Cytomegalovirus-induced thrombocytopenia. An unusual case report.

A 21-year-old man had severe thrombocytopenia resistant to corticosteroid therapy. Viral studies of cytomegalovirus were 1:1,024. Although the cytomegalovirus titer returned toward normal (1:16 titer) during a period of three months, thrombocytopenia persisted and continued to remain refractory to corticosteroid therapy. Initial bone marrow morphology, platelet size, and platelet survival and sequestration were not typical of idiopathic thrombocytopenic purpura, and it is doubtful that splenectomy would have been helpful. However, when restudied six months later, platelet size was greatly increased, platelet survival was severely shortened (half-time, 2 1/4 hours), and intense splenic trapping was evident. Splenectomy was performed and resulted in normalization of the platelet count. Cytomegalovirus-associated thrombocytopenic purpura is an unusual disease that may take an unpredictable clinical course. Careful study of the mechanism of thrombocytopenia appears worthwhile when early recovery does not occur.     

Cytomegalovirus mononucleosis with severe thrombocytopenia

In October 1998, a 37-year-old man was admitted because of petechiae and thrombocytopenia following flu-like symptoms. On admission, there were numerous petechiae on the back and extremities. The WBC count was 3,700/microliter with 3% atypical lymphocytes, the lymphocyte CD4/CD8 ratio 0.37, and the platelet count 1,000/microliter. Mild splenomegaly was detected by CT. Results of blood chemistry and coagulation tests were normal. A bone marrow aspirate was normocellular with no signs of dysplasia, and the megakaryocyte count was normal. The patient was initially diagnosed as having virus infection-associated thrombocytopenia. Steroid therapy was started immediately, and the platelet count rose to 15 x 10(4)/microliter on day 21. The PA-IgG level was 652 ng/10(7) platelets. Mild liver dysfunction developed, and atypical lymphocytes increased in number thereafter. Because IgM anti-cytomegalovirus (CMV) antibody (Ab) was positive and IgG CMV Ab was negative, a diagnosis of CMV mononucleosis was made. Gancyclovir was therefore started. Four months later, steroid therapy was discontinued, and partial remission has since been maintained. In healthy individuals, CMV infection is usually latent, and the development of mononucleosis is rare. So far, 11 cases of CMV-induced mononucleosis associated with severe thrombocytopenia have been reported in immunocompetent adults.     

Mechanisms of thrombocytopenia in varicella

51Cr-labeled platelet and 125I-labeled fibrinogen kinetic studies in four thrombocytopenic children with varicella infection revealed marked platelet destruction (platelet survival times 0.1, 0.4, 1.0, and 2.4 days) and relatively normal fibrinogen disappearance. The platelet count was directly related to the platelet survival time. Marrow megakaryocyte mass was increased twofold to fourfold. IgG or IgM antiplatelet antibody was present on autologous platelets in the three patients tested. These data suggest that thrombocytopenia in some patients with varicella is the consequence of immune mediated platelet destruction.     

Improvement of thrombocytopenia with disappearance of HCV RNA in patients treated by interferon-alpha therapy: possible etiology of HCV-associated immune thrombocytopenia

We evaluated the relationship between the severity of thrombocytopenia and the serum hepatitis C virus (HCV) RNA level to investigate the mechanism of thrombocytopenia in patients with HCV infection. Patients who had chronic hepatitis without splenomegaly were divided into two groups according to the platelet count, which were 18 patients with a platelet count < or =150 x 10(9)/L and 22 patients with a platelet count >150 x 10(9)/L. HCV RNA, platelet-associated immunoglobulin G (PAIgG), rheumatoid factor (RF), and other immunological parameters were measured and correlations were investigated. Patients in the low platelet group had higher levels of PAIgG, Th1 cells, thrombopoietin (TPO), and RF than those in the normal platelet group (textitP < 0.05). Twenty-two patients completed 6 months of IFN therapy and were followed for more than 1 yr afterwards. Twelve patients who responded to IFN therapy with clearance of HCV showed an increase of the platelet count, whereas the 10 patients who did not respond to IFN showed a decrease of the platelet count. The improvement of thrombocytopenia after interferon therapy suggests a contribution of HCV infection to this condition.     

Regulation of thrombopoiesis: effects of the degree of thrombocytopenia on megakaryocyte ploidy and platelet volume

We have established a murine model and techniques with which to serially study thrombocytopoiesis after induction of experimental immune thrombocytopenia of variable severity and duration. Bone marrow megakaryocyte ploidy distribution was determined by using unfractionated bone marrow, a polyclonal megakaryocyte-specific probe, and two-color, fluorescence-activated flow cytometry. With these techniques, the modal megakaryocyte ploidy class in normal murine bone marrow was 16N. Serial studies of bone marrow megakaryocyte ploidy after the induction of acute, severe thrombocytopenia (platelet count, less than 0.05 X 10(6) microL) demonstrated no detectable change in the ploidy distribution at 12, 24, and 36 hours after the onset of thrombocytopenia. At 48 hours, the modal ploidy class shifted from 16N to 32N, and the 64N class increased significantly (P less than .001). The ploidy distribution returned to normal 120 hours after the onset of thrombocytopenia. A lesser degree of thrombocytopenia (platelet count reduction to 0.100 to 0.200 X 10(6)/microL) delayed the modal ploidy class shift from 16N to 32N until 72 hours after the onset of thrombocytopenia. Chronic, severe thrombocytopenia (platelet count, less than 0.05 X 10(6)/microL for seven days) resulted in a modal ploidy class shift from 16N to 32N during the thrombocytopenic phase and an enhanced increase in the 64N megakaryocyte class during the recovery phase. Mean platelet volume (MPV) was simultaneously measured on isolated total platelet populations after induction of thrombocytopenia. MPV was significantly increased (P less than .001) as early as eight hours after the onset of acute, severe thrombocytopenia, 40 hours before a shift in the ploidy distribution. Mild thrombocytopenia (platelet count reduction to 0.400 X 10(6)/microL) was not associated with a ploidy shift but did result in a significantly increased MPV (P less than .001). These studies demonstrate that the temporal relationship and magnitude of the effects of thrombocytopenia upon megakaryocyte ploidy distribution are dependent upon the degree and the duration of the thrombocytopenic stimulus and that the effects of experimental thrombocytopenia on platelet volume and megakaryocyte ploidy are dissociated.     

Hepatic fibrosis plays a central role in the pathogenesis of thrombocytopenia in patients with chronic viral hepatitis

The pathogenesis of thrombocytopenia in chronic hepatitis is not well known. This study evaluated the relationship between liver injury, serum thrombopoietin, splenomegaly and thrombocytopenia in chronic viral hepatitis. Two hundred and nine patients were enrolled, 85 with splenomegaly and 124 without. Thrombocytopenia was present in 71% and 23% of patients with or without splenomegaly respectively. In subjects with low platelet count, those with splenomegaly showed significantly lower platelet numbers than those without splenomegaly. The spleen size correlated with portal hypertension. An inverse correlation between spleen size and platelet count was observed (r = -0.54; P < 0.0001). In patients without splenomegaly, thrombocytopenia was associated with the grade of fibrosis; platelet counts were the highest in patients with fibrosis 0-2, lower in those with grade 3 (P < 0.008) and lowest in those with grade 4 (P < 0.05). These findings were independent of demographic and biochemical characteristics, hepatic necroinflammatory activity, portal hypertension and splenomegaly. Patients with normal platelet counts showed higher thrombopoietin levels than those with low platelet counts (P < 0.0001). An inverse correlation between thrombopoietin levels and fibrosis grade was observed (r = - 0.50; P < 0.0001). Median thrombopoietin levels were 58 and 27 pg/ml for fibrosis grade 0-1 and grade 4 respectively (P < 0.001). These data indicate that advanced hepatic fibrosis, causing an altered production of thrombopoietin and portal hypertension, plays the central role in the pathogenesis of thrombocytopenia in chronic viral hepatitis.     

Splenectomy for thrombocytopenia in chronic lymphocytic leukemia

The role of peripheral platelet destruction as a reversible etiology of thrombocytopenia in chronic lymphocytic leukemia (CLL) was evaluated in nine patients with CLL and refractory thrombocytopenia who underwent splenectomy. The patients' ages ranged from 54 to 74 years. Progressive thrombocytopenia refractory to antineoplastic agents and corticosteroids had been present for a mean of 23.4 months. The platelet counts were 4,000-57,000/microliter, and were generally higher in those patients with larger spleens. The spleens ranged from 180 to 4050 gm. Seven patients responded completely to splenectomy, achieving platelet counts greater than 150,000/microliter, and in one other patient, the count rose to greater than 100,000/microliter. The platelet count of one patient failed to respond to surgery. Those patients with massive splenomegaly developed higher, more rapidly rising platelet counts postoperatively. No operative mortality was encountered. Median hospitalization was seven postoperative days. All patients experienced an increased sense of well-being. Median follow-up time is 9 months.     

Regulation of megakaryocyte ploidy in vivo in the rat

The relationship between the bone marrow (BM) megakaryocyte and the circulating platelet was explored. Incremental changes in platelet count were made in rats by infusion of antiplatelet antibody or by platelet transfusion, and the response of megakaryocytes was measured by flow cytometry. Proportional changes in megakaryocyte ploidy were demonstrated: As the platelet count declined, ploidy increased; as the platelet count increased, ploidy decreased. Even moderate degrees of thrombocytopenia and thrombocytosis (48% and 177% of the normal platelet count) were associated with changes in ploidy. These changes were not the results of the technique used to alter the platelet count because reinfusion of platelets after 3 hours of thrombocytopenia prevented any ploidy change. These studies proved that the circulating platelet and the megakaryocyte constitute a classic feedback loop whose activity can be measured by the degree of ploidization of the megakaryocyte. The minimal duration of thrombocytopenia necessary to promote megakaryocyte ploidy changes was approximately 10 hours. Using a BM culture assay, we identified a plasma factor which induced alterations in megakaryocyte ploidy and whose level is inversely proportional to the platelet count.     

Measurement of platelet-associated IgG in animal models of immune and nonimmune thrombocytopenia

Platelet-associated IgG (PAIgG) is elevated in idiopathic thrombocytopenic purpura (ITP), but it also is elevated in other thrombocytopenic disorders traditionally considered to be nonimmune. Consequently it is possible that elevated PAIgG is a nonspecific finding secondary to thrombocytopenia. To study this issue we developed a rabbit model of immune and nonimmune mediated thrombocytopenia. The mechanism of the thrombocytopenia was validated by platelet survival studies. Immune thrombocytopenia was produced by injection of antirabbit platelet serum that was raised in guinea pigs. Nonimmune aregenerative thrombocytopenia was produced by irradiation of the animals; nonimmune consumptive thrombocytopenia was produced by injection of adenosine diphosphate (ADP). PAIgG was measured in a direct binding assay using 125I-labeled staphylococcal protein A (SpA). Washed platelets from normal, nonthrombocytopenic rabbits bound an average of 81 molecules of SpA per platelet (81 +/- 168, mean +/- 2 SD, n = 39). Infusion of the antiplatelet antiserum produced thrombocytopenia with a rise in PAIgG that was closely correlated with the level of PAIgG (r = 0.86, n = 12). The thrombocytopenia was consumptive, as shown by a very short platelet life span using 111In- labeled platelets. In contrast, both nonimmune thrombocytopenic states resulted in an equal or greater drop in the platelet count but no change in the level of PAIgG. The animals with aregenerative thrombocytopenia had normal or only moderately reduced platelet life spans; however, in every animal the level of PAIgG was not different from the nonthrombocytopenic controls, irrespective of the platelet count. Similarly, the level of PAIgG was unchanged in those rabbits with nonimmune consumptive thrombocytopenia following infusion of ADP (82 +/- 55 molecules of SpA per platelet, mean +/- SD, n = 6). These studies indicate that elevated PAIgG is a specific finding of immune thrombocytopenia and is not secondary to thrombocytopenia itself. Indirectly these results support our hypothesis that immune mechanisms contribute to more thrombocytopenic disorders than was once thought likely.     

Acute vancomycin-dependent immune thrombocytopenia as an anamnestic response

Drug-related thrombocytopenia is a well-described but relatively rare complication of antibiotic therapy. In this entity, platelet destruction is immune-mediated, often resulting in a precipitous drop in platelet count over a short period of time. Most of these cases of thrombocytopenia are drug-dependent, as discontinuation of the offending agent frequently results in a timely return to baseline, pre-exposure platelet levels. We report the case of a 61-year-old male patient receiving vancomycin and ceftazidime for lower extremity wet gangrene who experienced a marked, acute reduction in platelet count 12 to 15 hours after starting antibiotic therapy. There was no readily apparent clinical or laboratory explanation for his thrombocytopenia. Pre- and post- antibiotic serum samples were preserved and sent for drug-dependent platelet antibody analysis. The pre-exposure specimen revealed the presence of IgG vancomycin-dependent platelet antibodies, while the post-exposure specimen demonstrated both IgG and IgM vancomycin-dependent platelet antibodies. Ceftazidime-dependent platelet antibodies were not identified in either sample. These findings indicate prior sensitization to vancomycin, with subsequent acute production of IgM anti-platelet antibodies after re-exposure to the antibiotic. The patient's antibiotics were held after the acute-onset of thrombocytopenia with subsequent restoration of normal platelet counts within 4 days of drug withdrawal, and the patient at no time experienced significant adverse bleeding events. Antibiotic therapy with vancomycin is a rare and perhaps overlooked cause for new-onset thrombocytopenia in hospitalized patients. This case illustrates that the development of severe thrombocytopenia within hours of vancomycin administration does not rule out drug-related immune clearance, as the rapid platelet destruction may indicate an anamnestic antibody response to the drug after previous exposure. In such a scenario, immediate discontinuation of vancomycin is recommended to improve platelet counts. From a laboratory perspective, retrieval of serum both pre- and post-administration of vancomycin is most helpful in determining a patient's drug-immunization status and can help guide safe drug use during future infections.     

Evidence for an Immunological Pathogenesis of Thrombocytopenia in Chronic Liver Disease

Objectives: To elucidate the roll of platelet-associated IgG (PA-IgG) in the mechanism of thrombocytopenia associated with chronic liver disease. Methods: Platelet count in blood, PA-IgG, and scintigraphic spleen/liver ratio us a marker of splenomegaly was examined in 214 individuals, including 16 controls showing nonspecific reactive change in liver biopsy and 198 patients with chronic liver disease. Results: The mean blood platelet count decreased significantly according to severity of liver disease, from control to liver cirrhosis. PA-IgG levels increased significantly in relation to severity of liver disease, as did spleen/liver ratio. In chronic hepatitis or liver cirrhosis, an inverse correlation was found between platelet counts and PA-IgG levels. An inverse correlation was also observed between platelet count and spleen/liver ratio in liver cirrhosis. The splenic embolization resulted in a significant rise in platelet count and a significant fall in PA-IgG in the 14 cirrhotic patients. Conclusions: These results may give support to evidence for an immunological mechanism mediated by PA-IgG for the thromhocytopenia occurring in chronic liver disease. In the case of liver cirrhosis, this mechanism would act in addition to platelet pooling in the spleen on thrombocytopenia. PA-IgG may also have an important role in thrombocytopenia associated with chronic hepatitis, in which splenic platelet pooling is less marked.     

Acquired amegakaryocytic thrombocytopenic purpura associated with immunoglobulin deficiency

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a haematological disorder characterized by severe thrombocytopenia due to an immunologically induced absence of megakaryocytes in an otherwise normal-appearing bone marrow. A 57-year-old male with a 6-month history of rectal and cutaneous bleeding is reported. Platelet count was 10 X 10(9)/l, while other haematological values were within the normal range, except for the presence of hypogammaglobulinaemia with decreased IgA and IgG. Both platelet median volume and half-life span were normal, and antiplatelet IgG determinations were negative. Bone marrow aspiration and biopsy showed no megakaryocytes, with a normal appearance of erythroblastic and granulopoietic series. An in vitro culture for megakaryocytic progenitor cells did not show any growth of megakaryocyte colonies. No inhibitory effect on the growth of normal marrow megakaryocytic colonies was observed when serum and lymphocytes of the patient were added. Following 4 weeks of prednisone therapy, the platelet count rose to 127 X 10(9)/l and the bone marrow aspirate showed some megakaryocytes. The possible pathogenetic mechanisms of this entity are discussed.     

111In-oxine platelet survivals in thrombocytopenic infants

Thrombocytopenia is a common occurrence (20%) in sick neonates, but the causes have not been well studied. In this report we demonstrate that thrombocytopenia in the neonate is characterized by increased platelet destruction as shown by shortened homologous 111In-oxine-labeled platelet life spans. Thirty-one prospectively studied thrombocytopenic neonates were investigated by measuring the 111In-labeled platelet life span, platelet-associated IgG (PAIgG), and coagulation screening tests. In every infant, the thrombocytopenia was shown to have a destructive component since the mean platelet life span was significantly shortened to 65 +/- 6 (mean +/- SEM) hours with a range of one to 128 hours compared with adult values (212 +/- 8; range, 140 to 260; gamma function analysis). The platelet survival was directly related to the lowest platelet count and inversely related to both the highest mean platelet volume and duration of the thrombocytopenia. In 22 infants the percent recovery of the radiolabeled platelets was less than 50%, which suggested that increased sequestration also contributed to the thrombocytopenia. Infants with laboratory evidence of disseminated intravascular coagulation (n = 8) or immune platelet destruction evidenced by elevated levels of PAIgG (n = 13) had even shorter platelet survivals and a more severe thrombocytopenia compared with the ten infants in whom an underlying cause for the thrombocytopenia was not apparent. Full-body scintigraphic images obtained in 11 infants showed an increased uptake in the spleen and liver, with a spleen-to- liver ratio of 3:1. This study indicates that thrombocytopenia in sick neonates is primarily destructive, with a subgroup having evidence of increased platelet sequestration.     

Micromethod for demonstrating increased platelet surface immunoglobulin G: findings in acute, chronic, and human immunodeficiency virus-1-related immunologic thrombocytopenias

A method has been developed for the demonstration of increased platelet surface IgG that uses 1 ml of blood regardless of the platelet count. Platelets are gel filtered to remove plasma and contaminating lymphocytes. They are then reacted with fluorescein-conjugated antihuman IgG and analysed by flow cytometry. Percent positive staining cells vary from 10% to 80% of total cells examined. A platelet antibody index is derived from the product of percent positive staining cells X mean fluorescence intensity of positive staining cells. All patients studied with chronic idiopathic thrombocytopenia purpura (ITP) or human immunodeficiency virus-1 (HIV-1)-related thrombocytopenia had increased platelet surface IgG. Twelve acute children and 11 chronic children had indices averaging 3.5- and 8.9-fold greater than 12 normal children, respectively. Five of 12 children with acute ITP had normal platelet IgG. There was no linear correlation between the platelet antibody index and platelet count. Platelets of patients with acute, chronic, or HIV-1-related ITP displayed autofluorescence. In chronic ITP, the percentage of platelets displaying autofluorescence had a significant negative correlation with the platelet count. This technique will be a valuable diagnostic tool in the pediatric population.     

Thrombocytopenia in Graves' disease: effect of T3 on platelet kinetics

A study was carried out in which the platelet count was decreased in approximately half the patients with hyperthyroidism and gradually increased with treatment. Platelet disappearance curves were curvilinear and the platelet survival was shortened in the hyperthyroid state. Patients maintained in a euthyroid state for 3 months or less continued to have a shortened platelet survival. The survival returned to normal after 6 months or more of euthyroid status. In order to clarify the cause of the decreased platelet count in the patients, animal experiments were performed. T3-injected rats had decreased platelet counts and shortened platelet survival. When platelets obtained from T3-injected rats were transfused to a control group of untreated rats, the platelet survivals were normal. When platelets obtained from the control group of rats were transfused to T3-injected rats, the platelet survivals were shortened. Disappearance of heat-damaged RBC from the circulation was also accelerated in T3-injected rats. This suggests that thrombocytopenia in Graves' disease is caused by an increased sequestration potency of the reticuloendothelial phagocyte system stimulated by thyroid hormone.     

Heparin-induced thrombocytopenia: association with a platelet aggregating factor and arterial thromboses.

Eleven patients with heparin-induced thrombocytopenia were studied. Thrombocytopenia appeared 3-16 days following the initiation of prophylactic or therapeutic doses of heparin. The mean lowest platelet count recorded was 48,000/mm3. When heparin was stopped, recovery from thrombocytopenia began within 24 hours and was complete by ten days. Two patients developed fatal thromboses, and two others had myocardial infarctions while thrombo-cytopenic. In the serum of seven patients, including three of the four with arterial thrombosis, a heparin-dependent platelet aggregating factor was present. The factor caused release of platelet 14C serotonin but did not lyse platelets. It was present in the globulin fraction of all positive sera, and in one serum studied it was isolated in the IgG/IgA immunoglobulin fraction. The factor was not present in 16 normal sera or in the sera of 15 nonthrombocytopenic patients receiving heparin. Our observations suggest that heparin-induced thrombocytopenia is common and that, in some patients it may be accompanied by severe arterial thrombosis. In vivo platelet aggregation is a possible explanation for the thrombocytopenia and the thrombosis in this disorder.     

Effect of splenectomy for management of thrombocytopenia associated with systemic lupus erythematosus: a case report

A 51-year-old female with systemic lupus erythematosus (SLE) was admitted in November 1987 because of general fatigue and muscular weakness. She was treated with prednisolone (PSL) 30 mg and azathioprine (AZP) 50 mg after failure in the management of thrombocytopenia by PSL 15 mg. She exhibited no splenomegaly. Muscular atrophy and weakness were seen in the proximal muscles. Her platelet count was 44,000/microliters. A bone marrow aspiration revealed an increase in megakaryocytes. The blood chemistry revealed a normal CPK level and an elevated LDH level, indicating a presence of steroid myopathy. A splenectomy was performed after an increase of platelet count by giving gamma-globulin 400 mg/kg for 5 days. The platelet count rose to 368,000/microliters on the 46th postoperative day. She was treated with PSL 5 mg and AZP 50 mg as postsplenectomy therapy. The splenectomy did not adversely affect other aspects of SLE, in particular, renal function. She had no major complications in the postoperative period. Her platelet count reached a plateau 4 months later and revealed 115,000/microliters 18 months postoperatively.     

Inter-relationships between platelet count,platelet IgG,serum IgG,immune complexes and severity of liver disease

Summary Thrombocytopenia is a common finding in subjects with chronic liver diseases. A variety of mechanisms may underlie this. Immunological disturbances are commonly a feature in chronic liver disease, including hyperglobulinaemia and the presence of autoantibodies and circulating immune complexes and immune mechanisms could therefore contribute to thrombocytopenia. We have investigated the relationships between blood platelet count, serum IgG and IgG immune complexes and IgG associated with platelets in 92 subjects with chronic liver disease (27 with chronic active hepatitis, 38 with primary biliary cirrhosis and 27 with alcoholic liver disease). Severity of liver impairment was a major determinant of degree of thrombocytopenia. Also, an inverse relationship was demonstrated between platelet count and platelet-associated IgG. In subjects with chronic active hepatitis the relationships between platelet count, serum IgG immune complexes and platelet-associated IgG were consistent with a role for immune mechanisms in general and immune complexes in particular as mediators of the thrombocytopenia.     

Menstrual cyclic thrombocytopenia

We studied three patients with cyclic thrombocytopenia which occurred in phase with the menstrual cycle. The platelet count in each patient reached a nadir of 5-20 x 10(9)/l at the onset of menses. Thrombocytopenia was associated with bruising, epistaxis and menorrhagia and was followed 5-14 d later by normal or elevated platelet counts (up to 900 x 10(9)/l). Repeat bone marrow examinations performed at the time of reduced platelet counts showed megakaryocytic hyperplasia. 111In-platelet-disappearance from the circulation was measured in one patient; T50, time to half activity, was shortened to 0.7 d during the period of thrombocytopenia and was prolonged to 3.2 d when the platelet count increased (normal platelet T50 is about 4.8 d). In two of three patients platelet-associated anti-glycoprotein Ib autoantibodies were present and remained elevated despite normalization of the platelet count. In both of two patients the decrease in platelet count at the onset of menses was associated with an increase in the expression of monocyte Fc gamma receptors. Based on the reported capacity of oestrogenic hormones to modulate macrophage Fc gamma receptor expression, we propose that hormonal changes during the menstrual cycle may alter the Fc gamma receptor-mediated clearance of antibody-coated platelets by macrophages, modulate platelet survival, and cause cyclic thrombocytopenia.     

Progressive systemic sclerosis complicated with immune thrombocytopenia during D-penicillamine therapy.

Immune thrombocytopenia is a rare complication of progressive systemic sclerosis (PSS). A 47-year-old female with PSS treated with D-penicillamine developed immune thrombocytopenia, which promptly responded to prednisolone and withdrawal of D-penicillamine. Platelet-associated IgG was elevated and the bone marrow megakaryocyte count was normal. There was an inverse relationship between the level of platelet-associated IgG and the platelet count. A lymphocyte stimulation test sensitized by D-penicillamine was positive. The present case suggests that immune thrombocytopenia may be regarded as one of the D-penicillamine-related immune abnormalities. To our knowledge, its association with PSS has never been reported.