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Expert Perspective: Hematologic Malignancies and Vasculitis.

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… Blood Coagul Fibrinolysis 2016 ; 27 ( 6 ): 648 – 652 . 26569516 10.1097/MBC.0000000000000446 70 Masciulli A , Ferrari A , Carobbio A , et al. Ruxolitinib for the prevention of thrombosis in polycythemia vera: a systematic review and meta‐analysis . …

Dual Antiplatelet Therapy and Cancer; Balancing between Ischemic and Bleeding Risk: A Narrative Review.

Cardiovascular (CV) events in patients with cancer can be caused by concomitant CV risk factors, cancer itself, and anticancer therapy. Since malignancy can dysregulate the hemostatic system, predisposing cancer patients to both thrombosis and hemorrhage, the administration of dual antiplatelet therapy (DAPT) to patients with cancer who suffer from acute coronary syndrome (ACS) or undergo percutaneous coronary intervention (PCI) is a clinical challenge to cardiologists. Apart from PCI and ACS, other structural interventions, such as TAVR, PFO-ASD closure, and LAA occlusion, and non-cardiac dis

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… Apart from the anticancer therapies, other causes of bleeding in oncologic patients are decreased synthesis of coagulation factors, vitamin K deficiency, excessive fibrinolysis, medication—such as anticoagulation and non-steroidal anti-inflammatory drugs—disseminated intravascular coagulation syndrome …

Al amyloidosis.

UNLABELLED: DEFINITION OF THE DISEASE: AL amyloidosis results from extra-cellular deposition of fibril-forming monoclonal immunoglobulin (Ig) light chains (LC) (most commonly of lambda isotype) usually secreted by a small plasma cell clone. Most patients have evidence of isolated monoclonal gammopathy or smoldering myeloma, and the occurrence of AL amyloidosis in patients with symptomatic multiple myeloma or other B-cell lymphoproliferative disorders is unusual. The key event in the development of AL amyloidosis is the change in the secondary or tertiary structure of an abnormal monoclonal LC,

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… Finally, AL amyloidosis is associated with a risk of potentially serious haemorrhagic complications, resulting from vascular infiltration, sometimes combined with deficit in coagulation factors (mainly in factor X, less commonly in factors V or IX) or with increased fibrinolysis [ 2 , 6 , 7 , 15 - 17 …

Endothelial dysfunction in congenital adrenal hyperplasia due to 21-hydroxylase deficiency: current knowledge and novel biomarkers.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a complex endocrine disorder characterized by impaired cortisol synthesis and androgen excess. Beyond its hormonal and metabolic implications, CAH has been increasingly associated with an elevated risk of cardiovascular complications, including endothelial dysfunction, a critical precursor to atherosclerosis and a risk factor for cardiovascular and metabolic diseases. This review explores the current knowledge on endothelial function in patients with CAH, focusing on the interplay between chronic hormonal imbalanc

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… PAI-1 | A protein that regulates fibrinolysis by inhibiting tissue and urokinase plasminogen activators. | Inhibits fibrinolysis, promotes thrombosis, and enhances vascular inflammation. | PAI-1 levels positively correlate with visceral and subcutaneous adipose tissue ( 38 ). …

EHA Guidelines on Management of Antithrombotic Treatments in Thrombocytopenic Patients With Cancer.

In cancer patients, thrombocytopenia can result from bone marrow infiltration or from anticancer medications and represents an important limitation for the use of antithrombotic treatments, including anticoagulant, antiplatelet, and fibrinolytic agents. These drugs are often required for prevention or treatment of cancer-associated thrombosis or for cardioembolic prevention in atrial fibrillation in an increasingly older cancer population. Data indicate that cancer remains an independent risk factor for thrombosis even in case of thrombocytopenia, since mild-to-moderate thrombocytopenia does n

Postoperative Natural Killer Cell Dysfunction: The Prime Suspect in the Case of Metastasis Following Curative Cancer Surgery.

Surgical resection is the foundation for the curative treatment of solid tumors. However, metastatic recurrence due to the difficulty in eradicating micrometastases remain a feared outcome. Paradoxically, despite the beneficial effects of surgical removal of the primary tumor, the physiological stress resulting from surgical trauma serves to promote cancer recurrence and metastasis. The postoperative environment suppresses critical anti-tumor immune effector cells, including Natural Killer (NK) cells. The literature suggests that NK cells are critical mediators in the formation of metastases i

Hematology

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… formation—fibrin–fibrin crosslinked by factor XIII and platelet–fibrin via GPIIb/IIIa Anticoagulation Pathways Antithrombin binds to thrombin and inhibits it Thrombin binds to thrombomodulin which activates protein C and S to cleave factors Va and VIIIa Factor Xa → tPA (by endothelial cells) → plasmin → fibrinolysis … Also ↑ platelet activation due to complements, tissue damage with ↑ tissue factor, ↓ fibrinolysis → ↑ thrombosis clinical features —hemolysis, thrombosis (hepatic vein, portal vein, splenic vein, renal vein), marrow aplasia, MDS, leukemia, infections, esophageal spasm, sexual dysfunction diagnosis —flow …

Hematology

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… formation—fibrin–fibrin crosslinked by factor XIII and platelet–fibrin via GPIIb/IIIa ANTICOAGULATION PATHWAYS Antithrombin binds to thrombin and inhibits it Thrombin binds to thrombomodulin which activates protein C and S to cleave factors Va and VIIIa Factor Xa → tPA (by endothelial cells) → plasmin → fibrinolysis … Also ↑ platelet activation and endothelial injury due to complement activation, ↑ tissue factor, ↓ fibrinolysis → ↑ thrombosis clinical features —hemolysis, venous thrombosis (hepatic vein, portal vein, splenic vein, renal vein), arterial thrombosis (rarer), marrow aplasia, MDS, leukemia, infections, …

Artificial Intelligence in the Management of Hereditary and Acquired Hemophilia: From Genomics to Treatment Optimization.

Hemophilia, an X-linked bleeding disorder, is characterized by a deficiency in coagulation factors. It manifests as spontaneous bleeding, leading to severe complications if not properly managed. In contrast, acquired hemophilia is an autoimmune condition marked by the development of inhibitory antibodies against coagulation factors. Both forms present significant diagnostic and therapeutic challenges, highlighting the need for advanced genetic, molecular, laboratory, and clinical assessments. Recent advances in artificial intelligence have opened new avenues for the management of hemophilia. M

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… Tranexamic acid combined with recombinant factor VIII increases clot resistance to accelerated fibrinolysis in severe hemophilia A. J. Thromb. Haemost. 2007;5:2408–2414. doi: 10.1111/j.1538-7836.2007.02755.x. 51. …

Septic Hyperinflammation-Is There a Role for Extracorporeal Blood Purification Techniques?

This manuscript investigates the role of extracorporeal blood purification techniques in managing septic hyperinflammation, a critical aspect of sepsis characterized by an uncontrolled immune response leading to multiorgan dysfunction. We provide an overview of sepsis, focusing on the dynamics of immune response, the involvement of neutrophils, and the role of the endothelium in the disease's progression. It evaluates the effectiveness of various blood purification methods, including high-cut-off membranes, high-volume hemofiltration, adsorption techniques, and albumin dialysis, in removing cy

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… The occurrence of DIC in sepsis is attributed to consumptive coagulopathy, driven by system-wide coagulation activation and accompanied by suppressed fibrinolysis. …

The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: "Crafting" a Microenvironment That Matters.

Myeloproliferative Neoplasms (MPN) are acquired clonal disorders of the hematopoietic stem cells and include Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis. MPN are characterized by mutations in three driver genes (JAK2, CALR and MPL) and by a state of chronic inflammation. Notably, MPN patients experience increased risk of thrombosis, disease progression, second neoplasia and evolution to acute leukemia. Extracellular vesicles (EVs) are a heterogeneous population of microparticles with a role in cell-cell communication. The EV-mediated cross-talk occurs via the trafficking of

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… Fibrinolysis. 2015;26:448–453. doi: 10.1097/MBC.0000000000000293. 93. Zhang W., Qi J., Zhao S., Shen W., Dai L., Han W., Huang M., Wang Z., Ruan C., Wu D., et al. Clinical significance of circulating microparticles in pH(-) myeloproliferative neoplasms. Oncol. …

Evans syndrome: clinical perspectives, biological insights and treatment modalities.

Evans syndrome (ES) is a rare and chronic autoimmune disease characterized by autoimmune hemolytic anemia and immune thrombocytopenic purpura with a positive direct anti-human globulin test. It is classified as primary and secondary, with the frequency in patients with autoimmune hemolytic anemia being 37%-73%. It predominates in children, mainly due to primary immunodeficiencies or autoimmune lymphoproliferative syndrome. ES during pregnancy is associated with high fetal morbidity, including severe hemolysis and intracranial bleeding with neurological sequelae and death. The clinical presenta

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… purpura, autoimmune hemolytic anemia, and Evans syndrome Mayo Clin Proc 2003 78 11 1340 1346 14601692 10.4065/78.11.1340 98 Rodella E Pacquola E Bianchini E Ramazzina E Paolini R Consolidation treatment with rituximab induces complete and persistent remission of mixed type Evans syndrome Blood Coagul Fibrinolysis …

Toxicity of CAR T-Cell Therapy for Multiple Myeloma.

BackgroundIdecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are novel chimeric antigen receptor (CAR)-T cell therapies targeting B-cell maturation antigen (BCMA), and both have recently gained approval by the US Food Drug Administration (FDA) for the treatment of relapsed and refractory multiple myeloma (RRMM).SummaryThese therapies offer unprecedented responses in RRMM but present new challenges including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), non-ICANS neurotoxicity, cytopenias, infections, and hypogammaglobul

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… CAR-T-Related Coagulopathies MM patients face an increased risk of coagulation dysfunction with CAR-T, possibly due to an imbalanced coagulation environment, platelet dysfunction, disrupted fibrinolysis, and fibrin polymerization. …

A differential diagnostic model based on immunological evaluation and routine laboratory tests: distinguishing multiple myeloma from other disorders with aberrant immunoglobulin elevation.

ObjectiveDevelop a diagnostic model using common hematological and immunological indicators to assist in the early screening and differential diagnosis of Multiple Myeloma (MM) in clinical settings, reducing the risk of misdiagnosis.MethodsA retrospective analysis was conducted on 274 newly diagnosed and treated MM patients and 137 connective tissue disease patients treated at Zhejiang Provincial People's Hospital from January 2008 to August 2023. Laboratory indicators, including complete blood count, biochemistry, coagulation function, and immunoglobulin markers, were collected. The cohort wa

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… Blood Coagulation Fibrinolysis: Int J Haemostasis Thromb. 2015;26:555–9. 54. Geng C, Yang G, Wang H, Zhang Z, Zhou H, Chen W. The Prognostic Role of Prothrombin Time and Activated Partial Thromboplastin Time in Patients with Newly Diagnosed Multiple Myeloma. …

Development and validation of a novel modified cancer cachexia index in patients with locally advanced gastric cancer undergoing neoadjuvant chemotherapy: a multicenter cohort study.

BACKGROUND: Although the cachexia index (CXI) is a well-established prognostic predictor in gastric cancer (GC) patients, its effectiveness in patients with locally advanced gastric cancer (LAGC) who have undergone neoadjuvant chemotherapy (NACT) remains unclear. METHODS: This multicenter study included 600 LAGC patients treated with NACT from January 2010 to June 2022. A modified CXI was constructed based on Random Forest model, calculated as (post-NACT subcutaneous adipose tissue area at L3) × (post-NACT serum albumin)/(post-NACT platelet count) . Patients were categorized into mCXI-low and

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… Coagulation and fibrinolysis in gastric cancer . Ann N Y Acad Sci 2017 ; 1404 : 27 – 48 . 28833193 10.1111/nyas.13454 [45] Zhang Y Liu N Liu C . High fibrinogen and platelets correlate with poor survival in gastric cancer patients . …

Renal Involvement in Mixed Cryoglobulinemic Vasculitis: Current Perspectives.

Cryoglobulinemia is a rare disorder characterized by the presence of abnormal proteins (cryoglobulins) in the blood that precipitate at low temperatures. It presents with a wide clinical spectrum, from mild symptoms to severe, life-threatening disease. In mixed cryoglobulinemia (MC), vascular damage results from immune complexes-typically monoclonal IgM with rheumatoid factor activity and polyclonal IgG (Type II), or polyclonal/oligoclonal IgM and IgG (Type III). These complexes can obstruct small blood vessels, leading to ischemia and leukocytoclastic vasculitis. Renal involvement occurs in a

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… Although only case reports and retrospective studies are available, thrombotic manifestations and the evidence of defects in the fibrinolysis process suggest the potential role of anticoagulants and fibrinolytics in selected patients with cryofibrinogenemia [ 33 , 52 ]. 9.1. …

Novel Insights in Venous Thromboembolism Risk Assessment Methods in Ambulatory Cancer Patients: From the Guidelines to Clinical Practice.

Many cancer patients will experience venous thromboembolism (VTE) at some stage, with the highest rate in the initial period following diagnosis. Novel cancer therapies may further enhance the risk. VTE in a cancer setting is associated with poor prognostic, a decreased quality of life, and high healthcare costs. If thromboprophylaxis in hospitalized cancer patients and perioperative settings is widely accepted in clinical practice and supported by the guidelines, it is not the same situation in ambulatory cancer patient settings. The guidelines do not recommend primary thromboprophylaxis, exc

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… Fibrinolysis 2023 34 70 74 10.1097/MBC.0000000000001159 35946469 67. Cella C.A. Di Minno G. Carlomagno C. Arcopinto M. Cerbone A.M. Matano E. Tufano A. Lordick F. De Simone B. Muehlberg K.S. …

Investigation of the efficacy and safety of eltrombopag to correct thrombocytopenia in moderate to severe dengue patients - a phase II randomized controlled clinical trial.

BACKGROUND: The dengue-infected patients with or without hemorrhagic manifestations, typically exhibit moderate to severe thrombocytopenia. A thrombopoietin receptor agonist - eltrombopag has been efficacious in correcting thrombocytopenia in patients with various pathological conditions including immune thrombocytopenia, chronic liver disease, and severe aplastic anemia. This study investigated the efficacy and safety of eltrombopag to correct dengue-mediated thrombocytopenia. METHODS: In this open-label, randomized controlled phase-II trial, patients with dengue fever (DF) and dengue hemorr

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… Thrombocytopenia in dengue: interrelationship between virus and the imbalance between coagulation and fibrinolysis and inflammatory mediators. Mediat Inflamm. 2015;2015 doi: 10.1155/2015/313842. 12. Hottz E.D., Oliveira M.F., Nunes P.C. …

The Role of Complement Activating Collectins and Associated Serine Proteases in Patients With Hematological Malignancies, Receiving High-Dose Chemotherapy, and Autologous Hematopoietic Stem Cell Transplantations (Auto-HSCT).

We conducted a prospective study of 312 patients (194 with multiple myeloma, 118 with lymphomas) receiving high-dose conditioning chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT). Polymorphisms of MBL2 and MASP2 genes were investigated and serial measurements of serum concentrations of mannose-binding lectin (MBL), CL-LK collectin and MASP-2 as well as activities of MBL-MASP-1 and MBL-MASP-2 complex were made. Serum samples were taken before conditioning chemotherapy, before HSCT and once weekly after (totally 4-5 samples); in minority of subjects also 1 and/or 3

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… Novel evidence that crosstalk between the complement, coagulation and fibrinolysis proteolytic cascades is involved in mobilization of hematopoietic stem/progenitor cells (HSPCs) . Leukemia ( 2014 ) 28 : 2148 – 54 . 10.1038/leu.2014.115 24667943 PMC4177021 61. …

Identifying novel genes and biological processes relevant to the development of cancer therapy-induced mucositis: An informative gene network analysis.

Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway A

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… Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis. 2010;21(1):28–34. doi: 10.1097/MBC.0b013e32833135e9 . 51. Fidlerova J, Kleiblova P, Bilek M, Kormunda S, Formankova Z, Novotny J, et al. …