TOC |
STAT
| Heme
Coagulopathies
Bleeding Disorders (1) |
Hypercoagulability
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
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"
7.Pregnancy
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
References:
Outlines in Clinical Medicine on Physicians' Online 1998
12271999