Medical Information: Indications for PT/INR Monitoring

The main indications for a patient to receive vitamin K antagonists (coumarin derivatives) and to monitor PT/INR values are the following:

Atrial Fibrillation

Atrial fibrillation is characterized by disorganized atrial activity which can cause clots to form within the cavity of the atria. Atrial fibrillation occurs in approximately 2-4% of persons over 60 years of age and in up to 10% of persons over 80. Where oral anticoagulation is indicated, a risk stratification must be performed. Patients with permanent atrial fibrillation with and without a history of thromboembolic events will need life-long oral anticoagulation (1, 2).

Anticoagulation
The intensity of anticoagulation, unless there are simultaneously other cardiovascular conditions, e.g. following mechanical mitral valve replacement, should be moderate, i.e., an INR of between 2 and 3 should be the target (3). According to a large European fibrillation study involving more than 1,000 patients, a risk reduction for stroke from 12% to 4% was achieved for this clinical picture (4). In other words, the number of stroke events can be reduced by 80 in every 1,000 patients treated with anticoagulants (4).

Mechanical Heart Valves

Permanent anticoagulation therapy is justified by an increased risk of thromboembolic complications after replacement of any valve with a mechanical prosthesis (5, 6). Mostly, heart valve defects are acquired later in life and are due to degenerative heart valve disease. Heart valve replacement becomes necessary when hereditary or acquired defects severely limit valve function.

Causes of heart valve defects (7):

• Congenital heart valve defect in the infant.
  
• Rheumatic fever - rarely seen nowadays in western industrial nations
  
• Changes to the valvular apparatus due to infection, immunological, ischaemic, traumatic or degenerative factors
  
• Acquired valvular stenosis may be a consequence of organic changes to the tissue of the valve; insufficiency may be a secondary consequence of ventricle volume load or congestive heart failure
  
  The indication for operation and/or interventional treatment of the heart valves is nowadays considered earlier (8). In Europe, corrective heart valve surgery is performed in approximately 25% of all heart operations: Mechanical heart valves are particularly long-lived, but require that the patient takes life-long oral anticoagulation medication (6). Biological heart valve prostheses have the benefit of not requiring prolonged anticoagulation, but calcify sooner and have to be replaced after 10 to 15 years (9).
  
  Anticoagulation
  Post-operative mortality and morbidity can be improved through individual adjustment of anticoagulation intensity, involvement of the patient, and the use of the international normalised ratio (INR) as control parameter. Studies such as ESCAT (Early Self Controlled Anticoagulation Trial) (10, 11) have shown that in cases where patients practise Self-Management they remain within their optimum therapeutic target range for much longer and so reduce significantly the rate of complications.
  
  

Other Indications for Anticoagulation Therapy

Myocardial Infarction
The most frequent heart disease in western countries is coronary heart disease. Every second patient with coronary heart disease suffers acute myocardial infarction (12, 13).

Anticoagulation
Oral anticoagulation is indicated following major anterior-wall infarction with severely reduced left-ventricular function with or without atrial fibrillation. Also, thrombi in the heart require anticoagulation following infarction. Recent acute phase studies (WARIS-II study, ASPECT II) show that combined administration of anti-aggregants and oral anticoagulants can bring about up to almost 30% reduction in risks compared to the administration of anti-aggregants alone (14, 15).

Thrombosis and Pulmonary Embolism
Various risk factors favour thrombotic events mainly in the deep veins of the leg and pelvis. Effective medications are available to prevent the spread of thrombosis and the consecutive occurrence of potentially fatal pulmonary embolism.

Anticoagulation
Heparin acts immediately to inactivate mainly factor Xa and thrombin. It has to be administered parenterally and is thus not suitable for long-term therapy. The action of the coumarins is based on reducing the activity of factors IX, VII, X and prothrombin (II). Several days are required for the onset of the anticoagulant effect of coumarin preparations, so that heparin and coumarins must be used in combination to treat acute thrombosis (16). Once the therapeutic range of anticoagulation (INR) has been reached, parenteral treatment with heparin may be terminated (16).

Acute Ischemic Stroke
Stroke is caused by an acute circulatory disturbance in a defined region of the brain. In 20% of cases a haemorrhagic insult is involved, in 80% of cases an ischaemic insult. Ischaemic cerebral stroke is the third most frequent cause of death in Europe. Improved management of risk factors such as arterial hypertension, atrial fibrillation, diabetes mellitus, hypercholesterolaemia, nicotine abuse and excessive alcohol consumption can reduce the incidence of stroke considerably.

Anticoagulation
Anticoagulation in patients with ischaemic cerebral insult should not be installed in every case, as there is no proof so far that any improvement in prognosis nor any lowering of the relapse risk can be achieved thereby (17). On the other hand, patients with proven cardiological pathology can benefit from anticoagulation therapy. Thrombocyte aggregation inhibitors administered within the first 48 h after the event reduce mortality and relapse occurrences minimally, but nevertheless statistically significantly (18, 19).

Statements based on references

1. Snow V, Weiss KB, LeFevre M, et al. Management of newly detected atrial fibrillation: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Intern Med 2003; 139:1009-1017.
   
2. Singer DE, Albers GW, Dalen JE, Go AS, Halperin JL, Manning WJ. Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126:429S-456S.
   
3. Vink R, Van Den Brink RB, Levi M. Management of anticoagulant therapy for patients with prosthetic heart valves or atrial fibrillation. Hematology 2004; 9:1-9.
   
4. Hart RG, Pearce LA, Koudstaal PJ. Transient ischemic attacks in patients with atrial fibrillation: implications for secondary prevention: the European Atrial Fibrillation Trial and Stroke Prevention in Atrial Fibrillation III trial. Stroke 2004; 35:948-951.
   
5. Vongpatanasin W, Hillis LD, Lange RA. Prosthetic Heart Valves. N Engl J Med 1996; 335:407-416.
   
6. Gohlke-Barwolf C. [Current recommendations for prevention of thromboembolism in patients with heart valve prostheses] (german article). Z Kardiol 2001; 90 Suppl 6:112-117.
   
7. Braunwald E. Valvular heart disease. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. Harrison's principles of internal medicine. New York: McGraw-Hill, 2001; 1343-1355.
   
8. Carabello BA, Crawford FA. Valvular Heart Disease. N Engl J Med 1997; 337:32-41.
   
9. Ennker Jr, Lauruschkat A. Mechanische vs. biologische Herzklappen. Z Kardiol 2001; 90.
   
10. Koertke H, Korfer R. International normalized ratio self-management after mechanical heart valve replacement: is an early start advantageous? Ann Thorac Surg 2001; 72:44-48.
    
11. Koertke H, Zittermann A, Minami K, et al. Low-dose international normalized ratio self-management: a promising tool to achieve low complication rates after mechanical heart valve replacement. Ann Thorac Surg 2005; 79:1909-1914; discussion 1914.
    
12. World Health Organization. Cardiovascular death and disability can be reduced more than 50 percent. Press release 2002.
    
13. Wong ND. Cardiovascular disease epidemiology - definitions, risk assessment, incidence, and tools. University of California Heart Disease Prevention Program 2002.
    
14. Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 2002; 347:969-974.
    
15. van Es RF, Jonker JJ, Verheugt FW, Deckers JW, Grobbee DE. Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet 2002; 360:109-113.
    
16. Buller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126:401S-428S.
    
17. Swanson RA. Intravenous heparin for acute stroke: what can we learn from the megatrials? Neurology 1999; 52:1746-1750.
    
18. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet 1997; 349:1569-1581.
    
19. CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet 1997; 349:1641-1649.
    
    

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