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 Coagulation and Disorders of Hemostasis

1. Physiology

  • Basic mechanisms of coagulation (extrinsic/intrinsic pathways of coagulation, the role of platelets).
  • Natural anticoagulant mechanisms (antithrombin III, proteins C and S, heparin cofactor II).
    Fibrinolysis.

2. Hypercoagulable states

  • Heparin-associated thrombocytopenia.'
  • Antithrombin III deficiency.
  • Protein C and S deficiency.
  • Factor V Leiden mutation.
  • Lupus anticoagulant/antiphospholipid syndrome.
  • Abnormalities of fibrinolysis.
  • Abnormal platelet aggregation.
  • Disseminated intravascular coagulation.

3. Bleeding disorders

  • Hemophilia A.
  • Hemophilia B.
  • von Willebrand disease.
  • Factor XI deficiency.
  • Factor V deficiency.
  • Factor VII deficiency.
  • Deficiencies of fibrinogen.
  • Platelet disorders.

4. Pharmacologic – nonpharmacologic interventions

  • Anticoagulant agents (structure, mechanism of action, complications, monitoring of the anticoagulant effect).
  • Heparin (unfractionated and low molecular weight).
  • Heparinoids (danaparoid).
  • Warfarin.
  • Hirudin.
  • Ancrod.
  • Antiplatelet agents (mechanism of action, complications).
  • Aspirin.
  • Dipyridamole.
  • Ticlopidine.
  • Clopidogrel.
  • Abciximab.
  • Fibrinolytic agents (source, mechanism of action, complications, monitoring of the fibrinolytic effect).
  • First-generation agents (streptokinase and urokinase).
  • Second-generation agents (recombinant tissue plasminogen activator and antistreplase).
  • Third-generation agents (reteplase).
  • Nonpharmacologic interventions.
  • Mechanical measures (early ambulation, elastic stockings, electrical calf muscle stimulation, external pneumatic compression).
  • Vena cava filters.
  • Pulmonary embolectomy.

References

Hassouna HI. Laboratory evaluation of hemostatic disorders. Hematol Oncol Clin North Am 1993;7:1161-1249.

This article is abroad review presenting in detail the roles of coagulation testing in the management of bleeding and thrombotic disorders. Limitations of coagulation testing in defining the hemostatic state, interpretation of abnormal coagulation test results and the possible relationship to excessive bleeding and thrombosis are thoroughly discussed.

Whiteman T, Hassouna HI. Hypercoagulable states. Hematol Oncol Clin North Am 2000;14:355-377.

The focus of this article is understanding mechanisms in the hypercoagulable state that enhance and maintain the production of thrombin in circulating blood while preventing its progression to thrombosis. These mechanisms include reactions that produce thrombin from prothrombin, feedback loop mechanisms that affect the rate of thrombin production from prothrombin and the inactivation of thrombin in blood.

Van Cott EM, Soderberg BL, Laposata M. Activated protein C resistance, the factor V Leiden mutation, and a laboratory testing algorithm. Arch Pathol Lab Med 2002;126:577-582.

This report describes the protein C/protein S pathway, the significance of activated protein C resistance and the factor V Leiden mutation, and the clinical testing used to detect activated protein C resistance and the factor V Leiden mutation. A proposed laboratory testing algorithm is also provided.

Triplett DA. Coagulation and bleeding disorders: review and update. Clin Chem 2000;46:1260-1269.

This review considers laboratory tests used to evaluate coagulation, including prothrombin time, activated partial thromboplastin time, thrombin time, and platelet count. It discusses hereditary disorders of platelets and/or coagulation proteins that lead to clinical bleeding as well as acquired disorders, including disseminated intravascular coagulation and acquired circulating anticoagulants.

Frangos SG, Chen AH, Sumpio B. Vascular drugs in the new millennium. J Am Coll Surg 2000;191:76-92.

This review discusses pharmacologic therapy of cardiovascular disorders including antiplatelet agents, anticoagulants, thrombolytics, and claudication-alleviating drugs. Each drug category is introduced with a brief review of the current "gold standard" medication, with emphasis on the limitations and weaknesses that the newer agents have been designed to overcome.

Posted June 2010