What medications can be used to prevent bleeding in patients at risk of bleeding, including those with bleeding disorders such as hemophilia or undergoing surgery?

Medications to Prevent Bleeding

Tranexamic acid is the first-line medication for bleeding prophylaxis across most clinical scenarios, administered at 1 g IV over 10 minutes followed by 1 g over 8 hours for massive hemorrhage, or 10 mg/kg IV 3-4 times daily for 2-8 days in hemophilia patients undergoing dental procedures. 1, 2

Primary Prophylactic Agents by Clinical Context

Surgical Prophylaxis in Patients at Bleeding Risk

For major surgery, tranexamic acid is the preferred prophylactic agent, used by 91% of clinicians (59% as monotherapy, 32% combined with desmopressin) 1. The 2025 Association of Anaesthetists guidelines strongly recommend tranexamic acid for all patients where blood loss >500 mL is anticipated 1.

For minor surgery, tranexamic acid remains preferred (79% of clinicians use it, with 72% as monotherapy) 1. Desmopressin can be added for patients with mild hemophilia A or von Willebrand disease type 1 when factor VIII levels are >5% 3, 4.

Massive Hemorrhage and Trauma

Tranexamic acid 1 g IV over 10 minutes followed by 1 g over 8 hours is the evidence-based regimen supported by the CRASH-2 trial, which demonstrated a one-third reduction in hemorrhage mortality when administered within 3 hours of injury 1. This dosing should not be exceeded, as higher doses increase seizure risk without improving efficacy 1.

Critical timing consideration: Tranexamic acid must be given within 3 hours of injury onset. Administration after 3 hours may increase mortality rather than reduce it 5, 6.

Inherited Bleeding Disorders

For hemophilia A patients (factor VIII >5%): Desmopressin 0.3 mcg/kg IV is indicated for minor bleeding episodes, administered 30 minutes before procedures 3, 4. Tranexamic acid 10 mg/kg IV can be used adjunctively but cannot replace factor replacement when hemostatic levels ≥50 IU/dL are required 3, 2.

For hemophilia A patients with inhibitors: Bypassing agents (recombinant factor VIIa or activated prothrombin complex concentrate) are first-line, not antifibrinolytics 1, 7. Tranexamic acid serves only as adjunctive therapy 3.

For von Willebrand disease type 1 (factor VIII >5%): Desmopressin 0.3 mcg/kg IV administered 30 minutes before procedures is first-line for prophylaxis 4. Tranexamic acid can be added for mucosal bleeding 3.

Factor concentrates are required for severe hemophilia or von Willebrand disease and should only be used under hemophilia center guidance 1.

Specific Dosing Algorithms

Tranexamic Acid Dosing by Indication

• Trauma/massive hemorrhage: 1 g IV over 10 minutes, then 1 g IV over 8 hours 1
• Hemophilia dental procedures: 10 mg/kg IV before extraction, then 10 mg/kg IV 3-4 times daily for 2-8 days 2
• Minor surgery prophylaxis: 10 mg/kg IV as single dose or 1 g IV 1
• Renal impairment: Reduce dose proportionally to creatinine clearance 1, 2

Infusion rate: No faster than 1 mL/minute to avoid hypotension 2

Desmopressin Dosing

• Standard dose: 0.3 mcg/kg IV over 15-30 minutes, administered 30 minutes before procedure 4
• Timing: Must be given 30 minutes prior to achieve peak effect 4
• Fluid restriction: Mandatory to prevent hyponatremia, especially in elderly patients 3

Contraindications and Safety Considerations

Tranexamic Acid Contraindications

Absolute contraindications 1, 2:

• Subarachnoid hemorrhage (risk of cerebral edema and infarction)
• Active intravascular clotting
• Severe hypersensitivity to tranexamic acid

Relative contraindications 1:

• Massive hematuria (risk of ureteric obstruction)
• Renal impairment (requires dose reduction as drug is renally excreted)

Desmopressin Contraindications

Do not use desmopressin in 3, 8, 4:

• Severe hemophilia A (factor VIII <2-5%)
• Hemophilia B (no effect on factor IX)
• Neonates (risk of hyponatremia and seizures)
• Patients with factor VIII antibodies
• Massive bleeding (ineffective in this setting)

Test dose required: Efficacy is unpredictable; always perform test dose before relying on desmopressin for hemostasis 3.

Bleeding Disorder of Unknown Cause (BDUC)

For patients with convincing bleeding history but normal laboratory tests, the 2024 ISTH guidelines recommend 1:

Surgical prophylaxis hierarchy:

1. First-line: Tranexamic acid (79% for minor surgery, 91% for major surgery)
2. If bleeding occurs during minor surgery: Desmopressin (56% of clinicians) or platelets (16%)
3. If bleeding occurs during major surgery: Platelets (48%) or fresh frozen plasma (19%)
4. Second-line if first-line fails: Recombinant factor VIIa (40% for major surgery, 30% for minor surgery)

Heavy Menstrual Bleeding Management

First-line: Tranexamic acid added to combined oral contraceptive pill (53% of clinicians) 1

Second-line: Intrauterine device insertion (51%) or combined oral contraceptive pill with tranexamic acid (13%) 1

Third-line: Combined desmopressin/oral contraceptive/tranexamic acid (34%) 1

Critical Pitfalls to Avoid

Timing errors with tranexamic acid: Do not administer beyond 3 hours post-injury in trauma, as this increases rather than decreases mortality 5, 6. The CRASH-2 trial showed clear harm with delayed administration.

Dosing errors: Do not exceed 1 g loading dose of tranexamic acid in adults. Higher doses increase seizure risk (particularly in cardiac surgery and traumatic brain injury) without improving hemostatic efficacy 1, 6.

Route of administration errors: Tranexamic acid is FOR INTRAVENOUS USE ONLY. Inadvertent neuraxial injection causes seizures 2.

Combination therapy risks: Do not combine recombinant factor VIIa with activated prothrombin complex concentrate except for life- or limb-threatening bleeds due to thrombotic risk 3, 7.

Desmopressin without testing: Never rely on desmopressin without prior test dose to confirm response, as 20-30% of patients do not respond adequately 3.

Aprotinin use: This agent is now restricted to named-patient basis only for highly specialized cardiac and liver transplant surgery due to risks of acute renal failure, myocardial infarction, heart failure, stroke, and anaphylaxis (1:200 first-time use) 1.

Thrombotic Risk Considerations

While the CRASH-2 trauma trial showed no increased thrombotic events and actually demonstrated reduced myocardial infarction with tranexamic acid 6, some trials in gastrointestinal bleeding reported increased thrombotic complications 9. The harm-benefit balance favors tranexamic acid use in severe life-threatening bleeding but is less clear for minor bleeding where the thrombotic risk may outweigh benefits 10.

Monitor for thrombosis in patients receiving tranexamic acid who have additional risk factors (malignancy, prolonged immobility, prior thrombosis) 10, 9.