Although patient and laboratory characteristics associated with response and relapse were identified, there was significant overlap between patient groups. Thus, our findings offer preliminary evidence and do not yet justify short- or long-term changes in the management of patients with TTP-HUS.

The adhesive strength of fibrin sealants has not been rigorously evaluated to date. The adhesive strength of six different concentrations of cryoprecipitated fibrinogen as well as the commercially available fibrin tissue adhesive Tissucol was tested under controlled conditions utilizing split-thickness skin grafts as the test adherand. This test configuration permitted the modeling of bonding strength for attachment of skin grafts as well as incorporate established engineering test standards for adhesives. An increase in fibrin concentration corresponded with an increase in shear adhesive strength. No significant increases in adhesive strength were attained after 5 min of bonding for all tested concentrations, except for the commercial adhesive, which attained the adhesive strength of an equivalent concentration of cryoprecipitated adhesive after 90 min. The adhesive strength, however, was an order of magnitude less than reported values of the tensile strength of fibrin material for similar concentrations. Therefore, it is important that the surgeon use a sufficiently high fibrinogen concentration for the specific clinical indication. The method of fibrin sealant preparation and/or the compounding adjuncts appear to have an effect on the development of adhesive strength.

No abstract

Thrombotic thrombocytopenic purpura (TTP) and myasthenia gravis (MG) are category I indications for therapeutic plasma exchange (TPE). This study was based on the hypothesis that the development of metabolic alkalosis during TPE is more common in TTP than in MG, based on our previous observations. In order to test it, we compared the levels of bicarbonate and potassium in both groups of patients undergoing plasmapheresis. Fifteen patients with TTP (190 procedures) and ten MG patients seen concurrently were studied. While baseline bicarbonate levels were similar among all patients, the post-procedure bicarbonate levels in TTP patients were mostly elevated with a mean +/- SD of 29.4 +/- 3.5 mEq/L, as opposed to decreased or unchanged in MG patients 26.3 +/- 3.1 mEq/L (mean +/- SD) (P = 1.4 x 10(-8)). Furthermore, alkalosis in the TTP group persisted throughout subsequent daily treatments. There was also a significant decrease between pre- and post-TPE potassium levels in TTP patients (P = 3 x 10(-21)) by paired Student's t test. Additionally, samples with levels <3.3 mEq/L were alkalotic 75% of the time. In the MG group, however, potassium was normal in 85% and 83% of the pre- and post-TPE samples, respectively. Consequently, the hypokalemia was significantly more marked in the TTP group (P = 0.0008). These data confirm that plasmapheresis commonly induces metabolic alkalosis in TTP patients, probably due to high citrate in fresh frozen plasma, the frequency of treatments, and perhaps decreased renal clearance due to disease involvement of the kidneys.

While therapeutic plasma exchanges (TPEs) performed with 5% albumin are considered safe, concerns regarding venous access and hypocalcemic toxicity remain. We reviewed the frequency of complications during TPEs performed with 5% albumin supplemented with calcium gluconate and potassium chloride for a 5 year period in our institution. Eighty-four adult patients (46 males and 38 females) underwent 581 plasma exchanges during the study period. The most common indications were myasthenia gravis (37%), acute inflammatory demyelinating polyradiculoneuropathy (31%), and chronic inflammatory demyelinating polyneuropathy (13%). All procedures used 2.2% ACD-A delivered at a calculated average rate of 0.26 mg/kg/min, which led to a mean dose of citrate per TPE of 2.18 +/- 0.48 g or 27.8 +/- 5.24 mg/kg of body weight. Venous access difficulties occurred in 85 procedures (14.6%), but most TPEs were completed successfully. Hypotension and citrate toxicity were seen in <5% of the TPEs and were mostly reversible. Only 17 exchanges (3%) had to be aborted because of the loss of venous access (n = 9), hypocalcemic toxicity (n = 3), hypotension (n = 2), panic attacks (n = 2), and one atypical reaction due to the interaction with an angiotensin converting enzyme inhibitor. Comparison between pre- and post-TPE potassium levels showed a statistically significant mean decrease of 7%, from 4.1 mequiv/l to 3.8 mequiv/l (P < 0.0001). We attribute the low rate of hypocalcemia to our practice of adding calcium and potassium to the replacement fluid and suggest that this method could become standard of care.

No abstract

Coupling of an inert polymer to the surface of red cells was examined as a potential means of covering blood group antigens and producing cells that could serve as universal donor cells for transfusion. Effective blockade of red cell antigens was achieved with N-hydroxysuccinimide-activated esters of polyethylene glycol. It was possible to block all antigens tested, but lower concentrations of reactants were required to block peptide-defined antigens than carbohydrate-defined antigens. Red cells remained intact after modification but were significantly damaged. Our results demonstrate the feasibility of antigenic blockade of red cells, but there is a need to reduce damage during coupling reactions to produce viable red cells.

A case is described of a 75-year-old woman with a history of pulmonary tuberculosis and Waldenström's macroglobulinemia who developed an inhibitor of coagulation factor XIII while taking isoniazid. The patient presented with a subcutaneous hematoma of the abdominal wall that extended from the xiphoid process to the symphysis pubis and measured 20 cm in diameter. Results of routine coagulation studies were normal with the exception of an increased solubility of the patient's plasma clot in 5M urea consistent with a deficiency of factor XIII activity. Persistence of the deficiency following a 1:2 dilution of the patient's plasma in normal plasma indicated the presence of an inhibitor. A sample of the patient's plasma was depleted of IgG by streptococcal protein G adsorption. The IgG-depleted plasma did not inhibit factor XIII activity, indicating that the inhibitory activity was not attributable to the underlying IgM paraprotein. The patient's purified IgG, on the other hand, inhibited factor XIII activity and the inhibitory activity could be neutralized by anti-IgG antibody. The patient's IgG also inhibited factor XIII-mediated incorporation of fluorescent monodansylcadaverine into casein. Binding of the patient's IgG to factor XIII concentrate was demonstrated by enzyme-linked immunosorbent assay and the IgG that bound to the factor XIII was demonstrated to be polyclonal. Isoniazid was discontinued after the patient was admitted to the hospital. Cryoprecipitate infusion controlled bleeding and reduced the inhibitor titer by 50%. Treatment with cyclophosphamide and prednisone, followed by extracorporeal immunoadsorption over a staphylococcal protein A column, did not reduce the inhibitor titer further. Plasma exchange therapy reduced the inhibitor titer to undetectable levels but failed to restore factor XIII activity. Infusions of factor XIII concentrate reproducibly restored factor XIII activity and were not associated with an anamnestic rise in the inhibitor titer. This represents the seventh reported case of an acquired inhibitor to factor XIII associated with the ingestion of isoniazid.