免疫吸附治疗在肾移植致敏受者中的应用

目的：探讨蛋白A免疫吸附（immunoads Orption，IA）治疗对清除肾移植致敏受者体内特异性抗HLA抗体的疗效和安全性。方法：10例肾移植致敏（PRA〉50％）受者用彤新蛋白A免疫吸附柱行IA治疗，测定治疗前后血免疫球蛋白及PRA水平。结果：10例患者IA治疗次数为4～15次（中位数9）。所有患者IA治疗后血清总IgG水平都明显下降（P〈0．001），IgA和IgM也较治疗前显著降低（P〈0．01）。PRA8例转阴，1例〈30％，1例仍为100％。结论：对于肾移植致敏受者，IA是一种特异性高、安全有效的治疗措施。     

Effect of hormone replacement therapy on CD4+ and CD8+ numbers, CD4+/CD8+ ratio, and immunoglobulin levels in hemodialysis patients

Uremia induces a suppression of the immune status. A large clinical literature suggests that estradiol (E2) plays a critical role in immune function. A large proportion of women hemodialysis patients faced early menopause and inadequate estrogen levels. The aim of the present study is to evaluate the effect of hormone replacement therapy on immune function in terms of CD4+ numbers (inducer/helper T cells), CD8+ numbers (cytotoxic/suppressor T cells), CD4+ / CD8+ ratio, and IgG, IgM, IgA levels in woman hemodialysis patients. In our study, 15 female hemodialysis patients (median age 32.6 range 24-45) were treated with triphasic estrogen/progesterone preparation (estradiol 2 mg for 10 days, and afterwards estradiol 2 mg+norethisterone 1 mg for another 10 days, and at the end estradiol 1 mg for 6 days) for 6 months. CD4+ numbers, CD8+ numbers, and IgG, IgA, and IgM levels were determined before and after HRT. The "paired-samples T" test was used for statistical analysis of pretreatment and posttreatment values. A significant increase was observed for CD4+ numbers (582 +/- 435 versus 637 +/- 445, p = 0.04) and CD4+/CD8+ ratio (1.4 +/- 0.16 to 2.4 +/- 0.3, p < 0.01) after hormone replacement therapy (HRT). Serum immunoglobulin levels were not changed significantly. In conclusion, in postmenopausal hemodialysis patients, HRT significantly increased CD4+ numbers and CD4+ / CD8+ ratio, but no effect was observed in IgM, IgG, and IgA levels. Long-term clinical effects of HRT on immune system should be investigated in dialysis patients with further studies.     

Bleeding complications in pediatric ABO-incompatible kidney transplantation

Background

ABO-incompatible renal transplantation (ABOi-RTx) following preconditioning with immunoadsorption (IA) and rituximab is a promising approach to facilitate living-related RTx. However, clinical experience is limited in pediatric patients.

Methods

Three patients underwent living-related ABOi-RTx in our center. Preoperative IA was performed six, ten and 11 times in patient one, two and three, respectively, to achieve isoagglutinin titers of ≤1:8 on the day of transplantation; rituximab was administered once. The immunosuppressive regimen further comprised tacrolimus, mycophenolate, methylprednisolone and basiliximab; immunoglobulin G (IgG) was infused on the day of ABOi-RTx.

Results

All three patients achieved normal renal function within 2–6 days post-RTx. Major postoperative bleeding occurred in two patients, with one requiring repeated blood transfusions and the other a surgical revision 4 h after RTx, despite local citrate anticoagulation use during the preoperative IA procedures in the latter patient. A pyelonephritis-associated increase of the isoagglutinin IgG/IgM titers to 1:64/1:128 led to a biopsy-proven acute humoral rejection in the third patient, which was treated successfully with plasma exchange and methylprednisolone pulses. The estimated glomerular filtration rate at 18, 8 and 23 months post-RTx was 96, 52 and 74 ml/min/1.73 m², respectively.

Conclusions

ABOi-RTx can successfully be performed in pediatric patients after preconditioning with quadruple immunosuppression, rituximab and IA. Caution is required regarding bleeding complications, which are most likely due to the unspecific binding of coagulation factors during repeated IA.     

Impact of Preemptive Fibrinogen Concentrate on Transfusion Requirements in Liver Transplantation: A Multicenter,Randomized, Double‐Blind,Placebo‐Controlled Trial

We hypothesized that preemptive fibrinogen administration to obtain an initial plasma level of 2.9 g/L would reduce transfusion requirements in liver transplantation. A randomized, multicenter, hemoglobin‐stratified, double‐blind, fibrinogen‐versus‐saline–controlled trial was conducted. The primary end point was the percentage of patients requiring red blood cells. We evaluated 51 patients allocated to fibrinogen and 48 allocated to saline; the primary end point was assessed using data for 92 patients because the electronic record forms were offline for three patients in the fibrinogen group and four in the saline group. We injected a median of 3.54 g fibrinogen preemptively in the fibrinogen group. Nine patients in the saline group (20.9%) required fibrinogen at graft reperfusion (compared with one patient [2.1%] in the fibrinogen group; p = 0.005). Blood was transfused to 52.9% (95% confidence interval [CI] 42.5–63.3%) in the fibrinogen group and 42.74% (95% CI 28.3–57.2%) in the saline group (p = 0.217). Relative risk for blood transfusion was 0.80 (95% CI 0.57–1.13). Thrombotic events occurred in one patient (2.1%) and five patients (11.4%) in the fibrinogen and saline groups, respectively. Seven patients (14.6%) in the fibrinogen group and nine (20.3%) in the saline group required reoperation. Preemptive administration of fibrinogen concentrate did not influence transfusion requirements.     

A prospective, randomized, blinded, and placebo-controlled trial of intraoperative intra-arterial urokinase infusion during lower extremity revascularization. Regional and systemic effects.

OBJECTIVE: This study was designed to evaluate the safety and regional and systemic effects of three doses of urokinase (UK) infused into the distal arterial circulation during routine operative lower extremity revascularization. METHODS: One hundred thirty-four patients were prospectively randomized to receive one of three bolus doses of UK (125,000, 250,000, or 500,000 U) or placebo (saline) infused into the distal circulation before lower extremity bypass for chronic limb ischemia. Regional (femoral vein) and systemic (arm) blood was sampled before drug infusion, prereperfusion, and postreperfusion, and systemic blood samples were obtained 2 hours postreperfusion. Assays evaluated plasma levels of fibrinogen, fibrin(ogen) degradation products (FDP), fibrin breakdown products (D-dimer and fragment B-beta 15-42), and plasminogen. Patients were monitored for clinically evident bleeding complications. The Wilcoxon rank-sum test was used to compare different drug doses with the placebo. RESULTS: Intraoperative bolus UK infusions produced no significant fibrinogen breakdown compared with placebo. There was a dose-related decline in plasminogen levels, which became significant at a dose of 500,000 U of UK (p < 0.001). There were dose-related increases in plasma FDP, which became significant at dose of 250,000 and 500,000 U (p < or = 0.005), and in plasma D-dimer, which were significant at all UK doses (p < 0.001). The changes in plasma fibrinogen and markers of fibrin breakdown were similar in the regional and systemic circulations. There was no increase in operative blood loss, blood replaced, or wound hematoma formation. There was an unexplained increased mortality in the placebo group (21.1% vs. 2.0%, p = 0.033). CONCLUSIONS: Intraoperative bolus UK infusion is safe, with no significant fibrinogen depletion or increased operative blood loss or wound hematoma formation. Dose-related plasminogen activation resulted in significant breakdown in cross-linked fibrin in the distal circulation. Intraoperative bolus UK infusion may be valuable as an adjunct in patients with chronic occlusive disease who are undergoing revascularization. Detailed randomized studies are indicated to establish clinical efficacy.     

Immunoglobulin class and specificity of lymphocytotoxic antibodies after kidney transplantation

The immunoglobulin class and specificity of the cytotoxic antibodies were investigated in sera collected during the first weeks following transplantation from 35 patients with functioning and 20 patients with failed grafts. No patient had had cytotoxic antibodies before the transplant, but 71.5% (25 of 35) of patients with functioning and 75% (15 of 20) of patients with failed graft subsequently developed them. The addition of dithiothreitol, which digests IgM antibodies, resulted in the disappearance of cytotoxicity in all positive sera from patients with a functioning graft. However, in the patients with failed grafts, the immunoglobulin class of the antibody varied; seven patients had only IgM antibodies, and seven had both IgM and IgG. After graft nephrectomy, IgG antibodies appeared in another six patients. In five of six patients with functioning grafts, mouse monoclonal antibodies blocked the cytotoxic activity; four with HLA-DQ monoclonal antibodies (Leu 10), one with HLA Class I (GD5). In the patients with failed grafts, blocking was seen in all nine patients studied; eight by GD5, six by Leu 10, and two by a monoclonal antibody to a monomorphic determinant of HLA-DR (100/77). Although the frequency of antibody-positive patients was similar in the successful and failed groups, the immunoglobulin class of the antibodies developed was IgM in the former group, whereas in the latter group some were IgM and others were IgG. Characterisation of the antibodies could be useful in the interpretation of a positive cross-match, since IgG antibodies are damaging to the graft whereas IgM antibodies are not.     

Characterization of ABH-subtype donor-specific antibodies in ABO-A-incompatible kidney transplantation

ABO-incompatible (ABOi) transplantation requires preemptive antibody reduction; however, the relationship between antibody-mediated rejection (AMR) and ABO-antibodies, quantified by hemagglutination (HA), is inconsistent, possibly reflecting variable graft resistance to AMR or HA assay limitations. Using an ABH-glycan microarray, we quantified ABO-A antigen-subtype (A-subtype)-specific IgM and IgG in 53 ABO-O recipients of ABO-A kidneys, before and after antibody removal (therapeutic plasma exchange [TPE] or ABO-A-trisaccharide immunoadsorption [IA]) and 1-year posttransplant. IgM binding to all A-subtypes correlated highly (R² ≥ .90) and A-subtype antibody specificities was reduced equally by IA versus TPE. IgG binding to the A-subtypes (II–IV) expressed in kidney correlated poorly (.27 ≤ R² ≤ .69). Reduction of IgG specific to A-subtype-II was equivalent for IA and TPE, whereas IgG specific to A-subtypes-III/IV was not as greatly reduced by IA (p < .005). One-year posttransplant, IgG specific to A-II remained the most reduced antibody. Immunostaining revealed only A-II on vascular endothelium but A-subtypes II-III/IV on tubular epithelium. These results show that ABO-A-trisaccharide is sufficient for IgM binding to all A-subtypes; this is true for IgG binding to A-II, but not subtypes-III/IV, which exhibits varying degrees of specificity. We identify A-II as the major, but importantly not the sole, antigen relevant to treatment and immune modulation in adult ABO-A-incompatible kidney transplantation.     

Removal of immunoglobulins by a protein A versus an antihuman immunoglobulin G-based system: evaluation of 602 sessions of extracorporeal immunoadsorption

Elimination of IgG can be achieved by extracorporeal immunoadsorption (IA) based on specific binding to either staphylococcal protein A (Excorim) or sheep polyclonal antibodies directed against human IgG (Therasorb). In 602 analyzed sessions of IA, elimination of IgG was 60% through 80% depending on the treated plasma volume, with no significant difference between the mentioned systems. However, the decrease of IgM and IgA was approximately 50% in the anti-IgG compared to 20-40% in the protein A system. Plasma albumin concentration decreased by 20% in the anti-IgG system compared to 15% in the protein A system, and hemoglobin values increased by 2% in the anti-IgG system and decreased by 6% in the protein A system. In conclusion, a clinical relevance for these findings cannot be ruled out, and the individual choice might depend on the clinical situation and laboratory findings.     

Immunoglobulin G-positive in B-cell cross-match decreases kidney allograft survival

We retrospectively studied all 1149 transplants performed at our center between 1993 and 2003 to determine the incidence and clinical effect of pretransplant B-positive cross-match on kidney graft survival. The patients were divided in two groups: B-negative (n = 1102) and B-positive in current sera (n = 47; 4.1%). AB-positive test was more frequent among regrafted patients (14% vs 3%; P = .00). Demographic data were not different between the groups. The overall rate of graft loss was similar (26% vs 24%, respectively; P = .86). However, early nonsurgical graft losses were more frequent among B-positive patients (46% vs 20%, respectively; P = .04). IgM was the most frequent immunoglobulin in the B-positive group (76% IgM and 24% IgG). There was no significant difference between B-negative and B-positive groups in the 1-, 5-, and 10-year graft survival rates (87% vs 83%, 73% vs 78%, 64% vs 66%, respectively; P = .87). The graft survival was significantly reduced comparing an IgG anti-B cell to the B-negative group (P = .03) as well as IgG compared to IgM (P = .004). In conclusion, only B-positive cross-match due to IgG decreased graft survival. Even though it is an uncommon situation (0.9%), this study stressed the clinical value of the B-cell cross-match as a tool to identify patients with a higher immunological risk.     

Antigenemia,immunoblotting, and enzyme immunoassay for early diagnosis of cytomegalovirus infection in renal transplant patients

Timely and rapid diagnosis of cytomegalovirus (CMV) infection is important for the management of transplant patients. We compared three serological assays, IgM immunoblot and IgG/IgM enzyme immunoassay (EIA), as well as the detection of CMV antigens in polymorphonuclear blood leukocytes (antigenemia), for their value in the early diagnosis of CMV infection. Thirty-one patients were monitored longitudinally for 3 months after renal transplantation. Laboratory documented CMV infection occurred in 20 patients. All of these cases showed a positive IgM immunoblot result that was confirmed by at least one of the other test assays (IgG EIA 19/20, antigenemia assay 13/20, and IgM EIA 12/20). All of the ten patients whose clinical picture was compatible with symptomatic CMV disease were positive for CMV infection according to IgM immunoblot and IgG EIA, nine were positive according to the antigenemia assay, and seven were positive according to IgM EIA. With reference to the temporal pattern, the antigenemia assay indicated CMV infection significantly earlier than the serological tests (P0.05). In symptomatic patients CMV antigen-positive leukocytes were, on the average, detected on the day of onset of symptoms, whereas detection by IgM immunoblot, IgG EIA, and IgM EIA followed 8, 13, and 14 days later, respectively. These results show that: (1) the CMV antigenemia assay is very useful for the early diagnosis of symptomatic CMV infections; (2) CMV antibodies, as an indicator of CMV infection, are detectable earlier and more frequently by IgM immunoblot than by IgG/IgM EIA; (3) compared to CMV anti-genemia, the IgM immunoblot indicated CMV infection more often but significantly later; and (4) only a combination of several diagnostic methods allows optimal detection of CMV infections in renal transplant patients.     

Plasma gamma globulin levels after splenectomy and spleen salvage

A series of plasma globulin studies was carried out on 108 patients who were operated on for splenic trauma during the last 3 years. The reasons for splenectomy or spleen salvage were; gunshot wounds in 22 patients (20.3%); stab injuries in 10 patients (9.2%) and blunt abdominal trauma in 76 patients (70.3%). Plasma gamma globulin determinations were made on the 8th postoperative day and at 3 months. In the splenectomy group; plasma gamma globulin determinations demonstrated a significant reduction in serum IgM levels (p less than 0.001) but no significant changes in IgA and IgG levels (p greater than 0.05). No changes were detected in IgA, IgG and IgM levels in the spleen salvage group (p greater than 0.05). We believe that the preservation of the traumatized spleen should be the prime aim of surgeons.     

Immunoglobulin M and Immunoglobulin G Subclass Distribution of Anti-galactose-Alpha-1,3-Galactose and Anti-N-Glycolylneuraminic Acid Antibodies in Healthy Korean Adults

BackgroundHuman preformed antibodies (Abs), anti-galactose-alpha-1,3-galactose (Gal) and anti-N-glycolylneuraminic acid (Neu5Gc), can react with porcine antigens of wild-type pigs. To provide basic population data of the Abs for potential application in clinical xenotransplantation, we developed enzyme-linked immunosorbent assay methods and investigated the serum titers of anti-Gal and anti-Neu5Gc Abs, including immunoglobulin (Ig) M and IgG along with its subclasses, in humans.MethodsAnti-Gal and anti-Neu5Gc Abs serum titers were measured in 380 healthy Korean adults using the in-house enzyme-linked immunosorbent assays. The frequency and median values of anti-Gal and anti-Neu5Gc were measured, and their class and subclass distribution were evaluated.ResultsThe detection frequencies of anti-Gal were 99.2%, 95.0%, 23.2%, 94.5%, 12.4%, and 3.4% for IgM, IgG, IgG1, IgG2, IgG3, and IgG4, respectively. The detection frequencies of anti-Neu5Gc Abs were 87.4%, 96.6%, 1.6%, 46.3%, 0.0%, and 0.0% for IgM, IgG, IgG1, IgG2, IgG3, and IgG4, respectively. The median values of anti-Gal IgM (1001.6 ng/mL) and IgG (1198.3 ng/mL) were significantly higher than those of anti-Neu5Gc Abs (IgM, 328.4 ng/mL; IgG, 194.7 ng/mL; P < .001). IgG2 titers of both anti-Gal and anti-Neu5Gc Abs correlated better with the IgG class than the titers of other IgG subclasses.ConclusionsThe titers of anti-Gal Abs were higher than those of anti-Neu5Gc Abs. IgG2 was the main IgG subclass in both anti-Gal and anti-Neu5Gc Abs. Variation in the titers of anti-Gal or anti-Neu5Gc Abs may partly explain the biological and immunologic changes that occur in recipients of xenotransplants.     

Hemostatic alterations in patients with acute, unilateral vestibular paresis.

OBJECTIVES: The etiopathogenesis of acute unilateral peripheral vestibulopathy (APV) still remains a matter of debate; ischemic changes in the circulation of the labyrinth may play a role. We consequently looked for possible hemostasis alterations in a group of patients with APV of an unknown nature. METHODS: We evaluated blood parameters known to be involved in circulation disorders, including total and HDL cholesterol, triglycerides, apolipoprotein A and B, lipoprotein(a), homocysteine, folate, prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, antithrombin III, protein C, protein S, activated protein C resistance, and anticardiolipin IgG and IgM antibodies. A series of 23 patients affected with APV were consecutively referred to our department, in the acute phase, before treatment, and in the follow-up phase after 4 to 6 weeks of pharmacologic washout. The aforementioned blood parameters were also measured in a series of 15 patients with Menière's disease. RESULTS: The patients with APV in the acute phase compared with the patients with Menière's disease in the acute phase exhibited increased plasma levels of fibrinogen (mean, 338.3 +/- 135.9 SD vs 271.3 +/- 69.8 SD mg/dL, P = 0.05), increased plasma levels of D-dimer (mean, 320 +/- 207.8 SD vs 226.7 +/- 138.7 SD NG/mL), enhanced plasma levels of lipoprotein(a) (41.4 +/- 38.6 SD vs 16 +/- 18.2 SD mg/dL, F = 5.67, P = 0.02), high leukocyte count (9.1 +/- 2.7 SD vs 6.5 +/- 1.3 SD x 10(3)/microL; F = 8.42, P < 0.006), and low serum folate concentration (5.3 +/- 1.8 SD vs 7.1 +/- 2.7 NG/mg; F = 4.34, P = 0.04). During follow-up the prothrombin time was prolonged (F = 4.34, P = 0.04) and leukocyte count decreased (F = 7.39, P < 0.019) in the APV patients, whereas fibrinogen, D-dimer, lipoprotein(a), and folate were unchanged. CONCLUSION: Our results provide evidence suggesting an involvement of the hemostatic system in APV.     

Hypogammaglobulinemia following cardiac transplantation: a link between rejection and infection.

BACKGROUND: Hypogammaglobulinemia (HGG) has been reported after solid organ transplantation and is noted to confer an increased risk of opportunistic infections. OBJECTIVES: In this study, we sought to assess the relationship between severe HGG to infection and acute cellular rejection following heart transplantation. METHODS: Between February 1997 and January 1999, we retrospectively analyzed the clinical outcome of 111 consecutive heart transplant recipients who had immunoglobulin G (IgG) level monitoring at 3 and 6 months post-transplant and when clinically indicated. RESULTS: Eighty-one percent of patients were males, mean age 54 +/- 13 years, and the mean follow-up period was 13.8 +/- 5.7 months. Patients had normal IgG levels prior to transplant (mean 1137 +/- 353 mg/dl). Ten percent (11 of 111) of patients developed severe HGG (IgG < 350 mg/dl) post-transplant. The average time to the lowest IgG level was 196 +/- 125 days. Patients with severe HGG were at increased risk of opportunistic infections compared to patients with IgG > 350 mg/dl (55% [6 of 11] vs. 5% [5 of 100], odds ratio = 22.8, p < 0.001). Compared to patients with no rejection, patients who experienced three or more episodes of rejection had lower mean IgG (580 +/- 309 vs. 751 +/- 325, p = 0.05), and increased incidence of severe HGG (33% [7 of 21] vs. 2.8% [1 of 35], p = 0.001). The incidence of rejection episodes per patient at 1 year was higher in patients with severe HGG compared to patients with IgG >350 (2.82 +/- 1.66 vs. 1.36 +/- 1.45 episodes/patient, p = 0.02). The use of parenteral steroid pulse therapy was associated with an increased risk of severe HGG (odds ratio = 15.28, p < 0.001). CONCLUSIONS: Severe HGG after cardiac transplantation may develop as a consequence of intensification of immunosuppressive therapy for rejection and hence, confers an increased risk of opportunistic infections. IgG level may be a useful marker for identifying patients at high risk.     

Inflammatory markers and platelet aggregation tests as predictors of hemoglobin and endogenous erythropoietin levels in hemodialysis patients

BACKGROUND/AIMS: Chronic inflammation is a common cause of severe anemia and hyporesponsiveness to recombinant erythropoietin (EPO) therapy in maintenance hemodialysis (HD) patients. We compared various acute-phase markers and ex vivo platelet aggregation tests in relation to clinical conditions in order to find factors predictive of hemoglobin (Hb) and endogenous EPO levels in a cross-section of clinically stable HD patients. METHODS: In 100 subjects, pre-HD blood levels of C-reactive protein (CRP), alpha(1)-acid-glycoprotein (AGP), alpha(1)-antitrypsin (AT), immunoglobulin (Ig) M and G (by nephelometry), antigens of endothelial von Willebrand factor (vWF), type 1 plasminogen activator inhibitor and thrombomodulin, interleukin-6, lipoprotein(a) [Lp(a)] and EPO (by ELISA), and albumin, fibrinogen, iron metabolism indices, thyroid-stimulating hormone, phosphorus, parathormone, total cholesterol, triglycerides, viral hepatitis B/C markers, liver enzyme, and aluminium were determined. Platelet aggregations in response to ristocetin (RIPA), adenosine diphosphate, and collagen were measured in whole blood (electric impedance method) and platelet-rich plasma (optical aggregometry). RESULTS: Hb levels inversely correlated with IgM, Lp(a), soluble vWF antigen, phosphorus, and all platelet aggregations in whole blood, but not in platelet-rich plasma. HD duration and triglycerides were positive correlates of anemia. In a multivariable analysis, increased IgM, short HD duration, increased Lp(a) and enhanced whole blood RIPA (in descending order of significance) were independent predictors of low Hb levels. In 51 patients not treated with recombinant EPO, serum levels of this hormone inversely correlated with whole blood RIPA, AT, age, vWF antigen, AGP, and positively with viral hepatitis marker. Anemia and EPO levels were not affected by gender, body mass index, cause of renal failure, residual renal function, HD dose, protein catabolic rate, use of different heparins or dialysate buffers, ACE inhibitor therapy, and parathyroid or thyroid function. In additional 10 patients, single HD session resulted in an increase in IgM levels associated with a fall in total lymphocyte counts. CONCLUSION: Subclinical inflammation is an important determinant of anemia in maintenance HD patients. Increased serum IgM reflecting a microinflammatory effect of HD procedures, enhanced whole blood RIPA as a surrogate of vascular endothelial damage, and Lp(a) as its promoter could be markers of such impaired erythropoiesis.     

IG-therasorb immunoapheresis in orthotopic xenotransplantation of baboons with landrace pig hearts

BACKGROUND: The major problem of xenotransplantation is, that hyperacute xenograft rejection (HXR) causes graft failure within minutes or a few hours because of natural antibodies and activation of the complement system. As a preclinical model we transplanted pig hearts orthotopically into baboons. To prevent HXR after orthotopic xenotransplantation (oXHTx), the immunoglobulins (Ig) and natural antibodies were adsorbed to reusable Ig-Therasorb immunoadsorption (IA) columns. METHODS: We performed three oXHTx of landrace pig hearts into baboons (19+/-6.8 kg), using extracorporeal circulation (ECC) connected to the IA unit. After separating the recipient's blood into plasma and cellular fraction by a plasma filter, plasma flow was directed to the Ig-Therasorb column coated with polyclonal sheep-antibodies against human IgG, IgM, and IgA. Intraoperative treatment consisted of 4 cycles of IA. For a control, we transplanted one pig heart into a baboon (16.9 kg) without applying IA. Perioperatively, serum concentrations of Ig, anti-pig-antibodies, complement and cardiac enzymes were determined. Tissue samples of myocardium were collected at the end of the study for immunohistochemical examinations, light microscopic examination (LM) and electron microscopic examination (EM). For cardiac monitoring after oXHTx, we used ECG, echocardiography, and invasive measurement of cardiac output. To prevent a mismatch of donor and recipient heart size, the donor pig had a 30-40% lower body weight than the recipient baboon. RESULTS: Four cycles of IA removed >80% of IgG, IgM, and IgA from plasma. The graft of the control animal failed after 29 min. The first oXHTx with IA was intentionally terminated after 100 min, the second oXHTx after 11 hr and the third oXHTx after 21 hr. All xenografts showed no histological signs of HXR. After weaning off ECC, these donor hearts worked in sinus rhythm without electrocardiographic ST-segment elevation. An excellent cardiac output was measured by echocardiography and thermodilution (2 L/min). Serological parameters indicating cardiac damage were significantly lower after IA if compared with the control experiment. Macroscopically, the xenograft of the control animal showed massive hemorrhage in comparison with the almost inconspicuous grafts after IA. The myocardium of the IA group demonstrated fewer deposits of Ig and complement components compared with the control animal. CONCLUSION: Baboons do not hyperacutely reject a porcine xenograft after antibody depletion by the Ig-Therasorb column. In our experiment only 4 cycles of immunoapheresis effectively prevented HXR after oXHTx of baboons. The Ig-Therasorb column is a reusable device, which can be handled easily in combination with the ECC. IA must be tested in oXHTx longterm survival experiments, especially in combination with transgenic pig organs, which could be a reliable preclinical approach for future clinical xenotransplantation.     

An algorithm for the management of coagulopathy from postpartum hemorrhage,using fibrinogen concentrate as first-line therapy

BackgroundWe constructed an algorithm for the management of coagulopathy from massive postpartum hemorrhage. Fibrinogen concentrate was administered preferentially, and the dose of both fibrinogen concentrate and fresh frozen plasma given was determined by the plasma fibrinogen concentration and prothrombin time. The efficacy of the algorithm and the amount of fibrinogen concentrate and fresh frozen plasma transfused were determined.MethodsThe study was conducted in a single teaching perinatal center. Nineteen patients were included between April 2011 and March 2014 (patient group). For a historical comparison group, we retrospectively analyzed the records of 19 patients who had been treated for coagulopathy from massive postpartum hemorrhage between April 2006 and March 2011 (control group).ResultsBlood loss was significantly lower in the patient group. No adverse events were associated with this management in either group. The dose of fibrinogen concentrate administered was significantly higher and that of fresh frozen plasma administered was significantly lower in the patient group.ConclusionThis algorithm appeared to help reduce blood loss and the total amount of fresh frozen plasma transfused when treating coagulopathy from postpartum hemorrhage, and may represent another strategy for achieving hemostasis in this setting.     

单中心免疫吸附治疗10年回顾性分析

目的评价免疫吸附疗法应用于自身免疫性疾病和高脂血症的效果及临床价值。方法回顾性分析我中心近10年来156例接受免疫吸附治疗的自身免疫性疾病及高脂血症患者的临床资料。所有患者均应用Citem10免疫吸附系统,使用了A蛋白、PH350、TR350、DNA、抗低密度脂蛋白胆固醇（LDL-C）抗体等5种不同吸附材料的吸附柱。监测自身免疫性疾病患者治疗前后免疫球蛋白、补体、自身抗体、血常规、肝功能、肾功能等指标,比较疾病活动评分以及器官损害指数;监测高脂血症患者治疗前后血脂水平。结果免疫吸附治疗后,自身免疫性疾病患者血浆IgG清除率为（76．71±7．59）％,治疗前后有统计学差异（P〈0．05）,IgA清除率为（44．54±5．92）％,治疗前后有统计学差异（P〈0．05）,IgM清除率为（45．76±5．65）％,治疗前后有统计学差异（P〈0．05）,血抗核抗体、抗双链DNA、乙酰胆碱受体抗体、类风湿性关节炎相关抗体或标记物阳性率降低。与治疗前相比,高脂血症患者血浆LDL-C、甘油三酯浓度显著降低,差异有统计学意义（P〈0．05）。所有患者病情显著好转,器官受损情况明显改善。结论免疫吸附疗法可迅速有效的清除自身抗体和血脂成分,使病情得到控制,保护受损脏器功能,对各种自身免疫性疾病及高脂血症均具有良好治疗效果,在病情进展阶段抓住时机应用免疫吸附疗法,效果更显著。     

The use of fibrinogen concentrate to correct hypofibrinogenaemia rapidly during obstetric haemorrhage

Haemorrhage is a common complication of childbirth with 0.65% of deliveries associated with significant (>1500 mL) peripartum blood loss. Hypofibrinogenaemia secondary to dilutional and consumptive coagulopathies can be challenging to correct quickly with conventional blood and plasma therapy. Fibrinogen concentrate offers rapid restoration of fibrinogen levels with a small volume infusion and minimal preparation time. It is effective in treating patients with congenital hypofibrinogenaemia, but there are few reports of its use in association with continuing obstetric haemorrhage. Six cases of obstetric haemorrhage, associated with hypofibrinogenaemia, treated with fibrinogen concentrate in conjunction with platelets, fresh frozen plasma, packed red blood cells, uterotonics and obstetric intervention are described. In all cases, laboratory assessed coagulation was rapidly normalised and severe haemorrhage improved. These cases suggest that fibrinogen concentrate may be an effective addition to conventional treatments for obstetric haemorrhage associated with hypofibrinogenaemia.