Speakers
Jennifer R. Green, MD, Assistant Professor of Medicine, Deptartment of Medicine, Vanderbilt School of Medicine, Nashville, TN
Summary
Patient at risk: some variables are considered from different bleeding assessment scores; these patients can predispose to bleeding on anticoagulation; the challenge in listing multiple variables is assessment becomes clinically cumbersome and difficult to use; when using bleeding assessment score, ensure the patient matches the bleeding risk assessment score used (eg, do not use score for patient with venous thromboembolism when assessing patient with acute atrial fibrillation)
Anemia: it is observed in people who have already exhibited bleeding and tend to rebleed; if there is an anatomic abnormality identified, microscopic bleeding could be converted into macroscopic bleeding, with the addition of a blood thinner
Risks for bleeding: malignancy, hypertension, and a history of bleeding were identified at the American Society of Hematology’s 2019 annual meeting as risks for bleeding with the re-initiation of anticoagulation after an interruption for perioperative patients on direct oral anticoagulants (DOACs); hypertension continues to emerge throughout the literature as a modifiable risk factor for hemorrhagic and ischemic cerebrovascular accidents
Chronic kidney and hepatic disease: appear through many bleeding risk assessment scores, and are relevant to patients with congenital bleeding disorders
Assessment of benefit and risk: it is important to note that assessment of benefit and risk changes over time; risk for patients with, eg, an intracranial hemorrhage and who cannot be anticoagulated may change in 2 wk when hemostasis has been achieved; thus reassessment provides an opportunity to rebalance the risks and benefits in individual patients
An algorithmic approach to minimizing bleeding risk: includes the choice of whether to change the decision about anticoagulation, the duration of anticoagulation, the safest choice of the drug, and the monitoring needed throughout their anticoagulation duration to make it a highly safe treatment approach
Inferior vena cava (IVC) filters: these filters are valuable; they are indicated in a patient who cannot be anticoagulated and has typically a lower extremity deep vein thrombosis (DVT) that is high risk, and has an, eg, intracranial hemorrhage, very large gastrointestinal (GI) bleed; the American Society of Clinical Oncology (ASCO) recommended against its use in a chronic thrombosis setting in a venous thromboembolism (VTE) that is >4 wk old, and for temporary interruption; only retrievable filters should be used and they should be taken out as soon as the patient gets back on an anticoagulant
Duration of anticoagulation: for provoked VTEs, the patient is anticoagulated for 3 mo in the absence of an ongoing risk factor; conversely, for unprovoked VTEs, a decision needs to be taken at 3 mo as to whether the benefit of long-term anticoagulation is outweighed by the risk of bleeding; thoughtful reassessment is very crucial
VTE bleed: is a 6-variable score that is used to estimate risks for major bleeding during long-term anticoagulation; high-risk patients identified in data set had a 4-fold increased risk for bleeding; this score has been validated in the direct thrombin inhibitors, vitamin K antagonists, and factor 10a inhibitors for edoxaban and rivaroxaban as a useful score; further validation is warranted in a prospective real-world cohort; besides, this score is weighted toward 2 points for active cancer defined as a diagnosis or treatment for active malignancy in the past 6 mo
DOACs and strategies to minimize risks: chronic renal or hepatic dysfunction increases risk when using DOACs; apixaban and rivaroxaban, in particular, are metabolized by the liver and excreted by the kidney; ≈67% of rivaroxaban and 27% of apixaban are excreted renally; apixaban is authorized for use in end-stage renal disease with dialysis (2.5-mg dosing preferred vs 5-mg dosing; needs additional study)
Chronic pain and the use of nonsteroidal anti-inflammatory drugs (NSAIDs): can be very challenging for some patients with chronic arthritis when they are given an anticoagulant and are told they must discontinue their chronic NSAIDs; alternative opportunities for the patients include neuropathic pain management, Tai chi, or sometimes narcotics; alcohol abuse or use can cause thrombocytopenia, and cirrhosis has its physiologic predisposition to bleeding and clotting
Body mass index: some concerns were raised about using the DOACs in patients weighing >120 kg; warfarin sometimes used for patients who weigh >120 kg; however, some significant drug-drug interaction that occurs with the DOACs and human immunodeficiency virus medicines might impact the clinical practice; besides, an increased risk for GI bleeding might occur with DOACs in those with anatomic abnormalities of the gut
Laboratory monitoring of DOACs: in 2018, the Joint Commission issued a National Patient Safety Goal regarding monitoring; this has been interpreted as every 6 mo renal and hepatic function monitoring is required for patients who have normal creatinine clearance and every 3 mo for those who have a borderline creatinine clearance
Warfarin: hypertension is a significant modifiable risk factor as the central nervous system (CNS) bleeding rate is slightly higher with warfarin than with DOACs; centralized anticoagulation monitoring services have good outcomes; avoid excess alcohol and consider opportunities for tissue repair; the commonly used selective serotonin reuptake inhibitors (SSRIs) have antiplatelet activity that does not cause clinical bleeding, but can lead to some mucosal bruising and epistaxis in patients with other risk factors (eg, bleeding disorders, use of anticoagulants)
Mitigation of risk for patients with cancer: the ASCO guidelines were recently updated to include edoxaban and rivaroxaban as treatments for VTE, but apixaban and dabigatran were excluded because of limited published data; an increased risk for GI bleeding in GI malignancies was observed in DOACs cases, and this was across all subsets of GI malignancies; rivaroxaban has been used in patients with primary CNS malignancies who develop an acute symptomatic DVT; a recent study showed that patients taking DOACs had no intracranial hemorrhage within 12 mo; it is considered DOACs might be safer than low molecular weight heparin in patients with primary CNS tumor; ASCO recommends that anticoagulation should be offered to patients who have primary CNS malignancy and an established VTE
Bariatric surgery: can influence drug levels; reduced caloric intake can affect bioavailability; rivaroxaban needs concurrent food administration for optimal bioavailability; decreased surface area for absorption and alkaline pH could impact medications (eg, dabigatran); location of drug absorption can possibly predict the effect on their pKa values; apixaban may primarily undergo gastric absorption in the small intestine, and a small amount possibly in the ascending colon; for dabigatran, the lower stomach and duodenum; for edoxaban, it is predominantly proximal small intestine; warfarin is proximal small intestine; vitamin K antagonist is preferred in patients who have had bariatric surgery; diluted thrombin time helps to decide whether bleeding patients should receive a hemostatic reversal agent or whether they need surgery; ecarin clotting time, ecarin chromogenic assay, and anti-factor Xa assay are used to measure therapeutic drug levels to determine if on-therapy or above-therapy levels are present
Readings
Balabhadra S et al. Association of inferior vena cava filter placement with rates of pulmonary embolism in patients with cancer and acute lower extremity deep venous thrombosis. JAMA Netw Open. 2020;3:e2011079. Published 2020 Jul 1. doi:10.1001/jamanetworkopen.2020.11079; Buchwald H et al. Bariatric surgery: a systematic review and meta-analysis [published correction appears in JAMA. 2005 Apr 13;293(14):1728]. JAMA. 2004;292:1724-1737. doi:10.1001/jama.292.14.1724; de Oliveira Manoel AL et al. The critical care management of spontaneous intracranial hemorrhage: a contemporary review. Crit Care. 2016;20:272; doi:10.1186/s13054-016-1432-0; Lake MB et al. Bleeding and selective serotonin reuptake inhibitors in childhood and adolescence. J Child Adolesc Psychopharmacol. 2000;10:35-38; doi:10.1089/cap.2000.10.35; Silczuk A et al. Thrombocytopenia in patients hospitalized for alcohol withdrawal syndrome and its associations to clinical complications. Alcohol Alcohol. 2019;54:503-509; doi:10.1093/alcalc/agz061; Wang X et al. Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage renal disease on hemodialysis. J Clin Pharmacol. 2016;56:628-636; doi:10.1002/jcph.628.