Distribution of indications and procedures within the framework of centers participating in the WAA apheresis registry.

The WAA apheresis registry was established in 2003 and an increasing number of centers have since then included their experience and data of their procedures. The registry now contains data of more than 74,000 apheresis procedures in more than 10,000 patients. This report shows that the indications for apheresis procedures are changing towards more oncological diagnoses and stem cell collections from patients and donors and less therapeutic apheresis procedures. In centers that continue to register, the total extent of apheresis procedures and patients treated have expanded during the latest years.

Adverse events in apheresis: An update of the WAA registry data.

Apheresis with different procedures and devices are used for a variety of indications that may have different adverse events (AEs). The aim of this study was to clarify the extent and possible reasons of various side effects based on data from a multinational registry. The WAA-apheresis registry data focus on adverse events in a total of 50846 procedures in 7142 patients (42% women). AEs were graded as mild, moderate (need for medication), severe (interruption due to the AE) or death (due to AE). More AEs occurred during the first procedures versus subsequent (8.4 and 5.5%, respectively). AEs were mild in 2.4% (due to access 54%, device 7%, hypotension 15%, tingling 8%), moderate in 3% (tingling 58%, urticaria 15%, hypotension 10%, nausea 3%), and severe in 0.4% of procedures (syncope/hypotension 32%, urticaria 17%, chills/fever 8%, arrhythmia/asystole 4.5%, nausea/vomiting 4%). Hypotension was most common if albumin was used as the replacement fluid, and urticaria when plasma was used. Arrhythmia occurred to similar extents when using plasma or albumin as replacement. In 64% of procedures with bronchospasm, plasma was part of the replacement fluid used. Severe AEs are rare. Although most reactions are mild and moderate, several side effects may be critical for the patient. We present side effects in relation to the procedures and suggest that safety is increased by regular vital sign measurements, cardiac monitoring and by having emergency equipment nearby.

Analyses of data of patients with Thrombotic Microangiopathy in the WAA registry.

UNLABELLED: Thrombotic Microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. The aim of this study was to investigate the outcome and prognostic variables of TMA-patients. MATERIALS AND METHODS: Data were consecutively retrieved from the WAA-apheresis registry (www.waa-registry.org) during 2003-2009. Included were all 120 patients (1237 procedures) who suffered from various forms of TMA, as registered by the ICD-10 code M31.1. Besides registry data, more extensive information was retrieved from the latest 64 patients. Adverse events of the TMA patients were compared to those of the other patients in the registry. RESULTS: The mean age was 46 years (range 11-85 years, 57% women). In 72% therapeutic apheresis was due to an acute indication while a long-term indication was present in 28%. Plasma exchange was performed by centrifugation and filtration technique (95% and 4%, respectively), and immunoadsorption in 1% of the patients. Only fresh frozen plasma was used as replacement fluid in 69% of procedures. Adverse events were more frequent than in the general apheresis population (10% versus 5%, RR 1.9, CI 1.6-2.3). No death occurred due to apheresis treatment. Three percent of the procedures were interrupted. Bronchospasm and/or anaphylactic shock were present in two patients and one patient suffered from TRALI. At admission 26% were bedridden and needed to be fed. The risk of dying during the treatment period was significantly higher if the patient also suffered from a compromising disease, such as cancer. There was an inverse correlation between the ADAMTS13 level and the antibody titer (r=-0.47, p=0.034). CONCLUSIONS: Patients with TMA have an increased risk for moderate and severe AE compared to the general apheresis population. Many patients were severely ill at admission. The prognosis is worse if the patient also has a severe chronic disease. Even slightly increased ADAMTS13-antibody titers seem to have a negative impact on the ADAMTS13 levels.

Thrombotic microangiopathy.

Thrombotic microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). There are many secondary causes of TMA, many of them could mimic TTP or HUS. This article presents a short overview on TMA. In conclusion TMA is the result of various etiology reasons and pathologic reactions with various clinical entities. It is important to focus on a thorough history including family history when deciding on a diagnosis. Analysis of ADAMTS 13 and ADAMTS 13-antibodies may help to decide continued therapy.

World apheresis registry 2003-2007 data.

OBJECTIVES: Seventy-five centers from many countries have applied for a login code to the WAA apheresis registry. Fifteen centers from 7 countries have been actively entering data at the internet site from 2003 until 2007. We report on data from the registry so far. METHODS: This is a web-based registry. A link is available from the WAA homepage (www.worldapheresis.org). So far data from 2013 patients (12,448 procedures) have been included. A median of 6 treatments have been performed (range 1-140). Mean age 51 years (range 1-94 years; 45% women). Seven percent of the patients were < or = 21 years and 4% were < or = 16 years. RESULTS: The purpose of the apheresis procedure was therapeutic in 67% and retrieval of blood components in 33%. Main indications: neurological and hematological diseases, lipid apheresis and stemcell collection (autologous, and some allogeneic). Blood access: peripheral vessels (71%), central dialysis catheter through jugular (6.5%) or subclavian veins (6.7%), femoral vein (8%) and AV fistula (4%). ACD was used for anticoagulation in 73% of the procedures. Albumin was mainly used as replacement fluid. Adverse events (AE) were registered in 5.7% of the procedures. AE was graded as mild (2.5%), moderate (2.7%) or severe (0.5%). No death occurred due to treatment. The procedures were interrupted in 2.6%. Most frequent AEs were blood access problems (29%), tingling around the mouth (20%), hypotension (18%), and urticaria (9%). There were significant differences between the centers regarding mild and moderate AEs. Data indicate that centers using continuous infusion of calcium had fewer AEs. CONCLUSION: There was a limited number of severe AEs. Centers use various standard procedures for apheresis. By learning from the experience of others the treatment quality will improve further. In the near future, an update of the registry will enable more extensive evaluation of the data.

[Hereditary form of thrombotic thrombocytopenic purpura]. / Vrozená forma trombotickté trombocytopenické purpury.

BACKGROUND: Thrombotic thrombocytopenic purpura is characterized by microvascular platelet clumping resulting in thrombocytopenia, microangiopathic hemolysis, neurological abnormality, and renal dysfunction. Similar manifestations also occur in patients with the hemolytic uremic syndrome or other types of disorders. Recent studies demonstrate that severe deficiency of the von Willebrand factor cleaving metalloprotease, ADAMTS 13, causes thrombotic thrombocytopenic purpura. Aim of our study was to characterize gene defects causing inherited type of disease. METHODS AND RESULTS: We investigated nine patients with recurrent type of disease with familiar origin and twelve relatives. Samples were taken in a remission of disease. We measured activity of ADAMTS13 (vWF-CP) with modified method of the quantitative immunoblotting of degraded vWF multimers. Mutation screening was carried out by sequencing all 29 exons and flanking intron regions of the ADAMTS13 gene. Five distinct mutations were found. Three of them are novel. CONCLUSIONS: Mutation analysis of the ADAMTS 13 gene brought interesting results in eight patients. We found a one single base frameshift insertion, 4143insA in 8 of 9 unrelated individuals. This investigation represents an advantage in the differential diagnosis of disease since the thrombotic thrombocytopenic purpura phenotype in childhood can be variable and rapid detection of mutation is helpful for the recurrence prevention.

Immunoadsorption therapy and complement activation.

Complement activation was studied in six patients treated with immunoadsorption columns Ig-ADSOPAK for myasthenia gravis. Mean therapy duration was 18.6 months (range 4-28 months). Prior and after each procedure, concentrations of C3 and C4 were examined, hemolytic activity of complement by a classic pathway (CH50) was determined, as well as terminal complement complex (TCC). After each immunoadsorption procedure, a decrease of C3 and C4 was noted (median 21.19% and 19.68%, respectively). The CH50 and TCC follow-up showed statistically significant complement activation. Median of TCC accrual was 60.21% and median of CH50 decrease was 23.24%. No clinical manifestations of complement activation were present. With increasing number of procedures a marked decrease of TCC activation was observed in five patients, which was statistically significant in three of them (p < 0.05). This finding may indicate an immunomodulating effect of long-term adsorption therapy. With increasing number of procedures, an inhibition in complement system reactivity occurs. This result, however, has to be confirmed on a larger group of patients.

Mycobacterium avium complex infection in AIDS: clinical features, treatment, and prevention.

Infection with Mycobacterium avium complex (MAC) may cause a serious disseminated bacterial infection in up to 40% of patients with advanced HIV infection. Disseminated MAC has a negative impact on quality of life and contributes significantly to morbidity and mortality. Prompt diagnosis and aggressive treatment can diminish those effects. Disseminated disease can be prevented in many patients with the use of rifabutin prophylaxis. Nurses play an important role in evaluating symptoms and educating patients about the prevention and treatment of disseminated MAC.

[Personal experience with therapeutic plasmapheresis using the AS.TEC 204 separator]. / Nase zkusenosti s lécebnými plazmaferézami na separátoru AS.TEC 204.

The authors experience with Fresenius AS.TEC 204 separator for therapeutic exchange plasmaphereses in patients with different diagnoses. The describe the technique of separation, evaluation of advantages of the apparatus. Minor modifications made by the author improve the process of separation. Although the apparatus does not make erythrophereses possible so far, it proved useful for exchange plasmaphereses.

[Thrombotic thrombocytopenic purpura--still a therapeutic problem. Case report of a patient on long-term therapy]. / Trombotická trombocytopenická purpura--stálý lécebný problém. Popis prípadu dlouhodobe léceného nemocného.

Thrombotic thromboctopenic purpura is a rare multisystemic life threatening disease the treatment of which is still a serious problem. The most successful therapy is plasmapheresis where the whole plasma volume of the patient is replaced by fresh frozen plasma or cryosupernatant. The authors describe a 34-year-old patient with the chronic relapsing form of the disease and repeated cerebrovascular attacks with an ischaemic genesis with developed organic psychosyndrome. The only effective treatment of the patient are exchange plasmaphereses replacing plasma by cryosupernatant after the patient became refractory to fresh frozen plasma. The authors describe the clinical development of the disease, its treatment by plasmaphereses and mention various ways of a venous approach and associated problems. Ensuring a venous approach in patients with this disease is of vital importance and in the terminal stage of the disease it is extremely difficult. A solution, though temporary, is implantation of a vascular prosthesis, Diastat. The functioning of the implant in this disease is however greatly threatened by the development of thrombotic occlusions.

[Plasma pH and anticoagulant solutions used in the plasmapheresis method of blood collection from donors]. / Závislost pH plazmy na pouzitém protisrázlivém roztoku pri odberu dárcovské krve technikou plazmaferézy.

The resulting pH of fresh frozen plasma for clinical use, collected by plasmapheresis from blood donors is influenced by the type of anticoagulant solution and its ratio with the donor's blood. The authors describe the use of three anticoagulant solutions with a different sodium citrate concentration and different ratios of donor blood. As compared with the physiological range of pH of the blood, the resulting pH value of the collected plasma, when using ACD-A and AB-16 solutions, varies within the range classified as acidosis, i.e. less than 7.36. When using a 4% sodium citrate solution the plasma pH value is in the area evaluated as alkalosis. The authors discuss indications for administration of fresh frozen plasma in clinically serious diseases and the influence of administration of this transfusion preparation on the acid-base balance as the transfusion recipients are threatened by the development of metabolic acidosis. Maintaining the pH value of fresh frozen plasma slightly above the physiological range of blood pH prevents in particular during massive plasma transfusions the possibility of deterioration of acidosis or its development.

Complications of primary palatoplasty: a twenty-one-year review.

The complications of 196 patients who underwent primary palatoplasties at North Carolina Memorial Hospital between 1963 and 1983 were reviewed. The von Langenbeck technique was utilized in 50 percent of the patients, the Wardill-Kilner technique in 45 percent, and the Dorrance technique in 5 percent. Intravelar veloplasties were performed in 34 percent of the patients. The incidence of postoperative complications was: deaths, 0 percent; malignant hyperthermia, 0 percent; aborted procedures, 0.5 percent; feeding difficulties, 0.5 percent; aspiration, 0.5 percent; reexploration for bleeding, 0.5 percent; pneumonia, 1 percent; upper respiratory tract infections, 2 percent; postoperative airway difficulties, 3 percent; oropharyngeal infections, 4 percent; and otitis media, 10 percent. Later evaluations demonstrated problems with otitis media in 17 percent of the patients and fistulas in 6 percent. An additional palatal operation of some type was later required in 22 percent of the patients, with 18 percent of the patients requiring a pharyngeal flap. Intravelar veloplasties were associated with a decreased incidence of secondary pharyngeal flaps but also an increased transfusion requirement. The Wardill-Kilner technique was associated with a higher incidence of postoperative fistulas, and the use of perioperative antibiotics was associated with fewer postoperative fistulas.

Evans' syndrome in a child with diabetes mellitus.

A patient suffering from infantile-onset insulin-dependent diabetes mellitus is reported in whom immune pancytopenia (Evans' syndrome) developed at the age of 2 1/2 years. Hepatosplenomegaly, chronic lymphadenopathy, and elevated levels of immunoglobulins G and M were also present. The course of Evans' syndrome was fatal in this patient. The association of Evans' syndrome with other immune disorders is discussed.

Characterization of protein kinase A and protein kinase C phosphorylation of the N-methyl-D-aspartate receptor NR1 subunit using phosphorylation site-specific antibodies.

Modulation of N-methyl-D-aspartate receptors in the brain by protein phosphorylation may play a central role in the regulation of synaptic plasticity. To examine the phosphorylation of the NR1 subunit of N-methyl-D-aspartate receptors in situ, we have generated several polyclonal antibodies that recognize the NR1 subunit only when specific serine residues are phosphorylated. Using these antibodies, we demonstrate that protein kinase C (PKC) phosphorylates serine residues 890 and 896 and cAMP-dependent protein kinase (PKA) phosphorylates serine residue 897 of the NR1 subunit. Activation of PKC and PKA together lead to the simultaneous phosphorylation of neighboring serine residues 896 and 897. Phosphorylation of serine 890 by PKC results in the dispersion of surface-associated clusters of the NR1 subunit expressed in fibroblasts, while phosphorylation of serine 896 and 897 has no effect on the subcellular distribution of NR1. The PKC-induced redistribution of the NR1 subunit in cells occurs within minutes of serine 890 phosphorylation and reverses upon dephosphorylation. These results demonstrate that PKA and PKC phosphorylate distinct residues within a small region of the NR1 subunit and differentially affect the subcellular distribution of the NR1 subunit.