Gail Rock

Management of thrombotic thrombocytopenic purpura.

The syndrome Thrombotic thrombocytopenic purpura (TTP) is not a common disorder, but the young age, acute onset, fulminant course and sometimes fatal nature of the disease make it remarkable. Although first described by Dr Eli Moschkowitz in 1924, the pathogenesis of the disorder has only recently begun to be truly understood (Moschkowitz, 1924). Moschkowitz (1924) reported the presentation of a 16year-old girl with fever, anaemia, central nervous system impairment, renal dysfunction and cardiac failure. The patient died after 2 weeks, with the autopsy showing hyaline thrombi in the terminal arterioles of the majority of organs ± a finding considered to be characteristic of the disorder. Over the years, a classical textbook description of a pentad of symptoms for TTP, consisting of microangiopathy, haemolytic anaemia, thrombocytopenia, fluctuating central nervous system abnormalities, fever and renal impairment, has developed. However, it now appears that the classical pentad is infrequently present in the early stages of disease. Only after there is widespread formation of microthrombi and a resultant impact on various organ systems does the full pentad express. In a series of 135 patients that we have recently reported, all patients had schistocytic haemolytic anaemia and thrombocytopenia (Rock et al, 1998). However, only 30 had fever and 86 had neurological abnormalities. Renal impairment was present in 18% of patients. These findings are supported by the literature; a review of published cases by Ridolfi & Bell (1981) reported that 98% of patients had microangiopathic haemolytic anaemia (MHA), 83% thrombocytopenic purpura, 84% neurological symptoms and 76% had renal disease. We have therefore proposed that TTP should be redefined as a syndrome of Coombs negative microangiopathic haemolytic anaemia and thrombocytopenia in the absence of other possible causes of these manifestations. In our experience, TTP occurs, for the most part, in previously healthy, relatively young individuals who suffer the sudden onset of a thrombotic disorder in which platelet microaggregates deposit in the arterial microvasculature. In our largest series of patients, 85 were women and 50 were men, with a mean age of 41 ́7 years (range 18±72) (Rock et al, 1998). Occlusion of small arterioles by platelet plugs containing variable quantities of von Willebrand factor (VWF) characterizes the disease. Electron microscopy has shown the thrombi to be composed of degranulated and altered platelets with little fibrinogen or fibrin (Asada et al, 1985).

The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis

IntroductionSepsis and septic shock are leading causes of intensive care unit (ICU) mortality. They are characterized by excessive inflammation, upregulation of procoagulant proteins and depletion of natural anticoagulants. Plasma exchange has the potential to improve survival in sepsis by removing inflammatory cytokines and restoring deficient plasma proteins. The objective of this study is to evaluate the efficacy and safety of plasma exchange in patients with sepsis.MethodsWe searched MEDLINE, EMBASE, CENTRAL, Scopus, reference lists of relevant articles, and grey literature for relevant citations. We included randomized controlled trials comparing plasma exchange or plasma filtration with usual care in critically ill patients with sepsis or septic shock. Two reviewers independently identified trials, extracted trial-level data and performed risk of bias assessments using the Cochrane Risk of Bias tool. The primary outcome was all-cause mortality reported at longest follow-up. Meta-analysis was performed using a random-effects model.ResultsOf 1,957 records identified, we included four unique trials enrolling a total of 194 patients (one enrolling adults only, two enrolling children only, one enrolling adults and children). The mean age of adult patients ranged from 38 to 53xa0years (nu2009=u2009128) and the mean age of children ranged from 0.9 to 18xa0years (nu2009=u200966). All trials were at unclear to high risk of bias. The use of plasma exchange was not associated with a significant reduction in all-cause mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.45 to 1.52, I2 60%). In adults, plasma exchange was associated with reduced mortality (RR 0.63, 95% CI 0.42 to 0.96; I2 0%), but was not in children (RR 0.96, 95% CI 0.28 to 3.38; I2 60%). None of the trials reported ICU or hospital lengths of stay. Only one trial reported adverse events associated with plasma exchange including six episodes of hypotension and one allergic reaction to fresh frozen plasma.ConclusionsInsufficient evidence exists to recommend plasma exchange as an adjunctive therapy for patients with sepsis or septic shock. Rigorous randomized controlled trials evaluating clinically relevant patient-centered outcomes are required to evaluate the impact of plasma exchange in this condition.

Haemolytic uraemic syndrome is an immune-mediated disease: role of anti-CD36 antibodies.

Haemolytic uraemic syndrome (HUS) is a disorder in which platelet microthrombi are formed that have a particular propensity to deposit in the kidney microvasculature, resulting in impaired renal function and thrombocytopenia. The mechanism of formation of these microthrombi is not known. In this study, we showed that plasma from five adult and six paediatric cases of HUS caused aggregation and release of adenosine triphosphate from normal platelets. The plasma reacted against platelet lysate in a protein blot and all samples showed reactivity against a band at 88u2003kDa, corresponding to the membrane antigen CD36. This was confirmed by probing with Mo91, a monoclonal antibody to CD36. CD36 was also identified in the immune complex formed by incubation of patient plasmas with normal platelet lysate. In other studies, bands of 32 and 7·7u2003kDa were obtained when purified verotoxin was protein blotted and probed with either patient plasma or with anti‐CD36 antibody Mo91 suggesting structural homologies between CD36 and verotoxin. While a direct cause–effect relationship is not yet established, the data support the concept of an immunological pathogenesis for HUS and suggest that molecular mimicry involving one or both of the homologous domains in membrane‐bound CD36 and verotoxin lead to the development of antibodies capable of inducing the pathophysiological events characteristic of HUS.

The effect of patient‐controlled analgesia on coadministered red blood cells

BACKGROUND:u2002 Patient‐controlled analgesia (PCA) provides effective pain control. The possibility of administrating opioids in the same line as red blood cells (RBCs) for patients with poor venous access has been entertained. The literature on this approach is not extensive, but generally cautionary.

Current perceptions of Canadian autologous blood donors

Background and Objectivesu2002 We determined the perceptions and motivations of autologous donors to establish their regard for this process and the new blood system established in 1999 in Canada.

The experience of treating patients with thrombotic thrombocytopenic purpura with solvent detergent plasma – response to McCarthy

The letter from Dr McCarthy is very interesting as it describes the treatment of a large number of patients with thrombotic thrombocytopenic purpura (TTP) albeit in an apparently nonrandomised fashion. In our paper (Rock et al, 2005), we described a study that was designed to compare cryosupernatant plasma (CSP) with fresh frozen plasma (FFP) in the treatment of TTP. The study was designed to enter a total of 236 patients, but was halted due to a lack of funding after only 52 patients were entered. The study was unable to show a significant difference between CSP and FFP; however, we did not accrue a sufficient number of patients to achieve statistical significance. This data appears to be similar to that reported by Dr McCarthy in his 62 patients treated with FFP and 48 patients with CSP who had 75% and 70% survival respectively. This data are also similar to that reported by Zeigler et al (2001), who did not find a significant difference in outcome in the 24 patients they treated with CSP or FFP. We take the point that the solvent detergent plasma (SDP) provided by Vitex had a decreased total amount of von Willibrand Factor (VWF) and lacked the very high molecular weight VWF multimers normally found in plasma. However, our study (Rock et al, 2005), as referred to by Dr McCarthy,

Patients’ quality of life after stopping plasma exchange: A pilot study

BACKGROUNDnPlasma exchange is being widely used to treat various serious medical conditions. There has been very little follow-up data to describe the quality of life (QOL) of plasma exchange-recipients after active plasma exchange has stopped.nnnOBJECTIVEnTo assess the QOL of plasma exchange recipients after stopping plasma exchange.nnnMETHODSnA pilot study, based on responses to a postal questionnaire and clinical data obtained from the patients charts, was carried out. The scores were computed from questionnaire responses and analyzed.nnnRESULTSnThe response rate was 59% with 58 patients completing a questionnaire three months after their final plasma exchange therapy. We identified significant heterogeneity in the quality of life of plasma exchange recipients after stopping plasma exchange therapy. This could be driven by different patient co-morbidities. We recommend that during follow up visits, a multi-disciplinary approach including consultation with a social worker might be considered for patients who may continue to have some limitations in their psychosocial activities post-discontinuation of plasma exchange. The high response rate to the questionnaire indicates that PLEX patients are interested in being involved in QOL studies, which suggests potential support for a prospective study of QOL with pre and post questionnaires and more detailed tracking of baseline co-morbidities.

Reply to Quintini et al

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Age of blood in inventory at a large tertiary care hospital

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Apheresis: four decades of practice.

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