Canad. Med. Ass. J. 818 SMYTHE AND OTHERS: PLATELET ECONOMY April 10, 1965, vol. 92 SOMMAIBE Le sulfinpyrazone (Anturan), administr6 .i doses th6rapeutiques pendant une p&iode de plusieurs semaines, a entrain6 une survie prolong6e des plaquettes et un ralentisse- ment du roulement biologique, tout en n'affectant gu.re Ia coagulation du sang. Les modifications portant sur la survie des plaquettes et leurs roulement biologique provenaient d'une diminution de l'adh6rence des plaquettes. Ii est done possible de r6aliser une 6conomie sensible des plaquet- tes chez l'homme sans, pour autant, toucher .i Ia coagulation sanguine. Canad. Med. Ass. J. April 10, 1965, vol. 92 SMYTHE AND OTHERS: PLATELET ECONOMY 819 TABLE 1.-CoAGUlATIoN TESTS Mean (harmonic) Mean (geometric) Mean plasma dotting time prothrombin time thromboplastin Mean platelet (minutes) (seconds) time (seconds) adhesive index No No No No Subject** Age Diagnosis therapy Suif. therapy Suif. therapy Suif. therapy Suif. Si.60 M.I. 10.4 7.6 - - 12.5 12.4 1.10 1.05 An.59 R.A. 9.7 6.0 14.0 12.3 11.4 11.9 0.96 1.25 Ma.50 Gout - - - - - - - - So.60 S.gout - - 15.0 15.0 14.1 13.3 1.28 1.32 Mi.65 Myel. - - - - - - - 1.12 Na.54 M.I. 9.0 9.1 14.5 13.3 11.3 12.6 1.89 1.24 Sh.41 M.I. 12.0 8.1 14.0 15.0 10.1 11.4 1.31 0.96 Ha.23 Normal 9.1 11.7 13.0 13.0 11.5 16.3 1.32 1.48 liar.62 S.gout - - - 18.1 - - - 1.23 She.69 Gout 10.7 12.7 15.0 14.9 10.9 14.0 1.26 0.87 Bu.41 Phieb. 10.5 12.6 13.2 13.8 10.2 12.1 1.47 1.25 By.57 Gout 10.6 12.6 15.4 14.4 12.1 12.0 1.48 1.45 Cl.35 Gout 15.4 9.9 14.5 15.8 12.0 10.1 1.09 1.16 Cia.42 Gout 7.0 11.8 14.7 13.6 12.0 12.5 1.20 1.09 Ca.51 Gout 6.7 8.5 13.7 14.8 11.8 13.2 1.69 1.14 Hu.38 Gout 9.8 12.0 14.0 14.7 11.4 11.3 1.18 1.08 Co.51 Gout 8.7 12.8 14.9 14.3 11.8 9.0 1.42 1.24 Mar.57 MI. 10.7 7.4 14.6 14.3 10.9 15.6 1.23 1.02 Da.71 M.I. 9.2 11.2 14.5 13.0 17.1 12.0 1.08 1.06 Ro.36 Normal 12.5 10.5 14.3 13.4 13.4 10.2 1.12 1.14 Ja.45 Normal 9.9 10.5 13.5 13.3 11.5 11.1 1.51 1.32 Meanof means.9.76 10.15 14.30 14.22 11.58 12.07 1.325 1.184 Significance of differences between means* t 0.421 t 0.283 t 0.968 t 1.949 Subjects 1 - 17 p <0.7 p <0.8 p <0.4 p <0.1 All subjects t 0.170 t 1.013 t 0.371 t 2.309 p <1.0 P <0.4 p <0.8 p <0.05 M.I. = myocardial infarct; R.A. = rheumatoid arthritis; S. gout = secondary gout; Myel. = myeloproliferative disease; Phieb. = phlebitis. *Based on paired difference analysis. **Subjects Mar, Da, Ro and Ja received therapy for only four weeks or less. Cohen'2 using radioactive di-isopropyl fluorophos- the period of treatment (Table II). The four sub- phate (DFP32). Platelet turnover values were cal- jects who did not show an effect (Mar, Da, Ro culated on the basis of the average platelet count and Ja) had been given the drug for only a period during the period of the study, using a formula of four weeks or less prior to the study. One of recorded elsewhere.'1 these subjects (Mar) was studied again after being on the drug for four months. At that time Statiatical Canuiderations his platelet half-life value was 4.65 days, which is considerably longer than the pre-treatment value. The statistical considerations involved in the Platelet survival in the 17 subjects receiving the evaluation of data of this type have been described drug for a period longer than five weeks was over elsewhere." 10, . Since the same subjects were 40% longer than that seen in the pre-treatment studied during a "treatment" period and a "no period. Platelet turnover showed a similar trend. treatment" period, the analysis of the data was All but two of the subjects receiving the drug for by paired differences. a period of five weeks or longer showed a reduction in platelet turnover. The average reduction (based RESULTS on the exponential model) produced in these 17 There was no difference in the clotting time for subjects by sulfinpyrazone therapy was over 40%. the subjects during the "no treatment" and "treat- ment" periods (Table I). Similarly, neither the DIsCUsSION plasma thromboplastin time nor the prothrombin These studies show that sulfinpyrazone, which has time showed any consistent trend. Twelve of 18 a uricosuric effect, also has a considerable influence subjects showed lower platelet adhesiveness during on platelet economy. The change in platelet survi- the "treatment" period than during the "no treat- val is striking and the effect on platelet turnover ment" period and there was a significant difference greater than that which has been observed with between the means (Table I). There was a signffi- most other manipulative procedures.3' 14,15 Since, in cant reduction in the mean platelet count during their usual therapeutic doses, drugs commonly used the period of therapy. All but four of the 21 sub- to treat thrombosis, such as bishydroxycoumarin and jects showed a longer platelet survival time during heparin, do not exert so great an effect, the question 820 SMYTHE AND onmiis: PLATELET Canad. Med. Ass. 3. ECONOMY April 10, 1965, vol. 92 TABLE 11.-PLATELET SURVIVAL AND TURNOVER Mean Platelet survival (days) Platelet turnover (No./c.mm./day) platelet count (No./c.mm.) Exponential Gaussian Exponential Gaussian No No No No No Subject therapy Suif. therapy Suif. therapy Suif. therapy Sulf. therapy Suif. Si.218,000 320,000 3.655 5.034 10.877 13.192 41,340 44,060 20,040 24,260 An.280,000 256,000 2.809 4.137 10.695 11.629 69,090 42,890 26,180 22,010 Ma.220,000 178,000 2.978 3.424 10.153 11.038 51,210 36,030 21,670 16,130 So.118,000 96,000 3.610 4.881 10.899 12.899 22,660 13,630 10,830 7,450 Mi.750,000 622,000 3.736 4.339 10.703 11.803 139,150 99,360 70,070 52,700 Na.260,000 245,000 3.038 5.997 10.335 13.774 59,320 28,320 25,160 17,790 Sh.220,000 178,000 2.840 4.787 10.523 13.110 53,690 25,770 20,910 13,580 Ha.372,000 144,000 3.734 4.035 11.189 12.081 69,050 24,740 33,250 11,920 Har.220,000 155,000 6.745 8.285 14.183 19.088 22610 12970 15510 8120 She.173,000 124,000 3.366 4.047 10.838 11.590 35:620 21,240. 15,960 10,700 Bu.470,000 309,000 2.708 5.611 10.389 14.340 120,300 38,170 45,240 21,550 By.233,000 232,000 3.510 3.744 11.300 11.283 46,010 42,950 20,620 20,560 Cl.224,000 247,000 2.008 4.831 9.680 12.970 77,320 35,440 23,140 19,040 Cia.214,000 182,000 2.476 2.927 9.933 11.461 59,910 43,100 21,540 15,880 Ca.182,000 122,000 2.517 3.953 9.385 11.835 50,120 21,390 19,390 10,310 Ru.180,000 170,000 2.230 7.150 9.886 15.420 55,950 16,480 18,210 11,020 Co.246,000 212,000 2.766 4.120 10.402 11.650 61,650 35,670 23,650 18,200 Mar. 308,000 244,000 4.133 3.127 12.095 10.625 51,650 54,090 25,470 22,960 Da.207,000 233,000 4.013 3.785 11.698 11.286 35,750 42,670 17,700 20,650 Ro.204,000 206,000 3.059 2.767 10.453 10.150 46,220 51,600 19,520 20,300 Ja.366,000 304,000 3.536 3.461 11.008 11.060 71,750 60,880 33,250 27,490 Mean or mean of means. 269,800 223,100 3.308 4.497 10.792 12.489 59,065 37,688 25,110 18,696 Significance of differences between means* t 2.607 t 5.206 t 5.862 t 5.498 t 4.459 Subjects 1-17 p <0.02 p <0.001 p <0.001 p <0.001 p <0.001 All subjects.. t 2.823 t 3.979 t 4.316 t 4.606 t 4.192 p <0.02 p <0.001 p <0.001 p <0.001 p <0.001 *Based on paired difference analysis.