Life threatening bleeding and emergency procedures in patients on vitamin K antagonists are indications for urgent reversal with prothrombin complex concentrate and vitamin K. Rapid reversal in these situations is emphasized in the literature and guidelines, but only very limited information is available on its real life use, especially on the timing of treatment in relation to presentation.
Materials and methods
We retrospectively audited emergency warfarin reversal in 131 consecutive patients. We studied the indication, use of vitamin K, time between presentation and administration of vitamin K and PCC, effectiveness in INR reduction and clinical outcome.
The median PCC dose was 26.8 IU/kg. The median INR was reduced from 3.1 to 1.2. Vitamin K (5 mg) was given in 91.6% of evaluable patients. We found significant delays in administration of PCC and vitamin K. The median time between presentation and administration of vitamin K/PCC was 3.6 and 5.2 hours respectively. The times in intracranial haemorrhage were 2.7 and 3.0 hours and in emergency procedures 17.4 and 15.9 hours respectively. Mortality related to bleeding was 7.6% overall but in patients with intracranial haemorrhage 22.8%. The thrombotic rate within 7 days of reversal was 1.5%.
The local protocol for reversal with PCC and vitamin K was adhered to well but the delay in pre-procedural patients, suggests that intravenous vitamin K alone may be sufficient in many cases and PCC administration can be avoided by better planning. Intracranial haemorrhage in warfarinised patients carries a high mortality. Treatment delays should be avoided by making PCC stocks available within emergency departments, simple dosing structures independent of INR and administering PCC without waiting for INR and CT scan results in those with strong suspicion of intracranial haemorrhage and clear trauma. Future reports and studies should always include the time from presentation to PCC treatment.
prothrombin complex concentrate; vitamin K antagonist; reversal; warfarin; haemorrhage
Cannulation of the internal jugular vein (CVC) is a blind surface landmark-guided technique that could be potentially dangerous in patients with very low platelet counts. In such patients, ultrasonography (US)-guided CVC may be a valid approach. There is a lack of published data on the efficacy and safety of urgent US-guided CVC performed in haematological patients with severe thrombocytopenia.
Materials and methods
We retrospectively studied the safety of urgent CVC procedures in haematological patients including those with severe thrombocytopenia (platelet count <30×109/L). From January 1999 to June 2009, 431 CVC insertional procedures in 431 consecutive patients were evaluated. Patients were included in the study if they had a haematological disorder and required urgent CVC insertion. Patients were placed in Trendelenburg's position, an 18-gauge needle and guide-wire were advanced under real-time US guidance into the last part of the internal jugular vein; central venous cannulation of the internal jugular vein was performed using the Seldinger technique in all the procedures. Major and minor procedure-related complications were recorded.
All 431 patients studied had haematological disorders: 39 had severe thrombocytopenia, refractory to platelet transfusion (group 1), while 392 did not have severe thrombocytopenia (group 2). The general characteristics of the patients in the two groups differed only for platelet count. The average time taken to perform the procedure was 4 minutes. Success rates were 97.4% and 97.9% in group 1 and group 2, respectively. No major complications occurred in either group.
US-guided CVC is a safe and effective approach in haematological patients with severe thrombocytopenia requiring urgent cannulation for life support, plasma-exchange, chemotherapy and transfusion.
central venous catheterisation; ultrasound; Seldinger technique; low platelet count; haematological malignancy
Fluid replacement results in dilutional coagulopathy. We investigated the potential role of fibrinogen, factor XIII and a combination of both to reverse dilutional coagulopathy, assessed by thromboelastometry (ROTEM
Material and methods
Blood samples from healthy volunteers were analysed undiluted and after 33% dilution
with albumin, gelatine, 130/0.4 hydroxyethyl starch or saline. Diluted samples were incubated with fibrinogen (3 g/70 kg bodyweight equivalent), factor XIII (10,000 IU/70 kg bodyweight equivalent), or a combination of both. Measurements were performed using an extrinsic activated assay (EXTEM
) and a functional fibrin polymerisation test (FIBTEM
Compared with baseline, EXTEM clotting time increased with hydroxyethyl starch, exceeding the upper limit of the reference value. Albumin prolonged clotting time within normal limits. Gelatine did not change clotting time, and saline reduced clotting time. Clot formation time increased in colloids only. Maximum clot firmness of both EXTEM and FIBTEM decreased with all fluids, but was less pronounced in saline. Incubation with fibrinogen had no effect on EXTEM maximum clot firmness but improved FIBTEM maximum clot firmness in saline (P <0.001) and albumin (P <0.05), but not gelatine and hydroxyethyl starch). Factor XIII had no effect on any EXTEM and FIBTEM maximum clot firmness results. Fibrinogen and factor XIII combined did not improve EXTEM maximum clot firmness. Fibrinogen and factor XIII did not change FIBTEM maximum clot firmness in hydroxyethyl starch but improved FIBTEM maximum clot firmness in albumin (P <0.001), gelatine (P <0.01) and saline (P <0.001).
ROTEM parameters in dilutional coagulopathy
cannot be improved with factor XIII alone in any tested diluent. The combination of fibrinogen and factor XIII is highly effective in raising FIBTEM maximum clot firmness after dilution with albumin, gelatine and saline back to normal values, but is ineffective in 130/0.4 hydroxyethyl starch.
In 2010, the Italian Society of Immunohaematology and Transfusion Medicine (SIMTI) carried out a survey of the incidence of haemolytic disease of the newborn (HDN) and the prevention of HDN caused by anti-Rh(D) in Italian Transfusion Structures (TS).
Materials and methods
A questionnaire divided into the following five sections was administered: (i) types of services provided and maintenance of legally required registers, (ii) immunoprophylaxis (IP), (iii) red cell typing and searches for irregular antibodies, (iv) evaluation of foetal-maternal haemorrhage (FMH), and (v) incidence of HDN in 2010. Of the 280 TS sent the questionnaire, 176 (63%) replied.
A HDN register was available in 55.5% of the TS (n =91). Immunoprophylaxis with a dose of anti-D IgG was given to all Rh(D) negative and Rh(D) variant puerpera with Rh(D) positive newborns: in more than 93% of cases the dose was between 1,500 IU (300 μg) and 1,250 IU (250 μg). Antenatal IP between the 25th and 28th week was proposed by 42 TS (26%). Seventy percent of the TS (n =115) did not make any evaluation of FMH. The number of births surveyed in 2010 was 203,384, the number of Rh(D) negative pregnancies was 13,569, while anti-D antibodies were present in 245 pregnancies. There were 111 cases of HDN due to anti Rh(D) incompatibility and in 40 of these, intrauterine transfusion (n =8) or exchange transfusion (n =32) was necessary. In 94 cases HDN was due to other irregular antibodies: in 4 of these cases intrauterine transfusion was needed and in 11 other recourse was made of exchange transfusion. Finally, there were 1,456 newborns with ABO HDN of whom 13 underwent exchange transfusion.
The data collected give a picture of the incidence of HDN in Italy and of the methods of managing IP and could form the basis for an update of the SIMTI recommendations on the management and prevention of this disease.
anti-D immunoprophylaxis; haemolytic disease of the newborn; anti-D immunoglobulins; FMH
The aim of this study was to determine the relationship between non-RhD immunisation and the consequent development of haemolytic disease of the newborn in pregnant women with a history of red blood cell transfusion compared to those without a history of transfusion.
Materials and methods
This retrospective cohort study included all pregnancies with red blood cellantibodies that were tested between 1993 and 2010. Data were obtained from the forms for immunisation tracking at the Department of Transfusion Medicine. Each form contained data on previous maternal transfusions, antibody specificities and whether the antibodies caused haemolytic disease of the newborn.
Clinically significant non-RhD antibodies was found in 214 of 108,000 pregnancies, of which the most frequent were anti-E (n =55), anti-K (n =54), and anti-c (n =52) antibodies. A history of red blood cell transfusion was identified in 102 (48%) of the pregnancies in which non-RhD antibodies were found (in 78% of the anti-K cases, 40% of the anti-c and 18% of the anti-E cases). Non-RhD antibodies caused haemolytic disease of the newborn in 44 cases of which 14 were very severe (2 anti-K, 8 anti-c, 3 anti-Rh17, 1 anti-E). The mother had a positive history of red blood cell transfusion in 39% of the cases of haemolytic disease of the newborn. Anti-c antibodies were involved in all cases with severe haemolytic disease of the newborn and a history of maternal red blood cell transfusion.
Primary prevention by using K-negative, Rhc-, RhE-, and RhC-compatible red blood cell transfusion for women younger than 45 years may prevent up to 40% of cases of haemolytic disease of the newborn. Rhc compatibile transfusion is the most important prevention strategy against severe haemolytic disease of the newborn caused by non-RhD antibodies.
haemolytic disease of newborn; prevention; RBC antibodies; maternal blood transfusions
Surgical intervention may pose significant risk of life-threatening bleeding in patients with von Willebrand's disease; prophylactic treatment with von Willebrand factor/factor VIII concentrate is generally indicated for von Willebrand's disease characterized by moderate to severe qualitative and quantitative deficiencies of Willebrand factor to raise and maintain both Willebrand factor and FVIII at haemostatic levels for surgical prophylaxis.
Materials and methods
Since prospective clinical data in such situations were lacking, two recent, prospective, multicentre studies evaluated the prophylactic perioperative use of the on Willebrand factor/ factor VIII concentrates, Humate-P® and Haemate P. Despite some differences in the two studies, one conducted in the USA (n =35) and one in the European Union (n =27), the designs were similar enough to allow for a limited pooled analysis of data. In both studies, preoperative loading doses and subsequent maintenance doses were calculated using individual subject-derived incremental in vivo recovery values, although von Willebrand factor:ristocetin cofactor and FVIII:coagulation activity target levels differed between the protocols. Efficacy was rated daily by the investigator as excellent, good, moderate, or poor.
Overall haemostatic efficacy (rating of excellent/good), assessed 24 hours after the last infusion (USA) or taken as the worst rating between surgery and day 14 (EU), was achieved in 95% of the pooled population of 62 adults and children. Efficacy did not appear to be affected by dosing variations. The rate of possibly related adverse events was low (8 subjects; 13%); one of these events was considered serious (pulmonary embolism).
This pooled analysis of a relatively large number of patients for a rare disease confirms the feasibility of pharmacokinetically guided dosing of von Willebrand factor/factor VIII concentrate and highlights its efficacy and safety in the prevention of excessive perioperative bleeding.
von Willebrand's disease; factor VIII; prophylaxis; elective surgery
Antibodies against the human neutrophil alloantigen-3a (HNA-3a) are involved in severe cases of transfusion-related acute lung injury (TRALI), but the susceptibility of patients towards HNA-3a antibody differs largely. HNA-3a antibodies induce granulocyte aggregation. However, it is unresolved whether plasma proteins are required for granulocyte aggregation.
Materials and methods
We investigated whether HNA-3a-antibody-induced aggregation of polymorphonuclear cells is dependent on plasma factors by using and modifying the granulocyte agglutination test (GAT).
Polymorphonuclear cells homozygous for HNA-3a did not aggregate when incubated with HNA-3a antibodies in a plasma-protein-free GAT setup. When the GAT was performed using polymorphonuclear cells re-suspended in phosphate-buffered saline containing proteins, HNA-3-mediated aggregation was observed. Moreover, using Tween®20 for blocking the plates, reconstituted the granulocyte aggregation in a protein-free medium. This indicates that granulocyte aggregation probably occurs by direct granulocyte-granulocyte interaction(s) or is mediated by substances released by neutrophils after activation.
Granulocyte aggregation induced by HNA-3a antibodies does not require human plasma proteins. Interindividual variability in the response to HNA-3a antibodies does not depend on differences in patient’s plasma proteins.
transfusion-related acute lung injury (TRALI); human neutrophil alloantigen-3a (HNA-3a); choline transporter-like protein 2 (CTL2); plasma factor; granulocyte agglutination test (GAT)
This study, conducted in the tertiary Foetal Medicine Unit at St Michael’s Hospital, Bristol, was designed to obtain information regarding neonatal outcomes of pregnancies affected by haemolytic disease of the foetus and newborn and managed by intrauterine transfusion, and to determine whether a change in intrauterine transfusion protocol in 2004 had improved safety. The new protocol included attendance of two Foetal Medicine Unit consultants, foetal sedation and use of the intrahepatic vein as an alternative route to placental cord insertion if deemed safer.
Materials and methods
Data for pregnancies affected by haemolytic disease of the foetus and newborn as a result of haemolytic red cell alloimmunisation and managed with intrauterine transfusion at St Michael’s Hospital between 1999 and 2009 were retrospectively collected using local databases, and medical note review.
Overall, 256 relevant intrauterine transfusions were performed. The median number of intrauterine transfusions per pregnancy was two. Ninety-three per cent of the live deliveries had 5-minute APGAR scores ≥9 and 98% were admitted to a Neonatal Intensive Care Unit/Special Care Baby Unit, requiring phototherapy (96%), top-up transfusions (44%: 23.2% immediate, 13.4% late, 7.3% both), and exchange transfusion (37%). An association was found between increased intrauterine transfusion number and reduced phototherapy duration and hospital admission: each additional intrauterine transfusion reduced the duration of phototherapy by 16% (95% CI: 0.72–0.98), and Neonatal Intensive Care Unit/Special Care Baby Unit admission by 44% (95% CI: 0.48–0.66). Following the change in intrauterine transfusion protocol, there was a significant reduction in the number of emergency Caesarean sections occurring directly after an intrauterine transfusion (n =5 vs 0; P =0.02). The foetal loss rate within 48 hours of an intrauterine transfusion was 1.9% per pregnancy, or 0.8% per intrauterine transfusion: no losses occurred under the new protocol (n =3 vs 0; P = NS).
Although the majority of neonates required admission to a Neonatal Intensive Care Unit/Special Care Baby Unit and phototherapy, the medium-term outcomes were positive. Importantly, the safety of the intrauterine transfusion procedure has improved significantly since the change in protocol.
neonatal outcomes; haemolytic disease; intrauterine transfusion; haemolytic disease of the foetus and newborn (HDFN); Rhesus
Frequent blood loss induces progressive depletion of iron stores, leading to iron deficiency and, ultimately, to overt iron-deficient anaemia. The erythropoietin-mediated bone marrow response to anaemia is under the control of hypoxia-inducible factors (HIF), the master regulators of oxygen and iron homeostasis. Since the HIF-1αPro-582-Ser variant is associated with elevated trans-activation capacity of hypoxia responsive elements of target genes, we investigated whether the HIF-1αPro-582-Ser polymorphism might influence the response to repeated blood withdrawals.
Materials and methods
Using polymerase chain reaction analysis and DNA sequencing, we retrospectively investigated the presence of HIF-1αPro-582-Ser in a series of 163 blood donors. Haematological findings, serum ferritin levels and frequency of donations were compared according to the mutational status of the HIF-1α gene.
We found that male carriers of the HIF-1αPro-582-Ser polymorphism had higher haemoglobin and ferritin levels than individuals homozygous for the wild-type allele. Moreover, the HIF-1αPro-582-Ser polymorphism protected regular blood donors from developing iron deficiency and anaemia and predicted uninterrupted donation activity.
These findings show for the first time that the HIF-1αPro-582-Ser polymorphism significantly affects red blood cell and iron homeostasis after blood loss, conferring to male carriers a resistance to anaemia. Regarding the female gender, large series of individuals should be investigated to establish whether there is an effect of the HIF-1αPro-582-Ser polymorphism in this population. Although these data need to be confirmed in prospective studies, they could have important implications in blood donor selection and donation procedures.
hypoxia-inducible factor; blood donors; iron deficiency
Chagas disease is a parasitic disease due to Trypanosoma cruzi, endemic in Central and Southern America, where the protozoon infects about 8–10 million people. In rural areas the infection is acquired mostly through reduviidae insect vectors, whereas in urban ones it is acquired mainly through the transfusion of blood products, vertical transmission and organ transplantation. The important migratory flows of the last decades have focused attention on possible T. cruzi transmission by transfusion also in non-endemic countries, and platelets have been recognised as the main origin of infection for recipients from serologically-positive Latino-American donors.
Materials and methods
In order to avoid the occurrence of transfusion-related cases, in 2010 systematic screening for anti-T. cruzi antibodies was started at the Umberto I Polyclinic in Rome, controlling blood donors born and/or coming from Latin-American countries in which the disease is endemic. The aim of this paper is to report the preliminary results achieved since the introduction of this screening.
Anti-T. cruzi antibodies have been detected to date in 3.9% out of the 128 people examined. A seropositive subject also proved positive by polymerase chain reaction analysis and showed very light parasitaemia.
The preliminary results are quite alarming. Indeed, serological findings exceed those reported in other non-endemic countries, and Italian travellers proved to be an insidious possible source of direct transmission. The need for systematic screening of at-risk blood donors also in non-endemic countries is emphasised.
Trypanosoma cruzi; Chagas disease; screening; transfusion
transfusion-transmissible infections; WNV; NAT; EQA; surveillance
In Italy, the circulation of human immunodeficiency virus (HIV) has expanded to include population groups that do not perceive themselves to be “at risk” of HIV infection and who do not even consider undergoing HIV testing. The aim of this study was to describe the socio-demographic and behavioural characteristics, and perceived risk of HIV infection in a sample of blood donors who reported never having been tested for HIV.
Materials and methods
A questionnaire was administered to a sample of donors who called the Italian National AIDS/STI Help Line and reported never having been tested for HIV.
The study sample consisted of 164 blood donors: 29.3% had given blood in the preceding 2 years. With regards to at-risk behaviours, 39.6% of the donors interviewed were heterosexuals who had sexual contacts with multiple partners, and 5.5% were men who had sex with multiple male partners. Sexual contacts with female sex workers were reported by 11.6% of first-time donors and 25.7% of repeat donors. Of the 164 donors interviewed, 125 (76.2%) said that the main reason that they had never been tested for HIV was that they did not consider themselves at risk. Among these, 56 (44.8%) reported that they would have sexual contacts with a sex worker, 52 (41.6%) reported that they would have sexual contacts with someone having more than one sexual partner, and 36 (28.8%) reported that they would have sexual contacts without using a condom.
All the donors interviewed reported that they had never been tested for HIV despite the fact that they had been certainly been tested upon blood donation. These results show that some sexual behaviours may not be perceived as behaviours at risk for acquiring HIV infection. These findings suggest that not all blood donors are knowledgeable about HIV risk behaviours and that an explicit pre-donation questionnaire and effective counselling continue to be important for the selection of candidate donors.
HIV infection; sexual behaviour; blood donors; telephone survey; Italy
Travel to malaria risk areas such as Mexico is a common source of donor deferral in Canada. On February 21st, 2011 the deferrable regions in Mexico were revised to permit donation if donors travelled to the state of Quintana Roo, Mexico, a popular ocean-side resort area.
Materials and methods
Canadian travel data and malaria deferral rates since 2007 were plotted to examine trends. Deferral records in one centre were accessed from January to April, 2011 to tabulate travel destinations of deferred donors immediately before and after the change.
Travel to Mexico and the Caribbean accounts for 63% of general population travel, and travel to Mexico has been increasing (P <0.05). Deferral for short-term malaria risk travel has a strong seasonal trend with peaks in the winter and troughs in the summer. Approximately 36,000 fewer donations were lost following the change, a reduction of 37% from the previous year. Deferrals in one centre increased for Caribbean/Central America after the change (P <0.05) consistent with the seasonal trend, but decreased for Mexico (P <0.05).
Deferrals for malaria risk travel are substantial. Careful revision and refinement of risk areas of travel can significantly reduce the burden of deferral.
malaria; Quintana Roo; donor deferral; blood safety
In Italy, the supply of plasma-derived medicinal products funded by the National Health Service can be through public healthcare facilities, accredited pharmacies or toll fractionation agreements between Regions and the manufacturer. Pharmaceutical public expenditure includes the supply related to the first two channels and costs can significantly vary because of channel-specific price reductions. This paper describes 2011 public expenditure for plasma-derived medicinal products purchased on the market, as well as the cost analysis per active substance.
Materials and methods
Analysis of the usage of plasma-derived medicinal products and of the related expenditure in public facilities has been carried out using medicinal product traceability data. The analysis related to the accredited pharmacies channel has been carried out using quantities for every medicinal package recorded by Pharmacy Associations and applying reference prices in force on March 1st, 2012 as well as discounts for the accredited pharmaceutical expenditure imposed by law.
At national and regional level, total and total per capita expenditures on plasma-derived medicinal products by market channel and funded by the National Health Service are shown. Analysis was conducted considering the active substances in three groups: substances included in toll fractionation agreements, recombinant coagulation factors, and other substances not included in toll fractionation agreements. In 2011, the national expenditure estimate for plasma-derived and recombinant medicinal product acquisition on the market was about € 535 million.
The purchased volumes and mean purchased prices per unit of each substance have a significant influence on the observed regional variability of the pharmaceutical public expenditure. A strategy of regional comparison aimed at both sharing a national range of reference for purchase prices and evaluating modalities for centralised purchasing is desirable.
plasma-derived medicinal products; Health Information System; market evaluation; costs; public expenditure
In Italy, the financial reimbursement for labile blood components exchanged between Regions is regulated by national tariffs defined in 1991 and updated in 1993–2003. Over the last five years, the need for establishing standard costs of healthcare services has arisen critically. In this perspective, the present study is aimed at defining both the costs of production of blood components and the related prices, as well as the prices of plasma-derived medicinal products obtained by national plasma, to be used for interregional financial reimbursement.
Materials and methods
In order to analyse the costs of production of blood components, 12 out 318 blood establishments were selected in 8 Italian Regions. For each step of the production process, driving costs were identified and production costs were. To define the costs of plasma-derived medicinal products obtained by national plasma, industrial costs currently sustained by National Health Service for contract fractionation were taken into account.
The production costs of plasma-derived medicinal products obtained from national plasma showed a huge variability among blood establishments, which was much lower after standardization. The new suggested plasma tariffs were quite similar to those currently in force. Comparing the overall costs theoretically sustained by the National Health Service for plasma-derived medicinal products obtained from national plasma to current commercial costs, demonstrates that the national blood system could gain a 10% cost saving if it were able to produce plasma for fractionation within the standard costs defined in this study.
Achieving national self-sufficiency through the production of plasma-derived medicinal products from national plasma, is a strategic goal of the National Health Service which must comply not only with quality, safety and availability requirements but also with the increasingly pressing need for economic sustainability.
sustainability; plasma; plasma-derived medicinal products; costs
Since the introduction of prophylaxis, physicians have tried to convert the clinical phenotype of severe haemophilia (SH) into that of moderate haemophilia (MH), but the outcome of patients with SH has never been compared to that of patients with MH.
Material and methods
The outcome of 80 patients with SH on long-term, intermediate dose prophylaxis was compared to that of 40 patients with MH in a single-centre study. Data on treatment history, activities (assessed by the IPAQ and HAL), quality of life (assessed by the SF-36 and EQ5D), and 5-year bleeding and clotting factor consumption were collected for patients born between 1970–1995.
The median age of the patients was 24 years (IQR 18–30). All patients with SH received long-term prophylaxis, which was started at a median age of 4.8 years (IQR 3.2–6.2). Among the patients with MH, ten (25%) received prophylaxis, starting at a median age of 10.8 years (IQR 3.8–13.8). The annual number of bleeds, including joint bleeds, was significantly higher in patients with SH (median 2.0 joint bleeds/year, IQR =0.8–3.7) than in patients with MH (median 0.8 joint bleeds/year, IQR =0–1.2). Due to greater use of prophylaxis, the annual clotting factor consumption of SH patients (median 2,120 IU/kg; IQR 1,514–2,768), was higher than that of MH patients (median 133 IU/kg; IQR 49–468). Patients with SH showed slightly but significantly more loss of clinical function (assessed by the Haemophilia Joint Health Score): a median of 8 points (IQR 3–15) vs a median of 2 points, IQR 0–6). Quality of life, as measured by the SF-36, EQ5D and physical activity, was similar between patients with disease of different severity, as well as compared to that of the general population.
When comparing unselected cohorts, the bleeding pattern of patients with SH does not appear to be fully converted to that of the milder bleeding pattern of MH by long-term, intermediate-dose prophylaxis, although activities and quality of life were similar.
moderate haemophilia; severe haemophilia; comparison; joint bleeding; HJHS
Blood loss during total joint arthroplasty strongly influences the time to recover after surgery and the quality of the recovery. Blood conservation strategies such as pre-operative autologous blood donation and post-operative cell salvage are intended to avoid allogeneic blood transfusions and their associated risks. Although widely investigated, the real effectiveness of these alternative transfusion practices remains controversial.
Materials and methods
The surgery reports of 600 patients undergoing total joint arthroplasty (312 hip and 288 knee replacements) were retrospectively reviewed to assess transfusion needs and related blood management at our institute. Evaluation parameters included post-operative blood loss, haemoglobin concentration measured at different time points, ASA score, and blood transfusion strategies.
Autologous blood donation increased the odds of receiving a red blood cell transfusion. Reinfusion by a cell salvage system of post-operative shed blood was found to limit adverse effects in cases of severe post-operative blood loss. The peri-operative net decrease in haemoglobin concentration was higher in patients who had predeposited autologous blood than in those who had not.
The strengths of this study are the high number of cases and the standardised procedures, all operations having been performed by a single orthopaedic surgeon and a single anaesthesiologist. Our data suggest that a pre-operative autologous donation programme may often be useless, if not harmful. Conversely, the use of a cell salvage system may be effective in reducing the impact of blood transfusion on a patient’s physiological status. Basal haemoglobin concentration emerged as a useful indicator of transfusion probability in total joint replacement procedures.
total hip arthroplasty; total knee arthroplasty; pre-operative autologous blood donation; post-operative blood cell salvage system; blood management
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.
transfusion; adverse reactions; washed red blood cells; haemovigilance
Haemoglobin screening methods need to be highly sensitive to detect both low and high haemoglobin levels and avoid unnecessary rejection of potential blood donors. The aim of this study was to evaluate the accuracy of measurements by HemoCue in blood donors.
Materials and methods
Three hundred and fourteen randomly selected, prospective blood donors were studied. Single fingerstick blood samples were obtained to determine the donors' haemoglobin levels by HemoCue, while venous blood samples were drawn for measurement of the haemoglobin level by both HemoCue and an automated haematology analyser as the reference method. The sensitivity, specificity, predictive values and correlation between the reference method and HemoCue were assessed. Cases with a haemoglobin concentration in the range of 12.5–17.9 g/dL were accepted for blood donation.
Analysis of paired results showed that haemoglobin levels measured by HemoCue were higher than those measured by the reference method. There was a significant correlation between the reference method and HemoCue for haemoglobin levels less than 12.5 g/dL. The correlation was less strong for increasing haemoglobin levels. Linear correlation was poor for haemoglobin levels over 18 g/dL. Thirteen percent of donors, who had haemoglobin levels close to the upper limit, were unnecessarily rejected.
HemoCue is suitable for screening for anaemia in blood donors. Most donors at Yazd are males and a significant percentage of them have haemoglobin values close to the upper limit for acceptance as a blood donor; since these subjects could be unnecessarily rejected on the basis of HemoCue results and testing with this method is expensive, it is recommended that qualitative methods are used for primary screening and accurate quantitative methods used in clinically suspicious cases or when qualitative methods fail.
blood donors; haemoglobin; haemoglobinometer; HemoCue; false deferral
Haemodilution during resuscitation after massive haemorrhage may worsen the coagulopathy and perpetuate bleeding.
Materials and methods
Blood samples from healthy donors were diluted (30 and-60%) using crystalloids (saline, Ringer’s lactate, PlasmalyteTM) or colloids (6% hydroxyethylstarch [HES130/0.4], 5% human albumin, and gelatin). The effects of haemodilution on platelet adhesion (Impact R), thrombin generation (TG), and thromboelastometry (TEM) parameters were analysed as were the effects of fibrinogen, prothrombin complex concentrates (PCC), activated recombinant factor VII (FVIIa), and cryoprecipates on haemodilution.
Platelet interactions was already significantly reduced at 30% haemodilution. Platelet reactivity was not improved by addition of any of the concentrates tested. A decrease in TG and marked alterations of TEM parameters were noted at 60% haemodilution. HES130/0.4 was the expander with the most deleterious action. TG was significantly enhanced by PCC whereas rFVIIa only caused a mild acceleration of TG initiation. Fibrinogen restored the alterations of TEM parameters caused by haemodilution including those caused by HES 130/0.4. Cryoprecipitates significantly improved the alterations caused by haemodilution on TG and TEM parameters; the effects on TG disappeared after ultracentrifugation of the cryoprecipitates.
The haemostatic alterations caused by haemodilution are multifactorial and affect both blood cells and coagulation. In our in vitro approach, HES 130/0.4 had the most deleterious effect on haemostasis parameters. Coagulation factor concentrates did not improve platelet interactions in the Impact R, but did have favourable effects on coagulation parameters measured by TG and TEM. Fibrinogen notably improved TEM parameters without increasing thrombin generation, suggesting that this concentrate may help to preserve blood clotting abilities during haemodilution without enhancing the prothrombotic risk.
haemodilution; coagulation factor concentrates; platelet function; thrombin generation; thromboelastometry
During transportation, platelet concentrates (PC) usually undergo a long period without agitation. Whether this interruption improves quality and viability or, contrariwise, has deleterious effects on PC stored for 48 hours (h) is unknown. The aim of this study was to investigate the effects of metabolic resting (6 h of interruption of agitation) vs continue agitation of PC stored for 48 h in the blood bank of Tehran.
Materials and methods
PC were prepared from platelet-rich plasma and stored in permeable bags in a shaker/incubator for 42 h at room temperature (20–24 ºC). Then, simply by stopping the agitator, the PC remained stationary (“resting”) without agitation for 6 h (WCA6h), prior to transfusion. In vitro measurements of platelet quality were carried out just after completion of the resting period and the results were compared with those of PC continuously agitated in the same day (designated as the control group, CA6h). The in vitro variables measured were swirling, ristocetin-induced aggregation (GPIb-related function), lactate dehydrogenase (LDH) concentration, platelet factor 4 (PF4) release and P-selectin expression (activation markers).
The mean platelet counts of the control group (CA6h) and rested (WCA6h) PC were not statistically different (P =0.548). Likewise, the mean pH values were not significantly different: WCA6h (7.16±0.08) and CA6h (7.22±0.16) (P =0.300). Although ristocetin-induced aggregation did not differ significantly between CA6h (79.2±4.4) and WCA6h (66.65±28.55) (P =0.186), WCA6h showed significantly less PFA release (P =0.015) and lower P-selectin expression (P =0.006).
We observed that PC stored under agitation for 42 h at 22–24 ºC in permeable bags and then rested for 6 h had better preserved pH, swirling and LDH and less platelet activation then PC kept under continuous agitation for the whole 48 h storage period.
platelet resting; metabolism; agitation effect; PF4; P-selectin
Volume reduction is a widely used procedure in umbilical cord blood banking. It concentrates progenitor cells by reducing plasma and red blood cells, thereby optimising the use of storage space. Sepax and AXP are automated systems specifically developed for umbilical cord blood processing. These systems basically consist of a bag processing set into which cord blood is transferred and a device that automatically separates the different components during centrifugation.
The aim of this study was to analyse and compare cell recovery of umbilical cord blood units processed with Sepax and AXP at Valencia Cord Blood Bank. Cell counts were performed before and after volume reduction with AXP and Sepax.
When analysing all the data (n =1,000 for AXP and n= 670 for Sepax), the percentages of total nucleated cell recovery and red blood cell depletion were 76.76±7.51% and 88.28±5.62%, respectively, for AXP and 78.81±7.25% and 88.32±7.94%, respectively, for Sepax (P <0.005 for both variables). CD34+ cell recovery and viability in umbilical cord blood units were similar with both devices. Mononuclear cell recovery was significantly higher when the Sepax system was used.
Both the Sepax and AXP automated systems achieve acceptable total nucleated cell recovery and good CD34+ cell recovery after volume reduction of umbilical cord blood units and maintain cell viability. It should be noted that total nucleated cell recovery is significantly better with the Sepax system. Both systems deplete red blood cells efficiently, especially AXP which works without hydroxyethyl starch.
cord blood; volume reduction; haematopoietic progenitors