TOC |  STAT Heme Coagulopathies          Bleeding Disorders (1)   |  Hypercoagulability         

A. Increased Bleeding Disorders

1.Factor XII Deficiency

2.Factor XI Deficiency: bleeding fairly common, particularly after surgery

3.Hemophilias   See outline "Hemophilias"

4.Von Willebrand's Disease

5.Disorders of Mixed Bleeding and Thromboembolic Events

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B. Thrombophilic Disorders  

1.Antithrombin Deficiency

2.Protein C Disorders

3.Protein S Deficiency

4.Antiphospholipid Syndrome

5.Hyperhomocysteinemia - See outline "Vascular Pathophysiology"

6.Oral Contraceptives - relative risk ~3 fold -   See outline "Contraceptives"


8.Estrogen Replacement Therapy

9.Malignancy -   See outline "Paraneoplastic Syndromes"

10.Factor VII H7H7 Genotype (H6H6 high risk)

C. Antithrombin Deficiency      Back to top  |   Home Page 

1.Previously called antithrombin 3 deficiency

2.Autosomal dominant inheritance, 1/2000 persons

3.Risk increased for venous thromboembolic disease

4.Increased risk for fetal loss (~5X normal risk)

5.Increased risk for thromboembolism in third trimester and peripartum

6.Purified antithrombin now available

D. Protein C Deficiency     Back to top  |   Home Page

1.Symptoms may occur in persons with <50% of normal levels

2.Effects of Protein C Deficiency [3,10,12]

3.Warfarin anticoagulant therapy appears to acutely decrease Protein C levels

4.This precedes the decrease in the other Vitamin K dependent zymogens

5.Skin necrosis may occur, especially with warfarin therapy

6.May accompany disseminated intravascular coagulopathy (DIC) and/or liver dysfunction

7.Usual therapy is lifelong warfarin, but this may not be optimal [12]

8.Warfarin does reduce risk of recurrent thromboembolism by about 50%

E. Clotting Factor V "Leiden" Mutation     Back to top  |   Home Page

1.Mutation at position 506 in Factor V, first described in Leiden

2.Frequently associated with hyperhomocytinuria and thrombosis [2]

3.Risks of Thromboembolic Events with Factor V Leiden [10]

4.Activated Protein C assays or DNA sequences must be measured to detect Leiden

F. Protein S Deficiency     Back to top  |   Home Page

1.Hereditary disease is best characterized; acquired deficiency may occur in cancers

2.Associated with increased risk of venous thromboembolic disease

3.Much increased risk for venous thromboembolism in third trimester and peripartum [6]

4.May become manifest first with warfarin therapy or with increased fetal loss [4]

5.Functional protein S deficiency may occur in patients with carcinomas

6.This may be related to the etiology Trousseau's Syndrome

G. Anti-Phospholipid Syndrome     Back to top  |   Home Page

1.Components of Syndrome

2.May be primary or associated with Systemic Lupus or other autoimmune disorders

3.Anti-phospholipid Ab reduce levels of annexin V and accelerate plasma coagulation [11]

H. Abnormal Platelets   Back to top  |   Home Page

1.Essential thrombocythemia

2.Heparin induced thrombocytopenia - thromboembolic events [1]

3.Homocysteinuria - possible effect on platelets and vascular endothelium

4.Coagulation Defects - von Willebrand's Disease, Chronic Renal Fialure (dialysis)

I. Evaluation of Procoagulants  Back to top  |   Home Page

1.Prothrombin Time (PT)

2.Partial Thromboplastin Time (PTT)

3.Inhibitor Screens

4.Thrombin Time

5.Reptilase Time

6.Factor V Leiden Mutation Screening

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Outlines in Clinical Medicine on Physicians' Online   1998