TITLE: HYPERCOAGULABLE STATES
AUTHORS: STEVEN R. DEITCHER, MD -- Department of Hematology and Medical Oncology
   MARCELO P.V. GOMES, MD -- Department of Hematology and Medical Oncology
REVIEWED: DECEMBER 15, 2003
    
Table 1:
Prevalence of Major Hypercoagulable States in Different Patient Populations
Hypercoagulable
State
General
Population (%)
Patients with
Single VTE (%)
Thrombophilic
Families (%)
Factor V Leiden
3-7
20
50
Prothrombin G20210A
1-3
6
18
Antithrombin deficiency
0.02
1
4-8
Protein C deficiency
0.2-0.4
3
6-8
Protein S deficiency
N/A
1-2
3-13
Hyperhomocysteinemia
5-10
10-25
N/A
Antiphospholipid antibodies
0-7
5-15
N/A
N/A=not readily available or unknown.

 

Table 2:
Established or Potential Hypercoagulable States
  • Activated protein C resistance
  • Alpha-macroglobulin deficiency
  • Anticardiolipin antibiodies
  • Antithrombin deficiency
  • Dysfibrinogenemia
  • Factor V Leiden
  • Factor V deficiency/excess
  • Factor VII excess
  • Factor VIII excess
  • Factor XI excess
  • Heparin cofactor II deficiency
  • Hyperhomocysteinemia
  • Hyperfibrinogenemia
  • Lupus anticoagulants
  • PAI-1 excess
  • Plasminogen deficiency
  • Protein C deficiency
  • Protein S deficiency
  • Prothrombin G20210A
  • tPA deficiency
  • TFPI deficiency
  • Thrombomodulin deficiency
PAI-1=plasminogen activator inhibitor-1; TFPI=tissue factor pathway inhibitor; tPA=tissue plasminogen activator

 

 

 

 

Table 3:
Unusual Venous Thrombotic Presentations of Certain Hypercoagulable States
VTE Presentation
Hypercoagulable Condition
Cerebral vein thrombosis Prothrombin G20210A, antiphospholipid antibodies, antithrombin deficiency, essential thrombocythemia, paroxysmal nocturnal hemoglobinuria
Cerebral vein thrombosis in women using oral contraceptive pills Prothrombin G20210A
Inferior vena cava, renal vein, mesenteric vein, portal and hepatic vein thrombosis Antiphospholipid antibodies, cancer, antithrombin deficiency, myeloproliferative syndromes, paroxysmal nocturnal hemoglobinuria
Migratory superficial thrombophlebitis(Trousseau's syndrome) Cancer (particularly adenocarcinoma of the gastrointestinal tract)
Recurrent superficial thrombophlebitis Factor V Leiden, polycythemia vera, deficiencies of natural anticoagulants
Warfarin skin necrosis Protein C and protein S deficiencies
Neonatal purpura fulminans Homozygous protein C and protein S deficiencies
Unexplained fetal loss (three or more first-trimester miscarriages or one second- or third-trimester unexplained death of a morphologically normal fetus) Antiphospholipid antibodies
  

 

Table 4:
Relative Risks of a First VTE in
Selected Hypercoagulable States
Hypercoagulable State Relative Risk of
Lifetime Single VTE
Factor V Leiden 2-10
Prothrombin G20210A 2-6
Factor V Leiden and
prothrombin G20210A
("double-heterozygous")		 20.0
Protein C deficiency 6.5-31*
Protein S deficiency 2-36*
Antithrombin deficiency 5-40*
Hyperhomocysteinemia 2-4
Lupus anticoagulant 11
Anticardiolipin antibodies 3.2
* Relative risks are highly variable, depending on whether they were derived from population- or family-based studies. Differences in risk can be explained in part by greater difficulty in obtaining reliable population-based estimates due to the overall low prevalence of these disorders. It is also possible that event rates were overestimated in early familial studies.

 

Table 5:
Interaction of Factor V Leiden and Oral Contraceptive Pill (OCP) Use in the Relative Risk of Venous Thromboembolic Disease
  
Relative
Risk
Absolute
Risk*
Noncarrier women
1
0.8/10000
Noncarrier women on OCP
4
3.2/10000
Factor V Leiden heterozygosity
7
5.7/10000
Factor V Leiden heterozygous woman
on OCP
35
28.5/10000
*Estimated number of cases of VTE per 10000 persons per year.28

 

Table 6:
Recommended Laboratory Evaluation for Patients Suspected of
Having an Underlying Hypercoagulable State
Screening Tests
Confirmatory Tests
  • Activated protein C resistance
  • Prothrombin G20210A mutation testing by PCR
  • Antithrombin, protein C, and protein S activity (functional) levels
  • Factor VIII activity level
  • Screening tests for lupus anticoagulants (sensititve aPTT, aPTT mixing studies, dilute Russell viper venom time)
  • Anticardiolipin antibody testing by ELISA
  • Fasting total plasma homocysteine level
  • Factor V Leiden PCR
  • Antigenic assays for antithrombin, protein C, and/or protein S
  • Confirmatory tests for lupus anticoagulants*
* Include at least one of the following: platelent neutralization procedure, hexagonal phase phospholipids, Textarin/Ecarin test, platelet vesicles, DVV Confirm.37
PCR=polymerase chain reaction; aPTT=activated partial thromboplastin time; ELISA=enzyme-linked immunosorbent assay.
  

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Copyright 2003 The Cleveland Clinic Foundation