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Heparin activity monitoring during vascular surgery
Heparin Activity Monitoring during Vascular Surgery
Wayne Jacobsen, MD, Loma Linda, California Floyd Brauer, MD, Loma Linda, California Louis L. Smith, MD, Loma Linda, California
Precise control of the clotting mechanism is an essential ingredient for successful vascular surgery. Heparin is frequently administered according to a variety of dose schedules by the vascular surgeons, usually without any attempt to monitor its anticoagulant effects. Institutional tradition or the surgeon’s whim seems to determine these variations. The activated coagulation time (ACT) [I] has become a valuable monitor of high dose heparin activity during cardiac surgery with cardiopulmonary bypass [2,3]. We elected to study the use of the ACT as a heparin activity monitor in vascular surgery since its use would offer several advantages to the surgeon and anesthesiologist if constant results could be obtained. The ACT method does not require sending blood to a central laboratory since it can he easily performed in the operating room in less than 3 minutes by personnel already there. The present study determines the value of the ACT as a monitor of anticoagulation activity in noncardiac vascular surgery since heparin doses are usually lower and clotting need not be entirely prevented. It was our hope that this study would help to answer several questions about heparin anticoagulation: Do current dose schedules provide adequate anticoagulation during the time interval needed? Does patient variability in sensitivity to heparin, or the rate of metabolism of heparin by the individual, alter the dose required? Finally, is heparin neutralization near the completion of surgery desirable? Methods This study was dividedinto two parts. The first objective was to determine individual patient response to a single heparin loading dose and thereafter to plot the rate of From the Departments of Anesthesia and Surgery, Loma Linda University, Loma Linda, California. Reprint requests should be addressed to Wayne Jacobsen, MD, Department of Surgery, Loma Linda University, Loma Linda, California 92350. Presented at the Forty-Ninth Annual Meeting of the Pacific Coast Surgical Association, Newport Beach, California, February 19-22. 1978.
Volume 138, July 1978
decay of this anticoagulant. Twelve patients undergoing vascular surgery were selected (11 males, 1 female) aged fifty-six to eighty-one years. The operations performed were abdominal aortic resection (5 patients), aortoiliac arterial reconstruction (3), femoropopliteal bypass (3), and femoroart.erial profundaplasty (1). The ACT was determined in blood samples taken from an inlying 18 gauge plastic cannula previously placed in the external jugular vein. The baseline ACT for each patient was obtained at the onset of operation. The heparin dose administered was that requested by the operating surgeon and was given intravenously. No attempt was made to alter the surgeon’s existing empirical protocol. The heparin dose employed varied from 6,000 to 8,000 units. The ACT was measured approximately 10 minutes after the loading dose of heparin was given, and measurement was repeated at hourly intervals thereafter. Subsequent doses of heparin were administered at the request of the surgeon during two of the operations; the additional dose employed was 2,000 units. Protamine was given as desired by the surgeon near the completion of each vascular surgical procedure to neutralize any residual heparin effect with a dose varying from 25 to 50 mg per patient. Seven patients received 6,000 units of heparin. Initially five patients demonstrated adequate anticoagulation, with two patients below effective levels. After 1 hour all patients were not effectively anticoagulated. Three patients received 8,000 units of heparin, with two having excess anticoagulat.ion. After 1 hour one patient was below effective anticoagulation levels and within 2 hours another was no longer anticoagulated. (Table IA.) Two patients received 7,000 units of heparin. Initially both were effectively anticoagulated but after 1 hour were below satisfactory levels. Heparin, 2,000 units, was administered, resulting in adequate anticoagulation in one patient but not the other. (Table IB.) The second objective was to determine the practicality of employing the ACT to determine adequate and reproducible heparin effect in those patients receiving this anticoagulant in an intermediate or low dose range. Patients included in this part of the study consisted of eight males and eight females ranging in age from fifty-four to seventy-three years. The surgical procedures were ab-
141
Jacobsen, Brauer, and Smith
TABLE IA
Data on 10 of 12 Patients Receiving 6,000 or 8,000 Units of Heparin
Baseline ACT Heparin (units) ACT 10 min 60 min 90 min 120 min
1
2
3
4
5
6
7
9
10
12
105 6,000
90 6,000
70 6,000
75 6,000
109 6,000
68 6,000
135 6,000
110 8,000
120 8,000
95 6,000
210 165 140
175 140
210 120
125 106
180 158 145
195 155
210 150
225 170
195 200
230 205
135
dominal aortic aneurysmectomy, (8 patients), bilateral renal artery endarterectomy (l), axilloaxillary artery bypass (l), aortoiliac arterial reconstruction (l), and bilateral iliac artery reconstruction (1). The baseline ACT was obtained prior to the onset of the operative procedure. The normal value for this test is less than 85 seconds. When anticoagulation was desired, heparin was administered in a dose of 100 unite per kg body weight intravenously. After 10 minutes a second ACT measurement was obtained which indicated patient response to the initial loading dose of heparin. The results of these two ACT tests were employed to construct a dose-response curve, as described by Bull et al [Z]. Projection was made from these two measurements for additional heparin needed to prolong the ACT to 200 f 20 seconds, since the prolongation proved to be linear. This arbitrary end point value for the ACT was similar to that suggested for adequate heparinization as determined by monitoring partial thromboplastin time [4-6]. This end point was chosen since it was shown in the first part of the study to cause a definite change in coagulation without producing undue hemorrhage. If the ACT was less than 180 seconds, additional heparin was given, the additional amount being determined from the doseresponse curve. The ACT measurement was repeated at intervals of 30 to 45 minutes to determine the level of anticoagulation. Appropriate amounts of heparin were administered as needed to maintain the ACT as close to 200 seconds as possible. At the conclusion of the vascular surgical procedure, an ACT measurement was obtained to determine the amount of circulating heparin present. Protamine was administered in a dose of 1.3 mg for each 100 unite of heparin present as determined by the doseresponse curve. This dose of protamine returned the ACT to within normal limits (60 to 90 seconds).
125
Results
The present study revealed individual patient variability in response to heparin. After the initial loading dose of heparin, the ACT ranged from a low of 125 seconds to a high of 230 seconds. The metabolic decay of heparin also varied markedly within the patient population studied. One hour after the administration of heparin, the clotting times ranged from 106 seconds td 205 seconds. Some ACTS decreased as much as 90 seconds during an hour while others decreased only 20 to 25 seconds, and one patient (patient 10) had essentially no change in coagulation time. This variability of patient response to heparin makes it impossible to maintain predictable or adequate levels of anticoagulation with the usual empirical formulas for heparin administrationduring vascular surgical procedures. Part II of this study demonstrated that it is possible to maintain precise control of anticoagulation when heparin is administered on the basis of heparin activity monitoring, preferably employing a doseresponse curve. (Table IIA and B.) The use of an initial loading dose of heparin consisting of 100 units per kg body weight resulted in an ACT which varied from 160 to 300 seconds with a mean of 216 seconds. Additional heparin was necessary in four patients (patients 1,8,13, and 15) to raise the ACT to an effective level. Seven patients (5,7,11,12,13,15, and 16) required additional heparin doses as surgery progressed for maintenance of adequate anticoagulation during the procedure. Comments
TABLE IB
Data on 2 of 12 Patlents Receiving 7,000 Unlts of Heparin
Baseline ACT Heparin (units) ACT 10 min 60 min Repeat heparin (units) ACT 10 min 60 min
142
8
11
90 7,000
110 7,000
200 160 2,000
180 155 2,000
190 135
155 120
To place heparin and protamine administration in vascular surgery on a rational scientific basis, anticoagulation must be monitored. A simple monitor of heparin activity is needed which can be used routinely in the operating room. Protamine titration is difficult to perform and is time-consuming [7]. Plasma heparin assay is also difficult to perform and does not quantitate the clotting response. The partial thromboplastin time is not easily measured in the operating
room. The ACT gives an indirect
measure
TheAmerican Journal of Surgery
ACT Monitoring
TABLE _______IIA
Data on 11 of 16 Patients Receiving Initial Heparin Dose of 1 mg/kg
Baseline ACT Heparin (units) ACT 10 min 30 min 60 min Heparin (units) ACT 10 min 30 min 60 min Protamine (mg) .----ACT --
1
2
3
4
5
100 6.000
100 5,600
85 5,000
120 7,000
60 5,000
160
240 200
210
300 250 185
220 150
10
11
14
75 7,500
105 6,500
55 5,700
125 5,000
73 6,000
95 8,000
210 240 190
175
225 210
210 120
195
225 180
3,000
240
240
180
25 80
of the heparin level but more significantly demonstrates the clotting response to a given dose of heparin while being easily performed in the operating suite. Our study, as well as the studies of several other investigators, has shown the ACT to be a simple, inexpensive, rapid, and accurate heparin monitor [1,2,8]. ACT is useful in vascular surgery to: (1) identify individual patient heparin sensitivity with a patient-controlled dose-response curve; (2) determine heparin activity decay; and (3) determine protamine requirement for heparin reversal. Our data show a linear dose response to heparin in the low dose range and demonstrate that it is possible to maintain the ACT at 200 seconds (f20) for the duration required by the surgeon. The 200 second end point appeared to give adequate prolongation of coagulation time without evidence of excessive bl.eeding. Measurement of ACT should be repeated every 30 to 40 minutes and additional heparin given if needed to avoid an undesirable decrease in the clotting time. We believe that empirical heparin administration for vascular surgery fails to provide adequate anticoagulation for all patients. The vascular surgical patient can be better served by using a heparin monitor which can provide adequate, safe levels of anticoagulation over as long a period of time as surgical needs may require. This can be accomplished b:y measuring the ACT and by establishing a doseresponse curve for heparin as well as protamine administration. Summary
Twelve patients undergoing vascular surgery were administered heparin according to preexisting protocols. The response to heparin and the rate of decay were measured by use of the activated coagulation
Volume 136, July 1978
9
2,000
60 100
50 95
-.-.__
-
8
6-
9,000
50 95
of Heparin
70 90
135 3,000
50 95
50 95
10 60
240 180 147 25 79
50 75
time (ACT). The results showed a significant patient variability to response to and decay of heparin. In addition,, a dose-response curve for heparin administration was established in sixteen patients undergoing vascular surgery. The ACT proved to be a simple and accurate monitor of heparin activity. It also made possible a steady state of anticoagulation throughout the duration of the vascular procedure. The reversal of the heparin effect could also be precisely determined by this test,
TABLE MB Data on 5 of 16 Patients Receiving Initial Dose In Whom Anticoagulation was Maintained
Baseline ACT Heparin (units) ACT 10 min 30 min 60 min Heparin (units) ACT 10 min 30 min 60 min Heparin (units) ACT 10 min 30 min 60 min Heparin (units) ACT 10 min 30 min 60 min Heparin (units) ACT 10 min 30 min Heparin (units) ACT Protamine (mg) -_ ACT
7
12
13
15
16
65 5,000
100 7.200
60 6,600
95 6.100
90 6,000
255
210 180 160 2,800
160
175
270
2.400
2,200
180 1,500
180 150
180
3,600
1.500
195 185 168 1.500
190 160
195 145
185 190
165
75 95
40 80
155 1,250
210 145 2,000 230 200 140
190 150 1,500
5,000 225 210 160 3,300
25 82
50 80
217 165 2,000 160 50 67
143
Jacobsen, Brauer, and Smith
References 1. Hattersley PG: Activated coagulation time of whole blood. JAMA 196: 436, 1966. 2. Bull BS, Huse WH. Brauer FS, Korpman RA: Heparin therapy during extracorporeal circulation. J Thorac Cardiovasc Surg 69: 665, 1975. 3. Mattox KL, Guinn GA, Rubio PA, Beall AC Jr: Use of the activated coagulation time in intraoperative heparin reversal for cardiopulmonary operations. Ann Thorac Surg 19(6): 634, 1975. 4. Estes JW: Heparin therapy. Intern Med Dig 6: 33. 1971. 5. Genton EM: Guidelines for heparin therapy. Ann intern M&60: 77, 1974. 6. Spector I, Conn M: Control of heparin therapy with activated partial thromboplastin times. JAMA 201: 157, 1967. 7. Bull M, Huse W, Bull B: Evaluation of tests used to monitor heparin therapy during extracorporeal circulation. Anesthesiology43: 346. 1975. 8. Hattersley PG: Progress report: the activated coagulation time of whole blood (ACT). Am J C/in /Who/ 66: 899, 1976.
Discussion
Robert C. Lim (San Francisco, CA): Those who are involved with cardiac surgery or with hemodialysis have recognized for some time individual sensitivity to heparin and the need for close monitoring of heparin activity. The use of ACT and a dose-response curve to individualize the heparin doses in cardiopulmonary bypass have been described by Bull et al [2] (Loma Linda University). As described in this presentation the use of the ACT technic has been extended to peripheral vascular surgical cases when heparin is needed. This, I believe, is a major step forward. Presently, in many institutions where vascular surgery is being done, heparin is still being given on an empiric basis. I concur with the authors that ACT is a very simple test and can be done easily in the operating room to help determine the adequate level of anticoagulation.
144
Our group in San Francisco General Hospital have utilized whole blood partial thromboplastin time (WBPTT) in monitoring heparin doses in patients on hemodialysis. This method is also very simple and paramedical personnel can easily be taught to do it. Our method is a modification of the “rapid bedside method” described by Blakely (Toronto). We prefer to use a dry heating block set at 37°C and have substituted Thrombofaxa (Ortho-Diagnostic, Inc) for platelin and kaolin. “Native” blood, 0.4 ml, is used, and the test is completed in 2 to 3 minutes. Gotch and Keen (San Francisco) have shown that this method has a linear relationship with the standard Lee-White clotting time. We have been very satisfied with this method and would recommend it. Like the authors, we have found a wide variation in patient sensitivity to heparin. In a study of fifty-three patients, the variation was as wide as 0.02 to 0.11 seconds/ unit. This means that at each extreme, one patient given 5,000 units of heparin bolus can raise his whole blood partial thromboplastin time from a baseline of 80 seconds to 180 seconds and another patient can raise it to 500+ seconds. The dose of heparin will vary with the patient’s plasma volume and will be influenced by other factors, such as shock, fever, liver disease, and intravascular clotting. I concur with the authors’ conclusion that in order to arrive at a proper heparin dose, a dose-response curve must be drawn on every patient whose treatment with heparin needs to be critically monitored. Louis L. Smith (closing): As a vascular surgeon and having struggled with the problem at times of inadequate anticoagulation, I would recommend this rather simple means of monitoring heparin activity in the individual undergoing peripheral vascular surgery. We have found this technic to be both simple and effective. After all, simplicity is frequently the surgeon’s best friend.
The
Amerlcan
Journal
ot Surgery
Wayne Jacobsen, MD, Loma Linda, California Floyd Brauer, MD, Loma Linda, California Louis L. Smith, MD, Loma Linda, California
Precise control of the clotting mechanism is an essential ingredient for successful vascular surgery. Heparin is frequently administered according to a variety of dose schedules by the vascular surgeons, usually without any attempt to monitor its anticoagulant effects. Institutional tradition or the surgeon’s whim seems to determine these variations. The activated coagulation time (ACT) [I] has become a valuable monitor of high dose heparin activity during cardiac surgery with cardiopulmonary bypass [2,3]. We elected to study the use of the ACT as a heparin activity monitor in vascular surgery since its use would offer several advantages to the surgeon and anesthesiologist if constant results could be obtained. The ACT method does not require sending blood to a central laboratory since it can he easily performed in the operating room in less than 3 minutes by personnel already there. The present study determines the value of the ACT as a monitor of anticoagulation activity in noncardiac vascular surgery since heparin doses are usually lower and clotting need not be entirely prevented. It was our hope that this study would help to answer several questions about heparin anticoagulation: Do current dose schedules provide adequate anticoagulation during the time interval needed? Does patient variability in sensitivity to heparin, or the rate of metabolism of heparin by the individual, alter the dose required? Finally, is heparin neutralization near the completion of surgery desirable? Methods This study was dividedinto two parts. The first objective was to determine individual patient response to a single heparin loading dose and thereafter to plot the rate of From the Departments of Anesthesia and Surgery, Loma Linda University, Loma Linda, California. Reprint requests should be addressed to Wayne Jacobsen, MD, Department of Surgery, Loma Linda University, Loma Linda, California 92350. Presented at the Forty-Ninth Annual Meeting of the Pacific Coast Surgical Association, Newport Beach, California, February 19-22. 1978.
Volume 138, July 1978
decay of this anticoagulant. Twelve patients undergoing vascular surgery were selected (11 males, 1 female) aged fifty-six to eighty-one years. The operations performed were abdominal aortic resection (5 patients), aortoiliac arterial reconstruction (3), femoropopliteal bypass (3), and femoroart.erial profundaplasty (1). The ACT was determined in blood samples taken from an inlying 18 gauge plastic cannula previously placed in the external jugular vein. The baseline ACT for each patient was obtained at the onset of operation. The heparin dose administered was that requested by the operating surgeon and was given intravenously. No attempt was made to alter the surgeon’s existing empirical protocol. The heparin dose employed varied from 6,000 to 8,000 units. The ACT was measured approximately 10 minutes after the loading dose of heparin was given, and measurement was repeated at hourly intervals thereafter. Subsequent doses of heparin were administered at the request of the surgeon during two of the operations; the additional dose employed was 2,000 units. Protamine was given as desired by the surgeon near the completion of each vascular surgical procedure to neutralize any residual heparin effect with a dose varying from 25 to 50 mg per patient. Seven patients received 6,000 units of heparin. Initially five patients demonstrated adequate anticoagulation, with two patients below effective levels. After 1 hour all patients were not effectively anticoagulated. Three patients received 8,000 units of heparin, with two having excess anticoagulat.ion. After 1 hour one patient was below effective anticoagulation levels and within 2 hours another was no longer anticoagulated. (Table IA.) Two patients received 7,000 units of heparin. Initially both were effectively anticoagulated but after 1 hour were below satisfactory levels. Heparin, 2,000 units, was administered, resulting in adequate anticoagulation in one patient but not the other. (Table IB.) The second objective was to determine the practicality of employing the ACT to determine adequate and reproducible heparin effect in those patients receiving this anticoagulant in an intermediate or low dose range. Patients included in this part of the study consisted of eight males and eight females ranging in age from fifty-four to seventy-three years. The surgical procedures were ab-
141
Jacobsen, Brauer, and Smith
TABLE IA
Data on 10 of 12 Patients Receiving 6,000 or 8,000 Units of Heparin
Baseline ACT Heparin (units) ACT 10 min 60 min 90 min 120 min
1
2
3
4
5
6
7
9
10
12
105 6,000
90 6,000
70 6,000
75 6,000
109 6,000
68 6,000
135 6,000
110 8,000
120 8,000
95 6,000
210 165 140
175 140
210 120
125 106
180 158 145
195 155
210 150
225 170
195 200
230 205
135
dominal aortic aneurysmectomy, (8 patients), bilateral renal artery endarterectomy (l), axilloaxillary artery bypass (l), aortoiliac arterial reconstruction (l), and bilateral iliac artery reconstruction (1). The baseline ACT was obtained prior to the onset of the operative procedure. The normal value for this test is less than 85 seconds. When anticoagulation was desired, heparin was administered in a dose of 100 unite per kg body weight intravenously. After 10 minutes a second ACT measurement was obtained which indicated patient response to the initial loading dose of heparin. The results of these two ACT tests were employed to construct a dose-response curve, as described by Bull et al [Z]. Projection was made from these two measurements for additional heparin needed to prolong the ACT to 200 f 20 seconds, since the prolongation proved to be linear. This arbitrary end point value for the ACT was similar to that suggested for adequate heparinization as determined by monitoring partial thromboplastin time [4-6]. This end point was chosen since it was shown in the first part of the study to cause a definite change in coagulation without producing undue hemorrhage. If the ACT was less than 180 seconds, additional heparin was given, the additional amount being determined from the doseresponse curve. The ACT measurement was repeated at intervals of 30 to 45 minutes to determine the level of anticoagulation. Appropriate amounts of heparin were administered as needed to maintain the ACT as close to 200 seconds as possible. At the conclusion of the vascular surgical procedure, an ACT measurement was obtained to determine the amount of circulating heparin present. Protamine was administered in a dose of 1.3 mg for each 100 unite of heparin present as determined by the doseresponse curve. This dose of protamine returned the ACT to within normal limits (60 to 90 seconds).
125
Results
The present study revealed individual patient variability in response to heparin. After the initial loading dose of heparin, the ACT ranged from a low of 125 seconds to a high of 230 seconds. The metabolic decay of heparin also varied markedly within the patient population studied. One hour after the administration of heparin, the clotting times ranged from 106 seconds td 205 seconds. Some ACTS decreased as much as 90 seconds during an hour while others decreased only 20 to 25 seconds, and one patient (patient 10) had essentially no change in coagulation time. This variability of patient response to heparin makes it impossible to maintain predictable or adequate levels of anticoagulation with the usual empirical formulas for heparin administrationduring vascular surgical procedures. Part II of this study demonstrated that it is possible to maintain precise control of anticoagulation when heparin is administered on the basis of heparin activity monitoring, preferably employing a doseresponse curve. (Table IIA and B.) The use of an initial loading dose of heparin consisting of 100 units per kg body weight resulted in an ACT which varied from 160 to 300 seconds with a mean of 216 seconds. Additional heparin was necessary in four patients (patients 1,8,13, and 15) to raise the ACT to an effective level. Seven patients (5,7,11,12,13,15, and 16) required additional heparin doses as surgery progressed for maintenance of adequate anticoagulation during the procedure. Comments
TABLE IB
Data on 2 of 12 Patlents Receiving 7,000 Unlts of Heparin
Baseline ACT Heparin (units) ACT 10 min 60 min Repeat heparin (units) ACT 10 min 60 min
142
8
11
90 7,000
110 7,000
200 160 2,000
180 155 2,000
190 135
155 120
To place heparin and protamine administration in vascular surgery on a rational scientific basis, anticoagulation must be monitored. A simple monitor of heparin activity is needed which can be used routinely in the operating room. Protamine titration is difficult to perform and is time-consuming [7]. Plasma heparin assay is also difficult to perform and does not quantitate the clotting response. The partial thromboplastin time is not easily measured in the operating
room. The ACT gives an indirect
measure
TheAmerican Journal of Surgery
ACT Monitoring
TABLE _______IIA
Data on 11 of 16 Patients Receiving Initial Heparin Dose of 1 mg/kg
Baseline ACT Heparin (units) ACT 10 min 30 min 60 min Heparin (units) ACT 10 min 30 min 60 min Protamine (mg) .----ACT --
1
2
3
4
5
100 6.000
100 5,600
85 5,000
120 7,000
60 5,000
160
240 200
210
300 250 185
220 150
10
11
14
75 7,500
105 6,500
55 5,700
125 5,000
73 6,000
95 8,000
210 240 190
175
225 210
210 120
195
225 180
3,000
240
240
180
25 80
of the heparin level but more significantly demonstrates the clotting response to a given dose of heparin while being easily performed in the operating suite. Our study, as well as the studies of several other investigators, has shown the ACT to be a simple, inexpensive, rapid, and accurate heparin monitor [1,2,8]. ACT is useful in vascular surgery to: (1) identify individual patient heparin sensitivity with a patient-controlled dose-response curve; (2) determine heparin activity decay; and (3) determine protamine requirement for heparin reversal. Our data show a linear dose response to heparin in the low dose range and demonstrate that it is possible to maintain the ACT at 200 seconds (f20) for the duration required by the surgeon. The 200 second end point appeared to give adequate prolongation of coagulation time without evidence of excessive bl.eeding. Measurement of ACT should be repeated every 30 to 40 minutes and additional heparin given if needed to avoid an undesirable decrease in the clotting time. We believe that empirical heparin administration for vascular surgery fails to provide adequate anticoagulation for all patients. The vascular surgical patient can be better served by using a heparin monitor which can provide adequate, safe levels of anticoagulation over as long a period of time as surgical needs may require. This can be accomplished b:y measuring the ACT and by establishing a doseresponse curve for heparin as well as protamine administration. Summary
Twelve patients undergoing vascular surgery were administered heparin according to preexisting protocols. The response to heparin and the rate of decay were measured by use of the activated coagulation
Volume 136, July 1978
9
2,000
60 100
50 95
-.-.__
-
8
6-
9,000
50 95
of Heparin
70 90
135 3,000
50 95
50 95
10 60
240 180 147 25 79
50 75
time (ACT). The results showed a significant patient variability to response to and decay of heparin. In addition,, a dose-response curve for heparin administration was established in sixteen patients undergoing vascular surgery. The ACT proved to be a simple and accurate monitor of heparin activity. It also made possible a steady state of anticoagulation throughout the duration of the vascular procedure. The reversal of the heparin effect could also be precisely determined by this test,
TABLE MB Data on 5 of 16 Patients Receiving Initial Dose In Whom Anticoagulation was Maintained
Baseline ACT Heparin (units) ACT 10 min 30 min 60 min Heparin (units) ACT 10 min 30 min 60 min Heparin (units) ACT 10 min 30 min 60 min Heparin (units) ACT 10 min 30 min 60 min Heparin (units) ACT 10 min 30 min Heparin (units) ACT Protamine (mg) -_ ACT
7
12
13
15
16
65 5,000
100 7.200
60 6,600
95 6.100
90 6,000
255
210 180 160 2,800
160
175
270
2.400
2,200
180 1,500
180 150
180
3,600
1.500
195 185 168 1.500
190 160
195 145
185 190
165
75 95
40 80
155 1,250
210 145 2,000 230 200 140
190 150 1,500
5,000 225 210 160 3,300
25 82
50 80
217 165 2,000 160 50 67
143
Jacobsen, Brauer, and Smith
References 1. Hattersley PG: Activated coagulation time of whole blood. JAMA 196: 436, 1966. 2. Bull BS, Huse WH. Brauer FS, Korpman RA: Heparin therapy during extracorporeal circulation. J Thorac Cardiovasc Surg 69: 665, 1975. 3. Mattox KL, Guinn GA, Rubio PA, Beall AC Jr: Use of the activated coagulation time in intraoperative heparin reversal for cardiopulmonary operations. Ann Thorac Surg 19(6): 634, 1975. 4. Estes JW: Heparin therapy. Intern Med Dig 6: 33. 1971. 5. Genton EM: Guidelines for heparin therapy. Ann intern M&60: 77, 1974. 6. Spector I, Conn M: Control of heparin therapy with activated partial thromboplastin times. JAMA 201: 157, 1967. 7. Bull M, Huse W, Bull B: Evaluation of tests used to monitor heparin therapy during extracorporeal circulation. Anesthesiology43: 346. 1975. 8. Hattersley PG: Progress report: the activated coagulation time of whole blood (ACT). Am J C/in /Who/ 66: 899, 1976.
Discussion
Robert C. Lim (San Francisco, CA): Those who are involved with cardiac surgery or with hemodialysis have recognized for some time individual sensitivity to heparin and the need for close monitoring of heparin activity. The use of ACT and a dose-response curve to individualize the heparin doses in cardiopulmonary bypass have been described by Bull et al [2] (Loma Linda University). As described in this presentation the use of the ACT technic has been extended to peripheral vascular surgical cases when heparin is needed. This, I believe, is a major step forward. Presently, in many institutions where vascular surgery is being done, heparin is still being given on an empiric basis. I concur with the authors that ACT is a very simple test and can be done easily in the operating room to help determine the adequate level of anticoagulation.
144
Our group in San Francisco General Hospital have utilized whole blood partial thromboplastin time (WBPTT) in monitoring heparin doses in patients on hemodialysis. This method is also very simple and paramedical personnel can easily be taught to do it. Our method is a modification of the “rapid bedside method” described by Blakely (Toronto). We prefer to use a dry heating block set at 37°C and have substituted Thrombofaxa (Ortho-Diagnostic, Inc) for platelin and kaolin. “Native” blood, 0.4 ml, is used, and the test is completed in 2 to 3 minutes. Gotch and Keen (San Francisco) have shown that this method has a linear relationship with the standard Lee-White clotting time. We have been very satisfied with this method and would recommend it. Like the authors, we have found a wide variation in patient sensitivity to heparin. In a study of fifty-three patients, the variation was as wide as 0.02 to 0.11 seconds/ unit. This means that at each extreme, one patient given 5,000 units of heparin bolus can raise his whole blood partial thromboplastin time from a baseline of 80 seconds to 180 seconds and another patient can raise it to 500+ seconds. The dose of heparin will vary with the patient’s plasma volume and will be influenced by other factors, such as shock, fever, liver disease, and intravascular clotting. I concur with the authors’ conclusion that in order to arrive at a proper heparin dose, a dose-response curve must be drawn on every patient whose treatment with heparin needs to be critically monitored. Louis L. Smith (closing): As a vascular surgeon and having struggled with the problem at times of inadequate anticoagulation, I would recommend this rather simple means of monitoring heparin activity in the individual undergoing peripheral vascular surgery. We have found this technic to be both simple and effective. After all, simplicity is frequently the surgeon’s best friend.
The
Amerlcan
Journal
ot Surgery