Development and Evaluation of a Disposable Device for Performing Simultaneous Duplicate Bleeding Time Determinations SUSAN R. BABSON, M.S., AND ARTHUR L. BABSON, PH.I
Babson, Susan R., and Babson, Arthur L.: Development and evaluation of a disposable device for performing simultaneous duplicate bleeding time determinations. Am J Clin Pathol 70: 406-408, 1978. A disposable bleeding time device that provides two simultaneous standardized incisions is described. The mean bleeding time of 47 normal adults was 4.1 min with a 95% range of 2.2-7.0 min. The standard deviation of duplicate bleeding times was 0.7 min, and the day-to-day standard deviation for individuals was 0.9 min. In a double-blind crossover study of 20 normal adults, the mean bleeding time increased from 3.7 to 6.2 min after ingestion of 1 g aspirin. The device is extremely simple to use and is essentially painless. Physical trauma is minimal. (Key words: Bleeding time; Standardized bleeding time; Disposable bleeding time device; Bleeding time, normal range; Bleeding time, aspirin effects.)
template bleeding time, the plastic template is held on the forearm and 9-mm incisions are made by running the blade the entire length of the slit. While the template bleeding time provides a wellstandardized incision, the equipment is cumbersome to use, it must be sterilized between uses, and making the incision can be traumatic for both operator and subject. To overcome these deficiencies, we have developed a disposable device that provides standardized incisions with ease and minimal trauma. Materials and Methods All prototype devices were constructed in the model shop of the Schick Safety Razor Division of the Warner-Lambert Company.* Blades were sterilized with alcohol, and a new blade was used for each subject. The final device was sterilized with ethylene oxide. Before performing a bleeding time determination, the volar surface of the forearm about 5 cm distal to the antecubital fossa was cleansed with alcohol and allowed to air-dry. With a sphygmomanometer on the upper arm inflated to 40 mm Hg, the bleeding time device was pressed firmly against the cleansed area and triggered while a stop watch was simultaneously started. Blood was blotted with Whatman No. 1 filter paper every 30 seconds; care was taken not to disturb the incisions. The end point was recorded when no more blood was absorbed onto the filter paper. Results Development
Device
The first model consisted of a small plastic housing containing a spring-loaded scalpel blade protruding 1 mm through a slit in the bottom of the device. Depress-
Received April 11, 1977; received revised manuscript May 20, 1977; accepted for publication May 20, 1977. Address reprint requests to Dr. Babson: Department of Diagnostics, Research and Development, The Warner-Lambert Research Institute, Morris Plains, New Jersey 07950. 0002-9173/78/0900/0406 $00.60 © Ai
of Prototype
* Mr. Evan Chen and Mr. Frank Ferraro provided technical assistance in the design and construction of the prototype devices. ican Society of Clinical Pathologists
406
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
THE BLEEDING TIME is the time between the infliction of a small standard cut and the moment when the bleeding stops. It is a direct test of the ability of platelets to function normally in primary hemostasis and has been recently reviewed in depth. 3 The bleeding time test originally described by Duke 4 was done by making a puncture wound in the earlobe with a lancet. Ivy and associates 7 increased the sensitivity of the test by making three puncture wounds on the forearm while maintaining a constant back pressure of 40 mm Hg with a pressure cuff on the upper arm. Puncture wounds often give discrepant replicate bleeding times because the cuts are small but deep, thus increasing the possibility of hitting a larger vessel or an area with few capillaries. Various procedures using shallow scalpel blade incisions to avoid the problems associated with puncture wounds have been described. 2,5 ' 6 These procedures are very technic-dependent. Mielke and colleagues 9 attempted to standardize the length and depth of the incisions by use of a scalpel blade mounted in a holder that allowed only a fixed portion of the blade to protrude and a plastic template with an 11-mm slit. In this procedure, which has also been called the
The Department of Diagnostics Research and Development, The Warner-Lambert Research Institute, Morris Plains, New Jersey
Vol. 70 • No. 3
LABORATORY SUGGESTIONS
Evaluation of Final Disposable Device The final bleeding time device employed in these studies is illustrated before and after triggering in
y
6O-1
40-
o 2
30-
u a
20-
U D Of
10-
o-Lft
=ft^ fst
91 '10
BLEEDING TIME IN MINUTES FIG. 2. The distribution of 206 individual bleeding times from 47 normal adults.
Figure 1. The geometry of the bottom of the unit and the blade and the depth of the cut are identical to those aspects of the third prototype model. A tearaway tab was added to prevent premature triggering. The devices are individually packaged in sterilized blister packs.t A report on the comparison of this device with the template technic and its use on hospital patients appears elsewhere.8 Normal Range Forty-seven normal adults were tested over a twomonth period from one to five times each. The replicate results for each individual were averaged. The average bleeding times ranged from 2.3 to 7.0 min, with a mean of 4.1 min. Log transformation gave a 95% normal range of 2.2-7.0 min. The distribution of 206 individual bleeding times is shown in Figure 2. The 9-minute time was paired with a 7!^-minute time. These values are suspect, as this individual had average bleeding times of 3, 4>/£, and VA minutes on three other occasions. The upper limit of normal in this study was considered to be 7 min. Reproducibility Twenty-three normal individuals were tested four times each over a period of several weeks. The standard deviation of duplicate bleeding times was 0.7 min, and the day-to-day standard deviation for individuals was 0.9 min. Bleeding Time after Aspirin To test the ability of the bleeding time device to detect increases in bleeding time after aspirin ingestion,
FIG. 1. The final bleeding time device before and after triggering. The right illustration shows the tear-away tab removed and the blades protruding.
t Available commercially as Simplate® II from General Diagnostics Division, Warner-Lambert Co., Morris Plains, N.J. 07950.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
ing a trigger on top of the housing released the blade, which traveled 9 mm transversely through the slit. It was difficult to control the depth of the resulting incision, and several volunteer subjects received cuts that produced significant scarring. This approach was therefore abandoned. The second model released the spring-loaded blade like a guillotine. The blade was made from a doubleedged razor blade cut to 9 mm wide. The bottom of the housing was convex in order that it might place the skin under slight tension when the unit was pressed on the arm, and a blade protrusion of 1.2 mm provided optimum depth of incision. The device was designed so that blades could be changed easily between subjects and the unit rapidly recocked for replicate incisions on the same subject. Thirteen normal volunteers had bleeding times of 2 to 7 min with a mean of 4.8 min. To see whether a smaller incision could be used, the cutting edges of several blades were reduced to various sizes. In limited studies, the bleeding times progressively lengthened as the length of the blade increased from 3 to 6 to 9 mm. To minimize trauma and still provide a sensitive test, we elected to proceed with the 6-mm incision. A third model was constructed, similar to the second, but it housed a 16-mm blade with a 4-mm recess in the center of the cutting edge. This produced two simultaneous incisions, each 6 mm long. This device was evaluated on 27 normal individuals, who had average bleeding times of 2 to 7 min. The mean of all measurements was 3.91 min, with a standard deviation of 1.24 min. No problem was encountered with blood flowing from one incision to the other, and the two incisions were close enough to be covered easily by a single small adhesive bandage. These results were sufficiently encouraging to persuade us to proceed with with development of a commercial device.
407
BABSON AND BABSON
408
Table I. The Effect of Aspirin on Bleeding Time Control (min)
Aspirin (min)
Present study Mean 1 SD
3.7 ± 1.1
6.2 ± 2.5
Bick el «/.' Mean 1 SD
3.7 ± 1.4
6.0 ± 2.2
Discussion The original Ivy bleeding time technic and most of its subsequent modifications recommend averaging the bleeding times of three individual cuts. Mielke and colleagues9 showed that when standardized incisions are made, two cuts provided as much information as three. The device described here is the first to provide duplicate standardized incisions simultaneously. This greatly simplifies the timing of the procedure, because the two wounds can be blotted together. The proximity of the two cuts was of some initial concern to us. In no instance, however, did blood from the two cuts flow together during the 30-sec intervals between blottings.
While it is difficult to quantitate pain, it was clearly brought out in this study that the subjects experienced little or no sensation of being cut. The audible click at the release of the blade distracted the subjects, and many were surprised to find that they had indeed been cut. This aspect could be particularly advantageous with children. The fact that the blade is completely hidden within the housing should also cause the device to produce far less fear and apprehension in children than a bare scalpel blade. Another factor that is difficult to quantitate is scarring. While the initial prototype, which employed a transverse movement of a scalpel blade, did result in noticeable scars in a few volunteers, we were impressed with the lack of visible scarring with the final device. References 1. Bick RL, Adams T, Schmalhorst WR: Bleeding times, platelet adhesion, and aspirin. Am J Clin Pathol 65:69-72, 1976 2. Borchgrevink CF, Waaler BA: The secondary bleeding time: A new method for the differentiation of hemorrhagic diseases. Acta Med Scand 162:361-374, 1958 3. Bowie EJW, Owen CA Jr: The bleeding time, Progress in Hemostasis and Thrombosis. Volume 2. Edited by Spaet TH. New York, Grune and Stratton, 1974, pp 249-271 4. Duke WW: The relation of blood platelets to hemorrhagic disease: Description of a method for determining the bleeding time and coagulation time and report of three cases of hemorrhagic disease relieved by transfusion. JAMA 55:1185-1192, 1910 5. Harker LA, Slichter SJ: The bleeding time as a screening test for evaluation of platelet function. N Engl J Med 287: 155-159, 1972 6. Hjort P, Stormorken H: A study of the in vitro and in vivo effects of a synthetic heparin-like anticoagulant: Dextran sulfate. Scan J Clin Lab Invest 9 Suppl 29:1-86, 1957 7. Ivy AC, Nelson D, Bucher Q: The standardization of certain factors in the cutaneous "verostasis" bleeding time technique. J Lab Clin Med 26:1812-1822, 1941 8. Kumar R, Ansell JE, Canoso RT, et al: Clinical trial of a new bleeding time device. Am J Clin Pathol (in press) 9. Mielke CH, Kaneshiro MM, Maher IA, et al: The standardized normal Ivy bleeding time and its prolongation by aspirin. Blood 34:204-215, 1969
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
a double-blind crossover study was conducted with ten healthy men and ten healthy women. Each person ingested four capsules containing either 1 g glucose or 1 g aspirin immediately after a baseline bleeding time determination. A second bleeding time was done 24 hours later. A week later, the treatments were crossed over. The mean bleeding time of 6.2 min after aspirin was significantly longer (P < 0.01) than the mean control time of 3.7 min or the mean post-placebo time of 3.8 min. As shown in Table 1, these results are almost identical to the recent findings of Bick and coworkers,1 who used the template method.9
A.J.C.P. • September 1978
Babson, Susan R., and Babson, Arthur L.: Development and evaluation of a disposable device for performing simultaneous duplicate bleeding time determinations. Am J Clin Pathol 70: 406-408, 1978. A disposable bleeding time device that provides two simultaneous standardized incisions is described. The mean bleeding time of 47 normal adults was 4.1 min with a 95% range of 2.2-7.0 min. The standard deviation of duplicate bleeding times was 0.7 min, and the day-to-day standard deviation for individuals was 0.9 min. In a double-blind crossover study of 20 normal adults, the mean bleeding time increased from 3.7 to 6.2 min after ingestion of 1 g aspirin. The device is extremely simple to use and is essentially painless. Physical trauma is minimal. (Key words: Bleeding time; Standardized bleeding time; Disposable bleeding time device; Bleeding time, normal range; Bleeding time, aspirin effects.)
template bleeding time, the plastic template is held on the forearm and 9-mm incisions are made by running the blade the entire length of the slit. While the template bleeding time provides a wellstandardized incision, the equipment is cumbersome to use, it must be sterilized between uses, and making the incision can be traumatic for both operator and subject. To overcome these deficiencies, we have developed a disposable device that provides standardized incisions with ease and minimal trauma. Materials and Methods All prototype devices were constructed in the model shop of the Schick Safety Razor Division of the Warner-Lambert Company.* Blades were sterilized with alcohol, and a new blade was used for each subject. The final device was sterilized with ethylene oxide. Before performing a bleeding time determination, the volar surface of the forearm about 5 cm distal to the antecubital fossa was cleansed with alcohol and allowed to air-dry. With a sphygmomanometer on the upper arm inflated to 40 mm Hg, the bleeding time device was pressed firmly against the cleansed area and triggered while a stop watch was simultaneously started. Blood was blotted with Whatman No. 1 filter paper every 30 seconds; care was taken not to disturb the incisions. The end point was recorded when no more blood was absorbed onto the filter paper. Results Development
Device
The first model consisted of a small plastic housing containing a spring-loaded scalpel blade protruding 1 mm through a slit in the bottom of the device. Depress-
Received April 11, 1977; received revised manuscript May 20, 1977; accepted for publication May 20, 1977. Address reprint requests to Dr. Babson: Department of Diagnostics, Research and Development, The Warner-Lambert Research Institute, Morris Plains, New Jersey 07950. 0002-9173/78/0900/0406 $00.60 © Ai
of Prototype
* Mr. Evan Chen and Mr. Frank Ferraro provided technical assistance in the design and construction of the prototype devices. ican Society of Clinical Pathologists
406
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
THE BLEEDING TIME is the time between the infliction of a small standard cut and the moment when the bleeding stops. It is a direct test of the ability of platelets to function normally in primary hemostasis and has been recently reviewed in depth. 3 The bleeding time test originally described by Duke 4 was done by making a puncture wound in the earlobe with a lancet. Ivy and associates 7 increased the sensitivity of the test by making three puncture wounds on the forearm while maintaining a constant back pressure of 40 mm Hg with a pressure cuff on the upper arm. Puncture wounds often give discrepant replicate bleeding times because the cuts are small but deep, thus increasing the possibility of hitting a larger vessel or an area with few capillaries. Various procedures using shallow scalpel blade incisions to avoid the problems associated with puncture wounds have been described. 2,5 ' 6 These procedures are very technic-dependent. Mielke and colleagues 9 attempted to standardize the length and depth of the incisions by use of a scalpel blade mounted in a holder that allowed only a fixed portion of the blade to protrude and a plastic template with an 11-mm slit. In this procedure, which has also been called the
The Department of Diagnostics Research and Development, The Warner-Lambert Research Institute, Morris Plains, New Jersey
Vol. 70 • No. 3
LABORATORY SUGGESTIONS
Evaluation of Final Disposable Device The final bleeding time device employed in these studies is illustrated before and after triggering in
y
6O-1
40-
o 2
30-
u a
20-
U D Of
10-
o-Lft
=ft^ fst
91 '10
BLEEDING TIME IN MINUTES FIG. 2. The distribution of 206 individual bleeding times from 47 normal adults.
Figure 1. The geometry of the bottom of the unit and the blade and the depth of the cut are identical to those aspects of the third prototype model. A tearaway tab was added to prevent premature triggering. The devices are individually packaged in sterilized blister packs.t A report on the comparison of this device with the template technic and its use on hospital patients appears elsewhere.8 Normal Range Forty-seven normal adults were tested over a twomonth period from one to five times each. The replicate results for each individual were averaged. The average bleeding times ranged from 2.3 to 7.0 min, with a mean of 4.1 min. Log transformation gave a 95% normal range of 2.2-7.0 min. The distribution of 206 individual bleeding times is shown in Figure 2. The 9-minute time was paired with a 7!^-minute time. These values are suspect, as this individual had average bleeding times of 3, 4>/£, and VA minutes on three other occasions. The upper limit of normal in this study was considered to be 7 min. Reproducibility Twenty-three normal individuals were tested four times each over a period of several weeks. The standard deviation of duplicate bleeding times was 0.7 min, and the day-to-day standard deviation for individuals was 0.9 min. Bleeding Time after Aspirin To test the ability of the bleeding time device to detect increases in bleeding time after aspirin ingestion,
FIG. 1. The final bleeding time device before and after triggering. The right illustration shows the tear-away tab removed and the blades protruding.
t Available commercially as Simplate® II from General Diagnostics Division, Warner-Lambert Co., Morris Plains, N.J. 07950.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
ing a trigger on top of the housing released the blade, which traveled 9 mm transversely through the slit. It was difficult to control the depth of the resulting incision, and several volunteer subjects received cuts that produced significant scarring. This approach was therefore abandoned. The second model released the spring-loaded blade like a guillotine. The blade was made from a doubleedged razor blade cut to 9 mm wide. The bottom of the housing was convex in order that it might place the skin under slight tension when the unit was pressed on the arm, and a blade protrusion of 1.2 mm provided optimum depth of incision. The device was designed so that blades could be changed easily between subjects and the unit rapidly recocked for replicate incisions on the same subject. Thirteen normal volunteers had bleeding times of 2 to 7 min with a mean of 4.8 min. To see whether a smaller incision could be used, the cutting edges of several blades were reduced to various sizes. In limited studies, the bleeding times progressively lengthened as the length of the blade increased from 3 to 6 to 9 mm. To minimize trauma and still provide a sensitive test, we elected to proceed with the 6-mm incision. A third model was constructed, similar to the second, but it housed a 16-mm blade with a 4-mm recess in the center of the cutting edge. This produced two simultaneous incisions, each 6 mm long. This device was evaluated on 27 normal individuals, who had average bleeding times of 2 to 7 min. The mean of all measurements was 3.91 min, with a standard deviation of 1.24 min. No problem was encountered with blood flowing from one incision to the other, and the two incisions were close enough to be covered easily by a single small adhesive bandage. These results were sufficiently encouraging to persuade us to proceed with with development of a commercial device.
407
BABSON AND BABSON
408
Table I. The Effect of Aspirin on Bleeding Time Control (min)
Aspirin (min)
Present study Mean 1 SD
3.7 ± 1.1
6.2 ± 2.5
Bick el «/.' Mean 1 SD
3.7 ± 1.4
6.0 ± 2.2
Discussion The original Ivy bleeding time technic and most of its subsequent modifications recommend averaging the bleeding times of three individual cuts. Mielke and colleagues9 showed that when standardized incisions are made, two cuts provided as much information as three. The device described here is the first to provide duplicate standardized incisions simultaneously. This greatly simplifies the timing of the procedure, because the two wounds can be blotted together. The proximity of the two cuts was of some initial concern to us. In no instance, however, did blood from the two cuts flow together during the 30-sec intervals between blottings.
While it is difficult to quantitate pain, it was clearly brought out in this study that the subjects experienced little or no sensation of being cut. The audible click at the release of the blade distracted the subjects, and many were surprised to find that they had indeed been cut. This aspect could be particularly advantageous with children. The fact that the blade is completely hidden within the housing should also cause the device to produce far less fear and apprehension in children than a bare scalpel blade. Another factor that is difficult to quantitate is scarring. While the initial prototype, which employed a transverse movement of a scalpel blade, did result in noticeable scars in a few volunteers, we were impressed with the lack of visible scarring with the final device. References 1. Bick RL, Adams T, Schmalhorst WR: Bleeding times, platelet adhesion, and aspirin. Am J Clin Pathol 65:69-72, 1976 2. Borchgrevink CF, Waaler BA: The secondary bleeding time: A new method for the differentiation of hemorrhagic diseases. Acta Med Scand 162:361-374, 1958 3. Bowie EJW, Owen CA Jr: The bleeding time, Progress in Hemostasis and Thrombosis. Volume 2. Edited by Spaet TH. New York, Grune and Stratton, 1974, pp 249-271 4. Duke WW: The relation of blood platelets to hemorrhagic disease: Description of a method for determining the bleeding time and coagulation time and report of three cases of hemorrhagic disease relieved by transfusion. JAMA 55:1185-1192, 1910 5. Harker LA, Slichter SJ: The bleeding time as a screening test for evaluation of platelet function. N Engl J Med 287: 155-159, 1972 6. Hjort P, Stormorken H: A study of the in vitro and in vivo effects of a synthetic heparin-like anticoagulant: Dextran sulfate. Scan J Clin Lab Invest 9 Suppl 29:1-86, 1957 7. Ivy AC, Nelson D, Bucher Q: The standardization of certain factors in the cutaneous "verostasis" bleeding time technique. J Lab Clin Med 26:1812-1822, 1941 8. Kumar R, Ansell JE, Canoso RT, et al: Clinical trial of a new bleeding time device. Am J Clin Pathol (in press) 9. Mielke CH, Kaneshiro MM, Maher IA, et al: The standardized normal Ivy bleeding time and its prolongation by aspirin. Blood 34:204-215, 1969
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
a double-blind crossover study was conducted with ten healthy men and ten healthy women. Each person ingested four capsules containing either 1 g glucose or 1 g aspirin immediately after a baseline bleeding time determination. A second bleeding time was done 24 hours later. A week later, the treatments were crossed over. The mean bleeding time of 6.2 min after aspirin was significantly longer (P < 0.01) than the mean control time of 3.7 min or the mean post-placebo time of 3.8 min. As shown in Table 1, these results are almost identical to the recent findings of Bick and coworkers,1 who used the template method.9
A.J.C.P. • September 1978
