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1.  Anaphylactic reaction to platelet transfusion as the initial symptom of an undiagnosed systemic mastocytosis: a case report and review of the literature 
The association between anaphylactic reactions and systemic mastocytosis is well documented. However, platelet transfusion has not previously been reported as a potential elicitor of anaphylaxis in the context of systemic mastocytosis.
Case presentation
We describe the clinicopathological findings of a 59-year-old Latin American man who presented to the emergency room with fatigue, leukocytosis, thrombocytopenia and mild hepatosplenomegaly. He developed two separate, temporally associated and severe anaphylactic reactions after receiving platelet transfusions. The result of a laboratory investigation for clerical errors and Coombs test was negative. Pre- and post-transfusion urine samples were negative for hemolysis. Bone marrow biopsy and aspirate smears performed demonstrated involvement by systemic mastocytosis, which had been previously undiagnosed.
We posit the transfusion reaction to be an anaphylactic reaction to transfused products as a result of heightened allergic sensitivity due to the underlying systemic mastocytosis. To the best of our knowledge, this is the first reported case of a severe anaphylactic-type reaction to blood products occurring in the setting of a previously undiagnosed systemic mastocytosis. Furthermore, it seems there are no published studies closely examining the relationship between hematopoietic neoplasms and transfusion reactions in general.
PMCID: PMC4304775  PMID: 25424186
Anaphylaxis; Platelet transfusion; Systemic mastocytosis; Transfusion reaction
2.  IgE- and IgG mediated severe anaphylactic platelet transfusion reaction in a known case of cerebral malaria 
Allergic reactions occur commonly in transfusion practice. However, severe anaphylactic reactions are rare; anti-IgA (IgA: Immunoglobulin A) in IgA-deficient patients is one of the well-illustrated and reported causes for such reactions. However, IgE-mediated hypersensitivity reaction through blood component transfusion may be caused in parasitic hyperimmunization for IgG and IgE antibodies.
Case Report:
We have evaluated here a severe anaphylactic transfusion reaction retrospectively in an 18year-old male, a known case of cerebral malaria, developed after platelet transfusions. The examination and investigations revealed classical signs and symptoms of anaphylaxis along with a significant rise in the serum IgE antibody level and IgG by hemagglutination method. Initial mild allergic reaction was followed by severe anaphylactic reaction after the second transfusion of platelets.
Based on these results, screening of patients and donors with mild allergic reactions to IgE antibodies may help in understanding the pathogenesis as well as in planning for preventive desensitization and measures for safe transfusion.
PMCID: PMC3613673  PMID: 23559774
Anaphylactic transfusion reaction; IgE mediated allergic transfusion reaction; investigation of transfusion reaction; platelet transfusion reactions
3.  Current understanding of allergic transfusion reactions: incidence, pathogenesis, laboratory tests, prevention and treatment 
British Journal of Haematology  2012;160(4):434-444.
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.
PMCID: PMC3594969  PMID: 23215650
allergic transfusion reaction; IgE; tryptase; basophil activation test; washed platelets
4.  Red Blood Cell Transfusion and Mortality in Trauma Patients: Risk-Stratified Analysis of an Observational Study 
PLoS Medicine  2014;11(6):e1001664.
Using a large multicentre cohort, Pablo Perel and colleagues evaluate the association of red blood cell transfusion with mortality according to the predicted risk of death for trauma patients.
Please see later in the article for the Editors' Summary
Haemorrhage is a common cause of death in trauma patients. Although transfusions are extensively used in the care of bleeding trauma patients, there is uncertainty about the balance of risks and benefits and how this balance depends on the baseline risk of death. Our objective was to evaluate the association of red blood cell (RBC) transfusion with mortality according to the predicted risk of death.
Methods and Findings
A secondary analysis of the CRASH-2 trial (which originally evaluated the effect of tranexamic acid on mortality in trauma patients) was conducted. The trial included 20,127 trauma patients with significant bleeding from 274 hospitals in 40 countries. We evaluated the association of RBC transfusion with mortality in four strata of predicted risk of death: <6%, 6%–20%, 21%–50%, and >50%. For this analysis the exposure considered was RBC transfusion, and the main outcome was death from all causes at 28 days. A total of 10,227 patients (50.8%) received at least one transfusion. We found strong evidence that the association of transfusion with all-cause mortality varied according to the predicted risk of death (p-value for interaction <0.0001). Transfusion was associated with an increase in all-cause mortality among patients with <6% and 6%–20% predicted risk of death (odds ratio [OR] 5.40, 95% CI 4.08–7.13, p<0.0001, and OR 2.31, 95% CI 1.96–2.73, p<0.0001, respectively), but with a decrease in all-cause mortality in patients with >50% predicted risk of death (OR 0.59, 95% CI 0.47–0.74, p<0.0001). Transfusion was associated with an increase in fatal and non-fatal vascular events (OR 2.58, 95% CI 2.05–3.24, p<0.0001). The risk associated with RBC transfusion was significantly increased for all the predicted risk of death categories, but the relative increase was higher for those with the lowest (<6%) predicted risk of death (p-value for interaction <0.0001). As this was an observational study, the results could have been affected by different types of confounding. In addition, we could not consider haemoglobin in our analysis. In sensitivity analyses, excluding patients who died early; conducting propensity score analysis adjusting by use of platelets, fresh frozen plasma, and cryoprecipitate; and adjusting for country produced results that were similar.
The association of transfusion with all-cause mortality appears to vary according to the predicted risk of death. Transfusion may reduce mortality in patients at high risk of death but increase mortality in those at low risk. The effect of transfusion in low-risk patients should be further tested in a randomised trial.
Trial registration NCT01746953
Please see later in the article for the Editors' Summary
Editors' Summary
Trauma—a serious injury to the body caused by violence or an accident—is a major global health problem. Every year, injuries caused by traffic collisions, falls, blows, and other traumatic events kill more than 5 million people (9% of annual global deaths). Indeed, for people between the ages of 5 and 44 years, injuries are among the top three causes of death in many countries. Trauma sometimes kills people through physical damage to the brain and other internal organs, but hemorrhage (serious uncontrolled bleeding) is responsible for 30%–40% of trauma-related deaths. Consequently, early trauma care focuses on minimizing hemorrhage (for example, by using compression to stop bleeding) and on restoring blood circulation after blood loss (health-care professionals refer to this as resuscitation). Red blood cell (RBC) transfusion is often used for the management of patients with trauma who are bleeding; other resuscitation products include isotonic saline and solutions of human blood proteins.
Why Was This Study Done?
Although RBC transfusion can save the lives of patients with trauma who are bleeding, there is considerable uncertainty regarding the balance of risks and benefits associated with this procedure. RBC transfusion, which is an expensive intervention, is associated with several potential adverse effects, including allergic reactions and infections. Moreover, blood supplies are limited, and the risks from transfusion are high in low- and middle-income countries, where most trauma-related deaths occur. In this study, which is a secondary analysis of data from a trial (CRASH-2) that evaluated the effect of tranexamic acid (which stops excessive bleeding) in patients with trauma, the researchers test the hypothesis that RBC transfusion may have a beneficial effect among patients at high risk of death following trauma but a harmful effect among those at low risk of death.
What Did the Researchers Do and Find?
The CRASH-2 trail included 20,127 patients with trauma and major bleeding treated in 274 hospitals in 40 countries. In their risk-stratified analysis, the researchers investigated the effect of RBC transfusion on CRASH-2 participants with a predicted risk of death (estimated using a validated model that included clinical variables such as heart rate and blood pressure) on admission to hospital of less than 6%, 6%–20%, 21%–50%, or more than 50%. That is, the researchers compared death rates among patients in each stratum of predicted risk of death who received a RBC transfusion with death rates among patients who did not receive a transfusion. Half the patients received at least one transfusion. Transfusion was associated with an increase in all-cause mortality at 28 days after trauma among patients with a predicted risk of death of less than 6% or of 6%–20%, but with a decrease in all-cause mortality among patients with a predicted risk of death of more than 50%. In absolute figures, compared to no transfusion, RBC transfusion was associated with 5.1 more deaths per 100 patients in the patient group with the lowest predicted risk of death but with 11.9 fewer deaths per 100 patients in the group with the highest predicted risk of death.
What Do These Findings Mean?
These findings show that RBC transfusion is associated with an increase in all-cause deaths among patients with trauma and major bleeding with a low predicted risk of death, but with a reduction in all-cause deaths among patients with a high predicted risk of death. In other words, these findings suggest that the effect of RBC transfusion on all-cause mortality may vary according to whether a patient with trauma has a high or low predicted risk of death. However, because the participants in the CRASH-2 trial were not randomly assigned to receive a RBC transfusion, it is not possible to conclude that receiving a RBC transfusion actually increased the death rate among patients with a low predicted risk of death. It might be that the patients with this level of predicted risk of death who received a transfusion shared other unknown characteristics (confounders) that were actually responsible for their increased death rate. Thus, to provide better guidance for clinicians caring for patients with trauma and hemorrhage, the hypothesis that RBC transfusion could be harmful among patients with trauma with a low predicted risk of death should be prospectively evaluated in a randomised controlled trial.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLOS Medicine Perspective by Druin Burch
The World Health Organization provides information on injuries and on violence and injury prevention (in several languages)
The US Centers for Disease Control and Prevention has information on injury and violence prevention and control
The National Trauma Institute, a US-based non-profit organization, provides information about hemorrhage after trauma and personal stories about surviving trauma
The UK National Health Service Choices website provides information about blood transfusion, including a personal story about transfusion after a serious road accident
The US National Heart, Lung, and Blood Institute also provides detailed information about blood transfusions
MedlinePlus provides links to further resources on injuries, bleeding, and blood transfusion (in English and Spanish)
More information in available about CRASH-2 (in several languages)
PMCID: PMC4060995  PMID: 24937305
5.  Detection of anti-IgA antibodies using the particle gel immunoassay: a rapid test for increased patient safety 
Blood Transfusion  2014;12(3):334-339.
Patient safety is a major issue in transfusion medicine and commands continuous efforts to develop valid control methods aiming to avoid serious transfusion-related complications. Anti-IgA antibodies can cause anaphylactic transfusion reactions in IgA-deficient individuals. Since standard quantitative methods for anti-IgA measurement require considerable time to be performed, in an emergency situation it can be a challenge to prevent or to quickly interpret and manage acute transfusion reactions suspected to be a consequence of anti-IgA. The purpose of this study was to test and validate at our transfusion centre a rapid assay for the identification of patients with anti-IgA antibodies.
Materials and methods
Forty-six samples (6 from healthy controls and 40 from IgA-deficient patients) were collected. Sera were analysed blindly by three different clinical laboratory technologists using two DiaMed particle gel immunoassays (ID-PaGIA) for IgA deficiency and for antibodies to IgA. The results were subsequently checked with the results of a fluorescence enzyme immunoassay conducted in the reference immunology laboratory.
The ID-PaGIA had a sensitivity of 91.7% and specificity of 97.1% for the IgA deficiency test. With regards to the detection of anti-IgA antibodies, the sensitivity was 89.3% and the specificity 100%. The reproducibility of the test was 100%.
The ID-PaGIA screening assays are suitable for the investigation of transfusion-related anaphylactic reactions in a routine blood bank laboratory. Although the gel card technique does not quantify the level of anti-IgA antibodies, it is readily available, providing an effective and simple method for the diagnosis of anti-IgA related anaphylaxis and guidance for the appropriate transfusion practice in an emergency.
PMCID: PMC4111814  PMID: 24887222
IgA deficiency; anti-IgA antibodies; anaphylactic transfusion reaction; particle gel immunoassay; transfusion urgency
6.  494 Skin Sensitization to Carmine Before Onset of Systemic Allergy to Ingested Carmine 
Allergic sensitization to food can occur through skin exposure. We investigated anaphylactic cases due to carmine, a food additive extracted from Dactylopius coccus.
Screening all patients, who visited our department from January 2000 to December 2009, we identified 2 new such cases. Both had history of rash induced by certain cosmetics containig carmine. We further investigated previous case reports of carmine allergy, whether skin sensitization antedated food allergy or not.
Case 1: A 26-year-old woman visited our hospital because of anaphylaxis occurred within 5 minutes after ingesting a Japanese YOKAN (sweetened and jellied bean paste). IgE antibodies against common food allergens including beans and wheat were all negative. As the paste contains carmine, we tested specific IgE antibody, which was positive. She had been avoiding using certain cheeks and lips for 2 years, since they cause erythema. These cosmetics emerged as containing carmine. Abstaining from the food additive made her free from anaphylaxis. Case 2: A 30-year-old woman came to our hospital for dyspnea, uriticaria, and bilateral blepharedema, immediately after drinking Campari soda. Her past history was prominent, as she had 4 episodes of anaphylaxis in 4 years, requiring emergency transport twice. All anaphylactic episodes occurred in Italian restaurants when she drank cocktails, which might contain carmine in Campari soda. She had been also sensitive to certain rouges since several years before the first onset of anaphylaxis. It became clear that the rouges contained carmine. In literatures, we found 22 cases with allergy to ingested carmine. It is surprising that all cases were women (aged 25 to 52), while occupationally sensitized patients are predominantly men. As far as we could know, 85.7 % of (6/7) mentioned cases had previous history of sensitization to cosmetics containing carmine.
In many cases with allergy against ingested carmine, the route of first sensitization was not via intestine but skin. This is similar to suspected peanut sensitization mechanism and might be a paradigm of food allergy. As allergic reaction to carmine mainly directed to impurities, using highly purified carmine is desired not only for foods but also for cosmetics.
PMCID: PMC3512794
7.  Pulmonary 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.
PMCID: PMC3076325  PMID: 21512622
Acute lung injury; Transfusion reaction; Transfusion risks
8.  Reactions Induced by Platelet Transfusions 
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.
PMCID: PMC3076327  PMID: 21512624
Platelet transfusion; Transfusion reactions; Bacterial contamination of blood products; Hemolytic transfusion reactions; Febrile nonhemolytic transfusion reactions
9.  Hemostatic Function and Transfusion Efficacy of Apheresis Platelet Concentrates Treated with Gamma Irradiation in Use for Thrombocytopenic Patients 
During the transfusion of blood components, the transfer of allogeneic donor white blood cells (WBCs) can mediate transfusion-associated graft-versus-host disease (TA-GVHD). To minimize the reaction, exposure of blood products to gamma irradiation is currently the standard of care. The aim of our study was to evaluate and compare hemostatic function, transfusion efficacy, and safety of gamma-irradiated single-donor apheresis platelet concentrates (PCs) and of conventional non-irradiated PCs in patients with chemotherapy-induced thrombocytopenia.
20 double-dose single-donor leukoreduced PCs were split in two identical units; one was gamma-irradiated with 25 Gy (study arm A) and the other remains non-irradiated (study arm B). Both units were stored under equal conditions. Hematologic patients were randomly assigned to receive gamma-irradiated or conventional non-irradiated PCs. Hemostatic function was evaluated by thrombelastography (TEG). TEG measurements were taken pre transfusion and 1 and 24 h post transfusion. TEG profiles were measured, noting the time to initiate clotting (R), the angle of clot formation (α), and the maximum amplitude (clot strength (MA)). Whole blood samples were collected from these thrombocytopenic patients at 1 and 24 h for PLT count increments (CIs) and corrected count increments (CCIs) with assessments of transfusion efficacy. Time to next PLT transfusion, transfusion requirement of RBCs, active bleeding, and adverse events (AEs), were analyzed.
No differences could be found in hemostatic function parameters (MA, R, and α) between study arms A and B (all p values > 0.096) pre transfusion as well as 1 and 24 h post transfusion. No differences between study arms A and B were observed for mean (± standard deviation (SD)) 1-hour CCI (12.83 ± 6.33 vs. 11.59 ± 5.97) and 24-hour CCI (6.56 ± 4.10 vs. 5.76 ± 4.05). Mean 1-hour CI and 24-hour CI were not significantly different in both study arms (p = 0.254 and p = 0.242 respectively). Median time to the next PC transfusion after study PC was not significantly different between groups: (2.4 vs. 2.2 days, p = 0.767). No differences could be found in transfusion requirement of red blood cells (p = 0.744) between both study arms. There were also no regarding bleeding, adverse events, and acute transfusion reaction(s).
This study confirms safety of gamma-irradiated PCs for treatment thrombocytopenia. Hemostatic function, transfusion efficacy, bleeding, and safety of single-donor apheresis PCs treated with gamma irradiation versus untreated control PCs are comparable.
PMCID: PMC4086760  PMID: 25053932
Hemostatic function; Transfusion efficacy; Apheresis platelet concentrates; Gamma irradiation; Thrombocytopenic patients
10.  Low-Dose Adrenaline, Promethazine, and Hydrocortisone in the Prevention of Acute Adverse Reactions to Antivenom following Snakebite: A Randomised, Double-Blind, Placebo-Controlled Trial 
PLoS Medicine  2011;8(5):e1000435.
In a factorial randomized trial conducted in Sri Lanka, de Silva and colleagues evaluate the safety and efficacy of pretreatments intended to reduce the risk of serious reactions to antivenom following snakebite.
Envenoming from snakebites is most effectively treated by antivenom. However, the antivenom available in South Asian countries commonly causes acute allergic reactions, anaphylactic reactions being particularly serious. We investigated whether adrenaline, promethazine, and hydrocortisone prevent such reactions in secondary referral hospitals in Sri Lanka by conducting a randomised, double-blind placebo-controlled trial.
Methods and Findings
In total, 1,007 patients were randomized, using a 2×2×2 factorial design, in a double-blind, placebo-controlled trial of adrenaline (0.25 ml of a 1∶1,000 solution subcutaneously), promethazine (25 mg intravenously), and hydrocortisone (200 mg intravenously), each alone and in all possible combinations. The interventions, or matching placebo, were given immediately before infusion of antivenom. Patients were monitored for mild, moderate, or severe adverse reactions for at least 96 h. The prespecified primary end point was the effect of the interventions on the incidence of severe reactions up to and including 48 h after antivenom administration. In total, 752 (75%) patients had acute reactions to antivenom: 9% mild, 48% moderate, and 43% severe; 89% of the reactions occurred within 1 h; and 40% of all patients were given rescue medication (adrenaline, promethazine, and hydrocortisone) during the first hour. Compared with placebo, adrenaline significantly reduced severe reactions to antivenom by 43% (95% CI 25–67) at 1 h and by 38% (95% CI 26–49) up to and including 48 h after antivenom administration; hydrocortisone and promethazine did not. Adding hydrocortisone negated the benefit of adrenaline.
Pretreatment with low-dose adrenaline was safe and reduced the risk of acute severe reactions to snake antivenom. This may be of particular importance in countries where adverse reactions to antivenom are common, although the need to improve the quality of available antivenom cannot be overemphasized.
Trial registration NCT00270777
Please see later in the article for the Editors' Summary
Editors' Summary
Of the 3,000 or so snake species in the world, about 600 are venomous. Venomous snakes, which are particularly common in equatorial and tropical regions, immobilize their prey by injecting modified saliva (venom) into their prey's tissues through their fangs—specialized hollow teeth. Snakes also use their venoms for self-defense and will bite people who threaten, startle, or provoke them. A bite from a highly venomous snake such as a pit viper or cobra can cause widespread bleeding, muscle paralysis, irreversible kidney damage, and tissue destruction (necrosis) around the bite site. All these effects of snakebite are potentially fatal; necrosis can also result in amputation and permanent disability. It is hard to get accurate estimates of the number of people affected by snakebite, but there may be about 2 million envenomings (injections of venom) and 100,000 deaths every year, many of them in rural areas of South Asia, Southeast Asia, and sub-Saharan Africa.
Why Was This Study Done?
The best treatment for snakebite is to give antivenom (a mixture of antibodies that neutralize the venom) as soon as possible. Unfortunately, in countries where snakebites are common (for example, Sri Lanka), antivenoms are often of dubious quality, and acute allergic reactions to them frequently occur. Although some of these reactions are mild (for example, rashes), in up to 40% of cases, anaphylaxis—a potentially fatal, whole-body allergic reaction—develops. The major symptoms of anaphylaxis—a sudden drop in blood pressure and breathing difficulties caused by swelling of the airways—can be treated with adrenaline. Injections of antihistamines (for example, promethazine) and hydrocortisone can also help. In an effort to prevent anaphylaxis, these drugs are also widely given before antivenom, but there is little evidence that such “prophylactic” treatment is effective or safe. In this randomized double-blind controlled trial (RCT), the researchers test whether low-dose adrenaline, promethazine, and/or hydrocortisone can prevent acute adverse reactions to antivenom. In an RCT, the effects of various interventions are compared to a placebo (dummy) in groups of randomly chosen patients; neither the patients nor the people caring for them know who is receiving which treatment until the trial is completed.
What Did the Researchers Do and Find?
The researchers randomized 1,007 patients who had been admitted to secondary referral hospitals in Sri Lanka after snakebite to receive low-dose adrenaline, promethazine, hydrocortisone, or placebo alone and in all possible combinations immediately before treatment with antivenom. The patients were monitored for at least 96 hours for adverse reactions to the antivenom; patients who reacted badly were given adrenaline, promethazine, and hydrocortisone as “rescue medication.” Three-quarters of the patients had acute reactions—mostly moderate or severe—to the antivenom. Most of the acute reactions occurred within an hour of receiving the antivenom, and nearly half of all the patients were given rescue medication during the first hour. Compared with placebo, pretreatment with adrenaline reduced severe reactions to the antivenom by 43% at one hour and by 38% over 48 hours. By contrast, neither hydrocortisone nor promethazine given alone reduced the rate of adverse reactions to the antivenom. Moreover, adding hydrocortisone negated the beneficial effect of adrenaline.
What Do These Findings Mean?
These findings show that pretreatment with low-dose adrenaline is safe and reduces the risk of acute severe reactions to snake antivenom, particularly during the first hour after infusion. They do not provide support for pretreatment with promethazine or hydrocortisone, however. Indeed, the findings suggest that the addition of hydrocortisone could negate the benefits of adrenaline, although this finding needs to be treated with caution because of the design of the trial, as does the observed increased risk of death associated with pretreatment with hydrocortisone. More generally, the high rate of acute adverse reactions to antivenom in this trial highlights the importance of improving the quality of antivenoms available in Sri Lanka and other parts of South Asia. The researchers note that the recent World Health Organization guidelines on production, control, and regulation of antivenom should help in this regard but stress that, for now, it is imperative that physicians carefully monitor patients who have been given antivenom and provide prompt treatment of acute reactions when they occur.
Additional Information
Please access these Web sites via the online version of this summary at
The MedlinePlus Encyclopedia has pages on snakebite and on anaphylaxis (in English and Spanish)
The UK National Health Service Choices website also has pages on snakebite and on anaphylaxis
The World Health Organization has information on snakebite and on snake antivenoms (in several languages); its Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins are also available
The Global Snakebite Initiative has information on snakebite
A PLoS Medicine Research Article by Anuradhani Kasturiratne and colleagues provides data on the global burden of snakebite
A PLoS Medicine Neglected Diseases Article by José María Gutiérrez and colleagues discusses the neglected problem of snakebite envenoming
PMCID: PMC3091849  PMID: 21572992
11.  The prevention of adverse reactions to transfusions in patients with haemoglobinopathies: a proposed algorithm 
Blood Transfusion  2013;11(3):377-384.
Transfusion therapy remains the main treatment for patients with severe haemoglobinopathies, but can cause adverse reactions which may be classified as immediate or delayed. The use of targeted prevention with drugs and treatments of blood components in selected patients can contribute to reducing the development of some reactions.
The aim of our study was to develop an algorithm capable of guiding behaviours to adopt in order to reduce the incidence of immediate transfusion reactions.
Materials and methods
Immediate transfusion reactions occurring over a 7-year period in 81 patients with transfusion-dependent haemoglobinopathies were recorded. The patients received transfusions with red cell concentrates that had been filtered prestorage. Various measures were undertaken to prevent transfusion reactions: leucoreduction, washing the red blood cells, prophylactic administration of an antihistamine (loratidine 10 mg tablet) or an antipyretic (paracetamol 500 mg tablet).
Over the study period 20,668 red cell concentrates were transfused and 64 adverse transfusion reactions were recorded in 36 patients. The mean incidence of reactions in the 7 years of observation was 3.1‰. Over the years the incidence gradually decreased from 6.8‰ in 2004 to 0.9‰ in 2010.
Preventive measures are not required for patients who have an occasional reaction, because the probability that such a type of reaction recurs is very low. In contrast, the targeted use of drugs such as loratidine or paracetamol, sometimes combined with washing and/or double filtration of red blood cells, can reduce the rate of recurrent (allergic) reactions to about 0.9‰. The system for detecting adverse reactions and training staff involved in transfusion therapy are critical points for reliable collection of data and standardisation of the detection system is recommended for those wanting to monitor the incidence of all adverse reactions, including minor ones.
PMCID: PMC3729128  PMID: 23736930
transfusion; adverse reactions; washed red blood cells; haemovigilance
12.  Risk Factors for Alloimmunisation after red blood Cell Transfusions (R-FACT): a case cohort study 
BMJ Open  2012;2(3):e001150.
Individuals exposed to red blood cell alloantigens through transfusion, pregnancy or transplantation may produce antibodies against the alloantigens. Alloantibodies can pose serious clinical problems such as delayed haemolytic reactions and logistic problems, for example, to obtain timely and properly matched transfusion blood for patients in which new alloantibodies are detected.
The authors hypothesise that the particular clinical conditions (eg, used medication, concomitant infection, cellular immunity) during which transfusions are given may contribute to the risk of immunisation. The aim of this research was to examine the association between clinical, environmental and genetic characteristics of the recipient of erythrocyte transfusions and the risk against erythrocyte alloimmunisation during that transfusion episode.
Methods and analysis Study design
Incident case–cohort study.
Secondary care, nationwide study (within the Netherlands) including seven hospitals, from January 2005 to December 2011.
Study population
Consecutive red cell transfused patients at the study centres.
The study cohort comprises of consecutive red blood cell transfused patients at the study centre.
Patients with transfusions before the study period and/or pre-existing alloantibodies.Cases defined as first time alloantibody formers; Controls defined as transfused individuals matched (on number of transfusions) to cases and have not formed an alloantibody.
Statistical analysis
Logistic regression models will be used to assess the association between the risk to develop antibodies and potential risk factors, adjusted for other risk factors.
Ethics and dissemination
Approval at each local ethics regulatory committee will be obtained. Data will be coded for privacy reasons. Patients will be sent a letter and an information brochure explaining the purpose of the study. A consent form in presence of the study coordinator will be signed before the blood taking commences. Investigators will submit progress summary of the study to study sponsor regularly. Investigators will notify the accredited ethics board of the end of the study within a period of 8 weeks.
Article summary
Article focus
Identifying transfusion-related risk factors of alloimmunisation against red blood cell (RBC) antigens.
Identifying clinical risk factors of alloimmunisation against RBC antigens.
Identifying environmental and genetic risk factors of alloimmunisation against RBC antigens.
Key messages
Alloimmunisation against RBC transfusion is a clinically relevant problem faced by transfusion specialists.
Identifying a high-risk group of responders who form allantibodies against transfused RBCs would be the next step towards transfusion of complete phenotyped matched RBC.
In synergy with other ongoing studies, cost-effectiveness of a phenotyped matched RBC approach will be assessed.
Strengths and limitations of this study
Multicentre, matched case–cohort design.
Good representative sample of controls from large base cohort of general population.
Cases and controls matched on the number of RBC transfusions.
Possibility that patients entering cohort have had transfusions prior to start of study period in other hospitals/non-study centres.
Previous pregnancies in women could play a role in alloimmunisation. Retrospective data will not allow for a comprehensive check on previous pregnancies.
There could be a few cases selected who are booster/secondary alloimmune responders, instead of first time ever alloantibody formers.
PMCID: PMC3358625  PMID: 22561355
13.  Unfurling the Rationale Use of Platelet Transfusion in Dengue Fever 
Dengue fever and dengue haemorrhagic fever have emerged as a global public health problem in recent decades. The practice of platelet transfusion has been adapted into the standard clinical practice in management of hospitalized dengue patients. The exact indications and situations in which platelet have to be transfused may vary greatly. Blood components especially platelet concentrates due to their short shelf life are frequently in limited supply. Hence, appropriate use of blood is required to ensure the availability of blood for patients in whom it is really indicated, as well as to avoid unnecessary exposure of the patients to the risk of transfusion reactions and transmission of blood borne infection. The present study was conducted to evaluate the appropriateness of platelet transfusion done in dengue patients with thrombocytopenia. The present study was conducted on 343 serologically confirmed dengue patients admitted at JSS University Hospital between 1st January and 30th August 2009. Clinical data, platelet count and platelet requirements were analyzed. Among the 343 serologically confirmed cases, the prevalence of thrombocytopenia (platelet count < 100,000/cumm) was 64.72% (222 patients) and bleeding manifestations were recorded in 6.12% (21 patients). 71 (20.7%) patients of dengue cases received platelet transfusion. Among them 34 (47.89%) patients had a platelet count <20,000/cumm, 28 patients (39.44%) had platelet counts in the range of 21–40,000/cumm while the remaining 9 (12.67%) patients had platelet count between 41–100,000/cumm. Out of 37 patients with a platelet count >20,000/cumm 11 patients had haemorrhagic manifestations such as petechiae, gum bleeding, epistaxis etc., which necessitates the use of platelet transfusion. However, the remaining 26 patients with platelet count >20,000/cumm and with no haemorrhagic manifestations received inappropriate platelet transfusion. Transfusion of 36.62% of platelet concentrate was inappropriate. The study emphasizes the need for development of specific guidelines for transfusion of blood components, constant interaction and co-ordination amongst clinicians and transfusion centre for implementation of these guidelines and a regular medical audit to review the optimal utilization of blood components.
PMCID: PMC3136676  PMID: 22654295
Dengue; Haemorrhagic fever; Platelet count; Platelet transfusion; Rationale use
14.  Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU: protocol for a randomised controlled trial 
Trials  2013;14:150.
Transfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients.
The Transfusion Requirements in Septic Shock (TRISS) trial is a multicenter trial with assessor-blinded outcome assessment, randomising 1,000 patients with septic shock in 30 Scandinavian ICUs to receive transfusion with pre-storage leuko-depleted RBC suspended in saline-adenine-glucose and mannitol (SAGM) at haemoglobin level (Hb) of 7 g/dl or 9 g/dl, stratified by the presence of haematological malignancy and centre. The primary outcome measure is 90-day mortality. Secondary outcome measures are organ failure, ischaemic events, severe adverse reactions (SARs: anaphylactic reaction, acute haemolytic reaction and transfusion-related circulatory overload, and acute lung injury) and mortality at 28 days, 6 months and 1 year.
The sample size will enable us to detect a 9% absolute difference in 90-day mortality assuming a 45% event rate with a type 1 error rate of 5% and power of 80%. An interim analysis will be performed after 500 patients, and the Data Monitoring and Safety Committee will recommend the trial be stopped if a group difference in 90-day mortality with P ≤0.001 is present at this point.
The TRISS trial may bridge the gap between clinical practice and the lack of efficacy and safety data on RBC transfusion in septic shock patients. The effect of restrictive versus liberal RBC transfusion strategy on mortality, organ failure, ischaemic events and SARs will be evaluated.
Trial registration NCT01485315. Registration date 30 November 2011. First patient was randomised 3 December 2011.
PMCID: PMC3679866  PMID: 23702006
Sepsis; Septic shock; Intensive care medicine; Red blood cell transfusion; Fluid therapy
15.  A preliminary comparison of the prevalence of transfusion reactions in recipients of platelet component from donors with and without HLA antibodies 
Vox sanguinis  2008;94(4):324-328.
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.
PMCID: PMC2663785  PMID: 18282262
Transfusion medicine reviews  2008;22(2):162-167.
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.
PMCID: PMC2361154  PMID: 18353255
Transfusion reactions; Anti-IgA; Blood; borne infections; Viral hepatitis; Transfusion safety; Passive-active immunization
17.  Platelet-activating Factor–mediated NF-κB Dependency of a Late Anaphylactic Reaction 
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.
PMCID: PMC2196087  PMID: 12835479
early anaphylaxis; biphasic anaphylaxis; mast cell; penicillin V; TNF-α
18.  Haptoglobin genotypic distribution (including Hp0 allele) and associated serum haptoglobin concentrations in Koreans 
Journal of Clinical Pathology  2004;57(10):1094-1095.
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.
PMCID: PMC1770454  PMID: 15452167
haptoglobin; genotyping; gene deletion; hypohaptoglobinemia; anhaptoglobinemia
19.  Post-transfusion purpura in an African-American man due to human platelet antigen-5b alloantibody: a case report 
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.
Case presentation
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.
PMCID: PMC3549824  PMID: 23234542
20.  Serious hazards of transfusion (SHOT) initiative: analysis of the first two annual reports 
BMJ : British Medical Journal  1999;319(7201):16-19.
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
PMCID: PMC28147  PMID: 10390452
21.  A case report of transfusion-transmitted Plasmodium malariae from an asymptomatic non-immune traveller 
Malaria Journal  2013;12:439.
The incidence of transfusion-transmitted malaria is very low in non-endemic countries due to strict donor selection. The optimal strategy to mitigate the risk of transfusion-transmitted malaria in non-endemic countries without unnecessary exclusion of blood donations is, however, still debated and asymptomatic carriers of Plasmodium species may still be qualified to donate blood for transfusion purposes.
Case description
In April 2011, a 59-year-old Dutch woman with spiking fevers for four days was diagnosed with a Plasmodium malariae infection. The patient had never been abroad, but nine weeks before, she had received red blood cell transfusion for anaemia. The presumptive diagnosis of transfusion-transmitted quartan malaria was made and subsequently confirmed by retrospective PCR analysis of donor blood samples. The donor was a 36-year-old Dutch male who started donating blood in May 2006. His travel history outside Europe included a trip to Kenya, Tanzania and Zanzibar in 2005, to Thailand in 2006 and to Costa Rica in 2007. He only used malaria prophylaxis during his travel to Africa. The donor did not show any abnormalities upon physical examination in 2011, while laboratory examination demonstrated a thrombocytopenia of 126 × 109/L as the sole abnormal finding since 2007. Thick blood smear analysis and the Plasmodium PCR confirmed an ongoing subclinical P. malariae infection. Chloroquine therapy was started, after which the infection cleared and thrombocyte count normalized. Fourteen other recipients who received red blood cells from the involved donor were traced. None of them developed malaria symptoms.
This case demonstrates that P. malariae infections in non-immune travellers may occur without symptoms and persist subclinically for years. In addition, this case shows that these infections pose a threat to transfusion safety when subclinically infected persons donate blood after their return in a non-endemic malaria region.
Since thrombocytopenia was the only abnormality associated with the subclinical malaria infection in the donor, this case illustrates that an unexplained low platelet count after a visit to malaria-endemic countries may be an indicator for asymptomatic malaria even when caused by non-falciparum Plasmodium species.
PMCID: PMC3866504  PMID: 24304475
Malaria; Blood transfusion; Blood safety; Blood donor screening; Plasmodium malariae; Transfusion-transmitted malaria; Blood-borne; Infection; Thrombocytopenia; Asymptomatic malaria; Look-back
22.  Transfusion related acute lung injury presenting with acute dyspnoea: a case report 
Transfusion-related acute lung injury is emerging as a common cause of transfusion-related adverse events. However, awareness about this entity in the medical fraternity is low and it, consequently, remains a very under-reported and often an under-diagnosed complication of transfusion therapy.
Case presentation
We report a case of a 46-year old woman who developed acute respiratory and hemodynamic instability following a single unit blood transfusion in the postoperative period. Investigation results were non-specific and a diagnosis of transfusion-related acute lung injury was made after excluding other possible causes of acute lung injury. She responded to symptomatic management with ventilatory and vasopressor support and recovered completely over the next 72 hours.
The diagnosis of transfusion-related acute lung injury relies on excluding other causes of acute pulmonary edema following transfusion, such as sepsis, volume overload, and cardiogenic pulmonary edema. All plasma containing blood products have been implicated in transfusion-related acute lung injury, with the majority being linked to whole blood, packed red blood cells, platelets, and fresh-frozen plasma. The pathogenesis of transfusion-related acute lung injury may be explained by a "two-hit" hypothesis, involving priming of the inflammatory machinery and then activation of this primed mechanism. Treatment is supportive, with prognosis being substantially better than for most other causes of acute lung injury.
PMCID: PMC2582242  PMID: 18957111
23.  Successful prevention of recurrent anaphylactic events with anti-immunoglobulin E therapy 
Asia Pacific Allergy  2014;4(2):126-128.
Anaphylaxis is a fatal and systemic allergic reaction, which can be prevented by avoiding exposure to a causative agent. However, the causative agent cannot be identified in all cases and may be hardly avoided. A 41-year-old man, diagnosed with idiopathic anaphylaxis, experienced 6 anaphylactic events over 7 months, requiring 4 emergency department (ER) visits and 3 epinephrine self-injections. Anti-immunoglobulin E (IgE) therapy was introduced to prevent further anaphylactic events. He experienced no anaphylactic events during 13 months of 4 monthly injections from the beginning until his most recent ER visit because of a similar anaphylactic event. We report a patient who experienced recurrent anaphylactic events that were prevented effectively by anti-IgE therapy with omalizumab. Anti-IgE therapy might be considered as an option to prevent anaphylactic events in patients for whom the causative agent(s) cannot be identified or avoided.
PMCID: PMC4005346  PMID: 24809019
Anaphylaxis; Omalizumab; Immunoglobulin E; Prevention and control; Immediate hypersensitivity
24.  Management of aplastic anemia in a woman during pregnancy: a case report 
Aplastic anemia is a rare disease caused by destruction of pluripotent stem cells in bone marrow. During pregnancy it could be life-threatening for both mother and child. The only causal therapy for aplastic anemia is bone marrow transplantation, which is contraindicated during pregnancy because of potential embryo toxicity. Treatment options are erythrocytes and platelet transfusions and immunosuppressive therapy. There is, however, no agreement about the optimal supportive care and treatment regime for this disorder during pregnancy.
Case Presentation
A 26-year-old nulliparous Asian woman with an uneventful medical history was admitted to the hospital at 14 weeks' gestation because of excessive vomiting. Routine laboratory tests showed pancytopenia (Hb 3.5 mmol/L, leukocytes 3.5 *109/L, platelets 45 *109L). A bone marrow biopsy confirmed aplastic anemia. Methylprednisolon, cyclosporine A, packed cells and platelet transfusions were initiated. At 33 weeks she developed neutropenia (0.1 *109/L) for which oral colistin and tobramycin were given prophylactically. At 35 weeks labor was induced, during which she developed a fever of 38.2°C. She gave birth spontaneously to a healthy son weighing 2415 grams, who had no signs of pancytopenia. After delivery the blood count of the patient did not recover and did not respond to medication. Eighteen weeks after delivery she died of sepsis complicated by cerebral bleeding and infarction due to severe thrombocytopenia and neutropenia, despite optimal supportive treatment.
This potential life-threatening disease has a relatively good prognosis for both mother and child after optimal treatment. Transfusion during pregnancy is the first choice treatment with recommended hemoglobin levels of >5.5 mmol/L and platelet counts of >20 *109/L. Cyclosporine A seems a reasonable alternative therapy with a reported success rate in non-pregnant patients of 70% when combined with antithymocyte globuline. Our patient died 18 weeks postpartum from cerebral bleeding and infarction due to severe thrombocytopenia despite intensive supportive treatment, methylprednisolon and cyclosporine A.
PMCID: PMC3048477  PMID: 21324109
25.  An association between decreased cardiopulmonary complications (TRALI and TACO) and implementation of universal leukoreduction of blood transfusions 
Transfusion  2010;50(12):2738-2744.
Cardiopulmonary adverse events after transfusion include acute lung injury (TRALI) and circulatory overload (TACO), which are potentially lethal and incompletely understood.
Study Design and Methods
To determine whether the incidence of TRALI and TACO was affected by leukoreduction we conducted a retrospective, before and after study of acute transfusion reactions for the seven years prior to and after introduction of universal leukoreduction in 2000, involving 778,559 blood components.
Substantial decreases occurred in the rates of TRALI (−83%; from 2.8 cases per 100,000 components pre- to 0.48 post-universal leukoreduction; p=0.01), TACO (−49%; 7.4 to 3.8 cases per 100,000; p=0.03) and febrile reactions (−35%; 11.4 to 7.4 cases per 10,000; p<0.0001). The incidence of allergic reactions remained unchanged (7.0 per 100,000 pre- and post-universal leukoreduction). These outcomes were primarily attributable to decreased TRALI/TACO associated with RBC and platelet transfusions (−64%) with notably smaller decreases associated with FFP or cryoprecipitate transfusions (−29%). The incidence of TRALI/TACO after 28,120 washed red cell and 69,325 platelet transfusions was zero.
These data suggest novel hypotheses for further testing in animal models, in prospective clinical trials, and via the new US Hemovigilance System : (1) Is TACO or TRALI mitigated by leukoreduction? (2) Is the mechanism of TACO more complex than excessive blood volume? (3) Does washing mitigate TRALI and TACO due to platelet and RBC transfusions?
PMCID: PMC2944002  PMID: 20561296

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