SEMINAR ON THROMBOSIS

JACOB 1. HA FT, MD, FACC, Guest Editor

Introduction

JACOB I. HAFT, MD

Newark, New Jersey

Since the initial description of-myocardial infarction and the demonstration that occluding clots in the cor- onary circulation are associated with infarction and sudden death, the mechanism of thrombus formation and methods to control clotting have been of interest to cardiologists and other physicians who treat patients with heart disease. The discovery that many patients with myocardial infarction die of pulmonary emboli added impetus to the performance of clinical trials of anticoagulation in patients admitted to the hospital with myocardial infarction. The initial studies dem- onstrated an impressive beneficial effect of anticoagu- lation, and very soon the use of heparin and warfarin, or its derivatives, was as routine in the management of the patient with a heart attack as was the use of oxygen, sedation and bed rest. As further well controlled studies were carried out, the initial overwhelming enthusiasm began to abate. The less impressive results with regard to the effect on death rate may have been due to better study design. However, earlier ambulation and other methods to decrease the incidence of venostasis and deep vein thrombophlebitis also may have played a part in decreasing the difference in mortality between pa- tients receiving anticoagulant therapy and control subjects. Throughout the late 1950’s and into the 1960’s numerous debates were conducted in the medical journals and at national meetings as to whether the benefit of anticoagulation outweighed the potential of bleeding complications. Cardiology rounds in hospitals throughout the country frequently discussed when and how to use anticoagulation in patients with myocardial infarction. “Definitive” study after “definitive” study appeared that purported to solve this clinical di- lemma.

With the large incidence of thrombophlebitis and pulmonary embolism that often follows myocardial infarction, the management of thrombophlebitis not necessarily associated with infarction has also become

From Saint Michael’s Medical Center, Newark, New Jersey. Address for reprints: Jacob I. Haft, MD, Saint Michael’s Medical

Center, Newark, New Jersey 07102.

the province of cardiologists in many hospitals. Over the years this development has led to the creation of more sophisticated methods for diagnosing and managing phlebitis and of many techniques, including small dose heparin therapy, for preventing its occurrence.

The use of antifibrin anticoagulation has been, of value in decreasing the incidence of thrombophlebitis and systemic emboli but has not been effective in pre- venting the progression or recurrence of myocardial infarction. Recently, attention has been turned to blood platelets and their role in the origin of myocardial in- farction. Blood platelets have been known for some time to play the initiating role in the formation of clots in the arterial system, maintaining the integrity of the vascular system and preventing bleeding. Inappropriate platelet aggregation in the arterial system could theoretically lead to occlusion of a narrowed area in a coronary artery and result in myocardial infarction. The availability of a wide variety of drugs already in use for other indica- tions that also have inhibiting effects on platelet aggregation have led to trials of antiplatelet drugs in patients with coronary artery disease. The report in the winter of 1978 of a beneficial effect of sulfinpyrazone in preventing death in patients with myocardial infarction has brought this newer method of affecting the clotting mechanism to the attention of cardiologists and phy- sicians who manage patients with coronary artery dis- ease. It has also excited interest in the lay public through various media reports. The theoretical suggestion that platelets may play a part in the origin of the arterio- sclerotic plaque has led to further interest in antiplatelet therapy.

The three papers in this Seminar review the current thinking on the use of anticoagulation in the manage- ment of coronary artery disease and thrombophlebitis and discuss the available data linking blood platelets with coronary artery disease and with myocardial in- farction.

In their paper, Frishman and Ribner review the cur- rent status of anticoagulation in the management of myocardial infarction. They discuss the value of anti-

June 1979 The &nerkan Journal of CARDfCLOGY Volume 43 1195

INTRODUCTION-HAFT

coagulation in the prevention of deep vein thrombosis and pulmonary embolism in patients with infarction. They also cover the value of anticoagulation in pre- venting peripheral and cerebral arterial emboli, further complications that occasionally change a benign post- infarction course into a catastrophic one. The. compli- cations of anticoagulant therapy and the various forms of anticoagulation are presented and the use of small dose heparin therapy after myocardial infarction is discussed. Recommendations are presented as to which patients should receive anticoagulant therapy, for how long and using what regimens.

New techniques for diagnosis and prevention of thrombophlebitis are reviewed by Sasahara, Sharma and Paresi. In recent years more precise methods for detecting early venous thrombosis have been developed. Sasahara et al. discuss in depth the relatively new technique of impedance plethysmography, which ap- pears to be a sensitive and relatively specific method for noninvasively documenting venous occlusion and for confirming the diagnosis of pulmonary embolism. Sa- Sahara et al. discuss the data available on the benefit of small dose heparin therapy, dextran and antiplatelet aggregating agents used for this purpose. Physical measures such as elevation of the legs, use of elastic stockings and early ambulation remain to be fully proved as effective preventative measures. Intermittent calf muscle compression with the external pneumatic boot has recently received attention as an effective measure in many patients for prevention of venous thrombosis. The authors review the data supporting the use of this device, especially in patients who are not candidates for small dose heparin therapy.

The final paper in the Seminar presents the data leading to the concept that blood platelets play a role in coronary artery disease. Evidence is available that platelet aggregates forming inappropriately in the vasculature of the heart can cause ischemic damage. Platelet aggregates can stimulate spasm and may be an initiating factor in the origin of the arteriosclerotic le- sion. Most of the coronary risk factors have been found to be associated with platelet function abnormalities. Findings such as these have been the stimulus for the performance of a number of clinical studies that have explored the value of various platelet aggregation in- hibiting drugs in the prevention of infarction or death in patients with coronary artery disease. The results of the studies of clofibrate, aspirin and the recent report of the use of sulfinpyrazone for this purpose are’pre- sented and discussed. Although all of the data on the value of the antiplatelet drugs is not yet formulated, on the basis of what is available, recommendations as to the use of these agents are presented.

Modification of the clotting mechanism has now be- come a recognized form of therapy. Although the “de- finitive” study with regard to the use of antifibrin drugs has not yet been performed, the large accumulation of data justifies the reasonable use of these agents. Anti- platelet therapy in coronary disease is only in its early stages now and further reports are needed that will define its theoretical benefit. It is our hope that this short symposium will serve to clarify the role of therapy aimed at modification of blood clotting in cardiovas- cular disease and to provide the background material with which the treating cardiologist can evaluate further developments in this field.

1196 June 1979 The American Journal of CARDIDLDGY Volume 43