TY - JOUR AU1 - Tan, Kiat T. AU2 - Lip, Gregory Y. H. AB - The excellent review by Jneid et al1 has drawn attention to the role of platelets in thrombotic disorders, such as the acute coronary syndromes. However, it should be borne in mind that the humble platelet is not necessarily the main culprit in a significant proportion of thromboembolic vascular disease. Therefore, the use of the aspirin-clopidogrel combination therapy may not be the best treatment for all thrombotic diseases. Thrombotic disorders can be classified into those that are predominantly due to platelet aggregates and those that are due to the fibrin deposition. Platelets are predominantly involved in thrombosis affecting the arterial system, so-called white thrombus. It is therefore not surprising that antiplatelet agents are most effective in atherosclerotic disease (eg, acute coronary syndromes and stroke).1 In contrast, thrombi that form in the low pressure systems (such as the venous system and the cardiac atria) are rich in fibrin and trapped erythrocytes; these are often referred to as "red thrombi." The importance of this distinction between red and white thrombi lies in the fact that antiplatelet agents are often the best treatment for disease involving white thrombus, whereas red thrombi may better treated by anticoagulation. This is clearly illustrated by the fact that dose-adjusted anticoagulation is the treatment of choice for the prevention of stroke in moderate- to high-risk patients with atrial fibrillation, with a stroke risk reduction of 62% (95% confidence interval, 48%-78%) with warfarin sodium use compared with controls, which is in marked contrast to a risk reduction of 22% (95% confidence interval, 2%-33%) seen with aspirin use compared with control.2 Indeed, this stroke risk reduction of 22% with aspirin therapy is very similar to the reduction in stroke risk seen with antiplatelet therapy in high-risk patients3 (eg, previous myocardial infarction and previous stroke or transient ischemic event), and, clearly, atrial fibrillation is commonly associated with vascular disease or risk factors, such as hypertension. The possibility therefore arises that while some platelet activation is present in atrial fibrillation, it is likely to be more related to underlying vascular disease, and since abnormalities of coagulation factors feature prominently in atrial fibrillation, which confers a prothrombotic or hypercoagulable state that is independent of underlying structural heart disease or associated comorbidity, anticoagulation is (unsurprisingly) a more effective thromboprophylactic agent than aspirin.4 Nonetheless, it has recently been suggested that the use of a combination of clopidogrel and aspirin therapy in patients with atrial fibrillation may be more beneficial than the use of aspirin alone, and as good as warfarin. We recently tested this hypothesis in a randomized trial of 70 patients with nonvalvular atrial fibrillation who were not already receiving treatment, who received either aspirin-clopidogrel combination therapy or dose-adjusted warfarin therapy (target international normalized ratio, 2-3).5 We demonstrated that the aspirin-clopidogrel combination therapy caused a decrease in platelet aggregation to adenosine diphosphate but did not affect any of the markers of coagulation. This is in contrast to the dramatic effect of administering dose-adjusted warfarin, which caused a marked reduction in the plasma levels of D dimer and prothrombin fragments 1 and 2 (indexes of thrombogenesis in atrial fibrillation). Our results are in broad agreement with those of the Clopidogrel in Atrial Fibrillation (CLAFIB) trial, which was published around the same time.6 We await data from ongoing clinical trials with interest. For now, we suggest that the use of antiplatelet agents, either alone or in combination, is unlikely to replace anticoagulation as the mainstay of preventing thromboembolic events in the venous system or the atria. Nonetheless, an exciting development in this field has been the discovery of factor X inhibitors7 (eg, fondaparinux sodium), which have already been proven to be of benefit in preventing deep vein thrombosis, and the oral thrombin inhibitors (eg, ximelagatran). It is our firm belief that these agents, which are given as a fixed oral dose without the need for anticoagulant intensity monitoring (a major inconvenience with warfarin), may prove to be far more beneficial than antiplatelet drugs in the prevention and treatment of conditions associated with red thrombi. References 1. Jneid HBhatt DLCorti RBadimon JJFuster VFrancis GS Aspirin and clopidogrel in acute coronary syndromes: therapeutic insights from the CURE study. Arch Intern Med. 2003;1631145- 1153PubMedGoogle ScholarCrossref 2. Hart RGBenavente OMcBride RPearce LA Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med. 1999;131492- 501PubMedGoogle ScholarCrossref 3. Antithrombotic Trialists' Collaboration, Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;32471- 86PubMedGoogle ScholarCrossref 4. Kamath SBlann ADLip GYH Platelets and atrial fibrillation. Eur Heart J. 2001;222233- 2242PubMedGoogle ScholarCrossref 5. Kamath SBlann ADChin BSLip GY A prospective randomized trial of aspirin-clopidogrel combination therapy and dose-adjusted warfarin on indices of thrombogenesis and platelet activation in atrial fibrillation. J Am Coll Cardiol. 2002;40484- 490PubMedGoogle ScholarCrossref 6. Muller IMassberg SZierhut W et al. Effects of aspirin and clopidogrel versus oral anticoagulation on platelet function and on coagulation in patients with nonvalvular atrial fibrillation (CLAFIB). Pathophysiol Haemost Thromb. 2002;3216- 24PubMedGoogle ScholarCrossref 7. Tan KTMakin ALip GYH Factor X inhibitors. Expert Opin Investig Drugs. 2003;12799- 804PubMedGoogle ScholarCrossref TI - Red vs White Thrombi: Treating the Right Clot Is Crucial JF - Archives of Internal Medicine DO - 10.1001/archinte.163.20.2534-a DA - 2003-11-10 UR - https://www.deepdyve.com/lp/american-medical-association/red-vs-white-thrombi-treating-the-right-clot-is-crucial-v0bDEeWEiU SP - 2534 EP - 2535 VL - 163 IS - 20 DP - DeepDyve ER -