Hereditary Thrombocytopenia Research Articles

Clinical case of hereditary thrombocytopenia in a 6 year old child with primary combined immunodeficiency condition

Clinical case of hereditary thrombocytopenia in a 6 year old child with primary combined immunodeficiency condition

неЩасливий випадок як поштовх до діагностики хвороби у 16-річного хлопця, пов’язаної з MYH9. Сюжет із практики гематолога

MYH9-related disease (MYH9-RD) is an autosomal dominant hereditary thrombocytopenia caused by mutations in the MYH9 gene with characteristic laboratory features - the presence of giant platelets and basophilic cytoplasmic inclusions in neutrophils (similar to Dele bodies). Patients with MYH9-RD are at high risk for deafness, cataracts, and renal dysfunction, most often occurring in adulthood. Platelet counts in patients with MYH9-RD range from severe thrombocytopenia to near-normal values, although they are usually stable. Propensity for hemorrhagic Complications correlate with platelet count and are usually absent or limited to minor bleeding in patients with mild thrombocytopenia, but may lead to spontaneous and potentially life-threatening bleeding with persistent platelet counts <50×109/l. Purpose - to describe a clinical case of a disease caused by a heterozygous mutation in the MYH9 gene with an emphasis on the importance of genetic tests for the final verification of the disease. Clinical case. Features of diagnosis caused by a heterozygous mutation in the MYH9 gene in a 16-year-old boy are described. Throughout the child's life, the manifestations of the hemorrhagic syndrome were moderate (periodically a small number of bruises on the skin, to which the parents did not pay much attention, bleeding from the gums when brushing the teeth), the child’s blood tests were performed occasionally without determining the number of platelets. The boy suffered a displaced radius fracture as a result of the injury. The orthopedic traumatologist performed an operation of limited reposition of bone fragments followed by implantation of a needle for proper bone fusion without complications. During a general blood test, thrombocytopenia was detected, which prompted the child to be consulted by a hematologist. During the examination at the Western Ukrainian Specialized Pediatric Medical Center, Lviv, it was noted in the hardware count of the hemogram that the number of platelets was 22.0-30.0×109/l, the microscopic count of platelets was 147.0-156.0×109/l, the entire population of platelets was represented by macroforms with mean platelet volume 14.9 fl. We found good aggregation of platelets with ristocytin, and reduced aggregation with epinephrine, arachidonic acid, and adenosine. Verification of the final diagnosis of MYH9-RD caused by a heterozygous mutation in the MYH9 gene occurred by genome sequencing. Therefore, the application of the genome sequencing technique can contribute to the early diagnosis of hereditary macrothrombocytopenia caused by a heterozygous mutation in the MYH9 gene. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

PB0357 Hereditary Thrombocytopenia with Platelet Sialic Acid Deficiency and Mutations in the GNE Genes

PB0357 Hereditary Thrombocytopenia with Platelet Sialic Acid Deficiency and Mutations in the GNE Genes

Thrombocytopenia Absent Radius (TAR)-Syndrome: From Current Genetics to Patient Self-Empowerment.

Thrombocytopenia absent radius (TAR) syndrome is a rare form of hereditary thrombocytopenia associated with a bilateral radial aplasia. TAR syndrome is genetically defined by the combination of a microdeletion on chromosome 1 which includes the gene RBM8A, and a single nucleotide polymorphism (SNP) in the second RBM8A allele. While most patients with TAR syndrome harbor a SNP in either the 5' UTR region or in intron 1 of RBM8A, further SNPs associated with TAR syndrome are still being identified. Here, we report on the current understanding of the genetic basis, diagnosis, and therapy of TAR syndrome and discuss patient self-empowerment by enabling networking and exchange between affected individuals and families.

Hereditary thrombocytopenia with familial novel mutation in MYH9 gene: A familial case report

One of the rarest types of hereditary thrombocytopenia is the MYH9-related disorder. This spectrum of disorders is characterized by large platelets with or without leukocyte inclusion bodies, a decrease in the total number of platelets, and autosomal dominant inheritance. Proteinuric nephropathy that frequently progresses to end-stage renal failure, as well as the beginning of progressive high-frequency sensorineural hearing loss in young adults, is also associated with MYH9-related disorder. In this case report, we presented three family members who had thrombocytopenia and in whom a heterozygous novel 22 bp deletion (c.4274_4295del) was detected which is located in exon 31 of the MYH9 gene. There was no evidence of bleeding in the family members we presented and thrombocytopenia was detected incidentally. Additionally, renal failure, hearing loss, presenile cataracts, and clinical symptoms were not detected in these family members. This novel mutation detected in the MYH9 gene has not been reported in the literature before.

Novel THPO variant in hereditary thrombocytopenia: A potential candidate variant for predisposition to myeloid neoplasm.

Hereditary thrombocytopenia is a heterogeneous group of congenital disorders with a wide range of symptoms depending on the severity of platelet dysfunction or thrombocytopenia. Because of its clinical phenotypes and the bone marrow morphology associated with this condition, hereditary thrombocytopenia can be misdiagnosed as primary immune thrombocytopenia and myelodysplastic syndrome. Therefore, genetic evidence is necessary for the accurate diagnosis of hereditary thrombocytopenia. Refractory cytopenia of childhood is a subgroup of myelodysplastic syndrome that was added to the World Health Organization classification in 2008. To investigate the germline and somatic variants associated with refractory cytopenia of childhood, we performed targeted multigene sequencing in three patients with refractory cytopenia of childhood. Of the three patients, one progressed from megakaryocytic hypoplasia with thrombocytopenia, and targeted multigene sequencing revealed THPO variants in this patient and his sister. We propose that the monoallelic deletion of THPO is a potential candidate for germline predisposition to myeloid malignancy.

Associations between serum biomarkers and non-alcoholic liver disease: Results of a clinical study of Mediterranean patients with obesity.

BackgroundTransient elastography is an ultrasound-based method to detect non-alcoholic fatty liver disease (NAFLD). Despite the simultaneously rising prevalence of fatty liver and metabolic disease, further information about metabolic risk indicators of fatty liver is still necessary.MethodsA Southern Italian population sample with obesity (N = 87) was cross-sectionally explored for associations among the presence of NAFLD, assessed by FibroScan, and clinical, biochemical and anthropometric parameters. Inclusion criteria were age >18 years, BMI ≥ 25 kg/m2, no ongoing supplemental or drug therapy, including oral contraceptives or osteoporosis medications; exclusion criteria were pregnancy, endocrinological diseases, cardiovascular diseases, neoplasia, renal or hepatic failure, hereditary thrombocytopenia, hepatitis B (HBV) or hepatitis C virus (HCV) infection, and excess alcohol consumption.ResultsThe study sample featured a female predominance (67%, N = 60), age range 18–64 years, and 40% prevalence of NAFLD, in accordance with the fibroscan-measured controlled attenuation parameter (CAP) threshold value above 302 dB/m. Males were slightly more frequently affected by NAFLD (51.4% vs. 48.6%, p = 0.01). Insulin levels, insulin resistance (quantified by HOMA-IR), diastolic blood pressure, BMI, visceral adipose tissue (VAT), and waist circumference were significantly higher in the NAFLD subset compared to their counterparts (p < 0.01, p < 0.01, p = 0.05, p < 0.01, p < 0.01, p < 0.01, respectively). Uric acid (p < 0.01) also showed a positive trend in the NAFLD group. Other liver steatosis parameters, measured by stiffness (p < 0.01), fatty liver index (FLI) (p < 0.01) and FibroScan-AST (FAST) (p < 0.01), were also significantly greater in the NAFLD group. In three nested linear regression models built to assess associations between CAP values and serum uric acid levels, a single unit increase in uricemia indicated a CAP increase by 14 dB/m, after adjusting for confounders (coefficient: 14.07, 95% CI 0.6–27.54).ConclusionsClinical-metabolic screening for NAFLD cannot ignore uricemia, especially in patients with obesity.

Diagnosis and management of thrombocytopenia in pregnancy.

Thrombocytopenia, defined as platelet count <150×109/L, is frequently observed by physicians during pregnancy, with an incidence of approximately 10% of all pregnancies. Most of the cases of thrombocytopenia in pregnancy are due to gestational thrombocytopenia, which does not confer an increased risk of maternal bleeding. However, because other causes can be associated with life-threatening events, such as severe bleeding, that can affect to maternal and fetal outcomes, differentiating other cause of thrombocytopenia, which includes preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, acute fatty liver of pregnancy, immune thrombocytopenia, hereditary thrombocytopenia, antiphospholipid syndrome, thrombotic thrombocytopenic purpura, and atypical hemolytic uremic syndrome, is important. Understanding the mechanisms and recognition of symptoms and signs are important to decide an adequate line of investigation. In this review, the approach to diagnosis and the management of the thrombocytopenia commonly observed in pregnancy are presented.

Heritable amegacariocytic thrombocytopenia: description of a clinical case

Annotation. Features of the clinical course and differential diagnosis of hereditary thrombocytopenia, characterized by the development of pancytopenia in childhood, are described. It was found that the main manifestation of this pathology is hemorrhagic syndrome, accompanied by the presence of polymorphic, polychrome, asymmetric hemorrhagic rashes, frequent bleeding from the mucous membranes. The Mpl gene (1p34) was sequestered to confirm the diagnosis and establish the genomic mutation. Complex diagnosis of this disease requires a comprehensive and interdisciplinary approach involving a coordinated team of hematologists, geneticists, immunologists, neurosurgeons and ophthalmologists.

Inborn errors of IKAROS and AIOLOS.

IKAROS is a pioneer protein of the IKZF family of transcription factors that plays an essential role in lymphocyte development. Recently, inborn errors of IKAROS have been identified in patients with B cell deficiency and hypogammaglobulinemia, and these patients often present with recurrent sinopulmonary infection. Autoimmunity and hematologic malignancies are other characteristic complications seen in the patients with IKAROS deficiency. Missense mutation involving asparagine at the 159th position results in combined immunodeficiency, often presenting with Pneumocystis jirovecii pneumonia. Inborn errors of AIOLOS, HELIOS, and PEGASUS have also been reported in patients with B cell deficiency, Evans syndrome, and hereditary thrombocytopenia, respectively. Here, we briefly review the phenotype and genotype of IKZF mutations, especially IKAROS.

Application of high-throughput sequencing for hereditary thrombocytopenia in southwestern China.

BackgroundThe aim of this study was to design and analyze the applicability of a 21‐gene high‐throughput sequencing (HTS) panel in the molecular diagnosis of patients with hereditary thrombocytopenia (HT).MethodsA custom target enrichment library was designed to capture 21 genes known to be associated with HTs. Twenty‐four patients with an HT phenotype were studied using this technology.ResultsOne pathogenic variant on the MYH9 gene and one likely pathogenic variant on the ABCG8 gene previously known to cause HTs were identified. Additionally, 3 previously reported variants affecting WAS, ADAMTS13, and GP1BA were detected, and 9 novel variants affecting FLNA, ITGB3, NBEAL2, MYH9, VWF, and ANKRD26 genes were identified. The 12 variants were classified to be of uncertain significance.ConclusionOur results demonstrate that HTS is an accurate and reliable method of pre‐screening patients for variants in known HT‐causing genes. With the advantage of distinguishing HT from immune thrombocytopenia, HTS could play a key role in improving the clinical management of patients.

Efficacy and Thrombotic Adverse Events of Romiplostim Use in Patients with Thrombocytopenia Related to Underlying Malignancies

Background: Chemotherapy-Induced Thrombocytopenia (CIT) often results in treatment delay, dose reduction, or need for alternate cancer therapy. There is no validated or approved treatment of CIT. At our institution, the thrombopoietin-receptor agonist romiplostim, is being tested in a phase II clinical trial to treat CIT (being reported separately). Further, since there is no alternative, some oncologists have been using romiplostim off-label/off study to treat CIT and prevent recurrence of CIT when chemotherapy is resumed. Raising the platelet count could potentially increase the risk of thrombosis. Therefore, as a Quality Assessment initiative, we conducted a retrospective analysis of all use of romiplostim in cancer patients at MSKCC to determine the efficacy for treatment of CIT, as well as rates of thrombosis.Methods: We performed a retrospective review of all romiplostim use in cancer patients at MSKCC from 1/1/2010 to 4/14/2017. Patients without cancer or patients whose thrombocytopenia was due to an unrelated indication, such as ITP, Evans syndrome, underlying cirrhosis, or hereditary thrombocytopenia syndromes, were not included in this analysis. All medical records, radiology reports, and romiplostim administration records were reviewed by one or more study investigator. The study was approved by the IRB.Results: From 1/1/2010 through 4/14/2017, romiplostim use was documented in 292 patients. We derived 239 patients with cancer-associated indications. 185 (77.4%) of patients had thrombocytopenia related to chemotherapy and/or radiation therapy. Other causes of thrombocytopenia included primary or metastatic cancer of the liver (n=21, 8.8%), bone metastases (n=16, 6.7%), immune thrombocytopenia related to lymphoma (n=11, 4.6%), or other (n=6, 2.5%). 184 patients had solid tumors (77%) and 55 had hematologic malignancy (23%).We performed an analysis of efficacy response to romiplostim in the cohort of solid tumor patients and lymphoid malignancies (lymphoma/myeloma), the two groups with the most patients (Table 1A). The analysis of lymphoma/myeloma below does not include stem cell transplant patients. One solid tumor patient died before any followup labs were available and is not included in the analysis.For both solid tumor and lymphoid malignancies, the mean platelet counts at least doubled by day 14. Resumption of chemotherapy was at the discretion of the treating oncologist, and beyond Day 14 the platelet counts reflected the competing effects of maintenance romiplostim support of the platelet counts and platelet suppression by chemotherapy. The majority of patients tolerated resumption of chemotherapy without reoccurrence of CIT (Data not shown).We analyzed the rates of thrombosis, adjusted for time of exposure to romiplostim (Table 1B). The cumulative romiplostim use in the 239 patients was 129 years. There were a total of 15 venous thromboembolic events (DVT and/or PE). This calculated to 11.6% VTE events per patient-year, well within the historical rate of thrombosis in patients with metastatic cancer or lymphoma on chemotherapy (i.e. Khorana AA et al, Cancer 2013;119:648-55). In addition, no episodes of ischemic stroke or myocardial infarction were identified in the cancer patients while on romiplostim.Discussion: In this retrospective analysis of romiplostim use in cancer patients, we found evidence of efficacy in patients with solid tumors and lymphoid malignancies. Platelet counts increased over two-fold within 14 days of initiation of romiplostim. And importantly, we did not find evidence of increased thrombotic rates compared with historical experience. How to optimally utilize romiplostim in cancer patients with thrombocytopenia is the focus of ongoing clinical research. [Display omitted] DisclosuresSoff:Janssen: Consultancy, Research Funding; Amgen: Consultancy, Research Funding.

How I treat immune thrombocytopenia – a global view

How I treat immune thrombocytopenia – a global view

Whole exome sequencing for diagnosis of hereditary thrombocytopenia.

Hereditary thrombocytopenia comprises extremely diverse diseases that are difficult to diagnose by phenotypes alone. Definite diagnoses are helpful for patient (Pt) management.To evaluate the role of whole exome sequencing (WES) in these Pts.Cases with unexplained long-standing thrombocytopenia and/or suggestive features were enrolled to the observational study. Bleeding scores and blood smear were evaluated. The variant pathogenicity from WES was determined by bioinformatics combined with all other information including platelet aggregometry, flow cytometry, and electron microscopy (EM).Seven unrelated Pts were recruited. All were female with macrothrombocytopenia. Clinical bleeding was presented in four Pts; extra-hematological features were minimal and family history was negative in every Pt. WES successfully identified all the 11 responsible mutant alleles; of these, four have never been previously reported. Pt 1 with GNE-related thrombocytopenia showed reduced lectin binding by flow cytometry, increased glycogen granules by EM and a novel homozygous mutation in GNE. Pts 2 and 3 had phenotypic diagnoses of Bernard Soulier syndrome and novel homozygous mutations in GP1BB and GP1BA, respectively. Pt 4 had impaired microtubule structures, concomitant delta storage pool disease by EM and a novel heterozygous TUBB1 mutation. Pt 5 had sitosterolemia showing platelets with reduced ristocetin responses and a dilated membrane system on EM with compound heterozygous ABCG5 mutations. Pts 6 and 7 had MYH9 disorders with heterozygous mutations in MYH9.This study substantiates the benefits of WES in identifying underlying mutations of macrothrombocytopenia, expands mutational spectra of four genes, and provides detailed clinical features for further phenotype-genotype correlations.

Observation of granulocyte function during ex vivo thrombus formation for patients with ANKRD26-associated thrombocytopenia

ANKRD26-associated thrombocytopenia is a non-syndromic hereditary thrombocytopenia for which there are currently no formal diagnostic criteria. It is known that the probability of myeloid leukemia in patients with pathogenetic variants in the ANKRD26 gene significantly increases, however, studies of the functioning of granulocytes in this pathology have not been conducted. Aims: Analysis of the functioning of granulocytes and platelets during ex vivo thrombosis in patients with ANKRD26-associated thrombocytopenia. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. Two patients and 10 healthy volunteers were included in the study. Intracellular signaling and platelet functional responses were observed by continuous flow cytometry. Ex vivo thrombus formation and granulocyte functioning were observed on a fluorescence microscope in parallel-plane flow chambers containing fibrillar collagen. Upon physiological activation (ADP, collagen) of patients’ platelets in vitro, there were no significant differences between the platelets of patients and healthy donors. However, the observed ex vivo size of platelet aggregates was significantly reduced in comparison with healthy donors and published data on patients with other thrombocytopenias. The observed number and activity (movement velocity) of granulocytes of patients was within normal values. However, significant morphological differences were observed for granulocytes of patients compared with granulocytes of healthy donors: there was an increased spreading of granulocytes, in particular, expressed in a large number of thin pseudopodia, as well as an increased curvature of the motion trajectories of granulocytes. Ex vivo observation of thrombus formation in patients with ANKRD26- associated thrombocytopenia, a significantly reduced thrombus size is observed with normal platelet activity and increased variability in the shape of granulocytes.

Germline mutations in the transcription factor IKZF5 cause thrombocytopenia

AbstractTo identify novel causes of hereditary thrombocytopenia, we performed a genetic association analysis of whole-genome sequencing data from 13 037 individuals enrolled in the National Institute for Health Research (NIHR) BioResource, including 233 cases with isolated thrombocytopenia. We found an association between rare variants in the transcription factor-encoding gene IKZF5 and thrombocytopenia. We report 5 causal missense variants in or near IKZF5 zinc fingers, of which 2 occurred de novo and 3 co-segregated in 3 pedigrees. A canonical DNA-zinc finger binding model predicts that 3 of the variants alter DNA recognition. Expression studies showed that chromatin binding was disrupted in mutant compared with wild-type IKZF5, and electron microscopy revealed a reduced quantity of α granules in normally sized platelets. Proplatelet formation was reduced in megakaryocytes from 7 cases relative to 6 controls. Comparison of RNA-sequencing data from platelets, monocytes, neutrophils, and CD4+ T cells from 3 cases and 14 healthy controls showed 1194 differentially expressed genes in platelets but only 4 differentially expressed genes in each of the other blood cell types. In conclusion, IKZF5 is a novel transcriptional regulator of megakaryopoiesis and the eighth transcription factor associated with dominant thrombocytopenia in humans.

Single-center clinical analysis of hereditary thrombocytopenia in children with chronic thrombocytopenia

Objective To know the detection rate of hereditary thrombocytopenia (HT) in children with chronic thrombocytopenia and its clinical and laboratory characteristics for an early clinical identification and diagnosis of HT in future. Methods Data of the children with thrombocytopenia, who had been treated in Beijing Children′s Hospital from April 2016 to May 2018 and whose present history lasted for more than 1 year and had poor response to immunotherapy were retrospectively collected.HT was screened in these patients by adopting next generation sequencing (NGS). Finally, clinical and laboratory characteristics of these children with HT were summarized and analyzed. Results A total of 161 children with chronic thrombocytopenia were included.Forty-three cases (26.7%) were found to have gene mutations.The genetic rules of the mutant gene, the family verification and the clinical manifestations of the proband and some related laboratory tests were analyzed and 24 cases (14.9%) can be diagnosed as HT.Among the HT patients, the proportion of males and females was 159, and the median onset of age was 0.58 years, which was significantly lower than that of non-HT cases (the median onset of age was 4.36 years), and the difference was statistically significant (P<0.001); the proportion of mucosal hemorrhage and visceral hemorrhage (31.8% and 13.7%) of HT was significantly higher than non-HT cases (15.3% and 0.6%), and the difference was statistically significant (P<0.001). Fifty percent of (12/24 cases) cases of HT had positive family history; according to the ave-rage platelet volume and platelet morphology in peripheral blood smear, HT could be divided into small platelet HT, po-sitive platelet HT and large platelet HT.Some cases had well response to immunotherapy but seemed easy to relapse du-ring the withdrawal period, while the others responded poorly to therapy.Different clinical manifestations of HT suggest different pathogenesis, which can be divided into the related types of megakaryocyte differentiation defect, megakaryocyte maturation defect, platelet release defect and platelet survival time shortening. Conclusions The pathogenesis and cli-nical phenotype of HT was different.Some of them were effective for immunotherapy, which were easily confused with immune thrombocy-topenla(ITP). It is clinically necessary to perform NGS in children with thrombocytopenia at early onset, abnormal platelet morphology, prolonged disease course or severe mucosal/visceral hemorrhage, in order to recognize HT timely to avoid delay in diagnosis and poor prognosis. Key words: Child; Hereditary thrombocytopenia; Next generation sequencing

The case of rare hereditary thrombocytopenia with a predisposition to the development of acute myeloid leukemia in twin children

Family thrombocytopenia/thrombocytopathy with a predisposition to the development of acute myeloid leukemia (AML) is a rare disease associated with a mutation in the RUNX1 gene. To date, there are data on this disease in no more than 70 families. We present a description of the clinical observation of this pathology in two twin children, and also offer an analysis of available literature on the pathogenetic aspects and prevalence of this rare disease. Patient's parents agreed to use personal dats and photos in research and publications.

A Heterozygous Mutation of G-Protein-Coupled Receptor 25 in a Family with Inherited Thrombocytopenia and Thrombosis

BackgroundInherited thrombocytopenia is associated with bleeding tendency and no association with thrombotic tendency has been reported. We found a Japanese family with autosomal dominant form of thrombocytopenia associated with arterial and venous thrombosis.AimsTo identify a causative gene for hereditary thrombocytopenia with thrombosis.MethodsA propositus was a 42-year-old Japanese woman with thrombocytopenia and deep vein thrombosis (DVT). She had normal activities of antithrombin, protein C, and protein S, and negative results for lupus anticoagulant and anti-cardiolipin antibodies. She has suffered from thrombocytopenia (20 - 50 x 109/L) for at least 20 years. Six members among her family pedigree had thrombocytopenia, and also suffered from thrombosis including mesenteric artery thrombosis, young-onset myocardial infarction, femoral artery thrombosis, repeated cerebral infarction, DVT, and pulmonary embolism. Importantly, the family members with these thrombotic disorders had exclusively thrombocytopenia. Whole exome sequencing was performed with venous blood from the 6 affected and 6 non-affected family members to identify a causative gene for thrombocytopenia.ResultsWe identified a heterozygous change (c.764G>T:p.G255V) in GPR25 gene, an uncharacterized G protein-coupled receptor. The mutation was completely linked with thrombocytopenia. The mutated residue was located at the transmembrane domain of GPR25. We generated anti-GPR25 monoclonal antibodies and confirmed that GPR25 was expressed on the platelet surface. The patient's platelets showed the same level of PAC1 (a monoclonal antibody recognizing the active conformation of integrin αIIbβ3) binding and P-selectin expression as platelets from healthy subjects. However, ADP-induced aggregation of patient's washed platelets was enhanced as compared with normal washed platelets. Moreover, the patient's platelets had an increase in thrombin + collagen-induced and A23187-induced Annexin V binding compared with platelets from healthy subjects.ConclusionWe identified a novel gene mutation responsible for inherited thrombocytopenia and thrombosis that may induce platelet hyper-reactivity. DisclosuresNo relevant conflicts of interest to declare.

Romiplostim for the management of perioperative thrombocytopenia.

Thrombocytopenic patients requiring invasive surgery have few options to improve their platelet count preoperatively. This is a single-centre, retrospective review of thrombocytopenic patients receiving the thrombopoietin receptor agonist romiplostim perioperatively to allow for surgical interventions. Patient characteristics, romiplostim use, and surgical and safety outcomes (bleeding, thrombosis, transfusions) were collected and analysed. Forty-seven patients underwent 51 surgical procedures (ranging from total hip arthroplasty to open cardiac surgery) with romiplostim support. Thrombocytopenia aetiologies included immune thrombocytopenia, chronic liver disease, haematological malignancy, drug-related thrombocytopenia, and hereditary thrombocytopenia. Median (range) platelet counts improved, from 47×109 /l (9-120×109 /l) at romiplostim initiation to 164×109 /l (28-603×109 /l) at the time of surgery (P<0·0001). A dose of 3μg/kg per week for 2 doses increased the platelet count to >100×109 /l in 79% of patients within 14days. In 96% of cases, surgery proceeded on schedule without delay or cancellation. Four patients had bleeding events unrelated to thrombocytopenia and 1 patient developed deep venous thrombosis. Six patients required red cell transfusion and 3 patients required platelet transfusion perioperatively. In conclusion, romiplostim was effective in increasing platelet counts to allow surgery to proceed safely and on schedule. Bleeding and thromboembolic events were within acceptable limits for this surgical population.