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Hypercoagulable States / Conditions


- See:
     - Coag Pathway
     - Pulmonary Embolus

- Discussion:
    - at greater than 40 years;
    - preexisting conditions such as heart disease, obesity, carcinoma,
            diabetes, varicose veins, and hypertension;
    - history of pre-existing embolism;
    - history of prolonged immobilization;
    - use of estrogens;
    - genetic factors:
          - protein C resistance
          - deficiency of antithrombin III
                   - is a plasma protease inhibitor that serves as a protease scavenger;
                   - any of the blood-clotting enzymes that move away from the growing clot rapidly form
                             a complex, and their activities are neutralized
                   - formation of complexes is accelerated by heparin, forms of which are located in the 
                             microvasculature on the surfaces of endothelial cells;
                   - inhibitor of the enzymes thrombin, Xa, IXa; Is activated by  heparin;
          - deficiency of heparain cofactor II
          - deficiency of protein S
          - deficiency of protein C
                   - when activated to Ca by thrombin bound to thrombomodulin, inhibits by proteolysis factors VIIIa and Va in reactions requiring prot S
                         and phospholipids as cofactors; Vit K dependent;
          - heterozygous carriers of both factor V leiden and the G20210A prothrombin mutation
                   - The Risk of Recurrent DVT among Heterozygous Carriers of Both Factor V Leiden and the G20210A Prothrombin Mutation.  NEJM Sept 9, 1999 Vol. 341, No. 11
          - elevated levels of factor XI
                   - in the report by JCM Meijers et al (N Engl J Med 2000;342:696-701), subjects who had factor XI levels above the 90th percentile,
                         as compared with those who had factor XI levels at or below that value, was 2.2 (95 percent confidence interval, 1.5 to 3.2);
                         - there was a dose-response relation between the factor XI level and the risk of venous thrombosis;
          - elevated levels of factor VIII:
                   - in the report by Paul A. Kyrle et al NEJM 2000, the authors evaluated the risk of a recurrence of thrombosis after an
                         initial episode of spontaneous venous thromboembolism among patients with high plasma levels of factor VIII.
                         - 360 patients w/ an average follow-up period of 30 months after a first episode of venous thromboembolism and discontinuation of oral anticoagulants;
                         - recurrent venous thromboembolism developed in 38 of the 360 patients (10.6 percent). Patients with recurrence had higher mean (±SD) plasma levels of
                                 factor VIII than those without recurrence (182±66 vs. 157±54 IU per deciliter, P=0.009). The relative risk of recurrent venous thrombosis was
                                 1.08 (95 percent confidence interval, 1.04 to 1.12; P<0.001) for each increase of 10 IU per deciliter in the plasma level of factor VIII;
                         - among patients with a factor VIII level above the 90th percentile of the values in the study population, the likelihood of recurrence at two years was
                                 37 percent, as compared with a 5 percent likelihood among patients with lower levels (P<0.001).
                         - among patients with plasma factor VIII levels above the 90th percentile, as compared with those with lower levels, the overall relative risk of
                                 recurrence was 6.7 (95 percent confidence interval, 3.0 to 14.8) after adjustment for age, sex, the presence or absence of factor V Leiden
                                 or the G20210A prothrombin mutation, and the duration of oral anticoagulation;
                         - the authors concluded that patients with a high plasma level of factor VIII have an increased risk of recurrent DVT;
                  - ref: High Plasma Levels of Factor VIII and the Risk of Recurrent Venous Thromboembolism
                                 NEJM -- August 17, 2000 -- Vol. 343, No. 7 
           - acquired risk factors:
                  - lupus anticoagulant
                  - anticardiolipin antibodies
                  - myeloproliferative disease


- Caprini Thrombosis Risk Factor Assessment:
  - Risk factors developed into point system
  - Caprini J.A. et al “Clinical assessment of venous thromboembolic risk in surgical patients” Semin Thromb Hemost 1991; 17
  - Patients assigned to:
  - Low risk (0-1 point) or minor surgery
  - Moderate risk (2 points) or major surgery
  - High risk (3-4 points) or Age >40
  - Very high risk (5+ points) or TKA/THA
  - Management based on risk
  - Low: Early ambulation/TED
  - Moderate: SC heparin or SCD
  - High: SC heparin or SCD or LMWH
  - Very High: LMWH +/- SCD or INR 2-3





References




Comparison of Enoxaparin and Warfarin for the Prevention of Venous Thromboembolic Disease After Total Hip Arthroplasty. Evaluation During Hospitalization and Three Months After Discharge
      CW Colwell et al JBJS July 1999, Vol 81-A, No 7.






Original Text by Clifford R. Wheeless, III, MD.

Last updated by Clifford R. Wheeless, III, MD on Sunday, July 20, 2008 3:40 pm