, Olga Goryacheva3PERIOPERATIVE ANTICOAGULATION MANAGEMENT: A HEMATOLOGIST–CARDIOLOGIST PERSPECTIVE ON RISK STRATIFICATION AND THERAPEUTIC DRUG MONITORING
Emmanuel Ifeanyi Obeagu1,2,3*, Olga Goryacheva3
1Division of Haematology, Department of Biomedical and Laboratory Science, Africa University, Mutare, Zimbabwe.
2Department of Molecular Medicine and Haematology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. 3Department of Internal Diseases, Perm State Medical University named after Academician E.A. Wagner, Perm, Russia.
Abstract
Direct oral anticoagulants (DOACs) are widely used for thromboprophylaxis in atrial fibrillation and venous thromboembolism. Their marketing emphasizes predictable pharmacokinetics and no need for routine monitoring. However, the perioperative period exposes critical limitations of this paradigm, especially in high‑risk populations excluded from landmark trials. This narrative review integrates hematology and cardiology perspectives. We critically examined real‑world evidence on perioperative DOAC management, focusing on patients with extreme body weight, renal or hepatic impairment, active malignancy, thrombocytopenia, bariatric surgery, and drug–drug interactions. Guideline recommendations and commercial influences were analyzed. Routine therapeutic drug monitoring (TDM) is unnecessary for low‑risk elective procedures in standard patients. However, selective TDM is essential in high‑risk populations where DOAC pharmacokinetics are unpredictable. We identified specific indications for TDM (extreme body weight, CrCl<50 mL/min, Child‑Pugh B cirrhosis, bariatric surgery, interacting drugs) and provided practical algorithms for elective, urgent and emergency surgery. Low‑Molecular‑Weight heparin (LMWH) is preferred when DOAC pharmacokinetics are unpredictable, including malabsorption syndromes, severe thrombocytopenia, and advanced liver disease. Marketing influences have perpetuated the “no monitoring” dogma despite accumulating evidence of harm in vulnerable subgroups. A one‑size‑fits‑all approach to perioperative anticoagulation is unsafe in complex patients. Selective TDM improves safety in high‑risk scenarios. LMWH remains a preferred alternative when DOAC pharmacokinetics are unpredictable. Clinicians should recognise marketing influences and adopt evidence‑based, individualised strategies.
Keywords: anticoagulants, drug safety, perioperative management, therapeutic drug monitoring, high risk populations.
INTRODUCTION
The introduction of direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban transformed the landscape of anticoagulation1. Fixed dosing, few dietary restrictions, and the absence of routine monitoring offered a welcome alternative to vitamin K antagonists (VKAs). Large randomized controlled trials (RE‑LY, ROCKET AF, ARISTOTLE, ENGAGE AF) established DOACs as first‑line therapy for atrial fibrillation (AF) and venous thrombo-embolism (VTE)2. However, the populations enrolled in these trials were highly selected. Patients with extreme body weight (body mass index [BMI] <18.5 kg/m² or >40 kg/m²), advanced kidney disease (creatinine clearance [CrCl] <30 mL/min), severe liver disease (Child‑Pugh B or C), active malignancy, thrombocytopenia, or prior bariatric surgery were largely excluded3,4. These exclusions leave clinicians without robust evidence for perioperative management in these growing patient groups.
As a haematologist (E.I.O.) and a cardiologist (O.G.), we recognize that haemostasis is not a one‑size‑fits‑all physiology; bleeding and thrombotic risks are dynamic and patient‑specific. Patients with AF often accumulate multiple comorbidities that individually may not contraindicate DOACs but collectively create unpredi-ctable pharmacokinetics. The perioperative period with its inherent bleeding and thrombotic risks is precisely when these vulnerabilities become critical.
This review integrates hematology and cardiology perspectives to provide practical, evidence based framework for perioperative anticoagulation. We identify high risk populations in whom therapeutic drug monitoring (TDM) should be considered, clarify when DOACs are preferred versus low molecular weight heparin (LMWH) or VKAs, and outline situations where anticoagulation should be deferred. We also examine the influence of pharmaceutical marketing on the “no monitoring” narrative and offer guidance grounded in real‑world data.
The “No Monitoring” paradigm: Marketing versus medicine
The statement that DOACs “do not require routine monitoring” was never intended to apply universally. In controlled trial populations, DOACs demonstrated predictable pharmacokinetics with low inter‑individual variability4. However, this statement became a powerful marketing tool that has often been over generalized to all patients, including those with altered physiology.
A growing body of real‑world data demonstrates that the “no monitoring” rule fails in specific high risk subgroups:
These cases underscore that the absence of monitoring does not mean the absence of risk; rather, it means risk is being managed blindly.
Risk stratification: Populations requiring special consideration
1. Extreme body weight
The Problem: obesity (BMI ≥40 kg/m² or weight >120 kg) and underweight (BMI <18.5 kg/m² or weight <60 kg) alter volume of distribution and clearance. Dabigatran shows an inverse correlation with weight, while apixaban and rivaroxaban are more weight neutral23.
Current recommendations: ISTH 2021 - apixaban and rivaroxaban can be used for VTE treatment in patients with BMI <50 kg/m² or weight <150 kg, Dabigatran and edoxaban should be avoided due to insufficient data; ACC/AHA 2023: for patients weighing ≤60 kg, apixaban dose reduction is recommended if also age ≥80 years or creatinine ≥1.5 mg/dL14,15.
Perioperative implications: standard discontinuation protocols apply for elective surgery, but TDM should be considered before high‑bleeding‑risk procedures in patients with BMI >40 or <18.5, especially when other risk factors coexist.
2. Renal Impairment
The Problem: renal clearance varies: dabigatran 80%, edoxaban 50%, rivaroxaban 35%, apixaban 27% [23]. Accumulation increases bleeding risk.
Current recommendations: if CrCl ≥30 mL/min: all DOACs can be used with appropriate dosing (rivaroxaban 15 mg daily for AF, dabigatran 110 mg twice daily)15.
CrCl 15–29 mL/min: apixaban is preferred (2.5 mg twice daily if dose reduction criteria met), Rivaroxaban is FDA‑approved for AF at 15 mg daily. Dabigatran and edoxaban are contraindicated. If CrCl<15 mL/min or dialysis: only apixaban has sufficient data; others should be avoided.
Perioperative implications: for elective surgery, extend discontinuation to 3–4 days when CrCl<50 mL/min. For urgent surgery, TDM is strongly recommended; the Milan study (2026) found that among patients with CrCl<50 mL/min undergoing hip fracture repair, 9.4% had DOAC concentrations >100 ng/mL despite >24 hours since last dose6.
3. Liver cirrhosis
The Problem: cirrhosis creates a hemostatic paradox- prolonged PT/INR suggests bleeding risk, but reduced protein C, protein S, and antithrombin III increase thrombotic risk.
Current recommendations: Child‑Pugh A - DOACs may be used; apixaban and edoxaban have favorable pharmacokinetic profiles. If Child‑Pugh B then avoids rivaroxaban (ACC/AHA); other DOACs may be used with caution. If Child‑Pugh C - all DOACs contra-indicated. Perioperative implications: screen for esophageal varices before elective surgery; ligate if high‑risk. TDM is reasonable for Child‑Pugh B patients undergoing high‑bleeding‑risk procedures19.
4. Bariatric surgery and malabsorption syndromes
The Problem: altered gastrointestinal anatomy reduces DOAC absorption. Data from a 2024 study of bariatric surgery patients showed that 24% of rivaroxaban users and 100% of dabigatran users had concentrations below the expected trough range17.
Recommendations: for patients with a history of bariatric surgery or active malabsorption, DOACs should be used with caution. TDM is essential to confirm therapeutic levels. LMWH may be a safer alternative until adequate absorption is confirmed.
5. Active Malignancy
The Problem: cancer patients have a 12‑ to 23‑fold increased VTE risk and frequently receive interacting drugs (e.g., tyrosine kinase inhibitors [TKIs]) that modulate P‑glycoprotein (P‑gp) and CYP3A413,20.
Current recommendations: Guidelines (ASCO, ISTH, ESC) - DOACs are recommended for VTE treatment in cancer patients without significant drug interactions or gastrointestinal malignancies20.
Gastrointestinal cancers: DOACs are associated with higher bleeding risk and should be used with caution.
Perioperative implications: for cancer surgery, VTE risk is high. DOACs may be used postoperatively when hemostasis is secure. TDM is indicated when patients receive interacting TKIs, have renal impairment, or have had prior bariatric surgery. LMWH remains a safe alternative, particularly in patients with thrombo-cytopenia or gastrointestinal lesions.
6. Thrombocytopenia
The Problem: platelet count <50,000/μL increases bleeding risk with any anticoagulant. Data from the 2023 multicenter Chinese study showed that thrombo-cytopenia alone (platelets <100,000/μL) was not inde-pendently associated with bleeding in multivariate analysis, but the combination of thrombocytopenia and anemia significantly increased bleeding risk (aOR 2.15)16.
Perioperative implications: platelets >100,000/μL - DOACs can be used with caution. Platelets 50,000–100,000/μL - DOACs are possible; dabigatran may have a better safety profile than rivaroxaban. Platelets 30,000–50,000/μL: transition to LMWH (e.g., enoxaparin 0.5 mg/kg once daily). Platelets <30,000/ μL: anticoagulation should be withheld unless absolutely necessary, and mechanical prophylaxis considered8,16.
7. Drug–drug interactions
The Problem: many commonly used medications modulate P‑gp or CYP3A4, affecting DOAC levels. A 2025 systematic review identified 240 DOAC–antineoplastic drug pairs; for 35% of these pairs, at least one source recommended caution or avoidance, with conflicting recommendations across sources13.
High‑risk interactions: 1) strong P‑gp/ CYP3A4 inhibitors (ketoconazole, ritonavir, clarithro-mycin, verapamil): increase DOAC exposure; 2) strong inducers (rifampin, carbamazepine, St. John’s wort): decrease DOAC exposure; 3) tyrosine kinase inhibitors (e.g., ibrutinib, cabozantinib): may inhibit P‑gp, leading to supratherapeutic levels and bleeding13,18.
Perioperative Implications: review all medications, including over‑the‑counter products. TDM is recomm-ended when patients are on interacting drugs, particularly before high‑bleeding‑risk surgery.
Perioperative management: Elective, urgent, and emergency surgery
1. Elective surgery
For elective procedures, standard periprocedural management relies on pharmacokinetic principles and procedure‑specific bleeding risk9. Low‑risk procedures (dental extractions, cataract surgery, skin biopsy) - no interruption or single dose omitted. Moderate/high‑risk procedures (laparotomy, joint replacement, spinal/ epidural anaesthesia): 2 days interruption (≈48 h) for apixaban/rivaroxaban/ edoxaban; 3–4 days for dabigatran.
Role of TDM - routine TDM is not required for elective surgery in patients without additional risk factors. However, in patients with CrCl<50 mL/min, extreme body weight, interacting drugs, or uncertain adherence, TDM should be considered to confirm that residual DOAC levels are <30 ng/mL before high‑bleeding‑risk procedures6.
2. Urgent surgery (e.g., hip fracture)
Urgent surgery (required within 48–72 hours) does not allow standard 2‑ to 4‑day interruption. The 2026 study by Milan et al. provides critical guidance. Key findings6: among patients with CrCl ≥50 mL/min, only 2.0% had DOAC concentrations >100 ng/mL at 24 hours after the last dose;among patients with CrCl<50 mL/min, 9.4% had concentrations >100 ng/mL at 24 hours.
Recommendations: if CrCl ≥50 mL/min and ≥24 hours since last dose: surgery may proceed without TDM; if CrCl<50 mL/min or timing of last dose uncertain: obtain DOAC level. If level <30 ng/mL, proceed; if 30–100 ng/mL, proceed with caution; if >100 ng/mL, consider delay or reversal agent if delay is not possible6.
3. Emergency surgery (life‑ or limb‑threatening)
For emergency surgery where delay is impossible, TDM should be performed if available, but clinical decisions may need to be made empirically.
Reversal options: dabigatran: idarucizumab (Prax- bind) 5 g IV is first‑line if life threatening bleeding or urgent surgery. Factor Xa inhibitors (rivaroxaban, apixaban, edoxaban): andexanet alfa (Andexxa) is indicated for life‑threatening bleeding. However, the 2026 SCA/STS consensus advises against routine use of andexanet alfa before emergency cardiac surgery due to heparin resistance7. If antidotes unavailable, then 4‑factor prothrombin complex concentrate (4F‑PCC) 25–50 IU/kg can be used as a hemostatic agent.TDM thresholds for emergency decision making:<30 ng/mL: safe to proceed with surgery; 30–100 ng/mL - increased bleeding risk; proceed with caution, consider PCC; >100 ng/mL: strong consideration for antidote if available21,22.
When to Avoid DOACs and use LMWH or no anticoagulation
Based on the risk factors discussed, we propose the following guidance:
1. DOACs Preferred (with monitoring if indicated: most patients without the risk factors listed below; Child‑Pugh A cirrhosis; CrCl ≥30 mL/min (with dose adjustment); BMI 18.5–40 kg/m²
2. LMWH Preferred Over DOACs: active cancer with gastrointestinal lesions or high bleeding risk; thrombocytopenia (platelets 30,000–50,000/μL); severe renal impairment (CrCl15–30 mL/min) when apixaban is not available or clinical judgment favors LMWH; bariatric surgery or malabsorption syndromes (at least until TDM confirms therapeutic DOAC levels); pregnancy or breastfeeding; mechanical heart valves - DOACs contraindicated.
3. Anticoagulation withheld (temporary or permanent)
Therapeutic drug monitoring: Indications and interpretation
TDM should be performed using calibrated assays6,10: Anti‑Xa chromogenic assay calibrated for rivaroxaban, apixaban, or edoxaban; diluted thrombin time (dTT) or ecarin clotting time (ECT) for dabigatran.
Indications for TDM:
Interpretation of DOAC levels in the perioperative context (adapted from6):<30 ng/mL- safe for most high‑bleeding‑risk procedures; 30–100 ng/mL - increased bleeding risk; proceed with caution; >100 ng/mL - consider delay, reversal agent, or alternative haemostatic support.
The unspoken influence of marketing on guidelines
The “no monitoring” narrative has been perpetuated by pharmaceutical marketing and has influenced clinical guidelines24. Several recent analyses have highlighted this tension. A 2025 commentary in JAMA Oncology noted that industry sponsored trials often present narratives that may not fully reflect the data, and that regulatory reviews (e.g., FDA) sometimes reveal concerns not evident in published articles24. A 2024 analysis of DOAC guideline disclosures found that a majority of panel members had financial ties to DOAC manufacturers. We believe that guidelines should be interpreted with awareness of these influences. The absence of monitoring is a marketing advantage, but it should not be conflated with clinical safety in complex patients. The real world evidence summarized here demonstrates that selective TDM improves safety in high risk perioperative scenarios.
Practical Algorithms
Algorithm 1: elective surgery
1. Assess procedure bleeding risk.
2. Assess patient risk factors (renal function, weight, liver disease, cancer, interactions, malabsorption).
3. If no risk factors: standard interruption per guidelines; TDM not needed.
4. If ≥1 risk factor: consider TDM to confirm residual level <30 ng/mL before high risk procedure.
Algorithm 2: urgent surgery (within 48–72 hours)
1. Determine time of last DOAC dose and measure CrCl.
2. If CrCl ≥50 mL/min and ≥24 hours since last dose: proceed without TDM.
3. If CrCl<50 mL/min or timing uncertain: obtain DOAC level.
Algorithm 3: emergency Surgery (immediate)
CONCLUSIONS
Perioperative anticoagulation management requires more than a one‑size‑fits‑all approach. While DOACs offer significant advantages, the “no monitoring” paradigm is not universally safe, particularly in the perioperative setting where bleeding and thrombotic risks intersect. Patients with extreme body weight, renal impairment, liver disease, cancer, bariatric surgery, thrombocytopenia, or drug interactions require individualized care that may include selective therapeutic drug monitoring. From the perspective of a hematologist and a cardiologist, we advocate forroutine use of DOACs in low‑risk patients without monitoring, as supported by evidence; selective TDM in high risk populations to confirm safe residual levels before surgery; preference for LMWH in situations where DOAC pharmacokinetics are unpredictable (e.g., malabsorption, severe thrombocytopenia, advanced liver disease). There is present a recognition of marketing influences that have shaped current guidelines, and a commitment to transparent, evidence based decision making. The ultimate goal is to provide safe, effective anticoagulation that minimizes both thrombotic and hemorrhagic complications in the perioperative period. By integrating clinical judgment with objective monitoring when indicated, we can achieve this goal even in the most complex patients.
ACKNOWLEDGEMENTS
The authors are grateful to Department of Biomedical and Laboratory Science, Africa University, Mutare, Zimbabwe to provide necessary facilities during this work.
AUTHOR’S CONTRIBUTIONS
Obeagu EI: formal analysis, conceptualisation, data organisation, writing original draft. Goryacheva O: data analysis, manuscript writing, literature survey. Final manuscript was checked and approved by the both authors.
DATA AVAILABILITY
The related author can provide the empirical data supporting the study's conclusions upon request.
CONFLICT OF INTEREST
There are no conflicts of interest in regard to this project.
REFERENCES