[Management of pediatric immune thrombocytopenia].

The new guidelines for pediatric immune thrombocytopenia (ITP) not only include changes to the name and staging of the disease, but also introduce the modified Buchanan's bleeding score for the assessment of bleeding symptoms. Treatments should aim to improve patients' health-related quality of life (HRQoL) based on a multidimensional assessment of not only platelet counts but also bleeding symptoms, as well as activity level, lifestyle, and access to healthcare. First-line therapy includes intravenous immunoglobulin therapy (IVIG) and short-term corticosteroids. Second-line therapy includes thrombopoietin receptor agonists, rituximab, and splenectomy. Many novel agents are also in development, with splenic-derived tyrosine kinase (Syk), Bruton's kinase (BTK), and fetal Fc receptor (FcRn) attracting attention as target molecules. Future developments in the treatment of pediatric ITP are eagerly awaited.

Exploring the impact of baseline platelet count on linezolid-induced thrombocytopenia: a retrospective single-center observation study.

BACKGROUND: Patients treated with linezolid (LZD) frequently develop thrombocytopenia, and previous studies have identified the risk factors for this condition. However, the relationship between the development of LZD-induced thrombocytopenia and baseline platelet count has varied according to different reports. AIM: To explore the relationship between platelet count and the development of LZD-induced thrombocytopenia. METHOD: Patients who underwent LZD at Hokkaido University Hospital in Japan from September 2008 to March 2023 were included. We collected data on patient characteristics and platelet counts at baseline and during LZD therapy from the electronic medical records. Thrombocytopenia was defined as a decrease in platelet count by 30% or more from baseline, or a platelet level < 100,000/µL. RESULTS: Two hundred and ninety-five patients who received LZD were included in this study, of whom 34.9% developed thrombocytopenia. In the early days of LZD treatment, the thrombocytopenia group showed a nearly 5% decrease in platelet count, while the non-thrombocytopenia group exhibited an increase of over 5%. Additionally, focusing on early onset thrombocytopenia (within 5 days), a baseline platelet count of < 150,000/µL was identified as a risk factor for early thrombocytopenia. Conversely, it was also observed that 24.7% of patients with a baseline platelet count ≥ 150,000/µL still developed early thrombocytopenia. CONCLUSION: Our findings suggest that while a baseline platelet count of < 150,000/µL is a risk factor for the early onset of thrombocytopenia, vigilant monitoring of platelet counts by clinical pharmacists in the early stages of LZD treatment is essential, regardless of baseline platelet levels.

Hematological abnormalities in liver cirrhosis.

Hematological abnormalities are common in cirrhosis and are associated with various pathophysiological mechanisms. Studies have documented a prevalence of thrombocytopenia, leukopenia, and anemia in patients with compensated cirrhosis of 77.9%, 23.5%, and 21.1%, respectively. These abnormalities carry significant clinical implications, including considerations for invasive procedures, infection risk, bleeding risk, and prognosis. Previously, cirrhosis was believed to predispose patients to bleeding due to alterations observed in classical coagulation tests such as prothrombin time, partial thromboplastin time, international normalized ratio, and thrombocytopenia. However, this understanding has evolved, and cirrhosis patients are now also acknowledged as being at a high risk for thrombotic events. Hemostasis in cirrhosis patients presents a complex phenotype, with procoagulant and anticoagulant abnormalities offsetting each other. This multifactorial phenomenon is inadequately reflected by routine laboratory tests. Thrombotic complications are more prevalent in decompensated cirrhosis and may correlate with disease severity. Bleeding is primarily associated with portal hypertension, endothelial dysfunction, mechanical vessel injury, disseminated intravascular coagulation, endotoxemia, and renal injury. This review comprehensively outlines hematologic index abnormalities, mechanisms of hemostasis, coagulation, and fibrinolysis abnormalities, limitations of laboratory testing, and clinical manifestations of bleeding and thrombosis in patients with liver cirrhosis.

Efficacy of Therapeutic Plasma Exchange or Cangrelor as an Adjunctive Strategy to Facilitate Cardiopulmonary Bypass in Patients with Heparin-Induced Thrombocytopenia: A Systematic Review and Meta-Analysis.

OBJECTIVE: Conduct a systematic review and meta-analysis of the efficacy of therapeutic plasma exchange (TPE) or intravenous cangrelor to prevent thromboembolism in patients with heparin-induced thrombocytopenia (HIT) who undergo cardiopulmonary bypass (CPB) with heparin. DESIGN: Systematic review and meta-analysis. SETTING: N/A. PARTICIPANTS: Adults having cardiac surgery with a history of HIT who received preoperative or intraoperative TPE or intravenous cangrelor as an adjunct to CPB with heparin. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: A systematic review was performed using MEDLINE, PubMed, and Google Scholar. The primary outcome was avoidance of thromboembolism (venous or arterial) during or after CPB. Proportional meta-analysis with a random effects model was used to calculate a weighted-pooled proportion/efficacy for the study's primary outcome. Fifty-seven patients in 17 reports received TPE as an adjunctive treatment to prevent HIT-related thrombosis related to heparinization during CPB and 3 (5.3%) experienced thrombosis. Proportional meta-analysis suggested a weighted-pooled freedom from perioperative thromboembolism rate of 91.0% (95% CI 82.6%-96.9%). Fifteen patients in 6 reports received intravenous cangrelor as an adjunctive treatment to prevent HIT-related thrombosis related to heparinization during CPB and 2 (13.3%) experienced thrombosis. Proportional meta-analysis suggested a weighted-pooled freedom from perioperative thromboembolism rate of 83.0% (95% CI 61.2%- 97.6%). CONCLUSIONS: TPE and cangrelor are feasible strategies to prevent thromboembolism in adults with HIT who require CPB with heparin. Given the relatively small number of cases in the published literature and a high likelihood for publication and detection biases, prudence remains warranted when using these strategies.

[Management of HIT/anti-PF4 disorders].

Heparin-induced thrombocytopenia (HIT) was widely known as a disease characterized by development of thrombosis with thrombocytopenia after heparin exposure. In addition, vaccine-induced immune thrombotic thrombocytopenia (VITT) has been described as a fatal disease involving simultaneous bleeding and thrombosis after COVID-19 adenovirus vector vaccination. These were caused by HIT antibodies and anti-PF4 antibodies, respectively, but both were autoantibodies that recognized PF4, and were found to have the same pathology with different severities. In recent years, many pathologies in which anti-PF4 antibodies are produced have been reported, and a new concept of anti-PF4 disorder has been proposed. Anti-PF4 disorders are often difficult to identify due to their diverse range of causes, and the prognosis varies greatly depending on whether anti-PF4 antibodies can be measured and early treatment performed after observation of thrombocytopenia of unknown cause or thrombosis at an unusual site. To avoid overlooking anti-PF4 disorders, clinicians should become familiar with the classification of these disorders and accurately select the necessary tests.

Systemic Lupus Erythematosus Presenting as Isolated Thrombocytopenia: A Case Report and Review of the Literature.

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by a low platelet count, which can lead to increased bleeding and bruising. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems and often presents with various hematologic abnormalities, including thrombocytopenia. A 32-year-old woman presented to the emergency department with petechiae, extensive ecchymosis, rectal bleeding, generalized body aches, anorexia, and weakness. Despite showing no clinical features of SLE, laboratory findings revealed severe thrombocytopenia and anemia. Initial treatment with low-dose steroids showed no improvement, but a high-dose steroid regimen significantly increased her platelet count. Further investigations revealed elevated ANA and positive anti-dsDNA, leading to a diagnosis of isolated thrombocytopenia as the initial manifestation of SLE. The subsequent findings of elevated ANA and positive anti-dsDNA confirmed the diagnosis of SLE, with ITP as its initial manifestation. This case underscores the importance of considering underlying autoimmune diseases in patients presenting with isolated thrombocytopenia after ruling out other causes. Early recognition and appropriate treatment of autoimmune conditions like SLE can significantly improve patient outcomes, even when initial presentations are atypical.

Middle meningeal artery embolization for organized chronic subdural hematoma combined with minimal evacuation surgery: Two case reports.

Organized chronic subdural hematoma (OCSDH) is a rare condition lacking standardized treatment protocols. Middle meningeal artery (MMA) embolization has recently demonstrated promising outcomes in managing chronic subdural hematoma (CSDH). We present 2 cases of OCSDH treated with endovascular embolization and minimal evacuation surgery. The first case involved an 83-year-old male with a history of left CSDH drainage, admitted urgently due to right hemiplegia and dysarthria. CT scans confirmed recurrent CSDH. A small craniotomy was performed to decompress the thick hematoma, followed by drain placement. Postoperative magnetic resonance imaging (MRI) indicated OCSDH. Seven days later, MMA embolization with 25% n-butyl-2-cyanoacrylate (NBCA) was performed under local anesthesia. The patient's symptoms improved, and the hematoma resolved within 6 months without recurrence. The second case involved a 76-year-old male with right CSDH and thrombocytopenia (platelet count of 19,000/µL), diagnosed with immune thrombocytopenia. MRI indicated OCSDH. Due to the risk associated with craniotomy, a burr hole perforation and MMA embolization were planned, accompanied by a platelet transfusion. Left MMA embolization with 20% NBCA was performed, followed by burr hole enlargement for decompression and drain placement. The patient's symptoms improved postoperatively, and his platelet count stabilized with steroid therapy and thrombopoietin. The hematoma resolved within 3 months without recurrence. These cases indicate that MMA embolization combined with small craniotomy or perforation may be an effective treatment strategy for OCSDH.

Evans syndrome in conjunction with rheumatoid arthritis and SLE: A unique case of autoimmune intersection.

Evans syndrome is a rare autoimmune disorder characterized by autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP), often linked with systemic lupus erythematosus (SLE). We present a case of a 25-year-old female with a history of rheumatoid arthritis (RA) who presented with new SLE symptoms, including left-sided weakness, pallor, and a photosensitive rash. Laboratory tests confirmed Evans syndrome, and MRI showed a cerebral infarction. Treatment with corticosteroids, hydroxychloroquine, and mycophenolate mofetil led to significant improvement. This case highlights the complexity of managing Evans syndrome in patients with coexisting autoimmune diseases like RA and SLE, emphasizing the need for early and aggressive treatment.

Postoperative bleeding after dentoalveolar surgery in patients with thrombocytopenia-are prophylactic platelet transfusions necessary?

PURPOSE: Benefits of prophylactic platelet (PLT) transfusion before dentoalveolar surgery are unclear. This study investigated the effect of prophylactic PLT transfusions on the incidence of postoperative bleeding (POB) in patients with thrombocytopenia and a PLT count ≤ 75*109/L. METHODS: The cohort in this retrospective study comprised 83 patients with thrombocytopenia ≤ 75*109/L who had undergone dentoalveolar surgery. Exclusion criteria were other coagulation deficiencies or medications that would affect hemostasis. In all, 144 teeth had been removed. POB events were extracted and compared between the group that had received prophylactic PLT transfusion before dentoalveolar surgery and the group that had not. RESULTS: POB events were observed in 5 of 83 patients (6.0%) who had a median PLT count of 35*109/L before any transfusion. The group with no postoperative bleeding (NPOB) had a median PLT count of 34*109/L. Two (4.2%) of the 48 patients who had received prophylactic PLT transfusions before dentoalveolar surgery developed POB. Three (8.6%) of the 35 patients who had not received a transfusion experienced POB. The difference between these two groups was not significant (p = 0.646). When two or more teeth were removed in the same session, a significantly higher incidence of POB was observed (p = 0.042). CONCLUSIONS: Our data indicate that prophylactic PLT transfusions in thrombocytopenic patients with PLT counts ≤ 75*109/L do not reduce the incidence of POB after dentoalveolar surgery. However, caution is warranted when extracting multiple teeth in the same surgical session since we found this to be significantly associated with an increased risk of POB.

Efficacy of human interleukin-11 analogs for treating dengue fever-associated thrombocytopenia: a prospective cohort.

AIM: Dengue fever (DF), carried by Aedes mosquitoes, affects millions worldwide. Platelet-inducing human IL-11 analogues may be effective in treating DF-associated thrombocytopenia. METHODOLOGY: A prospective study was done at Dr. Ziauddin Hospital, a tertiary care hospital in Karachi, Pakistan, from September 2023 to April 30, 2024. RESULTS: This study recruited 300 DF patients characterized by thrombocytopenia (platelet count < 30,000), including 159 in the treatment and 141 in the control group. The median age of patients was 34 ± 11.05 years, with 187 males (62.3%) and 113 females (37.7%). The treatment group had a higher proportion of fever (80%, p < 0.0001) and headache (96%, p = 0.012) compared to the control group; however, no significant changes were observed in other clinical parameters between the two groups. Following treatment for 5 days, platelet counts of the treatment group increased significantly in response to IL-11 treatment compared to the control group at all time intervals (day 0, day 1, day 2, day 3, day 4, and day 5). Following treatment, males consistently exhibited higher platelet counts than females (all p < 0.05). In addition, patients admitted on day 3 of their course of illness showed a significantly slow response to the treatment compared to those admitted on day 5. Although young individuals exhibited a significant increase in platelet count, the age showed no significant intergroup differences. CONCLUSIONS: IL-11 analogs have promising potential for treating DF-associated thrombocytopenia. Additional investigation is necessary to refine administration protocols and examine the wider therapeutic ramifications of IL-11 in managing DF.

Outcomes of Hip Arthroplasty in Patients with Preoperative Thrombocytopenia.

Background: Thrombocytopenia is a condition where platelet counts are below the normal range (< 150 × 103/µL), resulting in a higher risk of bleeding and affecting the results of hip arthroplasty. We assessed the impact of preoperative platelet counts on the clinical results of patients who underwent hip arthroplasty. Methods: Between April 2003 and March 2023, 437 patients (451 hips), who had preoperative thrombocytopenia of less than 150 × 103/µL platelets, underwent hip arthroplasty. Preoperative platelet levels were categorized into severe thrombocytopenia (< 50 × 103/µL) and non-severe thrombocytopenia (50-149 × 103/µL). Total blood loss, operation time, requirement of transfusion, amount of transfusion, duration of surgical wound oozing, length of hospital stay, mortality rate at 1 year after surgery, and any complication were compared between the 2 groups. Results: No notable differences were observed in the surgery time or the total amount of blood loss between the groups. The requirement of transfusion and the amount of transfused blood were higher in the severe thrombocytopenia group. Prolonged oozing was found in around 18% in both groups, while periprosthetic joint infections occurred in 3 of the non-severe thrombocytopenia group. No significant difference was noted in the duration of hospital stay (25.6 ± 18.3 days vs. 19.4 ± 16.6 days, p = 0.067) and 1-year mortality (22.2% vs. 11.8%, p = 0.110). Conclusions: Hip arthroplasties are safe for patients with low platelet counts and do not lead to prolonged hospital stays. On the other hand, patients with severe thrombocytopenia tend to need blood transfusions more frequently than those with less severe thrombocytopenia.

Immune or inherited thrombocytopenia? A population-based cohort study on children and adolescents presenting with a low platelet count.

BACKGROUND: Thrombocytopenia is a common hematologic finding in children and adolescents. Immune thrombocytopenia (ITP) is the most common cause of this finding, but the differential diagnosis includes a growing list of genetic disorders. We aimed to report differences in phenotypes of patients with ITP, inherited platelet disorder (IPD)/primary immunodeficiency disorder (PID), and other causes, with a focus on differentiating ITP from inherited thrombocytopenia. PROCEDURE: This retrospective, population-based observational cohort from 2006 to 2020 involved 506 Finnish children under 16 years of age presenting with isolated thrombocytopenia. RESULTS: Of the 506 participants, 79.7% had ITP, 6.7% had IPD/PID, and 13.6% had other causes of thrombocytopenia. A platelet count of ≤12 × 109/L best distinguished between ITP and other reasons with a sensitivity of 60% and a specificity of 80%. Among patients with the lowest platelet count of less than 10 × 109/L, 95.9% had ITP, 3.3% had IPD/PID, and 0.8% had other causes. Severe bleeding events were reported in 20 patients (4.0%), but there were no cases of intracranial or fatal bleeding due to thrombocytopenia. Up to 50% of patients with a high suspicion of inherited thrombocytopenia remained without a specific diagnosis despite genetic testing. CONCLUSIONS: ITP remains the most common cause of thrombocytopenia. A platelet count of ≤12 × 109/L often leads to an ITP diagnosis. Genetic disorders are rare but should be suspected in patients with persisting thrombocytopenia, especially with platelet counts constantly above 12 × 109/L, a positive family history, or atypical clinical features.

Real-world evidence of avatrombopag for the treatment of immune thrombocytopenia intolerant or ineffective to eltrombopag/hetrombopag.

Due to the limited real-world research on the application of avatrombopag (AVA) for immune thrombocytopenia (ITP) in China, we evaluated the effectiveness and safety of AVA in clinical practice. We included 121 adult ITP patients treated with AVA across three medical centres. Based on the reasons for choosing AVA, these patients were divided into eltrombopag (ELT)/hetrombopag (HET) intolerance group (IG), and ELT/HET unresponsive group (UG). Compared with UG, more patients in IG had a history of liver disease and received fewer treatments before AVA. Amongst all patients, 83% had platelet response (≥30 × 109/L) after AVA and 62% achieved complete response (≥100 × 109/L, CR). Sixty-two percent in IG and 56% in UG were able to discontinue more than one concomitant ITP medication. A total of 17 patients underwent multiple switches of thrombopoietin receptor agonists (TPO-RAs), resulting in an 88% platelet response rate. Sixty-three patients discontinued AVA, 27% were due to unaffordability. AVA was well tolerated in most patients. In the ITP population, AVA proved effective and safe, particularly in patients intolerant or unresponsive to ELT/HET. Patients benefited from TPO-RAs switches, particularly those undergoing multiple switches. However, many patients struggled with the long-term financial burden of AVA.

Enhancing the Safety and Efficacy of Trastuzumab Emtansine (T-DM1) Through Nano-Delivery System in Breast Cancer Therapy.

Trastuzumab emtansine (T-DM1), an antibody-drug conjugate, revolutionizes breast cancer therapy by specifically delivering DM1 to human epidermal growth factor receptor 2 (HER2) overexpressing tumor cells, effectively inhibiting cell division and proliferation. While T-DM1 demonstrates superior efficacy and tolerability, T-DM1-induced thrombocytopenia remains a significant adverse event leading to treatment discontinuation. To address this issue, the study investigates the feasibility of using poly(lactic-co-glycolic acid) (PLGA) nanoparticles as a delivery vehicle to conjugate T-DM1, aiming to alleviate T-DM1-induced thrombocytopenia. The T-DM1-conjugated PLGA nanoparticles (NPs-T-DM1) reduce binding to megakaryocytes without compromising the targeting ability for HER2. Administration of NPs-T-DM1 not only significantly inhibits tumor growth but also reduces damage to megakaryocytes, inhibits T-DM1-induced thrombocytopenia, and remarkably improves the safety of antibody-conjugated drugs. This work presents a promising strategy to enhance the safety and efficacy of T-DM1 in antitumor therapy, offering significant potential for advancing clinical application in HER2-positive breast cancer patients.

Soluble cytotoxic T-lymphocyte antigen-4 (sCTLA-4) in children with immune cytopenia: relation to disease activity.

Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is a costimulatory receptor exhibiting a potent inhibitory signal on antigen-activated immune responses. A soluble form, sCTLA-4, has been identified and was found to be increased in several autoimmune diseases. We aimed to evaluate serum levels of sCTLA-4 in different immune cytopenias, and to determine its possible relation to the disease activity. We measured serum levels of sCTLA-4 in 47 patients with immune cytopenias and compared them to 47 age- and sex-matched healthy controls. sCTLA-4 levels were significantly higher in patients with immune cytopenias compared to healthy controls (p < 0.001), however, levels were comparable between different groups of immune cytopenias (p = 0.084). Serum sCTLA-4 inversely correlated with age at diagnosis and hemoglobin level (p = 0.048, and p = 0.039 respectively), while it directly correlated with disease duration (p = 0.023) as well as markers of hemolysis including reticulocyte count, serum LDH and indirect bilirubin (p = 0.025; p = 0.019; p = 0.004 respectively). In the AIHA group, serum sCTLA-4 levels were significantly lower in patients in remission compared to patients with active disease (p = 0.026). Children with immune cytopenia exhibit significantly higher levels of circulating sCTLA-4 which correlated with disease activity, yet the prognostic significance and its use to tailor treatment regimen require additional studies.

Dogs may carry Leishmania tropica and Leishmania major in their blood circulation: a molecular and hematological study.

BACKGROUND: Dogs may be infected with species of Leishmania parasites that are disseminated through blood circulation and invade the internal organs. In this study, we aim to detect the parasite in the blood of dogs using the PCR technique. The present work was performed from February 2022 to May 2023 in Fars Province, southern Iran, where the disease is endemic. RESULTS: In total, 7(5.1%) out of 135 blood samples, six were identified as Leishmania tropica and one as Leishmania major. We found no trace of Leishmania infantum, which is always known for visceral infection. In addition, no sign of cutaneous lesions or a significant disease was seen in the animals infected with both species. Of 48 dogs with anemia, two were Leishmania positive. The mean value of hematological parameters in the infected dogs was within the normal range except for a significant reduction in the platelet measures (p < 0.05). CONCLUSIONS: Our data revealed that both Leishmania species, tropica and major, may manifest as viscerotropic leishmaniasis. More investigations are needed to understand the conditions under which these species choose the type of infection. Moreover, our data emphasize the role of asymptomatic dogs in carrying these parasites, a crucial factor in spreading the disease.

Effect and safety of recombinant human thrombopoietin on haematopoietic reconstitution after allogeneic haematopoietic cell transplantation.

Delayed platelet engraftment (DPE) and thrombocytopenia are common complications following myeloablative conditioning in the advanced stage of allogeneic haematopoietic cell transplantation (allo-HCT), and they are associated with transplantation-related mortality and poor prognosis. Therefore, promoting haematopoietic reconstitution after allo-HCT plays a key role in improving patient outcomes. The aim of this retrospective study was to assess the effectiveness and safety of recombinant human thrombopoietin (rhTPO) in promoting haematopoietic reconstruction after allo-HCT. The study included 210 patients who underwent transplantation, with 158 in the rhTPO group and 52 in the control group. Of the total patient population, 120 were males and 90 were females, with a median age of 31 years (range=6 to 59 years). The results showed that the rhTPO group had a median platelet engraftment time that was 14.1 days shorter than that of the control group (14.1 days vs. 21.9 days; P < 0.001). The time for platelet count recovery to 50 × 10^9/L was also shorter in the rhTPO group than in the control group (21.7 days vs. 30.3 days; P < 0.001). Additionally, the granulocyte engraftment time was shorter in the rhTPO group (14.3 days vs. 18.2 days; P < 0.001). There was no significant difference in overall survival (OS) between the rhTPO group and the control group at 2 years after transplantation (77.2% vs. 65.4 %; P = 0.08). Furthermore, there were no significant differences in the amount of platelet transfusions, the rate of platelet engraftment, the rate of DPE, or the incidence of Grade 4 haemorrhage between the groups. Moreover, no adverse reactions were found in the rhTPO group. This study demonstrated that rhTPO administration after allo-HCT effectively reduced the time required for platelet and granulocyte engraftment and was safe.

Risk of venous thromboembolism after discontinuing prophylactic or therapeutic anticoagulation in patients with haematologic malignancies because of thrombocytopenia.

Although the rates of thrombocytopenia in patients with hematologic malignancies are well known, clinical reports of patients with haematological malignancies presenting with thrombocytopenia who developed venous thromboembolism (VTE) are rare. Defining the risk of VTE in patients with hematologic malignancies in whom anticoagulation is discontinued could help to individualize concepts of anticoagulation. We performed a retrospective analysis of medical records of patients with hematologic malignancies and thrombocytopenia grade 3 (25 × 109/L to < 50 × 109/L) or more severe in 2019-2022 in the Department of Haemato-Oncology at HELIOS Klinikum Krefeld. Data from 67 patients (34 (51%) males, 33 (49%) females) aged between 22 and 82 years (38 leukaemia, 23 lymphoma, 6 other) were included. Prophylactic anticoagulation was performed in 59 (88%) patients and therapeutic due to atrial fibrillation in 8 (12%). Anticoagulation was discontinued in 37 (55%) patients due to thrombocytopenia. Thrombotic events occurred in eight (12%) and minor bleeding in two (3%) patients. Seven patients developed a deep vein thrombosis (DVT) or superficial vein thrombosis (SVT) of the upper limbs, only one patient had a thrombosis of the femoral veins. Thrombotic event were much more frequent in patients suffering from leukaemia compared to lymphoma. Two thrombotic events occurred despite continued prophylaxis (2 of 30, 6.6%), the other six after discontinuing of anticoagulation (6 of 37, 16.2%). Both bleedings occurred in the group with continued anticoagulation. Five of the six patients with a thrombotic event, but without anticoagulation, received anticoagulation again despite a low platelet count and no bleeding was observed. Only one patient with jugular vein thrombosis and a platelet count around 4 × 109/L remained without anticoagulation and no thrombus formation was observed. Risk of VTE in our patients with haematologic malignancies in whom anticoagulation is discontinued due to thrombocytopenia grade 3 is about 2.5 times higher than in patients in whom anticoagulation is continued and predominantly affects patients with leukaemia and upper extremity.

Nicotinamide enhances Treg differentiation by promoting Foxp3 acetylation in immune thrombocytopenia.

Imbalanced nicotinamide adenine dinucleotide (NAD+) homeostasis has been reported in multiple autoimmune diseases and supplementation with NAD+ precursors has consistently demonstrated positive therapeutic benefits for these conditions. Immune thrombocytopenia (ITP) is an acquired autoimmune disease, in which the decreased number and impaired function of regulatory T cells (Tregs) contribute to the main pathogenesis. Here we found NAD+ level was decreased in the plasma and CD4+ T cells of ITP patients. Supplementation with NAD+ precursor nicotinamide (NAM), but not nicotinamide mononucleotide (NMN), increased Treg frequency and ameliorated thrombocytopenia in an ITP murine model. Moreover, whilst both NAM and NMN restored cytosolic NAD+ level in the CD4+ T cells from ITP patients, only NAM promoted Treg differentiation. Mechanistically, Sirtuin1 (Sirt1), a major consumer of NAD+, was highly expressed in the CD4+ T cells of ITP patients, potentially contributing to the low level of NAD+. NAM, which could act as Sirt1 inhibitor, promoted Foxp3 acetylation and stability in induced Tregs derived from naïve CD4+ T cells of ITP patients. These findings suggest that NAM holds promise as a novel therapeutic strategy for restoring immune balance in ITP.