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Bone Marrow Transplantation Aug 2021Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic stem cell transplant (HSCT) with high morbidity and... (Review)
Review
Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic stem cell transplant (HSCT) with high morbidity and mortality. The triad of endothelial cell activation, complement dysregulation, and microvascular hemolytic anemia has the potential to cause end organ dysfunction, multiple organ dysfunction syndrome and death, but clinical features mimic other disorders following HSCT, delaying diagnosis. Recent advances have implicated complement as a major contributor and the therapeutic potential of complement inhibition has been explored. Eculizumab has emerged as an effective therapy and narsoplimab (OMS721) has been granted priority review by the FDA. Large studies performed mostly in pediatric patients suggest that earlier recognition and treatment may lead to improved outcomes. Here we present a clinically focused summary of recently published literature and propose a diagnostic and treatment algorithm.
Topics: Child; Complement System Proteins; Hematopoietic Stem Cell Transplantation; Humans; Multiple Organ Failure; Thrombotic Microangiopathies; Transplants
PubMed: 33875812
DOI: 10.1038/s41409-021-01283-0 -
Haematologica Aug 2020The acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder with laboratory findings similar to those of inherited von Willebrand disease. However, unlike... (Review)
Review
The acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder with laboratory findings similar to those of inherited von Willebrand disease. However, unlike the inherited disease, AvWS occurs in persons with no personal and family history of bleeding and is often associated with a variety of underlying diseases, most frequently lymphoproliferative, myeloproliferative and cardiovascular disorders. After the presentation of a typical case, in this narrative review we discuss the more recent data on the pathophysiology, clinical, laboratory and therapeutic aspects of this acquired bleeding syndrome. We chose to focus particularly on those aspects of greater interest for the hematologist.
Topics: Cardiovascular Diseases; Hemorrhage; Hemorrhagic Disorders; Humans; Syndrome; von Willebrand Diseases; von Willebrand Factor
PubMed: 32554559
DOI: 10.3324/haematol.2020.255117 -
Frontiers in Immunology 2023Sepsis is accompanied by thrombocytopenia and the severity of the thrombocytopenia is associated with mortality. This thrombocytopenia is characteristic of disseminated... (Review)
Review
Sepsis is accompanied by thrombocytopenia and the severity of the thrombocytopenia is associated with mortality. This thrombocytopenia is characteristic of disseminated intravascular coagulation (DIC), the sepsis-associated coagulopathy. Many of the pathogens, both bacterial and viral, that cause sepsis also directly activate platelets, which suggests that pathogen-induced platelet activation leads to systemic thrombosis and drives the multi-organ failure of DIC. In this paper we review the mechanisms of platelet activation by pathogens and the evidence for a role for anti-platelet agents in the management of sepsis.
Topics: Humans; Blood Platelets; Disseminated Intravascular Coagulation; Thrombocytopenia; Blood Coagulation Disorders; Sepsis; Anemia
PubMed: 37350961
DOI: 10.3389/fimmu.2023.1210219 -
Medicina (Kaunas, Lithuania) Nov 2020Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia caused by increased platelet destruction and impaired... (Review)
Review
Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia caused by increased platelet destruction and impaired platelet production. First-line therapies include corticosteroids, intravenous immunoglobulin, and anti-D immunoglobulin. For patients who are refractory to these therapies, those who become corticosteroid dependent, or relapse following treatment with corticosteroid, options include splenectomy, rituximab, and thrombopoietin-receptor agonists, alongside a variety of additional immunosuppressive and experimental therapies. Despite recent advances in the management of ITP, many areas need further research. Although it is recognized that an assessment of patient-reported outcomes in ITP is valuable to understand and guide treatment, these measures are not routinely measured in the clinical setting. Consequently, although corticosteroids are first-line therapies for both children and adults, there are no data to suggest that corticosteroids improve health-related quality of life or other patient-related outcomes in either children or adults. In fact, long courses of corticosteroids, in either children or adults, may have a negative impact on a patient's health-related quality of life, secondary to the impact on sleep disturbance, weight gain, and mental health. In adults, additional therapies may be needed to treat overt hemorrhage, but unfortunately the results are transient for the majority of patients. Therefore, there is a need to recognize the limitations of current existing therapies and evaluate new approaches, such as individualized treatment based on the probability of response and the size of effect on the patient's most bothersome symptoms and risk of adverse effects or complications. Finally, a validated screening tool that identifies clinically significant patient-reported outcomes in routine clinical practice would help both patients and physicians to effectively follow a patient's health beyond simply treating the laboratory findings and physical symptoms of ITP. The goal of this narrative review is to discuss management of newly diagnosed and refractory patients with ITP, with a focus on the limitations of current therapies from the patient's perspective.
Topics: Adult; Child; Humans; Neoplasm Recurrence, Local; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Splenectomy; Thrombocytopenia
PubMed: 33266286
DOI: 10.3390/medicina56120667 -
Clinical Interventions in Aging 2023Many epidemiological studies have shown that the incidence of immune thrombocytopenia (ITP) increases after age 60 years and peaks in patients over age 80 years.... (Review)
Review
Many epidemiological studies have shown that the incidence of immune thrombocytopenia (ITP) increases after age 60 years and peaks in patients over age 80 years. Therefore, ITP is a concern for physicians taking care of older patients, especially regarding its diagnosis and management. The diagnostic work-up should exclude other causes of thrombocytopenia and secondary ITP, including myelodysplastic syndrome and drug-induced ITP. The treatment decision is influenced by an increased risk of bleeding, infectious diseases and thrombosis in this population and should take into account comorbidities and concomitant medications such as anticoagulant drugs. First-line treatment is based on short corticosteroids courses and intravenous immunoglobulin, which should be reserved for patients with more severe bleeding complications, with their higher risk of toxic effects as compared with younger patients. Second-line treatment should be tailored to the patient's history, comorbidities and preferences. Preferred second-line treatments are thrombopoietin receptor agonists for most groups and guidelines given their good efficacy/tolerance ratio, but the thrombotic risk is increased in older people. Other second-line options that can be good alternatives depending on the clinical context include rituximab, dapsone, fostamatinib or immunosuppressive drugs. Splenectomy is less often performed but remains an option for fit patients with chronic refractory disease. Emerging treatments such as Syk or Bruton tyrosine kinase inhibitors and FcRn antagonists are becoming available for ITP and may modify the treatment algorithm in the near future. The aim of this review is to describe the particularities of the diagnosis and treatment of ITP in older people, including the response and tolerance to the currently available drugs. We also discuss some situations related to co-morbidities that can frequently lead to adapt the management strategy in older patients.
Topics: Aged; Aged, 80 and over; Humans; Glucocorticoids; Immunoglobulins, Intravenous; Purpura, Thrombocytopenic, Idiopathic; Rituximab; Thrombocytopenia
PubMed: 36726813
DOI: 10.2147/CIA.S369574 -
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 -
Blood Mar 2021Microangiopathic hemolytic anemia (MAHA) with thrombocytopenia, suggests a thrombotic microangiopathy (TMA), linked with thrombus formation affecting small or larger... (Review)
Review
Microangiopathic hemolytic anemia (MAHA) with thrombocytopenia, suggests a thrombotic microangiopathy (TMA), linked with thrombus formation affecting small or larger vessels. In cancer patients, it may be directly related to the underlying malignancy (initial presentation or progressive disease), to its treatment, or a separate incidental diagnosis. It is vital to differentiate incidental thrombotic thrombocytopenia purpura or atypical hemolytic uremic syndrome in cancer patients presenting with a TMA, as they have different treatment strategies, and prompt initiation of treatment impacts outcome. In the oncology patient, widespread microvascular metastases or extensive bone marrow involvement can cause MAHA and thrombocytopenia. A disseminated intravascular coagulation (DIC) picture may be precipitated by sepsis or driven by the cancer itself. Cancer therapies may cause a TMA, either dose-dependent toxicity, or an idiosyncratic immune-mediated reaction due to drug-dependent antibodies. Many causes of TMA seen in the oncology patient do not respond to plasma exchange and, where feasible, treatment of the underlying malignancy is important in controlling both cancer-TMA or DIC driven disease. Drug-induced TMA should be considered and any putative causal agent stopped. We will discuss the differential diagnosis and treatment of MAHA in patients with cancer using clinical cases to highlight management principles.
Topics: Aged; Anemia, Hemolytic; Antineoplastic Agents; Disease Management; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Neoplasms; Organ Transplantation; Thrombotic Microangiopathies
PubMed: 33512445
DOI: 10.1182/blood.2019003810 -
Journal of Thrombosis and Haemostasis :... Jan 2022Prolonged prothrombin time and thrombocytopenia are common in patients with cirrhosis. These parameters do not reflect the overall hemostatic rebalance or bleeding risk... (Review)
Review
Prolonged prothrombin time and thrombocytopenia are common in patients with cirrhosis. These parameters do not reflect the overall hemostatic rebalance or bleeding risk in the periprocedural setting; however, attempts to correct these parameters remain frequent. We review the literature on periprocedural bleeding risk, bleeding risk factors, and the risk and benefits of hemostatic interventions in patients with cirrhosis. We provide guidance recommendations on evaluating bleeding risk in this patient group and management of hemostatic abnormalities in the periprocedural setting.
Topics: Blood Coagulation; Blood Coagulation Disorders; Hemostasis; Humans; Liver Cirrhosis; Thrombocytopenia
PubMed: 34661370
DOI: 10.1111/jth.15562 -
Anaesthesia, Critical Care & Pain... Apr 2020
Topics: Anticoagulants; Heparin; Humans; Thrombocytopenia
PubMed: 32299756
DOI: 10.1016/j.accpm.2020.03.012 -
International Journal of Molecular... Jan 2023Transplant-associated thrombotic microangiopathy (TA-TMA) constitutes a significant contributor to the increased morbidity and mortality after allogenic hematopoietic... (Review)
Review
Transplant-associated thrombotic microangiopathy (TA-TMA) constitutes a significant contributor to the increased morbidity and mortality after allogenic hematopoietic stem cell transplantation (allo-HSCT). TA-TMA is a heterogenous disease, characterized by the triad of endothelial cell activation, complement dysregulation and microvascular hemolytic anemia, which may affect all organs. The lack of consensus diagnostic criteria, along with the common clinical features mimicking other diseases that complicate allo-HSCT, make the diagnosis of TA-TMA particularly challenging. Significant effort has been made to recognize specific risk factors predisposing to the development of TA-TMA and to identify serum biomarkers predicting the development of the disease. With regard to treatment, therapeutic plasma exchange (TPE) has been traditionally used, although with doubtful efficacy. On the other hand, the pivotal role of complement activation in the pathophysiology of TA-TMA has led to the exploration of the therapeutic potential of complement inhibitors in this setting. Eculizumab has been proposed as a first-line therapeutic agent in TA-TMA, owing to the very promising results in both pediatric and adult clinical trials. Pharmacokinetic and pharmacodynamic studies and CH50 levels are of paramount importance in the allo-HSCT setting, as a different dosing schedule (more intensive-in dose and frequency-at the beginning) seems to be required for successful outcomes. Furthermore, Narsoplimab, a MASP-2 inhibitor, recently received a Breakthrough Therapy Designation from the FDA for the treatment of TA-TMA after allo-HSCT. Finally, the decision to withdraw the CNIs, although initially advised by the Bone and Marrow Transplant Clinical Trials Network Committee, remains debatable owing to the controversial results of recent clinical trials. This review summarizes the current updates on pathophysiology, diagnosis and therapeutic approaches and emphasizes future goals and perspectives.
Topics: Adult; Child; Humans; Complement System Proteins; Complement Activation; Hematopoietic Stem Cell Transplantation; Complement Inactivating Agents; Thrombotic Microangiopathies
PubMed: 36674666
DOI: 10.3390/ijms24021159