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Hematology/Oncology Clinics of North America

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HYPERCOAGULABLE STATES - 04/09/11

Doi : 10.1016/S0889-8588(05)70138-6 
Terence Whiteman, MD *, Houria I. Hassouna, MD, PhD *

Résumé

The hypercoagulable state places an individual at risk for, but does not in itself inevitably lead to, thrombosis. This article focuses on the 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 (1) reactions that produce thrombin from prothrombin, (2) feedback-loop mechanisms that affect the rate of thrombin production from prothrombin, and (3) the inactivation of thrombin in blood. The fibrinolytic system is involved in clot lysis but not in thrombin production and inactivation.

The hypercoagulable state has been defined as the potential to develop thrombosis in association with hereditary and noninherited genetic mutations and acquired disorders.2, 3, 4, 5, 6, 9, 10, 13, 19, 31, 39, 40, 45, 46, 47 The most commonly encountered disorders include

1
Genetic disorders of the hemostatic system:
•
Heterozygote antithrombin, protein C, and protein S nonsense mutations associated with decreased protein levels and activity10, 13, 31, 58
•
Abnormal clotting Factor V that resists proteolytic degradation by protein C8, 10
•
Heterozygote antithrombin, protein C, and protein S missense mutations (Missense mutations are characterized by normal protein levels and decreased anticoagulant activity.)16, 31
•
Compound heterozygote missense mutations involving both protein C and S16
•
Heterozygote mutations involving both Factor V Leiden mutation and protein C, protein S, or antithrombin13, 25
•
Inherited regional fibrinogen variants that decrease the rate of fibrin polymerization.21, 27 The physiologic pathway for thrombin inactivation is by specific binding to fibrin and incorporation into the fibrin clot. Fibrin produced from variant forms of fibrinogen does not effectively incorporate thrombin into clots.
•
Vascular malformations, congenital heart disease23
2
Risk factors associated with other genetic disorders
•
Diabetes
•
Polycythemia rubra vera
•
Sickle cell disease47
•
Thalassemia
•
Elevated ⍺-lipoprotein
•
Homocystinemia50
•
Hypertriglyceridemia
•
Chronic renal failure
•
Obstructive pulmonary disease
•
Paroxysmal nocturnal hemoglobinuria
3
Select acquired risk factors
•
Physiologic factors, including neonatal and postpartum states and pregnancy
•
Acquired coagulation and platelet disorders,5, 14, 15, 23 including thrombocytosis, abnormal fibrinogen variants, lupus anticoagulant, and antiphospholipid antibodies
•
Acquired antithrombin, protein C, or protein S deficiencies
•
Cardiovascular conditions,23, 33, 38, 40, 43 including mitral valve prolapse, heart failure, prosthetic heart valves, atrial fibrillation, hypertension with elevated angiotensin II, injured vessel wall, valvular insufficiency, abdominal aortic surgery, angioplasty, coronary bypass, central venous catheters, other indwelling vascular access devices, cardiopulmonary bypass2, 3, 4, 5, 37, 40, 46, 47, 51, 54
•
Therapeutic agents: oral contraceptives,43, 46 androgens, l-asparaginase, warfarin, thrombolytic therapy,17, 54, 63 and Factor IX concentrates
•
Surgical intervention: hepatic resections, gynecologic surgery, hip and knee replacements, laparoscopic cholecystectomy
•
Malignancies: acute promyelocytic leukemia, pancreatic and prostate cancers, metastatic tumors
•
Infections: gram-negative sepsis, acute pancreatitis
•
Nephrotic syndrome, cerebral infarcts37
These conditions are summarized in the following box.

Genetic Disorders Associated with Hypercoagulability


    Hemostatic System Other Systems Antithrombin Diabetes Protein C Polycythemia rubra vera Protein S Sickle cell anemia Abnormal clotting Factor V Congenital heart disease Fibrinogen variants Thalassemia Elevated lipoprotein ⍺ Homocystinemia Hypertriglyceridemia Paroxysmal nocturnal hemoglobinuria

    Hemostatic System Other Systems 
Antithrombin Diabetes 
Protein C Polycythemia rubra vera 
Protein S Sickle cell anemia 
Abnormal clotting Factor V Congenital heart disease 
Fibrinogen variants Thalassemia 
 Elevated lipoprotein ⍺ 
 Homocystinemia 
 Hypertriglyceridemia 
 Paroxysmal nocturnal hemoglobinuria 

The most intriguing aspect of the hypercoagulable states, and one which has received little attention, is the low frequency with which they are associated with thrombosis.46 For example, in pregnancy and other acquired and inherited hypercoagulable states, the calculated incidence of associated thrombosis, although slightly higher than in the general population, is less than 10%. This article provides information needed for the diagnosis and management of the hypercoagulable patient. It is divided in three sections: (1) a review of the regulatory systems that govern the hemostatic state; (2) a clinical presentation of the hypercoagulable anticoagulant deficiency genotype and the more common phenotype associated with disseminated intravascular coagulation; and (3) molecular markers.

Le texte complet de cet article est disponible en PDF.

Plan


 Address reprint requests to Houria I. Hassouna, MD, PhD, Department of Medicine, B-239 Clinical Center, Michigan State University, East Lansing, MI 48824–1313, e-mail: hassouna@msu.edu


© 2000  W. B. Saunders Company. Publié par Elsevier Masson SAS. Tous droits réservés.© 1986  © 1994 
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Vol 14 - N° 2

P. 355-377 - avril 2000 Retour au numéro
Article précédent Article précédent
  • A COMPREHENSIVE REVIEW OF VITAMIN K AND VITAMIN K ANTAGONISTS
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  • Pierre Toulon, Patricia Perez

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