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Summary: Corticosteroids remain the first‐line treatment of immune thrombocytopenia (ITP), but increase the risk of osteoporosis and fractures. Bisphosphonates are used for the treatment of osteoporosis, but their usage among patients with ITP has not been systemically described. We investigated the risk of fractures and the use of bisphosphonates in adult patients with primary (pITP) and secondary ITP (sITP) compared with matched comparators in a nationwide registry‐based cohort study. We identified 4030 patients with pITP (median age 60 years [IQR, 40–74]), 550 with sITP (median age 59 years [IQR, 43–74]) and 182 939 age–sex‐matched general population comparators. All individuals were followed for incident fractures. Bisphosphonate use was estimated for calendar‐years and in temporal relation to the ITP diagnosis. Adjusted cause‐specific hazard ratio (csHR) for any fracture was 1.37 (95% confidence interval [CI] 1.23; 1.54) for pITP and 1.54 (1.17; 2.03) for sITP. The first‐year csHR was 1.82 (1.39; 2.40) for pITP and 2.78 (1.58; 4.91) for sITP. Bisphosphonate use over calendar‐years and in the early years following ITP diagnosis was higher among patients with ITP diagnosis compared with the general population. In conclusion, the risk of fractures and the use of bisphosphonates are higher in patients with ITP compared with the general population. [ABSTRACT FROM AUTHOR]

Although bleeding is one of the main symptoms of primary immune thrombocytopenia (ITP), risk factors for bleeding have yet to be fully established. Low platelet count (PC; <20–30 × 109/L) is generally indicative of increased risk of bleeding. However, PC and bleeding events cannot be fully correlated; many other patient‐ and disease‐related factors are thought to contribute to increased bleeding risk. Furthermore, even though ITP patients have thrombocytopenia and are at increased risk of bleeding, ITP also carries higher risk of thrombotic events. Factors like older age and certain ITP treatments are associated with increased thrombotic risk. Women's health in ITP requires particular attention concerning haemorrhagic and thrombotic complications. Management of bleeding/thrombotic risk, and eventually antithrombotic therapies in ITP patients, should be based on individual risk profiles, using a tailored, patient‐centric approach. Currently, evidence‐based recommendations and validated tools are lacking to support decision‐making and help clinicians weigh risk of bleeding against thrombosis. Moreover, evidence is lacking about optimal PC for achieving haemostasis in invasive procedures settings. Further research is needed to fully define risk factors for each event, enabling development of comprehensive risk stratification approaches. This review discusses risk‐based and individualised management of bleeding and thrombosis risk in adults with primary ITP. [ABSTRACT FROM AUTHOR]

Introduction: COVID‐19 is associated with an increased risk of venous thromboembolism (VTE), but there is great variation among reported incidence rates. Most previous studies have focused on hospitalized patients with COVID‐19, and only a few reports are from population‐based registries. Methods: We studied the 90‐day incidence of VTE, associated risk factors and all‐cause mortality in hospitalized and nonhospitalized patients with COVID‐19 in a nationwide cohort. Data on hospitalizations and outpatient visits were extracted from two national registries with mandatory reporting linked by a unique national identification number carried by all Norwegian residents. We performed Cox proportional hazards regression to determine risk factors for VTE after infection with SARS‐CoV‐2. Results: Our study included 30,495 patients with positive SARS‐CoV‐2 polymerase chain reaction with a mean (SD) age of 41.9 (17.3) years, and 53% were males. Only 2081 (6.8%) were hospitalized. The 90‐day incidence of VTE was 0.3% (95% CI: 0.21–0.33) overall and 2.9% (95% CI: 2.3–3.7) in hospitalized patients. Age (hazard ratio [HR] 1.28 per decade, 95% CI: 1.11–1.48, p < 0.05), history of previous VTE (HR 4.69, 95% CI: 2.34–9.40, p < 0.05), and hospitalization for COVID‐19 (HR 23.83, 95% CI: 13.48–42.13, p < 0.05) were associated with risk of VTE. Conclusions: The 90‐day incidence of VTE in hospitalized and nonhospitalized patients with COVID‐19 was in the lower end compared with previous reports, with considerably higher rates in hospitalized than nonhospitalized patients. Risk factors for VTE were consistent with previously reported studies. [ABSTRACT FROM AUTHOR]

Summary: Immune thrombocytopenia (ITP) is an autoimmune haematological disorder characterized by immune‐mediated thrombocytopenia and a variable risk of bleeding. Despite the availability of multiple treatment options, some patients are considered refractory since they do not achieve a platelet count response to multiple treatments and are at risk of bleeding. The term 'refractory' has been used to identify this patient group; however, with the advent of multiple lines of treatment, its meaning has become ambiguous. To address this issue, we reviewed previous definitions of refractory ITP, solicited the views of ITP experts and collected data from registries to inform a definition. Twenty ITP experts who attended the 7th Expert Meeting of the Intercontinental Cooperative ITP Study Group in September 2022 answered a web‐based survey: 95% felt that there was a need for a new definition of refractory ITP for clinical and research purposes. The use of the term refractory, accompanied by a clear indication of the type and timing of failed treatments, was supported by 85% of respondents. Preliminary data on the frequency of refractory patients from the McMaster and Norwegian ITP Registries demonstrated that the proportion of adult ITP patients who had failed first‐line therapy, rituximab, thrombopoietin receptor agonists, any immune suppressant medication and splenectomy ranged from 0.4% to 3.8%. We propose a definition of refractory ITP that could be evaluated in future studies. [ABSTRACT FROM AUTHOR]

The absence of reliable biomarkers in immune thrombocytopenia (ITP) complicates treatment choice, necessitating a trial‐and‐error approach. Machine learning (ML) holds promise for transforming ITP treatment by analysing complex data to identify predictive factors, as demonstrated by Xu et al.'s study which developed ML‐based models to predict responses to corticosteroids, rituximab and thrombopoietin receptor agonists. However, these models require external validation before can be adopted in clinical practice.Commentary on: Xu et al. A novel scoring model for predicting efficacy and guiding individualised treatment in immune thrombocytopenia. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19615 [ABSTRACT FROM AUTHOR]

Registries are essential tools for a better comprehension of rare disease epidemiology and management.1 Immune thrombocytopenia (ITP) is a rare disease with an annual incidence rate of about three per 100 000 individuals.2 Knowledge has been generated in ITP epidemiology during the last decade thanks to large cohorts of patients with ITP, including the recognition of factors related to variations in incidence, clinical course, predictors of chronicity, risk factors for bleeding, infection and thrombosis, as well as the determination of real-world treatment strategies.3 Nevertheless, many issues remain unknown in ITP (Table S1). In the Nordic chronic ITP registry, also called Nordic Country Patient Registry for Romiplostim (NCPRR), the diagnosis of ITP has been further validated by medical chart review of all included patients. [Extracted from the article]

Regulatory agencies are increasingly considering real‐world evidence (RWE) to support label expansions of approved medicines. We conducted a comparative effectiveness study to emulate a proposed randomized trial of romiplostim vs. standard‐of‐care (SOC) therapy among patients with recently diagnosed (≤12 months) immune thrombocytopenia (ITP), that could support expansion of the romiplostim label. We discuss challenges that we encountered and solutions that were developed to address those challenges. Study size was a primary concern, particularly for romiplostim initiators, given the rarity of ITP and the stringent trial eligibility criteria. For this reason, we leveraged multiple data sources (Nordic Country Patient Registry for Romiplostim; chart review study of romiplostim initiators in Europe; Flatiron Health EMR linked with MarketScan claims). Additionally, unlike the strictly controlled clinical trial setting, platelet counts were not measured at regular intervals in the observational data sources, and therefore the end point of durable platelet response often used in trials could not be reliably measured. Instead, the median platelet count was chosen as the primary end point. Ultimately, while we observed a slightly higher median platelet count in the romiplostim group vs. SOC, precision was limited because of small study size (median difference was 11 × 109/L (95% CI: −59, 81)). We underscore the importance of conducting comprehensive feasibility assessments to identify fit‐for‐purpose data sources with sufficient sample size, data elements, and follow‐up. Beyond technical challenges, we also discuss approaches to increase the credibility of RWE, including systematic incorporation of clinical expertise into study design decisions, and separation between decision makers and the data. [ABSTRACT FROM AUTHOR]

Summary: Immune thrombocytopenia (ITP) is an acquired immune‐mediated disorder. Bleeding is the primary symptom that presents in varying severities. ITP has a negative impact on health‐related quality of life (HRQoL). The ITP Life Quality Index (ILQI) was developed as a 10‐item patient‐reported outcome measure to assess impact on HRQoL in ITP. The objective of the present study was to confirm the content validity of the ILQI with a qualitative interview study in the UK involving 15 adult participants with ITP. Combined concept elicitation (CE) and cognitive debriefing (CD) interviews were conducted to explore the symptoms and impacts associated with ITP and confirm content validity of the draft ILQI. The CE phase elicited 14 ITP symptom concepts, including: bruising (all 15 patients, 100%), fatigue (14, 93·3%) and bleeding gums/blood blisters (13, 86·7%). Impacts included decreased ability to participate in sport (all 15 patients, 100%) and anxiety (12, 80%). The CD phase resulted in an adjustment to the ILQI recall period from 1 week to 'the past month'. Updates were made to improve relevance and response options. The qualitative interviews support the content validity of the ILQI and confirm that the concepts assessed are relevant and consistently understood and interpreted by adult patients with ITP. [ABSTRACT FROM AUTHOR]

Summary: Infection with coronavirus disease‐2019 (COVID‐19) may predispose for venous thromboembolism (VTE). There is wide variation in reported incidence rates of VTE in COVID‐19, ranging from 3% to 85%. Therefore, the true incidence of thrombotic complications in COVID‐19 is uncertain. Here we present data on the incidence of VTE in both hospitalised and non‐hospitalised patients from two ongoing prospective cohort studies. The incidence of VTE after diagnosis of COVID‐19 was 3·9% [95% confidence interval (CI): 2·1–7·2] during hospitalisation, 0·9% (95% CI: 0·2–3·1) in the three months after discharge and 0·2% (95% CI: 0·00–1·25) in non‐hospitalised patients, suggesting an incidence rate at the lower end of that in previous reports. [ABSTRACT FROM AUTHOR]

Objectives: To examine predictors for bone marrow biopsy (BMB) and the outcome following BMB in patients with chronic immune thrombocytopenia (cITP). Methods: We identified patients diagnosed with cITP during 2009‐2017 and obtained information on BMB, cITP treatment and subsequent thrombotic events, hospitalized bleeding, hematological cancer, and death using data from population‐based healthcare databases and medical records in Denmark, Norway, and Sweden. Results: Among 4471 adults (≥18 years) with cITP, 1683 (37.6%) underwent BMB before cITP diagnosis, while cumulative BMB incidence after cITP diagnosis date was 3.1% at 1 year and 7.5% at 5 years. Predictors of having a BMB after cITP diagnosis included older age, male sex, low baseline platelet count, splenectomy, and number of cITP treatments. Compared with patients without BMB, patients with BMB had higher rates of thrombotic events (1 year adjusted hazard ratio [HR] 1.53 [95% CI, 0.92‐2.54]), hospitalized bleeding episodes (1 year adjusted HR 1.72 [95% CI, 1.15‐2.58]), hematological cancer (1 year adjusted HR 35.26 [95% CI 17.67‐70.34]), and all‐cause mortality (1 year adjusted HR 1.97 [95% CI, 1.44‐2.68]). Conclusion: Patients who undergo BMB after cITP diagnosis represent a subset of patients with more severe disease and increased rates of complications as well as hematological malignancies. [ABSTRACT FROM AUTHOR]

Summary Patient characteristics and platelet responses at romiplostim initiation according to the duration of immune thrombocytopenia (ITP) are poorly understood. Amongst romiplostim‐exposed adults with ITP lasting ≥6 months during 2009–2018 in Denmark, Sweden, and Norway, we examined characteristics at romiplostim initiation, romiplostim dosage, and durable platelet response (≥75% of measurements ≥50 × 109/L at 14–24 weeks) for subcohorts with newly diagnosed (duration <3 months), persistent (3–12 months), or chronic (>12 months) ITP initiating romiplostim. The 285 romiplostim initiators comprised 81 (28%) with newly diagnosed, 47 (16%) with persistent, and 157 (55%) with chronic ITP. More patients with newly diagnosed ITP than longer ITP duration, had low comorbidity levels, two or more prior ITP therapies, and previous bleeding requiring hospitalisation. The median romiplostim doses were similar across subcohorts. During treatment, median platelet counts were similar across subcohorts (75–76 × 109/L), and the durable platelet response was 64.6%, 52.9%, and 52.7% for newly diagnosed, persistent, and chronic ITP, respectively. After treatment cessation, the median platelet count was 138 × 109/L, 68 × 109/L, and 71 × 109/L, respectively. In conclusion, newly diagnosed patients, compared with romiplostim initiators with longer disease duration, had more severe ITP, higher frequency of durable platelet response, and higher median platelet count after cessation. [ABSTRACT FROM AUTHOR]

Summary: RITP was a double‐blind randomized, 78‐week follow‐up trial in which 109 adults with immune thrombocytopenias (ITP) who failed to achieve adequate response to steroids, were randomized to receive rituximab or placebo. Here, we provide the duration of response, splenectomy and mortality rates based on extended follow‐up after completion of the RITP study. Extended follow‐up data were retrospectively collected for 72 (83%) patients out of the 84 patients who were not splenectomized during the initial RITP study. For the present analysis, median [interquartile range] duration of follow‐up after randomization was 72 [62–82] months. Median duration of response among patients who achieved an initial response was significantly longer in patients who received rituximab (8·2 [5·5–16·7] months) as compared to placebo (1·8 [1·3–3·6] months), P = 0·036. Overall, 35 patients underwent splenectomy (13 in the rituximab, and 22 in the placebo arm, P = 0·12). Eleven patients (10%) died during the study: five in the rituximab and six in the placebo arms, including four deaths from severe bleeding. Although most rituximab‐treated patients eventually relapsed, a longer duration of response and a trend towards lower splenectomy rate were observed in rituximab‐treated patients. [ABSTRACT FROM AUTHOR]

Fostamatinib demonstrated efficacy in phase 3 trials of adults with immune thrombocytopenia (ITP). Post hoc analysis compared patients who received fostamatinib as second‐line therapy (after steroids ± immunoglobulins) versus third‐or‐later‐line therapy (after ≥2 prior lines of therapy including a second‐line agent). Platelet responses ≥50 000/µl were observed in 25/32 (78%) second‐line and 54/113 (48%) third‐or‐later‐line patients. Bleeding events were less frequent in second‐line (28%) versus third‐or‐later‐line (45%) patients. Responses once achieved tended to be durable in both groups. The safety profile was similar in both groups. In this post hoc analysis, fostamatinib was more effective as second‐line than third‐or‐later‐line therapy for ITP. [ABSTRACT FROM AUTHOR]

Summary Immune thrombocytopenia (ITP) refractory to multiple therapies may require a combination of drugs targeting different mechanisms and targets. In this retrospective, multicentre, international study, we report the safety and effectiveness of avatrombopag and fostamatininb in combination administered to 18 patients with multirefractory ITP. Overall, the combination response was achieved in 15 patients (83.3%), with a median time from combination start to best response of 15 days (IQR: 8–35 days). After a median follow‐up of 256 days (IQR: 142.8–319), 5 patients relapsed (26.7%), all during tapering or stopping one drug. Adverse events were described in 6 of 18 patients (33%). [ABSTRACT FROM AUTHOR]

Further confounding the concept of "maintenance-free" is that some treatment effects persist after the treatment ends; B-cell depletion may last for months or years after rituximab and splenectomy creates a lifelong disorder of asplenia. In this quest for clarity, whether "response", "durability" or "remission" is the result of ongoing maintenance treatment is relevant given that many ITP therapies such as the TPO-RA may be ongoing. The last 15 years have shown great progress in the management of immune thrombocytopenia (ITP), ranging from the introduction and licensing of two thrombopoietin receptor agonists (TPO-RA), eltrombopag and romiplostim, to more recently, a Syk tyrosine kinase inhibitor (fostamatinib) and two other TPO-RA (avatrombopag and hetrombopag). [Extracted from the article]

Objectives: The study investigates the hypothesis that inflammation in myelofibrosis (MF) like in myeloma and lymphoma, may disturb iron distribution and contribute to anaemia. Methods: A cross‐sectional study of 80 MF and 23 ET patients was performed. Results: About 35% of anaemic MF patients had functional iron deficiency (FID) with transferrin saturation <20 and normal or elevated S‐ferritin (<500 µg/L). In ET, FID was rare. In MF patients with FID, 70.6% were anaemic, vs 29.4% in patients without FID (P = 0.03). Hepcidin was significantly higher in MF patients with anaemia, including transfusion‐dependent patients, 50.6 vs 24.4 µg/L (P = 0.01). There was a significant negative correlation between Hb and inflammatory markers in all MF patients: IL‐2, IL‐6 and TNF‐α, (P < 0.01‐0.03), LD (P = 0.004) and hepcidin (P = 0.03). These correlations were also seen in the subgroup of anaemic MF patients (Table). Tsat correlated negatively with CRP (P < 0.001). Symptom burden was heavier in MF patients with FID, and MPN‐SAF quality of life scores correlated with IL‐6 and CRP. Conclusions: The inflammatory state of MF disturbs iron turnover, FID is common and contributes to anaemia development and impairment of QoL. Anaemic MF patients should be screened for FID. [ABSTRACT FROM AUTHOR]

Abstract: Background: Patients with Philadelphia chromosome‐negative myeloproliferative neoplasms (MPNs) have higher risks of developing thromboembolisms compared to the general population. International guidelines on the management of MPNs therefore include recommendations concerning thromboembolism prophylaxis. In clinical practice, strict adherence to guidelines may be challenging and dependent on factors such as physician experience, outpatient clinic setting, and access to therapy; however, no data exist on physician adherence or patient compliance to thromboembolism prophylaxis in MPNs. Objectives: The Nordic Myeloproliferative Neoplasm Study Group (NMPN) performed a survey among Nordic hematology specialists with the aim of documenting the implementation of international recommendations in a region of Northern Europe with similar healthcare systems. Results: The study showed that Nordic specialists managed their patients in accordance with international guidelines concerning medical intervention, but to a lesser degree regarding the management of additional cardiovascular risk factors. The survey also drew attention to the common clinical dilemma of combining antiaggregatory agents with vitamin K antagonists (VKA), or novel oral anticoagulants (NOAC), as well as phlebotomy limits in female polycythemia vera patients. Conclusions: The results of this study highlight the importance of considering all risk factors for thrombosis and an optimal collaboration with the primary healthcare sector. [ABSTRACT FROM AUTHOR]

Abstract: Objective: In myeloproliferative neoplasms (MPN), interferon‐alpha (IFN‐α) is an effective treatment with disease‐modifying properties but currently with no clear predictors of treatment outcome. Recent genomewide association studies in chronic hepatitis C have found a strong influence of genetic polymorphism near the IL28B (IFNL3) gene in response to IFN‐α treatment. In this study, we sought to evaluate the prognostic impact of IL28B rs12979860, rs8099917, and rs12980275 on IFN‐α treatment response in myeloproliferative neoplasms. Method: We retrospectively evaluated 100 patients with MPN treated with IFN‐α. The hematologic treatment response on IFN‐α was compared between patients and correlated with host genetic variations in IL28B. The genotypes of IL28B were determined by allelic discrimination assays. Results: The CC genotype of rs12979860 was found significantly associated with hematologic response in polycythemia vera (PV) with a complete response (CR) in 79% (CC) compared to 48% (non‐CC), (P = .036). No association between the genotypes and treatment response on hydroxyurea was found. Conclusion: These results imply an effect of IL28B genotype on the outcome of IFN‐α treatment in MPN. [ABSTRACT FROM AUTHOR]

In this single-center, population-based, and retrospective study, we analyzed the outcome of 49 patients with solitary bone plasmacytoma (SBP) and 28 patients with solitary extramedullary plasmacytoma (SEP), all treated with radiotherapy. Laminectomy was performed in 18/30 SBP patients with vertebral involvement and tumour resection in 10 SEP patients. Overall survival and cause of death for each patient were compared to 5 sex-, age-, and residency-matched individuals from the normal population. Response (complete and partial) was achieved in 94% of SBP and 96% of SEP patients. Relapse rates were higher in SBP (65%) compared to patients with SEP (18%) (P < .01). Only one in-field relapse was identified for the whole series. Ten- and 15-year overall survival, progression free survival (PFS) and multiple myeloma free survival (MMFS) for patients with SBP were 60%/41%, 25%/17%, and 33%/33%. Corresponding values for patients with SEP were 67%/54%, 57%/44%, and 91%/91%. SBP patients had significantly shorter PFS and MMFS compared to SEP patients (P < .01 for both). Only two of the SEP patients developed multiple myeloma and no patient in the whole series progressed to multiple myeloma later than 10 years after diagnosis. Unlike for SEP, the major cause of death among SBP patients was multiple myeloma (49%). Compared to matched normal population, no increased risk of death from secondary malignancies or cardiovascular disease was observed. Positive predictors in SBP patients were for overall survival age <60 years, combined laminectomy and radiotherapy and radiotherapy dose >40 gray, for PFS tumour size <6 cm and combined laminectomy and radiotherapy and for MMFS tumour size <6 cm. Radiotherapy confers excellent local control in both SEP and SBP patients; however, the challenge is to prevent development of multiple myeloma in patients with SBP. [ABSTRACT FROM AUTHOR]

Background Polycythemia vera ( PV), essential thrombocythemia ( ET) and myelofibrosis ( MF) are clonal disorders collectively named as myeloproliferative neoplasms ( MPN). Published data on epidemiology of MPN after the discovery of the JAK2 mutation and the 2008 WHO classifications are scarce. We aimed to study the incidence rates, prevalence and survival of MPN in Norway during the period 1993-2012. Method We identified 2453 persons diagnosed with MPN from the Cancer Registry of Norway between 1993 and 2012. We report age-adjusted incidence rates, prevalence, relative survival and standardised mortality rates. Results The overall age-adjusted yearly incidence rate of PV increased from 0.4/10⁵ to 0.7/10⁵, ET increased from 0.3/10⁵ to 1.0/10⁵ and MF from 0.2/10⁵ to 0.5/10⁵. Prevalence of PV, ET and MF was 9.2, 8.6 and 3.0 per 10⁵ inhabitants, respectively. The five-year relative survival ( RS) of ET and PV was slightly reduced with no improvement. The five-year RS of MF was 58.1% (2008-2012). Standardised mortality rate ( SMR) was 1.9 (95% CI 1.2 - 2.7). Conclusions The incidence rates of ET, PV and MF doubled and tripled during the years 2007-2012 as compared to 1995-2006. This increment in incidence rates may be related to identification of the JAK2 mutation and the derived 2008 WHO guidelines for MPN. The RS was only slightly reduced in PV and ET, but was substantially reduced in MF. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the incidence of thrombotic/thromboembolic conditions in a population-based cohort of adult Scandinavians with incident of chronic immune thrombocytopenia (cITP). The variables considered include incidence rates of arterial thrombosis (AT) and venous thromboembolism (VTE), splenectomized and non-spectomized patients, and gender difference. A higher incidence of VTE in splenectomized patients is recorded.

The study objectives were to determine the intensity and duration of pain, factors that may influence pain experience during and after trephine biopsy, and to assess bleeding and infectious complications related to the procedure. Patients scheduled for trephine biopsy were recruited to the study. Local anesthesia was applied in all patients. Pain intensity was recorded twice daily by the patients using the numeric rating scale ( NRS). Bleeding was graded into four grades. Median age of 184 patients was 63 yr. Maximum NRS level was measured at time of biopsy (T0); 167 (91%) patients experienced pain at T0. Median (Q1 : Q3) NRS was 3 (1; 5). Median duration of pain was 36 h. Fourteen patients reported pain for more than 7 d. Significant inverse correlation was found between NRS at T0 and age. Pain duration at rest correlated with NRS at T0 and age, while pain duration in activity correlated with NRS at T0, age, and with body mass index ( BMI). Mild and moderate bleeding at T0 occurred in 97 (54%) and 18 (10%) patients, respectively; no severe bleeding or infectious complications were registered. Secondary bleeding occurred in two patients; both required hospitalization. In conclusion, the study shows that despite the application of local anesthetic, more than 50% of the patients experienced pain of ≥3 points. Procedure-related bleeding is mild to moderate and managed by local pressure only. [ABSTRACT FROM AUTHOR]

The article presents information on venous thromboembolism and coagulation activities in patients with immune thrombocytopenia (ITP) treated with thrombopoietin receptor agonists (Tpo-RAs). The ITP patients who had received Tpo-RA at the New York Presbyterian Hospital, New York between 2004 and 2011 were evaluated for inclusion. None of the patients included in this study developed venous thromboembolism whilst on Tpo-RA.

Summary This study assessed the grade of bone marrow (BM) fibrosis and its association with a seromarker for collagen-III formation and fibrosis-related cytokines in 25 immune thrombocytopenia (ITP) patients treated with thrombopoietin receptor agonists (Tpo-RA) who had at least one BM biopsy. Assessment of 8 pre- and on-treatment BM biopsies revealed statistically significant increases in reticulin. Reticulin in biopsies performed after a median of 1·4 years of treatment was graded: MF-0 in 3 (12%), MF-1 in 19 (76%), MF-2 in 2 (8%) and MF-3 in 1 (4%). No cytogenetic or flow-cytometric abnormalities were detected. Median pretreatment Procollagen III N-propeptide (PIIINP) (6·6 μg/l) was significantly higher than on-treatment levels (5·6 μg/l); both were higher than controls (3·4 μg/l; P < 0·001). PIIINP was negatively correlated with treatment duration ( r = −0·49) suggesting a decelerated reticulin production over time. There was a trend towards an association between grade of reticulin and PIIINP. Transforming growth factor (GF)-beta and basic-Fibroblast GF were not different between patients and controls but Hepatocyte GF (HGF), an anti-fibrotic cytokine, was significantly elevated in patients. In conclusion, low-grade BM reticulin fibrosis is seen in most ITP patients on Tpo-RA. The novel findings of decreasing PIIINP and elevated HGF need further investigation to explore their significance in BM fibrogenesis. [ABSTRACT FROM AUTHOR]