Unraveling the immunologic response in thrombotic thrombocytopenic purpura.
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ADAM Proteins↗
Biomedical subjects
P Knöbl
Publications and source records attributed to P Knöbl.
Antiplatelet therapy prior to carotid endarterectomy--still room for improvement.
BACKGROUND: Antiplatelet therapy is one of the most important modalities for secondary prevention of ischemic events. The aim of this prospective study was to evaluate the current practice of antiplatelet therapy in patients with high grade stenosis of the internal carotid artery (ICA), who were referred by neurologists, stroke physicians and cardiologists for carotid endarterectomy. PATIENTS AND METHODS: Patients referred to our department for carotid endarterectomy with ICA stenosis (> 70% according to NASCET criteria) were prospectively evaluated regarding atherosclerosis risk factors and current antiplatelet therapy. During a 7 month period, 235 patients were scheduled for carotid endarterectomy. Their mean age was 70 years (range 42 years to 95 years), 91 patients were female (39%), 144 male (61%). 122 patients (52%) had a symptomatic ICA stenosis, 113 (48%) an asymptomatic ICA stenosis. RESULTS: Of the 235 patients, 29 were either on low molecular weight heparin or vitamin K antagonists for reasons other than ICA stenosis and were therefore excluded from analysis. Therefore, 206 patients (88%) were evaluated for antiplatelet therapy prescribed by their admitting physicians. Of these patients, 77 (37%) (42 (41%) symptomatic and 35 (34%) asymptomatic patients) did not receive any antithrombotic therapy prior to admission for surgery. The majority of patients received aspirin preoperatively (106 patients, 51.5%) 13 (6%) patients were on clopidogrel and 10 (5%) on dual therapy with Aspirin and clopidogrel. CONCLUSIONS: More than one third of patients awaiting carotid endarterectomy did not receive any antiplatelet therapy, despite high grade ICA stenosis. Since this practice does not meet the current guidelines, campaigns to increase the awareness of this problem are urgently needed.
Adult↗
Antithrombotic strategies in vascular surgery: evidence and practice.
BACKGROUND: The aim of this study was to evaluate the current practice of peri and postoperative antithrombotic therapy in vascular surgery in Austria and to compare this with the results of randomised prospective clinical trials. METHODS: A questionnaire assessing intra, postoperative and long-term antithrombotic treatment in 13 different surgical procedures (three supra-aortic, three aorto-iliac reconstructions and seven inguinal and infra-inguinal arterial reconstructions) was sent to all 22 institutions training vascular surgical fellows in Austria. RESULTS: Intraoperative antithrombotic therapy was quite consistently performed with unfractionated heparin (UFH) with or without acetylsalicylic acid (ASA). Early and long-term postoperative therapy differed considerably. Most centres used low molecular weight heparin (LMWH) for early postoperative therapy after vascular reconstructions, in > 75% combined with ASA and/or clopidogrel. Long-term therapy consisted of antiplatelet agents in all centres. Vascular grafts were anticoagulated with UFH in 25% of the centres in the early postoperative period, the remaining institutions used LMWH +/- antiplatelet agents. For long-term antithrombotic therapy cumarins were used in 75% of the centres, predominantly for venous grafts. Distal prosthetic grafts were mainly treated with antiplatelet agents. Intraoperative antithrombotic therapy was in accordance to present guidelines, postoperative antithrombotic therapy, however, differed considerably between the participating institutions and the results of available controlled studies. CONCLUSION: Optimal antithrombotic strategies during and after vascular surgery are still under debate, and current practice often differs from available evidence. Vascular surgical societies should be encouraged to define recommendations on antiplatelet therapy and anticoagulation for different vascular interventions.
Austria↗
Impact of cytogenetics on the prognosis of adults with de novo AML in first relapse.
Karyotype is an important prognostic factor in patients with newly diagnosed acute myeloblastic leukaemia (AML). The prognostic value of cytogenetics on the outcome of patients with AML in relapse has not yet been well defined. We analysed the clinical outcome of 152 patients with de novo, chemotherapy-treated AML in first relapse according to the cytogenetic classification of the United Kingdom Medical Research Council. The rate of second complete remission (CR) (88, 64 and 36%) and the probability of survival at 3 years (43, 18 and 0%) were significantly different between the favourable, intermediate and adverse cytogenetic risk groups, respectively. Compared to the favourable group, the relative risk (RR) of death (multivariate analyses) was 2.6 (confidence interval (CI): 1.5-4.4, P<0.001) for the intermediate and 3.7 (CI: 1.7-7.9, P=0.001) for the adverse group. The prognostic value of the duration of first CR was confirmed (RR of death: 2.0 (CI: 1.0-4.0) for each additional year in first CR), whereas the FLT3 mutation obtained at diagnosis did not markedly influence the outcome of patients with AML in relapse. In conclusion, our results indicate that both karyotype and the duration of first CR are independent prognostic factors for patients with de novo AML in first relapse.
Acute Disease↗
Fibrin sealant produced by the CryoSeal FS System: product chemistry, material properties and possible preparation in the autologous preoperative setting.
BACKGROUND AND OBJECTIVES: The CryoSeal FS has been introduced as an automated device for the production of fibrin sealant from small volumes of plasma. We tested this device and compared the product with commercially available fibrin sealants and with the requirements of the European Pharmacopoeia. MATERIALS AND METHODS: The CP3 program and disposables required were used to manufacture fibrin sealant. The chemistry and mechanical properties of the product were investigated. RESULTS: The cryoprecipitate generated with CryoSeal contains concentrated fibrinogen and critical clotting factors. The efficiency of the production process is poor, but the production procedure itself is simple and not time-consuming. The volume of plasma required allows application in the preoperative autologous setting. CONCLUSIONS: The CryoSeal FS is an automated device for cryoprecipitation and production of thrombin. It can be implemented easily in the clinical routine, although, owing to product specifications, the efficacy of the CryoSeal fibrin sealant requires further clinical trials.
Blood Component Removal↗
Stability of coagulation factors in thawed, solvent/detergent-treated plasma during storage at 4 degrees C for 6 days.
BACKGROUND AND OBJECTIVES: Transfusion of fresh-frozen plasma is still a pillar in emergency medicine for using to prevent dilutional coagulopathy or disseminated intravascular coagulation after severe blood loss, but thawing procedures can delay its availability. On the other hand, the wastage of plasma, once thawed and not transfused within a defined time-period, represents an inefficient handling of economic resources and is contradictory to blood donor intentions. In this study we investigated the stability of coagulation factor activities and plasma protein levels during 6 days of storage of thawed solvent/detergent (S/D)-treated plasma at +4 degrees C. Our results may form the basis for reconsideration of expiry times of thawed S/D-treated plasma. MATERIALS AND METHODS: Five units of S/D-treated plasma (Octaplas) were thawed and warmed to 20 degrees C, then recooled and stored at +4 degrees C for 6 days. The activities of coagulation factors II, V, VII, VIII, IX, X, XI and XII, fibrinogen, antithrombin (AT), protein C, protein S and von Willebrand factor antigen (vWF:Ag) were measured on days 0, 1, 2, 3 and 6. RESULTS: Except for protein S, the activities of all coagulation factors and inhibitors were at least 0.5 U/ml during storage at 4 degrees C for 6 days. The mean levels, during storage, of factors IX, X, XI and XII, vWF:Ag, fibrinogen and protein C were at least 94%, and of factors II, V and VIII, and AT at least 78%, of the levels immediately after thawing; the activity of factor VII decreased to 83% and of protein S to 43% of the baseline values. CONCLUSIONS: Thawed S/D-treated plasma stored at +4 degrees C for up to 6 days still contains sufficient coagulation activities and plasma proteins to be regarded as suitable for transfusion in the established indications.
Blood Coagulation Factors↗
Prolonged red cell aplasia after major ABO-incompatible allogeneic hematopoietic stem cell transplantation: removal of persisting isohemagglutinins with Ig-Therasorb immunoadsorption.
Delayed donor red cell engraftment and prolonged red cell aplasia (PRCA) are well-recognized complications of major ABO-incompatible myeloablative and non-myeloablative hematopoietic stem cell transplantation (HSCT). There is an intense debate about the impact on outcome, severity of hemolysis, association with graft-versus-host disease and survival after blood group-incompatible stem cell transplantation. Therefore, therapeutic strategies should be considered to avoid these possible complications. We present five patients, who received allogeneic HSCT from human leukocyte antigen-identical donors for hematological malignancies, which were treated with Ig-Therasorb immunoadsorption (five treatments/week) to remove persisting incompatible isohemagglutinins. After a median of 17 treatments (range 9-25), all the patients became transfusion independent with the presentation of donor's blood group. No side effects occurred during treatment. Ig-Therasorb immunoadsorption seems to be a promising therapeutic method for rapid, efficient and safe elimination for persisting isohemagglutinins for patients with PRCA after allogeneic hematological stem cell transplantation.
ABO Blood-Group System↗
Immunoadsorption for the treatment of a patient with severe thrombotic thrombocytopenic purpura resistant to plasma exchange: kinetics of an inhibitor of ADAMTS13.
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ADAM Proteins↗
Autologous blood stem cell transplantation in refractory systemic lupus erythematosus with severe pulmonary impairment: a case report.
For patients with severe forms of autoimmunity, including systemic lupus erythematosus (SLE), purging autoreactive T cells from the immune repertoire by transplanting autologous hematopoietic stem cells (ASCT) is a therapeutic option. We describe an 18-year-old woman with SLE who had been treated with corticosteroids, azathioprine, cyclophosphamide (CYC), and immunopheresis for 4 years, during which time mechanical ventilation for lupus pneumonitis had been repeatedly required. After the patient was conditioned by administration of CYC and antithymocyte globulin, a total of 8.87 x 10(6) purified CD34+ cells per kg of body weight was infused. Hematopoietic regeneration was observed within 9 days. Twenty-one months after ASCT, the patient continues to be in complete clinical remission, with no signs of SLE-related disease activity and without any immunosuppressive medications. Her pulmonary function has returned to normal. Although a longer followup is required for assessment of the durability of response, the patient's course indicates that ASCT may be a way to reinduce tolerance in patients with SLE.
Adolescent↗
[Pathophysiology and therapy of sepsis-associated coagulation disorders].
Sepsis and septic shock are very complex and dynamic clinical syndromes. A systemic response to an infection or other triggers can induce a cascade consisting of toxins--leukocytes--cytokines--mediators of inflammation--endothelial cell dysfunction--activation of blood coagulation--intravascular fibrin deposition--alteration of microcirculation, resulting in a damage of organs. Multi organ failure and sepsis are therefore tightly connected. The associated disturbances of blood coagulation range between a simple activation of coagulation with a transient increase of activation markers (i.e. D-dimer), similar to an acute-phase reaction and full blown disseminated intravascular coagulation with consumption coagulopathy. This article summarizes these pathophysiological mechanisms, shows available diagnostic tools and differential diagnoses, and discusses therapeutic options for sepsis and multi organ failure.
Animals↗
The LDH ratio as a marker for response to plasma exchange in HUS/TTP of the adult.
BACKGROUND: Plasma exchange improved the outcome of thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) of the adult markedly, but a high number of non-responders remain. Identifying these patients at an early stage would help to optimize therapy. AIM: determine the value of serologic measures in predicting the response to plasma exchange. MATERIAL AND METHODS: We performed a retrospective chart review of 30 patients with HUS/TTP of the adult treated with plasma exchange. According to the treatment protocol, a mean of 42 +/- 8.2 ml plasma per kilogram of body weight was exchanged daily for 3 days and continued every second day thereafter. Prior to each session, clinical status and serologic markers for hemolysis and kidney function were obtained. To assess the early individual response to plasma exchange, the decline of LDH from the first to the third cycle was calculated as: LDH concentration before the third session/LDH concentration before the first session (LDH ratio). RESULTS: During the observation period (median 195, range 6-1500 days), 80% of the patients responded to therapy with plasmapheresis. None of the serologic measures or clinical signs obtained before initiation of plasma exchange showed a significant correlation with the outcome. After 2 sessions of plasma exchange, only LDH and platelet level had improved markedly in responding patients. The LDH ratio was the best predictive marker for the individual response. An LDH ratio < 0.6 predicted a favorable outcome with a sensitivity of 0.96 and a specificity of 0.83. CONCLUSION: The LDH ratio might be a useful marker for separating patients responding to plasma exchange from those not responding at an early stage.
Adult↗
Impact of the factor II: G20210A variant on the risk of venous thromboembolism in relatives from families with the factor V: R506Q mutation.
OBJECTIVES: Factor V: R506Q mutation and the prothrombin G20210A variant (factor II: G20210A variant) are associated with an increased risk of venous thromboembolism (VTE). In cohorts of unrelated patients a cosegregation of both mutations has been shown to be associated with an increased risk of developing VTE. The aim of this study was to investigate the impact of the coinheritance of both mutations on the risk of VTE in relatives of symptomatic carriers of the factor V: R506Q mutation and the factor II: G20210A variant. PATIENTS AND METHODS: Four families with 48 family members were investigated for the presence of the factor V: R506Q mutation and the factor II: G20210A mutation, and their clinical history was evaluated. RESULTS: VTE was more frequent in family members with a combined defect (3/10; 30%) compared to those with a single mutation (1/16; 6%) or without a defect (1/12; 8%). The probability for VTE for 40-yr-old individuals with both mutations, a single mutation and no mutation was 56%, 12% and 20%, respectively. CONCLUSIONS: These data suggest that the G to A transition at position 20210 of the prothrombin gene leads to an increase in the risk of VTE in carriers of the factor V: R506Q mutation. The determination of the factor II: G20210A variant in index patients carrying a factor V: R506Q mutation and, if present, in family members may help to identify individuals who are at high risk for VTE.
Adolescent↗
Treatment of coagulation inhibitors with extracorporeal immunoadsorption (Ig-Therasorb).
Coagulation inhibitors may occur as alloantibodies in patients with congenital factor deficiencies or as autoantibodies in patients with a previously normal coagulation. We treated 10 patients with factor VIII inhibitors (three haemophiliacs and seven patients with acquired factor VIII inhibitors) and one patient with a factor V inhibitor using extracorporeal immunoadsorption to immobilized antibodies against human immunoglobulins (Ig-Therasorb). The initial inhibitor titre was between 18 BU/ml and 540 BU/ml. Nine patients had signs of bleeding. Eighty-nine immunoadsorption sessions were performed in the 11 patients (8.1 +/- 5.1 per patient), each processing 6980 +/- 880 ml of plasma in 3.8 +/- 0.5 h. The mean reduction of the inhibitor titre was 71.9 +/- 19.4% per session. Serum IgG, IgA and IgM levels decreased by 68.7 +/- 10.1%, 55.7 +/- 12.7% and 48.6 +/- 11.1% respectively. In two haemophiliac patients, an initial titre reduction prior to an immune tolerance protocol was performed. Another haemophiliac patient was treated because of acute cerebral bleeding. In six out of eight patients with acquired inhibitors, a durable elimination was achieved within a median of 18 d. Treatment was safe and well-tolerated and seems to be a promising method in the treatment of patients with coagulation inhibitors, especially when a fast inhibitor titre reduction is necessary.
Adult↗
Platelet-reactive HLA antibodies associated with low posttransfusion platelet increments:a comparison between the monoclonal antibody-specific immobilization of platelet antigens assay and the lymphocytotoxicity test.
BACKGROUND: Platelet-reactive HLA antibodies are a major reason for low posttransfusion platelet increments. The clinical importance and value of the test systems for their in vitro determination is still controversial. STUDY DESIGN AND METHODS: A prospective analysis of HLA antibodies was performed in sera obtained once a week for at least 4 consecutive weeks from 55 patients (female/male, 28/27; age: median, 49 years; range, 18-69) undergoing intensive chemotherapy and in need of prophylactic platelet transfusions. All sera (n = 330) were analyzed by the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay and by the standard lymphocytotoxicity test (LCT). RESULTS: In the MAIPA, 24.5 percent of sera (81/330) obtained from 22 patients contained HLA antibodies. These were detected significantly more often by the MAIPA assay than by the LCT (24.5% vs. 8.2%). Fifty-five sera (20 patients) were positive in the MAIPA assay only. In 15 patients, HLA antibodies were transient. In 3 patients, HLA antibodies were detected earlier by the MAIPA assay than by the LCT. Significantly more sera obtained at the time of low posttransfusion platelet increments were positive in MAIPA alone, rather than in both MAIPA and the LCT (44% vs. 17%). CONCLUSION: The MAIPA assay is more sensitive than the standard LCT in detecting platelet-reactive HLA antibodies. These MAIPA-positive/LCT-negative HLA antibodies affect the posttransfusion platelet increment.
Adolescent↗
Efficacy of standard treatment in patients with Hodgkin's disease--a single center experience.
Sixty-two consecutive patients with newly diagnosed Hodgkin's Disease (HD) were treated at our institution between 1991 and 1998 in accordance with protocols which we considered as optimal standard therapy. In patients with localised disease, extended field irradiation alone was used initially but short duration chemotherapy followed by involved field irradiation was given later. Initially, MOPP/ABV chemotherapy was considered the standard treatment regimen for advanced HD, subsequently it was replaced by ABVD treatment. At 5 years patients with localised HD have a projected overall survival of 95% and a failure-free survival of 72%. Relapses in patients treated with radiotherapy alone (6/16 cases) could be successfully managed with chemotherapy in most cases (5/6). In advanced HD, projected 5-year survival and failure-free survival are 100% and 80%, respectively. No treatment-related deaths or secondary malignancies were registered.
Adolescent↗
The "typical" immunophenotype of acute promyelocytic leukemia (APL-M3): does it prove true for the M3-variant?
The immunophenotypes of 12 acute promyelocytic leukemias (APL-M3; eight hypergranular, four microgranular) with documented PML-RAR-alpha fusion gene are presented. Bone marrow mononuclear cells were immunophenotyped using a panel of 20 monoclonal antibodies. The hypergranular APLs exhibited a mature myeloid phenotype as it has been described to be typical for M3. No lineage infidelity was detectable in classic M3 cases. In contrast, among the four cases of M3 variant, all leukemias showed marked expression of CD34 and two of four cases expressed the HLA-DR antigen. The CD2 antigen was expressed in three of four cases. Furthermore, one case showed expression of the CD56 antigen, and one case was positive for the blood group H antigen. The data suggest that microgranular APL is a heterogeneous entity with regard to the immunologic phenotype.
Adult↗
Fludarabine therapy in Waldenström's macroglobulinemia.
Seven patients with macroglobulinemia (six previously untreated, one with minimal pretreatment) were treated with fludarabine (25 mg/m2/day for 5 days, repeated every 4 weeks). The median age was 58 years. The time from diagnosis to treatment with fludarabine was 4.5 months to 175 months (median 32.6 months). The patients received six (n =5), five (n =1), and three (n = 1) courses of fludarabine. One patient showed only a slight decrease of immunoglobulin (Ig) M (from 5,750 mg/dl to 4,700 mg/dl) and no improvement of anemia. Therefore, treatment was stopped after three cycles. In the other six patients, a marked reduction of IgM levels (from 6,140 mg/dl to 1,220 mg/dl median), a normalization of hemoglobin (from 10.8 g/dl to 12.3 g/dl median), a reduction of lymphocyte count (from 1992/>microl to 652/microl median), and a reduction of beta2 microglobulin (from 2.3mg/l to 1.8 mg/l median) were achieved. A 50% IgM reduction was achieved 5.4 months (median) after the beginning of therapy, and the maximum response was observed 17.3 months (median) after the end of treatment. The responses were sustained without further therapy in six patients for 20.8-55.2 months. In one patient, disease progression was observed 12.5 months after the end of therapy. Fludarabine therapy was well tolerated with few side effects. In three patients, febrile episodes occurred. No opportunistic infections were recorded. We conclude that fludarabine is an effective treatment in previously untreated or in minimally pretreated patients with Waldenström's macroglobulinemia.
Adult↗
Excellent disease eradication by myeloablative therapy and stem-cell transplantation in patients with acute myelogenous leukemia.
Between February 1982 and 1999, 118 consecutive patients (65 male, 53 female) with acute myelogenous leukemia (AML), with a median age of 35 years (range 17-56 years), received stem-cell grafts from a human leukocyte antigen-identical sibling (n = 71), one-antigen-mismatched family member (n=2), matched unrelated donor (n=15), one-antigen-mismatched unrelated donor (n = 4) or an autologous (n = 26) graft. At the time of transplant, 56 patients were in the first complete remission (CR), 27 in the second CR, 6 in untreated relapse, 17 in primary refractory, and 12 in refractory relapse. The French-American-British classification (FAB) subtypes were as follows: M1 (n=25), M2 (n=28), M3 (n=11), M4 (n =32), M5 (n=16), M6 (n = 6). For conditioning, most patients underwent total body irradiation-containing regimens. As of 28 February, 1999, probability of leukemia-free survival (LFS) is 58% for patients after related and 45% after unrelated stem-cell transplantation (SCT). The probability of LFS is 70% for patients given allogeneic transplants in the first CR compared with 33% for those beyond the first CR at SCT. In autologous stem-cell graft recipients, the probability of LFS is 37%. Transplant-related mortality was 28% after related, 20% after unrelated, and 4% after autologous SCT. Probability of relapse for patients given related-donor stem-cell grafts in the first CR and beyond the first CR is 30% and 67%, 55% after unrelated and 63% after autologous stem-cell grafting. Thus, myeloablative therapy followed by allogeneic stem-cell infusion has a high curative potential for patients with AML in remission and offers substantial benefits to patients in advanced disease.
Adolescent↗