Cryoglobulins are serum immunoglobulins that precipitate at temperatures below 378C and re-dissolve on warming. Cryoglobulinaemia leads to variable symptoms including characteristic purpura, ischaemia of extremities, renal failure, peripheral neuropathy, abdominal pain secondary to intestinal ischaemia and arthralgias. Cryoglobulin testing is underutilized in clinical practice. It has been neglected in clinical laboratories and by clinicians due to several factors, such as the length of time it takes for serum cryoglobulin analysis to be performed in the laboratory, the perceived difficulty in getting optimal sampling conditions and a failure to appreciate that even apparently low levels of cryoglobulin can be associated with severe symptoms in some patients. The most important variable confounding standardization of cryoglobulin testing is improper sample handling. A recent report critically appraising the current practice of cryoglobulin evaluation in 137 laboratories in Europe by United Kingdom National External Quality Assurance Scheme (UKNEQAS) illustrated the wide variability in practice. Although many clinical laboratories perform cryoglobulin evaluation, there are widespread differences in the methodology used and the care with which this is carried out and this leads to considerable intralaboratory and interlaboratory variability. The most common sources of error are false-negative results due to loss of cryoprecipitate during transport and storage. Better standardization is needed to avoid missed diagnoses and improve the comparability of results. Laboratories should ensure that sample temperature is maintained at 378C until the serum is separated. In this article, we briefly review the classification and clinical features of cryoglobulins and suggest best practice guidelines for laboratory detection and identification of cryoglobulins.
To assess current practice in the detection, analysis, and reporting of cryoglobulins, a questionnaire was sent to 140 laboratories. Only 36% of laboratories used standard procedures (tube preheating, transport in container, and sedimentation and/or centrifugation at 37°C) to ensure that the temperature did not drop below 37°C until after serum separation. Time periods allowed for cryoprecipitation at 4°C varied from 12 h to 9 days, with 30% of laboratories allowing precipitation for Ͻ3 days. After cryoprecipitation, 81% of laboratories resolubilized the cryoprecipitate at 37°C, and 77% further immunotyped the cryoprecipitate. After analysis, 5% referred the sample for confirmation, 58% provided a nonquantitative report, and 37% reported the cryoglobulin concentration in the cryoprecipitate as cryocrit, total protein concentration, and/or immunoglobulin concentration. Only 3 laboratories (2%) provided cryoprecipitate-specific reference values for total protein content, and none provided reference values for immunoglobulins. We believe standardization is needed for cryoglobulin detection to avoid missed diagnoses and improve the comparability of results. Laboratories should ensure that sample temperature does not drop below 37°C until after serum separation. The serum should cryoprecipitate at 4°C for at least 3 (preferably 7) days. The cryoprecipitate should be washed and resolubilized at 37°C for further analysis.
Critical illness requiring support in an intensive care unit (ICU) is common after blood and marrow transplantation, occurring in > 20% in some series. Attempts have been made to identify patients at highest risk of respiratory, cardiac, hepatic, and renal failure before transplantation. Whereas demographic features, such as age and presence of active malignancy, are strongly associated with complications after transplant, only a few specific laboratory studies are useful in identifying high-risk individuals. Pulmonary function testing is associated with fatal pulmonary complications, and hepatic function tests are associated with fatal veno-occlusive disease of the liver. Knowledge of the predictive value of specific risk factors is important to the evaluation of patients considered for transplant.Critical illness requiring mechanical ventilation, invasive hemodynamic monitoring, vasopressors, dialysis, and aggressive supportive care is common following bone marrow transplantation (BMT). In four series of BMT patients, 23% required mechanical ventilation, 1 24% developed acute renal failure requiring hemodialysis, 2 15% developed severe hepatic venoocclusive disease, 3 and 43% developed cardiac complications, 4 with mortality rates of 96%, 84%, 98%, and 9%, respectively. The care of BMT patients presents numerous challenges to pulmonary/critical care medicine physicians.
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