The Safety of Low Dose Heparin Prophylaxis

Joyce M. Rocko, MD, Jersey City, New Jersey

Fayez Mikhail, MD, Jersey City, New Jersey

Francisco Trilles, MD, Jersey City, New Jersey

Joseph J. Timmes, MD, Jersey City, New Jersey

In recent years impressive evidence has accumulated that the incidence of postoperative deep vein thrombosis can be reduced by prophylactic measures [1,2]. There have been several controlled clinical trials [3-91 clearly showing that low doses of heparin given subcutaneously or intravenously at pro- grammed times pre- and postoperatively are highly effective in reducing the incidence of postoperative deep vein thrombosis. Many surgeons are well aware of this regimen but do not use it for fear of excessive bleeding, troublesome problems of administration, and doubt about laboratory monitoring.

Reported herein are the results of a trial we de- signed to determine specifically whether or not, in a routine surgical environment, heparin (Liquaemin Sodium”) can be administered according to a pro- phylactic regimen, in a manner easily understood by the staff, without the need for laboratory monitoring, and without increased bleeding that would interfere with surgical procedures. Thirty-two patients of varying ages with diversified surgical procedures were included in the study.

Material and Methods

Patients’ ages ranged from 15 to 79 years: six patients less than 40 years old; eight 40-49 years; four 50-59 years; eight 60-69 years; and six 70-79 years. The patients were considered to be at high risk of deep venous thrombosis and/or pulmonary embolism associated with their opera- tion or postoperative course. (Table I.) The reason for the trial was explained to each patient, or the patient’s parents in the case of minors, and consent was obtained before they entered the study. A major surgical operation was consid- ered to be one that was performed under general anesthe- sia, lasted for more than 30 to 45 minutes, and required

From the Department of Surgery, Jersey City Medical Center, Jersey City, and the New Jersey College of Medicine and Dentistry at Newark, Newark, New Jersey.

Reprint requests should be addressed to Joyce M. Rocko, MD, Department of Surgery, Jersey City Medical Center, Baldwin Avenue, Jersey City, New Jersey 07304.

postoperative hospitalization of at least five days. Patients receiving anticoagulant therapy were excluded from the study.

(1) Control blood studies were performed before heparin prophylaxis was initiated. Citrated whole blood was ob- tained for prothrombin time, partial thromboplastin time, fibrinogen, platelet count, hematocrit, complete blood count, and differential.

(2) Heparin, 5,000 USP units, was injected subcuta- neously 2 hours before surgery, with 5,000 USP units ad- ministered every 12 hours for five days postoperatively.

(3) Partial thromboplastin times were monitored on alternate days.

(4) After five days of heparin administration, 5 cc of blood was drawn to repeat the preadministration stud- ies.

(5) A notation was made of any changes in the tests performed, with particular attention to platelet counts and fibrinogen levels,

(6) All values f b o o servations were recorded on case re- port forms, with nurses instructed to make note of any excessive bleeding throughout the clinical course.

Results

In general the laboratory hematologic measure- ments were unchanged and fell either within or close to laboratory norms. There was no significant change in baseline levels of platelets, prothrombin and par- tial thromboplastin times, and fibrinogen from day

TABLE I Procedures Performed on the 32 Patients

Procedure Number of Patients

Biliaty tract 5 Gastric 4 Small bowel 4 Appendicular 4 Breast 1 Hernia 2 Thoracic 7

Amputation 3 Colon 1 Others 1

799 The American Journal of Surgery

Heparin Prophylaxis

1 to day 5. There appears to be no discernible dif- ference caused by the administration of subcuta- neous heparin. Of similar if not greater importance was the absence of any form of intraoperative or postoperative bleeding.

It is of interest that none of the thirty-two patients had clinical evidence of deep vein thrombosis or pulmonary embolism, and none complained of undue discomfort resulting from the regimen of subcuta- neous heparin injections.

Comments

It has been estimated that 20 million cases of deep venous thrombosis occur each year in the United States, with a resultant 2 million cases (10 per cent) of pulmonary embolism. Since an estimated 10 per cent of all patients with pulmonary embolism die, the 200,000 deaths per year is staggering [lo]. Sharnoff [II] in 1969 reported that the incidence of pulmonary embolism can be reduced by the prophylactic ad- ministration of anticoagulant therapy, and interest has recently centered on the prevention of deep ve- nous thrombosis in surgical patients using low doses of heparin.

If our concept of pathogenesis is correct-that deep vein thrombi usually arise in areas where stasis occurs beginning at the base of a valve pocket where the circulation is slowest-then the incidence of deep vein thrombosis, and therefore of associated pul- monary embolism, can be markedly reduced by measures that decrease stasis, interfere with coagu- lation, or both. Since the documented findings [12] that 50 per cent of postoperative thrombi have formed by the time a patient arrives in the recovery room and many of the rest form very shortly there- after, one method of minimizing stasis-ambula- tion-has not proved sufficiently effective. Fur- thermore, it has been demonstrated [12] that elastic stockings and leg exercises have not significantly reduced the incidence of deep vein thrombosis in high risk patients. Avoidance of this stasis requires maintenance of normal venous flow in the lower ex- tremities during the entire period of high risk in- cluding the time spent in the operating room. This is done most effectively by the use of anticoagulants. But there is great reluctance on the part of surgeons to administer the recommended doses of these anticoagulants, particularly in patients who have recently undergone or are scheduled for surgery, because of the fear of bleeding and the need to reg- ulate therapy through laboratory monitoring [23].

Antithrombin III is an alpha 2 globulin found in normal plasma which inhibits several coagulation

proteases. Heparin accelerates the inhibitory reaction between antithrombin III and these proteases. Al- though heparin does not increase the amount of cir- culating antithrombin III, it vastly increases, even when administered in small quantities, the rate at which antithrombin III inhibits these proteases [14]. Antithrombin III is particularly effective against factor Xa and thrombin, although the primary physiologic target of antithrombin III in terms of preventing thrombus formation is factor Xa rather than thrombin. It would be essential to prevent the hypercoagulability of the blood, thereby possibly diminishing venous thrombosis, by increasing by several fold the activity of antithrombin III. Ac- cordingly, it would seem reasonable that if a tendency to thrombosis could be treated before intravascular coagulation were initiated, less antithrombin III may be required. This is explained by the view [15] that the enzymatic coagulation sequence functions as a biologic amplification system; it would require less energy to stop the system at the Xa stage than at the subsequent thrombin stage.

Summary

In a recent survey, eight of ten general surgeons claimed to have a high awareness of the prophylactic use of heparin sodium in subanticoagulant doses, although the use of low dose heparin is considerably lesser. Actual use of this regimen occurs in 4 per cent of surgical patients. Surgeons are reluctant to use anticoagulant therapy in a prophylactic manner due to (1) the fear of bleeding in intra- and postoperative patients and (2) the necessity of regulating the anticoagulant therapy by means of laboratory mon- itoring. Heparin has recently gained prominence for prophylactic use particularly in older patients undergoing surgery and in those prone to thrombosis for other reasons [16].

The efficacy of low dose heparin in preventing fatal postoperative pulmonary embolism was investigated in the multicenter trial of Kakkar and his associates [3,4,12]. The recommendations for prophylactic use of low dose heparin on a large scale in “high risk” patients undergoing major surgery were further confirmed in our present study of thirty-two surgical patients. We have demonstrated that in a routine surgical environment heparin can be administered according to a prophylactic regimen in a manner easily understood by the staff, without the need of extensive and costly laboratory monitoring, and without bleeding that would have interfered with the surgical procedures.

voh!me 135. Juno 1978 799

Rocko et al

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