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. Pathogenic mechanisms, markers and scores for risk assessment, diagnosis and therapy issues, current prophylaxis recommendations, and special settings, such as palliative care, pediatrics, and COVID-19 patients were discussed. Emerging areas of interest in cancer associated VTE are the role of immunotherapy, platelet activation markers, genetic alterations and real-world systems-based approaches to prevention and treatment.

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). Those without preexisting VTE were then randomized into observation or dalteparin prophylaxis groups and were screened with serial US every 4 weeks for up to 12 weeks and imaged with contrast-enhanced chest CT at 12 weeks. Any additional imaging performed during the study period was also evaluated for VTE. RESULTS: Baseline prevalence of incidental VTE was 9% (n = 10) with 58% percent of VTEs diagnosed by screening US. Incidence of VTE in the randomized phase of the trial was 16% (n = 16) with 21% (n = 10) of patients in the control arm and 12% (n = 6) of patients in the dalteparin arm developing VTE, a non-significant 9% absolute risk reduction (HR = 0.69, 95% CI 0.23-1.89). Sixty-nine percent of these patients were asymptomatic with 31% of patients diagnosed by screening US. CONCLUSIONS: Adding screening US to routine oncologic surveillance CT in high-risk ambulatory cancer patients with a Khorana score ≥3 can lead to increased VTE detection, with potential for decreased morbidity, mortality, and health care spending.

Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update.

PURPOSE: To provide updated recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. METHODS: PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs published from August 1, 2014, through December 4, 2018. ASCO convened an Expert Panel to review the evidence and revise previous recommendations as needed. RESULTS: The systematic review included 35 publications on VTE prophylaxis and treatment and 18 publications on VTE risk assessment. Two RCTs of direct oral anticoagulants (DOACs) for the treatment of VTE in patients with cancer reported that edoxaban and rivaroxaban are effective but are linked with a higher risk of bleeding compared with low-molecular-weight heparin (LMWH) in patients with GI and potentially genitourinary cancers. Two additional RCTs reported on DOACs for thromboprophylaxis in ambulatory patients with cancer at increased risk of VTE. RECOMMENDATIONS: Changes to previous recommendations: Clinicians may offer thromboprophylaxis with apixaban, rivaroxaban, or LMWH to selected high-risk outpatients with cancer; rivaroxaban and edoxaban have been added as options for VTE treatment; patients with brain metastases are now addressed in the VTE treatment section; and the recommendation regarding long-term postoperative LMWH has been expanded. Re-affirmed recommendations: Most hospitalized patients with cancer and an acute medical condition require thromboprophylaxis throughout hospitalization. Thromboprophylaxis is not routinely recommended for all outpatients with cancer. Patients undergoing major cancer surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days. Patients with cancer should be periodically assessed for VTE risk, and oncology professionals should provide patient education about the signs and symptoms of VTE.Additional information is available at www.asco.org/supportive-care-guidelines.

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. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic reviews. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 30 recommendations, including for major surgery in general (n = 8), orthopedic surgery (n = 7), major general surgery (n = 3), major neurosurgical procedures (n = 2), urological surgery (n = 4), cardiac surgery and major vascular surgery (n = 2), major trauma (n = 2), and major gynecological surgery (n = 2). CONCLUSIONS: For patients undergoing major surgery in general, the panel made conditional recommendations for mechanical prophylaxis over no prophylaxis, for pneumatic compression prophylaxis over graduated compression stockings, and against inferior vena cava filters. In patients undergoing total hip or total knee arthroplasty, conditional recommendations included using either aspirin or anticoagulants, as well as for a direct oral anticoagulant over low-molecular-weight heparin (LMWH). For major general surgery, the panel suggested pharmacological prophylaxis over no prophylaxis, using LMWH or unfractionated heparin. For major neurosurgery, transurethral resection of the prostate, or radical prostatectomy, the panel suggested against pharmacological prophylaxis. For major trauma surgery or major gynecological surgery, the panel suggested pharmacological prophylaxis over no prophylaxis.

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. However the approach to manage patients with pancytopenia in the current era of genomics is not well defined in the literature and is widely variable in practice. Herein, we conducted a systematic review to help devise an algorithm and management approach for pancytopenia, which serves as a general consultative approach.

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. Our research group and others have focused on understanding and predicting risk of cancer-associated VTE. This narrative review describe research efforts conducted over the past decade, beginning with the 2008 publication of the first validated risk assessment tool in this setting. We describe current applications of the "Khorana score" including identification of high- and low-risk patients, selecting and excluding patients for thromboprophylaxis and screening high-risk patients for early detection of VTE. New approaches to risk prediction including precision medicine and next-generation sequencing are discussed. Finally, we offer suggestions on improving the field of risk prediction in this setting in the near future.

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. Data from 1143 randomized patients was used. We analyzed the groups for anticoagulation intensity (time within target range; TTR), international normalized ratio (INR) variability (variance growth rate B1; VGR) and dose adjustment frequency. We assessed how these parameters associated with clinically relevant vascular events (CRVE), ie TE or MB or clinically relevant non-MB. TTR was highest in Fiix-warfarin patients without CRVE (median 82%;IQR 72-91) and lowest in PT-warfarin patients with TE (62%;56-81). VGR was lowest in Fiix-warfarin patients without CRVE (median VGR B1 0.17; 95% CI 0.08-0.38) and with TE (0.20;0.07-0.26) and highest in PT-warfarin patients with TE (0.50;0.27-0.90) or MB (0.59;0.07-1.36). The mean annual dose adjustment frequency was lowest in Fiix-warfarin patients with TE (mean 5.4;95% CI 3.9-7.3) and without CRVE (mean 6.0; 5.8-6.2) and highest in PT-warfarin patients with TE (14.2;12.2-16.3). Frequent dose changes predicted MB in both study arms. Compared to patients monitored with PT, high anticoagulation stability in Fiix-warfarin patients coincided with their low TE rate. Those with bleeding had high variability irrespective of monitoring method. Thus, although further improvements are needed to reduce bleeding, stabilization of anticoagulation by Fiix-PT monitoring associates with reduced TE.

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. Subjects were screened with lower extremity ultrasounds every 4weeks on study and with chest CT at 12weeks. The primary efficacy endpoint was all VTE over 12weeks and primary safety endpoint was clinically relevant bleeding events over 13weeks. The study was terminated early due to low accrual. RESULTS: Of 117 enrolled patients, 10 (8.5%) had VTE on baseline screening and were not randomized. Of 98 randomized patients, VTE occurred in 12% (N=6/50) of patients on dalteparin and 21% (N=10/48) on observation (hazard ratio, HR 0.69, 95% CI 0.23-1.89). Major bleeding was similar (N=1) in each arm but clinically relevant bleeding was higher in dalteparin arm (N=7 versus 1 on observation) (HR=7.0, 95% CI 1.2-131.6). There was no difference in overall survival. CONCLUSIONS: Thromboprophylaxis is associated with a non-significantly reduced risk of VTE and significantly increased risk of clinically relevant bleeding in this underpowered study. The Khorana score successfully identifies patients with high incidence of VTE both at baseline and during treatment. Future studies should continue to focus on risk-adapted approaches to reduce the burden of VTE in cancer. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00876915.

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. Representing a convergence of research priorities between the two NIH Institutes, the workshop addressed epidemiologic, basic science, clinical, and translational issues in cancer-associated VTE. Cancer Res; 76(13); 3671-5. ©2016 AACR.

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. Ambulatory adults on warfarin with an INR target of 2-3 managed by an anticoagulation dosing service using software-assisted dosing at the National University Hospital of Iceland, Reykjavik, Iceland, were eligible for inclusion in this study. We excluded patients undergoing electroconversion and nursing home residents. Patients were randomly assigned (1:1) to either the Fiix-PT monitoring group or the PT monitoring group by block randomisation. A blinded research INR (R-INR) based on results of the respective test was reported to the dosing staff. Participants were contacted by a study nurse at 4-week intervals to elicit information about thromboembolism or bleeding otherwise unknown to the anticoagulation management centre. The primary efficacy outcome was a composite of objectively diagnosed non-fatal and fatal arterial or venous thromboembolism, including myocardial infarction and transient ischaemic attacks, assessed in all eligible patients who were randomised (intention-to-monitor population). The safety endpoint was major bleeding or other clinically relevant bleeding, assessed in the per-protocol population. We assumed a 3% annual thromboembolism incidence and a non-inferiority margin of 2·5%. This trial is registered with ClinicalTrials.gov, number NCT01565239. FINDINGS: Between March 1, 2012, and Feb 28, 2014, we enrolled 1156 patients. 573 patients were assigned to Fiix-PT and 575 to PT-INR monitoring after exclusion of four patients from each group for various reasons. Median follow-up was 1·7 years (IQR 1·1-1·9). During days 1-720, ten (1·2% per patient year) thromboembolic events occurred in the Fiix-PT group versus 19 (2·3% per patient year) in the PT group (relative risk [RR] 0·52, 95% CI 0·25-1·13; pnon-inferiority<0·0001). Major bleeding occurred in 17 of 571 patients in the Fiix group (2·2% per patient year) versus 20 of 573 patients in the PT group (2·5% per patient year; RR 0·85, 0·45-1·61; pnon-inferiority=0·0034). Anticoagulation stability was improved with Fiix-PT monitoring as manifested by fewer tests, fewer dose adjustments, increased time in range and less INR variability than reported with standard PT monitoring. INTERPRETATION: Monitoring of warfarin with Fiix-PT improved anticoagulation and dosing stability and was clinically non-inferior to PT monitoring. Results from this trial suggest that during vitamin K antagonist treatment INR monitoring could be replaced by Fiix-PT and that this would lead to at least a non-inferior clinical outcome compared with monitoring with PT-INR. FUNDING: Innovation Center Iceland, University of Iceland Science Fund, Landspitali Science Fund and Actavis.

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. RESULTS: Of the 53 publications identified and reviewed, none prompted a change in the 2013 recommendations. RECOMMENDATIONS: Most hospitalized patients with active cancer require thromboprophylaxis throughout hospitalization. Routine thromboprophylaxis is not recommended for patients with cancer in the outpatient setting. It may be considered for selected high-risk patients. Patients with multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or dexamethasone should receive prophylaxis with either low-molecular weight heparin (LMWH) or low-dose aspirin. Patients undergoing major surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days. Extending prophylaxis up to 4 weeks should be considered in those undergoing major abdominal or pelvic surgery with high-risk features. LMWH is recommended for the initial 5 to 10 days of treatment for deep vein thrombosis and pulmonary embolism as well as for long-term secondary prophylaxis (at least 6 months). Use of novel oral anticoagulants is not currently recommended for patients with malignancy and VTE because of limited data in patients with cancer. Anticoagulation should not be used to extend survival of patients with cancer in the absence of other indications. Patients with cancer should be periodically assessed for VTE risk. Oncology professionals should educate patients about the signs and symptoms of VTE.

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. RESULTS: The study population comprised 35 patients. Pancreatic and gastro-esophageal cancers were the most common diagnoses. Of these, 8 (23%) developed a VTE. This included 5 patients with DVT alone (14%), 1 patient with PE alone (3%) and 2 (6%) with both. Ultrasound examinations identified asymptomatic DVT in 9.3% of patients at baseline; 0% at weeks 4 and 8 and 5.6% at week 12. Restaging CT scans identified asymptomatic PE in one patient at week 6 and in one patient at week 9 with subsequent DVT at week 10. CONCLUSIONS: Screening for asymptomatic VTE has not been previously used as a clinical strategy in ambulatory cancer patients. We report that one-tenth of patients at baseline had occult DVT and in this high-risk population, screening at baseline may be of value.

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. This is particularly true in cancer-associated thrombosis as extensive new evidence shows that thrombocytosis and platelet activation are predictive biomarkers of VTE. The role of therapeutic anti-platelet agents has been proven effective at preventing VTE in non-cancer patients, and there are early data suggesting benefit in cancer patients as well. This review summarizes platelet-related predictive biomarkers of cancer-associated thrombosis, platelet-mediated mechanisms for VTE promotion in cancer patients, and anti-platelet agents in prevention of VTE.

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). STUDY DESIGN AND METHODS: F2 -IsoP and IsoF levels in RBC supernatants were measured by mass spectrometry during storage and after washing. The effects of stored supernatants, cell-free Hb, or a key F2 -IsoP, 8-iso-prostaglandin F2α (PGF2α ), on PLT function were examined in vitro. RESULTS: F2 -IsoPs, IsoFs, and Hb accumulated in stored RBC supernatants. Prestorage leukoreduction reduced supernatant F2 -IsoPs and IsoFs levels, which increased again over storage time. Stored RBC supernatants and 8-iso-PGF2α induced PLT activation marker CD62P (P-selectin) expression and prothrombotic thromboxane A2 release. Cell-free Hb did not alter PLT mediator release, but did inhibit PLT spreading. Poststorage RBC washing reduced F2 -IsoP and IsoF levels up to 24 hours. CONCLUSIONS: F2 -IsoPs and IsoFs are produced by stored RBCs and induce adverse effects on PLT function in vitro, supporting a potential novel role for bioactive lipids in adverse transfusion outcomes. F2 -IsoP and IsoF levels could be useful biomarkers for determining the suitability of blood components for transfusion. A novel finding is that cell-free Hb inhibits PLT spreading and could adversely influence wound healing. Poststorage RBC washing minimizes harmful lipid mediators, and its use could potentially reduce transfusion complications.

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. Recent clinical trials of prophylaxis and treatment of VTE in cancer patients are reviewed here. In addition, consensus guidelines and expert opinion regarding management of VTE in specific challenging situations are presented.

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. RESULTS: The study population consisted of 207 subjects with lung cancer. The median age was 66 years and 55% were female (n = 115). Thirty-one patients (14.9%) experienced at least 1 VTE event with 32.2% (10/31) of these incidentally discovered. Incidental events comprised 29.4% (n = 5) of pulmonary embolisms, 11.1% (n = 2) of deep vein thrombosis, and 100% (n = 3) of visceral events. The median survival for patients with incidental VTE was 23.4 months (95% confidence interval [CI], 4.8-32.1) compared with 45.8 months (95% CI, 34.1-56.8) in patients without VTE (HR 2.4; 95% CI, 1.2-4.9; P = .01), but in a subgroup analysis of stage IV patients overall survival was not significantly different (HR, 0.94; P = .33). Patients with clinically suspected VTE had the lowest median survival at 13.1 months (95% CI, 6.4-18.9) which was significantly lower than patients without VTE (HR, 2.7; 95% CI, 1.6-4.5; P = .002), but not significantly different from patients with incidental VTE (HR, 1.2; 95% CI, 0.4-2.0; P = .7). In multivariate analysis, occurrence of VTE (HR, 2.3; 95% CI, 1.3-3.8; P = .002) was significantly associated with mortality when adjusting for age, stage, and histology. CONCLUSIONS: One-third of VTE events in lung cancer patients are incidentally discovered and VTE has negative clinical effect in lung cancer patients.

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. An Update Committee reviewed evidence to determine which recommendations required revision. RESULTS: Forty-two publications met eligibility criteria, including 16 systematic reviews and 24 randomized controlled trials. RECOMMENDATIONS: Most hospitalized patients with cancer require thromboprophylaxis throughout hospitalization. Thromboprophylaxis is not routinely recommended for outpatients with cancer. It may be considered for selected high-risk patients. Patients with multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or dexamethasone should receive prophylaxis with either low-molecular weight heparin (LMWH) or low-dose aspirin. Patients undergoing major cancer surgery should receive prophylaxis, starting before surgery and continuing for at least 7 to 10 days. Extending prophylaxis up to 4 weeks should be considered in those with high-risk features. LMWH is recommended for the initial 5 to 10 days of treatment for deep vein thrombosis and pulmonary embolism as well as for long-term (6 months) secondary prophylaxis. Use of novel oral anticoagulants is not currently recommended for patients with malignancy and VTE. Anticoagulation should not be used for cancer treatment in the absence of other indications. Patients with cancer should be periodically assessed for VTE risk. Oncology professionals should provide patient education about the signs and symptoms of VTE.

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 4.3 % up to day 39 after surgery. Low-molecular-weight heparin is the most thoroughly studied thromboprophylactic agent following MOS and demonstrates good effectiveness with an acceptable rate of bleeding complications. Warfarin, rivaroxaban, dabigatran, and apixaban have all been studied in large trials in comparison with low-molecular-weight heparin and also show an acceptable benefit: risk ratio. Mechanical approaches including graduated compression stockings, intermittent pneumatic compression and venous foot pump also offer protection against VTE, but there is less evidence is available regarding their effectiveness and risks. Combination therapy consisting of an antithrombotic agent and mechanical device is probably more effective than either alone. The appropriate use of thromboprophylaxis after MOS results in reduced VTE with acceptable bleeding risks.

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. STUDY DESIGN AND METHODS: PLT functions of normal PLTs of all ABO types were assessed before and after incubation with normal saline, ABO-identical plasma samples, or O plasma samples with varying titers of anti-A and anti-B (anti-A/B). Assays used for this assessment include PLT aggregation, clot kinetics, thrombin generation, PLT cytoskeletal function, and mediator release. RESULTS: Exposure of antigen-bearing PLTs to O plasma with moderate to high titers of anti-A/B significantly inhibits aggregation, prolongs PFA-100 epinephrine closure time, disrupts clot formation kinetics, accelerates thrombin generation, reduces total thrombin production, alters PLT cytoskeletal function, and influences proinflammatory and prothrombotic mediator release. CONCLUSIONS: Our findings demonstrate a wide range of effects that anti-A/B have on PLT function, clot formation, thrombin generation, PLT cytoskeletal function, and mediator release. These data provide potential explanations for clinical observations of increased red blood cell utilization in trauma and surgical patients receiving ABO-nonidentical blood products. Impaired hemostasis caused by anti-A/B interacting with A and B antigens on PLTs, soluble proteins, and perhaps even endothelial cells is a potential contributing factor to hemorrhage in patients receiving larger volumes of ABO-nonidentical transfusions.