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 Coagulation Disorders

Richard M. Green, M.D., Donald Silver, M.D.

Includes:

  • Bleeding Disorders/ Intraoperative Bleeding
  • Heparin Associated Thrombocytopenia
  • Hypercoagulable States
  • Low Molecular Weight Heparin
  • Antiplatelet Agents Including Ticlopidine

I. Heparin

1. To understand the role of antithrombin III and the dual action of heparin on thrombin (factor II) and factor Xa (IX a and XI a also).

2. To be familiar with its half-life, routes of administration and its uses both in terms of prevention of thrombosis and in treatment for thrombotic conditions.

3. To be familiar with the hematologic and nonhematologic complications.

4. To understand the intraoperative use including monitoring techniques and reversal.

5. To understand the mechanism of action and complications of protamine sulfate.

II. Low Molecular Weight Heparin (LMWH)

1. To understand the rationale for its development and its advantages over unfractionated heparin.

2. To understand the different mechanism of action as compared to unfractionated heparin.

3. To understand why it can be used without monitoring.

4. To understand why it is less hemorrhagic than unfractionated heparin.

5. To understand the clinical applications particularly in the patient with heparin induced thrombocytopenia and prophylaxis for venous thrombosis.

6. To understand the cost benefits of out patient treatment of venous thrombosis.

III. Heparin-induced Thrombocytopenia (HIT)

1. To understand the incidence of the syndrome in patients receiving heparin, the incidence of thrombotic complications and the mortality rate.

2. To understand the risk factors associated with its development.

3. To understand the differences between Type I and Type II HIT.

4. To understand the diagnostic criteria necessary to make the diagnosis.

5. To understand the pathophysiology of antibody formation.

6. To understand the principles of management.

7. To understand the limitations of the various diagnostic tests including platelet aggregation studies, the serotonin release assay and the PF4/heparin ELISA assay.

8. To understand when further anticoagulation is indicated and what agents are available and under development.

IV. Coumadin

1. To understand the mechanism of action including the roles of proteins C and S.

2. To understand why heparin should be given for the first 3-4 days of coumadin treatment.

3. To understand the medical conditions, foods and common drugs that affect coumadin's anticoagulant activity.

4. To understand how to minimize the complications of coumadin therapy.

5. To understand the American College of Chest Physicians recommendations of appropriate INR levels. This should include a working knowledge of the conditions which require higher levels.

6. To understand how and when to reverse anticoagulation in patients with and without hemorrhage.

7. To understand how to manage patients requiring surgery.

V. Antiplatelet therapy

1. To understand the role of platelets in primary and secondary hemostasis .

2. To understand the role of platelets in pathologic thrombosis.

3. To understand the structure of the platelet and the function of each zone.

4. To understand the sequence of platelet activation including a knowledge of the glycoprotein complexes and the role of von Willebrand's factor.

5. To understand the various platelet agonists and antagonists are their relative strengths.

6. To have a working knowledge of antiplatelet agents currently available and their mechanisms of action. This includes an understanding of the relative strengths of the antagonists: aspirin, ticlopidine , dextran , and dipyridamole .

7. To be familiar with the mechanism of action of some antiplatelet agents under investigation including von Willebrand factor monoclonal antibody, aurintricarboxylic acid, glycoprotein IIb/IIIa receptor antagonists, thromboxane/endoperoxide receptor inhibitors, prostaglandin E 1 prostacyclin , proteolytically inactive mutant thrombins , and trapidil .

VI. The Detection of Abnormal Bleeding

1. To understand the relevant historical information in patients with a bleeding disorder.

2. To understand the coagulation studies that should be done routinely and those that should be done when a bleeding disorder is suspected.

3. To understand the importance of spontaneous ecchymosis and petechiae .

4. To understand the specific clinical presentation, genetic transmission and factor deficiency in hemophilia A, hemophilia B and von Willebrand's disease.

5. To understand the purpose of the bleeding time, the significance and common causes of an abnormal test.

6. To understand how to evaluate the intrinsic coagulation cascade and what drugs and factor deficiencies affect it.

7. To understand the significance of circulating inhibitors such as the lupus anticoagulant.

8. To understand how to evaluate the extrinsic coagulation cascade and what drugs or factor deficiencies affect it.

9. To have a working knowledge of the work-up and management of perioperative bleeding.

VII. The Use of Blood Products for Surgical Bleeding

1. To understand the risks of blood products and why transfusion practices have changed.

2. To understand the indications for red cell transfusions including a knowledge of the myocardial work requirements at hemoglobin levels of <7g/dL, between 8 and 10 g/ dL and >10g/dL.

3. To understand the risks of and indications for administration of fresh-frozen plasma and cryoprecipitate.

4. To understand the indications for platelet transfusions in asymptomatic patients, patients who require a surgical procedure, and patients who have spontaneous bleeding.

VIII. Use of Desmopressin (DDAVP ) in Vascular Surgery

1. To understand the properties, mechanism of action, and indications for its use.

2. To understand the phenomenon of tachyphylaxis including why it occurs and its significance.

IX. Hypercoagulability Syndromes

1. To understand the significant history, work-up and treatment for antithrombin III deficiency, protein C and S deficiency, factor V ( Leiden ) mutation [activated protein C resistance].

2. To understand the role of pregnancy and oral contraceptives on thrombosis.

3. To understand the need for thromboembolism prophylaxis in the various acute phase reactions such as trauma or operation.

4. To understand the significance of antiphospholipid antibodies including the types of patients at risk and the management implications.

5. To understand the role of screening in routine patients and high risk patients.

6. To understand the effects of coumadin , heparin and antiplatelet agents on lab measurements for hypercoagulability .

7. To understand the differential diagnosis and management of intraoperative clotting including the management of intimal injury, heparin induced thrombosis or antithrombin III deficiency.

X. Ancrod

1. To understand the derivation, mechanism of action, and uses.

2. To understand its effect on blood viscosity and its possible benefit in patients with arterial ischemia.

3. To understand the differences between the fibrinolytic activity of ancrod as compared to urokinase .

4. To understand the risks of too rapid defibrination .

5. To understand the risks of a lack of fibrin on wound healing.

6. To understand the management of ancrod induced bleeding complications.

Posted June 2010