Thrombotic complications in patients with cancer: Advances in pathogenesis, prevention, and treatment-A report from ICTHIC 2021.

Venous thromboembolism (VTE) is a common complication in cancer patients, resulting in deep vein thrombosis (DVT) or pulmonary embolism (PE), and is responsible for high morbidity and mortality. This article discusses evidence and future perspectives on pathogenesis and prevention and treatment of thrombotic complications in patients with cancer. In April 2021, international basic researchers and clinicians met for the virtual edition of the 10th International Conference on Thrombosis & Hemostasis Issues in Cancer.

Vascular Imaging in the Asymptomatic High-risk Cancer Population: A Role for Thrombosis Screening and Therapy Management.

Objectives: We retrospectively examined the venous thromboembolism (VTE) events diagnosed in the Prophylaxis of High-Risk Ambulatory Cancer Patients Study (PHACS), a multi-center randomized trial, to assess the value of screening vascular imaging for the diagnosis of incidental VTE in high-risk cancer patients.

Methods: A total of 117 asymptomatic cancer patients with a Khorana score ≥3 starting a new systemic chemotherapy regimen were enrolled in a prospective randomized control trial. Patients underwent baseline venous ultrasound (US) of the lower extremities (LEs) and screening contrast-enhanced chest computed tomography (CT).

American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients.

Background: Venous thromboembolism (VTE) is a common source of perioperative morbidity and mortality.

Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about preventing VTE in patients undergoing surgery.

Methods: ASH formed a multidisciplinary guideline panel balanced to minimize bias from conflicts of interest.

Approach to pancytopenia: Diagnostic algorithm for clinical hematologists.

Pancytopenia is a relatively common phenomenon encountered in clinical practice. The evaluation of a patient with pancytopenia requires a comprehensive approach and identifying the underlying cause can be challenging given the wide range of etiologies including drugs, autoimmune conditions, malignancies, infections, hemophagocytosis, and inheritable conditions. Recent advances in molecular hematology which include genomic profiling and next-generation sequencing have helped gain major insights into various hematological conditions and can guide diagnosing specific diseases in a shorter time at lower costs.

Risk prediction of cancer-associated thrombosis: Appraising the first decade and developing the future.

Cancer-associated venous thromboembolism (VTE) has major consequences for patients, including morbidity and risk of mortality. However, there is substantial variation in risk depending on a multitude of clinical risk factors and many cancer patients are at low risk for VTE. This critical concept of risk variation has led to efforts to identify patients at high or low risk for developing VTE.

Reduced anticoagulation variability in patients on warfarin monitored with Fiix-prothrombin time associates with reduced thromboembolism: The Fiix-trial.

Fiix-prothrombin time (Fiix-PT) differs from traditional PT in being affected by reduced factor (F) II or FX only. In the randomized controlled Fiix-trial, patients on warfarin monitored with Fiix-PT (Fiix-warfarin patients) had fewer thromboembolisms (TE), similar major bleeding (MB) and more stable anticoagulation than patients monitored with PT (PT-warfarin patients). In the current Fiix-trial report we analyzed how reduced anticoagulation variability during Fiix-PT monitoring was reflected in patients with TE or bleeding.

Dalteparin thromboprophylaxis in cancer patients at high risk for venous thromboembolism: A randomized trial.

Background: Ambulatory cancer patients at high-risk for venous thromboembolism (VTE) can be identified using a validated risk score (Khorana score). We evaluated the benefit of outpatient thromboprophylaxis with dalteparin in high-risk patients in a multicenter randomized study.

Methods: Cancer patients with Khorana score≥3 starting a new systemic regimen were screened for VTE and if negative randomized to dalteparin 5000units daily or observation for 12weeks.

Thrombosis in Cancer: Research Priorities Identified by a National Cancer Institute/National Heart, Lung, and Blood Institute Strategic Working Group.

The risk for venous thromboembolism (VTE) is increased in cancer and particularly with chemotherapy, and it portends poorer survival among patients with cancer. However, many fundamental questions about cancer-associated VTE, or Trousseau syndrome, remain unanswered. This report summarizes the proceedings of a working group assembled by the NCI and NHLBI in August 2014 to explore the state of the science in cancer-associated VTE, identify clinically important research gaps, and develop consensus on priorities for future research.

Fiix-prothrombin time versus standard prothrombin time for monitoring of warfarin anticoagulation: a single centre, double-blind, randomised, non-inferiority trial.

Background: Rapid fluctuations in factor VII during warfarin anticoagulation change the international normalised ratio (INR) but contribute little to the antithrombotic effect. We aimed to assess non-inferiority of anticoagulation stabilisation with a warfarin monitoring method affected only by factors II and X (Fiix-prothrombin time [Fiix-PT]) compared with standard PT-INR monitoring that includes factor VII measurement as well.

Methods: The Fiix trial was a single centre, double-blind, prospective, non-inferiority, randomised controlled clinical trial.

Venous thromboembolism prophylaxis and treatment in patients with cancer: american society of clinical oncology clinical practice guideline update 2014.

Purpose: To provide current recommendations about the prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer.

Methods: PubMed and the Cochrane Library were searched for randomized controlled trials, systematic reviews, meta-analyses, and clinical practice guidelines from November 2012 through July 2014. An update committee reviewed the identified abstracts.

Screening high-risk cancer patients for VTE: a prospective observational study.

Background: The utility of screening for venous thromboembolism (VTE) in cancer patients is unknown. We evaluated this in a prospective cohort study of cancer patients initiating a new chemotherapy regimen and deemed high-risk (score ≥3) based on a validated Risk Score.

Methods: Patients were evaluated with baseline and Q4 (±1) week serial ultrasonography for up to 16 weeks; additionally, computed tomography scans for restaging were also evaluated for VTE.

Platelets and cancer-associated thrombosis.

Platelets have a newly appreciated and important role in many cancer-related processes, including tumor growth and metastases, angiogenesis, and promotion of a hypercoagulable state. Cancer patients commonly experience venous thromboembolism (VTE), a leading cause of mortality and a source of considerable morbidity and cost. The role of platelets in arterial thrombosis is well established, but emerging evidence supports the concept that platelets are also involved in initiation of VTE.

Cancer-associated thrombosis.

Cancer-associated thrombosis accounts for almost one-fifth of all cases of venous thromboembolism (VTE) and is a leading cause of death, morbidity, delays in care, and increased costs. Our understanding of risk factors for cancer-associated thrombosis has expanded in recent years, and investigators have begun to use biomarkers and clinical prediction models to identify those cancer patients at greatest risk for VTE. The Khorana Risk Model, which is based on easily obtained biomarkers and clinical factors, has now been validated in several studies.

Isoprostane and isofuran lipid mediators accumulate in stored red blood cells and influence platelet function in vitro.

Background: Stored red blood cells (RBCs) release hemoglobin (Hb) that leads to oxidative damage, which may contribute to thrombosis in susceptible transfusion recipients. Oxidative stress stimulates the generation of a new class of lipid mediators called F2 -isoprostanes (F2 -IsoPs) and isofurans (IsoFs) that influence cellular behavior. This study investigated RBC-derived F2 -IsoPs and IsoFs during storage and their influence on human platelets (PLTs).

Prevalence and clinical significance of incidental and clinically suspected venous thromboembolism in lung cancer patients.

Background: It is unclear what proportion of VTE events in lung cancer patients are incidentally discovered and whether incidental events affect mortality.

Patients And Methods: We conducted a retrospective cohort study of lung cancer patients seen at the University of Rochester between January 1, 2006 and December 31, 2008 with the goal of quantifying and characterizing VTE events. Multiple clinical variables and mortality outcomes were compared using Kaplan-Meier survival analysis and multivariate Cox proportional hazards.

Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update.

Purpose: To provide recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. Prophylaxis in the outpatient, inpatient, and perioperative settings was considered, as were treatment and use of anticoagulation as a cancer-directed therapy.

Methods: A systematic review of the literature published from December 2007 to December 2012 was completed in MEDLINE and the Cochrane Collaboration Library.

Prevention of VTE in patients having major orthopedic surgery.

Venous thromboembolism (VTE) is a serious risk after major orthopedic surgery (MOS) including total knee replacement, total hip replacement and hip fracture surgery. This risk can be reduced with several pharmacologic and mechanical prophylactic approaches, and the choice among them depends on their ability to reduce VTE with an acceptable increase in adverse events, especially major bleeding complications. Improvements in medical and surgical care have led to a progressive decrease in the risk of VTE after MOS with an estimated baseline risk with contemporary practice of approximately 4.

Alterations of platelet function and clot formation kinetics after in vitro exposure to anti-A and -B.

Background: ABO-mismatched platelets (PLTs) are commonly transfused despite reported complications. We hypothesized that because PLTs possess A and B antigens on their surface, ABO-mismatched transfused or recipient PLTs could become activated and/or dysfunctional after exposure to anti-A or -B in the transfused or recipient plasma. We present here in vitro modeling data on the functional effects of exposure of PLTs to ABO antibodies.

Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

Background: VTE is a serious, but decreasing complication following major orthopedic surgery. This guideline focuses on optimal prophylaxis to reduce postoperative pulmonary embolism and DVT.

Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.

Approach to outcome measurement in the prevention of thrombosis in surgical and medical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

This article provides the rationale for the approach to making recommendations primarily used in four articles of the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines: orthopedic surgery, nonorthopedic surgery, nonsurgical patients, and stroke. Some of the early clinical trials of antithrombotic prophylaxis with a placebo or no treatment group used symptomatic VTE and fatal PE to measure efficacy of the treatment. These trials suggest a benefit of thromboprophylaxis in reducing fatal PE.

Pioglitazone inhibits platelet function and potentiates the effects of aspirin: a prospective observation study.

Background: Thiazolidinediones (TZDs) are agonists of PPARγ and exert beneficial metabolic effects in patients with diabetes. They may also affect platelet function.

Objectives: To characterize potential platelet inhibitory effect of pioglitazone alone and in the presence of aspirin.

Critical role of factors II and X during coumarin anticoagulation and their combined measurement with a new Fiix-prothrombin time.

Vitamin K antagonists (VKA) are monitored with prothrombin time (PT) based assays that are equally sensitive to reductions in factors II, VII or X. We compared the effect of vitamin K dependent (VKD) coagulation factors on PT and also on rotational thromboelastometric (ROTEM) parameters. The PT was equally sensitive to reductions in factors II, VII or X but ROTEM parameters correlated poorly with the PT in anticoagulated patients´ plasmas.

Vaginal bleeding in early pregnancy and circulating markers of thrombin generation.

Objective: To determine if subjects experiencing acute vaginal bleeding in early pregnancy have increased plasma markers of thrombin generation compared to nonbleeding controls.

Methods: Subjects with clinically apparent acute (within 24 h of sample collection) vaginal bleeding between 6 and 20 weeks estimated gestational age and without known thrombophilias were enrolled, along with nonbleeding controls, and underwent collection of maternal plasma. Concentrations of thrombin-antithrombin (TAT) and fragment 1 + 2 (F1 + 2) were determined by enzyme-linked immunosorbent assay.