Brief Reports

In Vivo Platelet Function Following Cardiopulmonary Bypass J. UMLAS From the Mount Auburn Hospital. Cambridge. Massachusetts,

and Harvard Medical School, Boston. Massachusetts

I n order to test the in vivo hemostatic function of platelets exposed to cardiopulmonary bypass, template bleeding times (TBT) were performed prebypass, three hours postbypass and 18 to 20 hours postoperatively in 22 patients undergoing open-heart surgery. The HarkerSlichter formula was applied to platelet counts below 1OO,OOO/cu mm to determine the expected T B T if the platelets function normally but were associated with a prolonged bleeding time merely from thrombocytopenia. Half of the patients received only frozen erythrocyte transfusions. Twenty of the 22 patients (91%)had normal or shorter than the expected TBT. Eight of the ten patients with platelet counts under lOO,OOO/cu mm had shorter than predicted TBTs. All of the patients receiving only frozen erythrocytes had normal or shorter than predicted TBTs. I t is concluded that in vivo platelet hemostatic function is usually normal postbypass, that routine platelet transfusions are therefore not necessary, and that most open-heart surgical procedures can be performed using frozen erythrocyte transfusions exclusively.

length and depth is made while the arm is subjected to a pressure of 40 mm of mercury by a sphygmomanometer. This bleeding time, known as the template bleeding time (TBT), is thus standardized and reproducible. It is dependent on platelet count and overall hemostatic function. Harker and Slichter2 have devised a formula for platelet counts under 1OO,OOO/cu mm which purports to show what the TBT should be for that platelet count if the platelets have normal hemostatic function. In this way, patients with thrombocytopenia but intact platelet hemostatic function can be separated from thrombocytopenic patients with abnormal function. Both groups would be expected to have abnormal bleeding times. The TBT and Harker-Slichter formula were used in a group of open-heart surgical patients to evaluate in vivo platelet hemostatic function.

THERAPID AND SUBSTANTIAL FALL in the blood platelet count after the onset of cardiopulmonary bypass is a well-known phenomenon. In addition, various in vitro abnormalities of platelet function during and after cardiopulmonary bypass have been r e p ~ r t e d . ~ . * Thus, . * . ~ some authors have felt that thrombocytopenia in the immediate postperfusion period is the main cause of impaired hemostasis in open-heart surgical patients.12 Others, however, have felt that postperfusion bleeding is uncommonly due to platelet problems and that platelet transfusions are not routinely Recently, Mielke, et u I . ~ modified the bleeding time by using a polystyrene template through which an incision of standard

Material and Methods Two groups of open-heart surgical patients were studied. Eleven patients were transfused with only previously frozen erythrocytes, receiving no other blood component. Eleven other patients received varying combinations of one- to four-day-old blood (whole blood or packed erythrocytes), frozen erythrocytes, and fresh frozen plasma but no platelet concentrates or freshly drawn blood. Platelet counts and TBTs were measured preoperatively, approximately three hours postcardiopulmonary bypass and approximately 18 to 20 hours postoperatively. Although platelet counts were also performed immediately after protamine therapy, TBTs were not performed at this juncture because it was felt that the hypothermia and peripheral vasoconstriction present at this time would interfere

Received for publication September 30, 1974; accepted November 24, 1974. Transfusion Nov.-Dec. 1975

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Table 1. Patients Receiving Only Frozen Erythrocyte Transfusions

Prebypass

Patients AC ME HA TSS EM JM SY PC MJ RM KM Mean '

Operation Plt. Ct. ASD CBG MVR AVR MVR BCBG CABG MVR TVP BCBG BCBG CBG

266 389 221 225 250 430 188 238 255 466 358 299 i94.7

TBT (min.)

Transfusion Perf usion Ti me 24 Hours (min.1

1S t

Plt. Ct.

2 134 4 174 3 115 3 6 4 4.5 128 3 135 3 91 6.5 70 4 3 6 3.8 i1.4

20 Hours Postoperative

3 Hours Postbypass

135 136 237 129 i50.5

TBT

Plt. Ct.

7 7 5.5 4 (13.9)" 3 1 5 (6.9)" 6 (12.3)* 4.5 6 6.5 5.5 k1.8

200 147 90 125 180 93 61 165 136 210 140.7 i49.4

O.R.

TBT

5 4.5 6 (6.6)" 4.5 2.5 4.5 (6.3)" 6 (14.7)" 3.5 6.5 4.5 4.8 51.2

*Measured TBT faster than predicted TBT (in parenthesis) for platelet count below **i 1 S.D. Pit. Ct.-p\atelet count ( X iO3/cu mm) TBT-template bleeding time

with the test and cause spurious results. Normal values for the platelet count and TBT at our hospita1 are 150 to 350,OOO/cu mrn and 1.0 to 7.5 minutes, respectively. When the platelet count was below 1OO,OOO/cu mm, the Harker-Slichter formulaz [30.5 = (platelet count/3850) = expected TBT] was ap-

3 3 4 8 1 7 4 2

2 2 2 1 3 3 3 5

3 8 2 4.1 i2.5

6 2 2 2.8 21.5

34 34 100 117 97 115 72 114 75 103 75 85.1 i30

lOO,OOO/cumm.

plied to determine if the platelets had normal hemostatic function.

Results The results from the 1 I patients receiving only frozen erythrocytes are shown in Table I . Three

Table 2. Patients Receiving Shelf Blood with or without Frozen Erythrocytes and Fresh Frozen Plasma

Prebypass

Patients WH ES J Mit JR JB RD' J Mil' AD MA ME MV"" Mean*+

Operation Plt. Ct. BCBG MVR TCBG AVR GBG CBG MVP MVR VA CBG VA MVP MVR

3 Hours Postbypass

TBT (min.) Plt. Ct.

371 236 384 334

2.5 3 3

90 116 70 89

309 178 170 351

4 3.5 5 2.5

75 77 50 199

232 229 294 280.7 275.8

4.5 2 6 3.6 i1.3

20 Hours Postoperative

Transfusion Perf usion Time O.R. 24 Hours (min.)

1S t

TBT

6 (6.6)" 6 9.5 (12.3)" 9 (7.4)++

Plt. Ct.

55 108 51 163

7.5(11)" 92 10.5 (12.5)" 16f17.5)" 76 3 175

130 3 113 4.5 8% 13 (7.7)"" 99.7 8 i40.1 k4.1

139

TBT

10.5 (16.2) 10 6 8 8.5 (17.3)' 9 4.5 11 4.5 (6.6)' 6110.8)' 3 6

123 7 109.1 6.2 k44.8 52.3

1 2 3 1

191 96 183 168

5 9 6 4

3 2 3 2

106 108 95 78

4 2 7 6.8 i2.9

1 8 1 2.5 22

"Measured TBT faster than predicted TBT (in parenthesis) for platelet count below lOO,OOO/cu mm. *+MeasuredTBT longer than predicted TBT (in parenthesis) for platelet count below lOO,OOO/cu mm. *+*+ 1 S.D.

49 113 103 117.3 244.6

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Table 3. Patients in Either Transfusion Group w i h Postbypass Platelet Counts Below lOO,OOO/cu mm

Prebypass

Patients JR MV TSS

SY PC WM J Mit JB RD J Mil Mean**

Operation Plt. Ct. AVR CBG MVR AVR CBG MVR TVP BCBG TCBG CBC MVP MVR

3 Hours Postbypass

TBT (min.) Plt. Ct.

334 294 225 188 238

3 6 3 3 6.5

371 384 309 178 170 272.1 t7a.7

2.5

a9

88 64 91 70

20 Hours Postoperative

Transfusions Perfusion Time 24 Hours (min.)

1S t

TBT

Plt. Ct.

9 (7.4)" 13 (7.6)" 4 (13.9)" 5 (6.9) 6 (12.3)

6 (7.1) 90 9.5 (12.31 70 7.5 (11) 4 75 10.5 (11.5) 3.5 77 16' (18.5) 5 50 8.5 (10.9) 4.05 76.4 ki.4 j113.4 ~ 3 . 8

TBT

163 123 90 93 61

4.5 7 6 (7.1) 4.5 (6.3) 6 (14.71

55 51 92

10.5 (16.2) 8.5 (17.3) 4.5 (6.6)

76 89.3 k35.7

6 (10.8) 6.4 (1 1.3) i2.0

O.R.

11 7 8 4 2

10 9 5 9 6 7.1 ~2.8

1 1 1 3 5

168 103 117 72 114

1

191 183 106 108 95 125.7 k40.3

3 3 2 3 2.3 k1.3

"Predicted TBT in parenthesis. *** 1 S.D.

of 1 I patients had platelet counts under lOO,OOO/ cu mm at three and 20 hours. All three had TBTs shorter than that predicted from their platelet count if the platelets had normal hemostatic function. The results from the I I patients receiving shelf and frozen blood and fresh frozen plasma are shown in Table 2. Seven of the I I patients had platelet counts below 1OO,OOO/cu mm a t three hours. Five of the seven had TBTs shorter than the predicted value for platelets with normal function and two had TBTs which were longer than the predicted value. No patient in either transfusion group had an abnormal TBT preoperatively. The TBTs for all 12 patients with platelet counts above 1OO,OOO/cu mm were in the normal range. The results for patients in either transfusion group with platelet counts under 100,OOO/cu mm are shown in Table 3. Both patients with platelet counts below 1OO,OOO/cu mm and TBTs longer than the predicted value at three hours postbypass corrected their platelet counts and TBTs by 18 to 20 hours postoperatively.

Discussion Frozen erythrocyte transfusions contain virtually no intact platelets.6 The original purpose in measuring TBTs in a group of patients receiving essentially platelet free previously frozen erythrocytes was to eliminate whatever effect refrigeration produces on even poorly surviving platelets in

shelf blood that would influence the TBT in the transfused recipient. Valerill showed that there was an immediate correction of the aspirin-induced prolonged TBT with platelet concentrates stored at 4 C. By including patients receiving only platelet free frozen erythrocytes, normal TBTs could not be attributed to this refrigeration effect on effete transfused platelets, only to the condition of the patients' own platelets. The 11 patients transfused exclusively with frozen erythrocytes therefore received no platelet support yet required no more transfusions in the operating room or in the first 24 hours postoperatively than the group receiving shelf blood. The platelet counts were higher at three and 20 hours in the former group and the TBTs were similar in patients from each group when the platelet counts were similar. Twenty of the 22 patients (91%) in both transfusion groups had TBTs which were normal or, in eight of the ten patients with platelet counts under 1OO,OOO/cu mm shorter than the predicted TBT for that platelet count. The results would suggest that these platelets therefore had normal or increased hemostatic function when tested

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by an in vivo test, the Mielke template bleeding time. It seems justified to conclude that in over 90 percent of patients, platelets demonstrate normal or increased hemostatic competence by in vivo testing and that it is unnecessary to routinely administer platelets following cardiopulmonary bypass. Further, frozen erythrocyte transfusions may be used exclusively in most open-heart surgical patients without compromising platelet numbers or in vivo function as compared with the use of shelf blood. Additional work in this laboratory also demonstrates no adverse effect on plasma coagulation using this mode of transfusion therapy. lo Acknowledgment The author is grateful to all the cardiovascular attending and house staff physicians for their cooperation in studying these patients.

References I.

Grindon, A., and P. J. Schmidt: Platelet-poor blood in open heart surgery. N. Engl. J. Med.

2.

Harker, L. A,, and S. J. Slichter: The bleeding time as a screening test for evaluation of platelet function. N. Engl. J. Med. 287:155, 1972. McKenzie, F. N., D. P. Dhall, K.'E. Arfors, S. Nordlund and N. A. Mathesar: Blood platelet behavior during and after open-heart surgery. Br. Med. J. 2:795, 1969. Mielke, C . H., Jr., M. de Leva], J. D. Hill, M. F. Macur and F. Gerbode: Drug influence on

280:1337,1969.

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4.

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platelet loss during extracorporeal circulation. J. Thorac. Cardiovasc. Surg. 66:845, 1973. 5. -, M. M. Kanishiro, 1. A. Maher, J. M. Weiner, and S. 1. Rapaport: The standardized normal Ivy bleeding time and its prolongation by aspirin. Blood 34:204, 1969. 6. Nusbacher, J.: In: Red Cell Freezing, Technical Workshop, Committee on Workshops of American Association of Blood Banks, 1973, p. 89. 7.

Pike, 0. M., J. E. Marquiss, R. S. Weiner and R. T. Breckenridge: A study of platelet counts during cardiopulmonary bypass. Transfusion 12:119, 1972.

8. Salzman, E. W. Blood platelets and extracorporeal circulation. Transfusion 3:274, 1963. 9. Signori, E. E., J. A. Penner and D. R. Kahn: Coagulation defects and bleeding in open-heart surgery. Ann. Thorac. Surg. 8521, 1969. 10. Umlas, J., and R. Sakhuja: The effect on blood coagulation of the exclusive use of frozen erythrocyte transfusion during and after cardiopulmonary bypass. J. Thorac. Cardiovasc. Surg. 70519, 1975. 1 I . Valeri, C. R.: Hemostatic effectiveness of liquidpreserved and previously frozen human platelets. N. Engl. J. Med. 290:353, 1974. 12. Wagstaffe, J. G., A. D.Clarke and P. W. Jackson: Reduction of blood loss by restoration of platelet levels using fresh autologous blood after cardiopulmonary bypass. Thorax 27:410, 1972. 13. Woods, J. E., H. F. Taswell, J. W. Kirklin and C. A. Owen, Jr: The transfusion of platelet concentrates in patients undergoing heart surgery. Mayo Clin. Proc. 42:318, 1967.

Joel Umlas, M.D., Mount Auburn Hospital, Cambridge, Mass.

In vivo platelet function following cardiopulmonary bypass.

In order to test the in vivo hemostatic function of platelets exposed to cardiopulmonary bypass, template bleeding times (TBT) were performed prebypas...
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