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An evaluation of the comparative actions of Tromexan and dicumarol is herein reported. Five hundred fourteen patients were studied; a total experience of 6,642 days of Tromexan therapy and 5,006 days of dicumarol therapy were reviewed and analyzed. Previous reports of the more rapid initial prolongation of the prothrombin times and more rapid return to normal following cessation of therapy with Tromexan were confirmed. During adequate therapy the protection against thromboembolism was approximately equal for the two drugs. In other respects and with minor variations Tromexan and dicumarol were found to be quite comparable. The general advantages of anticoagulant therapy in the prevention of deaths and thromboembolic complications in myocardial infarction were comfirmed.

The use of heparin and dicumarol has provided important information regarding the effectiveness and the difficulties of anticoagulant therapy. Neither, however, is an ideal anticoagulant; therefore a search for new substances with advantages over them must be continued. Tromexan, which is administered orally, appears to have the advantages of more rapid utilization and more rapid cessation of action than dicumarol, although the mode of action is similar in that it produces a hypoprothrombinemia. It does require accurate prothrombin tests for satisfactory clinical use. It appears to be less prone to producing hemorrhagic complications. Animal and clinical experiences with Tromexan are herewith presented.

There is considerable interest and some difference of opinion about the relative clinical usefulness of many oral anticoagulant agents. In this study the more commonly used agents are evaluated with respect to their action on the clotting process as measured by thrombelastography. This test does not necessarily provide an evaluation of all aspects of the clinical action of an anticoagulant.

Marcumar [3-(1'-phenyl-propyl)-4-hydroxycoumarin] is a new anticoagulant. Marcumar acts more rapidly than Dicumarol, but not quite as rapidly as Tromexan. The action is more prolonged than Dicumarol. As with other anticoagulants, the administration of Marcumar requires conscientious observation and accurate prothrombin complex determinations.

Coronary thrombosis with myocardial infarction is an extremely serious disease to the individual and to the nation. It kills at least 200,000 persons a year and cripples unknown numbers. The modern treatment is herein outlined. Established therapy is reviewed and evaluated. The use and technics for the control of anticoagulant therapy are discussed.

There have been conflicting reports as to whether the ingestion of fat increases the tendency for the blood to clot, and hence, by implication, the risk of thromboembolic complications in man. In this study the effect of a single meal containing a large amount of fat was compared with that of a practically purely carbohydrate isocaloric meal. Under carefully controlled conditions the clotting time varied widely under fasting conditions, and after both fat and carbohydrate meals the clotting time became longer, shorter, or remain unchanged. The results were unpredictable and although a slight trend toward shortened clotting times was evidenced after the fat meals, the results did not reach accepted statistical standards of probability.

The present knowledge regarding the pathogenesis of thrombosis is reviewed. New conceptions and technics involving physical principles are outlined. Hitherto unemphasized aspects of thrombosis are discussed. The present status of anticoagulant therapy is summarized. The effects of other factors on the action of anticoagulants are considered.

Great interest continues in the treatment of cerebrovascular vascular accidents with anticoagulant agents. This paper presents a preliminary report of a cooperative study of this subject and indicates the methodology and protocol of the study, problems inherent in it, and preliminary findings of the first two years, without drawing definite conclusions.

As anticoagulant therapy has become more widespread and a greater knowledge has been accumulated regarding the mode of action of coumarin derivatives, problems arising from the use of different thromboplastin preparations have been subjected to greater scrutiny. This paper presents an evaluation of the dependability and significance of different types of tissue thromboplastin in the determination of effects of coumarin derivatives. The main difference between thromboplastin extracts seems to be that brain preparations have a factor VII-like activity. As the exact evaluation of factor VII activity appears to be of primary importance in patients treated with coumarin derivatives, a thromboplastin preparation that does not contain factor VII activity is recommended.

Experience with long-term anticoagulant therapy during the past seven years has been summarized. This report is based on the records of 227 individuals treated as private or outpatient clinic patients for from four weeks to seven years. Where adequate laboratory facilities are available outpatient long-term therapy may be satisfactorily controlled by physicians familiar with the use of anticoagulant drugs. Their correct use will lessen the incidence of thromboembolic episodes in patients who have previously suffered from such complications.

One hundred fifty individuals of different ages without evidence of peripheral vascular impairment (100 normal persons and 50 patients with history of cerebral vascular disease) were examined with the Allen test; the radial and ulnar arteries were examined in both hands. A false-positive test could easily be obtained spontaneously or be provoked by intentional hyperextension of the hand more than 20° beyond the straight position. In the straight position of the hand, the time for appearance of rubor after opening of the hand exceeded 5 seconds in 34% of the normal persons. When a relaxed slight flexion at the wrist joint was used, the flush after opening the hand appeared at an average of 3 seconds for the ulnar artery and 2.75 for the radial artery. In 50 normal individuals examined with optimal technique described, no individual artery required more than 6 seconds for the flush to appear after opening of the hand. The authors recommend that the Allen test be performed with the patient's hand slightly flexed and relaxed.

The effects of the use of Paritol administered intravenously to 35 individuals are herein reported. This synthetic anticoagulant produces a prolongation of the clotting time similar to that produced by heparin but of longer duration, if appropriate dosage is used. As with heparin, at therapeutic clotting time levels, the prothrombin time is slightly prolonged. Certain untoward effects have been noted and are described. Further studies with Paritol appear justified in order to evaluate its usefulness as a rapidly acting anticoagulant.

Experience with long-term anticoagulant therapy during the past seven years has been summarized. This report is based on the records of 227 individuals treated as private or outpatient clinic patients for from four weeks to seven years. Where adequate laboratory facilities are available outpatient long-term therapy may be satisfactorily controlled by physicians familiar with the use of anticoagulant drugs. Their correct use will lessen the incidence of thromboembolic episodes in patients who have previously suffered from such complications.

Thromboembolic complications frequently occur following myocardial infarction. Following the general acceptance of anticoagulant therapy for the treatment of myocardial infarction, there have been some authors who have recommended that this therapy be withheld from "mild cases," unless they develop thromboembolic complications. It is the belief of the present authors that this is not justified unless there are contraindications for anticoagulant treatment, provided that proper facilities are available. Summaries of experience with 14 so-called "good risk" cases of myocardial infarction who developed a total of 18 certain and 4 probable thromboembolic complications are presented. As a result, there were 4 major amputations in 3 patients, 1 of whom died. Other complications are discussed in detail.

Studies were carried out regarding the effect of intravenous trypsin on rabbits. These included investigations into the toxicity and the tendency for the production of intravascular coagulation. The effect on artificial preformed thrombi was also observed. It was found that in the doses used, the intravenous administration of trypsin was not efficacious in the treatment of intravascular thrombosis. These studies failed to provide evidence to justify its use as a therapeutic agent in man.

The nitroglycerin-flicker test, as suggested and modified by Krasno and Ivy, has been used to test normal individuals and patients with a variety of cardiovascular diseases. The hypothesis that this test would serve as an index of the presence of vascular disease or spasm elsewhere in the body than the retina was explored. These studies have failed to justify the drawing of conclusions based on the results of this test regarding the presence or absence of generalized vascular disease or of localized vascular disease or spasm elsewhere than the retinal vessels. It is concluded that the use of this test in mass surveys to detect cardiovascular disease is not justified.

In summary, the total world evidence suggests that in the absence of compelling contraindications and with the availability of satisfactory laboratory and clinical facilities, patients suffering with acute myocardial infarction should receive adequate anticoagulant therapy during the first month, and that the risk of reinfarction and death is reduced if this is continued for 1 to 2 years after the first month. More long-term studies should be conducted to evaluate this treatment for succeeding years. This form of therapy presents certain difficulties that must be weighed against the possible gains in deciding whether or not to continue it.

The intravenous injection of trypsin into rabbits resulted in marked changes in the rhythm and alteration in the P, QRS, S-T and T deflections of the electrocardiogram.

In the course of a physical examination one is often confronted with the question whether the inability to palpate a pulse in a usual location is the result of arterial spasm, occlusive arterial disease, or an aberrant location of the artery. Evidence is presented that the sublingual administration of glyceryl trinitrate (nitroglycerin) will frequently solve this problem. If the absent or markedly diminished pulse becomes bounding and objective tests confirm this, it can be concluded that the reduced pulsation was due to spasm of the artery under study. This is a simple test readily applied in clinical practice.

The hyperabduction syndrome was described in 1945. This report includes information and experience gained from the study of 52 patients suffering from its consequences and of many others in whom the diagnosis was necessarily considered. The signs and symptoms and age and sex incidence are summarized. Among the most striking findings was the fact that Raynaud's syndrome occurred in 20 of the 52 patients, an incidence far greater than anticipated in the general population. In some patients elimination of the hyperabduction position abolished Raynaud's syndrome. So far as we can determine this relationship has not been previously reported.

The various measures available for the therapy of a patient with a stroke have been discussed. The value of vigorous conservative therapy has been emphasized. The role of anticoagulant drugs has been detailed. This mode of therapy seems most efficacious in treatment of recurrent transient ischemic attacks and the slowly progressive stroke. The value of anticoagulants in the acute phase of cerebral thrombosis and in long-term postinfarction therapy is not clear as yet. The role of anticoagulant drugs in treatment of cerebral embolism seems well established. It may be wise to delay institution of these drugs for 24 to 36 hours after the acute stroke. Surgical procedures give promise of value in certain well-defined syndromes. The patient with cerebral hemorrhage remains a formidable therapeutic problem.