Variation in Haemostasis and VTE Prophylaxis in Elective Adult Cranial Neurosurgery: A Global Survey of Perioperative Practice

This global survey of 456 neurosurgeons reveals substantial worldwide variation in perioperative haemostasis and venous thromboembolism prophylaxis practices for elective adult cranial surgery, driven by a mix of geographical socioeconomic factors and true clinical equipoise, thereby establishing an empirical foundation for future guideline development and trial design.

The Gist

Imagine you are a chef preparing a very delicate, high-stakes dish: brain surgery. The goal is to fix a problem inside the skull without causing a disaster. But there's a tricky balancing act happening in the kitchen:

1. The Risk of Clotting: If the patient doesn't move much after surgery (like a car sitting in a garage too long), their blood can get thick and form dangerous clots (like sludge in a pipe). This is called a VTE (Venous Thromboembolism).
2. The Risk of Bleeding: If you give the patient medicine to stop those clots (like adding a powerful solvent to the pipes), you might accidentally cause a leak or a flood inside the tight space of the skull. This is an intracranial hemorrhage.

The "recipe" for managing this risk is supposed to be the same everywhere, but this new study found that neurosurgeons around the world are using completely different recipes.

The Global Survey: A Taste Test

The authors (a team of brain surgeons and blood experts) sent out a digital questionnaire to 456 brain surgeons from 78 different countries. They wanted to know: How do you actually handle this clotting vs. bleeding dilemma in your daily practice?

Here is what they found, translated into everyday terms:

1. The "No Recipe" Problem

In a perfect world, every chef follows the same official cookbook. In reality:

• 13% of surgeons said their hospital didn't even have a plan (no recipe at all).
• 23% said they didn't follow any specific cookbook, just making it up as they went.
• 12% were trying to follow multiple cookbooks at once, which is confusing.

2. The "Rich vs. Poor" Kitchen

The study found that what happens in the operating room often depends on how much money the hospital has (High-Income vs. Low/Middle-Income countries).

• The "Rich Kitchen" (High-Income Countries): These surgeons tend to be more cautious about stopping blood-thinning pills before surgery. They wait longer to start them back up after surgery, and they run more expensive lab tests to check the blood.
• The "Resource-Limited Kitchen" (Low/Middle-Income Countries): These surgeons often start blood-thinners sooner after surgery. Why? Because if a patient gets a clot, they might not have access to a CT scanner or a blood bank to fix it quickly. So, they try to prevent the clot earlier, even if it feels riskier. They also tend to give blood transfusions at higher levels (keeping the "fuel tank" fuller) because they can't afford to run low.

3. The "Mechanical vs. Chemical" Debate

Surgeons have two main tools to stop clots:

• Mechanical: Squeezing the legs with special stockings or air pumps (like a massage machine). 81% of surgeons use these.
• Chemical: Giving drugs like heparin (like adding a chemical agent to the blood).
• The Timing Game: When do you start the drugs? Some wait 24 hours, some wait 48, and some wait until they see a fresh CT scan to make sure there's no bleeding. There is no agreement on the exact time. It's like a group of drivers arguing over whether to start driving 10 minutes or 30 minutes after the engine is turned on.

4. The "True Confusion" (Clinical Equipoise)

This is the most important finding. The researchers used math to figure out why the surgeons disagreed.

• Contextual Differences: Some disagreements happen because of the environment (e.g., "I can't start drugs early because I don't have a CT scanner").
• True Equipoise (The "We Just Don't Know" Zone): Many disagreements happened even when the surgeons had the same resources and experience. They just genuinely didn't know the answer. It's like a group of expert pilots all flying the same plane but choosing different altitudes because no one has ever proven which altitude is actually the safest.

The Big Takeaway

The study concludes that we are flying blind in many areas. Because there is so much variation and so much genuine uncertainty, we need to stop guessing and start testing.

The authors are calling for large, international clinical trials (like a massive taste-test competition) to finally figure out:

• When is the perfect time to start blood thinners?
• Do we really need a CT scan before starting them?
• Does the "recipe" change based on the patient's country or the surgeon's experience?

In short: Brain surgeons are currently trying to walk a tightrope between bleeding and clotting, but everyone is walking it at a different speed and with different safety nets. This study is a wake-up call to build a single, scientifically proven safety net for everyone.

Technical Summary

1. Problem Statement

Venous thromboembolism (VTE) is a major cause of perioperative morbidity and mortality in cranial neurosurgery. However, managing VTE prophylaxis presents a critical clinical dilemma: balancing the prevention of thromboembolic events against the risk of catastrophic intracranial hemorrhage (ICH), which can lead to neurological deterioration or death in the confined intracranial space.

Despite the high stakes, clinical practice varies widely globally. Existing evidence is limited by a scarcity of high-quality randomized controlled trials (RCTs), and international guidelines (e.g., NICE, ASH, ESAIC) often provide cautious, divergent, or absent recommendations regarding the timing of chemical prophylaxis and pre-operative antiplatelet cessation. Furthermore, systemic disparities between High-Income Countries (HICs) and Low- and Middle-Income Countries (LMICs)—such as access to imaging, blood products, and critical care—may drive divergent risk tolerances. There is a lack of empirical data mapping contemporary real-world practice to distinguish between variation driven by resource constraints and variation driven by genuine clinical uncertainty (equipoise).

2. Methodology

Study Design:
A global, cross-sectional, two-stage internet-based survey conducted between November 2023 and May 2025.

Participants:

• Target: Practicing neurosurgeons performing elective adult cranial surgery.
• Scope: 585 total responses; 456 met inclusion criteria (representing 322 units across 78 countries).
• Demographics: 71% from HICs, 29% from LMICs. Coverage included Europe (60%), Americas (18%), Asia (15%), Africa (6%), and Australasia (1%).

Survey Instrument:

• Developed by a multidisciplinary team (neurosurgeons, haematologists, academics) following CHERRIES guidelines.
• Domains: Pre-operative haemostasis decision-making, mechanical/chemical VTE prophylaxis timing, VTE surveillance, and self-reported complication rates.
• Duration: Limited to <10 minutes to ensure completion.

Data Analysis:

• Descriptive Statistics: Summarized practices (counts, proportions, means).
• Stratification: Data were analyzed by subspecialty, years post-certification, and geographical income status (HIC vs. LMIC).
• Equipoise Quantification: A novel dual-metric framework was employed to distinguish "True Clinical Equipoise" from contextual variation:
  • Heterogeneity: Measured using Shannon Entropy (categorical) and Coefficient of Variation (quantitative).
  • Influence: Measured by averaging effect sizes (Cramer's V, Eta-squared, etc.) across stratifying variables (income, continent, experience).
  • Definition of True Equipoise: High heterogeneity (>0.50) coupled with low contextual influence (<0.20), indicating variation is not explained by demographics or resources but by unresolved clinical uncertainty.

3. Key Contributions

• First Global Mapping: This is the first large-scale international survey specifically targeting peri-operative haemostasis and VTE prophylaxis in adult elective cranial neurosurgery.
• Quantification of Uncertainty: The study moves beyond descriptive reporting to mathematically quantify "true clinical equipoise," identifying specific domains where variation is due to a lack of evidence rather than resource limitations.
• Contextual vs. Clinical Drivers: It distinguishes between practices driven by systemic constraints (e.g., LMICs adopting more conservative strategies due to limited imaging/blood access) and those driven by genuine clinical disagreement.
• Trial Design Foundation: The data provides an empirical baseline for designing future pragmatic RCTs, ensuring eligibility criteria and intervention strategies are grounded in real-world practice.

4. Key Results

Guideline Adherence:

• 13% of departments had no formal VTE plan.
• 23% of surgeons followed no specific guidelines; 12% used multiple guidelines.
• Commonly cited guidelines included ASH, NICE, and European society recommendations, though reliance varied by region.

Pre-operative Haemostasis:

• Testing: Routine testing for Hb, platelets, and hematocrit was universal (>95%). Fibrinogen testing was more common in HICs (26% overall).
• Transfusion Thresholds: LMIC respondents favored higher transfusion thresholds (>90 g/L) compared to HICs (70–90 g/L).
• Antiplatelet Cessation: While most stopped agents ≥7 days pre-op, significant variation existed. HICs generally omitted antiplatelets for longer durations than LMICs (e.g., Aspirin: HIC mean 6.3 days vs. LMIC 6.0 days).

Prophylaxis Strategies:

• Mechanical: Near-universal use. TEDs (81%) and IPCs (62%) were typically initiated pre- or intra-operatively.
• Chemical (LMWH):
  • 99% of respondents intended to use LMWH post-operatively.
  • Imaging Gating: 57% required a post-op CT/MRI before initiating LMWH.
  • Timing: LMWH was initiated on average 31.4 hours post-surgery (median 24h).
  • Variation: No significant variation in initiation timing was found based on income, seniority, or subspecialty after correction.

Surveillance:

• Inpatient VTE assessment was consistent; outpatient assessment was less frequent in HICs compared to LMICs.
• Ultrasound/Doppler was the primary modality for DVT (92%); CT Pulmonary Angiogram (CTPA) for PE (52%).

Equipoise Analysis:

• True Equipoise Found: Many core decisions (timing of post-op imaging, factors for earlier chemoprophylaxis) showed high heterogeneity with low contextual influence. This suggests these are areas of genuine clinical uncertainty suitable for RCTs.
• Context-Driven Variation: Decisions regarding haematology referral and DVT/PE investigation showed high influence from geography and income, reflecting resource constraints.

5. Significance and Conclusion

The study concludes that while some variation in VTE prophylaxis is driven by systemic resource disparities (particularly between HICs and LMICs), a substantial portion of global practice variation reflects true clinical equipoise.

• Implication for Research: The identification of high-heterogeneity/low-influence domains provides a clear roadmap for future pragmatic RCTs. Specifically, trials should focus on the optimal timing of post-operative chemoprophylaxis and the necessity of imaging-gated initiation.
• Implication for Guidelines: Current guidelines are insufficient to standardize care. Future guideline development must be informed by the evidence generated from these targeted trials rather than expert consensus alone.
• Global Health: The findings highlight that in resource-constrained settings, risk-averse strategies (higher transfusion thresholds, shorter antiplatelet holds) are often adopted due to limited rescue capabilities, underscoring the need for context-aware, rather than one-size-fits-all, global guidelines.

By mapping real-world practice, this study establishes the necessary empirical foundation to reduce practice variation and improve patient safety in cranial neurosurgery globally.