Asplenia and spleen hypofunction.

Asplenia (the congenital or acquired absence of the spleen) and hyposplenism (defective spleen function) are common causes of morbidity and mortality. The spleen is a secondary lymphoid organ that is responsible for the regulation of immune responses and blood filtration. Hence, asplenia or hyposplenism increases susceptibility to severe and invasive infections, especially those sustained by encapsulated bacteria (namely, Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae type b). Asplenia is predominantly due to splenectomy for either traumatic events or oncohaematological conditions. Hyposplenism can be caused by several conditions, including haematological, infectious, autoimmune and gastrointestinal disorders. Anatomical disruption of the spleen and depletion of immune cells, especially IgM memory B cells, seem to be predominantly responsible for the clinical manifestations. Early recognition of hyposplenism and proper management of asplenia are warranted to prevent overwhelming post-splenectomy infections through vaccination and antibiotic prophylaxis. Although recommendations are available, the implementation of vaccination strategies, including more effective and immunogenic vaccines, is needed. Additionally, screening programmes for early detection of hyposplenism in high-risk patients and improvement of patient education are warranted.

Platelet phenotype and function in the absence of splenic sequestration (Review).

The spleen, in addition to its role in immunity, plays key roles in erythrocyte maintenance and platelet sequestration. Loss of the spleen via splenectomy occurs in approximately 6.4 to 7.1 per 100 000 people per year globally, commonly as a life-saving emergency procedure in trauma and a therapeutic procedure in hematological and hematological malignant conditions. It is associated with increased risk of life-threatening infection and thromboembolism, presumably via loss of splenic function, but the underlying mechanisms behind post-splenectomy thromboembolism are unclear. The splenectomized individual has a two-fold risk of thromboembolism as compared to non-splenectomized individuals and the risk of thromboembolism is elevated both post-operatively and in the longer term. Although those splenectomized for hematological conditions or hematological malignant conditions are at highest risk for thromboembolism, an increase in thromboembolic outcomes is also observed amongst individuals splenectomized for trauma, suggesting underlying disease state is only a partial factor. Although the physiological role of the splenic platelet pool on platelets is unclear, platelet changes after splenectomy suggest that the spleen may play a role in maintaining platelet quality and function. In hypersplenic conditions, sequestration can increase to sequester up to 72% of the total platelet mass. Following splenectomy, a thrombocytosis is commonly seen secondary to the loss of the ability to sequester platelets. Abnormal platelet quality and function have been observed as a consequence of splenectomy. These platelet defects seen after splenectomy may likely contribute to the increase in post-splenectomy thromboembolism. Here we draw upon the literature to characterize the post-splenectomy platelet and its potential role in post-splenectomy thromboembolism.

Prevalence and distribution of functional splenic tissue after splenectomy.

BACKGROUND: Individuals splenectomised for trauma have lower infection rates than those splenectomised for other conditions. Residual functional splenic tissue (FST) after splenectomy may provide ongoing immunological protection. AIMS: To quantify the prevalence and volume of residual FST post-splenectomy using standard testing. METHODS: Splenectomised adults were recruited from the Spleen Australia clinical registry. Eligible individuals had been splenectomised at least 1 year prior to their visit and resided in Victoria. Splenic function was identified by evaluating Howell-Jolly bodies and IgM memory B cells. A 99m-Technetium-labelled, heat-denatured erythrocyte scintigraphic scan was performed if splenic function was detected. RESULTS: Initially, 75 splenectomised individuals (all cause) were recruited, with a median of 58 years of age and who were splenectomised a median of 14 years previously. The most common indications for splenectomy were trauma (30.7%) and haematological disease (28.0%). Scintigraphy identified FST in nine individuals (12.0%). Eight had been splenectomised for trauma. In this cohort, 34.8% of individuals splenectomised for trauma had residual FST. To explore our findings further, 45 additional individuals were recruited, predominately individuals splenectomised for trauma. Twenty-five individuals completed assessments by December 2018. An additional 11 individuals had FST, of whom 9 had been splenectomised for trauma. Overall, we identified 20 individuals with residual FST. Volumes ranged from 2.2 to 216.0 cc. We saw individuals with accessory spleens and splenotic nodules and an individual with both. Seventeen individuals had been splenectomised for trauma. CONCLUSIONS: Residual FST is commonly seen in individuals splenectomised for trauma. It can present in varying distributions and of varying volume. The clinical significance is unclear.

Post-splenectomy sepsis: preventative strategies, challenges, and solutions.

Removal of the spleen had already been established as a routine technique to treat splenic trauma and other diseases affecting the spleen before the anatomy, physiology, and function of the spleen were known in the mid-twentieth century. It is now widely accepted that the splenectomized individual is at increased risk for infection, in particular, overwhelming post-splenectomy infection (OPSI). OPSI is a syndrome of fulminant sepsis occurring in splenectomized (asplenic) or hyposplenic individuals that is associated with high mortality and morbidity. Poorly opsonized bacteria such as encapsulated bacteria, in particular, Streptococcus pneumoniae, are often implicated in sepsis. The spleen is a reticuloendothelial organ that facilitates opsonization and phagocytosis of pathogens, in addition to cellular maintenance. Splenectomy is associated with an impairment in immunoglobulin production, antibody-mediated clearance, and phagocytosis, leading to an increased risk of infection and sepsis. Early identification of the at-risk patient, early blood cultures prior to antibiotic administration, urgent blood smears and fast pathogen-detection tests, and sepsis bundles should be utilized in these patients. Prompt management and aggressive treatment can alter the course of disease in the at-risk splenectomized patient. Overwhelming post-splenectomy infection can be prevented through vaccination, chemoprophylaxis, and patient education. This article evaluates post-splenectomy sepsis by summarizing the anatomy and function of the spleen, physiological changes after splenectomy that predispose the splenectomized patient to infection, and current management and prevention strategies.

Initial modelling and updates on cost effectiveness from the first 10 years of a spleen registry.

OBJECTIVE: To validate our estimates from our original model and re-evaluate the cost-effectiveness of Spleen Australia, the Australian post-splenectomy registry, using our original model with updated model parameters based on advances in the literature and experience of the registry over the past decade. METHODS: We revisited a decision model from 2005, comparing 1,000 hypothetical registered patients with asplenia or hyposplenism against 1,000 who were not registered, and updated the model parameters. The cost-effectiveness of the registry was evaluated from a healthcare perspective in terms of additional cost per case of overwhelming post-splenectomy infection (OPSI) avoided and as additional cost per life year gained. RESULTS: Over a cohort lifetime the registry was associated with an additional cost of $125,724 per case of OPSI avoided or $19,286 per life year gained. CONCLUSIONS: Despite our initial over-estimation of immunisation and chemoprophylaxis uptake and increases in unit costs, our re-evaluation confirmed use of the registry to be cost-effective. Implications for public health: Improved outcomes for patients with asplenia or hyposplenism can be achieved by a cost-effective registry. Additional research into effectiveness of interventions, OPSI prevalence associated with varying intervention use, and compliance rates over time after registration would provide improved accuracy of cost-effectiveness estimates.

Impact of a spleen registry on optimal post-splenectomy vaccination and care.

Objective: To evaluate quality of patient knowledge and rates of adherence to guidelines amongst splenectomised patients registered to the Spleen Australia registry. Method: Registrants recruited for assessment of residual splenic function post-splenectomy also underwent an assessment of quality of knowledge and a review of their long-term management. Eligible patients were ≥ 18 years of age, registered to the Spleen Australia clinical registry and had been splenectomised at least 1 year prior to their visit. Quality of knowledge was assessed using a validated questionnaire used in similar studies. Receipt of immunisations was validated by record review. Chemoprophylaxis use was self-reported by patients. Adherence was evaluated using Australian guidelines. Results: 77 patients were evaluated for education and adherence. 58% were female, mean age was 58 years, and median duration since splenectomy was 14 years. Most common indications for splenectomy were trauma and haematological conditions. 77% had good knowledge of key educational points to reduce chances of infection. Adherence to immunisations varied with poor adherence to vaccines introduced after 2010. Only 6 patients were adherent to all recommended immunisations. Increasing duration since registration was associated with poorer 13vPCV (p = 0.008) and 4vMenCV adherence (p = 0.001). Over 70% either currently or had previously used daily chemoprophylaxis and 66% had a supply of emergency antibiotics. Conclusions: Although registrants are receiving initial and booster vaccinations, they do not receive newly recommended vaccines. In order to maintain long-term adherence, we recommend streamlining health information systems, improving awareness strategies and improving financial access to vaccinations in the community with additional awareness of the activities of the registry.

Bone Marrow Defects and Platelet Function: A Focus on MDS and CLL.

The bloodstream typically contains >500 billion anucleate circulating platelets, derived from megakaryocytes in the bone marrow. This review will focus on two interesting aspects of bone marrow dysfunction and how this impacts on the quality of circulating platelets. In this regard, although megakaryocytes are from the myeloid lineage leading to granulocytes (including neutrophils), erythrocytes, and megakaryocytes/platelets, recent evidence has shown that defects in the lymphoid lineage leading to B cells, T cells, and natural killer (NK) cells also result in abnormal circulating platelets. Current evidence is limited regarding whether this latter phenomenon might potentially arise from (a) some form of as-yet-undetected defect common to both lineages; (b) adverse interactions occurring between cells of different lineages within the bone marrow environment; and/or (c) unknown disease-related factor(s) affecting circulating platelet receptor expression/function after their release from megakaryocytes. Understanding the mechanisms underlying how both myeloid and lymphoid lineage bone marrow defects lead to dysfunction of circulating platelets is significant because of the potential diagnostic and predictive value of peripheral platelet analysis for bone marrow disease progression, the additional potential effects of new anti-cancer drugs on platelet function, and the critical role platelets play in regulation of bleeding risk, inflammation, and innate immunity.