Management of Acute Episodes of Clarkson Disease (Monoclonal Gammopathy-Associated Systemic Capillary Leak Syndrome) With Intravenous Immunoglobulins.

Monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome (ISCLS, Clarkson disease) is a rare disorder defined by transient but recurrent bouts of hypotensive shock and anasarca resulting from plasma extravasation. Although prophylactic treatment with high-dose intravenous immunoglobulins (IVIG, 1-2 g/kg/mo) prevents most disease flares, its utility for acute episodes of ISCLS is unclear. Here, we report the results of a retrospective study of subjects with acute ISCLS treated at or near the onset of symptoms with IVIG. We found that administration of IVIG with minimal additional intravenous fluids was safe and associated with rapid clinical improvement. IVIG given close to the onset of ISCLS-related symptoms is associated with a favorable outcome.

Markers of endothelial glycocalyx dysfunction in Clarkson disease.

BACKGROUND: Clarkson disease (monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome, ISCLS) is a rare idiopathic condition marked by transient, relapsing-remitting episodes of systemic microvascular hyper-permeability, which liberates plasma fluid and macromolecules into the peripheral tissues. This pathology manifests clinically as the abrupt onset of hypotensive shock, hemoconcentration, and hypoalbuminemia. METHODS: We analysed endothelial glycocalyx (eGCX)-related markers in plasma from patients with ISCLS during acute disease flares and convalescence by ELISA and comprehensive proteomic profiling. We evaluated eGCX-related components and gene expression in cultured endothelial cells using RNA-sequencing, real-time PCR, and fluorescence staining. RESULTS: Serum levels of eGCX-related core components including hyaluronic acid (HA) and the core proteoglycan soluble syndecan-1 (sCD138) were elevated at baseline and during acute ISCLS flares. Serial measurements demonstrated that sCD138 levels peaked during the recovery (post-leak) phase of the illness. Proteomic analysis of matched acute and convalescent ISCLS plasma revealed increased abundance of eGCX-related proteins, including glypicans, thrombospondin-1 (TSP-1), and eGCX-degrading enzymes in acute compared to remission plasma. Abundance of endothelial cell damage markers did not differ in acute and baseline plasma. Expression of several eGCX-related genes and surface carbohydrate content in endothelial cells from patients with ISCLS did not differ significantly from that observed in healthy control cells. CONCLUSIONS: eGCX dysfunction, but not endothelial injury, may contribute to clinical symptoms of acute ISCLS. Serum levels of of eGCX components including sCD138 may be measured during acute episodes of ISCLS to monitor clinical status and therapeutic responses.

Intravenous Immunoglobulins Tapering and Withdrawal in Systemic Capillary Leak Syndrome (Clarkson Disease).

BACKGROUND: The systemic capillary leak syndrome (SCLS), also known as Clarkson disease, is a very rare condition characterized by recurrent life-threatening episodes of vascular hyperpermeability in the presence of a monoclonal gammopathy. Extended intravenous immunoglobulin (IVIG) treatment is associated with fewer recurrences and improved survival, but the optimal treatment dosage and duration remain unknown. OBJECTIVE: We aim to evaluate the safety of IVIG tapering and withdrawal in patients with SCLS. METHODS: We conducted a retrospective multicenter study including all adult patients with monoclonal gammopathy-associated SCLS from the EurêClark registry who received at least 1 course of IVIG. The primary end point was overall survival according to IVIG withdrawal. RESULTS: Fifty-nine patients of mean ± SD age 51 ± 13 years were included. Overall cumulative probabilities of 2-, 5-, 10- and 15-year survival were 100%, 85%, 72%, 44%, respectively. The IVIG was withdrawn at least once in 18 patients (31%; W+ group) and never in 41 patients (69%; W- group). Cumulative probabilities of 10-year survival in W+ versus W- groups were 50% and 83% (log rank test, P = .02), respectively. Relapse rate and the median number of relapses in the W+ versus the W- groups were 72% versus 58% (P = 0.3) and 2.5 (0.3-4) versus 1 (0-2) (P = .03), respectively. The IVIG tapering was not statistically associated with increased person-year incidence of attacks using a mixed linear model. CONCLUSIONS: The IVIG withdrawal was associated with increased mortality and higher rate of recurrence in SCLS patients. The IVIG tapering might be cautiously considered in stable SCLS patients.

Electronic remote blood issue combined with a computer-controlled, automated refrigerator for major surgery in operating theatres at a distance from the transfusion service.

BACKGROUND: The difficulty of supplying red blood cells within an adequate time to patients undergoing surgery is a known problem for transfusion services, particularly if the operating theater is located at some distance from the blood bank. The consequences frequently are that more blood is ordered than required; several units are allocated and issued; and unused units must be returned to the blood bank. Some sparse reports have demonstrated that remote blood issue systems can improve the efficiency of issuing blood. STUDY DESIGN AND METHODS: This study describes a computer-controlled, self-service, remote blood-release system, combined with an automated refrigerator, installed in a hospital at which major surgery was performed, located 5 kilometers away from the transfusion service. With this system, red blood cell units were electronically allocated to patients immediately before release, when the units actually were needed. Two 2-year periods, before and after implementation of the system, were compared. RESULTS: After implementation of the system, the ratio of red blood cell units returned to the transfusion service was reduced from 48.9% to 1.6% of the issued units (8852 of 18,090 vs. 182 of 11,152 units; p < 0.0001), and the issue-to-transfusion ratio was reduced from 1.96 to 1.02. An increase in the number of transfused red blood cell units was observed, probably mainly due to changes in the number and complexity of surgical procedures. No transfusion errors occurred in the two periods. CONCLUSION: The current results demonstrate that the remote blood-release system is safe and useful for improving the efficiency of blood issue for patients in remote operating theatres.

The use of telemedicine in Italian Blood Banks: a nationwide survey.

BACKGROUND: Telemedicine is defined as the use of electronic information and communication technologies to provide health care between distant people. Many activities in transfusion medicine could benefit from the application of telemedicine. To map the spread of the use of telemedicine in transfusion medicine in Italy, the Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) performed a nationwide survey: the results are presented in this paper. MATERIALS AND METHODS: A survey, dealing with different aspects of the use of telemedicine, was performed by sending a questionnaire to 280 Italian Blood Centres. The survey was designed to evaluate the diffusion of telemedicine and the features of the systems, with special attention to the systems' safety and legal adequacy. One section of the questionnaire was designed to identify the features of the systems considered essential by the respondents. RESULTS: Out of 280 Blood Services contacted, 196 (70%) filled in at least one of the questions of the online questionnaire. Globally the use of some form of telemedicine was reported by 70% of the respondents. Telemedicine is used for remote validation of laboratory tests by 32% of the Centres that responded, for remote biological validation of blood units by 34% and for assignment of blood components by 29%. Less frequently, telemedicine is used to control electronic refrigerators, for electronic blood requests and for bed-side identification of patients. DISCUSSION: The use of telemedicine is widespread in Italian Blood Services. There appears to be some heterogeneity between structures with regards to the evaluation of the systems' safety and their legal adequacy. No telemedicine system should be introduced into practice until it has proven to have the same standards of safety as the corresponding "on site" activity.

An estimate of future transfusion needs in the province of Ravenna made on the basis of Italian national statistics and past consumption.

BACKGROUND: After years of surpluses in numerous blood components in the province of Ravenna, there is now evidence that the increased use of such products is leading to an ever less abundant self-sufficiency. The concern about the possible loss of self-sufficiency, in a province in which the population of donors does not seem to be adequate to compensate for transfusion domands, led us to verify consumption and future prospects in greater detail. MATERIALS AND METHODS: In order to plan future transfusion needs, past consumption was analysed dividing the population into several age groups. This historical use of blood products was projected into the scenario of the population in years to come to estimate needs and their increases over time. RESULTS: The use of transfusion products is very different in different age groups, increasing notably with age. Age factor was identified as the most important factor determining blood product consumption. DISCUSSION: It will, therefore, be the aging of the population that causes an increase in blood product requirements. Projections from the Italian Institute of Statistics considering age groups of the population up to 2051 enable predictions of transfusion needs, in the absence of drastic interventions on the appropriateness of transfusion practices. Considering that the public and private hospitals of Ravenna predominantly admit subjects from its own territory, these predictions appear realistic, provided that new reasons for consumption are not introduced.

Blood transfusion practice: a nationwide survey in Italy.

BACKGROUND: Blood transfusion is a complex activity. Some of the components of this activity are implementation of standard procedures, evaluation of appropriateness of the blood use, methods for bedside identification of patients and the release of blood in emergencies, during out-of-routine hours and from hospitals lacking a Blood Centre. An overview about how these issues are managed in Italy could be of interest. MATERIALS AND METHODS: A survey dealing with some issues regarding blood release was performed, using a questionnaire sent to 278 Italian Blood Centres. RESULTS: Out of the 278 Centres, 179 (64%) returned the questionnaire. The geographic distribution of the Centres that responded (80 in the north, 46 in the centre and 53 in the south of Italy) offers a good picture of the Italian reality. Globally there seems to be a relatively uniform application of procedures and guidelines, of methods to identify patients, and of evaluating transfusion appropriateness. The systems used to deal with emergency blood release and blood release in non-routine conditions are more variable. The use of technological resources seems to be disappointingly low. DISCUSSION: Although many aspects of the blood transfusion process should be improved, the picture that emerged from the survey seems to show, on the whole, a fair quality of blood transfusion practice in Italian Blood Centres.

Red cell transfusion in orthopaedic surgery: a benchmark study performed combining data from different data sources.

BACKGROUND: Previous studies have shown the usefulness of combining information from different data sources to identify and analyse variations in transfusion practices. Good knowledge of the conditions leading to blood use is a fundamental requirement for the assessment of the appropriateness of blood transfusion. MATERIALS AND METHODS: In this study we combined blood transfusion data obtained from the Blood Bank information system with patients' data from the Hospital Discharge Database, based on the ICD9 classification system, from 1,827 surgical procedures performed in seven different orthopaedic divisions in the Ravenna area between January and December 2009. Hip and knee replacement surgery (primary or revision) and operations following femoral fractures (partial hip replacement and reduction with internal fixation) were considered. For a subgroup of patients clinical and transfusion data were also combined with haemoglobin values obtained from the laboratory information system. RESULTS: Of the 1,827 surgical procedures, 1,038 (56.8%) were followed by transfusion of red cells. The likelihood of receiving a transfusion varied depending on the patient's sex (49% for males, 60% for females), age, and on the surgical procedure, being higher for interventions following femoral fractures and for revisions of hip replacement: about 70% of patients undergoing these interventions required transfusion. A large variability in transfusion rates was observed between the seven divisions, which was only partially explained by the different types of surgery (post-traumatic or elective) performed by any of them: relevant variations were also observed for the same type of intervention. DISCUSSION: Combining information from different data sources could be a time-sparing way to gain useful information about transfusion practices, so contributing to optimising blood usage.