Search Results (21)

Background/Objectives: The assessment of platelet kinetics (APK) is recommended for patients with chronic idiopathic thrombocytopenic purpura (chITP). The aim of this study was to examine the importance of APK as a prognostic instrument in the selection of therapy in children with chITP. Methods: Retrospective, observational research, which included chITP children who were treated and subjected to APK in Serbia for 25 years (total number was 152). Results: In the acute phase of the disease, 15% of patients had life-threatening bleeding, 15% were asymptomatic, and there were no cases of fatal bleeding. Mean platelet life was 0.89 ± 0.47 days. A total of 45% of patients had normal platelet production, and 35% had very low production. Among the patients, 55% exhibited splenic platelet sequestration, 35% had mixed sequestration, and 10% showed hepatic platelet sequestration. Platelet lifespan and production indices were less reliable parameters, due to numerous contradictory results, especially when compared with the location of platelet sequestration. Distribution of bleeding and therapy-resistant patients was dominant with mixed sequestration. Good therapy responders had dominant splenic sequestration. In the chronic phase of the disease, initial therapy was sufficient for 40–45% of patients, while another 25% required second-line therapy, regardless of platelet sequestration location. A total of 25% percent of patients had undergone splenectomy, and all of them were in stable remission. The remaining 10%, which represented the most severe cases, required all available therapies, had equally mixed and liver sequestration, and splenectomy showed no effect. Conclusions: APK may be a determining factor for the selection of splenectomy as a therapeutic option in case of predominantly splenic sequestration. Although the platelet production index has been explored in several studies, its clinical relevance remains controversial. In our findings, it did not contribute to therapeutic decision-making and may even lead to misinterpretation. The factors distinguishing the minority of bleeding and therapy-resistant patients with similar laboratory profiles remain unclear. Full article

Background/Objectives: Maternal thrombocytopenia, affecting approximately 10% of pregnancies, may be physiological (e.g., gestational thrombocytopenia) or pathological (e.g., immune thrombocytopenic purpura, aplastic anemia, preeclampsia, systemic lupus erythematosus). While gestational thrombocytopenia is typically benign, its severity and etiology may impact maternal and neonatal outcomes. This study examined the association between severe and moderate thrombocytopenia during pregnancy and perinatal outcomes, focusing on maternal hemorrhage and neonatal thrombocytopenia. Methods: A retrospective analysis was conducted of 182 pregnant women with thrombocytopenia who delivered at Incheon St. Mary’s Hospital and Seoul St. Mary’s Hospital between 2009 and 2019. Participants were classified into two groups: severe thrombocytopenia (platelet count <50 × 10⁹/L) and moderate thrombocytopenia (50–150 × 10⁹/L). Maternal hemorrhagic outcomes, transfusion needs, and neonatal platelet counts were evaluated. Statistical analyses were performed using univariate methods. Results: Severe thrombocytopenia was associated with greater blood loss during delivery, increased transfusion requirements, and elevated neonatal thrombocytopenia rates. Moderate to severe thrombocytopenia was more frequently identified in neonates delivered by mothers with immune thrombocytopenic purpura than in those delivered by mothers with gestational thrombocytopenia. Conclusions: Both the severity and etiology of maternal thrombocytopenia significantly affect the risk of maternal hemorrhage and neonatal thrombocytopenia. Careful prenatal assessment is essential to optimize management and reduce complications. Full article

Background/Objectives: Chronic idiopathic thrombocytopenic purpura (chITP) is an autoimmune disease which develops in 10–30% of patients with newly diagnosed idiopathic thrombocytopenic purpura (ndITP). It is defined as thrombocytopenia which lasts longer than 12 months, with extremely diverse clinical expressions. The aim is to present the most significant clinical and laboratory characteristics of children with chITP. Methods: This is retrospective, observational research, which included children between 2–18 years with chITP who were treated in the Republic of Serbia for 25 years. We analyzed clinical data from personal and family medical histories and different laboratory analyses. Results: The total number of respondents was 152, with female predominance (F:M = 1.27:1) and mild predominance of adolescents. Of the patients, 15% were asymptomatic, but 15% had periodically life-threatening bleeding. Transfusion was not required for 70% of patients. Thirty-five percent of patients had chITP alone, and 45% had high titer levels of autoantibodies. The most frequent comorbidity was Hashimoto thyroiditis (15%). The same percentage (45%) of family members were reported with and without autoimmune diseases. Twenty-five percent of patients were resistant to initial therapy. Helicobacter pylori was detected in 20%, 70% had higher levels of lactate dehydrogenase (LDH), three patients had sufficient serum vitamin D levels, splenomegaly was found in 25%, and accessory spleen in 14% of patients. Around 50% of patients had a platelet count between 20–50 × 10⁹/L, and 40% below 20 × 10⁹/L. Mean platelet volume (MPV) was 10.6 ± 1.4 fL. No dysplastic changes were noted in bone marrow aspirate. Initial first-line therapy was sufficient for 45% of patients, second-line therapy was administered in 25%, splenectomy was performed in 20%, and 10% received all available treatments. Conclusions: The severe clinical form of pediatric chITP is accompanied by a low platelet count, the presence of autoimmune comorbidities, a positive family medical history, resistance to initial therapy, hypovitaminosis D, and rare megakaryocytes in the bone marrow. Full article

Odontogenic myxoma (OM) is a rare, benign intraosseous tumor that arises from the dental follicle, dental papilla, or periodontal ligament. It typically affects the mandible, maxilla, and sinuses, more frequently in women than men. The histopathology of OM is characterized by a myxoid stroma with varying degrees of collagenization and spindle cells. Treatment is surgical, but there are no standardized guidelines. Available options include enucleation and curettage, with conservative approaches offering better aesthetics and functionality but a higher recurrence risk. This case report aims to discuss a rare presentation of OM in the anterior part of the mandible of a 22-year-old female patient with Hashimoto’s thyroiditis and idiopathic thrombocytopenic purpura. The patient presented with painless swelling and tooth mobility in the symphysis region. Radiographic evaluation revealed a unilocular lesion extending from the left second incisor to the right first incisor, with no root resorption. Histopathological analysis confirmed the OM diagnosis. Due to the patient’s young age and the size of the lesion, a conservative treatment approach was chosen, with the potential for future implant-prosthodontics rehabilitation. The case underscores the importance of thorough clinical, radiological, and histopathological assessment to ensure accurate diagnosis and management of OM. Long-term follow-up is essential due to the increased risk of recurrence in younger patients. Full article

Flow cytometry plays a fundamental role in the diagnosis of leukemias and lymphomas, as well as in the follow-up and evaluation of minimally measurable disease after treatment. In some instances, such as in the case of acute promyelocytic leukemia (APL), rapid diagnosis is required to avoid death due to serious blood clotting or bleeding complications. Given that promyelocytes do not express the glycophosphatidylinositol (GPI)-anchored protein CD16 and that deficient CD16 expression is a feature of some CD16 polymorphisms and paroxysmal nocturnal hemoglobinuria (PNH), we included the GPI anchor probe FLAER aerolysin in the APL flow cytometry probe panel. Initial tests showed that FLAER binding was absent in pathological promyelocytes from APL patients but was consistently detected with high intensity in healthy promyelocytes from control bone marrow. FLAER binding was studied in 71 hematologic malignancies. Appropriate control cells were obtained from 16 bone marrow samples from patients with idiopathic thrombocytopenic purpura and non-infiltrated non-Hodgkin’s lymphoma. Compared with the positive FLAER signal in promyelocytes from healthy bone marrow, malignant promyelocytes from APL patients showed weak or negative FLAER binding. The FLAER signal in APL promyelocytes was also lower than that in control myeloid progenitors and precursors from patients with other forms of acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia, or myelodysplastic syndrome. Minimal measurable disease studies performed in APL patients after treatment found normal promyelocyte expression when minimal measurable disease was negative and FLAER-negative promyelocytes when disease relapse was detected. The inclusion of FLAER in the flow cytometry diagnosis and follow-up of APL could be very helpful. Decreased FLAER binding was found in all cases of APL, confirmed by the detection of the PML-RARA fusion transcript and, to a lesser extent, in the other AMLs studied. This study also revealed FLAER differences in other acute leukemias and even between different precursors (myeloid and lymphoid) from healthy controls. However, the reason for FLAER’s non-binding to the malignant precursors of these leukemias remains unknown, and future studies should explore the possible relation with an immune escape phenomenon in these leukemias. Full article

Background/objectives: Fostamatinib is a spleen tyrosine kinase (SYK) inhibitor approved for the treatment of adult patients with chronic immune thrombocytopenia (ITP). There is little information about dose tapering and sustained remission after discontinuation in ITP. In this retrospective multicenter study, we evaluated efficacy and safety of fostamatinib in adult patients with ITP before, during, and after tapering/discontinuation (T/D). Methods: T/D was performed on subjects who achieved complete platelet response (CR) with progressive, conditional dose reduction every four weeks. Results: Sixty-one patients were included from 14 reference centers between October 2021 and May 2023. In subjects that completed T/D (n = 9), the median time from treatment initiation to response was 21 days (IQR: 7.5–42), median time from treatment initiation to CR was 28 days (IQR: 28–42), median time from treatment initiation to the start of tapering was 116 days (IQR: 42–140), and duration of tapering was 112.5 days (IQR: 94.5–191). The median platelet count was 232 × 10⁹/L (IQR: 152–345 × 10⁹/L) at tapering and 190 × 10⁹/L (IQR: 142.5–316.5 × 10⁹/L) at discontinuation. With a median follow-up since discontinuation of 263 days (IQR: 247–313 days), only two patients have relapsed (at 63 and 73 days). Fostamatinib was restarted, achieving a new CR. Platelet counts higher than 100 × 10⁹/L in week 12 were the only positive predictive factors for successful tapering and discontinuation. Conclusions: Sustained response in patient with ITP treated with fostamatinib could be developed. The prognostic factors and recommended scheme of tapering still have to be evaluated. Full article

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy (TMA) related to a severe ADAMTS13 deficiency, the specific von Willebrand factor (VWF)-cleaving protease. This deficiency is often immune-mediated (iTTP) and related to the presence of anti-ADAMTS13 autoantibodies that enhance its clearance or inhibit its VWF processing activity. iTTP management may be challenging at extreme ages of life. International cohorts of people with TTP report delayed diagnoses and misdiagnoses in children and elderly people. Child-onset iTTP shares many features with adult-onset iTTP: a female predominance, an idiopathic presentation, and the presence of neurological disorders and therapeutic strategies. Long-term follow-ups and a transition from childhood to adulthood are crucial to preventing iTTP relapses, in order to identify the occurrence of other autoimmune disorders and psychosocial sequelae. In contrast, older iTTP patients have an atypical clinical presentation, with delirium, an atypical neurological presentation, and severe renal and cardiac damages. They also have a poorer response to treatment and prognosis. Long-term sequelae are highly prevalent in older patients. Prediction scores for iTTP diagnoses are not used for children and have a lower sensitivity and specificity in patients over 60 years old. ADAMTS13 remains the unique biological marker that is able to definitely confirm or rule out the diagnosis of iTTP and predict relapses during follow-ups. Full article

Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and Rho-anti-D antibodies are the commonly used initial treatments for ITP. However, many ITP patients either do not respond or do not maintain a response to initial therapy. Splenectomy, rituximab, and thrombomimetics are the commonly used second-line treatment. More treatment options include tyrosine kinases inhibitors (TKI), including spleen tyrosine kinase (Syk) and Bruton’s tyrosine kinase (BTK) inhibitors. This review aims to assess the safety and efficacy of TKIs. Methods: Literature was searched on PubMed, Embase, WOS, and clinicaltrials.gov using keywords, “tyrosine kinase” and “idiopathic thrombocytopenic purpura”. PRISMA guidelines were followed. Results: In total, 4 clinical trials were included with 255 adult patients with relapsed/refractory ITP. In all, 101 (39.6%) patients were treated with fostamatinib, 60 (23%) patients with rilzabrutinib, and 34 (13%) with HMPL-523. Patients treated with fostamatinib achieved a stable response (SR) and overall response (OR) in 18/101 (17.8%) and 43/101 (42.5%) of the patients, respectively, while SR and OR were achieved in 1/49 (2%) and 7/49 (14%) of the patients, respectively, in the placebo group. Patients treated with HMPL-523 (300 mg dose expansion) achieved an SR and OR in 5/20 (25%) and 11/20 (55%) of the patients, respectively, while SR and OR were achieved in 1/11 (9%) of the patients treated with the placebo. Patients treated with rilzabrutinib achieved an SR in 17/60 (28%) patients. Dizziness (1%), hypertension (2%), diarrhea (1%), and neutropenia (1%) were serious adverse events in fostamatinib patients. Rilzabrutinib or HMPL-523 patients did not require a dose reduction due to drug-related adverse effects. Conclusions: Rilzabrutinib, fostamatinib, and HMPL-523 were safe and effective in the treatment of relapsed/refractory ITP. Full article

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by isolated cryptogenic thrombocytopenia due to a transient or persistent reduction in platelet count. Many patients with ITP have shown improved platelet count after Helicobacter pylori eradication therapy. However, there have been no studies regarding H. pylori in the oral cavity of patients with ITP. Here, we describe a patient with ITP whose oral samples exhibited H. pylori. A 64-year-old woman with ITP came to our hospital with chief complaints that required oral surgery, including tooth extraction and cystectomy. Bacterial DNA from H. pylori was confirmed on the extracted tooth, but was not detected in the saliva taken at the time. Bacterial DNA from H. pylori was detected on the suture around the extraction socket, which was removed at 10 days post-operation. However, H. pylori DNA was not detected in other oral samples at 10 or 30 days post-operation. A urea breath test was carried out in the gastrointestinal clinic at 60 days post-operation, which revealed no presence of H. pylori in the gastrointestinal tract. These results suggest that teeth with severe bacterial infections may be a potential reservoir of H. pylori for patients with ITP. Full article

In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, genetic virus variants are still circulating among vaccinated individuals with different disease symptomatology. Understanding the protective- or disease-associated mechanisms in vaccinated individuals is relevant to advances in vaccine development and implementation. To address this objective, serum-protein profiles were characterized by quantitative proteomics and data-analysis algorithms in four cohorts of uninfected and SARS-CoV-2-infected vaccinated individuals with asymptomatic, non-severe, and severe disease symptomatology. The results show that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective- or disease-associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In non-severe cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins, including the spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2. Full article

With the recent outbreak of the COVID-19 pandemic and emergency use authorization of anti-SARS-CoV-2 vaccines, reports of post-vaccine immune thrombocytopenia (ITP) have gained attention. With this systematic review, we aim to analyze the clinical characteristics, therapeutic strategies, and outcomes of patients presenting with ITP after receiving COVID-19 vaccination. Medline, Embase, and Ebsco databases were systematically explored from inception until 1 June 2022. Case reports and case series investigating the association between the anti-SARS-CoV-2 vaccine and ITP were included. We found a total of 66 patients. The mean age of presentation was 63 years with a female preponderance (60.6%). Sixteen patients had pre-existing ITP. The mean time from vaccine administration to symptom onset was 8.4 days. More ITP events were triggered by mRNA vaccines (BNT162b2 (n = 29) > mRNA-1273 (n = 13)) than with adenoviral vaccines (ChAdOx1-S AstraZeneca (n = 15) > Ad26.COV2-S (n = 9)). Most of the patients were treated with steroids or IVIG, or both. The overall outcome was promising, with no reported deaths. Our review attempts to increase awareness among physicians while evaluating patients presenting with thrombocytopenia after receiving the vaccine. In our solicited opinion, the rarity of these events and excellent outcomes for patients should not change views regarding the benefits provided by immunization. Full article

Idiopathic thrombocytopenic purpura (ITP) is a common hematological disease and the abnormal platelet destruction in the spleen is a critical pathological mechanism for ITP. However, the metabolomic change in the spleen caused by ITP is still unclear. In the present study, the metabolomic information of 18 ITP and 20 normal spleen samples were detected by using ¹H high-resolution magic angle spinning NMR spectroscopy (¹H MAS NMR). Compared with normal spleen, the concentrations of acetate, alanine, glutamine, glycerol, isoleucine, lysine, valine, phenylalanine, leucine, and methanol in ITP spleen tissue were elevated and 3-hydroxybutyric acid, ascorbate, asparagine, ethanol, glycogen, low-density lipoprotein, malonate, myo-inositol, glycerophosphocholine, pyroglutamate, and taurine were decreased. Amino acids metabolic pathways, such as branched-chain amino acids pathway, were identified as the main involved pathways based on enrichment analysis. The decrease in taurine level in the spleen was the most obvious metabolic signature involving ITP with high sensitivity and specificity to distinguish the spleen of ITP from the normal (CI: 0.825–0.982). Notably, the level of taurine in the spleen was negatively correlated with the efficacy of splenectomy (r = 0.622, p = 0.006). Collectively, the data from our study revealed previously unknown ITP-related metabolomic changes in the spleen and found a potential diagnostic and efficacy-predictive biomarker for ITP treatment. Full article

Background: Although platelets, which contain large amounts of phospholipids, play an important role in blood coagulation, there is still no routine assay to examine the effects of platelets in blood coagulation. Methods: Hemostatic abnormalities in patients with thrombocytopenia, including those with idiopathic thrombocytopenic purpura (ITP), were examined using clot wave analysis (CWA)–small-amount tissue-factor-induced FIX activation (sTF/FIXa) and thrombin time (TT). Results: Although there were no marked differences in the three parameters of activated partial thromboplastin time (APTT) between normal healthy volunteers and typical patients with ITP, the peak heights of the CWA-sTF/FIXa were markedly low in patients with ITP. The three peak times of the CWA-sTF/FIXa in patients with a platelet count of ≤8.0 × 10¹⁰/L were significantly longer than those in patients with a platelet count > 8.0 × 10¹⁰/L and the peak heights of the CWA-sTF/FIXa in patients with a platelet count of ≤8.0 × 10¹⁰/L were significantly lower than those in patients with >8.0 × 10¹⁰/L. The peak heights of the CWA-APTT in patients with ITP were significantly lower than in patients with other types of thrombocytopenia. The three peak heights of the CWA-sTF/FIXa in ITP patients were significantly lower than those in patients with other types of thrombocytopenia. The CWA-TT showed lower peak heights and longer peak times in patients with ITP in comparison to patients with other types of thrombocytopenia. Conclusions: The CWA-sTF/FIXa and CWA-TT results showed that blood coagulation is enhanced by platelets and that the blood coagulation ability in ITP patients was low in comparison to healthy volunteers and patients with other types of thrombocytopenia. Full article

The occurrence of chronic myeloid leukemia (CML), or other myeloproliferative diseases, after the development of idiopathic thrombocytopenic purpura (ITP) is very rare in the current medical literature. Considering the advances in ITP management, and the wide use of new drugs for ITP and CML, we report an unusual case with this association. Our case report focused on a 64-year-old man with long-standing ITP treated with eltrombopag, who developed hyperleukocytosis during follow-up; after specific laboratory exams, it was diagnosed as CML and he began treatment with imatinib. The treatment with eltrombopag was balanced with imatinib to stabilize his platelet count. Data on bcr-abl and JAK2 transcripts were collected and revealed an optimal response with the achievement of negativization of both molecular signatures. We could demonstrate that treatment with imatinib and eltrombopag was well tolerated and allowed complete molecular remission of CML to be achieved, as well as of ITP. Full article

Autoimmune disorders are often associated with low platelet count or thrombocytopenia. In immune-induced thrombocytopenia (IIT), a common mechanism is increased platelet activity, which can have an increased risk of thrombosis. In addition, or alternatively, auto-antibodies suppress platelet formation or augment platelet clearance. Effects of the auto-antibodies are linked to the unique structural and functional characteristics of platelets. Conversely, prior platelet activation may contribute to the innate and adaptive immune responses. Extensive interplay between platelets, coagulation and complement activation processes may aggravate the pathology. Here, we present an overview of the reported molecular causes and consequences of IIT in the most common forms of autoimmune disorders. These include idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), drug-induced thrombocytopenia (DITP), heparin-induced thrombocytopenia (HIT), COVID-19 vaccine-induced thrombosis with thrombocytopenia (VITT), thrombotic thrombocytopenia purpura (TTP), and hemolysis, the elevated liver enzymes and low platelet (HELLP) syndrome. We focus on the platelet receptors that bind auto-antibodies, the immune complexes, damage-associated molecular patterns (DAMPs) and complement factors. In addition, we review how circulating platelets serve as a reservoir of immunomodulatory molecules. By this update on the molecular mechanisms and the roles of platelets in the pathogenesis of autoimmune diseases, we highlight platelet-based pathways that can predispose for thrombocytopenia and are linked thrombotic or bleeding events. Full article