Chronic Renal Failure as a Possible Risk Factor for Allergic Reaction in Therapeutic Plasma Exchange Using Fresh Frozen Plasma

The incidence of allergic reactions in patients with chronic renal failure during plasma exchange using fresh frozen plasma is not well known. We retrospectively reviewed 62 patients who underwent plasma exchange between January 2013 and May 2018. The most common indication for plasma exchange was desensitization/preconditioning for kidney transplant (61.3%, 38/62). The incidence of allergic reactions was significantly higher in patients with chronic renal failure than patients without (57.1% vs. 25.0%, P = 0.029). Also, the incidence of allergic reactions tended to be higher in peritoneal dialysis patients (75%, 3/4) than in hemodialysis (58.8%, 10/17) and preemptive kidney transplant (58%, 11/19). These results suggested the relationship of chronic renal failure and the incidence of allergic reactions in patients undergoing therapeutic plasma exchange using fresh frozen plasma.     

76例输血患者临床输血不良反应情况调查

目的:了解输血患者临床输血不良反应发生情况,为制定预防措施提供理论依据。方法:对2007-01-2013-06各种血液制品输注患者发生输血不良反应病例进行统计分析。结果:①在4 559例输血患者中发生不良反应76例,不良反应发生率为1.67%,其中发生发热反应31例,占40.79%,发生过敏反应45例,占59.21%,没有发生溶血性输血反应。②在各种血液制品中,以冰冻血浆不良反应发生率最高,为3.83%,以滤白细胞悬浮红细胞不良反应发生率最低,为0.72%。各种血液制品不良反应发生率比较,差异有统计学意义(χ2=31.71,P0.01)。③输血不良反应发生率随输血次数的增加而升高(χ2=22.16,P0.01)。结论:提高对血液制品的认识、严格掌握输血适应证以及应用滤除白细胞的技术等是降低输血不良反应发生率、提高输血安全性的重要措施。     

Current understanding of allergic transfusion reactions: incidence,pathogenesis, laboratory tests,prevention and treatment

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.     

Allergies,motif de recours aux urgences. Épidémiologie,l’urgence,l’après-urgence

The emergency room is frequently a place of recourse for patients having an allergic reaction. The most serious allergic emergencies seen in the emergency room are anaphylaxis and severe asthma. However, data on the incidence of anaphylaxis for outpatients are rare. The incidence of anaphylactic shock occurring outside hospitals would be equivalent to one to three cases for 100,000 habitants in a year. The allergens responsible were Hymenoptera stings, drugs given orally (nonsteroidal anti-inflammatory drugs and penicillin) and foods. Recent reports suggest that severe anaphylactic reactions to food are an increasing problem. Emergency room physicians must be trained to provide rapid management according to widely accepted protocols. After the acute anaphylactic reaction, cooperative interactions among emergency room personnel, patients and the allergist is necessary to maximize the possibility of preventing recurrences because anaphylaxis is a potentially life-threatening condition.     

Complications of therapeutic plasma exchange: experience with 4857 treatments

Plasma exchange (PE) is a technique of extracorporeal blood purification which removes large molecular weight substances from plasma. The Department of Dialysis, Zagreb University Hospital Center's database, which includes data on 509 patients, or 4857 PE treatments, was retrospectively analyzed to test the safety of PE. A total of 231 adverse reactions were recorded (4.75% of treatments). The most common complications were paresthesias (2.7%), hematoma at the puncture site (2.4%), clotting (1.7%), mild to moderate allergic reactions (urticaria; 1.6%) and bleeding (0.06%). True anaphylactoid reactions were recorded in five procedures. The incidence of severe, potentially life-threatening adverse reactions was 0.12%. The prophylactic use of calcium and potassium was responsible for a low incidence of electrolyte disturbances. There was no lethal outcome associated with PE. When carried out by experienced staff, PE is a relatively safe procedure. The use of fresh frozen plasma is associated with a higher rate of adverse reactions.     

An animal model of allogeneic donor platelet refractoriness: the effect of the time of leukodepletion.

Approximately 50% of multi-transfused individuals become refractory to random donor platelets. Recent clinical data suggest that those patients receiving leukocyte-depleted blood products are less likely to become refractory to random donor platelets than recipients of non-leukocyte-depleted products. Leukocyte depletion can be performed immediately after collection of a unit of whole blood before its storage (prestorage leukodepletion) or just before the transfusion of the blood product to a recipient, after its storage (poststorage leukodepletion). However, the most appropriate time for the leukodepletion of blood products has not been established. The present study was undertaken to establish an animal model of allogeneic platelet refractoriness, and to compare the effect of prestorage and poststorage leukodepletion on the frequency of refractoriness to allogeneic donor platelets. In this model, two strains of rabbits were used: California Black rabbits were used as blood donors, while New Zealand White rabbits were used as recipients. Eight weekly infusions of nonleukodepleted allogeneic fresh blood resulted in an allogeneic platelet refractory rate of 91.2% (31/34). The prestorage leukodepletion of the donor blood was associated with a significantly higher allogeneic platelet survival and lower refractory rate (33.3%) to allogeneic platelets than poststorage leukodepletion (66.7%). Furthermore, the data suggest that cell-free plasma products are capable of inducing refractoriness to allogeneic donor platelets; the stored plasma having a greater likelihood of inducing such refractoriness than fresh plasma. Thus, these data provide evidence that the prestorage leukodepletion of allogeneic donor blood is associated with a lower frequency of refractoriness and better allogeneic platelet survival than poststorage leukodepletion.     

Platelet function in anaphylaxis.

Human platelets, following immunological or nonimmunological activation, are capable of releasing a variety of biologically active mediators and are able to actively participate in hypersensitivity reactions, including anaphylaxis. These cells constitutively express functional receptors for the Fc fragment of IgE, both the low affinity receptor (Fc epsilonRII) and the high affinity receptor (Fc epsilonRI), and could be activated via IgE. Alterations in platelet function have been demonstrated in patients with allergy and nonallergic hypersensitivity, including hypersensitivity to acetylsalicylic acid. Moreover, activated platelets may be responsible for anaphylactic transfusion reactions. Various haemostatic disturbances, particularly a drop in platelet number, were observed during anaphylactic shock. The current review summarises the data from human and experimental studies on platelet function in anaphylactic reactions.     

Frozen Platelet Plates for Platelet Antibody Detection and Cross-Match

We performed 2 studies aimed at developing a frozen platelet panel suitable for platelet cross-matching. The stability of the most important platelet membrane glycoproteins and the reactivity of antigens of the human platelet antigen (HPA) and of the human leukocyte antigen (HLA) systems were evaluated with the platelet suspension immunofluorescence test (PSIFT) in a panel of platelets frozen in microplates with 6% dimethylsulfoxide. In study No. 1 we evaluated platelet reaction with a broad-spectrum weak anti-HLA and a potent anti-HPA-1a antiserum and the expression of glycoproteins Ib and IIb/IIIa complex on platelet membrane before freezing and after 0.5, 1, 2, 3, 4, 5, 6 and 12 months of storage at -80°C. In study No. 2 we examined platelet reactivity with anti-HPA-1b, -HPA-2a, -HPA-3a, -HLA-A2, -HLA-A3 of platelets stored frozen for 12 months in parallel with fresh platelets from the same donors. Study No. 1 showed that glycoprotein expression was stable and that the weak anti-HLA and the potent anti-HPA-1a antibodies were clearly detected during 12 months at -80°C. Of the 35 paired PSIFT performed in study No. 2 with fresh and frozen/thawed platelets incubated with anti-HPA-1b, -HPA-2a, -HPA-3a -HLA-A2, -HLA-A3 antisera and AB serum, concordant reactions were obtained in all cases with the exception of 1 case of HLA-A3-positive platelets incubated with anti-HLA-A3 antiserum, that was reactive with frozen/thawed platelets but nonreactive with fresh platelets from the same donor. The discrepant finding obtained with fresh platelets from 1 donor could be due to the well-known variable and weak association of HLA antigens to platelet membrane. We conclude that frozen platelet plates can be stored and used for at least 12 months for detecting platelet-reactive antibodies in patients' sera.     

Refractoriness to platelet transfusion

This review discusses the causes of refractoriness to platelet transfusions and presents three options for its management. Platelet refractoriness is a complication of platelet transfusion that affects variable proportions of patients, mostly depending on their diagnosis, previous immunologic stimuli, and type of blood products used for transfusion. A large recent study showed that platelet refractoriness develops in 13% of patients with acute leukemia transfused with traditional blood products and in 3 to 4% of recipients of white cell-reduced blood components. Options to manage platelet refractoriness include platelets from HLA-typed donors, platelet cross-matching, and the antibody specificity prediction method. The selection of the most convenient approach depends on local skills and the available economic and organizational resources. Finally, emerging concepts are presented which could impact the management of platelet refractoriness.     

Chronic intravascular coagulation associated with chronic myelocytic leukemia. Use of heparin in connection with a surgical procedure.

A women with Philadelphia chromosome-positive chronic myelocytic leukemia lived nearly 12 years from the time of diagnosis. During most of this period she received no therapy, and marked cyclic oscillations in the white blood cell count were documented. The last two years of her illness were marked by a hemorrhagic disorder associated with hypofibrinogenemia, thrombocytopenia, increased plasma fibrinopeptide A concentration and markedly elevated serum levels of fibrin degradation products. The coagulation disorder was rapidly reversible on several occasions with heparin therapy. After treatment with heparin and platelet transfusions, the patient underwent successful resection of a large ovarian cyst with excellent hemostasis during the procedure. Postoperatively, the administration of heparin and platelets was discontinued and a large wound hematoma developed. After resumption of therapy with heparin and platelets, the remainder of her postoperative course was uneventful. The literature on the subject is reviewed and tentative guidelines are offered concerning the management of patients with intravascular coagulation who require diagnostic or therapeutic surgical procedures.     

The annual cost of blood transfusions in the United Kingdom

This study estimated the annual cost of blood transfusions in the UK during 1994/1995. The analysis was based on published data, information derived from interviews with relevant NHS personnel and a purpose-designed structured questionnaire of blood donors. The cost to the UKs blood transfusion services of providing blood and blood products for transfusion was £165.5 million in 1994/1995. During this period, 2.75 million conventional donations of whole blood and 144 000 apheresis donations of platelets and plasma were collected: 2.58 million units of red blood cells were issued, resulting in ≈ 866 000 red blood cell transfusions; 334 000 units of fresh frozen plasma and 1.16 million units of platelets were issued, resulting in ≈ 17 000 and 188 000 isolated plasma and platelet transfusions, respectively. Hospital resource use attributable to providing blood transfusions during 1994/1995 cost the NHS £52.6 million. In total, blood transfusions cost the NHS £218.2 million during 1994/1995. Of this, red blood cell transfusions accounted for 76% of the annual cost, isolated platelet transfusions 16%, isolated plasma transfusions 1% and other products 7%. Donors incurred direct costs of £3.1 million and indirect costs of £11.2 million were accrued due to lost productivity. Additionally, blood donors gave up 2.5 million hours of their leisure time donating blood.     

Transfusion triggers for blood components

Whereas there are general guidelines for acceptable transfusion therapy, optimal transfusion therapy has not been determined for most clinical settings. Recent research has focused on controlled studies of red cell transfusion in specific clinical settings. Better determinations of oxygen delivery and consumption are needed to guide clinicians in determining whether transfusion is justified for patients during the perioperative period, those with coronary artery disease, and those in intensive care units. For sickle cell disease, the role of transfusion for acute complications can be life saving; however, the role of chronic transfusion regimens awaits further research into efficacy. Finally, whereas criteria for the prophylactic transfusion of platelets in hematologic diseases are well described, relatively little information is available on the value of platelet transfusion where the absolute count is less than 100,000 but greater than 50,000. The value of fresh frozen plasma components, both standard and sterilized, also requires elucidation.     

283例临床输血反应的分析

目的：回顾性分析我院近年来发生的输血反应。方法：对2006年1月-2009年9月期间输注各种血液成分的住院病例进行调查。结果：该期间共有41545人次的住院患者输注了111462U的各种血液成分,主要是去白红细胞悬液、新鲜冰冻血浆和冷沉淀;观察到283例发生了输血反应,反应发生率为0．25％,其中非溶血性发热性输血反应和过敏性输血反应占98．59％;不同的血液成分中,输注去白红细胞悬液、新鲜冰冻血浆和冷沉淀的输血反应发生率分别为0．16％、0．42％和0．30％。结论：急性输血反应主要是非溶血性发热性输血反应和过敏性输血反应,以输注新鲜冰冻血浆的反应发生率最高。     

Pathophysiology of febrile nonhemolytic transfusion reactions.

Most febrile nonhemolytic transfusion reactions (FNHTR) to platelets are caused by cytokines that accumulate in the product during storage. There have been numerous studies that have demonstrated high concentrations of leukocyte- and platelet-derived cytokines in stored platelet products. The mechanism of cytokine accumulation is not understood; however, recent studies have suggested that leukocyte apoptosis and/or monocyte activation during the manufacturing process may play a role. Additional support of cytokines as a cause of FNHTR is provided by a recently published randomized controlled trial that shows that removal of the supernatant plasma from platelets before transfusion significantly lowers the frequency of reactions and eliminates most of the severe reactions associated with platelet transfusions. Although cytokines appear to play a major role in causing platelet reactions, there is little evidence to support their role in causing erythrocyte reactions. Hence, it appears that most febrile nonhemolytic transfusion reactions to erythrocytes are probably the result of an incompatibility between leukocytes in the erythrocyte product and antibodies in the recipient's plasma. Recent studies have confirmed that the concentrations of proinflammatory cytokines in a wide variety of stored erythrocyte products are low. Also, there is no clinical evidence to suggest that the small quantities of cytokines present in stored erythrocyte products contribute to acute reactions to these products when transfused.     

Survival of baboon biotin-X-N-hydroxysuccinimide and (111)In-oxine-labelled autologous fresh and lyophilized reconstituted platelets

BACKGROUND AND OBJECTIVES: In accordance with Food and Drug Administration (FDA) regulations, platelets can be stored in the liquid state at 22 degrees C for only 5 days. Platelets frozen with 6% dimethylsulphoxide (DMSO) can be stored at -80 degrees C for 2 years, and platelets frozen with 5% DMSO can be stored at -150 degrees C for 3 years. Studies are being conducted to determine the effects of lyophilization of platelets. In the present study, we assessed the survival of autologous lyophilized-reconstituted platelets in the baboon. MATERIALS AND METHODS: We studied fresh baboon platelets and baboon platelets that had been treated with paraformaldehyde, frozen, lyophilized, thawed and reconstituted. Aliquots of these platelets were labelled with (111)In-oxine or biotin-X-N-hydroxysuccinimide (biotin-X-NHS) before autotransfusion, and measurements were made of the in vivo recovery and lifespan. We also evaluated the response of fresh and lyophilized platelets to in vitro agonists by measuring the level of platelet surface markers and heterotypic aggregates in the peripheral blood following the autotransfusions. RESULTS: The (111)In-oxine- or biotin-X-NHS-labelled lyophilized, reconstituted platelets exhibited survival times of less than 15 min. These platelets did not respond to stimulation with agonists to decrease platelet GPIb and increase platelet P-selectin and platelet GPIIb-IIIa levels 1 min post-transfusion and they accumulated more procoagulant factor V than did the fresh platelets. CONCLUSIONS: Lyophilized reconstituted baboon platelets labelled with (111)In-oxine or biotin-X-NHS before autotransfusion exhibited an in vivo circulation time of less than 15 min. Further study of the lyophilized, reconstituted platelets is required to evaluate their haemostatic function.     

Exchange Transfusions with Frozen Blood

Abstract. On 15 newborn infants, 31 exchange transfusions were performed, 11 with previously frozen red blood cells resuspended in albumin-electrolyte-glucose solution, 4 with previously frozen red blood cells resuspended in fresh frozen plasma and 16 with ACD blood.
Good clinical effects were obtained in all cases and no untoward clinical reactions were noticed. More pronounced decreases in vB pH and vB standard bicarbonate were noted after exchange transfusions with frozen blood than after ACD blood transfusions. Small and unimportant changes of plasma electrolytes were recorded following exchange transfusions with frozen blood. The P-haemoglobin concentrations were higher in the frozen blood than in the ACD blood, resulting in an increase of P-haemoglobin following exchange transfusion with frozen blood.
The wash-out effect of the frozen blood was indicated by a reduction of platelets, fibrinogen and IgG during the exchange transfusions to 20% of the original value. Furthermore, a decrease in coagulation capacity was observed as revealed by considerable changes in TT and APTT values.
For newborn infants with suspected or manifest coagulation disorders and for newborn infants needing more than one exchange transfusion, frozen, thawed and washed red blood cells should be resuspended in fresh or fresh frozen plasma when used as transfusion blood.     

重症患者血小板输注的临床研究

目的：探明重症患者血小板（PLT）减少的发生率及PLT输注的目的、指征、效果以及血小板减少对患者预后的影响。方法：采用回顾性方法分析临床资料,血小板减少定义为PLT〈100×109/L,根据PLT减少的程度分为轻度减少,PLT〈100×109/L;中度减少,PLT〈50×109/L;重度减少,PLT〈20×109/L。结果：53.4%（206例）重症患者住院期间曾出现PLT〈100×109/L,与PLT未减少患者相比PLT减少患者有较高的死亡率（P〈0.05）,需要输注较多的血小板（P〈0.05）、新鲜冰冻血浆（P〈0.05）和红细胞（P〈0.05）。结论：约50%重症监护病房住院患者在住院过程中出现过PLT〈100×109/L,血小板减少患者需要较多的输血支持,有较高的死亡率。     

The Viability of Stored Human Platelets

Viability of normal human platelets preserved for short intervals at 4 C. wasstudied by in vitro labelling with Na₂Cr⁵¹O₄. As a criterion of viability twoparameters were used: (1) the survival time of the infused platelets, and (2)the maximum percentage of platelet radioactivity which could be recoveredin the circulation after infusion. From these two parameters the platelet viability index was calculated, and for stored platelets this was expressed in percent of the value obtained with freshly prepared platelets.

After 3 hours of storage at 4 C. the platelet viability index was reduced to62 per cent. With longer periods of storage the viability of the platelets fellrapidly with viability indices of 12 per cent after 24 hours and 2 per cent after48 hours. No significant difference was seen whether the platelets were storedas whole blood, as platelet-rich plasma, or as platelet concentrates suspendedin a plasma medium. When stored in saline the platelets lost their viabilitymore rapidly and the viability index was less than 5 per cent after only 24 hours.When the platelets were stored for 24 hours in a DAS-gelatin medium, theirviability fell to insignificant levels within 24 hours.

Platelets frozen in glycerol-plasma and stored for 24 hours at —75 C. showedreduction of viability to one-fifth the value obtained with fresh, unfrozen platelets. Even without storage the frozen platelets showed similar values of viability.

From these results the following conclusions may be drawn:

1. Conventional methods of storage at 4 C. result in rapid loss of plateletviability. An inverse, almost logarithmic, relationship exists between time ofstorage at 4 C. and platelet viability. The glycerol-freezing technique, althoughbetter than most available methods, induces a great loss in platelet viability.

2. At present no method can be advised by which platelets can be preservedin viable form even for relatively short periods of time. However, it is important to know that in the absence of plasma, platelet viability is lost morerapidly than in a plasma medium.

3. From the data obtained, it seems advisable for the practice of platelettransfusion to infuse platelets within less than 3 hours after collection.

4. Methods of improving the viability of stored blood platelets based upontheir metabolic needs are strongly warranted and are now under study.

Submitted on June 6, 1960 Accepted on July 13, 1960     

Risks and side effects of therapy with plasma and plasma fractions

Transfusion of plasma can lead to adverse reactions or events. Immune-mediated reactions are most common--these include allergic and anaphylactic reactions, transfusion-related acute lung injury (TRALI) and haemolysis. They can range in severity from mild to fatal. Fluid overload and citrate toxicity can occur after rapid or massive transfusion. In developed countries, microbial transmission rates are low because of donor selection and testing. Pathogen reduction processes can be applied to either single-unit components (methylene blue) or plasma pools (solvent-detergent). They have the unwanted effect of reducing some coagulation factors but reduce viral transmission risk even further. Reactions associated with plasma products or fractions also include allergic reactions, although TRALI is rare. Viral transmission risk is very low because of the use of two independent viral inactivation steps. Different products have particular specific unwanted effects: intravenous immunoglobulin has been associated with thrombotic events, renal toxicity and aseptic meningitis; coagulation factors are associated with development of inhibitors and thrombotic events. The risk of transmission of variant Creutzfeldt-Jakob disease in both plasma components and pooled plasma products is as yet unknown. If anything, the low titre of prion infectivity in the blood of an infected individual (approximately 10 infectious units/ml) will be massively diluted by the thousands of units of plasma in the pool. Subsequent manufacturing processes also remove prions from the final product.     

Fibrinogen concentrates for bleeding trauma patients: what is the evidence?

Introduction A balanced transfusion of red blood cells, fresh frozen plasma and platelets are recommended for massively bleeding trauma patients. Fibrinogen concentrates could potentially lessen or replace the need for fresh frozen plasma and/or platelet transfusions. Objective To provide a review of the literature covering the application of fibrinogen concentrates in trauma care. Methods PubMed and Cochrane database search, ‘fibrinogen’ and (‘concentrate’ or ‘trauma’), not ‘congenital’, 10 years. Results Only four papers were identified. None were randomized controlled trials. The main conclusion of these papers was that administration of fibrinogen sometimes together with prothrombin complex concentrate might improve haemostasis in trauma patients resuscitated with synthetic colloids. Conclusion Evidence for the use of fibrinogen concentrate to trauma patients with massive bleeding is lacking. Well‐designed prospective, randomized, double‐blinded studies evaluating the effect of fibrinogen concentrate, as the only intervention, are urgently needed.