Isolated thrombocytopenia in patients infected with HIV: treatment with intravenous gammaglobulin

Isolated thrombocytopenia occurs frequently in patients infected with HIV. Studies of mechanisms of thrombocytopenia and clinical response to therapy suggest that the thrombocytopenia is often antibody mediated (ITP). The best approach to treatment of these patients is uncertain in that the routine modalities (steroids, splenectomy, vinca alkaloids) that are used to increase the platelet count in patients with classic ITP are known to be immunosuppressive. We report here the results of intravenous gammaglobulin (IVGG) treatment of 22 patients with HIV-related acute and chronic ITP who had severe thrombocytopenia and bleeding symptoms. Only one patient had an opportunistic infection at the time of treatment. Eight patients were homosexual, eight had hemophilia, three were i.v. drug abusers, two children had congenital acquisition of HIV, and one was the wife of an HIV + i.v. drug abuser. The average pretreatment platelet count was 22,000/microliter (hemophiliacs were treated at higher platelet counts than were the other patients), and the mean peak platelet count measured on days 5 to 8 was 182,000/microliter. Nineteen of 22 patients had peak platelet counts greater than 50,000/microliter following IVGG and 17/22 had peak counts greater than 100,000/microliter. After the initial infusions, all but three refractory patients could maintain adequate platelet counts with IVGG alone infused no more often than once every 2 weeks. The outcomes for the 22 patients after multiple maintenance IVGG infusions were remission, 5; stable without therapy, 1; maintenance, 13; and refractory, 3. The eight hemophiliacs with ITP responded better than did the eight homosexual ITP patients; their mean peak platelet count was 227,000/microliter versus 142,000/microliter in the homosexuals. In summary, patients with HIV-related ITP without opportunistic infections responded well to IVGG, with peak platelet counts comparable to those of ITP patients not infected with HIV. IVGG may be a useful therapy of ITP in HIV+ patients, since it appears to be less immunosuppressive than are conventional therapies, and none of the 22 HIV+ patients developed an opportunistic infection while receiving IVGG alone.     

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.     

Thrombocytopenia during immunotherapy with interleukin-2 by constant infusion

PURPOSE: To elucidate some of the possible mechanisms that lead to interleukin-2 (IL2)-induced thrombocytopenia. PATIENTS AND METHODS: We evaluated retrospectively the effects of immunotherapy with IL2 in 76 patients with disseminated cancer. The lymphokine was administered by constant infusion, daily for 6 days a week for 4 consecutive weeks. RESULTS: A significant decrease in platelet counts was seen after the first 6 days of therapy in all but two patients: 14 patients experienced grade 2 or 3 toxicity, 21 had grade 1 toxicity, and although the decrease in platelet counts could not be graded as toxicity in the remaining 41 patients, there was an average decrease of 32% from baseline platelet counts in 39 (p less than 0.0001). Thrombocytopenia appeared to be secondary to peripheral platelet destruction, since bone marrow biopsy specimens obtained during thrombocytopenia showed hyperplastic megakaryocytopoiesis. IL2 is inactivated by tubular resorption, and severity of thrombocytopenia was strongly correlated with IL2-induced renal dysfunction (p = 0.0004). Additionally, both renal dysfunction and thrombocytopenia were related to total dose of IL2 and were more pronounced in patients with worse baseline renal function and lower baseline platelet counts. The incidence of thrombocytopenia increased with subsequent IL2 therapy: life-threatening thrombocytopenia (less than 25,000/microL) was seen in nine of 57 patients, five of whom required transfusional platelet support. CONCLUSION: On the basis of preliminary observations, we hypothesize that thrombocytopenia induced by IL2 is caused by accelerated clearance of platelets by the reticuloendothelial system.     

Procainamide-induced thrombocytopenia

An 81-year-old female developed marked thrombocytopenia associated with numerous megakaryocytes in the bone marrow, but without anemia or leukopenia, after taking procainamide (3 g/day) for a period of 2 months. Despite continuation of this medication, treatment with prednisone led to rapid rise in platelet count, and withdrawal of steroid was followed by prompt recurrence of thrombocytopenia. The platelet counts returned to normal after discontinuation of procainamide, and readministration of this drug was followed by reappearance of thrombocytopenia. These observations indicate that exposure to procainamide can cause isolated thrombocytopenia, probably due to immune-mediated destruction of platelets, and that treatment with prednisone may be promptly beneficial in patients with procainamide-induced severe thrombocytopenia and bleeding.     

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.     

Delayed-onset heparin-induced thrombocytopenia and thrombosis

BACKGROUND: Heparin-induced thrombocytopenia is a prothrombotic drug reaction caused by platelet-activating antibodies that recognize complexes of platelet factor 4 and heparin. OBJECTIVE: To describe a syndrome termed delayed-onset heparin-induced thrombocytopenia, in which thrombocytopenia and thrombotic events begin 5 or more days after withdrawal of heparin. DESIGN: Case series. SETTING: Secondary and tertiary care hospitals. PATIENTS: 12 patients who presented with serologically confirmed, delayed-onset heparin-induced thrombocytopenia, including 6 outpatients presenting after hospital discharge. MEASUREMENTS: The platelet serotonin-release assay was used to measure IgG-induced heparin-dependent and heparin-independent platelet activation; an enzyme immunoassay that detects IgG against platelet factor 4-heparin complexes was also used. RESULTS: Patients with delayed-onset heparin-induced thrombocytopenia presented with thrombocytopenia and associated thrombosis a mean of 9.2 days (range, 5 to 19 days) after stopping heparin therapy. Nine patients received additional heparin, with further decrease in platelet counts. Compared with controls, patients with delayed-onset heparin-induced thrombocytopenia had higher titers of IgG antibodies to platelet factor 4-heparin and greater IgG-induced heparin-dependent and heparin-independent platelet activation. CONCLUSIONS: Delayed-onset heparin-induced thrombocytopenia should be suspected when patients present with thrombocytopenia and thrombosis up to 3 weeks after exposure to heparin. This syndrome could be caused by high titers of platelet-activating IgG induced by heparin.     

Partial inhibition of platelet aggregation by nebulized pentamidine in severe haemophiliacs

The antiparasite agent pentamidine has been shown to inhibit human platelet aggregation in vitro at concentrations that (potentially) may be attained in patient plasma after the administration of the drug by nebulizer. We measured platelet aggregation in platelet-rich plasma (PRP) before and after the administration of 300 mg nebulized pentamidine to 10 HIV-positive patients with severe haemophilia on prophylaxis against Pneumocystis carinii pneumonia. All patients had normal platelet counts. PAF-acether, U46619, collagen and ADP at different concentrations were used as agonists. Platelet aggregation was lower in PRP samples taken at the end of pentamidine administration and 1 h thereafter than in samples taken at the same time points in control experiments (without the administration of pentamidine). The inhibition of platelet aggregation was mild and tended to be overcome by higher concentrations of platelet agonists. The bleeding time was prolonged from 5 to 15 min in one patient but did not change in the remaining nine patients. In conclusion, this controlled study shows that nebulized pentamidine inhibits platelet aggregation in HIV-positive haemophiliacs without significantly affecting their bleeding times. Although this mild inhibitory effect may not be clinically relevant in haemophiliacs with normal platelet counts despite their defect in intrinsic coagulation, patients with HIV-related thrombocytopenia should be monitored to detect any excessive prolongation of their bleeding times after nebulized pentamidine.     

Efficacy,plasma concentrations and adverse effects of a new sustained release procainamide preparation

To assess the efficacy, plasma drug concentrations and adverse effects of a new sustained release preparation of procainamlde, 33 patients with heart disease were studied in an acute dose-ranging protocol and a chronic treatment protocol. Patients initially received a daily dose of 3 g of sustained release procainamide; this dose was increased by 1.5 g daily until ventricular premature depolarizations were suppressed by 75 percent or more, adverse drug effects occurred or a total daily dose of 7.5 g of sustained-release procainamide was reached. Twenty-five patients (76 percent) had at least a 75 percent reduction (range 75 to 100 percent [mean ± standard deviation 91 ± 8.2]) in ventricular premature depolarization frequency at a dosage of 4.8 ± 1.46 g/day (range 3.0 to 7.5). Despite the 8 hour dosing interval, the variation between maximal and minimal plasma procainamide and N-acetylprocainamide concentrations under steady state conditions was very small. Mean maximal procainamide and N-acetylprocainamide plasma concentrations were 10.4 +- 6.02 and 12.0 ± 7.40 μg/ml, respectively. The respective mean minimal concentrations were 6.8 ± 4.50 and 8.7 ± 5.99 μg/ml In nine patients (27 percent) treatment with sustained release procainamide resulted in conversion of the antinuclear antibody test from negative to positive. Adverse drug effects occurred in 17 (52 percent) of the subjects. In general, adverse effects were minor and abated within 24 hours after administration of the drug was stopped. One patient had the procainamide-induced systemic lupus erythematosus-like syndrome.     

The long-term use of zidovudine in patients with severe immune-mediated thrombocytopenia secondary to infection with HIV.

Various treatments for HIV-related thrombocytopenia have been reported. Since etiologies of the thrombocytopenia may differ with regard to risk group treatment outcomes may also vary. We have recently studied the long-term use of zidovudine in individuals with sexually transmitted HIV infection and severe thrombocytopenia. Twenty-five men, median age 34 years (range, 23-51 years), were treated with zidovudine (1000 mg/day) for a median duration of 12 months (range, 2.5- less than 26 months). Nineteen patients (76%) had had episodes of symptomatic bleeding secondary to thrombocytopenia prior to study entry. All patients bleeding symptoms resolved with therapy. Six (24%) achieved a complete response, with normalization of platelet counts, while 11 patients (44%) achieved a partial response, giving an overall response rate of 68%. The median time to partial or complete normalization of platelet counts was 12 weeks (range, 4-62 weeks). Toxicities were minimal during the study period. Only one patient developed an AIDS-defining diagnosis while on therapy. We conclude that patients with sexually transmitted HIV infection and immune thrombocytopenia may need a prolonged period of therapy with zidovudine to achieve a platelet response. Other treatment modalities may be required for the 30% of patients who do not respond to zidovudine.     

Severe neutropenia associated with sustained-release procainamide

Neutropenia is a rare complication of procainamide therapy. However, over a period of 20 months, 8 patients developed severe neutropenia while taking a sustained-release preparation of the drug. Seven patients presented with fever and constitutional symptoms and one patient was asymptomatic. Bone marrow examinations showed myeloid aplasia or maturation arrest in 5 patients and myeloid hyperplasia in 1. Neutropenia resolved within 30 days of drug withdrawal, and all patients survived. A case-control study showed a significant association between sustained-release procainamide therapy and severe neutropenia in 5 of 114 patients (4.4%) recovering from open-heart surgery (Mantel-Haenszel chi square = 13.84; p less than 0.001). Thus, life-threatening neutropenia may be common with sustained-release procainamide preparations.     

Lethal heparin-associated pulmonary embolism--case reports

Thrombocytopenia is a known adverse reaction occurring in some patients receiving heparin. Two different types of heparin-induced thrombocytopenia have been described. Heparin-induced thrombocytopenia type I is a mild thrombocytopenia after 1 to 4 days of heparin therapy, attributed to a direct interaction between heparin and circulating platelets. No specific treatment is necessary. Heparin-induced thrombocytopenia type II is a severe thrombocytopenia mediated by an immunologic mechanism. Type II generally develops after 5 to 10 days of heparin therapy and can be associated with potentially devastating thromboembolic complications. The incidence of heparin-induced thrombocytopenia type II is below 3%. Thromboembolic events are always accompanied by a decrease in the platelet count, however, complications in the absence of absolute thrombocytopenia have been reported. Diagnosis of HIT type II is based on clinical features and laboratory studies for the heparin-dependent platelet antibody. Immediate cessation of heparin administration is essential. Several alternative anticoagulant therapies have been studied and have shown promising results when used for this purpose. Two patients undergoing coronary artery bypass surgery are presented in whom pulmonary embolism developed due to heparin-induced thrombocytopenia type II. In both cases, platelet counts were within the subnormal range at the time of the first thromboembolic complication. The clinical, therapeutic, and prognostic implications are discussed.     

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 × 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 α2b-interferon (IFN-α) 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-α therapy. In conclusion, the ability of IFN-α to increase platelet counts in HCV-positive thrombocytopenic patients supports mechanisms involving a direct role for HCV inhibiting platelet production.     

Isolated thrombocytopenia after allogeneic bone marrow transplantation: existence of transient and chronic thrombocytopenic syndromes

Isolated thrombocytopenia after bone marrow transplantation was investigated in 65 fully engrafted patients surviving at least 60 days posttransplant. Twenty-four patients (37%) developed this complication, which occurred most frequently in patients receiving pretransplant preparation with total body irradiation or busulfan. Two distinct thrombocytopenic syndromes were identified: (1) transient thrombocytopenia (nine patients), in which a normal platelet count (greater than 100,000/microL) was initially established by day +40 but then diminished to less than 10,000 to 45,000/microL on day +40 to +70, with subsequent resolution of the thrombocytopenia by day +90; (2) chronic thrombocytopenia (15 patients), in which a platelet count greater than 100,000/microL was not achieved at any time during the first four months posttransplant, despite the simultaneous presence of normal granulocyte and reticulocyte counts. Although the transient syndrome did not adversely affect prognosis, the chronic syndrome carried a high mortality (21% actuarial survival at 1,000 days posttransplant compared with 67% survival for all patients, P less than .01) and had a high association with both severe (grades 3 to 4) acute graft-versus-host disease (GVHD) and chronic GVHD. In three of nine patients with transient thrombocytopenia, a temporal association with trimethoprim-sulfamethoxazole administration was observed, whereas in all other patients, no drug association could be found. Bone marrow biopsies in those patients with drug-associated thrombocytopenia showed decreased numbers of megakaryocytes, whereas biopsies in the remainder of the transiently thrombocytopenic patients demonstrated adequate numbers of platelet precursors, suggesting peripheral platelet destruction or ineffective thrombopoiesis. Biopsies in the chronic thrombocytopenic patients included those with and without adequate numbers of platelet precursors, although the association with chronic GVHD was strongest in patients demonstrating normal numbers of megakaryocytes. We conclude that isolated thrombocytopenia represents a significant complication of bone marrow transplantation, particularly in patients receiving hematopoietic ablative preparatory regimens, and that it is the chronic, not the transient, thrombocytopenic syndrome that is associated with an adverse patient prognosis.     

Long-term lorcainide therapy in patients with ventricular tachycardia

One hundred patients inducible at electrophysiologic studies underwent serial drug testing with procainamide, lidocaine, and lorcainide to determine comparative efficacy. Acute intravenous administration was followed by repeat programmed electrical stimulation (PES) studies on separate days for each antiarrhythmic drug. Lorcainide prevented ventricular tachycardia (VT) induction in 69% of the 100 patients studied, procainamide was effective in 50% of the 75 patients studied, and lidocaine prevented VT induction in 30% of 53 patients. Following PES and serial drug testing, 46 patients were started on lorcainide, nine patients on procainamide, and 45 patients were started on other antiarrhythmic drug regimens. Seventy percent of the patients have remained on lorcainide therapy, while 47% have continued on other drug therapies started over a 20.5 +/- 3.2-month mean follow-up period. Despite sleep-wake disturbances and a need for sedation at night, lorcainide therapy was tolerated well in this population and remained an effective antiarrhythmic with prolonged administration.     

Heparin-induced thrombocytopenia: A prospective study

Thrombocytopenia is a well-described complication of heparin therapy. Few studies describe the incidence of thrombocytopenia when low-dose heparin (10,000–15,000 units/day) is used for prophylaxis of deep venous thrombosis. In our study, ten of 66 courses (15%) of heparin prophylaxis in coronary care unit patients were accompanied by a mild thrombocytopenia with platelet counts below 150 ± 10³/mm³. In all cases the platelet count returned to normal despite continued heparin therapy. Patients who became thrombocytopenic had significantly lower initial platelet counts. No cases of severe thrombocytopenia were seen (platelet count below 100 ± 10³/mm³). No patient developed thrombosis, bleeding or elevated fibrin split products. Mild thrombocytopenia occuring after 2–5 days of low-dose heparin is common, but clinically insignificant.     

Superior effect of intravenous anti-D compared with IV gammaglobulin in the treatment of HIV-thrombocytopenia: results of a small, randomized prospective comparison

This small, prospective, randomized study compared increases in platelet counts and duration of response after intravenous gammaglobulin (IVIG) and IV anti-D in patients with HIV-related thrombocytopenia (HIV-TP). Nine Rh+, nonsplenectomized HIV-positive patients with thrombocytopenia were treated sequentially, in random order, with IVIG and IV anti-D in a cross over design, receiving each therapy for 3 months. Peak platelet counts and duration of effect after each treatment were compared. In addition, viral load measurements and CD4 counts were followed serially, as well as thrombopoietin levels. IV anti-D resulted in a mean peak platelet count of 77 x 10(9)/L compared to only 29 x 10(9)/L after IVIG (P = 0.07). The mean duration of response was significantly longer in patients treated with anti-D (41 days) compared to IVIG (19 days, P = 0.01). No consistent changes were seen in the CD4 counts or viral load measurements as a result of either therapy. Thrombopoietin levels were normal in all patients despite often severe thrombocytopenia. Anti-D was more efficacious than IVIG for the treatment of HIV-TP, confirming and extending previous results. Anti-D should be the first line therapy in HIV-positive, Rh+ patients, when antiretroviral agents are not indicated, not effective, or there is an urgent need to increase the platelet count.     

Plasma soluble interleukin-2 receptor levels in patients with idiopathic thrombocytopenic purpura

Soluble interleukin-2 receptor (sIL-2R) was measured in the plasma of 31 patients with idiopathic thrombocytopenic purpura (ITP) and 22 normal controls. When thrombocytopenia persisted longer than 6 months, the diagnosis of chronic ITP was made. Twenty patients had acute ITP, 11 patients had chronic ITP, and all patients received high-dose methylprednisolone (HDMP) (30 mg/kg/d for 3 days, 20 mg/kg/d for 4 days). The sIL-2R levels of the patients were determined before being giving HDMP and 14 days after the end of HDMP therapy. Platelet counts were determined before administration of HDMP, one day after the end of HDMP therapy, and once every 28 days for 7 months thereafter. There was not a significant difference between the mean pre-treatment plasma sIL-2R levels of both acute and chronic ITP groups (P > 0.05), and these were higher than that of the control group (P < 0.001). The mean post-treatment sIL-2R level of the chronic ITP group was significantly higher than those of both the control and post-treatment acute ITP groups (P < 0.001). There were negative correlations between the plasma sIL-2R levels and platelet counts of both group patients in the pre-treatment period and between post-treatment sIL-2R levels and platelet counts in chronic ITP group (P < 0.05). We think that there was a good correlation between prognosis of ITP and sIL-2R levels after HDMP therapy, and platelet counts in patients with ITP are linked to sIL-2R levels. Am. J. Hematol. 57:119–123, 1998. © 1998 Wiley-Liss, Inc.     

Autoimmune thrombocytopenia: a complication of fludarabine therapy in lymphoproliferative disorders

We describe two cases of autoimmune thrombocytopenia precipitated by fludarabine therapy in patients with chronic lymphatic leukaemia. Both were treated with high dose steroids and initially responded with recovery of normal platelet counts. One patient developed recurrent autoimmune thrombocytopenia on two occasions following re-exposure to the drug when his disease had become refractory to all other treatments. A retrospective review of the case notes of 45 patients with lymphoproliferative disorders treated with fludarabine over the past 6 years indicated the development of autoimmune thrombocytopenia in 4.5% (two out of 45) and autoimmune haemolytic anaemia in 6.7% (three of the 45).     

Platelets in hyperthyroidism: 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.     

Thrombocytopenia in patients with rheumatoid arthritis on long-term treatment with low dose methotrexate

Summary We reviewed the records of 315 patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX) and evaluated the conditions contributing to thrombocytopenia. Thirteen out of 315 patients with RA presented with low platelet counts ( 100.000/mm³). The age of these patients (51±12.6 years) did not correlate with thrombocytopenia (r=0.211, p>0.05).Thrombocytopenia resulted from coadministration of MTX and NSAID or multiple drug interactions. We observed a significant (r=0.48, p<0.05) increase of discontinuation of NSAID's but not of MTX therapy (r=0.42, p>0.05) with a mounting weekly dosage of MTX (12.5±5 mg orally). There was a significant correlation between this weekly dosage of MTX coadministered on the same day with NSAID and thrombocytopenia (r=0.6, p<0.05).In most cases (9/13) MTX was not or just temporarily withdrawn. Three of the remaining patients had multiple drug interactions. Reintroduction of low dose MTX treatment in patients having had thrombocytopenia could be performed safely, if thrombocytopenia occurred as a result of concomitant application of MTX and NSAID and no other multiple drug interactions. Preferably, MTX and NSAID should be given to these risk patients on separate days or intervals considering half time clearance of NSAIDs. This procedure has avoided the reoccurrence of thrombocytopenia and controlled further drug interactions of NSAIDs and MTX in our patients.