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    • Basic and Clinical Science Course - Excerpt
  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    1 Update on General Medicine

    Chapter 8: Hematologic Disorders

    Disorders of Hemostasis

    Disorders of hemostasis may be due to defects in platelet number or function or to problems in formation of a fibrin clot (coagulation). A basic understanding of the hemostatic process and the manifestations associated with specific abnormalities helps the ophthalmologist with both medical and surgical management. (See Fig 8-1 for a diagram of blood-clotting pathways.) For the purpose of laboratory test interpretation, the coagulation cascade can be divided into intrinsic and extrinsic pathways. However, it is now understood that this is an oversimplification. For example, factor IX (an intrinsic factor) can be activated by factor VII (an extrinsic factor).

    Hemostasis is initiated by damage to a blood vessel wall. This event triggers constriction of the vessel, followed by accumulation and adherence of platelets at the site of injury. Coagulation factors in the blood are activated, leading to formation of a fibrin clot. Slow fibrinolysis ensues, dissolving the clot while the damage is repaired. Circulating inhibitors are also present, modulating the process by inactivating coagulation factors to prevent widespread clotting. Normal endothelium plays a critical role in naturally anticoagulating blood by preventing fibrin accumulation. The following physiologic antithrombotic components can produce this effect:

    • antithrombin

    • protein C and/or protein S

    • tissue factor pathway inhibitor

    • the fibrinolytic system

    Figure 8-1 Blood-clotting pathways.

    Antithrombin (formerly AT III) inactivates thrombin. Activated protein C (APC), with its cofactor protein S, functions as a natural anticoagulant by destroying factors Va and VIIa. Thrombin itself activates protein C. Although inherited deficiencies of antithrombin, protein C, or protein S are associated with a lifelong thrombotic tendency, tissue factor pathway inhibitor deficiency has not yet been related to the hypercoagulable state (see the section “Thrombotic disorders” later in this chapter).

    Laboratory Evaluation of Hemostasis and Blood Coagulation

    Various techniques are used to assess the status of a patient’s hemostatic mechanisms. Following are some of the most common tests:

    • Platelet count. Minor bleeding may occur at platelet counts below 50,000/μL. Abnormal bleeding at higher platelet counts suggests abnormal platelet function. Below 20,000/μL, spontaneous bleeding may be serious.

    • Tests of platelet function.

      • Bleeding time. This was the first test of in vivo platelet function. However, because it is operator-dependent, insensitive, time-consuming, and poorly reproducible, it will likely be phased out.

      • Platelet function analyzer. This rapid and simple test measures the ability of activated platelets in a high-shear environment to occlude an aperture; it replaces in vivo bleeding time.

      • Platelet aggregometry. Various techniques include impedance whole blood, light transmission, and the VerifyNow assay. Light transmission aggregometry is the current gold standard test for measuring platelet function and inhibition.

      • Activated partial thromboplastin time (aPTT). The aPTT test incorporates factors I, II, V, VIII, IX, X, XI, and XII; prekallikrein; and high-molecular-weight kininogen. The aPTT test is most commonly used to measure the effect of heparin therapy. Platelet abnormalities do not affect the result of this test.

      • Prothrombin time (PT). The PT test measures the integrity of factors I, II, V, VII, and X. It requires a 30% concentration of the vitamin K–dependent factors II, VII, and X (but not factor IX, a part of the intrinsic pathway) and therefore is prolonged in conditions affecting these factors (see Disorders of Blood Coagulation later in this chapter). The PT test is most commonly used to monitor anticoagulant therapy. The action of heparin may slightly prolong PT.

    Efforts have been made to tailor anticoagulation therapy to the problem being treated. For example, treatment or prevention of deep venous thrombosis is thought to require less oral anticoagulation therapy than treatment of endocardial mural thrombi or cardiac replacement valves. However, because of variation in test results among and within laboratories, the international normalized ratio (INR) was developed. The INR modifies the standard PT ratio (patient PT to control PT) to reflect the particular thromboplastin reagent used by a laboratory. The resulting reported INR value is an expression of the ratio of the patient’s PT to the laboratory’s mean normal PT. Thus, for prevention or treatment of deep venous thrombosis, the recommended INR value (comparable to subsequent values measured over time or across laboratories) is 2.0–3.0; for tissue replacement valves, 2.0–3.0; and for mechanical replacement valves, 2.5–3.5.

    Genetic testing in the form of a DNA assay is also available to determine the correct warfarin dose for an individual patient, especially in cases in which resistance to the drug is suspected. This knowledge has substantially reduced the risk of bleeding and clotting events.

    Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.

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    2022-2023 Basic and Clinical Science Course, Section 01: Update on General Medicine
    2022-2023 Basic and Clinical Science Course, Section 02: Fundamentals and Principles of Ophthalmology
    2022-2023 Basic and Clinical Science Course, Section 03: Clinical Optics and Vision Rehabilitation
    2022-2023 Basic and Clinical Science Course, Section 04: Ophthalmic Pathology and Intraocular Tumors
    2022-2023 Basic and Clinical Science Course, Section 05: Neuro-Ophthalmology
    2022-2023 Basic and Clinical Science Course, Section 06: Pediatric Ophthalmology and Strabismus
    2022-2023 Basic and Clinical Science Course, Section 07: Oculofacial Plastic and Orbital Surgery
    2022-2023 Basic and Clinical Science Course, Section 08: External Disease and Cornea
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    2022-2023 Basic and Clinical Science Course, Section 10: Glaucoma
    2022-2023 Basic and Clinical Science Course, Section 11: Lens and Cataract
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