Neonatal metabolism and endocrinology studied by exchange transfusion.

The work reviewed here illustrates how a therapeutic procedure, exchange transfusion of newborn infants, may be used to gather information which is both of practical value to infants treated in this way and also of value in the study of human neonatal physiology. The scientific deductions that can be drawn are weakened by the uncontrolled nature of the subjects available for study but this problem can be mitigated by changing one variable at a time between two groups of clinically similar infants undergoing transfusion and paying attention only to large changes in whatever is measured. In this way it has been possible to show that the glucose of ACD blood stimulates insulin and GH secretion and that the stimulation of insulin secretion is less, and that of GH more, if the transfusion is performed via the umbilical artery rather than via the vein. Arterial transfusions may be more stressful than venous ones since they are associated with greater growth hormone, ACTH and glucocorticoid release. Citrate, the other additive in ACD blood, causes a fall in ionised plasma calcium levels resulting in a stimulation of PTH secretion and mobilisation of calcium and phosphorus. Transfusion with heparinised blood is therefore preferred by some because normoglycaemia is preserved during and for three hours after transfusion, whereas post-transfusion hypoglycaemia may occur after ACD transfusion. However, heparin transfusion causes a marked rise in plasma FFA levels which may interfere with the binding of bilirubin by albumin. In either type of transfusion the side-effects may be minimised by feeding the baby afterwards, as soon as practicable. Thyroid hormones are washed out of the infant during transfusion but normal thyroid balance is restored quickly afterwards. The temperature of the donor blood does have thermal effects on the baby but these are less than might be expected due to the rapid equilibration of donor blood temperature with that of the room. The metabolic consequences of transfusion with cold blood are less than might be anticipated due in part to the glucose infusion that is part of an ACD transfusion.     

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.     

Clinical Experience with Transfusion of Cryopreserved Platelets

S ummary . Multiple units of platelet concentrate obtained by plateletpheresis of normal, 'random'or HL-A matched donors were pooled and frozen in polyolefin bags using 5% dimethylsulphoxide (DMSO) as a cryoprotective agent and a controlled freezing rate of 1°/min. The platelets were stored at approximately — 120° C for as long as 201 days, thawed rapidly at 37°, washed once and resuspended in ACD plasma prior to transfusion. Two different final concentrations of platelets (˜ 2.7 and 9.0 × 10¹²/1.) were studied. Twenty-three thrombocytopenic patients have received a total of 40 frozen platelet transfusions. The mean freeze-thaw loss was 21% and was similar for both platelet concentrations. All transfusions were well tolerated and there were no side effects attributable to the small amounts of DMSO infused. Increments in platelet counts I h after transfusion ranged from 0 to 102 × 10⁹/1. with an overall mean corrected increase in evaluable patients of 12 800 (increase × surface area (m²)/number of platelets transfused × 10¹¹). Corrected increases tended to be greater with the low concentration of platelets. Overall, the increase in count for the frozen platelet transfusions was 65% of the increments obtained with fresh platelet transfusions administered within I week of the frozen platelets. Bleeding times were partially corrected after four out of six transfusions with post-transfusion counts greater than 50 × 10⁹/1., and active haemorrhage was controlled in some patients by frozen platelet transfusions. These results indicate that pooled platelets can be frozen, thawed and transfused with reasonable efficiency. The frozen platelets can circulate and function haemostatically and may eventually play an important role in supportive care.     

The role of blood transfusion in the management of upper and lower intestinal tract bleeding

Patients with gastrointestinal (GI) haemorrhage use 13.8% of all red blood cell transfusions in England. This review addresses the evidence for red blood cell, fresh frozen plasma and platelet transfusions in acute and chronic blood loss, from both the upper and lower intestinal tract. It reviews the indications for transfusion in GI bleeding, the haematological consequences of massive blood loss and massive transfusion, and the importance of managing coagulopathy in bleeding patients. It also looks at the safety and risks of blood transfusion, and provides clinicians with evidence to reduce unnecessary transfusion. Large controlled clinical trials of blood transfusion specifically in GI bleeding are required, along with further research into the use of adjuvant therapies such as recombinant activated factor VIIa. Changing clinician behaviour to reduce inappropriate blood transfusion remains a key target for future transfusion research.     

Delayed intravascular haemolysis following multiple asymptomatic ABO‐incompatible red blood cell transfusions in a patient with hepatic failure

ABO‐incompatible red blood cell (RBC) transfusions have rarely been associated with delayed haemolysis. However, we report the case of a 75‐year‐old man (blood type O) with hepatic disease, who received 5 units of incompatible type B RBCs over 8 days. The patient did not develop symptomatic or biochemical evidence of haemolysis until 7–8 days after the first incompatible RBC unit. The patient had a low anti‐B antibody titre (1 : 64) prior to the first transfusion. The onset of haemolysis was temporally associated with an increase in anti‐B and the infusion of fresh‐frozen plasma. In conclusion, a patient with hepatic failure experienced a delayed haemolytic transfusion reaction after receiving multiple ABO‐incompatible RBC transfusions that were initially well‐tolerated. We speculate that the delayed haemolysis may have resulted from an anamnestic antibody response to the initial incompatible transfusion, or possibly as a result of the transfusion of fresh‐frozen plasma, which might have repleted low complement levels.     

Prevalence of TT virus before and after blood transfusion in patients with chronic liver disease treated surgically for hepatocellular carcinoma

BACKGROUND: To examine the prevalence of TT virus (TTV) before and after blood transfusion, we retrospectively examined serum samples obtained from 55 patients who received blood transfusions before, during and after resection of hepatocellular carcinoma. METHODS: TT virus DNA was extracted from serum samples and detected by nested polymerase chain reaction. Before transfusion, seven (12.7%) were positive for TTV. Patients were transfused whole blood or separated blood components (fresh frozen plasma, platelet and/or red blood cells), the total amount of transfused fresh frozen plasma ranging from 12 to 271 (median 38) units. RESULTS: Seven (14.6%) of the 48 TTV-negative patients became positive for TTV-DNA 1 month after transfusion. Only one of the seven patients, who was already positive for HCV-RNA, exhibited elevation of alanine aminotransferase. Five of the newly infected seven patients become negative for TTV during a 2 year follow up. CONCLUSIONS: Our findings suggest that the proportion of patients with TTV was relatively high in this sample, and that the prevalence of TTV transmission by blood components was also relatively high (14.6%). Although TTV persisted for more than 6 months in some patients, infection was not noticeable during the course of chronic liver disease.     

机洗冰冻红细胞在日常及突发事件中伤员救治的应用

目的:机器洗涤冰冻红细胞在日常和突发事件中的紧急抢救可行性。方法:选择日常及交通伤患者的大出血中冰冻红细胞输注,观察各种指标。结果:患者在输注冰冻红细胞后各项指标正常,效果明显,无输血反应。结论:冰冻红血细胞可应用于日常和紧急大出血的抢救。     

Endoscopic findings and management of dengue patients with upper gastrointestinal bleeding

There are 100 million cases of dengue infection, 500,000 cases of dengue hemorrhagic fever, and 25,000 deaths annually due to dengue worldwide. Gastrointestinal bleeding is the most common type of severe hemorrhage in dengue fever. However, there are no reports about the clinical applications of endoscopic therapy for upper gastrointestinal bleeding (UGI) in dengue patients. From June 17, 2002 to January 30, 2003, 1,156 patients with confirmed dengue virus infection were treated at Kaohsiung Chang Gung Memorial Hospital in Taiwan. We analyzed those patients who had received endoscopic therapy for UGI. The characteristic endoscopic findings, therapeutic courses, and amount of blood component transfused were collected from their charts for statistical analysis. Among the 1,156 dengue patients, 97 (8.4%) had complications of UGI bleeding during hospitalization. The endoscopic findings included hemorrhagic (and/or erosive) gastritis in 67% of the patients, gastric ulcer in 57.7%, duodenal ulcer in 26.8%, and esophageal ulcer in 3.1%. Of the 73 patients with peptic ulcer, 42 (57.5%) met the endoscopic criteria (recent hemorrhage) for endoscopic hemostasis therapy. Peptic ulcer patients with recent hemorrhage required more transfusions with packed red blood cells (P = 0.002) and fresh frozen plasma (P = 0.05) than those without recent hemorrhage. Among these 42 patients with recent hemorrhage, endoscopic injection therapy was conducted in 15 patients (group A). The other 27 patients (group B) did not receive endoscopic therapy. After endoscopy, patients in group A required more transfusions with packed red blood cells (P = 0.03) and fresh frozen plasma (P = 0.014) than did patients in group B. There were no significant differences between groups A and B in duration of hospital stay and amounts of transfused platelet concentrate after endoscopy. Medical treatment with blood transfusion is the mainstay of management of UGI bleeding in dengue patients. Patients having peptic ulcer with recent hemorrhage require more transfusions with packed red blood cells and fresh frozen plasma for management of UGI bleeding than those without recent hemorrhage. However, when peptic ulcer with recent hemorrhage is encountered during the endoscopic procedure, endoscopic injection therapy is not an effective adjuvant treatment of hemostasis in dengue patients with UGI bleeding.     

Plasma pH and anticoagulant solutions used in the plasmapheresis method of blood collection from donors

The resulting pH of fresh frozen plasma for clinical use, collected by plasmapheresis from blood donors is influenced by the type of anticoagulant solution and its ratio with the donor's blood. The authors describe the use of three anticoagulant solutions with a different sodium citrate concentration and different ratios of donor blood. As compared with the physiological range of pH of the blood, the resulting pH value of the collected plasma, when using ACD-A and AB-16 solutions, varies within the range classified as acidosis, i.e. less than 7.36. When using a 4% sodium citrate solution the plasma pH value is in the area evaluated as alkalosis. The authors discuss indications for administration of fresh frozen plasma in clinically serious diseases and the influence of administration of this transfusion preparation on the acid-base balance as the transfusion recipients are threatened by the development of metabolic acidosis. Maintaining the pH value of fresh frozen plasma slightly above the physiological range of blood pH prevents in particular during massive plasma transfusions the possibility of deterioration of acidosis or its development.     

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.     

Effective Reduction of Blood Product Use in a Community Teaching Hospital: When Less Is More

Background

The increased morbidity and mortality associated with liberal blood product usage have been convincingly demonstrated. The clinical problems they pose have prompted development of more restrictive evidence-based transfusion criteria. Education alone has a limited impact on the adoption of these criteria into practice. New York Methodist Hospital undertook a proactive approach to reduce unnecessary transfusions.

Method

In November 2008, an interventional monitoring program to ensure adherence to transfusion criteria for packed red blood cells (PRBC), platelets, fresh frozen plasma (FFP), and cryoprecipitate transfusions was started. Blood bank technologists routinely monitored transfusion requests against a list of established criteria and experienced clinicians reviewed and adjudicated transfusion requests when the blood bank technologist's action was appealed.

Results

Transfusion usage decreased sharply in Year 1 (November 2008-October 2009) and continued to decrease in Year 2 (November 2009-October 2010). PRBC use decreased by 30.1% and 37.7%, with a 47.6% decrease in multi-unit transfusions; platelet use decreased by 24.3% and 41.2%; fresh frozen plasma use decreased by 41.8% and 31.1%; and cryoprecipitate use decreased by 38.7% and 56.1% during monitoring Years 1 and 2, respectively. Decreases occurred despite a 4.0% increase in hospital admissions during the monitoring years. The decreased blood product usage was accompanied by 28.6% reduction in complications. A 26.1% decrease in blood product requests from Year 1 to Year 2 suggested a practice change by the ordering physicians themselves. The total cost of blood products decreased by $2,235,676.

Conclusion

We established a successful method to reduce transfusions of all blood products using strict adherence to evidence-based criteria and continuous monitoring. Our model translates into improved patient safety by decreasing the number of unnecessary transfusions. This also led to a significant reduction in hospital expenses.     

Splenic platelet-sequestration following routine blood transfusion is reduced by filtered/washed blood products

The mean fall in the platelet count following 23 routine transfusions of 3-5 units packed cells for anaemia was 32.5%. This was significantly reduced to 12.5% in 15 similar transfusions through a 40 microns microaggregate filter (P less than 0.01) and to 4.6% following five transfusions through a polyester fibre filter (P less than 0.005). In 10 transfusions with frozen or polyester fibre filtered, washed red cells, the decrease in platelet count was 4.2% (P less than 0.001). A study of 111In-oxine labelled autologous platelets in nine patients indicated that the fall in platelet count was due to increased splenic sequestration. Since thrombocytopenia following routine transfusion is reduced by procedures which filter the packed cells, the decrease in platelets is probably caused by their adherence to infused microaggregate debris causing their premature removal from the circulation. Patients with preexisting thrombocytopenia who receive red cell transfusions for anaemia, should therefore receive blood products depleted of microaggregate debris in order to avoid exacerbation of thrombocytopenia and haemorrhagic complications.     

Post-Transfusion Purpura: Initiation by Leukocyte-Poor Red Cells in a Polytransfused Woman

An elderly, multiparous, multiply transfused woman developed post-transfusion purpura (PTP) after the transfusion of 2 units of leukocyte-poor red cells and was successfully treated by plasmapheresis and corticosteroids. Her pre-PTP transfusion history was characterized by frequent, multiple transfusions of platelet antigen-containing blood products 12 to 5.5 years prior to the onset of disease and, apart from the initiating transfusion, only frozen red cells in the 5.5 years immediately preceding the onset of thrombocytopenia. Leukocyte-poor red cells thus appear capable of initiating PTP. Use of a few units of frozen red cells may result in a shorter than normal refractory period, after which time PTP may occur upon exposure to sufficient platelet antigen.     

Early Immunization against Platelet Glycoprotein Ilia in a Newborn Glanzmann Type I Patient

Alloimmunization against platelet glycoprotein IIb and/or IIIa is a complication rarely observed during the evolution of type I Glanzmann's thrombasthenic patients. The occurrence of such alloantibodies is usually due to repeated blood transfusion and greatly complicates the treatment of these patients since they prevent effective platelet transfusion and might, theoretically, cause posttransfusion purpura. We describe the case of a newborn thrombasthenic patient who developed an IgG platelet allo-antibody 1 month after birth. The diagnosis of Glanzmann's thrombasthenia was complicated by the rare platelet phenotype (PLA1-negative PLA2-positive) of the healthy mother, which was probably heterozygous for the abnormal thrombasthenic gene. Immunofluorescence and immunoblotting techniques demonstrated that the patient antibody was principally directed against the platelet glycoprotein IIIa. Surprisingly, this patient had only received four blood transfusions (fresh frozen plasma on days 1 and 2, and standard red blood cell concentrates on days 5 and 6) before the discovery of the antibody, suggesting prior in utero sensitization. This study emphasizes the need for early diagnosis of the disease. Thrombasthenic patients should be transfused with deleukocyted platelet-free blood products.     

False-positive Aspergillus antigenemia due to blood product conditioning fluids

The presence of Aspergillus antigens in blood transfusion components from different manufacturers was analyzed. Galacomannans were found in transfused patients, pooled platelet concentrates, fresh frozen plasma, and packed red cells collected using Fresenius Kabi bags. Galacomannans were also found in blood collection anticoagulant and platelet additive solution from this manufacturer.     

Effect of Different Resuspension Media on the Post-thaw Characteristics of Frozen Blood

Summary. Red blood cells frozen by the low-glycerol fast-freezing technique were thawed, deglycerolized and resuspended in various media. The use of ACD-saline for resuspension markedly reduced in vitro haemolysis such that the red cells could be transfused up to 5 d after thawing. At this time the cells contained satisfactory levels of potassium and organic phosphates, while bacterial contamination was negligible. For the past 4 years we have operated a small bank of previously frozen red blood cells which were thawed and resuspended in this way. Over 3500 units have been transfused after 1–5 d post-thaw storage without untoward effects.     

Massive transfusion – evaluation of current clinical practice and outcome in two large teaching hospital trusts in Northern England

Background and Objectives  Although numerous guidelines exist for the management of massive blood loss, there have been few data confirming whether these guidelines are observed in practice or whether compliance results in improved outcome. We have performed a retrospective audit of cases of massive transfusion in two major teaching hospital trusts in Northern England to investigate the use of blood components and patient outcome.
Materials and Methods  The massive transfusion population was electronically derived from a list of all blood component transfusions in 2006. Data from the intensive care and patient administration databases established hospital outcome. Factors independently predictive of survival were identified by logistic regression. Data are presented as medians and interquartile ranges. Odds ratios (OR) are given with 95% confidence intervals.
Results  Two hundred and four patients had a massive transfusion. Although only 1·3% of all transfused patients, the massive transfusion group used 10% of the total blood products. Their mortality rate was 34%. Factors independently predictive of survival were: a ratio of fresh frozen plasma: red blood cells > 1·1, OR 7·22 (1·95–26·68), and elective surgery, OR 4·56 (1·88–11·05). Factors independently predictive of death were: age (per year), OR 0·97 (0·95–0·99), liver disease, OR 0·25 (0·09–0·70), male gender, OR 0·41 (0·19–0·89), vascular surgery, OR 0·34 (0·12–0·96) and number of adult packs of platelets transfused, OR 0·69 (0·57–0·83).
Conclusion  Massive transfusion occurs rarely but has a high mortality and requires a disproportionate amount of blood products. An increased ratio of fresh frozen plasma to red blood cells was associated with improved outcome.     

Severe ABO Haemolytic Disease Due to High Titre IgG Anti-B in an A2 Mother

Abstract. A group B premature infant (mother group A₂), which was transfused 12 ml fresh frozen plasma and subsequently required three exchange transfusions, was found to be suffering from ABO haemolytic disease of the newborn. It was considered that the principal factor responsible for the degree of jaundice experienced by the infant was the swamping of its 'protective mechanism' by maternal high-titre IgG anti-B, and that its prematurity and the administration of fresh frozen plasma had only minimal effect.     

Neonatal red blood cell transfusions

Red blood cell and blood product transfusion in the fetus, neonate, and premature infant are often administered with poorly defined indications and unintentional adverse consequences. Products may be altered in an effort to limit potential adverse events or may be specially selected to meet the unique needs of a specific diagnosis. One area of particular concern to neonatologists is selection blood for small volume (5-15 mL/kg) transfusions in premature infants. For infants, use of red blood cells collected in anticoagulant-additive solutions and administered in small aliquots over the shelf life of the product to decrease donor exposure has supplanted the use of fresh red blood cells with each transfusion resulting in a donor exposure. The safety of this practice has been documented and procedures established to aid a transfusion service in making these products available. Less well established are the indications for transfusion in this population; hemoglobin or Hematocrit alone are likely insufficient unless clinical findings like oxygen desaturation, apnea, and bradycardia are part of the criteria used to define transfusion need. The comorbidities that increase oxygen demands in these infants, like bronchopulmonary dysplasia and increased oxygen consumption to accommodate growth, must be part of the decision to transfuse. Noninvasive methods or assays that will reflect the unique pathophysiology of oxygen delivery and peripheral oxygen offloading are needed.     

Pediatric hemostasis and use of plasma components

Indications for fresh frozen plasma (FFP), once used routinely in the support of critically ill infants and children, have become more specific as evolving evidence has confirmed or disproved the efficacy of plasma in various circumstances. FFP is currently indicated to treat the coagulopathies of massive hemorrhage, liver failure and disseminated intravascular coagulation and sepsis. Whole blood reconstituted from FFP and packed red cells is the product of choice for exchange transfusion, as well as for circuit priming. In the US, FFP remains the only approved source of factors V, XI, protein C, protein S and plasminogen. Cryoprecipitate is used chiefly as a source of fibrinogen, factor VIII and factor XIII in consumptive coagulopathy; recombinant or viral inactivated plasma derivatives are preferred for congenital deficiencies of factor VIII and von Willebrand factor. Recombinant and highly purified, viral inactivated, plasma-derived proteins are preferred over FFP for congenital and acquired deficiencies. This chapter reviews evidence to support the use of plasma and plasma derivatives for pediatric patients.