5.4 per 10,000 components; p=0.025). A progressive reduction in de novo red cell alloimmunization incidence also occurred (−50% by 2009; p=0.03).
Providing ABO identical platelets to almost all patients was feasible in our setting by changing ordering and inventorying procedures, and making the ABO identical policy a staff priority. Unexpected and striking reductions in febrile and allergic reactions, and red cell alloimmunization were observed, of uncertain causal relationship to this ABO policy change, which will require further study.