Laboratory Assessment of Hemostasis

Many of the bleeding disorders can be diagnosed and monitored by way of laboratory testing. When a significant coagulation disorder occurs in the vascular or platelet phase a clinical bleeding problem is observed immediately after injury, or during invasive medical or dental procedures. Conversely, when a significant disorder affects the coagulation phase (clotting factors), the clinical bleed will most likely not be observed until several hours or longer after the injury or invasive procedure.

Various laboratory screening tests can be ordered by the dentist when the patient reports a bleeding disorder, when the patient responds positively to a family history of a bleeding disorder; or when the clinician observes a sign/symptom of a bleeding problem during the clinical exam. Patients with unknown bleeding problems should be referred to their physician or to a hematologist for further evaluation. Laboratory tests provide an assessment of adequate numbers of platelets, proper functioning of platelets, sufficient levels of plasma coagulation factors, and proper functioning of the fibrinolytic pathway. When evaluating defects in the hemostatic system prior to invasive dental treatment, dental professionals should become familiar with the following common blood laboratory tests.1

Common Blood Laboratory Tests

Platelet Count is a routine blood laboratory test that provides a quantitative assessment of circulating platelets in the vascular system. A normal platelet count should be within the range of 150,000 to 450,000 cells/mm3 of blood.8 When the platelet count is less than 100,000 cells/mm3, thrombocytopenia is diagnosed. Patients presenting with a platelet count between 50,000 and 100,000 cells/mm3 will predictably bleed mildly with severe trauma or with dental surgical procedures. When the platelet count is less than 20,000 cells/mm3 an excessive and prolonged bleed is predictable; thus, this high-risk condition will require medical attention prior to dental invasive procedures.2 Ultimately, thrombocytopenia can prevent the formation of a hemostatic plug, resulting in hemorrhage.

The Ivy Bleeding Time laboratory test has been routinely used as a screening test for assessing adequacy of platelet function. Abnormal platelet function is termed thrombocytopathy. When performed, the bleeding time test calculates the time required for a standard skin incision to stop bleeding by the formation of a hemostatic plug.9 The normal range of the Ivy Bleeding Time test is usually between 2 and 10 minutes.8

Over the years, this test was presumed to provide a measurement of bleeding risk in patients by way of a prolonged bleeding time result. Consequently, its current use and application have been deemed very limited because of its recognized unreliability to predict bleeding risk based on an abnormal test result.10,11 This test fails to produce quantifiable and useful information for several reasons. According to an original article by authors Peterson et al., the following major conclusions were drawn regarding this test:10

  1. Given the normal results of a standard bleeding time test one cannot exclude the possibility of a significant clinical bleed with invasive dental procedures.
  2. Without a positive medical history finding related to a bleeding disorder/platelet disorder, the bleeding time test is not a “useful predictor” of an excessive bleed when performing invasive dental procedures; and
  3. The results of a prolonged bleeding time cannot reliably identify patients who are taking anti-platelet therapy; thus, a prolonged bleeding time cannot be linked to the ingestion of aspirin or NSAIDs.10,11 Therefore, the bleeding time test is merely a tool to screen for platelet disorders; it is not an effective clinical testing method for predicting the quantity of a bleed associated with an increased bleeding time in such patients.10

Platelet Function Analyzer (PFA-100) is a sophisticated laboratory screening testing devise that is currently being used in place of the Ivy Bleeding Time test. Platelet function tests or platelet function assay (PFA) evaluate the qualitative function of platelets.

These tests provide an assessment of platelet adhesion, platelet activation and platelet aggregation during the development of a platelet plug, or primary hemostasis.2,12 Generally, these tests measure the time it takes for a clot to form (platelets to clump together) to prevent blood loss as the closure time. The PFA test (and other platelet function tests) has not been shown to predict the likelihood that a patient will bleed excessively during invasive procedures; although, it's full clinical utility has yet to be established.12,13

Prothrombin Time (PT), measures the patient’s ability to form a definitive clot by monitoring the proper functioning of the extrinsic coagulation pathway (Factor VII) and the common pathway (Factors V, X, prothrombin and fibrinogen). Factors VII, X and prothrombin are Vitamin K-dependent for their synthesis and become unstable when coumarin-like drugs are prescribed.2,5,9 A normal coagulation profile indicates adequate levels or percentages of clotting factors in the extrinsic and common pathways. Generally, the laboratory testing range is between 11–15 seconds.8 Testing results beyond 15 seconds indicate an abnormal or prolonged PT. This outcome is indicative of deficient coagulation factors needed to form a fibrin clot, resulting in a prolonged bleed in the body. An active bleed caused by anticoagulation therapy, coumarin-like drugs, is most commonly monitored by the international normalized ratio (INR) laboratory test.

International Normalized Ratio (INR) In 1983, the World Health Organization Committee on Biological Standards established a more precise laboratory testing method, the INR, to monitor patients taking anticoagulation drugs (warfarin therapy). Consequently, laboratory materials (thromboplastin reagents) and laboratory techniques were internationally instituted for the purpose of standardizing the assigned values. Patients with a normal coagulation profile result in an INR value of 1.0.11,14 The “low intensity” INR range is between 2.0 and 3.0; and the “high-intensity” INR range is between 2.5 and 3.5. What governs the intensity of anticoagulation therapy? The intensity is determined by the patient’s predisposition to abnormal clotting. Patients diagnosed at high risk clot formation, will require higher intensity of anticoagulation.4 From a pharmacological standpoint, anticoagulant drugs inactivate Factor VII within the extrinsic pathway by inhibiting Vitamin K action; Vitamin K is required by the liver to synthesize Factor VII.

Activated Partial Thromboplastin Time (aPTT) also measures the patient’s ability to effectively form a definitive clot by evaluating the effectiveness of the intrinsic and common pathways of the coagulation cascade.2,5,9 It tests for deficiencies in the intrinsic pathway, specifically factors VIII, IX, XI, XIII; and deficiencies in the common pathway, specifically factors V and X, prothrombin and fibrinogen. A normal aPTT is usually 25 to 40 seconds.8 The aPTT is the laboratory test most often used by physicians to monitor heparin therapy and to diagnose the hemophilias, which result in a prolonged or increased aPTT time.2,9,11

Thrombin Time laboratory test assesses the conversion of fibrinogen to insoluble fibrin by adding thrombin to the patient’s blood sample.2,8 Specifically, this test bypasses the extrinsic, intrinsic and common pathways to determine the stability of the clot. Normally, the range of this test is between 9 and 13 seconds.2 A prolonged time, in excess of 16 to 18 seconds, is considered abnormal.2

Table 2. Blood Laboratory Tests that Evaluate Hemostasis and Bleeding Disorders.2,4,8,14
Laboratory TestsMeasures Normal Function*Normal Values/RangesImportance in Diagnosing Bleeding Disorders*Abnormal Values/Ranges
Platelet CountAdequate platelet numbers150,000 to 450,000/mm3Assess thrombocytopenia or inadequate numbers of platelets100,000 cells/mm3
Ivy Bleeding TimeAdequate platelet function2-10 minutesScreening test for thrombocytopathy; von Willebrand’s diseaseProlonged time:
>9-10 minutes
Platelet Function TestsAssess function of platelets: attachment, activation, and aggregation Discriminates between normal and abnormal function of platelets
Prothrombin Time (PT)Assess the time it takes to form a fibrin clot when calcium and tissue factor are added to the plasma (extrinsic pathway: coagulation function of factor VII; common pathway: factors V, X, prothrombin and fibrinogen)11 to 15 secondsAssess defects in the extrinsic pathway of the coagulation system: anticoagulant therapy (warfarin); Prothrombin deficiency, vitamin K deficiency; liver disease; antiplatelet drugsProlonged time:
>30 seconds
International Normalized Ratio (INR)

Coagulation function of the extrinsic pathway: Factors V, VII, X, prothrombin and fibrinogen

1.0Monitors oral anticoagulation therapy: warfarinINR greater than 1.2 in patients not on anticoagulation therapy. In patients on anticoagulants, therapeutic range is between 2.0 and 3.5
Partial Thromboplastin Time (activated aPTT)Assess the time it takes to form a fibrin clot when calcium and partial thromboplastin containing phospholipids are added to the plasma (intrinsic pathway: coagulation function of factors VIII, IX, XI and XII25 to 40 secondsAssess defects in the intrinsic pathway of the coagulation system: anticoagulant therapy (heparin); von Willebrand’s disease; hemophilia A and BProlonged time:
45 to 50 seconds
Thrombin TimeThrombin is added to blood to convert fibrinogen to fibrin24 to 35 secondsAssess defects in the conversion of fibrinogen to fibrinProlonged or beyond normal
*Normal values or ranges may vary among different laboratories.