Early vs. Late Tourniquet Release and Phlebotomy-Induced Hemolysis in the Emergency Department: The TOURNI-ED Randomized Trial

NCT07617103 | Not Yet Recruiting

• 1 other identifier: 09.2026.829
• Study Type: interventional
• Target: 792
• Locations: 1 country
• Sites: 1

Brief Summary

BACKGROUND: Hemolysis is the most common preanalytical error in emergency department (ED) laboratories, affecting 17-26% of blood samples collected in the ED and leading to test cancellations, repeat venipuncture, delayed diagnoses, and increased healthcare costs. Venous stasis created by tourniquet application during phlebotomy is a recognized contributing factor to hemolysis. While clinical guidelines recommend releasing the tourniquet once blood flow is established, the optimal timing of tourniquet release in relation to tube filling sequence has not been systematically evaluated. OBJECTIVE: The primary objective of this trial is to determine whether early release of sphygmomanometer-applied venous stasis (released after the first tube fills) reduces hemolysis rates compared to late release (released after the last tube fills) during routine phlebotomy in ED patients triaged as green or yellow category. DESIGN: Single-center, parallel-group, superiority randomized controlled trial with 1:1 allocation ratio. The trial was prospectively registered prior to the enrollment of the first participant. PARTICIPANTS: Adult patients (≥18 years) presenting to the emergency department with triage category green (semi-urgent) or yellow (urgent), for whom blood collection is indicated as part of routine clinical care. Patients requiring blood collection from an intravenous catheter, those with known coagulation disorders, and those who decline to participate are excluded. INTERVENTIONS: Group A (Early Release): Sphygmomanometer inflated to 60 mmHg for venous stasis; tourniquet released immediately after the first tube (sodium citrate, blue cap) completes filling. Remaining tubes (SST/gel, yellow cap; K2-EDTA, purple cap) are collected after release. Group B (Late Release): Sphygmomanometer inflated to 60 mmHg; tourniquet maintained throughout all tube filling and released only after the last tube (K2-EDTA, purple cap) completes filling. Tube collection order follows the CLSI H03-A6 standard for both groups. PRIMARY OUTCOME: Hemolysis rate, defined as the proportion of serum separator tube (SST/yellow cap) samples with a Hemolysis Index (HI) ≥ 1+ (corresponding to free hemoglobin ≥50 mg/dL), is assessed by the clinical chemistry laboratory analyzer. The outcome assessor (laboratory technician) is blinded to group assignment. SECONDARY OUTCOMES: (1) Distribution of ordinal hemolysis index categories (-, 1+, 2+, 3+, 4+, 5+) in SST samples; (2) Proportion of hemolyzed samples requiring repeat blood collection; (3) Total blood collection duration (seconds) from sphygmomanometer inflation to last tube filling completion; (4) Complication rate (hematoma, nerve injury, vasovagal reaction, arterial puncture, multiple puncture attempts). SAMPLE SIZE: A total of 792 participants (396 per group) are required based on an assumed hemolysis rate of 12% in the late release group and 6% in the early release group (50% relative risk reduction), α=0.05 (two-tailed), 80% power (Fleiss with pooled variance), plus 10% dropout buffer. RANDOMIZATION: Simple randomization using a computer-generated random number list (randomizer.org). The allocation sequence is maintained by a designated person not involved in enrollment or data collection. Allocation is revealed sequentially at the point of care. STATISTICAL ANALYSIS: Primary analysis: Chi-square test comparing hemolysis rates between groups (intention-to-treat population). Secondary analyses: Mann-Whitney U test for ordinal HI distribution; logistic regression for adjusted odds ratio. Bonferroni correction applied to multiple secondary comparisons (adjusted α = 0.017). Per-protocol analysis performed as a sensitivity analysis. Missing data handled using complete case analysis with sensitivity analysis.

Conditions

Hemolysis; Blood Specimen Collection; Phlebotomy; Venous Stasis

Keywords

hemolysis; phlebotomy; tourniquet; venous stasis; emergency department; blood collection; hemolysis index; randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• Hemolysis Rate (Proportion of Hemolyzed Serum Separator Tube Specimens)

  The proportion of serum separator tube (SST/yellow cap) specimens with a Hemolysis Index (HI) of ≥1+ (corresponding to free hemoglobin concentration ≥50 mg/dL), as measured by the clinical chemistry laboratory analyzer. The HI is reported on a six-category ordinal scale: (-) \<50 mg/dL; (1+) 50-99 mg/dL; (2+) 100-199 mg/dL; (3+) 200-299 mg/dL; (4+) 300-500 mg/dL; (5+) \>500 mg/dL. A specimen is classified as hemolyzed if HI ≥1+.

  Measured at the time of laboratory analysis, within 2 hours of blood collection

Secondary Outcomes (4)

• Ordinal Distribution of Hemolysis Index Categories

  Measured at the time of laboratory analysis, within 2 hours of blood collection

• Proportion of Specimens Requiring Repeat Blood Collection Due to Hemolysis

  Within the same emergency department visit (up to 24 hours post-collection)

• Total Blood Collection Duration

  Measured during the blood collection procedure

• Procedural Complication Rate

  During the blood collection procedure and up to 30 minutes post-procedure

Study Arms (2)

Early Release Group (Group A)

EXPERIMENTAL

Venous stasis is applied using a sphygmomanometer inflated to 60 mmHg. The sphygmomanometer is released (deflated to 0 mmHg) immediately after the first blood collection tube (sodium citrate, 2.7 mL, blue cap) completes filling. The second (SST/gel separator, 5 mL, yellow cap) and third (K2-EDTA, 3 mL, purple cap) tubes are collected without active venous stasis. The tube collection order follows the CLSI H03-A6 guidelines for all participants.

Procedure: Sphygmomanometer-Applied Venous Stasis with Varied Release Timing During Phlebotomy

Late Release Group (Group B)

ACTIVE COMPARATOR

Venous stasis is applied using a sphygmomanometer inflated to 60 mmHg. The sphygmomanometer is maintained at 60 mmHg throughout the multi-tube collection sequence and released (deflated to 0 mmHg) only after the third and final collection tube (K2-EDTA, 3 mL, purple cap) has filled. This reflects current common nursing practice in the emergency department setting.

Procedure: Sphygmomanometer-Applied Venous Stasis with Varied Release Timing During Phlebotomy

Interventions

Sphygmomanometer-Applied Venous Stasis with Varied Release Timing During Phlebotomy PROCEDURE

A standard aneroid sphygmomanometer is used in place of a conventional tourniquet rubber strap to apply venous stasis at a standardized pressure of 60 mmHg prior to venipuncture. Blood is collected in three tubes in the following order: (1) sodium citrate tube (blue cap, 2.7 mL), (2) serum separator tube/SST (yellow cap, 5 mL), (3) K2-EDTA tube (purple cap, 3 mL). The intervention variable is the timing of sphygmomanometer release: immediately after tube 1 (Group A, early release) versus after tube 3 (Group B, late release).

Also known as: Tourniquet Release Timing; Venous Stasis Duration; Phlebotomy Technique Modification

Early Release Group (Group A); Late Release Group (Group B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• Presenting to the emergency department and triaged as green (semi-urgent) or yellow (urgent) category according to the Emergency Severity Index (ESI) or equivalent institutional triage system
• Blood collection (venipuncture) indicated as part of routine clinical care by the attending emergency physician
• Ability to provide written informed consent
• Accessible antecubital or forearm vein suitable for standard venipuncture (not requiring intravenous catheter placement for blood collection)

You may not qualify if:

• Blood collection performed via an existing intravenous catheter or central venous access device
• Known or suspected coagulation disorder (e.g., hemophilia, thrombocytopenia with platelet count \<50,000/uL, current anticoagulant therapy with active bleeding)
• Active upper extremity injury, infection, lymphedema, or arteriovenous fistula at the potential collection site
• Triage category red (resuscitation) at the time of blood collection
• Declined informed consent
• Previously enrolled in this study (re-enrollment not permitted)
• Pregnancy (due to potential vascular changes affecting hemolysis rate)
• Known hemolytic anemia or other hematological condition associated with baseline elevated hemolysis

Sponsors & Collaborators

• Marmara University Pendik Training and Research Hospital: lead

Study Sites (1)

Marmara University Pendik Training and Research Hospital

Pendik, Istanbul, 34899, Turkey (Türkiye)

Location

Related Publications (6)

• Ayten S, Koşer M, Cumhur A, et al. Comparison of the Hemolysis Rate According to Biochemistry Test Results of Patients Admitted to The Emergency Department with the Results of the Hemcheck Device. Eurasian J Emerg Med. 2025;24(2):126-31. doi:10.4274/eajem.galenos.2024.80947

  RESULT

• Lv L, Li C, Wei W, Sun S, Ren X, Pan X, Li G. Optimization of sparse-view CT reconstruction based on convolutional neural network. Med Phys. 2025 Apr;52(4):2089-2105. doi: 10.1002/mp.17636. Epub 2025 Feb 2.

  PMID: 39894762 RESULT

• Tomar SL, Carden DL, Dodd VJ, Catalanotto FA, Herndon JB. Trends in dental-related use of hospital emergency departments in Florida. J Public Health Dent. 2016 Jun;76(3):249-57. doi: 10.1111/jphd.12158. Epub 2016 Apr 22.

  PMID: 27103213 RESULT

• Calleja R, Mielke N, Lee R, Johnson S, Bahl A. Hemolyzed Laboratory Specimens in the Emergency Department: An Underappreciated, but Frequent Problem. J Emerg Nurs. 2023 Sep;49(5):744-754. doi: 10.1016/j.jen.2023.06.001. Epub 2023 Jun 27.

  PMID: 37389514 RESULT

• Ersoy S, Ilanbey B; Kirsehir, Turkey. A Single-Center Prospective Study of the Effects of Different Methods of Phlebotomy in the Emergency Department on Blood Sample Hemolysis Rates. J Emerg Nurs. 2023 Jan;49(1):134-139. doi: 10.1016/j.jen.2022.08.005. Epub 2022 Sep 20.

  PMID: 36137822 RESULT

• Wollowitz A, Bijur PE, Esses D, John Gallagher E. Use of butterfly needles to draw blood is independently associated with marked reduction in hemolysis compared to intravenous catheter. Acad Emerg Med. 2013 Nov;20(11):1151-5. doi: 10.1111/acem.12245.

  PMID: 24238318 RESULT

MeSH Terms

Conditions

Hemolysis; Varicose Ulcer; Emergencies

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Varicose Veins; Vascular Diseases; Cardiovascular Diseases; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Disease Attributes

Central Study Contacts

Emir Ünal

CONTACT

+905327766010; emirunal@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome assessors (laboratory technicians performing Hemolysis Index analysis) are blinded to group assignment. Specimens are labeled with participant ID only; group allocation information is not accessible to laboratory personnel. Participants and care providers cannot be blinded because of the intervention's procedural nature.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2026
• First Posted: June 1, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: June 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Following a peer-reviewed publication
• Access Criteria: Reasonable written request to the principal investigator (emirunal@gmail.com).

Locations

TU (1)