Management of Kell isoimmunization--evaluation of a Doppler-guided approach.
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OBJECTIVE: To assess the role of peak systolic velocity in the middle cerebral artery (MCA-PSV) in the management of pregnancies complicated by Kell isoimmunization. METHODS: Sixteen fetuses were monitored by conventional protocol (Group 1) and eight fetuses by an MCA-PSV-guided protocol (Group 2). The conventional protocol included a weekly ultrasound evaluation and measurement of maternal anti-Kell titers every 4-6 weeks. In Group 2 Doppler assessment of the MCA-PSV was performed at intervals of 4 to 7 days and MCA-PSV>1.5 multiples of the median (MoM) was considered as an indication for fetal blood sampling (FBS). RESULTS: No parameter emerged as a reliable predictor of isoimmunization severity in Group 1. In Group 2, no FBS was necessary in one case since the MCA-PSV values obtained during the follow-up were <1.29 MoM. In two cases the first FBS was already indicated after 1 week of follow-up, but five other fetuses were followed for 3-9 weeks before FBS was indicated. All fetuses with MCA-PSV>1.5 MoM prior to intrauterine transfusion (IUT) had severe fetal anemia on FBS. In fetuses with severe anemia on the first FBS, the MCA-PSV values 7 days before the first FBS were <1.29 MoM (four cases), between 1.29 and 1.5 MoM (two cases) and >1.55 MoM (one case). CONCLUSIONS: In the management of Kell isoimmunization invasive procedures may be avoided by implementing MCA-PSV measurements. Delineation of appropriate intervals between reassessments, the reliability of MCA-PSV following repeated IUTs, and cut-off values for FBS await further study. (+info)
Incidence and risk factors for the development of prolonged and severe intrahepatic cholestasis after liver transplantation.
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Predictive factors for intrahepatic cholestasis after orthotopic liver transplantation (OLT) have not yet been established. We sought to identify the incidence and risk factors associated with prolonged severe intrahepatic cholestasis (PSIC) after OLT. We assessed 428 consecutive patients undergoing their first OLT. PSIC was diagnosed if a serum bilirubin concentration was greater than 100 micromol/L and/or a 3-fold increase of alkaline phosphatase occurred within the first month after OLT and was sustained for at least 1 week in the absence of biliary complications. Multivariable logistic regression identified factors independently associated with PSIC. PSIC developed in 107 patients (25%). Independent risk factors by multivariable analysis were intraoperative transfusion of cryoprecipitate and platelets; nonidentical blood group status; suboptimal organ appearance; inpatient status before transplantation; and bacteraemia in the first month after transplantation. In contrast, acute liver failure, older age, and higher levels of serum sodium and serum potassium were all associated with a reduced likelihood of developing PSIC in the first month. There were 47 deaths in the PSIC group (44%) as opposed to 65 deaths in the non-PSIC group (20%) after OLT. A poor preoperative clinical status in conjunction with a suboptimal graft was associated with PSIC after OLT. Avoidance of suboptimal livers and ABO nonidentical grafts for young patients with poor synthetic function and for pretransplant inpatients may lessen this complication and reduce the associated early mortality. (+info)
Renal transplantation across the ABO barrier.
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Some patients with end-stage renal disease do not have suitable living related donors due to ABO incompatibility. Crossing the ABO barrier has long been considered an absolute contraindication to kidney transplantation. Although transplantation using A2 kidneys has been performed in a few centers over the past two decades with variable success, the presence of blood group antigens can cause immediate or early graft loss due to preformed antibody-mediated hyperacute rejection. Over the past few years, novel protocols designed to reduce anti-donor antibodies have allowed successful transplantation across the ABO barrier. This requires careful preoperative conditioning, which will be described in this article. (+info)
Utilizing list exchange and nondirected donation through 'chain' paired kidney donations.
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In a list exchange (LE), the intended recipient in an incompatible pair receives priority on the deceased donor waitlist (DD-waitlist) after the paired incompatible donor donates a kidney to a DD-waitlist candidate. A nondirected donor's (ND-D) kidney is usually transplanted directly to a DD-waitlist candidate. These two established practices would help even more transplant candidates if they were integrated with kidney paired donation (KPD). We consider a scenario in which the donor of an LE intended recipient (LE-IR) donates to a compatible KPD intended recipient (KPD-IR), and the KPD donor (KPD-D) donates to the waitlist (an LE-chain). We consider a similar scenario in which an ND-D donates to a KPD-IR and the KPD-D donates to the DD-waitlist (an ND-chain). Using data derived from the New England Program for Kidney Exchange (NEPKE) and from OPTN/SRTR recipient-donor distributions, simulations are presented to evaluate the potential impact of chain exchanges coordinated with KPD. LE donors (LE-D) and ND-D who are ABO-O result in the highest number of additional transplants, while results for ABO-A and B donors are similar to each other. We recommend that both LE and ND donations be utilized through chain exchanges. (+info)
Interleukin-8 production in red blood cell incompatibility.
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Hemolytic transfusion reactions (HTR) are characterized by fever, shock, organ system failure, intravascular coagulation, and possibly death. The same findings may be associated with sepsis. Neutrophils have been implicated in the pathogenesis of HTR, although a mechanism for neutrophil activation has not been shown. In addition, the possible role that cytokines may play in HTR has not been investigated. We show that interleukin-8 (IL-8), a cytokine with chemotactic and neutrophil-activation properties, is produced in whole blood following addition of ABO-incompatible red blood cells, in a dose- and time-dependent manner related to the degree of hemolysis, and is inhibited by inactivation of complement. IL-8 production is accompanied by increased gene expression in the buffy coat. This observation has implications for the understanding of the pathogenesis of and for the treatment of HTR. (+info)
Isolated donor specific alloantibody-mediated rejection after ABO compatible liver transplantation.
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Antibody-mediated rejection (AMR) after liver transplantation is recognized in ABO incompatible and xeno-transplantation, but its role after ABO compatible liver transplantation is controversial. We report a case of ABO compatible liver transplantation that demonstrated clinical, serological and histological signs of AMR without evidence of concurrent acute cellular rejection. AMR with persistently high titers of circulating donor specific antibodies resulted in graft injury with initial centrilobular hepatocyte necrosis, fibroedematous portal expansion mimicking biliary tract outflow obstruction, ultimately resulting in extensive bridging fibrosis. Immunofluorescence microscopy demonstrated persistent, diffuse linear C4d deposits along sinusoids and central veins. Despite intense therapeutic intervention including plasmapheresis, IVIG and rituximab, AMR led to graft failure. We present evidence that an antibody-mediated alloresponse to an ABO compatible liver graft can cause significant graft injury independent of acute cellular rejection. AMR shows distinct histologic changes including a characteristic staining profile for C4d. (+info)
Autoimmune hemolytic anemia (AIHA) is most often idiopathic. However, in recent years, AIHA has been noted with increased incidence in patients receiving purine nucleoside analogues for hematologic malignancies; it has also been described as a complication of blood transfusion in patients who have also had alloimmunization. As the technology of hematopoietic stem cell transplantation has become more widespread, immune hemolysis in the recipients of ABO-mismatched products has become better recognized. The syndrome is caused by passenger lymphocytes transferred from the donor, and although transient, can be quite severe. A similar syndrome has been observed in recipients of solid organ transplants when there is ABO-incompatibility between donor and recipient. Venous thromboembolism is a little-recognized, though likely common, complication of autoimmune hemolytic anemia (AIHA), and may in some instances be related to coexistent antiphospholipid antibodies. While AIHA is a well-documented complication of malignant lymphoproliferative disorders, lymphoproliferative disorders may also paradoxically appear as a consequence of AIHA. A number of newer options are available for treatment of AIHA in patients refractory to corticosteroids and splenectomy. Newer immunosuppressives such as mycophenolate may have a role in such cases. Considerable experience has been accumulating in the last few years with monoclonal antibody therapy, specifically rituximab, in difficult AIHA cases; it appears to be a safe and effective option. (+info)
Synthetic blood group antigens for anti-A removal device and their interaction with monoclonal anti-A IgM.
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Removal of blood group antibodies against the donor organ prior to ABO-incompatible transplantation can prevent episodes of hyperacute rejection. We are developing a specific antibody filter (SAF) device consisting of immobilized synthetic Atrisaccharide antigens conjugated to polyacrylamide (Atri-PAA) to selectively remove anti-A antibodies directly from whole blood. In this study, we evaluated eight anti-A IgM monoclonal antibodies (mAbs) using Enzyme-Linked Immunosorbent Assay (ELISA) to determine their specificity for binding to Atri-PAA. Five of the eight mAbs met our criteria for specificity by binding to Atri-PAA with at least five times greater affinity compared to the negative controls. These selected mAbs will be studied for their binding characteristics to Atri-PAA which will aid in the development of the SAF. The study of kinetics of antibody removal and quantification of antibody removal will be used in our mathematical model to maximize the antibody removal rate and binding capacity of the SAF. (+info)