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Antithrombotic Therapy

Perioperative planning has three separate decisions: preventing a new postoperative VTE, interrupting treatment for an existing thrombotic indication, and treating major bleeding. A prophylactic heparin dose does not replace therapeutic anticoagulation for a mechanical valve or recent PE. Conversely, therapeutic bridging is not an appropriate substitute for an ordinary postoperative prophylaxis plan.

For each patient, establish the indication and last dose, renal function, previous thrombosis or bleeding, procedural bleeding consequences, and any neuraxial catheter plan. Record both interruption and restart instructions. Drug selection and reversal doses are maintained in the VTE prophylaxis and anticoagulation reversal pharmacology hubs.

See also: ERAS, Pulmonary Embolism, Cardiovascular Risk.

VTE Risk in Urologic Surgery​

Risk varies with the operation, open versus minimally invasive access, lymph-node dissection, and the patient. A single percentage for all prostatectomies, urethroplasties, or pelvic reconstructions is misleading.[1] The non-cancer systematic review found substantial procedural variation and frequent low-certainty estimates.[1]

The 2024 European perioperative VTE guideline's urology chapter recommends:[2]

SettingPractical implication
Ambulatory day surgery such as ureteroscopy, circumcision, vasectomy or hydrocelectomyThe panel recommends against pharmacological and mechanical prophylaxis (Grade 1B for each); encourage mobilization.
Open radical cystectomy or open radical prostatectomy with extended lymphadenectomyPharmacological prophylaxis is recommended (Grade 1A or 1B by risk stratum); mechanical prophylaxis is suggested (Grade 2C).
Other operationsCombine procedure/approach and patient factors rather than extending one recommendation to every pelvic operation. Prior VTE, age and BMI affect the balance.

When pharmacological prophylaxis is indicated, that chapter favors starting on postoperative day 1 and continuing 2–4 weeks, with the postoperative course counted from surgery. “Four weeks” does not mean an additional 28 days after discharge. Active bleeding, reintervention and neuraxial timing can change the start or restart. LMWH is established; a DOAC may be considered in selected patients, with particular caution when ileus or poor oral absorption is expected.[2]

Using a Risk Score​

Caprini can inform an institutional prophylaxis protocol for urologic surgery. The 2012 ACCP general/abdominopelvic surgery framework uses scores of 0 (very low risk), 1–2 (low), 3–4 (moderate) and ≥5 (high). Moderate risk does not automatically require combined mechanical and pharmacological prophylaxis: acceptable options depend on bleeding risk. High-risk patients without major bleeding risk generally receive pharmacological prophylaxis with added mechanical measures; selected abdominal or pelvic cancer operations warrant extended prophylaxis.[3]

The ACCP Caprini table assigns points for age 41–60 (1), 61–74 (2) or ≥75 (3) years; BMI >25 (1); oral contraceptives or hormone replacement therapy (1); malignancy (2); central venous access or bed confinement >72 hours (2); and prior VTE or thrombophilia (3). Major open or laparoscopic surgery >45 minutes adds 2 points.[3] An individual score should therefore be interpreted alongside the actual procedure, mobility and bleeding consequences. A prior VTE or established thrombophilia merits particular attention, but a family history alone does not establish antithrombin deficiency or justify concentrate administration.

Choosing and Delivering Prophylaxis​

Use the drug-class hub for agent doses, renal adjustment, obesity considerations, HIT history and oral-agent evidence. Do not automatically replace a once-daily enoxaparin regimen with 30 mg twice daily merely because a patient is labeled “high risk.” Check the specific indication and local protocol.[19]

Mechanical prophylaxis is useful when indicated and during selected periods when bleeding prevents anticoagulation, but is not mandatory for every ambulatory operation. Reassess daily whether the pharmacological plan can safely start; document the intended completion date and teach the patient how to obtain and take the discharge medication.

Chronic Anticoagulation — Bridging and Periprocedural Management​

Warfarin​

Do not bridge routinely. In BRIDGE, 1,884 patients with atrial fibrillation were randomized, and 1,813 contributed 30-day outcome data: arterial thromboembolism was 0.4% without bridging versus 0.3% with bridging, while major bleeding was 1.3% versus 3.2%.[4] It was not a mechanical-valve trial.[4]

PERIOP2 tested postoperative bridging. All participants received dalteparin 200 IU/kg at 72 and 48 hours before surgery, then 100 IU/kg at 24 hours. In the randomized postoperative regimen, high-bleeding-risk procedures, including genitourinary cancer surgery and prostate resection or biopsy, received prophylactic dalteparin 5,000 IU daily or placebo; low-risk procedures received therapeutic dalteparin 200 IU/kg daily (maximum 18,000 IU) or placebo.[5] Among 1,470 analyzed patients with AF and/or a mechanical valve, 90-day major thromboembolism was 1.2% with postoperative placebo versus 1.0% with dalteparin; no significant benefit was found. The trial excluded particularly high-risk valve situations, including multiple mechanical valves, Starr–Edwards valves and a mechanical valve with prior stroke or TIA.[5]

Guideline recommendations require context. For elective VKA interruption, CHEST 2022 strongly recommends against heparin bridging for AF (moderate-certainty evidence), conditionally suggests against it for a mechanical valve and for VTE as the sole indication (very-low-certainty evidence), and conditionally suggests bridging for VKA-treated patients classified as high risk for thromboembolism (very-low-certainty evidence).[6] AHA/ACC 2024 says preoperative parenteral bridging can be effective in patients with cardiovascular disease at high thrombotic risk undergoing noncardiac surgery who need VKA interruption (Class 2a, C-LD), and recommends against routine bridging in most patients with cardiovascular disease undergoing elective noncardiac surgery who need oral anticoagulant interruption (Class 3: Harm, C-LD).[8] Resolve these exceptional cases jointly with the anticoagulation or cardiology team; a valve type alone should not trigger an automatic postoperative full-dose heparin order.[6][8]

If interruption is required, warfarin is commonly stopped five days before surgery. Check INR sufficiently early to act (often the preceding day) and use the institutional correction plan if still excessive. Restart timing depends on hemostasis and the procedure; early restart does not immediately restore therapeutic anticoagulation.[5][6]

Direct Oral Anticoagulants​

Use a renal-function and bleeding-risk protocol, with the last actual dose documented. The PAUSE protocol (3,007 patients with AF on apixaban, dabigatran or rivaroxaban) omitted the DOAC for 1 day before a low-bleeding-risk procedure and 2 days before a high-bleeding-risk procedure, and resumed 1 day after a low-risk procedure and 2–3 days after a high-risk one. No heparin bridging or routine coagulation testing to guide care was used. Across all procedure-risk strata, 30-day major bleeding was 0.90–1.85% and arterial thromboembolism 0.16–0.60%; in high-bleeding-risk subgroups, major bleeding was 12/406 (2.96%) with apixaban, 2/228 (0.88%) with dabigatran, and 11/373 (2.95%) with rivaroxaban.[17] Dabigatran is renally cleared, so PAUSE lengthened its interruption when CrCl was below 50 mL/min (2 days before a low-risk and 4 days before a high-risk procedure).[17] CHEST 2022 likewise suggests against bridging a DOAC and suggests resuming more than 24 hours after surgery rather than within 24 hours. Resume only when hemostasis permits.[6]

AgentLow-bleeding-risk procedureHigh-bleeding-risk procedureResume
Apixaban, rivaroxaban, CrCl ≥30 mL/minOmit 1 dayOmit 2 daysDay 1 (low risk); day 2–3 (high risk) [8]
Dabigatran, CrCl ≥50 mL/minOmit 1 dayOmit 2 daysSame [17]
Dabigatran, CrCl 30–<50 mL/minOmit 2 daysOmit 4 daysSame [17]

The AHA/ACC 2024 guideline reproduces this schedule (its Table 13) and adds a row for apixaban, edoxaban or rivaroxaban with CrCl below 30 mL/min: omit 3 days before a high-bleeding-risk procedure and 2 days before a low- or moderate-risk one. It defines minimal bleeding risk as a 30-day major-bleeding risk near 0% (for example cataract surgery or minor dermatologic procedures), low or moderate as under 2% and high as 2% or more, and gives no interruption for minimal-risk procedures. Resume a DOAC once hemostasis is secure and full anticoagulation is appropriate, as early as 6 hours after surgery; resume a VKA at the previous dose as early as 12 to 24 hours after a low- or moderate-risk procedure.[8]

PAUSE-2, a 159-patient pilot trial, found similar residual DOAC levels with the PAUSE and ASRA-based approaches in patients undergoing high-bleed-risk or neuraxial procedures; it was not powered for clinical outcomes.[18]

For neuraxial and deep plexus blocks, use ASRA's dose-specific intervals below; ASRA suggests against DOAC reversal solely to enable these blocks in routine patients (grade IIC).[9] Severe renal impairment, interacting drugs, traumatic puncture or an indwelling catheter require a separate anesthesia plan. When therapeutic anticoagulation must remain withheld, decide whether prophylactic anticoagulation is appropriate in the interim; do not silently convert prophylaxis into treatment.

Urologic Bleeding Considerations​

Bleeding consequences differ by operation: transurethral prostate resection, open prostatectomy or nephrectomy, and reconstructive operations with large dissected raw surfaces carry more risk than cystoscopy or minor scrotal and penile procedures. Guidelines for urologic practice give inconsistent recommendations by drug, indication and procedure; a plan shared with the prescriber can address those differences.[20] For BPH surgery in men at high bleeding risk or who must stay on anticoagulant or antiplatelet therapy, the AUA 2026 guideline states that clinicians may offer HoLEP, ThuLEP, photoselective vaporization or prostatic artery embolization .[21]

Antiplatelet Therapy​

POISE-2 did not show a perioperative cardiovascular benefit from routine aspirin. Among 10,010 noncardiac-surgery patients, death or nonfatal MI was 7.0% with aspirin versus 7.1% with placebo; major bleeding was 4.6% versus 3.8%.[7]

For surgery requiring antiplatelet interruption after a drug-eluting stent, AHA/ACC 2024 generally favors waiting ≥12 months after PCI for ACS or ≥6 months for chronic coronary disease; time-sensitive surgery may be considered after ≥3 months when delay is more harmful. After prior PCI, continue aspirin 75–100 mg perioperatively when possible (Class 1, B-R); if oral anticoagulant monotherapy must be interrupted, substitute aspirin when feasible until the anticoagulant is safely resumed (Class 1, B-NR).[8] Early surgery requiring DAPT interruption needs multidisciplinary planning. In patients with CAD needing time-sensitive surgery ≤30 days after bare-metal stenting or <3 months after drug-eluting stenting, AHA/ACC recommends continuing DAPT unless bleeding risk outweighs stent-thrombosis prevention (Class 1, B-NR). Elective surgery ≤30 days after either stent type that requires antiplatelet interruption is potentially harmful (Class 3: Harm, B-NR).[8] In patients with chronic coronary disease without prior PCI, continuing aspirin may be considered when the risk of cardiac events outweighs the risk of bleeding (Class 2b, B-R); routine perioperative initiation is not beneficial (Class 3: No Benefit, B-R).[8]

If interruption is chosen, AHA/ACC Table 12 lists the minimum time from drug interruption to restored platelet function as aspirin 4 days, clopidogrel 5–7 days, prasugrel 7–10 days and ticagrelor 3–5 days.[8] Plan the postoperative restart rather than leaving antiplatelets indefinitely discontinued.[8]

Timing Around Neuraxial Anesthesia​

Prophylactic UFH does require timing precautions before spinal or epidural placement. The following summarizes selected ASRA 2025 recommendations; higher doses, renal dysfunction and combined antithrombotics require the full guideline.[9]

RegimenSelected timing requirements
SC UFH 5,000 units twice/three times dailyNeedle placement ≥4–6 hours after dosing, or assess normal coagulation. Remove a catheter ≥4–6 hours after a dose; subsequent low-dose UFH may follow immediately.
Low-dose LMWHPlacement ≥12 hours after dosing. Twice-daily postoperative dosing requires catheter removal before starting and a ≥4-hour delay after removal. With once-daily dosing, remove ≥12 hours after the last dose and delay the next ≥4 hours.
SC UFH 7,500–10,000 units twice daily, or up to 20,000 units dailyNeuraxial block ≥12 hours after the dose and confirmed normal coagulation (grade IIC). Above 10,000 units per dose or 20,000 units daily, wait ≥24 hours and confirm normal coagulation. Indwelling catheters are not established as safe above 5,000 units per dose or 15,000 units daily; individualize and add enhanced neurologic monitoring.
High-dose LMWHPlacement ≥24 hours after the last dose (grade IC); consider an anti-Xa level if sooner, particularly above age 75 or with CrCl ≤30 mL/min (target ≤0.1 IU/mL). Resume high-dose LMWH ≥24 hours after surgery of low or moderate bleeding risk and 48–72 hours after high-bleeding-risk surgery. Remove the catheter ≥4 hours before the first postoperative dose, and give that dose ≥24 hours after placement, whichever is later (grade IC).

The first postoperative low-dose LMWH requires ≥12 hours after needle or catheter placement; a twice-daily regimen starts the following day. After bloody needle or catheter placement, ASRA suggests delaying postoperative LMWH initiation for 24 hours and discussing the plan with the surgeon (grade IIC).[9] ASRA uses longer, dose-specific DOAC intervals, for example high-dose apixaban ≥72 hours before placement. ASRA also recommends against giving antiplatelet drugs, standard heparin or dextran while an indwelling neuraxial catheter is in place with LMWH (grade IA). Neither a normal INR nor a generic 24-hour DOAC hold establishes neuraxial safety. ASRA's fifth edition also uses drug-specific assays: a residual apixaban, rivaroxaban, edoxaban or dabigatran level below 30 ng/mL (anti-Xa activity ≤0.1 IU/mL for the factor Xa inhibitors) is acceptable for neuraxial block.[9]

The fifth edition gives these DOAC intervals before needle placement as conservative suggestions (grade IIC). Classify the regimen using ASRA's dose-and-indication table: apixaban 2.5 mg twice daily for dose-reduced atrial fibrillation stroke prevention is high dose, whereas the same dose for extended VTE prevention or orthopedic postoperative prophylaxis is low dose. Check a drug level when placement is planned before the applicable interval has elapsed.[9]

DOACLow doseHigh dose
Apixaban≥36 hours≥72 hours
Rivaroxaban≥24 hours (≥30 hours if CrCl <30 mL/min)≥72 hours
EdoxabanNo FDA-approved low-dose indication≥72 hours
Dabigatran≥48 hours≥72 hours if CrCl ≥50 mL/min; 120 hours if CrCl 30–49 mL/min

For dabigatran, ASRA suggests against neuraxial or deep plexus or peripheral block when CrCl is below 30 mL/min unless a plasma level is obtained and is below 30 ng/mL. After a low-dose DOAC, needle placement or catheter removal should precede the first postoperative dose by ≥6 hours; after a high-dose DOAC, by ≥24 hours. If a DOAC is given unexpectedly with a catheter in place, the drug is withheld for the same interval as before placement, or until the level is acceptable, before the catheter is removed.[9]

Other agents. ASRA recommends stopping warfarin 5 days before the block and confirming that the INR has normalized to the local laboratory range before needle placement (grade IB). Catheters are suggested for removal when the INR is below 1.5, and neurologic assessment continues for at least 48 hours after removal (grade IIC). For thienopyridines, ASRA suggests waiting 5–7 days after clopidogrel and 7–10 days after prasugrel (grade IIC), 5 days after ticagrelor (grade 2C; the fourth edition gave 5–7 days) and 2 days after cilostazol (grade IIC). NSAIDs, including aspirin, alone do not add enough risk to alter block timing or catheter management (grade IC). Fondaparinux at 2.5 mg daily is held for 36 hours in young and 42 hours in elderly patients with normal renal function, for at least 58 hours with CrCl 30–50 mL/min, and neuraxial block is not suggested with CrCl below 30 mL/min. At 5–10 mg daily it is held for at least 70 hours in young and 105 hours in elderly patients with normal renal function (all grade IIC). Catheters are removed at least 6 hours before the first postoperative dose at the higher dose. ASRA suggests against neuraxial techniques with parenteral thrombin inhibitors (argatroban, bivalirudin, desirudin).[9]

Deep and superficial blocks. For deep plexus or deep peripheral blocks, ASRA recommends applying the neuraxial guidance (grade IC). For other plexus or peripheral blocks, performance, catheter maintenance and catheter removal depend on site compressibility, vascularity and the consequences of bleeding (grade IIC).[9]

Enoxaparin, fondaparinux and the DOAC labels carry a boxed warning for epidural or spinal hematoma with neuraxial anesthesia or spinal puncture. The enoxaparin label lists indwelling epidural catheters, concomitant NSAIDs, platelet inhibitors or other anticoagulants, traumatic or repeated punctures, and spinal deformity or surgery as risk factors, and directs frequent neurologic checks with urgent treatment of any deficit.[19] With CrCl <30 mL/min, it advises considering at least 24 hours after a renally adjusted 30-mg once-daily dose or 48 hours after 1 mg/kg once daily before catheter removal.[19]

Reversal of Antithrombotic Agents​

Identify the drug, last dose, renal clearance, bleeding site and urgency while arranging local bleeding control and resuscitation. An abnormal laboratory result without major bleeding does not by itself require emergency reversal. The reversal hub maintains the agent-specific doses and contraindications.

  • Warfarin: urgent major-bleeding reversal commonly uses 4-factor PCC with IV vitamin K; PCC does not replace vitamin K's sustained effect; Kcentra contains heparin and is contraindicated in known HIT or DIC.[24]
  • Dabigatran: idarucizumab 5 g IV (two 2.5 g/50 mL vials) is indicated for emergency surgery or urgent procedures and for life-threatening or uncontrolled bleeding.[23]
  • Factor Xa inhibitors: US commercial sales of andexanet ended December 22, 2025. Four-factor PCC is used off-label under major-bleeding protocols; it is not an FDA-approved specific antidote to apixaban or rivaroxaban.[10]
  • UFH/LMWH: Dose protamine to estimated circulating UFH and time since its last dose: 1 mg neutralizes at least 100 USP heparin units, but less may be needed as heparin clears.[22] Give slowly, no more than 50 mg over 10 minutes, and reassess coagulation tests.[22] Protamine reverses UFH more completely than enoxaparin; the Lovenox label states that anti-Xa activity is never completely neutralized (maximum about 60%).[19] Its boxed warning describes severe hypotension, cardiovascular collapse and pulmonary hypertension; it flags rapid administration and prior exposure, while listing fish allergy, prior vasectomy and cardiac dysfunction as possible risk factors.[22]

In PATCH, 190 adults taking antiplatelet therapy with acute spontaneous supratentorial intracerebral hemorrhage were randomized; platelet transfusion worsened the three-month modified Rankin Scale distribution (adjusted common OR 2.05, 95% CI 1.18–3.56).[11]

Heparin-Induced Thrombocytopenia (HIT)​

For postoperative UFH recipients, ASH suggests platelet checks at least every other day from day 4 to day 14 or until heparin stops; if heparin was given in the prior 30 days, begin on day 0 (conditional, very-low-certainty recommendation). Assess the 4Ts pretest probability, including alternative causes of postoperative thrombocytopenia.[12] Low-probability cases generally should not undergo HIT testing or empiric treatment. Intermediate- or high-probability cases need prompt cessation of heparin exposure and a non-heparin anticoagulation plan while immunoassay and, when indicated, functional testing proceed. For suspected HIT with a high-probability 4Ts score, ASH recommends therapeutic-intensity non-heparin anticoagulation ; with intermediate probability, ASH conditionally suggests therapeutic intensity when there is another therapeutic indication or bleeding risk is not high, and prophylactic intensity only when there is no other therapeutic indication and bleeding risk is high.[12]

For acute HIT, argatroban or bivalirudin may suit unstable patients or those needing urgent procedures; fondaparinux or a DOAC can be appropriate in clinically stable patients with suitable renal or hepatic function. A DOAC does not always require waiting for platelet recovery. Avoid starting warfarin before platelet recovery, usually ≥150 × 10⁹/L; if acute HIT develops while the patient is taking warfarin, stop it and give IV vitamin K when starting a non-heparin anticoagulant.[12] Involve hematology for selection, transition and duration.[12]

Heparin Resistance and Antithrombin Concentrate​

An unexpectedly short aPTT or ACT is not synonymous with antithrombin deficiency. Confirm dose and delivery, the clinical target and the assay. Inflammation-associated factor VIII or fibrinogen elevation can shorten aPTT despite adequate heparin. For therapeutic UFH monitoring, 2026 ISTH guidance suggests anti-Xa testing as optimal and aPTT as acceptable; for one-stage anti-Xa assays, it suggests those without added antithrombin.[25] Depending on the cause, specialist management may involve additional heparin, antithrombin supplementation or a direct thrombin inhibitor. There is no universal preferred rescue strategy.[13]

Confirmed Hereditary Antithrombin Deficiency​

The current THROMBATE III label covers adults and children with hereditary deficiency for treatment or prevention of thromboembolism and perioperative or peripartum prevention. The labeled loading calculation is (120 − baseline functional AT%) × weight (kg) / 1.4; subsequent dosing targets 80–120% activity. A maintenance dose of approximately 60% of loading every 24 hours must be individualized using functional activity, including peak and trough measurements. For perioperative prevention, the THROMBATE III label recommends maintaining normal antithrombin activity for 2–8 days, with duration guided by the procedure, clinical condition and thrombotic history.[14] Increased consumption can require more frequent testing and adjustment.[14]

Heparin effect increases after antithrombin replacement and may require dose reduction. Suspected hypersensitivity requires stopping the infusion and emergency treatment, not simply slowing it. These hereditary-deficiency instructions are not an approved sepsis-DIC or bypass-resistance regimen.[14]

Acquired Deficiency and Sepsis​

Do not use antithrombin routinely for critically ill patients merely because activity is low. The Cochrane review found no statistically significant mortality difference and increased bleeding (RR 1.58, 95% CI 1.35–1.84).[15] In the antithrombin subgroup of a 2025 DIC meta-analysis (two randomized trials; 47 treated and 48 controls), DIC resolution was higher (OR 5.21, 95% CI 2.10–12.90), while 28-day mortality and bleeding estimates were imprecise and did not establish a difference.[16] For diagnosed sepsis-associated DIC, the 2024 Japanese Society on Thrombosis and Hemostasis guideline recommends antithrombin (GRADE 1B).[26]

Practical Perioperative Checklist​

  1. Confirm indication, thrombotic history, last dose, renal function and interacting medication.
  2. Define the procedure's bleeding consequences and a procedure-appropriate VTE prevention plan.
  3. Identify recent PCI, very high thrombotic risk or suspected HIT before issuing generic interruption orders.
  4. Agree the neuraxial placement and removal schedule with anesthesia.
  5. Record interruption, any exceptional bridging decision, and the condition and time for restarting each drug.
  6. At discharge, reconcile the therapeutic and prophylactic plans, intended stop date, medication access and bleeding and VTE return precautions.

Pharmacology Hub Companions​

TopicSource of truth
Procedure-specific prevention, interruption, bridging and restart decisionsThis workflow
Agent doses, renal adjustment and prophylaxis evidenceVTE prophylaxis
Reversal agents, doses, contraindications and current availabilityAnticoagulation reversal

References​

1. Tikkinen KAO, Craigie S, Agarwal A, et al. Procedure-specific risks of thrombosis and bleeding in urological non-cancer surgery: systematic review and meta-analysis. Eur Urol. 2018;73:236–241. doi:10.1016/j.eururo.2017.02.025

2. Tikkinen KAO, Cartwright R, Jensen AG, et al. European guidelines on peri-operative venous thromboembolism prophylaxis: first update. Chapter 12: Urology. Eur J Anaesthesiol. 2024;41:618–621. doi:10.1097/EJA.0000000000002012. Full guideline chapter.

3. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: ACCP evidence-based clinical practice guidelines. Chest. 2012;141:e227S–e277S. doi:10.1378/chest.11-2297

4. Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med. 2015;373:823–833. doi:10.1056/NEJMoa1501035

5. Kovacs MJ, Wells PS, Anderson DR, et al. Postoperative low molecular weight heparin bridging treatment for patients at high risk of arterial thromboembolism (PERIOP2): double blind randomised controlled trial. BMJ. 2021;373:n1205. doi:10.1136/bmj.n1205

6. Douketis JD, Spyropoulos AC, Murad MH, et al. Perioperative management of antithrombotic therapy: an American College of Chest Physicians clinical practice guideline. Chest. 2022;162:e207–e243. doi:10.1016/j.chest.2022.07.025

7. Devereaux PJ, Mrkobrada M, Sessler DI, et al. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014;370:1494–1503. doi:10.1056/NEJMoa1401105

8. Thompson A, Fleischmann KE, Smilowitz NR, et al. 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM guideline for perioperative cardiovascular management for noncardiac surgery. J Am Coll Cardiol. 2024;84:1869–1969. doi:10.1016/j.jacc.2024.06.013

9. Kopp SL, Vandermeulen E, McBane RD, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine evidence-based guidelines (fifth edition). Reg Anesth Pain Med. Published online January 29, 2025. doi:10.1136/rapm-2024-105766

10. US Food and Drug Administration. Update on the safety of Andexxa. December 2025. FDA safety communication.

11. Baharoglu MI, Cordonnier C, Al-Shahi Salman R, et al. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH). Lancet. 2016;387:2605–2613. doi:10.1016/S0140-6736(16)30392-0

12. Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018;2:3360–3392. doi:10.1182/bloodadvances.2018024489

13. Maier CL, Connors JM, Levy JH. Troubleshooting heparin resistance. Hematology Am Soc Hematol Educ Program. 2024;2024:186–191. doi:10.1182/hematology.2024000659

14. US Food and Drug Administration. THROMBATE III (antithrombin III [human]) prescribing information. Revised July 2025. Full prescribing information.

15. Allingstrup M, Wetterslev J, Ravn FB, Møller AM, Afshari A. Antithrombin III for critically ill patients. Cochrane Database Syst Rev. 2016;2:CD005370. doi:10.1002/14651858.CD005370.pub3

16. Li W, Sheng S, Zhu F. Efficacy and safety of antithrombin or recombinant human thrombomodulin in the treatment of disseminated intravascular coagulation: a systematic review and meta-analysis. Thromb Res. 2025;249:109302. doi:10.1016/j.thromres.2025.109302

17. Douketis JD, Spyropoulos AC, Duncan J, et al. Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant (PAUSE). JAMA Intern Med. 2019;179:1469–1478. doi:10.1001/jamainternmed.2019.2431

18. Douketis JD, Li N, St John M, et al. Perioperative management of direct oral anticoagulants in patients having a high-bleed-risk surgery or neuraxial procedure: the PAUSE-2 pilot randomized trial. J Thromb Haemost. 2025;23:2226–2234. doi:10.1016/j.jtha.2025.03.003

19. Sanofi-Aventis. Lovenox (enoxaparin sodium) injection prescribing information: boxed warning, spinal/epidural hematomas. DailyMed.

20. Dimitropoulos K, Omar MI, Chalkias A, et al. Perioperative antithrombotic (antiplatelet and anticoagulant) therapy in urological practice: a critical assessment and summary of the clinical practice guidelines. World J Urol. 2020;38:2761–2770. doi:10.1007/s00345-020-03078-2

21. Goueli R, Badlani GH, Welliver C, et al. Management of lower urinary tract symptoms attributed to benign prostatic hyperplasia: AUA guideline (2026) Part III: procedural/surgical management. J Urol. 2026;216:161–170. doi:10.1097/JU.0000000000005099

22. Fresenius Kabi. Protamine sulfate injection prescribing information. DailyMed.

23. Boehringer Ingelheim. Praxbind (idarucizumab) injection prescribing information. DailyMed.

24. CSL Behring. KCENTRA (prothrombin complex concentrate [human]) prescribing information. Revised May 2023. DailyMed.

25. Gouin-Thibault I, Frere C, Castellucci LA, et al. "How to monitor and manage unfractionated heparin in practice (Part 1)? Guidance from the SSC of the ISTH." J Thromb Haemost. 2026;24(8):3051–3062. doi:10.1016/j.jtha.2026.05.013

26. Yamakawa K, Okamoto K, Seki Y, et al. "Clinical practice guidelines for management of disseminated intravascular coagulation in Japan 2024. Part 1: sepsis." Int J Hematol. 2025;121(5):592–604. doi:10.1007/s12185-024-03896-9