-
Journal of Hematology & Oncology Jan 2023Primary immune thrombocytopenia (ITP) is an immune-mediated bleeding disorder characterized by decreased platelet counts and an increased risk of bleeding. Multiple... (Review)
Review
Primary immune thrombocytopenia (ITP) is an immune-mediated bleeding disorder characterized by decreased platelet counts and an increased risk of bleeding. Multiple humoral and cellular immune abnormalities result in accelerated platelet destruction and suppressed platelet production in ITP. The diagnosis remains a clinical exclusion of other causes of thrombocytopenia. Treatment is not required except for patients with active bleeding, severe thrombocytopenia, or cases in need of invasive procedures. Corticosteroids, intravenous immunoglobulin, and anti-RhD immunoglobulin are the classical initial treatments for newly diagnosed ITP in adults, but these agents generally cannot induce a long-term response in most patients. Subsequent treatments for patients who fail the initial therapy include thrombopoietic agents, rituximab, fostamatinib, splenectomy, and several older immunosuppressive agents. Other potential therapeutic agents, such as inhibitors of Bruton's tyrosine kinase and neonatal Fc receptor, are currently under clinical evaluation. An optimized treatment strategy should aim at elevating the platelet counts to a safety level with minimal toxicity and improving patient health-related quality of life, and always needs to be tailored to the patients and disease phases. In this review, we address the concepts of adult ITP diagnosis and management and provide a comprehensive overview of current therapeutic strategies under general and specific situations.
Topics: Adult; Humans; Blood Platelets; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Thrombocytopenia
PubMed: 36658588
DOI: 10.1186/s13045-023-01401-z -
Blood Jun 2023Neonatal thrombocytopenia, defined as the presence of a circulating platelet count <150 × 109/L, is a common abnormality in babies admitted to neonatal intensive care... (Review)
Review
Neonatal thrombocytopenia, defined as the presence of a circulating platelet count <150 × 109/L, is a common abnormality in babies admitted to neonatal intensive care units. Thrombocytopenia that is typically mild and self-limiting often accompanies neonatal stress in scenarios such as premature delivery or intrauterine growth restriction. However, the differential diagnosis of neonatal thrombocytopenia is wide and includes potentially life-threatening disorders, such as bacterial sepsis, viral infection, and necrotizing enterocolitis. Distinguishing these causes of thrombocytopenia from entities such as genetic thrombocytopenia and fetal and neonatal alloimmune thrombocytopenia is critical for the accurate quantitation of significant adverse events, such as intracranial bleeding, and for the selection of treatments, such as platelet transfusion. In this review, we focus on common differential diagnoses of neonatal thrombocytopenia and highlight how the landscape of diagnosis and management is changing with recent advances in genomic technology and the completion of pivotal clinical trials of platelet transfusion practice. Increasing evidence highlights the need for judicious and restrictive use of platelet transfusions in neonates.
Topics: Humans; Infant, Newborn; Intracranial Hemorrhages; Platelet Count; Platelet Transfusion; Prenatal Care; Thrombocytopenia, Neonatal Alloimmune
PubMed: 36787503
DOI: 10.1182/blood.2022018017 -
Blood Nov 2022Platelet transfusions are commonly administered for the prevention or treatment of bleeding in patients with acquired thrombocytopenia across a range of clinical... (Review)
Review
Platelet transfusions are commonly administered for the prevention or treatment of bleeding in patients with acquired thrombocytopenia across a range of clinical contexts. Recent data, including randomized trials, have highlighted uncertainties in the risk-benefit balance of this therapy, which is the subject of this review. Hemovigilance systems report that platelets are the most frequently implicated component in transfusion reactions. There is considerable variation in platelet count increment after platelet transfusion, and limited evidence of efficacy for clinical outcomes, including prevention of bleeding. Bleeding events commonly occur despite the different policies for platelet transfusion prophylaxis. The underlying mechanisms of harm reported in randomized trials may be related to the role of platelets beyond hemostasis, including mediating inflammation. Research supports the implementation of a restrictive platelet transfusion policy. Research is needed to better understand the impact of platelet donation characteristics on outcomes, and to determine the optimal thresholds for platelet transfusion before invasive procedures or major surgery (eg, laparotomy). Platelet transfusion policies should move toward a risk-adapted approach that does not focus solely on platelet count.
Topics: Humans; Platelet Transfusion; Thrombocytopenia; Hemorrhage; Blood Platelets; Platelet Count
PubMed: 35926105
DOI: 10.1182/blood.2022016558 -
Archivos Argentinos de Pediatria Jun 2021Thrombocytopenia, defined as a platelet count below 100 x 109/L, is a very common finding in the neonatal period, especially in critically ill infants and preterm... (Review)
Review
Thrombocytopenia, defined as a platelet count below 100 x 109/L, is a very common finding in the neonatal period, especially in critically ill infants and preterm newborns. Its causes are multiple: it may be due both to pediatric conditions and to other factors involved in the fetal-placental-maternal interface. This initial article describes the causes of thrombocytopenia, proposes a diagnostic approach to manage a thrombocytopenic newborn infant, and provides a detailed description of the different conditions corresponding to thrombocytopenia of immune etiology. It also describes the different causative mechanisms and reviews the varying characteristics of thrombocytopenia secondary to maternal immune thrombocytopenia and neonatal alloimmune thrombocytopenia. The different treatment approaches to each of the different conditions are described both for their pre- as well as their postnatal management. The severity of thrombocytopenia and the serious complications and sequelae associated with the neonatal alloimmune thrombocytopenia are highlighted.
Topics: Diagnosis, Differential; Female; Humans; Infant; Infant, Newborn; Placenta; Platelet Count; Pregnancy; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia, Neonatal Alloimmune
PubMed: 34033425
DOI: 10.5546/aap.2021.eng.e202 -
Haematologica Jun 2022Chemotherapy-induced thrombocytopenia (CIT) is a common complication of the treatment of non-hematologic malignancies. Many patient-related variables (e.g., age, tumor...
Chemotherapy-induced thrombocytopenia (CIT) is a common complication of the treatment of non-hematologic malignancies. Many patient-related variables (e.g., age, tumor type, number of prior chemotherapy cycles, amount of bone marrow tumor involvement) determine the extent of CIT. CIT is related to the type and dose of chemotherapy, with regimens containing gemcitabine, platinum, or temozolomide producing it most commonly. Bleeding and the need for platelet transfusions in CIT are rather uncommon except in patients with platelet counts below 25x109/L in whom bleeding rates increase significantly and platelet transfusions are the only treatment. Nonetheless, platelet counts below 70x109/L present a challenge. In patients with such counts, it is important to exclude other causes of thrombocytopenia (medications, infection, thrombotic microangiopathy, post-transfusion purpura, coagulopathy and immune thrombocytopenia). If these are not present, the common approach is to reduce chemotherapy dose intensity or switch to other agents. Unfortunately decreasing relative dose intensity is associated with reduced tumor response and remission rates. Thrombopoietic growth factors (recombinant human thrombopoietin, pegylated human megakaryocyte growth and development factor, romiplostim, eltrombopag, avatrombopag and hetrombopag) improve pretreatment and nadir platelet counts, reduce the need for platelet transfusions, and enable chemotherapy dose intensity to be maintained. National Comprehensive Cancer Network guidelines permit their use but their widespread adoption awaits adequate phase III randomized, placebo-controlled studies demonstrating maintenance of relative dose intensity, reduction of platelet transfusions and bleeding, and possibly improved survival. Their potential appropriate use also depends on consensus by the oncology community as to what constitutes an appropriate pretreatment platelet count as well as identification of patient-related and treatment variables that might predict bleeding.
Topics: Antineoplastic Agents; Humans; Neoplasms; Platelet Count; Platelet Transfusion; Thrombocytopenia
PubMed: 35642485
DOI: 10.3324/haematol.2021.279512 -
Clinical Chemistry and Laboratory... Nov 2019This review evaluates the role of platelets in bleeding risk among patients with hematological disease and thrombocytopenia. Platelets are pivotal in primary hemostasis,... (Review)
Review
This review evaluates the role of platelets in bleeding risk among patients with hematological disease and thrombocytopenia. Platelets are pivotal in primary hemostasis, and possess non-hemostatic properties involved in angiogenesis, tissue repair, inflammation and metastatis. Also, platelets safeguard vascular integrity in inflamed vessels. Overall, bleeding risk depends on the underlying disease, and patients with cancer and platelet count <6-10 × 109/L have a markedly increased bleeding risk, while the platelet count does not correlate with bleeding risk at higher platelet counts. Other factors might affect platelet properties and thus bleeding risk, for example, drugs, low hematocrit, coagulation system impairments or transfusion of dysfunctional donor platelets. For patients with leukemia and immune thrombocytopenia, reduced platelet activation, platelet aggregation, or thrombopoiesis, reflected by the reduced presence of reticulated platelets, are associated with bleeding phenotype. However, mechanistic insight into the cause of reduced platelet function in different thrombocytopenic conditions is sparse, except for some inherited platelet disorders. Promising tools for platelet function studies in thrombocytopenia are flow cytometry and biomarker studies on platelet constituents. An important message from this current paper is that bleeding risk assessment must be tailored to specific patient populations and cannot be applied broadly to all patients with thrombocytopenia.
Topics: Blood Coagulation; Blood Platelets; Blood Transfusion; Female; Hematologic Diseases; Hemorrhage; Hemostasis; Humans; Leukopenia; Male; Platelet Activation; Platelet Aggregation; Platelet Count; Platelet Function Tests; Risk Factors; Thrombocytopenia
PubMed: 31465290
DOI: 10.1515/cclm-2019-0380 -
Frontiers in Immunology 2022Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder featured by increased platelet destruction and deficient megakaryocyte maturation. First-line... (Review)
Review
Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder featured by increased platelet destruction and deficient megakaryocyte maturation. First-line treatments include corticosteroids, intravenous immunoglobulin and intravenous anti-D immunoglobulin. Second-line treatments consist of rituximab, thrombopoietin receptor agonists and splenectomy. Although most patients benefit from these treatments, an individualized treatment approach is warranted due to the large heterogeneity among ITP patients. In addition, ITP patients may relapse and there remains a subset of patients who become refractory to treatments. The management of these refractory patients is still a challenge. This review aims to summarize emerging therapeutic approaches for refractory ITP in several categories according to their different targets, including macrophages, platelets/megakaryocytes, T cells, B cells, and endothelial cells. Moreover, current management strategies and combination regimens of refractory ITP are also discussed.
Topics: Blood Platelets; Endothelial Cells; Humans; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Splenectomy; Thrombocytopenia
PubMed: 36003388
DOI: 10.3389/fimmu.2022.953716 -
Clinical Chemistry and Laboratory... Jun 2020Background As coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression... (Meta-Analysis)
Meta-Analysis Review
Background As coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression towards severe and fatal forms of this illness. In this study we aimed to evaluate the discriminative ability of hematologic, biochemical and immunologic biomarkers in patients with and without the severe or fatal forms of COVID-19. Methods An electronic search in Medline (PubMed interface), Scopus, Web of Science and China National Knowledge Infrastructure (CNKI) was performed, to identify studies reporting on laboratory abnormalities in patients with COVID-19. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe and mortality, i.e. non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate weighted mean difference (WMD) with 95% confidence interval (95% CI) for each laboratory parameter. Results A total number of 21 studies was included, totaling 3377 patients and 33 laboratory parameters. While 18 studies (n = 2984) compared laboratory findings between patients with severe and non-severe COVID-19, the other three (n = 393) compared survivors and non-survivors of the disease and were thus analyzed separately. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly elevated in patients with both severe and fatal COVID-19. Interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease. Conclusions Several biomarkers which may potentially aid in risk stratification models for predicting severe and fatal COVID-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.
Topics: Betacoronavirus; Biomarkers; COVID-19; Coronavirus; Coronavirus Infections; Humans; Inflammation; Interleukin-10; Interleukin-6; Leukocyte Count; Lymphocyte Count; Pandemics; Platelet Count; Pneumonia, Viral; Risk Factors; SARS-CoV-2; Severity of Illness Index
PubMed: 32286245
DOI: 10.1515/cclm-2020-0369 -
International Journal of... 2021Entecavir (ETV) is widely used in the treatment of hepatitis B, but there are only a few reports about entecavir-associated thrombocytopenia, and it is considered as an...
Entecavir (ETV) is widely used in the treatment of hepatitis B, but there are only a few reports about entecavir-associated thrombocytopenia, and it is considered as an immediate response and inappropriate to continue the treatment with other nucleoside analogues. Now, we report the third case, and this case was delayed response and we switched to treatment with tenofovir (TDF). There was a 66-year-old female who was infected with hepatitis B virus (HBV). Her platelet count decreased from 111*10/L to 3*10/L and was prone to gum bleeding and skin ecchymosis after she received ETV treatment for 88 days. As a treatment option, ETV was replaced by TDF immediately, frequent platelets transfusions and thrombopoietin were applied for several days, daily prednisone of 50 mg was concomitantly taken, and then platelet count improved after 10 days. She was diagnosed with entecavir-associated thrombocytopenia after analysis of the temporal relationship and exclusion of other causes of thrombocytopenia by blood and bone marrow examinations. Our case suggested that the platelet count should be monitored regularly in patients during ETV treatment, and it may be a feasible option to choose TDF to maintain antiviral treatment when entecavir-associated thrombocytopenia occurs.
Topics: Aged; Antiviral Agents; Drug Monitoring; Drug Substitution; Female; Glucocorticoids; Guanine; Hepatitis B; Humans; Platelet Count; Platelet Transfusion; Prednisone; Tenofovir; Thrombocytopenia; Treatment Outcome
PubMed: 34823407
DOI: 10.1177/20587384211059676 -
Current Opinion in Hematology Nov 2021This review highlights recent advancements in understanding the regulation of platelet numbers, focusing on mechanisms by which carbohydrates (glycans) link platelet... (Review)
Review
PURPOSE OF THE REVIEW
This review highlights recent advancements in understanding the regulation of platelet numbers, focusing on mechanisms by which carbohydrates (glycans) link platelet removal with platelet production in the bone marrow in health and disease.
RECENT FINDINGS
This review is focused on the role of carbohydrates, specifically sialic acid moieties, as a central mediator of platelet clearance. We discuss recently identified novel mechanisms of carbohydrate-mediated platelet removal and carbohydrate-binding receptors that mediate platelet removal.
SUMMARY
The platelet production rate by megakaryocytes and removal kinetics controls the circulating platelet count. Alterations in either process can lead to thrombocytopenia (low platelet count) or thrombocytosis (high platelet count) are associated with the risk of bleeding or overt thrombus formation and serious complications. Thus, regulation of a steady-state platelet count is vital in preventing adverse events. There are few mechanisms delineated that shed light on carbohydrates' role in the complex and massive platelet removal process. This review focuses on carbohydrate-related mechanisms that contribute to the control of platelet numbers.
Topics: Blood Platelets; Humans; Megakaryocytes; Platelet Count; Polysaccharides; Thrombopoiesis
PubMed: 34605444
DOI: 10.1097/MOH.0000000000000682