0021-972X/90/7002-0491$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright© 1990 by The Endocrine Society
Vol. 70, No. 2 Printed in U.S.A.
Platelets in Hyperthyiroidism: Studies on Platelet Counts, Mean Platelet Volume, 111-Indium-Labeled Platelet Kinetics, and Platelet-Associated Immunoglobulins G and M* SIMON PANZER, ALEXANDER HAUBENSTOCK, AND ERICH MINAR First Medical Clinic, University of Vienna, Vienna, Austria
lifespan was significantly shortened in the patients with hyperthyroidism compared with the control group (median, 163.8 h; range, 128.5-206 h; us. 180.0 h; range, 138.3-231.5 h; P < 0.05). Platelet turnover averaged 45.6 (range, 25.6-71.9) x 109/L-day; values above the limit of normal were found in 7 of 15 patients with hyperthyroidism. Three patients with Graves' disease had elevated levels of PAIgG; 1 of these patients had elevated levels of PAIgM and was the only patient with thrombocytopenia (PC, 96 X 109/L). Various combinations of statistical correlations between the degree of hyperthyroidism, pretreatment PC and MPV, platelet kinetic studies, levels of PAIg, and serum levels of antithyroid antibodies revealed no significant differences. These findings suggest that the platelet changes observed in hyperthyroidism, such as lower PC and increased MPV, together with the shortened platelet lifespan reflect metabolically rather than immunologically mediated phenomena, although these may be involved in cases with marked thrombocytopenia. (J Clin Endocrinol Metab 70: 491, 1990)
ABSTRACT. We compared in 15 patients with hyperthyroidism (11 with Graves' disease, 3 with toxic adenoma, and 1 with multinodular goiter) platelet counts (PC) and mean platelet volume (MPV) before and 3 weeks after initiation of antithyroid drug therapy when the patients were euthyroid. In addition, platelet kinetic studies of autologous 111-indium-labeled platelets and platelet-associated immunoglobulins G and M (PAIgG and PAIgM, respectively) were investigated. The control group for the platelet kinetic studies consisted of 2 patients with diffuse nontoxic goiter and 86 patients who were studied for evaluation of their arteriosclerotic vascular disease. After 3 weeks of antithyroid drug therapy there was a significant increase in PC and a decrease in MPV compared with the pretreatment values (pretreatment PC median, 215 x 109/L; range, 96-350 x 109/L; PC median 3 weeks later, 248 x 109/L; range, 157-384 x 109/L; P < 0.005; pretreatment MPV median, 10.6 fL; range, 9.1-13.2 fL; MPV 3 weeks later, 9.9 fL; range, 8.4-11.0 fL; P < 0.005). Ill-Indium platelet recovery was normal in all subjects. Platelet
A
also been reported in Graves' disease (8, 9). Very recently, an increased mean platelet volume (MPV) was found in patients with hyperthyroidism (10), which was found to be reversed upon achievement of euthyroidism (11). To date, no study has combined all of these parameters to analyze platelet changes in hyperthyroidism. The present experiments, using 111-indium-labeled platelet kinetics and measurements of levels of plateletassociated Ig (PAIg), suggest that in hyperthyroid patients with a normal PC, metabolic rather than immunemediated influences on platelets occur, which are reflected by the changes in pre- and posttreatment PC and MPV.
N ASSOCIATION of thrombocytopenia with hyperthyroidism has been observed previously (1, 2). The mechanism by which thrombocytopenia is induced in hyperthyriodism is not fully understood. Severe autoimmune thrombocytopenia has been reported (3), and the findings of elevated levels of platelet immunoglobulin G (IgG) in about 50% of patients with Graves' disease or Hashimoto's thyroiditis supported the general assumption of an an immune-mediated mechanism (4). On the other hand, an increase in megakaryocytes in the bone marrow (5) and a shortened platelet survival time (6, 7) have been reported in hyperthroid subjects, even when platelet counts (PC) were normal. Hypersplenism resulting in platelet pooling and causing thrombocytopenia has
Patients Received July 30, 1989. Address all correspondence and requests for reprints to: Simon Panzer, M.D., Immunobiology Research Center, Department of Laboratory Medicine and Pathology, University of Minnesota, Box 724, 420 Delaware Street SE, Minneapolis, Minnesota 55455. * This work was supported by grants from the Hochschuljubilaeumsstiftung der Stadt Wien and the Medizinisch-Wissenschaftlicher Fonds des Buergermeisters der Bundeshauptstadt Wien.
Fifteen female patients with newly diagnosed hyperthyroidism (aged 17-78 yr) gave their informed consent to participate in these studies. Hyperthyroidism resulted from diffuse toxic goiter (Graves' disease) in 11 patients, toxic adenoma in 3 patients, and multinodular goiter in 1 patient. The 15 patients were seen consecutively in the thyroid out-patient clinic. One 491
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PANZER, HAUBENSTOCK, AND MINAR
492
patient (patient 11; Table 1) was referred from the hematology out-patient clinic where she had been evaluated for an otherwise unexplained thrombocytopenia. The patients had no other relevant diseases, nor did they use any medication. None of the patients had a palpable spleen or lymphadenopathy. In the patient with thrombocytopenia (patient 11) the spleen was also of normal size by ultrasound. There was no evidence of clinical bleeding tendency. Patients were treated with 80 mg methimazole/day, orally, for the first week, 60 mg methimazole/day, orally, for the second week, and 40 mg methimazole/day, orally, for the third week. The hyperthyroid state at presentation and the euthyroid state after 3 weeks of therapy were confirmed by clinical assessment and serum levels of total T4 and free thyroid index (FTI; Table 1). The patients were not retrospectively selected by the achievement of euthyroidism. Two patients with diffuse nontoxic goiter served as controls for both platelet survival studies and determination of PAIgG and PAIgM. Eighty-six patients with arteriosclerotic vascular disease (60 men and 26 women, aged 41-79 yr) served as additional controls for the platelet survival studies.
Materials and Methods Thyroid function tests and antithyroid antibodies Serum T4 and FTI were determined by RIA (Bio-Rad Laboratories, Richmond, CA). Antithyroglobulin (Behring Werke, Marburg, West Germany) and antithyroid microsomal antibodies (Melisa, Freiburg, West Germany) were measured in the routine clinical laboratory.
JCE & M • 1990 Vol 70 • No 2
TABLE 1. Patient characteristics and values of T4/FTI, PC, and MPV before and after treatment of hyperthryoidism (n = 15) and in euthyroid patients with goiter (n = 2)
Patient no.
Age Diagnosis" (yr)
1 2 3 4 5 6 7 8 9 10 11
17 77 25 63 47 72 34 36 64 22 78
12
66
13
47 75 47 27
GD GD GD GD GD GD GD GD GD GD GD TA TA TA MG DG
45
DG
14
15 16 17
T4/FTI (nmol/L)6 Pre
Post
>257/>1.50 245/1.40 255/1.44 201/1.37 184/1.28 185/1.29 >257/>1.50 215/1.24 165/1.26 243/1.40 255/1.54 188/1.41 175/1.24 181/1.22 190/1.27 108/ND 103/ND
67/0.81 98/ND 106/ND 66/ND 135/ND 104/ND 120/ND 118/ND 144/1.09 165/1.06 92/ND 86/ND 126/ND 130/ND 170/1.07 ND/ND ND/ND
PC MPV (fL; (X107L; pre/post) pre/post) 267/308 243/346 350/384 199/230 192/238 175/186 228/259 197/241 201/248 252/270 96/157 193/281 220/269 215/207 208/248 159/ND 229/ND
10.4/9.6 10.6/9.8 9.1/8.5 11.1/10.5 9.7/9.6 10.8/10.6 13.2/11.0 11.0/10.3 10.9/8.4 10.5/10.1 11.8/10.6 10.2/9.6 10.4/9.5 10.1/10.1 9.8/9.9 9.9/ND 11.3/ND
Normal value T4 64-144 150-350 9.0-13.0 FTI 0.86-1.13 " GD, Graves' disease; TA, toxic adenoma; MG, multinodular goiter; DG, diffuse nontoxic goiter. 6 Pre, Before treatment; Post, after treatment; ND, not done.
50) (18). The platelet adhesion immunoflourescence test (19) was applied to screen the sera for platelet-binding IgG antibodies to platelets from blood group O donors with known HLA class I and P1A1/2 and Baka phenotypes. Statistical analyses
Complete blood counts and platelet indices Freshly drawn blood specimens were anticoagulated in siliconized glass tubes containing K3-EDTA (Vacutainer, Becton Dickinson Co., Rutherford, NJ). Blood cell and platelet profiles were performed with a TOA Sysmex E-4000 (TOA Medical Electronics Co. Ltd., Kobe, Japan). Blood cell profiles were performed at least 1 h after venipuncture (12) according to the manufacturer's manual. 111-Indium-labeled platelet kinetic studies Before initiation of antithyroid drug therapy, autologous platelets were labeled with 111-indium-oxine as described previously (13, 14). Recovery was estimated from a 30 min blood sample. Platelet lifespan was computed by the multiple hit system (15). In addition, linear and exponential curves were calculated (least square fitting procedure) to obtain the best fit. Platelet turnover was calculated from the peripheral blood platelet count, the platelet lifespan, and the correction factor applied for the exchangeable splenic platelet pool (16). Platelet-reactive Igs PAIgG and PAIgM were quantitated by a competitive enzyme-linked immunoassay (17). Calibration curves were constructed from serial dilutions of standard sera with known amounts of IgG and IgM (Behring Werke). Upper limits of normal values were 2.2 fg/platelet for both IgG and IgM (n =
Data were analyzed with nonparametric tests; the KruskalWallis test was applied to screen for differences in the results of the platelet kinetic investigations between hyperthyroid patients and the control group, the Wilcoxon rank test for paired data was applied to 1) compare the pretreatment PC and MPV, to correlate 2) the pretreatment PC and MPV with the degree of hyperthyroidism, 3) the platelet kinetic studies with T4 and FTI studies, the PAIg levels, and the pretreatment PC and MPV, and 4) the PAIg levels with the PC, MPV, and antithyroid antibody levels. P < 0.05 was considered the limit for rejection of a single null hypothesis.
Results Thyroid function tests Clinical characteristics of the patients with thyroid disorders and the results of the pre- and posttreatment thyroid function studies are shown in Table 1. Serum T4 levels were also routinely measured in all control patients with arteriosclerotic vascular disease and were within the normal range in all patients (data not shown). Complete blood counts and platelet indices
After 3 weeks of antithyroid drug therapy, all 15 patients with hyperthyroidism were euthyroid (Table 1). The PC increased from a median value of 215 X 109/L
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PLATELETS IN HYPERTHYROIDISM
(range, 96-350 X 109/L) to 248 X 109/L (range, 157-384 x 109/L; P < 0.005), and the MPV decreased from a median value of 10.6 fL (range, 9.1-13.2 fL) to 9.87 fL (range, 8.4-11.0 fL; P < 0.005; Table 1). No significant changes were observed in the red blood cell count (median, 5.27-5.11 X 1012/L), hematocrit (median, 0.43-0.42 volume fraction), mean red cell volume (median, 82.482.8 fL), and white blood cell count (median, 6.17-7.23 X 109/L). There was no statistical correlation between the pretreatment PC and MPV values and the serum T4 and FTI levels.
493
though platelet survival was shorter than normal in only 1 patient of the 15 with hyperthyroidism, platelet lifespan in this group was significantly shorter than that in the control group (P < 0.05; Fig. 1). Although 7 of the 15 patients with hyperthyroidism had platelet turnover rates above the upper limit of normal, they were not significantly higher than the rate in the control group (of note, also, in the control group few patients had increased platelet turnover). There was no statistical correlation between the platelet kinetic studies and the serum T4 and FTI levels, and the pretreatment PC and MPV values.
Ill-Indium platelet kinetic studies The results of the Ill-indium platelet kinetic studies in the 17 patients with thyroid disorders are shown in Table 2. Recovery was within the normal range in all 17 patients. The average platelet lifespan in the 15 hyperthyroid patients was 163.8 h (range, 128-206 h), and the median platelet turnover rate was 45.6 X 109/L-day (range, 25.6-71.9 X 109/L-day). Platelet turnover rates were above the upper limit of normal in 7 of the 15 hyperthyroid patients. All 7 patients had normal platelet counts. Five of the seven patients had Graves' disease, 1 patient had a toxic adenoma, and 1 had multinodular goiter (patients 1, 2, 3, 7, 10, 13, and 15). In the control group, consisting of 86 patients with arteriosclerotic vascular disease and 2 patients with diffuse nontoxic goiter, the median platelet lifespan was 180 h (range, 138.3231.5 h), and the median platelet turnover rate was 38.7 x 10 9 /Lday (range, 26.1-83.3 x 109/L-day). Even
PAIg Results of PAIg studies are shown in Table 3. PAIgG was elevated in 3 of 15 patients with hyperthyroidism. All 3 patients had Graves' disease (33% of the 11 patients with Graves' disease). PAIgM was also elevated in 1 of these 3 patients (Table 3). Interestingly, this patient (no. 11) was thrombocytopenic when first seen, but had a normal PC after 3 weeks of antithyroid drug therapy alone (Table 1). Normal values of PAIg were found at follow-up evaluation. There was no statistical correlation between the PAIg levels and pretreatment PC and MPV, and the results of the platelet kinetic studies. None of the tested sera contained platelet-binding IgG. Antithyroid antibodies Nine of 11 patients with Graves' disease had elevated antithyroid antibody levels, whereas none of the patients
TABLE 2. Results of 111-indium-labeled platelet kinetic studies in 17 patients with thyroid disease Patient no. 1
2 3 4 5
6 7 8 9 10 11 12 13 14 15 16 17 Normal value"
Recovery (%) 71.4 44.9 80.3 45.2 54.3 67.2 49.0 66.0 71.0 58.9 50.2 48.3 58.8 64.3 54.3 61.1 61.8
Lifespan (h) 158.3 149.8 163.8 177.0 206.9 166.6 193.4 193.4 187.2 128.5 152.2 193.9 152.0 159.0 166.0 169.7 201.5
Turnover (xiOYL-day) 51.0 77.9 57.4 44.7 36.9 33.7 49.0 29.3 26.8 71.9 25.6 45.2 52.9 45.6 46.0 29.9 39.7
>45.0
144-224
22.6-45.8
° Derived from 86 patients with arteriosclerotic vascular disease. The Patients' thyroid disorders are identified in Table 1.
S 144
145-160
161-176
177-192
193-208
209-231
platelet life-span (hours)
FIG. 1. 111-Indium-labeled autologous platelet survival studies in 15 patients with hyperthyroidism (•) and 86 control patients with arteriosclerotic vascular disease (M). A shift to the left of the relative frequency of patients with hyperthyroidism is shown compared to the control patients (P < 0.05).
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PANZER, HAUBENSTOCK, AND MINAR
494
TABLE 3. Levels of PAIgG, PAIgM, and antithyroid antibodies in 17 patients with thyroid disease Patient no. 1 2 3 4 5 6 7 8 9 10 11
12 13 14 15 16 17
Normal value
PAIgG (fg/platelet) 0.38 0.65 0.24 0.70 0.85 3.60 3.60 1.60 0.50 0.36 >10.00 0.50 0.44 1.50 0.55 0.55 0.80
Vol. 70, No. 2 Printed in U.S.A.
Platelets in Hyperthyiroidism: Studies on Platelet Counts, Mean Platelet Volume, 111-Indium-Labeled Platelet Kinetics, and Platelet-Associated Immunoglobulins G and M* SIMON PANZER, ALEXANDER HAUBENSTOCK, AND ERICH MINAR First Medical Clinic, University of Vienna, Vienna, Austria
lifespan was significantly shortened in the patients with hyperthyroidism compared with the control group (median, 163.8 h; range, 128.5-206 h; us. 180.0 h; range, 138.3-231.5 h; P < 0.05). Platelet turnover averaged 45.6 (range, 25.6-71.9) x 109/L-day; values above the limit of normal were found in 7 of 15 patients with hyperthyroidism. Three patients with Graves' disease had elevated levels of PAIgG; 1 of these patients had elevated levels of PAIgM and was the only patient with thrombocytopenia (PC, 96 X 109/L). Various combinations of statistical correlations between the degree of hyperthyroidism, pretreatment PC and MPV, platelet kinetic studies, levels of PAIg, and serum levels of antithyroid antibodies revealed no significant differences. These findings suggest that the platelet changes observed in hyperthyroidism, such as lower PC and increased MPV, together with the shortened platelet lifespan reflect metabolically rather than immunologically mediated phenomena, although these may be involved in cases with marked thrombocytopenia. (J Clin Endocrinol Metab 70: 491, 1990)
ABSTRACT. We compared in 15 patients with hyperthyroidism (11 with Graves' disease, 3 with toxic adenoma, and 1 with multinodular goiter) platelet counts (PC) and mean platelet volume (MPV) before and 3 weeks after initiation of antithyroid drug therapy when the patients were euthyroid. In addition, platelet kinetic studies of autologous 111-indium-labeled platelets and platelet-associated immunoglobulins G and M (PAIgG and PAIgM, respectively) were investigated. The control group for the platelet kinetic studies consisted of 2 patients with diffuse nontoxic goiter and 86 patients who were studied for evaluation of their arteriosclerotic vascular disease. After 3 weeks of antithyroid drug therapy there was a significant increase in PC and a decrease in MPV compared with the pretreatment values (pretreatment PC median, 215 x 109/L; range, 96-350 x 109/L; PC median 3 weeks later, 248 x 109/L; range, 157-384 x 109/L; P < 0.005; pretreatment MPV median, 10.6 fL; range, 9.1-13.2 fL; MPV 3 weeks later, 9.9 fL; range, 8.4-11.0 fL; P < 0.005). Ill-Indium platelet recovery was normal in all subjects. Platelet
A
also been reported in Graves' disease (8, 9). Very recently, an increased mean platelet volume (MPV) was found in patients with hyperthyroidism (10), which was found to be reversed upon achievement of euthyroidism (11). To date, no study has combined all of these parameters to analyze platelet changes in hyperthyroidism. The present experiments, using 111-indium-labeled platelet kinetics and measurements of levels of plateletassociated Ig (PAIg), suggest that in hyperthyroid patients with a normal PC, metabolic rather than immunemediated influences on platelets occur, which are reflected by the changes in pre- and posttreatment PC and MPV.
N ASSOCIATION of thrombocytopenia with hyperthyroidism has been observed previously (1, 2). The mechanism by which thrombocytopenia is induced in hyperthyriodism is not fully understood. Severe autoimmune thrombocytopenia has been reported (3), and the findings of elevated levels of platelet immunoglobulin G (IgG) in about 50% of patients with Graves' disease or Hashimoto's thyroiditis supported the general assumption of an an immune-mediated mechanism (4). On the other hand, an increase in megakaryocytes in the bone marrow (5) and a shortened platelet survival time (6, 7) have been reported in hyperthroid subjects, even when platelet counts (PC) were normal. Hypersplenism resulting in platelet pooling and causing thrombocytopenia has
Patients Received July 30, 1989. Address all correspondence and requests for reprints to: Simon Panzer, M.D., Immunobiology Research Center, Department of Laboratory Medicine and Pathology, University of Minnesota, Box 724, 420 Delaware Street SE, Minneapolis, Minnesota 55455. * This work was supported by grants from the Hochschuljubilaeumsstiftung der Stadt Wien and the Medizinisch-Wissenschaftlicher Fonds des Buergermeisters der Bundeshauptstadt Wien.
Fifteen female patients with newly diagnosed hyperthyroidism (aged 17-78 yr) gave their informed consent to participate in these studies. Hyperthyroidism resulted from diffuse toxic goiter (Graves' disease) in 11 patients, toxic adenoma in 3 patients, and multinodular goiter in 1 patient. The 15 patients were seen consecutively in the thyroid out-patient clinic. One 491
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PANZER, HAUBENSTOCK, AND MINAR
492
patient (patient 11; Table 1) was referred from the hematology out-patient clinic where she had been evaluated for an otherwise unexplained thrombocytopenia. The patients had no other relevant diseases, nor did they use any medication. None of the patients had a palpable spleen or lymphadenopathy. In the patient with thrombocytopenia (patient 11) the spleen was also of normal size by ultrasound. There was no evidence of clinical bleeding tendency. Patients were treated with 80 mg methimazole/day, orally, for the first week, 60 mg methimazole/day, orally, for the second week, and 40 mg methimazole/day, orally, for the third week. The hyperthyroid state at presentation and the euthyroid state after 3 weeks of therapy were confirmed by clinical assessment and serum levels of total T4 and free thyroid index (FTI; Table 1). The patients were not retrospectively selected by the achievement of euthyroidism. Two patients with diffuse nontoxic goiter served as controls for both platelet survival studies and determination of PAIgG and PAIgM. Eighty-six patients with arteriosclerotic vascular disease (60 men and 26 women, aged 41-79 yr) served as additional controls for the platelet survival studies.
Materials and Methods Thyroid function tests and antithyroid antibodies Serum T4 and FTI were determined by RIA (Bio-Rad Laboratories, Richmond, CA). Antithyroglobulin (Behring Werke, Marburg, West Germany) and antithyroid microsomal antibodies (Melisa, Freiburg, West Germany) were measured in the routine clinical laboratory.
JCE & M • 1990 Vol 70 • No 2
TABLE 1. Patient characteristics and values of T4/FTI, PC, and MPV before and after treatment of hyperthryoidism (n = 15) and in euthyroid patients with goiter (n = 2)
Patient no.
Age Diagnosis" (yr)
1 2 3 4 5 6 7 8 9 10 11
17 77 25 63 47 72 34 36 64 22 78
12
66
13
47 75 47 27
GD GD GD GD GD GD GD GD GD GD GD TA TA TA MG DG
45
DG
14
15 16 17
T4/FTI (nmol/L)6 Pre
Post
>257/>1.50 245/1.40 255/1.44 201/1.37 184/1.28 185/1.29 >257/>1.50 215/1.24 165/1.26 243/1.40 255/1.54 188/1.41 175/1.24 181/1.22 190/1.27 108/ND 103/ND
67/0.81 98/ND 106/ND 66/ND 135/ND 104/ND 120/ND 118/ND 144/1.09 165/1.06 92/ND 86/ND 126/ND 130/ND 170/1.07 ND/ND ND/ND
PC MPV (fL; (X107L; pre/post) pre/post) 267/308 243/346 350/384 199/230 192/238 175/186 228/259 197/241 201/248 252/270 96/157 193/281 220/269 215/207 208/248 159/ND 229/ND
10.4/9.6 10.6/9.8 9.1/8.5 11.1/10.5 9.7/9.6 10.8/10.6 13.2/11.0 11.0/10.3 10.9/8.4 10.5/10.1 11.8/10.6 10.2/9.6 10.4/9.5 10.1/10.1 9.8/9.9 9.9/ND 11.3/ND
Normal value T4 64-144 150-350 9.0-13.0 FTI 0.86-1.13 " GD, Graves' disease; TA, toxic adenoma; MG, multinodular goiter; DG, diffuse nontoxic goiter. 6 Pre, Before treatment; Post, after treatment; ND, not done.
50) (18). The platelet adhesion immunoflourescence test (19) was applied to screen the sera for platelet-binding IgG antibodies to platelets from blood group O donors with known HLA class I and P1A1/2 and Baka phenotypes. Statistical analyses
Complete blood counts and platelet indices Freshly drawn blood specimens were anticoagulated in siliconized glass tubes containing K3-EDTA (Vacutainer, Becton Dickinson Co., Rutherford, NJ). Blood cell and platelet profiles were performed with a TOA Sysmex E-4000 (TOA Medical Electronics Co. Ltd., Kobe, Japan). Blood cell profiles were performed at least 1 h after venipuncture (12) according to the manufacturer's manual. 111-Indium-labeled platelet kinetic studies Before initiation of antithyroid drug therapy, autologous platelets were labeled with 111-indium-oxine as described previously (13, 14). Recovery was estimated from a 30 min blood sample. Platelet lifespan was computed by the multiple hit system (15). In addition, linear and exponential curves were calculated (least square fitting procedure) to obtain the best fit. Platelet turnover was calculated from the peripheral blood platelet count, the platelet lifespan, and the correction factor applied for the exchangeable splenic platelet pool (16). Platelet-reactive Igs PAIgG and PAIgM were quantitated by a competitive enzyme-linked immunoassay (17). Calibration curves were constructed from serial dilutions of standard sera with known amounts of IgG and IgM (Behring Werke). Upper limits of normal values were 2.2 fg/platelet for both IgG and IgM (n =
Data were analyzed with nonparametric tests; the KruskalWallis test was applied to screen for differences in the results of the platelet kinetic investigations between hyperthyroid patients and the control group, the Wilcoxon rank test for paired data was applied to 1) compare the pretreatment PC and MPV, to correlate 2) the pretreatment PC and MPV with the degree of hyperthyroidism, 3) the platelet kinetic studies with T4 and FTI studies, the PAIg levels, and the pretreatment PC and MPV, and 4) the PAIg levels with the PC, MPV, and antithyroid antibody levels. P < 0.05 was considered the limit for rejection of a single null hypothesis.
Results Thyroid function tests Clinical characteristics of the patients with thyroid disorders and the results of the pre- and posttreatment thyroid function studies are shown in Table 1. Serum T4 levels were also routinely measured in all control patients with arteriosclerotic vascular disease and were within the normal range in all patients (data not shown). Complete blood counts and platelet indices
After 3 weeks of antithyroid drug therapy, all 15 patients with hyperthyroidism were euthyroid (Table 1). The PC increased from a median value of 215 X 109/L
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PLATELETS IN HYPERTHYROIDISM
(range, 96-350 X 109/L) to 248 X 109/L (range, 157-384 x 109/L; P < 0.005), and the MPV decreased from a median value of 10.6 fL (range, 9.1-13.2 fL) to 9.87 fL (range, 8.4-11.0 fL; P < 0.005; Table 1). No significant changes were observed in the red blood cell count (median, 5.27-5.11 X 1012/L), hematocrit (median, 0.43-0.42 volume fraction), mean red cell volume (median, 82.482.8 fL), and white blood cell count (median, 6.17-7.23 X 109/L). There was no statistical correlation between the pretreatment PC and MPV values and the serum T4 and FTI levels.
493
though platelet survival was shorter than normal in only 1 patient of the 15 with hyperthyroidism, platelet lifespan in this group was significantly shorter than that in the control group (P < 0.05; Fig. 1). Although 7 of the 15 patients with hyperthyroidism had platelet turnover rates above the upper limit of normal, they were not significantly higher than the rate in the control group (of note, also, in the control group few patients had increased platelet turnover). There was no statistical correlation between the platelet kinetic studies and the serum T4 and FTI levels, and the pretreatment PC and MPV values.
Ill-Indium platelet kinetic studies The results of the Ill-indium platelet kinetic studies in the 17 patients with thyroid disorders are shown in Table 2. Recovery was within the normal range in all 17 patients. The average platelet lifespan in the 15 hyperthyroid patients was 163.8 h (range, 128-206 h), and the median platelet turnover rate was 45.6 X 109/L-day (range, 25.6-71.9 X 109/L-day). Platelet turnover rates were above the upper limit of normal in 7 of the 15 hyperthyroid patients. All 7 patients had normal platelet counts. Five of the seven patients had Graves' disease, 1 patient had a toxic adenoma, and 1 had multinodular goiter (patients 1, 2, 3, 7, 10, 13, and 15). In the control group, consisting of 86 patients with arteriosclerotic vascular disease and 2 patients with diffuse nontoxic goiter, the median platelet lifespan was 180 h (range, 138.3231.5 h), and the median platelet turnover rate was 38.7 x 10 9 /Lday (range, 26.1-83.3 x 109/L-day). Even
PAIg Results of PAIg studies are shown in Table 3. PAIgG was elevated in 3 of 15 patients with hyperthyroidism. All 3 patients had Graves' disease (33% of the 11 patients with Graves' disease). PAIgM was also elevated in 1 of these 3 patients (Table 3). Interestingly, this patient (no. 11) was thrombocytopenic when first seen, but had a normal PC after 3 weeks of antithyroid drug therapy alone (Table 1). Normal values of PAIg were found at follow-up evaluation. There was no statistical correlation between the PAIg levels and pretreatment PC and MPV, and the results of the platelet kinetic studies. None of the tested sera contained platelet-binding IgG. Antithyroid antibodies Nine of 11 patients with Graves' disease had elevated antithyroid antibody levels, whereas none of the patients
TABLE 2. Results of 111-indium-labeled platelet kinetic studies in 17 patients with thyroid disease Patient no. 1
2 3 4 5
6 7 8 9 10 11 12 13 14 15 16 17 Normal value"
Recovery (%) 71.4 44.9 80.3 45.2 54.3 67.2 49.0 66.0 71.0 58.9 50.2 48.3 58.8 64.3 54.3 61.1 61.8
Lifespan (h) 158.3 149.8 163.8 177.0 206.9 166.6 193.4 193.4 187.2 128.5 152.2 193.9 152.0 159.0 166.0 169.7 201.5
Turnover (xiOYL-day) 51.0 77.9 57.4 44.7 36.9 33.7 49.0 29.3 26.8 71.9 25.6 45.2 52.9 45.6 46.0 29.9 39.7
>45.0
144-224
22.6-45.8
° Derived from 86 patients with arteriosclerotic vascular disease. The Patients' thyroid disorders are identified in Table 1.
S 144
145-160
161-176
177-192
193-208
209-231
platelet life-span (hours)
FIG. 1. 111-Indium-labeled autologous platelet survival studies in 15 patients with hyperthyroidism (•) and 86 control patients with arteriosclerotic vascular disease (M). A shift to the left of the relative frequency of patients with hyperthyroidism is shown compared to the control patients (P < 0.05).
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PANZER, HAUBENSTOCK, AND MINAR
494
TABLE 3. Levels of PAIgG, PAIgM, and antithyroid antibodies in 17 patients with thyroid disease Patient no. 1 2 3 4 5 6 7 8 9 10 11
12 13 14 15 16 17
Normal value
PAIgG (fg/platelet) 0.38 0.65 0.24 0.70 0.85 3.60 3.60 1.60 0.50 0.36 >10.00 0.50 0.44 1.50 0.55 0.55 0.80
