Significant Increase In Platelet Count Research Articles

Raltitrexed as Monochemotherapy Induces a Statistically Significant Increase in Platelet Count

(2002). Raltitrexed as Monochemotherapy Induces a Statistically Significant Increase in Platelet Count. Acta Oncologica: Vol. 41, No. 3, pp. 315-316.

Effects of alcohol ingestion post-exercise on platelet aggregation

The present study examined the influence of ingesting a moderate dose of alcohol on platelet count and platelet aggregation during recovery following exercise. Nineteen subjects (11 male and 8 female) were studied immediately after a standardised cycle ergometer test and during the 24-h period of recovery. In random order, alcohol (0.7 g/kg body mass) was given 1 h after exercise on one test occasion, while an equal volume of alcohol-free solution was administered on the other. Venous blood samples were obtained at baseline, post-exercise, and at 1, 5, and 22 h post-alcohol ingestion. Blood alcohol level increased significantly 1 h after the ingestion of alcohol, but decreased and returned to the resting baseline level at 5 h during recovery. Males and females subjects exhibited similar mean values of platelet count, platelet aggregation, and beta-thromboglobulin concentration at rest and following exercise and recovery. A significant increase in platelet count and a decrease in platelet aggregation using adenosine diphosphate (ADP) was found following exercise. Although plasma beta-thromboglobulin level (pooled data for males and females) showed an increase by 26.0% (from a mean pre-exercise value of 22.3–28.1 IU/ml), this rise was not significant ( P>.05). The post-exercise increase in platelet count was mainly due to exercise-induced plasma volume loss. During recovery, while the increase in platelet count post-exercise returned to the baseline level in control and alcohol trials, the optical density of platelet aggregation remained significantly depressed at 5-h during recovery in the alcohol trial but not in the normal control condition. It is concluded that exercise induces significant reduction in platelet aggregation and the consumption of alcohol after physical exercise delays the normal return of platelet aggregation to the resting baseline levels during recovery.

Alpha-interferon therapy induces improvement of platelet counts in children with chronic idiopathic thrombocytopenic purpura.

To investigate alpha-interferon (IFN) therapy for children with chronic idiopathic thrombocytopenic purpura (ITP). Patients with refractory ITP lasting more than 12 months from diagnosis were included if they had platelet counts <50 x 10(9)/L and had received no treatment during the past month. Patients received IFN (3 x 10(6) U/m2 per dose), three times per week for 4 weeks; if partial (<150 x 10(9)/L) or no response was obtained, the same dose was continued for another 8 weeks. In patients with favorable response and subsequent decrease to pre-treatment values, an additional 4 weeks of treatment could be administered. Fourteen patients (ages 4-20 y) receiving 17 IFN courses were included. Mean initial platelet count was 29 +/- 15 x 10(9)/L. A significant increase was achieved during 14 of 17 courses (82.4%). All but two responses were transitory, and platelets returned to initial values after IFN discontinuation (mean 44 +/- 26 days). Considering the best response achieved by each patient, we observed: 1) 10 patients who achieved a sustained improvement of platelet count throughout the treatment period, decreasing to initial values after therapy was stopped; 2) one patient who achieved platelet count >150 x 10(9)/L, remaining with normal platelets at 18 months; 3) one patient who achieved platelet count >150 x 10(9)/L, remaining with platelets between 100 and 140 x 10(9)/L at 48 months; 4) one patient who had no response; and 5) one patient in whom therapy worsened the thrombocytopenia. A mild to moderate flu-like syndrome and a moderate decrease of the absolute neutrophil count were the only side effects observed. Interferon therapy induces a significant increase of platelet count and seems to be a valid alternative therapy to attempt the achievement of prolonged remission in refractory ITP, to defer splenectomy in younger children, or to improve platelet count before planned splenectomy.

Thrombotic thrombocytopenic purpura--possibilities of treatment and results.

Results of treatment of 13 patients fulfilling the criteria for TTP are presented. Thrombocytopenia was present in all patients (100%). Eleven of 13 patients (84.6%) had conciousness disorder, and seven of 13 patients (53.8%) had renal impairment. Immunosuppressive therapy with plasmapheresis and replacement of removed volume with fresh frozen plasma in a dosage of 25 ml/kg body weight resulted in statistically significant increase of platelet count (p = 0.0033), and significant improvement of consciousness as defined by increased Glasgow Coma Score (GCS) (p = 0.0524). In two patients, renal function recovered and, in one patient, hemodialysis was no longer needed. This improvement in a small patient group has no statistical significance.

Clinical and immunological evaluation of primary splenic irradiation in chronic lymphocytic leukemia: a study of 24 cases.

Little is known about the effects of primary splenic irradiation (SI) in B-cell chronic lymphocytic leukemia (B-CLL) on subpopulations of lymphocytes, immunoglobulins, and the induction of autoantibodies against erythrocytes and platelets. Twenty-four untreated patients with B-CLL were studied prospectively. One patient was excluded from analysis because of intercurrent death. Of the remaining 23 patients, 7 were female and 16 were male, with an average age of 68.4 and 61.2 years, respectively. Treatment consisted of a weekly dose of I Gy up to a total dose of 10 Gy to the spleen. Standardized evaluation was done 2 weeks before and 6 weeks after SI. Twenty patients completed the course of SI. In 14 patients there was a partial response and in 9 patients the disease remained stable. The number of leukocytes decreased rapidly and significantly, with a decrease in the fraction of lymphocytes and an increase in the neutrophil count (all P<0.0001). There was a significant increase in platelet count, but not in hemoglobin level. Nausea, slight diarrhea, pleuropneumonia, granulopenia with fever (all n=1), urinary tract infection and high fever (n=1), and thrombocytopenia occurred (n=2). One patient received transfusion of packed cells because of upper digestive tract bleeding for which cessation of SI was not necessary. The number of malignant cells showed a significant decrease (P<0.01). No significant changes in CD4/CD8 ratio were found. The number of CD4+ and CD8+-cells, however, decreased significantly (P<0.01 and 0.03, respectively). DAT remained unchanged in most (93%) and tests for antibodies to platelets in 83% of the patients. No significant changes in immunoglobin levels were observed.

Interleukin 11 significantly increases plasma von Willebrand factor and factor VIII in wild type and von Willebrand disease mouse models

AbstractInterleukin (IL)-11 is a cytokine with thrombopoietic activity that has been shown to increase plasma von Willebrand factor (vWf) in preliminary clinical studies. This led to further evaluation of the effect of recombinant human (rh)IL-11 on vWf and factor VIII (FVIII) secretion. In vitro, rhIL-11 did not increase vWf production by cultured endothelial cells, which suggests an indirect mechanism. Also, in vivo, plasma vWf was not elevated in mice shortly after a single intravenous (IV) bolus injection of 250 or 1000 μg/kg rhIL-11. The effect of continuous exposure to rhIL-11 was accessed by treating wild type mice for 7 consecutive days with subcutaneous 250 μg/kg/d rhIL-11. Platelet counts increased by 25% and 40% after 4 and 7 days, respectively. Plasma vWf and FVIII levels increased 2-fold after 4 and 7 days. Surprisingly, no effect of rhIL-11 on vWf or FVIII messenger RNA was observed, which suggests that the regulation by rhIL-11 occurs after transcription. No increase in soluble P-selectin was observed after rhIL-11 treatment, indicating that platelet activation is not the source of elevated vWf. Similarly to wild type mice, vWf heterozygous mice responded to rhIL-11 treatment by a significant increase in platelet counts and vWf and FVIII levels. Importantly, in vWf-deficient mice, rhIL-11 also induced a significant increase in FVIII independent of vWf and was able to reduce skin bleeding time. These results suggest that a clinical evaluation of the effects of rhIL-11–induced vWf/FVIII elevation in maintaining hemostasis in mild hemophilia A or von Willebrand disease would be worthwhile.

Release of cytokines and soluble cytokine receptors after intravenous anti-D treatment in children with chronic thrombocytopenic purpura.

Immunoglobulin anti-D administration is one of several methods used in treating children with chronic immune thrombocytopenic purpura. Fc receptor blockade of the reticuloendothelial cell system and of mononuclear phagocytes is an important mechanism of the action of anti-D in ITP. Recently other possible mechanisms by which anti-D works in ITP have been considered. The aim of this study was to obtain a better understanding of the effect of anti-D administration on cytokine, soluble cytokine receptors and platelet count in children with chronic ITP and to determine the pre-treatment plasma cytokine profile in this group of patients. Eighteen children with chronic ITP were examined. In our study the impact of anti-D on the cytokine network was evaluated by analysing serum levels of IL-6, IL-8, tumor necrosis alpha and soluble TNF receptors I and II by the EASIA method before and 1, 3, 20 and 40 h then seven days and one month after anti-D infusion. Anti-D caused a significant increase in platelet count 20 h postinfusion in 10 out of 18 children, 96 h postinfusion in three children and 168 h postinfusion in one child. The mean duration of the response was four weeks. A significant and rapid increase in plasma levels of IL-6, IL-8 and TNF-alpha was seen within 1 to 20 h after anti-D infusion. This increase was accompanied by a prolonged elevation of soluble TNF receptors. There was a significant correlation between TNF-alpha and IL-8, IL-8 and IL-6, TNF-alpha and sTNFRI, and sTNF receptors I and II. These data demonstrate that anti-D infusion caused changes in the cytokine network and raises the question of whether the therapeutic effectiveness of anti-D is related to its immunomodulating properties.

Possibilities and limits of treatment in patients with thrombotic thrombocytopenic purpura

Results of treatment of 18 patients fulfilling the criteria for TTP are presented. Thrombocytopenia was present in all patients (100%). Sixteen of the 18 patients (88.8%) had mental status changes, and seven of the 18 patients (38.8%) had renal impairment. One patient had a secondary type of TTP, caused by non-Hodgkin's lymphoma of the large intestine (that was diagnosed later) and was excluded from the study. Immunosuppresive therapy with steroids, plasma exchange and replacement of removed volume with fresh frozen plasma in a dosage of 25 ml/kg body weight resulted in a statistically significant increase of platelet count (P = 0.00222), and a significant improvement in consciousness defined by increased GCS after 2 weeks (P = 0.00222). In two patients renal function recovered, and in one of them hemodialysis was no longer needed. This improvement in a small group of patients had no statistical significance. TTP recurred in seven patients. High doses of steroids caused serious side effects in two patients: in one patient, steroid diabetes, and in the other one, intestinal perforation.

HCV-associated thrombocytopenia: clinical characteristics and platelet response after recombinant alpha2b-interferon therapy.

Hepatitis C virus (HCV) has been proposed as a possible causative agent of chronic thrombocytopenia. We investigated HCV infection in a series of 51 unselected Spanish patients with chronic acquired thrombocytopenia. Anti-HCV and HCV viraemia were detected in 13/51 (22.5%) of cases; this prevalence was particularly significant when compared with HCV seropositivity in age-matched controls (0.4%). Anti-HCV-positive patients, four men and nine women with a median age of 59.3 years (range 36-72), had a mean platelet count of 55.8 x 109/l (range 12-96). Only one of our HCV-positive thrombocytopenic patients had hypersplenism. Platelet-associated IgG (PAIgG) was negative, as measured by immunofluorescent flow cytometric analysis in 11/13 HCV-positive thrombocytopenic patients. Thus, thrombocytopenia in our HCV-positive patients appeared to be non-autoimmune mediated. In six patients, a trial of recombinant alpha2b-interferon (IFN-alpha) given at a dose of 3 MU three times per week for 6-24 months gave a durable (> 1 year) and significant increase in platelet count in all six patients. The maximum increase occurred after 6 months of IFN-alpha therapy. In conclusion, the ability of IFN-alpha to increase platelet counts in HCV-positive thrombocytopenic patients supports mechanisms involving a direct role for HCV inhibiting platelet production.

Comparison of ω-3 fatty acids and sulfasalazine in ulcerative colitis

Fish oil ω-3 fatty acids exert antiinflammatory effects on patients with ulcerative colitis. However, a comparative study in patients with mild to moderate ulcerative colitis receiving only sulfasalazine or ω-3 fatty acids has not been performed. We sought to detect changes in the inflammatory disease activity with the use of either fish oil ω-3 fatty acids or sulfasalazine in patients with ulcerative colitis. Ten patients (five male, five female; mean age = 48 ± 12 y) with mild to moderate active ulcerative colitis were investigated in a randomized cross-over design. They received either sulfasalazine (2 g/d) or ω-3 fatty acids (5.4 g/d) for 2 mo. Disease activity was assessed by clinical and laboratory indicators, sigmoidoscopy, histology, and whole-body protein turnover (with 15N-glycine). Treatment with ω-3 fatty acids resulted in greater disease activity as detected by a significant increase in platelet count, erythrocyte sedimentation rate, C-reactive protein, and total fecal nitrogen excretion. No major changes in protein synthesis and breakdown were observed during either treatment. In conclusion, treatment with sulfasalazine is superior to treatment with ω-3 fatty acids in patients with mild to moderate active ulcerative colitis.

Thrombocytopoietic effect of heparin given in chronic immune thrombocytopenic purpura

Our previous in-vitro and in-vivo studies showed that heparin enhanced murine and human megakaryocytopoiesis. 20 patients with chronic immune thrombocytopenic purpura were randomly divided into two groups and given 10 mg per day of prednisone for 30 days, for haemostatic purposes. One group received in addition heparin (1250 IU twice a day subcutaneously for 30 days). From day 10, a significant increase in platelet count was observed in eight of the ten patients treated with heparin (p<0·05), with return to the initial value after heparin cessation in six of the responders. These data demonstrate the effectiveness of heparin and suggest its use or that of other related compounds for therapy of chronic immune thrombocytopenic purpura.

ＩＴＰおよび類縁疾患におけるビスコクラウリン型アルカロイド製剤の血小板増加作用と骨髄の変化：光顕および電顕的検討

Cepharanthin (Ceph), a complex of biscoclaurine alkaloids, is known to be effective for increasing platelet counts particularly in patients with idiopathic thrombocytopenic purpura (ITP). We investigated the thrombopoietic effect of a high-dose Ceph treatment on thrombocytopenic patients. The morphological changes of the bone marrow in these patients were investigated by light and electron microscopy. The diseases consisted of 7 ITPs, 4 refractory cytopenias (RCs), and 2 aplastic anemias (AAs). The patients were divided into two groups: (1) prednisolone (PSL)+Ceph and (2) Ceph groups. The PSL+Ceph group consisted of 5 ITP and 1 RC-patients. These patients were refractory to prior PSL therapy, and were subsequently given 60mg of Ceph daily in addition to the PSL therapy. The Ceph group consisted of 2 ITP, 3 RC and 2 AA-patients. In the PSL+Ceph group, 5 out of 6 patients showed significant increase in platelet counts after the initiation of additional Ceph treatment. In the Ceph group, 2 RC patients showed slight increase in platelet counts. Thus, the Ceph treatment was found to be effective for increasing platelet counts, particularly when it was combined with the PSL therapy. To investigate the changes of bone marrow cells caused by the Ceph treatment, the bone marrows of the patients in the PSL+Ceph and Ceph groups were examined by light and electron microscopy. The following findings were seen in the bone marrow obtained during the Ceph treatment: Most of the macrophages showed a foam cell appearance. These cells had many vacuoles containing myelin-like structures. Some macrophages also showed remarkable acid phosphatase activity. Megakaryocytes had aggregated glycogen particles in the cytoplasm. These morphological findings were considered to be caused by the Ceph treatment, and they might be related to the mechanisms of thrombopoiesis.

Quantitative Changes in Platelet Counts following Major Urological Pelvic Surgery

Postperative quantitative changes in platelet counts have been reported following various extensive surgical procedures. It is generally accepted that reactive thrombocytosis at levels less than 1,000,000/mm3 is a benign condition and is not associated with increased risk of postoperative thrombohemorrhagic complications. The role of prophylactic treatment with platelet inhibitors in these situations is controversial. We assessed retrospectively the timing and the extent of postoperative thrombocytosis in 85 consecutive patients following major urological pelvic surgery and evaluated its possible clinical significance to hemorrhagic and thromboembolic complications, in view of the coincidence of multiple potential risk factors for thromboembolism in these patients. 73 (85.9%) patients demonstrated marked postoperative changes of platelet counts. In 12 patients (14.1%) we found only minor fluctuations in platelet counts throughout the postoperative period. Two distinct groups of 26 and 47 patients respectively could be identified among these 73 patients, who differed in the rate and extent of changes in platelet counts. Those fluctuations were characterized by an early decrease in platelet levels (mean percentage change of 40 and 60% in groups I and II respectively). This was followed by a gradual increase leading to delayed thrombocytosis (mean percentage change of 225 and 305% in groups I and II respectively). Thromboembolic complications were diagnosed in 5 patients. The occurrence of thromboembolism preceded any significant increase in platelet counts in all 5 patients. There was no correlation between the timing of thromboembolic complications and timing and extent of the change in platelet count. We conclude that reactive thrombocytosis following major urological pelvic surgery is a frequent innocuous finding and is not associated with hemorrhagic or thromboembolic complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Subcutaneous Administration of Recombinant Human Erythropoietin on Plasma Protein C, Protein S, and Antithrombin III Levels in Patients on Continuous Ambulatory Peritoneal Dialysis

The effect of subcutaneous administration of recombinant human erythropoietin (rHuEPO) on plasma natural coagulation inhibitors (protein C, protein S, and antithrombin III) was evaluated in 10 uremic patients on continuous ambulatory peritoneal dialysis (CAPD). These patients were commenced on a 16 week-course of twice weekly rHuEPO by the subcutaneous route. The hemoglobin increased significantly from 6.9 +/- 1.3 g/dl to 9.6 +/- 1.9 g/dl after subcutaneous rHuEPO treatment (p less than 0.01) at an average dose of 84 +/- 9 U/kg body wt/week. With rHuEPO therapy, a significant increase in platelet counts was observed, albeit within the normal range. A significant increase in the prothrombin time was demonstrated at 6 weeks after treatment and increased activated partial thromboplastin time was observed at 6 weeks and 16 weeks after rHuEPO administration although these measurements still remained in normal range. CAPD patients have comparable or even higher plasma levels of natural coagulation inhibitors compared with healthy controls supporting our previous findings that patients on CAPD have normal plasma levels due to an effective compensatory production despite peritoneal losses of these proteins with CAPD. No change in either the immunological or the functional activity of these natural coagulation inhibitors was demonstrated with rHuEPO therapy and clinical thrombosis was not observed during and after rHuEPO therapy. We conclude that there is no laboratory evidence of increased risk of thrombogenesis due to reduction of natural coagulation inhibitors with rHuEPO therapy.

Effects of Splenectomy on Immune Thrombocytopenic Purpura in (NZW x BXSB) F1 Mice: Analyses of Platelet Kinetics and Anti-Platelet Antibody Production

Effects of splenectomy on platelet kinetics and production of anti-platelet antibodies were studied in male (NZW x BXSB) F1 (W/B F1) mice, which are known as the animal model of immune thrombocytopenic purpura (ITP). Studies on organ localization of radiolabeled platelets revealed that splenic uptake significantly increases in W/B F1 mice in comparison with that of normal controls. W/B F1 mice showed a significant increase in platelet counts and, in contrast with sham-operated controls, high levels of platelet counts were maintained up to 6 weeks after splenectomy. Platelet lifespans (PLSs) did not reach normal levels, although prolonged PLSs were observed. In addition, platelet-associated antibody (PAA) values showed a tendency towards transient decrease, but there was no change in platelet-bindable serum antibodies (PBAs). These findings indicate that the suppression of anti-platelet antibody production is essential to the treatment of ITP; splenectomy may not be effective in treating severely affected ITP patients because, although the spleen is one of the major sites of platelet sequestration and antibody production, reticulo-endothelial systems (RESs) (liver, bone marrow, lymphnodes, etc.) other than the spleen are also responsible for the destruction of platelets. We therefore consider the W/B F1 mouse to be a useful model of human ITP, and believe that it provides valuable information for the development of new therapeutic agents in patients with ITP, especially those who do not respond to splenectomy.

Effect of human recombinant erythropoietin on bleeding time, platelet number and function in children with end-stage renal disease maintained by haemodialysis

We studied platelet number and function in nine anaemic children with end-stage renal disease during a clinical trial with recombinant human erythropoietin (rHu-EPO). All the children showed a correction in both haematocrit and haemoglobin levels which was followed by a significant reduction in bleeding time. We also observed a significant increase in platelet count after both 6 and 12 weeks of therapy; at the same time mean platelet volume decreased and a normal platelet mass was maintained. The mean baseline platelet aggregation response to ADP was normal, but was decreased to collagen (P less than 0.05 vs normal control). Platelet production of thromboxane B2 in serum was also lower than normal controls. After correction of anaemia with rHu-EPO, platelet aggregation improved in patients with a decreased baseline response, and mean levels of thromboxane B2 became normal. In conclusion, the treatment with rHu-EPO improved haemostatic balance not only by correcting anaemia, but also by increasing platelet count and function.

Clinical and Immunologic Effects of Combination Therapy with Intravenous Immunoglobulins and AZT in HIV-Infected Patients

30 patients with HIV infection were enrolled to evaluate the clinical efficacy and toxicity of zidovudine (AZT), 0.5 g/day p.o. (Group A) vs. AZT 0.5 g/day p.o. plus intravenous immunoglobulins (IVIG), 0.4 g/kg of body weight for three consecutive days, followed by one treatment of 0.6 g/kg of body weight every fourth week (Group B), over a period of one year. The study was open and randomized. The treatment groups were compared using the following study variables: 1) type of infections, recurrences and severity; 2) change in CD4+ T and CD8+ T cell count; 3) change in platelet count; 4) change in TNF alpha serum levels; 5) the probability of not developing an opportunistic infection over a period of 12 months. Patients from Group B developed less pathological events in comparison to Group A. No significative differences were evident with regard to values of T cell subsets obtained before and after treatment in each group and between the two groups. On the contrary, in 12 out of 15 patients from Group B there was a significant increase in platelet count. In both groups there was a significant decrease of mean serum levels of TNF alpha when a comparison was made between time 12 vs. time 6. However, when data were expressed as single values, in three subjects from Group B TNF alpha was still detectable by time 12 vs. 9 individuals in Group A. The cumulative probabilities of developing an opportunistic infection over the 12 months of treatment in the Group A subjects were significantly higher than in the Group B subjects (p less than 0.01). Adverse effects--nausea and gastric pain--were reported for 3 individuals (20%) from Group A and 4 patients (26%) from Group B. In conclusion, patients treated with AZT are especially likely to benefit from IVIG prophylaxis.

A three-year evaluation of hemostatic function in Singaporean Norplant-2 rod acceptors

A longitudinal study of hemostatic function was carried out on 100 Singaporean acceptors using Norplant-2 rods for contraception. The results at the end of three years indicate a possible increased predisposition to thrombosis, as evidenced by significant increases in platelet count and aggregability. The prothrombin time (PT) and activated partial thromboplastin time (APTT) continued to remain shortened at the end of three years of use. There was also a general fall in most of the vitamin K coagulation factors. There is thus still an indication of a possible enhanced potential for hypercoagulation at the end of three years of Norplant-2 rod use.

A three-year evaluation of hemostatic function in Singaporean Norplant acceptors

In a longitudinal study involving 100 Singaporean women, results indicate that the acceptors persist in having a possibly increased predisposition to thrombosis, as evidenced by a significant increase in platelet count and aggregability. Furthermore, the shortened prothrombin time and activated partial thromboplastin time, together with changes in vitamin K factors, still indicate the possible enhanced potential for hypercoagulation.

Platelets in Hyperthyiroidism: Studies on Platelet Counts, Mean Platelet Volume, 111-Indium-Labeled Platelet Kinetics, and Platelet-Associated Immunoglobulins G and M*

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 10(9)/L; range, 96-350 X 10(9)/L; PC median 3 weeks later, 248 X 10(9)/L; range, 157-384 X 10(9)/L; P less than 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 less than 0.005). 111-Indium platelet recovery was normal in all subjects. Platelet lifespan was significantly shortened in the patients with hyperthyroidism compared with the control group (median, 163.8 h; range, 128.5-206 h; vs. 180.0 h; range, 138.3-231.5 h; P less than 0.05). Platelet turnover averaged 45.6 (range, 25.6-71.9) X 10(9)/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 10(9)/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.