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![Temporal relationships between time from diagnosis and initial thrombosis. Time from diagnosis to first thrombosis stratified by (A) arterial and (B) venous thrombosis. Time zero corresponds to diagnosis and numbered rows represent individual patients. The ends of horizontal bars correspond to initial thrombotic events, such that patients with bars to the left of time zero had initial thromboses before a POEMS diagnosis, and patients with bars to the right of time zero had initial thromboses after diagnosis. Time of symptom onset is indicated by diamond symbols. Line‐associated thromboses are not included [Color figure can be viewed at wileyonlinelibrary.com]](publication/356562489/figure/fig1/AS:11431281244327919@1715890117974/Temporal-relationships-between-time-from-diagnosis-and-initial-thrombosis-Time-from.png)
Temporal relationships between time from diagnosis and initial thrombosis. Time from diagnosis to first thrombosis stratified by (A) arterial and (B) venous thrombosis. Time zero corresponds to diagnosis and numbered rows represent individual patients. The ends of horizontal bars correspond to initial thrombotic events, such that patients with bars to the left of time zero had initial thromboses before a POEMS diagnosis, and patients with bars to the right of time zero had initial thromboses after diagnosis. Time of symptom onset is indicated by diamond symbols. Line‐associated thromboses are not included [Color figure can be viewed at wileyonlinelibrary.com]
Source publication
Thromboses are prevalent in POEMS syndrome, but few risk factors for POEMS‐associated thrombosis have been identified. The objective of this study is to identify novel risk factors for POEMS‐associated thrombosis. In this retrospective cohort of 230 POEMS patients, 27% developed thrombosis. Arterial events were slightly more common than venous. Str...
Citations
... Up to 40% of patients have arterial and venous thrombosis 47,48 at presentation or during active treatment which is likely due to underlying disease, patient immobility from neurological impairment as well as treatment including immunomodulatory drugs (IMiDs) and steroids. The greatest risk is before treatment initiation and during active disease. ...
Polyneuropathy Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes syndrome is a rare multisystem condition with a range of manifestations which are often overlooked as trivial comorbidities, until their whole triggers the possibility of the diagnosis. The diagnosis is typically delayed by 12-16 months, by which time patients can be severely disabled. There are no established consensus guidelines. We provide clinicians a comprehensive blueprint for managing POEMS from diagnostic suspicion through the work-up, selection of therapy, follow-up, and treatment of relapse based on published evidence and our large single-center experience. A multidisciplinary approach is essential including expert hematologists, neurologists, histopathologists, radiologists, and neurophysiologists. The aim of treatment is to eradicate the underlying plasma cell dyscrasia, but there are limited trial data to guide treatment decisions. Supportive care considerations include management of endocrinopathy, neuropathy, thrombosis, and infection. Response assessment is centered on clinical, neuropathy, hematological, vascular endothelial growth factor, and radiological criteria. Future clinical trials are welcomed in this setting where evidence is limited.
... 49 The greater rates of arterial disease were later replicated in a cohort of 230 patients. 50 Both studies demonstrate the greatest risk period appeared to be prior to therapy or during active disease. Prophylactic anticoagulation alongside antiplatelet therapy has been advocated until remission and VEGF below 1000 pg/ ml. ...
POEMS syndrome is a rare multisystem paraneoplastic disorder due to an underlying low‐level plasma cell dyscrasia. Due to its rarity, there are limited data to guide treatment and there are no consensus guidelines. Therapy choices are dictated by patient characteristics, disease factors and local funding arrangements. The goals of therapy are to eradicate the underlying clone in order to improve quality of life and overall survival. Most evidence has been garnered in the front‐line setting. Localised disease responds well to radiotherapy, whilst for those with systemic disease, the best outcomes are demonstrated with induction chemotherapy followed up with high‐dose melphalan and stem cell rescue if eligible. For transplant‐ineligible patients lenalidomide–dexamethasone remains a preferred treatment option. Data in the relapse setting are scarce. Supportive care including management of neuropathy, endocrinopathy, thrombotic risk and anti‐infective agents is necessary. Future international collaboration is crucial to define optimal treatment strategies particularly in the relapse setting.
... High Hb/hematocrit (Hct), as happens in excessive erythrocytosis, increases the risk of thrombosis [8] but also has an associated increased blood viscosity [9]. After Hb adjustment, its concentration in these cases is reduced but the effect on thrombosis and hyperviscosity is maintained intact but despite that, we are diagnosing after mathematical criteria that excessive erythrocytosis is lower than occurs. ...
Abstract: (1) Background: Current diagnosis of anemia in high altitude populations uses an adjustment of observed hemoglobin (Hb) values. Such an approach has been challenged by findings in different populations in Tibet, Ethiopia and the Andes as inappropriate, as it might incorrectly classify an individual with complete iron stores as anemic. We aimed to assess the suitability of this approach in adult men and women from Cusco, Peru (3400 m); (2) Methods: Complete blood count and iron status biomarkers were measured in 345 subjects (189 females and 156 males), iron status biomarkers were quantified with enzyme-linked immunoassays; (3) Results: Anemia prevalence was overestimated when the altitude-adjustment factor was applied. Hematological parameters were better correlated to iron status biomarkers in the non-adjusted anemia category. When stratified by sex, only women showed a significant association between Hb and other hematological parameters with iron storage and availability (Hepcidin and TFR-F); (4) Conclusion: The prevalence of anemia is overestimated with current guidelines. The rate of anemia using non-adjusted Hb values is more closely related to the rates of anemia or iron deficiency when used hematological parameters, markers of iron status, and measurements of hepcidin and erythropoietin. Sex differences related to iron status were observed, suggesting that men are at a higher risk of iron overload than women at high altitudes. It could be highlighted that a personalized approach is important when assessing a subject, taking in to account hematological parameters as well as origin (Southern Andean or other).
Introduction/Aims
Vascular thrombosis is prevalent among patients with polyneuropathy, organomegaly, endocrinopathy M‐protein, and skin changes (POEMS) syndrome. The endothelial cells in the endoneurium are often hypertrophied and the lumen is frequently occluded. Consequent local hypoxia may increase vascular endothelial growth factor (VEGF), which induces hypercoagulation and vascular permeability.
Methods
This study presents two patients in the fifth decade of life, who had rare nerve biopsy findings of vascular occlusion mainly by platelets. Before the cases presented here, we encountered nine confirmed POEMS patients whose nerve biopsies did not show similar findings.
Results
A small artery and a vein were occluded, but no atherosclerotic changes were observed. The endothelial cells that adhered to the packed platelets lost their junctions.
Discussion
Platelet aggregation, degranulation, and ischemia may cause a loose endothelial barrier and leak proinflammatory cytokines, such as interleukin‐12. This may increase production of VEGF and may cause nerve demyelination. Small vessel platelet thrombosis may contribute to the pathogenesis of this disorder.
Disease Overview
POEMS syndrome is a life‐threatening condition due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder, sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis.
Diagnosis
The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria.
Risk Stratification
Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. Risk factors include low serum albumin, age, pleural effusion, pulmonary hypertension, and reduced estimated glomerular filtration rate.
Risk‐Adapted Therapy
For those patients with a dominant plasmacytoma, first‐line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement should receive systemic therapy. Corticosteroids are temporizing, but alkylators and lenalidomide are the mainstays of treatment, the former either in the form of low‐dose conventional therapy or as high‐dose conditioning for stem cell transplantation. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Daratumumab combinations also appear promising based on case series. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.
POEMS syndrome is a rare form of plasma cell dyscrasia. Difficulties arise already at the stage of making the diagnosis (complex and heterogeneous clinical picture) and continue during the course of treatment (lack of guidelines for therapy, data coming mainly from reports and short series of patients). In this article we review the current state of knowledge on POEMS syndrome diagnostics, clinical characteristics, prognosis, reported treatment outcomes and the emergence of the new therapeutic strategies.
