Introduction

The bleeding time is a clinical laboratory test used to evaluate platelet function. It involves creating a standardized incision and timing the cessation of bleeding. The historical indications included the pre-operative assessment of patients taking aspirin or NSAIDs and screening for von Willebrand disease. Unfortunately, it is insensitive and lacks reproducibility.[1] The platelet function assay (ie, PFA-100) has largely replaced bleeding time. Despite standardization of methods, the sensitivity and specificity of the bleeding time for platelet-mediated coagulopathy are low.

Many hospitals and health systems have removed the test without any demonstrated harm. In most cases, a thorough history and physical examination are the only workups needed for the preoperative assessment of bleeding risk. When assessing the clinical effectiveness of platelet aggregation, a modern platelet function assay can provide the necessary information. This is being increasingly utilized in the treatment of intracranial hemorrhage in patients receiving various antiplatelet agents before pooled platelet transfusion.

Specimen Collection

While measuring the bleeding time requires trained personnel, no gross specimen collection is necessary. Modern alternative platelet function analyzers require a small aliquot of peripheral blood. Technicians utilize standardized instruments to perform and interpret the test.  

Procedures

This test is performed via two primary methods based on the length and location of the incision. The IVY method is the most common. The patient’s arm is positioned at the level of the heart, and a blood pressure cuff is inflated to 40 mmHg. After cleansing with alcohol, a standardized device is used to create a 10mm-long and 1mm-deep incision on the volar forearm. Using a timer, the blood is blotted every 2 minutes. The time stops when there is no further bleeding after blotting. The Duke method involves a stab incision in the patient’s cleaned finger or earlobe with a lancet. Otherwise, the methodology is the same. The IVY method is more accurate but carries an increased risk of scarring. The Duke method is less accurate and carries a higher hematoma rate. Either method carries the risks of infection and bleeding. In addition, the discomfort is not insignificant. Different normal ranges exist for each method, further confounding the interpretation of results by lay clinicians.

Indications

The measurement of bleeding time is mostly of historical value in the screening of qualitative platelet abnormalities. It was used to screen for bleeding disorders and quantify platelet function in patients taking aspirin or non-steroidal anti-inflammatory medications. The American College of Clinical Pathologists' position statement identifies a carefully conducted clinical history that includes family and previous dental, obstetric, surgical, traumatic injury, transfusion, and drug histories as the best predictor of bleeding risk.[2] As most hospitals and laboratories have removed this exam from their offerings, it has become less frequently used. Most current uses are likely grounded in physician preference rather than clinical research.

Potential Diagnosis

Other potential diagnoses to consider include:

•  Thrombocytopenia

  • Decreased platelet count impairs primary hemostasis. Sepsis, drug reactions, hematologic malignancies, autoimmune conditions, and vitamin deficiencies are among the non-inherited causes. Spontaneous bleeding is generally not a problem until counts fall below 30,000.
• Von Willebrand Disease (vWD)

  • Von Willebrand disease is an inherited deficiency in the quantity or function of the platelet aggregation protein Von Willebrand factor. Rather than a bleeding time, modern workup includes a complete blood count, factor VIII levels, ristocetin cofactor activity, and a GP-Ib binding assay.
• Disseminated Intravascular Coagulation (DIC)

  • DIC is a symptom of other severe disease processes like sepsis, burns, trauma, pregnancy, and malignancy. The coagulopathy is consumptive from the formation of blood clots throughout the peripheral vasculature. Thrombocytopenia, low fibrinogen, and a high INR are the classic laboratory abnormalities.
• Glanzmann’s 

  • Glanzmann's thrombasthenia is an autosomal recessive inherited defect in the fibrinogen binding receptor glycoprotein IIb/IIIa.
• Bernard-Soulier Disease

  • Bernard-Soulier Syndrome is a rare autosomal recessive genetic defect in glycoprotein Ib, causing giant platelets with perceived thrombocytopenia. Platelet transfusion is the treatment of choice.
• Platelet Function Inhibiting Medications (aspirin, clopidogrel, ticagrelor, etc.)

  • Aspirin and other novel antiplatelet agents inhibit platelet aggregation and secretio,n overall inhibiting their function.

Normal and Critical Findings

Normal bleeding time: 

• Duke – Less than 3 minutes 
• IVY – Less than 8 minutes 

Times greater than 5 minutes in the Duke method and 10 minutes in the IVY method are concerning for coagulopathy. Abnormalities would require further evaluation with a focus on the coagulation pathway of interest.

Interfering Factors

Anything that alters platelet function can interfere with the bleeding time. Some examples include aspirin, thrombocytopenia, and uremia. Additional factors include the test procedure and the technician's subjective observation. As with all subjective tests, this one is susceptible to human error.

Complications

Both methods carry a risk of local scarring due to the incision; however, this risk is greater with the IVY technique. Local pain, infection, hematoma, and aberrant results are other potential complications. The risk of misdiagnosis due to the poor sensitivity and specificity of bleeding time is an often unaccounted complication.

Patient Safety and Education

The University of Utah Health Sciences Center undertook a retrospective review of bleeding complications in kidney biopsy 5 months before and after discontinuation of the bleeding time test. There were no statistically significant differences in post-procedural complications, DDAVP administration, or transfusions between the two groups. Additionally, the clinicians surveyed did not alter their workup and treatment of these patients.[3] This data supports the removal of bleeding time from the workup of presurgical patients. Although the test is safe, its use continues to be scrutinized due to its low sensitivity and specificity. If your doctor requests this test, inquire whether a platelet function assay would be a more suitable option. Consultation with a hematologist is the recommended course of action if the clinical picture is unclear.

Clinical Significance

Clinicians have sought a global test to assess the adequacy of primary hemostasis. While the bleeding time seems a logical fit, it has proven to be a poor predictor of clinical bleeding. Its diagnostic sensitivity and specificity are also disappointingly low. “The bleeding time is affected by a large number of diseases, drugs, physiologic factors, test conditions, and therapeutic actions, not all of them platelet-related.”[4] In May 2011, a double-blinded, randomized controlled trial demonstrated that several point-of-care platelet function analyzers were equal to or superior to bleeding time in the diagnosis of aspirin- and clopidogrel-mediated coagulopathy.[5] With the adoption of modern platelet function analyzers, this test has largely been abandoned.  

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References

1.

Kruse-Jarres R, Singleton TC, Leissinger CA. Identification and basic management of bleeding disorders in adults. J Am Board Fam Med. 2014 Jul-Aug;27(4):549-64. [PubMed: 25002009]

2.

Peterson P, Hayes TE, Arkin CF, Bovill EG, Fairweather RB, Rock WA, Triplett DA, Brandt JT. The preoperative bleeding time test lacks clinical benefit: College of American Pathologists' and American Society of Clinical Pathologists' position article. Arch Surg. 1998 Feb;133(2):134-9. [PubMed: 9484723]

3.

Lehman CM, Blaylock RC, Alexander DP, Rodgers GM. Discontinuation of the bleeding time test without detectable adverse clinical impact. Clin Chem. 2001;47(7):1204-11. [PubMed: 11427450]

4.

Rodgers RP, Levin J. A critical reappraisal of the bleeding time. Semin Thromb Hemost. 1990 Jan;16(1):1-20. [PubMed: 2406907]

5.

Chen F, Maridakis V, O'neill EA, Beals C, Radziszewski W, de Lepeleire I, Van Dyck K, Depré M, Bolognese JA, de Hoon J, Jacquemin M. A randomized clinical trial comparing point-of-care platelet function assays and bleeding time in healthy subjects treated with aspirin or clopidogrel. Platelets. 2012;23(4):249-58. [PubMed: 21919555]

Disclosure: Andrew Russeau declares no relevant financial relationships with ineligible companies.

Disclosure: Hacen Vall declares no relevant financial relationships with ineligible companies.

Disclosure: Biagio Manna declares no relevant financial relationships with ineligible companies.