bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial translocation in organ donors: clinical observations and potential risk factors
Authors: Kane Timothy D. , Johnson Scott R. , Alexander J. Wesley , Craycraft Thomas K.
Published: September 2024

Thirty‐nine solid‐organ donors were evaluated to determine the incidence of bacterial translocation to mesenteric lymph nodes. In addition, clinical variables from 59 local recipients of renal allografts from these donors were examined to assess whether translocation in donors was associated with increased morbidity in the recipients of organs from node‐positive donors. Ileocecal lymph node cultures were positive in 18 of 39 donors (46%). Sixteen donors (41%) were hypotensive [systolic blood pressure (SBP)< 90 mmHg] and 27 (69%) received blood product transfusions before organ donation. The presence of hypotension and blood product transfusion were associated with positive and negative cultures, respectively. In 24 (41%) of 59 organs transplanted from donors with periods of hypotension, significantly more (16 of 24, 67%) were associated with positive lymph node cultures than with negative cultures (8 of 24, 33%; p=0.029). In recipients of organs from node‐positive versus node‐negative donors there was a trend toward higher incidence of infection (32% vs. 25%), need for hemodialysis post‐transplant (29% vs. 23%), graft loss within 1 yr (24% vs. 19%), and lack of blood transfusion prior to organ procurement (43% vs. 23%), although these variables were not significantly different between the groups. Hypotension or inadequate resuscitation may contribute to increased bacterial translocation to mesenteric lymph nodes. The overall impact upon the recipients of organs from donors with demonstrable translocation to lymph nodes remains undefined.
Graft outcome in cadaver renal transplants treated with full‐dose cyclosporine induction without antibody, irrespective of graft function
Authors: Douzdjian Viken , Bhaskar S. Shanmuga , Baliga Prabhakar K. , Rajagopalan P. R.
Published: September 2024

Cyclosporine (CSA) induction has been shown to prolong delayed graft function which in turn may compromise graft outcome. In this study we report our experience with full‐dose CsA induction without antibody treatment irrespective of graft function and stress the importance of achieving therapeutic CsA levels in the early post‐transplant period. The records of 293 first cadaver renal transplant recipients who were transplanted between January 1992 and December 1995 were reviewed. Patients were divided into those who had immediate graft function (IGF, n=197) and the ones who had delayed graft function (DGF, n=96). Twenty‐six (13%) patients in the IGF group and 27 (28%) patients in the DGF group experienced at least one episode of acute rejection (AR), (P=0.002). Patient and graft survival rates at 1, 2 and 5 yr were similar in the IGF and DGF groups. Cox regression analysis revealed that the absence of both DGF and AR was independently associated with a 0.44 times lower risk of graft failure (P=0.06), whereas AR without DGF was associated with a 1.9 times increased risk of graft failure (P=0.02). DGF, with or without AR, did not affect the risk of graft failure. Logistic regression analysis showed that DGF was associated with a 3.6 times higher risk of AR (P=0.003). A non‐traumatic cause of donor death and preservation time > 24 h were associated with 1.9 and 2.4 times higher risks of DGF (P=0.1, P=0.08), whereas female donor gender reduced the risk of DGF by 0.6 (P=0.1). In conclusion, our results suggest that full‐dose CsA induction with achievement of therapeutic target levels in the early post‐transplant period is associated with an acceptable graft outcome. Graft outcome was not compromised by delayed function, whereas acute rejection was an independent predictor of graft failure.
Anemia following renal transplantation: erythropoietin response and iron deficiency
Authors: Miles Anne Marie V. , Markell Mariana S. , Daskalakis Paula , Sumrani Nabil B. , Hong Joon , Sommer Bruce G. , Friedman Eli A.
Published: September 2024

To define the etiology of anemia post‐renal transplantion, we assessed hematologic parameters and EPO levels in 38 anemic and 16 nonanemic control renal transplant recipients (RTRS) with varying degrees of allograft function at periods >3 months post‐transplantation. Significant differences between the two groups were found for serum creatinine (Cr) 291.7±26.5 vs. 203.3±26.5 μmol/l, p<0.01; iron 9.3±0.92 vs. 13.6±1.7 μmol/l, p<0.05; and ferritin 345.5±90.8 vs. 91.1±18.5 μg/l, p<0.01. Serum. EPO levels were inappropriately low in anemic patients with no significant correlation between EPO and Cr or hematocrit (Hct) levels. Serum iron was the only predictive factor for anemia on regression analysis (p<0.05). Ferritin levels did not correlate with serum iron or Hct, and may be falsely elevated in iron deficient RTRS. Iron deficiency, poor renal function and inappropriately low EPO levels are major contributors to the 12% of our outpatient renal transplant population who are anemic.
Changes in phenotypes of apolipoprotein E and apolipoprotein(a) in liver transplant recipients
Authors: Fernández‐Miranda Consuelo , Cancelas Pilar , de la Calle Angel , Gómez Ramon , Moreno Enrique , Gómez‐Gerique Juan , del Palacio Angel
Published: September 2024

The aim of this study has been to confirm that liver is the main site of apolipoprotein (apo) E and apo(a) synthesis, based in the changes of their phenotypes after transplantation. Apo E phenotypes were studied in 34 patients and apo(a) phenotypes in 27 of them before and after liver transplant. Thirteen patients changed the apo E phenotype after transplantation. Eight patients with E3/3 phenotype changed to the others with 2 or 4 alleles. Three patients with E4/3 phenotype changed to E3/3, one changed from E3/2 to E3/3 and another one changed from E4/2 to E3/2 phenotype after transplantation. Twenty one of the 27 patients changed the apo(a) phenotype. Thirteen of them also changed lipoprotein (Lp)(a) serum concentration at least twofold, showing in 11 an increase and in 2 a decrease, in relation with the change to phenotype associated with high and low Lp(a) concentration, respectively. Changes in apo E and apo(a) phenotypes in liver transplant recipients studied show that most of these apolipoproteins are synthesized by the liver.
Variations of the intrahepatic bile ducts: application in living related liver transplantation and splitting liver transplantation
Authors: Cheng Yu Fan , Huang Tung Liang , Chen Chao Long , Chen Yaw Sen , Lee Tze Yu
Published: September 2024

The variations in the anatomy of intrahepatic bile ducts complicate operations in living related liver transplantation (LRLT) and therefore preoperative delineation of the biliary system is important to achieve a successful outcome. The aim of this study was to establish a standard relationship between the biliary variations and the methods of the graft splitting and anastomosis. Of 958 endoscopic retrograde cholangiographies with good visualization of bile duct branches were selected and were available for evaluation of their ramifications and variants. According to drainage of right hepatic duct and left hepatic duct, we classified the bile ducts into two major groups. Unusual routes of the intrahepatic ducts were present in 105 cases (11% in group A) the right sectoral duct drained into the left hepatic duct directly; in 200 cases (21% in groups B) the duct of segment IV drained into right side or common hepatic duct; and in 29 cases (3% in groups B) the duct of segment II and III drained into the CBD and right hepatic duct separately. There is no specific bile duct variation that forbids someone from LRLT and SLT, but unusual intrahepatic ducts routes may require a change both in the cutting plane during graft retrieval and pattern of ductoenteral anastomosis to avoid potential complications to both donors and recipients. Cholangiography for screening intrahepatic duct variations is therefore important for safe bile drainage for both donors and recipients.
Graft‐versus‐host disease after liver and small bowel transplantation in a child
Authors: Reyes Jorge , Todo Satoru , Green Michael , Yunis Eduardo , Schoner David , Kocoshis Samuel , Furukawa Hiro , Abu‐Elmagd Kareem , Tzakis Andreas , Bueno Javier , Starzl Thomas E.
Published: September 2024

An 8‐month‐old child with an immunodeficiency disorder characterized by abnormal lymphocyte function and by low IgG and IgA levels had combined liver and small bowel transplantation under tacrolimus and steroid immunosuppression for the treatment of short gut syndrome and hepatic cirrhosis. The patient developed an early postoperative episode of Pneumocystis carinii pneumonia, and a subsequent surgical complication, prompting discontinuance of tacrolimus. A skin rash eventually shown to be graft‐versus‐host disease (GVHD) developed in the flank on the 12th post‐transplant day and gradually became generalized. Peritonitis, sepsis, multisystem organ failure including the liver allograft led to death on the 23rd post‐operative day. The mechanisms leading to post‐transplant GVHD under the specific circumstances in this case are discussed.
Potential for bilateral nephrectomy to reduce oxalate release after combined liver and kidney transplantation for primary hyperoxaluria type 1
Authors: Mizusawa Youichi , Parnham Alan P. , Falk Michael C. , Burke John R. , Nicol David , Yamanaka Junichi , Lynch Stephen V. , Strong Russell W.
Published: September 2024

Primary hyperoxaluria type 1 (PH‐1) is frequently associated with end stage renal failure due to urinary calculi, obstructive uropathy and interstitial deposits of calcium oxalate. The currently accepted treatment for PH‐1 is liver transplantation to replace the deficient enzyme peroxisomal alanine glycoxylate aminotransferase (AGT) and a simultaneous renal transplant to restore renal function. The transplanted kidney may become significantly impaired or fail when systemic calcium oxalate is eliminated by renal excretion. The native kidneys are a major source of this oxalate. This study was undertaken to determine whether there is a difference in oxalate clearance following combined liver‐kidney transplant in patients with PH‐1 by comparing the effect of native kidney nephrectomy at the time of transplantation against leaving the native kidneys in situ. Regression analysis was used to compare daily urinary oxalate excretion corrected for body surface area. There was a significant reduction in urinary oxalate excretion (P<0.05) in the patient who had undergone bilateral nephrectomy compared to the patient whose native kidneys remained in situ for the first 100 d following combined liver and kidney transplantation. No difference was observed in the serum oxalate levels between patients over the same period or in the renal function assessed by creatinine clearance corrected for body surface area. Total body oxalate load was not determined in this study. A larger study should be undertaken to examine the benefits of nephrectomy in reducing oxalate deposition in recently inserted allografts for patients with PH‐1.
Significance of the donor age effect on kidney transplants
Authors: Terasaki Paul I. , Gjertson David W. , Cecka J. Michael , Takemoto Steve , Cho Yong Won
Published: September 2024

The shortage of cadaveric donor kidneys for transplantation has forced a re‐evaluation of the limits on donor age acceptability. However, as more kidneys from older donors have been transplanted, a significantly lower graft survival has been noted among their recipients. The impact of utilizing older donor kidneys and the relative importance of donor age with respect to other factors has not been clarified. A total of 43 172 cadaver donor transplants reported to the UNOS Scientific Renal Transplant Registry between 1987 and 1995 were the subjects of this study. Cox regression analysis was utilized to assess the joint effects on graft survival of donor age and HLA mismatch, recipient sex, race, age, original disease, donor death cause, cold ischemia time, and transplant year. Increased first day anuria, dialysis requirement, and discharge serum creatinine were noted with increasing donor age. Moreover, long‐term graft and patient survival diminished as donor age increased. The 5‐yr graft survival of zero HLAA,B,DR mismatched kidneys fell steadily from 81% when the donor was aged 21‐30 to 39% when the donor was over age 60. The reported causes of kidney transplant failure were remarkably similar for old and young donors. The best transplant results were obtained with zero HLA‐A,B,DR mismatched transplants from young donors and the worst with older donor kidneys, regardless of HLA compatibility. We calculated that up to 21% of kidney failures resulted from insufficient renal mass due to age and were incorrectly attributed to chronic rejection.
Poor initial graft function after orthotopic liver transplantation: can it be predicted and does it affect outcome? An analysis of 125 adult primary transplantations
Authors: Maring John K. , Klompmaker Ids J. , Zwaveling Jan H. , Kranenburg Koos , Vergert Els M. Ten , Slooff Maarten J. H. ,   Liver Transplant Group Groningen
Published: September 2024

Donor liver shortage is a persistent problem in liver transplantation. A more liberal donor acceptance policy may be a possible solution. However, this might put recipients at risk for initial poor function or even non‐function of the graft. Therefore risk factors for initial graft dysfunction should be identified, preferably by using an uniform definition of primary graft dysfunction or non‐function. We retrospectively analysed 125 adult liver transplantations in order to identify risk factors for initial poor function and primary non‐function. Donor, recipient pretransplant and surgical parameters were evaluated. Since there is no consensus on the criteria of dysfunction we used two definitions known from literature. No risk factors for postoperative dysfunction could be identified for either of the two definition sets. Furthermore, the definition set that included ALAT, prothrombin time and bile production in the first 72 h to identify poor graft function showed no relation with graft or recipient outcome. The other set, using ASAT and prothrombin time, determined from day 2 to day 7, showed that patients with a primary dysfunction had significantly higher morbidity and mortality compared to patients with a well functioning graft. We conclude that initial poor function after liver transplantation remains unpredictable. irrespective of the way it is defined. Moreover, our analysis shows that initial poor function can also develop in recipients that receive ‘non‐marginal’ grafts without prolonged ischemia times. These results may support a more liberal selection of donor livers.
Hepatic arterial complications in pediatric segmental liver transplantations from living donors: assessment with color Doppler ultrasonography
Authors: Fujimoto Masazumi , Moriyasu Fuminori , Nada Takayuki , Inomoto Takuya , Tanaka Koichi , Yamaoka Yoshio
Published: September 2024

To investigate the clinical utility of color Doppler ultrasonography in detecting hepatic arterial complications in pediatric living‐related liver transplantation, we studied peak systolic velocity (Vp) and pulsatility index (PI) in intrahepatic artery during and after surgery in 122 transplants. Six cases with hepatic artery thrombosis were detected by Doppler studies. In 2 cases with dampened waveforms at intraoperative flowmetry (Vp≤23 and PI≤0.6), thrombosis occurred soon after surgery. A further 2 cases had a rapid decrease in Vp and PI values postoperatively, leading to absence of arterial signals. Follow‐up Doppler studies suspected collateral formation after thrombosis in 2 survivors. Normal Doppler waveforms were obtained in all of the 116 cases without arterial complications. Among them, 6 cases had absent signals or dampened waveforms at initial intraoperative flowmetry (Vp≤30 and PI≤0.9), and maneuvers such as re‐reanastomosis of the artery improved flow signals with an increase in Vp and PI values. Serial intraand post‐operative Doppler examinations are useful for early detection of arterial complications.
Long‐term prognosis of renal transplant surviving for over 10 yr, and clinical, renal and rehabilitation features of 20‐yr successes
Authors: Yasumura Tadaki , Oka Takahiro , Nakane Yoshihiro , Ohmori Yoshihiro , Aikawa Ichiro , Yoshimura Norio , Nakai Ichiro , Hamashima Takashi , Nakajima Hiroo , Nakamura Kenji
Published: September 2024

Long‐term mortality and morbidity was evaluated in 267 patients with a minimum follow‐up of 10 yr and the physical status, graft function and quality of life in 15 patients with a functioning graft surviving for over 20 yr were reviewed. Actual patient and graft survival rates were 80.2% and 51.1% at 10 yr (n=267) and 56.4% and 32.7% at 20 yr (n=55), respectively. Although the rate of graft failure due to rejection was 4 times higher than that of patient death within 10 yr, it decreased to the level of patient death in the second decade. Dominant causes of death in patients with graft surviving for over 10 yr were hepatic failure due to viral hepatitis and malignancies. In 15 patients with graft currently surviving beyond 20 yr, while all patients have excellent graft function, malignancy occurred in 5, viral hepatitis in 3, aseptic necrosis in 3, and diabetes mellitus in one patient. No patient has suffered cardiovascular complications. Despite a high rate of morbidity, they show a satisfying status of rehabilitation (full time working 11/ 15, 73.3%). In order to attain more improved QOL in patients with longterm surviving renal transplant, close follow‐up aiming at diminution of complications is required throughout the period after transplantation.
Vulnerability to psychologic distress and depression in patients with end‐stage liver disease due to hepatitis C virus
Authors: Singh Nina , Gayowski Timothy , Wagener Marilyn M. , Marino Ignazio R.
Published: September 2024

Psychosocial sequelae and quality of life impairment in patients with end‐stage liver disease due to hepatitis C virus (HCV) are not known. Quality of life, psychological distress (Profile of Mood States scale), depression (Beck Depression Inventory), and coping (Ways of Coping scale) were prospectively assessed in 82 liver transplant candidates; comparisons were made between patients with HCV hepatitis versus patients with other liver diseases. Patients with HCV were significantly younger than all other patients (p = 0.002). Total mood disturbance (p = 0.038), tension and anxiety (0.047), confusion and bewilderment (p = 0.035) and depression and dejection (p = 0.035), as assessed by Profile of Mood States Scale were significantly higher in patients with HCV than other patients. Patients with HCV were significantly more depressed as assessed by Beck Inventory scores (p = 0.014). Karnofsky performance scores, Child‐Pugh score, and liver function tests were not significantly different for patients with HCV vs. all other patients. However, somatic manifestations of the illness (e.g. pain) were greater in patients with HCV and may have contributed towards greater depression in these patients. Our findings warrant replication in other studies, since depression is a modifiable and treatable disorder.
Evaluation of neurotoxicity in pediatric renal transplant recipients treated with tacrolimus (FK506)
Authors: Neu Alicia M. , Furth Susan L. , Case Barbara W. , Wise Barbara , Colombani Paul M. , Fivush Barbara A.
Published: September 2024

The presence of severe and mild neurotoxicity in our pediatric renal transplant recipients treated with tacrolimus was determined by chart review (severe neurotoxicity) and patient survey (mild neurotoxicity). 14 patients were studied (mean age 15 yr, 5 month,± 4.4 yr). 1 patient experienced seizures, felt to be related to malignant hypertension. No other episode of severe neurotoxicity was documented. Most patients (12/14) reported at least one mild neurologic symptom, and half stated their symptoms were present at least ‘most of the time‘. The most frequent complaints were myalgias (7/14, 50%) and tremors (7/14, 50%) followed by fatigue (5/14, 38%). Severe neurotoxicity may be relatively infrequent in pediatric renal transplant patients treated with tacrolimus. Milder neurologic complaints may be commonly seen in this population, but in general are not severe enough to cause discontinuation of tacrolimus.
Preservation of pancreatic endocrine function by hemodynamic stabilization following brain death
Authors: Yoshida Hiroyoshi , Hiraide Atsushi , Iwai Atsushi , Kawaguchi Naomasa , Yoshioka Toshiharu , Sugimoto Tsuyoshi
Published: September 2024

A protocol achieving for long‐term hemodynamic stability enabled us to evaluate pancreatic endocrine function for up to 1 wk following brain death. The glucose disappearance rate was significantly lower in brain‐dead patients (N = 21) than in normal controls (N = 10) (p<0.001). In 19 brain‐dead patients whose plasma epinephrine concentrations exceeded 0.4 ng/ml, the mean early insulin release was significantly lower than in controls, while early insulin release was markedly higher in the remaining two patients. It is possible that early insulin released may be due to increased plasma epinephrine concentrations following brain death. Late insulin release in brain‐dead patients was not lower, but was higher than controls and was accompanied by a decrease in the glucose disappearance rate. No evidence of abnormalities in histopathology of pancreas was detected at autopsy. Our results indicate that intrinsic insulin secretory function can be preserved during the first week following brain death.
Use of ciprofloxacin as a prophylactic agent in urinary tract infections in renal transplant recipients
Authors: Neto Miguel Moysés , Costa Roberto S. , Reis Marlene A. , Ferraz Agenor S. , Saber Luciana T. S. , Batista Maria Estela P. N. , Muglia Valmir , Garcia T. M. P. , Figueiredo José Fernando C.
Published: September 2024

The most common form of bacterial infection in renal transplant recipients is urinary tract infection (UTI), and some studies have shown that prophylaxis can reduce this incidence. In the present investigation we evaluated 80 patients submitted to renal transplantation at the Renal Transplant Unit of the University Hospital of Ribeirao Preto, SP. The study was prospective, double blind and randomized. The patients were divided into two groups, one receiving placebo and the other ciprofloxacin at the dose of 250 mg twice a day for the first 10 d and 250 mg/d for 6 months after transplantation. Of the 41 patients who received ciprofloxacin 28 completed the study, and of the 39 patients who received placebo 30 completed the study. The largest number of UTI occurred in the placebo group, with a significant difference from the ciprofloxacin group during the first month after surgery (p<0.05). In the group treated with ciprofloxacin, only 6/40 patients (15%) developed UTI, as opposed to 19/39 (48.7%) for the placebo group. The total number of infectious episodes was higher in the placebo group (26) than in the ciprofloxacin group (12). The medication was well tolerated throughout the study period.
Coronary artery bypass after single lung transplant: a case report
Authors: Salerno Christopher T. , Harrison Bernard , Hertz Marshall , Shumway Sara
Published: September 2024

Chronic obstructive pulmonary disease (COPD) is the most common indication for adult single lung transplantation. These patients commonly have one or more risk factors for coronary artery disease. Traditionally previous lung transplantation has been considered a contraindication to coronary artery bypass grafting (CABG). This report describes a case of CABG 3 yr after single lung transplantation and briefly discusses the risks of cardiac surgery in lung transplant patients.
Molecular Basis of Red Cell Protein Antigen Deficiencies
Authors: Cartron Jean‐Pierre
Published: September 2024

Blood group antigens reside on cell surface molecules of wide structural and functional diversity. Although all are serologically detectable on red blood cells, most are also expressed in non erythroid tissues, but with a few exceptions their biological role on erythrocytes and tissues often remains elusive. Deficiencies of these molecules seen either in rare blood group « null » phenotypes and/or associated with red cell membrane disorders, offer the opportunity to clarify their role in the cell membrane and to correlate their molecular abnormalities with cell dysfunctions. This review will summarize some of the present knowledge on these defects and on gene targeting studies developed to analyze the function of these molecules in animal models.
New Tools in Assessing Immune Reconstitution after Hematopoietic Stem Cell Transplantation
Authors: Toubert Antoine , Clave Emmanuel , Talvensaari Kimmo , Douay Corinne , Charron Dominique
Published: September 2024

Background and Objectives:

Immune functions are impaired after allogeneic stem cell transplantation for several months depending on the age of the recipient, initial pathology, degree of HLA and minor histocompatibility antigens mismatches, origin and manipulation of the graft (unmanipulated or T‐cell depleted bone marrow transplantation, cord blood) and post‐transplantation events (acute or chronic graft‐versus‐host disease. relapse and infectious complications).

Material and Methods, Results and Conclusion:

In addition to lymphocyte phenotyping and functional assays, new tools are now available to monitor specific aspects of the immune response in the follow‐up of hematopoietic stem cell transplantation : reconstitution of T cell cell diversity (spectratyping or Immunoscope), thymic function (TREC or “T‐cell receptor rearrangement excision DNA circles”) and antigen‐specific T cell responses (HLA tetramers).
The Molecular Basis of Inherited Thrombophilia
Authors: Manucci P.M.
Published: September 2024

Even though it has been known for centuries that inherited defects of blood coagulation cause lifelong bleeding disorders. the existence of the counterpart, inherited thrombotic disorders, has been appreciated for only a few decades. Inherited thrombophilia can be defined as a genetically determined tendency to venous thromboembolism which characteristically occurs at a young age with no apparent cause and tends to recur. This article reviews the prevalence, biochemical and molecular basis of inherited thrombophilia, describes the main clinical manifestations and provides general guidelines for treatment. It is restricted to the more frequent and well‐established causes of thrombophilia: antithrombin, protein C and protein S deficiency; resistance to activated protein C caused by mutations in coagulation factor V and the gain‐of‐function mutation of factor II (prothrombin). Other causes of inherited thrombophilia are much rarer, such as dysfibrinogenemia, or not firmly established, such as abnormalities of the fibrinolytic system (plasminogen. histidin‐rich glycoprotein) and thrombomodulin.
Therapeutic Hemapheresis as of 2000
Authors: Valbonesi M , Bruni R , De Luigi MC
Published: September 2024

The main task of therapeutic hemapheresis remains doing the right thing and doing the right thing right. If objective results have been slow to take hold it is in large part because several physicians have resisted continuous improvement since therapeutic apheresis was considered so efficient to boomerang preventing elimination of unnecessary procedures and treatments. The right thing to do is treating patients who may respond in a specific phase of their disease, frequently along with the right drugs. Doing right the right thing is to take advantage of the new technologies and, medical culture which have led apheresis to the recent complexity and efficacy. In the following pages we are trying to update the state‐of‐the‐art and new trends which characterize therapeutic apheresis at the beginning of 2000.
Old and New Tests: Where Will It End?
Authors: Holland Paul V.
Published: September 2024

Testing has improved the safety of the blood supply. We have excellent serologic tests in place now and are implementing nucleic acid based tests to identify asymptomatic carriers of viruses during the infectious part of the pre‐seroconversion (window) period. However, the blood supply was already quite safe after a variety of other mechanisms had been put into place besides testing to screen out individuals at risk of carrying the most important transfusion transmissible agents. An important safety factor is the use of volunteer, unpaid (unremunerated) blood donors. The best alternative to implementing yet more tests to reduce, but not eliminate, the minute residual risks of transfusion transmission of such agents as HIV, HBV and HCV is the application of microbial inactivation technology to blood and blood components. Such microbially inactivated, cellular blood components should not have the risk of transmitting infectious agents, but may have other, different risks, since nothing has yet been shown to be one hundred percent safe (i.e., risk free). The use of a test to detect carriers of spongiform encephalopathies to prevent their theoretical transmission by transfusion may cause harm to donors and might increase risk for recipients by decreasing the available blood supply.
Monoclonal Antibodies to Rh D ‐ Development and Uses
Authors: Scott Marion L , Voak Douglas
Published: September 2024

Monoclonal anti‐D has proved impossible to make in rodent systems. Human monoclonal anti‐D has been produced using EBV transformed peripheral B cells, coupled with fusions to myeloma cell lines. More recently molecular biology techniques have been used to produce monoclonal anti‐D. The range of monoclonal anti‐D produced is considered. The selection of monoclonal anti‐D for use as blood grouping reagents for typing donors and recipients is reviewed all types of D positive should be typed as positive when donors are considered. However, DV patients should be typed as D negative. Considerations for the development of monoclonal anti‐D for prophylactic use are reviewed.
Site Directed Mutagenesis of the Human Rh D Antigen: Molecular Basis of D Epitopes
Authors: Avent Neil D. , Liu Wendy , Scott Marion L , Jones Jeffrey W. , Voak Douglas
Published: September 2024

Previous attempts to define the molecular configuration of D epitopes has been confined to the analysis of the serological profile and Rh D molecular structure of partial D phenotypes. There are numerous drawbacks in this approach, most fundamental of which is that with the exception of RoHar partial D phenotypes are defined by the loss of D epitope expression, and is thus difficult to directly correlate a specific amino acid to a particular D epitope. Furthermore, most partial D phenotypes are associated with multiple amino acid changes in the mutant Rh protein species associated with partial D expression. In our study we have applied site directed mutagenesis to introduce RhD amino acids in a stepwise manner to a Rh CE cDNA. This cDNA was introduced into K562 cells using retroviral mediated gene delivery, and D epitope expression analysed by flow cytometry. Our study provides evidence for at least six different epitope clusters on the external face of the Rh D protein. The relative predicted positions of these epitope clusters has resulted in us presenting a model for the hypothetical arrangement of external Rh D protein loops.
Molecular Genetics of ABO
Authors: Yamamoto Fumiichiro
Published: September 2024

This year commemorates the 100th anniversary of the discovery of the ABO blood group system by Karl Landsteiner. His findings of red cell agglutination by serum and recognition of blood groups laid the scientific basis for safe practice of blood transfusion. Even though dozens of blood systems have been identified, the ABO system still remains to be one of the most important systems in transfusion medicine. In 1990, we elucidated the molecular genetic basis of three major alleles at the ABO locus. Since then we have witnessed the progress in our understanding of ABO genes and A and B glycosyltransferases specified by a variety of functional alleles at this locus. Mutations affecting the activity and specificity of the enzymes have been identified. Not only has ABO genotyping become possible, but it has also become possible to genetically engineer the activity and specificity of the enzymes. We are now at a point of embarking upon the quest of understanding the functional significance of ABO polymorphism.
Molecular Genetics of H
Authors: Oriol Rafael , Candelier Jean‐Jacques , Mollicone Rosella
Published: September 2024

Background and Objectives:

Formal genetics of ABO, H‐h and Se‐se systems illustrate that these three systems are genetically independent

Materials and Methods:

Population analysis of phenotypes and family segregation of the ABH related genetic markers

Results:

Inactivating mutations of FUT1 and FUT2 are compatible with a structural gene model assuming that FUT1 and FUT2 genes encode for two distinct enzymes, one encoding for the H antigen expressed in red cells (FUT1) and the other encoding for the H gene expressed in saliva (FUT2)

Conclusion:

Most inactivating mutations of FUT1 and FUT2 genes are located in the coding region of the genes and are nonprevalent sporadic mutations of relative recent appearance
Molecular Genetics of RH
Authors: Flegel Willy A. , Wagner Franz F.
Published: September 2024

Background and Objectives:

The two Rhesus proteins, RhD and RhCE, constitute one of the clinically most relevant blood group antigen system. In the last two years, the understanding of RH molecular genetics has increased considerably. The State of the current knowledge was briefly summarised.

Materials and Methods:

Recent reviews, original work since 1999 and own results were utilised.

Results:

The structure of the RH gene locus comprising RHD, RHCE and SMP1 was presented. True RHD genotyping became feasible by establishing the molecular basis of the most prevalent RH haplotype in whites harbouring the RHD gene deletion and of the RHD pseudogene RHD Ψ in Africans. Molecular and serologic characteristics of weak D and partial D alleles were compared. Closely related alleles for both, weak D and Partial D, were collated as examples contributing to the understanding of RH phylogeny.

Conclusion:

The RH gene locus is a model system for molecular polymorphism in clustered genes and suitable for studying molecular evolution in humans. It lends itself for developing molecular diagnostics because its genetics is appropriately complex and challenging; yet the expressed phenotypes have been studied for decades and are well understood. Legal and ethical issues that are rightfully of public concern would not be infringed if RH genotyping will be attempted on a massive scale.
Molecular Genetics of Granulocyte Polymorphisms
Authors: Bux Jürgen
Published: September 2024

Background and Objectives:

Granulocyte (neutrophil) antibodies have been implicated in transfusion‐related acute lung injury (TRALI) and immune neutropenias. In the last decade enormous efforts have been made to characterize the involved alloantigens.

Materials and Methods:

Review of the literature

Results:

The NAI, NA2, and SH antigens have been identified as polymorphic forms of the neutrophil Feyreceptor IIIb encoded by three alleles. The antigens. MART and OND have been located on leucocyte adhesion molecules (β2 integrins) and were found to be due to single nucleotide mutations in the αM (CD11b) and αL (CD11a) subunits. Recently, we succeeded in throwing light on the primary structure of the NB1 antigen. On the basis of these findings a new nomenclature has been introduced for human neutrophil alloantigens (HNA nomenclature). Glycoprotein location has made the development of antigen‐specific immunoassays possible and antigen characterization on the molecular level now allows genotyping by DNA techniques.

Conclusion:

Considerable progress has been made in the characterization of granulocyte antigens. Further studies will improve our diagnostic tools and will facilitate the prevention and management of transfusion reactions and immune neutropenias.
Flow Cytometry: The Standard for Monitoring the Onset of Apheresis and for the Evaluation of Stem and Progenitor Cell Graft Quality.
Authors: Gutensohn K. , Magens M. M. , Kuehnl P.
Published: September 2024

Several high‐quality protocols exist that describe the methodological and technical aspects of the flow cytometric analyses of stem and progenitor cells. In addition, recent advances in automation and quantitative analyses show promising results. For further improvement of the test quality and more objective control, internal as well as external quality control is mandatory. In addition, cost aspects move into the focus of interest and have to be considered. Alternative methods such as volumetric capillary cytometry or haematological analyzers are of limited use for stem and progenitor cell analyses. Currently, flow cytometry represents the gold standard for monitoring the onset of apheresis and to evaluate the quality of stem and progenitor cell grafts. In the near future, only in vitro diagnostics that are CE‐labelled or FDA‐approved should be used for these analyses.
Flow Cytometric Analysis of Platelets
Authors: Michelson Alan D.
Published: September 2024

Background and Objectives:

Despite recent progress in our understanding of platelet function in vitro, there remains a remarkable paucity of methods to study platelet function in vivo.

Materials and Methods:

We have developed novel three color whole blood flow cytometric methods for tracking of infused platelets and measurement of their function in vivo.

Results:

These methods were used to demonstrate that circulating P‐selectin‐positive (degranulated) platelets rapidly lose surface P‐selectin to the plasma pool, but continue to circulate and function.

Conclusions:

1) These studies strongly suggest that the measurement of platelet surface P‐selectin in platelet concentrates stored in the blood bank should not be used as a predictor of platelet survival or function in vivo. 2) The described methods provide the means to answer many previously difficult to address questions about in vivo platelet function in transfusion medicine.
Prenatal Determination of Fetal Blood Group Status
Authors: Avent Neil D. , Finning Kirstin M. , Martin Peter G. , Soothill Peter W.
Published: September 2024

Background and Objectives:

The prenatal determination of fetal blood group status by molecular techniques has been used in the clinical management of alloimmunised pregnancies for seven years, in particular for the definition. of fetal Rh D. c and E, K, Fya and Jk statusa. This has arisen in response to the definition of the molecular bases of human group polymorphism.

Materials and Methods:

PCR‐based amplification assays have been designed to define fetal blood group status, where the source of template DNA is normally derived from amniotic fluid or chorionic villus. Recently, non‐invasive methods have been explored to obtain fetal DNA from maternal peripheral blood.

Results:

PCR‐based tests are now available to screen for all fetal medicine significant blood group antigens. The Rh system is the most complex. and assays to define Rh genotype have been modified in reponse to our increased understanding of the molecular biology of this blood group system.

Conclusion:

Prenatal diagnosis of fetal blood group status is now in widespread use in the clinical management of HDN. Non‐invasive testing. if applied in the clinical setting may invoke a dramatic increase in the numbers of pregnancies that may be analysed prenatally.
Perioperative Transfusion Triggers for Red Blood Cells
Authors: Spahn Donath R.
Published: September 2024

Perioperative transfusion triggers for red blood cell (RBC) transfusion include physiologic signs of inadequate oxygenation of the entire organism or a specific organ. hemoglobin (Hb) concentration and logistic aspects such as experience of anesthesiologists and surgeons, predictability and magnitude of blood loss and time required for a Hb determination and RBC delivery. At a Hb concentration <6 g/dL a RBC transfusion may be given. however, if the patient is hemodynamically stable one may opt not to transfuse. With Hb concentrations between 6 g/dL and 10 g/dL physiologic signs of inadequate oxygenation decide on RBC transfusion. In absence of hypovolemia signs of inadequate oxygenation include tachycardia and hypotension. an 02 extraction >50%, a a mixed‐venous O2 partial pressure <4.3 kPa (32 mmHg), a decrease of O2 consumption >10% (not otherwise explained) and signs of locally deficient Oxygenation such as myocardial ischemia. At Hb concentrations >10 g/dL. RBC transfusions are rarely, if ever, indicated.
Platelet Substitutes
Authors: Blajchman Morris A.
Published: September 2024

Many experimental approaches have been explored to produce hemostatically active novel human platelet products and substitutes capable of long‐term storage. These include: platelet storage in the frozen state: storage in the cold (4° C) in the liquid state; photochemical methods for the inactivation of viruses. bacteria and protozoa: infusible platelet membranes; and rehydrated lyophilized platelets. In addition to products using human platelets as their primary manufacturing source. other approaches have been used to make non‐platelet‐derived substitutes that might be capable of in vivo hemostasis. These include production of red blood cells, or liposomes, bearing hemostatically active agents on their surfaces; and fibrinogen‐coated albumin microcapsules or microspheres. The development of platelet substitutes is an increasing scientific and technological endeavor and there are many reasons to believe that platelet substitutes will become more efficacious and safer to use over time. Ultimately, such work will result in safe and effective platelet substitutes being available for clinical use in thrombocytopenic or other patients with increased risk for bleeding.
Clinical Use of Intravenous Immunoglobulins
Authors: Nydegger Urs E , Mohacsi Paul J. , Escher R. , Morell A.
Published: September 2024

Prophylaxis and treatment with i.v. immunoglobulins must envisage preparations from normal or hyperimmunised human donors, animals (horses and rabbits) as well as monoclonal and genetically and proteomically engineered chimeric or recombinant antibodies. The latter group of antibody sources from the bioreactor source must be seen in the context of traditional antibody therapy, including passive immunization, general antibody substitution and provision of lost immune regulatory capacities such as downregulation of complement activation, attenuation of Fc receptor apparatus as well as anti‐idiotypic potential. Beyond summarizing the present evidence based indications the present review is an outlook at the doorstep for future possibilities to improve precision of antibody dependent treatments and avoiding side effects which formerly compromised widespread use.
Extracorporeal Photochemotherapy ‐ Present and Future
Authors: Knobler Robert
Published: September 2024

Extracorporeal photochemotherapy (ECP) was introduced by Edelson and co‐workers in 1985. Since then the therapy, though still controversial in specific indications, has received wide acceptance and is presently been used in over 160 centers in Europe and the U.S.A. for a number of important dermatological and non‐dermatological indications. Convincing data in the past few years has documented that ECP is associated with a very low side‐effect profile. As of 2000 ECP continues to be used in the treatment of cutaneous T‐cell lymphoma, alone or in combination with other treatment modalities, and increasingly in the management of additional T‐cell mediated diseases, acute as well as chronic Graft versus Host Disease (GVHD) after allogeneic bone marrow transplantation in particular. ECP has also been shown to play an important role in the treatment of acute as well as chronic allograft rejection, in renal, lung, and cardiac transplant recipients and lately steroid steroid refractory inflammatory bowel disease. A number of mechanisms for its efficacy have been proposed whereby at present induction of anticlonotypic immunity directed against pathogenic clones of T lymphocytes may be an important concept. Treatment related apoptotic death of involved T cells and concurrent activation of antigen presenting cells may also closely relate to mechanisms associated with this therapy.
Progress in Improving the Pathogen Safety of Red Cell Concentrates
Authors: Chapman John
Published: September 2024

Current methods of preparing red cell concentrates do not include a process step to decontaminate pathogens potentially present in the transfusion product. Although substantial progress has been made in the reduction of the frequency of transmission of HIV, HCV, HBV and HTLV‐I as a result of the implmentation of diagnostic screening processes, the need for further reduction in transmission rate of these viruses remains. In addition, there are viruses which are known to be be present in blood but for which no screening test has been implemented to remove contaminated units from the blood supply. These viruses include but are not limited to TTV, HGV and Parvo B19. Finally, the lack of a pathogen inactivation process for red cells maintains the blood supply in a state of vulnerability to new viruses or virus variants as they enter the donor population. Recently, substantial progress has been made in the research and development of a class of chemical compounds designated as INACTINETM These compounds are being investigated for their potential to inactivate viruses in red cells without adversely affecting their physiologic function. One of the INACTINET compounds, designated as PEN110, is now in the clinical trial phase of development.
New Developments in Plasma Fractionation and Virus Inactivation
Authors: Morgenthaler Jean‐Jacques
Published: September 2024

Ethanol fractionation has been used for fifty years to prepare therapeutic proteins from human plasma. Although the method has been very successful, there are now newer techniques available, which might at least in part replace. ethanol fractionation. Whether or not this will occur depends on the economic benefits the new methods offer. Although transmission of viruses through blood products is nowadays fortunately a rare event, the search for alternative inactivation and/or removal methods for viruses continues. The small, non‐enveloped viruses are particularly difficult to deal with, and any new method should address this problem with a high. priority. Transmission of spongiform encephalopathies (Creutzfeld‐Jakob and similar diseases) by blood and blood products has not been observed so far. Preliminary experimental evidence indicates that the putative causative agent(s) are removed from the final products during fractionation.
Leukocyte Counting During Process Control of Leukoreduced Blood Components
Authors: Dzik Walter H.
Published: September 2024

Background and Objectives:

To describe the characteristics of counting assays used for process control of leukoreduction.

Materials and Methods:

Literature review. Results: Counting assays with good performance characteristics are an essential element of the process control of leukoreduction. A recent multicenter study by a Working Party of the ISBT has evaluated three widely used methods for counting low numbers of leukocytes in leukoreduced blood.

Conclusion:

Automated methods provide greater accuracy and and better inter‐laboratory precision than Nageotte hematocytometry. However, deterioration of performance as a result of prolonged sample shipment remains an obstacle to centralized testing services. Although several mathematical approaches have been used to model the distribution of residual leukocytes in leukoreduced blood, no single model has been shown to be clearly superior.