A case of sarcoidosis and idiopathic thrombocytopenic purpura accompanied with invasive pulmonary aspergillosis]

A 54-year-old woman with a 21-year history of sarcoidosis was admitted to our hospital with dyspnea on exertion, weight loss, and the appearance of consolidation in chest radiographs. The serum level of soluble IL-2 receptor was high, and CT findings demonstrated mediastinal, hilar and abdominal lymphadenopathy. The histological findings of subpleural consolidation in a transbronchial lung biopsy of the left lung showed giant cells; and those of a CT-assisted biopsy of a retroperitoneal lymph node revealed non-caseous epithelioid cell granulomas. After the biopsy, severe thrombocytopenia (6,000/microliter) developed. With prednisolone treatment, the platelet count rose to normal and the subpleural consolidation on chest radiography was improved. Five weeks later, the had a productive cough with fever, rapidly progressive cavitary lesions and consolidation on chest radiography. Aspergillus fumigatus was detected in the sputum by PCR, and Aspergillus antigen was detected in the serum. She died of progressive respiratory failure, in spite of therapy with amphotericin B and itraconazole. We report a rare case of sarcoidosis and idiopathic thrombocytopenic purpura accompanied with invasive pulmonary aspergillosis.     

Immune thrombocytopenic purpura associated with pulmonary tuberculosis

A 22-year-old woman was admitted into our hospital because of generalized purpura and abnormalities in her chest X-ray. Isolated thrombocytopenia and elevated platelet-associated IgG levels were detected, while the bone marrow examination was normal. Mycobacterium tuberculosis was detected in the bronchoalveolar lavage fluid, and consequently she was diagnosed as having active tuberculosis. High-dose immunoglobulin therapy combined with anti-tuberculosis drugs not only rapidly and continuously corrected thrombocytopenia but also cured pulmonary tuberculosis. This case suggests a causal association between immune thrombocytopenia and tuberculosis as well as the safety and efficacy of the anti-tuberculosis drugs combined with high-dose immunoglobulin therapy.     

Secondary immune thrombocytopenic purpura

PURPOSE OF REVIEW: The American Society of Hematology and British Committee for Standards in Haematology guidelines for the diagnosis and management of immune thrombocytopenic purpura focused entirely on primary disease, and secondary forms were not addressed. The guidelines did not address thrombocytopenia resulting from autoimmune disorders or chronic infections such as Helicobacter pylori, hepatitis C virus or HIV. RECENT FINDINGS: Antiphospholipid antibodies can be detected in roughly 50% of patients diagnosed with primary immune thrombocytopenic purpura, and are not associated with distinctive clinical features. The incidence of thrombotic events is controversial. The prevalence of H. pylori infection in adult patients may not be different from that of the general healthy population matched for age and geographical area. Eradication of the infection can produce platelet responses in a variable number of individuals and is less costly and toxic when compared with standard therapy. Finally, patients with risk factors (multiple sex partners, intravenous drug abuse, blood transfusion recipients) and chronic thrombocytopenia should be screened for hepatitis C virus or HIV infection and should be treated for these infections, not immune thrombocytopenic purpura. SUMMARY: In secondary forms of immune thrombocytopenic purpura, when the hematologist plays a consultative role, priority should be treatment of the underlying disorder.     

Childhood immune thrombocytopenic purpura

Childhood immune thrombocytopenic purpura (ITP) is acute and generally seasonal in nature, suggesting that infectious or environmental agents may trigger the immune response to produce platelet-reactive autoantibodies 4 to 8 weeks following an infection. In general, the patient is well apart from the diffuse bruising and petechiae indicative of a profound thrombocytopenia. Over a period of 6 months, the thrombocytopenia resolves in approximately 85% of children, while the remaining 15% with persistent platelet consumption are designated as chronic ITP patients. The peak age of acute ITP is 2 to 5 years of age, a period when children experience the greatest frequency of viral infections. Children with the chronic form of ITP mirror the adult phenotype, in that females predominate, and there is no seasonal fluctuation of the disease. Evidence from our laboratory suggests that the activated platelet itself may play a role in perpetuating autoantibody production and immune dysregulation associated with ITP. Current data on lymphocyte studies and cytokine alterations noted in response to the variety of regimens used in children with ITP suggest that acute ITP is accompanied by autoantibodies to GPIb and a cytokine profile that is proinflammatory in nature. Early recognition of the immune dysregulation driving acute versus chronic ITP will distinguish those children who might benefit from immunotherapy versus those who will recover without therapeutic intervention.     

Active pulmonary tuberculosis manifesting with idiopathic thrombocytopenic purpura: a rare presentation

A 17-year-old girl presented with a 3-day history of epistaxis, vaginal bleeding and petechiae over the lower extremities. The patient had been feeling unwell with productive cough, fever, chills, poor appetite and weight loss for 2 months. Laboratory findings revealed anemia and thrombocytopenia, whereas bone marrow examination was unremarkable. She was diagnosed as having idiopathic thrombocytopenic purpura (ITP) in association with active tuberculosis (TB). The patient was treated with intravenous immunoglobulin (IVIg) and corticosteroid along with anti-TB drugs. During the follow-up period there was no recurrence of thrombocytopenia or TB. It is important to consider TB in the differential diagnosis of ITP, particularly in high TB-burden areas.     

Pathophysiology of immune thrombocytopenic purpura

In 1951, the young hematologist in training, Dr. William Harrington, infused himself with plasma from a patient with immune thrombocytopenic purpura (ITP). He rapidly developed severe, but transient, thrombocytopenia and was at risk for serious hemorrhage. Thus, the humoral autoimmune cause of ITP was established. Since 1953, when Dr. Harrington's in vivo studies ended, in vitro investigations have aimed to determine the molecular and cellular details of immune-mediated platelet destruction.     

Thrombotic thrombocytopenic purpura associated with primary tuberculosis

Summary Thrombotic thrombocytopenic purpura (TTP) during infectious diseases is a known, but rare event. In this paper a case of TTP associated with primary infection byMycobacterium tuberculosis is described. Various therapeutic approaches were used with the patient: fresh frozen plasma infusions and plasma exchange, specific anti-tuberculous therapy, anti-platelet drugs and steroids. A complete remission occurred 3 months after the onset of the acute disease. A hypothesis on the pathogenesis of TTP might be an increased pro-coagulant activity of interleukin 1 (IL-1) on endothelial cells.

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Thrombotische thrombozytopenische Purpura bei primärer Tuberkulose

Zusammenfassung Das Auftreten einer thrombotischen thrombocytopenischen Purpura (TTP) während infektiöser Erkrankungen ist bekannt, aber selten. Wir beschreiben einen Fall von TTP im Zusammenhang mit einer Primärinfektion durchMycobacterium tuberculosis. Der Patient wurde mit verschiedenen therapeutischen Methoden behandelt: frischem gefrorenem Plasma, Infusionen und Plasmaaustausch, spezifischer anti-tuberkulöser Therapie, Thrombozyten-Inhibitoren und Kortikosteroiden. 3 Monate nach dem Ausbruch der akuten Krankheit trat eine vollständige Heilung ein. Die Pathogenese der TTP könnte durch die vermehrte prokoagulatorische Aktivität von Interleukin 1 (IL-1) auf endotheliale Zellen erklärt werden.

     

Pregnancy in women with immune thrombocytopenic purpura

Thirty-six women with immune thrombocytopenic purpura were studied during 37 pregnancies, and maternal characteristics with predictive value for the fetal platelet count were determined. Nine neonates were thrombocytopenic, with a platelet count of less than 50 x 10(9)/L in eight. Four of these nine neonates delivered to a subgroup of 31 mothers were studied prospectively; the frequency of thrombocytopenia in neonates of women with immune thrombocytopenic purpura was thus 13%. Only two of these nine neonates presented with hemorrhagic syndromes (two, petechial purpura; one, intracranial bleeding). The frequency of neonatal thrombocytopenia was higher in mothers with deep thrombocytopenia and in those who had not responded to corticosteroid treatment following diagnosis. No prognostic value could be assigned to the other maternal characteristics studied, such as a history of splenectomy, maternal treatment at the time of delivery, or the presence of platelet autoantibodies evaluated either with the platelet immunofluorescence test or the platelet Western blot immunoassay.     

Fisher syndrome associated with immune thrombocytopenic purpura

We describe a 51-year-old man with Fisher syndrome (FS) and immune thrombocytopenic purpura (ITP) that developed after upper respiratory infection (URI). Laboratory investigations demonstrated immunoglobulin (Ig) G class of anti-GQ1b autoantibody and reduced platelet count with platelet-associated IgG, which spontaneously improved in parallel with neurologic symptoms. Thus the possible association of ITP should be considered when encountering a patient with FS. This patient suggests that there may be a certain infectious agent causing URI, leading to the co-occurrence of FS and ITP.     

免疫性血小板减少性紫癜合并IgA肾病

目的：认识免疫性血小板减少性紫癜（ITP）合并IgA肾病这一新的临床病症，并对其可能的机制进行探讨。方法：回顾分析3例ITP合并IgA肾病患者的临床病理特征及治疗后的转归。结果：3例患者均经骨髓穿刺确诊为ITP，肾活检确认为IgA肾病。经激素等治疗后，ITP和IgA肾病均可得到缓解。结论：ITP可以合并IgA肾病。IgA肾病的发生可以继发于IPT，也不排除二者均源于骨髓干细胞功能异常的可能性。     

A case of anaphylactoid purpura associated with nephrosis followed by pulmonary tuberculosis

A 54-year old man was admitted to our hospital because of high fever, productive cough and purpura in both legs in June 2005. Urinalysis showed microscopic hematuria and proteinuria. Chest radiograph showed consolidation of right upper field. Because acid-fast bacilli and polymerase chain reaction test for Mycobacterium tuberculosis were positive in bronchial lavage fluid, we made a diagnosis of pulmonary tuberculosis, and prescribed antituberculosis therapy with isoniazid, rifampicin, ethambutol and pyrazinamide. In addition, anaphylactoid purpura was diagnosed by skin biopsy. In July 2005, renal function was deteriorated and nephrosis appeared. We treated with corticosteroid in addition to antituberculosis therapy. His symptoms and renal dysfunction improved. We report a rare case of an anaphylactoid purpura following occurence of pulmonary tuberculosis.     

Bleeding manifestations in severely thrombocytopenic children with immune thrombocytopenic purpura

OBJECTIVE: To report the observations on various bleeding manifestations in children with immune thrombocytopenic purpura (ITP) having severe thrombocytopenia (platelet count (PC) < 20,000/microl) and to compare the differences in bleeding manifestations at levels of PC at < 10,000/microl compared with between 10,000 and 20,000/microl. STUDY DESIGN: It is a retrospective analysis of bleeding manifestations in children with ITP (n = 58) having severe thrombocytopenia recorded between July 1999 and June 2002. A total of 164 episodes of severe thrombocytopenia were observed. During 31 episodes (18.9%), no bleeding manifestations were observed. When bleeding was observed cutaneous bleeds were the commonest manifestations occurring in 124 episodes. Of these 124 instances, in 82 (66.1%) episodes only cutaneous bleeding was observed while in remaining 42 (33.9%) episodes cutaneous bleeding was associated with other bleeding sites. Other common bleeds observed included epistaxis 22 (13.4%), oral bleeding 21 (12.8%) and gastro-intestinal bleeding 5 (3.04%). Comparison of the bleeding manifestations during episodes when the PC was < 10,000/microl and those between 10,000 and 20,000/microl showed that in 76.6% episodes with the count at > 10,000/microl no or only cutaneous bleeds were observed (clinically mild disease) compared to 59.45% episodes with episodes having PC < 10,000/microl (z score 2.37, p < 0.05). There was no statistically significant difference in proportion of patients having clinically mild disease during acute or chronic phase of the disease. CONCLUSION: During episodes of severe thrombocytopenia, most children have clinically mild disease. When the PC is < 10,000/microl clinically mild disease is observed less often compared to episodes with PC 10,000-20,000/microl. Based on these observations, it can be recommended that during severe thrombocytopenia, particularly when the PC is between 10,000-20,22,000/microl, patients can be safely managed with watchful waiting without any specific therapeutic intervention.     

A case of pulmonary tuberculosis case with pancytopenia accompanied to bone marrow gelatinous transformation]

A 45-year-old man did not visit a doctor in spite of his complains, cough and sputum lasting, for six months, and he finally could not eat without beer, and as a result, he lost his body weight and currently 52 kg. He became unconsciousness, was carried to a hospital, and was referred to our hospital. His sputum examination for acid fast bacilli was smear positive, Gaffky 6, for M. tuberculosis. His chest roentogenogram revealed large cavitary lesions in bilateral lung fields. On blood examination, WBC was 1100/microL, RBC was 256 x 10(4)/microL, and PLT was 13.4 x 10(4)/microL. Total protein was 4.7 g/dl, albumin was 1.9 mg/dl, and total cholesterol was 65 mg/dl. We tried to aspirate bone marrow from his sternum, but it was impossible. Hence we did biopsy of his ilium. The pathology of his bone marrow revealed gelatinous transformation. It was thought that the marked delay in visiting a doctor caused general consumption and loss of apetite, thus led to gelatinous transformation and finally pancytopenia.     

新月体性紫癜肾炎合并肺结核1例分析

1 病历资料 1.1 病史资料患者男,49岁.因"发现血压高2年,关节红肿伴双下肢水肿1个月,尿少1周"于2006-12-29收入我科.2年前发现高血压,血压最高160/100 mmHg(1 mmHg=0.133 kPa).间断口服卡托普利,末正规监测血压,未行尿常规检查.2个月前,在当地医院行X线胸片检查诊断肺结核,予异烟肼、乙胺丁醇、利福平、吡嗪酰胺四联抗痨治疗;1个月前,患者出现踝关节红肿伴双下肢凹陷性水肿,同时伴口渴多饮,无明显多尿,当地医院检查发现血尿酸高,糖耐量异常,诊断"痛风,糖耐量异常",经药物治疗(用药不详)后关节红肿基本消退,双下肢水肿无减轻.患者小腿胫前及前臂出现红色丘疹,压之不退色.     

Pathogenesis of chronic immune thrombocytopenic purpura

PURPOSE OF REVIEW: This article summarizes recent insights into the pathophysiology of immune thrombocytopenic purpura, a disorder in which autoantibodies against cell-specific glycoproteins (GPIIb-IIIa, GPIb-IX and others) accelerate platelet destruction. RECENT FINDINGS: Autoantibodies are produced by a limited number of B-cell clones. Platelet antibodies may also impair megakaryocyte development and platelet turnover, thromobopoietin levels are normal or only modestly increased and a compensatory increase in platelet production is not effective in many patients. Patients may show impaired immune regulation manifested by increased proliferation of helper T lymphocytes. Cytotoxic T lymphocytes from patients can lyse platelets in vitro. If cytotoxic T lymphocytes are also capable of perturbing megakaryocyte function, this mechanism may contribute to impaired platelet production. Polymorphisms in the Fcgamma-RIIIa gene may correlate with response to certain forms of therapy and similar genetic approaches may help to identify subsets of patients that differ in their natural history and response to various interventions. SUMMARY: Better understanding of autoantibody development, inhibition of thrombopoiesis and Fcgamma receptor and other polymorphisms will assume increased importance in elucidating the pathogenesis and targeting treatment of chronic immune thrombocytopenic purpura.     

The epidemiology of immune thrombocytopenic purpura

PURPOSE OF REVIEW: This review updates the American Society of Hematology and British guidelines on immune thrombocytopenic purpura incidence, prevalence, and natural history, with recent observations from the peer-reviewed medical literature. RECENT FINDINGS: This analysis was conducted using literature-indexing systems to identify relevant articles. Information about the incidence and prevalence of immune thrombocytopenic purpura is limited, with nearly all data coming from Europe. Recent reports have confirmed earlier studies suggesting that the disease occurs in five out of 100,000 children per year, and that spontaneous recovery is typical. Intracranial hemorrhage occurs in 0.5-1.0% of affected children, and half are fatal. The incidence in adults is roughly two in 100,000 per year and may be more common in older adults than previously recognized. A female predominance occurs only among middle-aged patients, and there is no racial variation in incidence. Spontaneous remission rates vary by report and range from 5 to 11%. SUMMARY: Spontaneous remission occurs more frequently in children than in adults, and intracranial bleeding is uncommon. The incidence increases with age, with a female predominance only among middle-aged adults. Adult patients with chronic disease may have a better prognosis than previously recognized, although only a small minority recover spontaneously.     

Antiphospholipid antibodies in adults with immune thrombocytopenic purpura

To determine the clinical significance of antiphospholipid antibodies (aPL) in patients with immune thrombocytopenic purpura (ITP), anticardiolipin (aCL) (IgG and IgM) and lupus anticoagulant (LA) were sought at diagnosis in 215 ITP adults with platelets <50 × 10⁹/l. aPL (aCL and/or LA) were detected in 55 patients (26%): aCL alone in 39 (18%), aCL and LA in 15 (7%) and LA alone in one (0·5%). LA was significantly associated with high IgG-aCL levels ( P  =   0·001). Among age, sex, initial platelet count, bleeding score, acute or chronic ITP outcome, only younger age was significantly associated with LA-positivity (mean age 29 ± 14 years vs. 45 ± 20 years, P  =   0·002). After a median follow-up of 31 months, 14/215 (7%) patients developed thrombosis (four arterial, 10 venous and/or pulmonary embolism); four of them (29%) had high aCL levels and LA. Multivariate analysis significantly associated thrombosis events only with age [hazard ratio (HR)   =   1·6; 95% confidence interval (CI): 1·2–2·4], LA (HR: 9·9; 95% CI: 2·3–43·4) or high IgG-aCL level (HR: 7·5; 95% CI; 1·8–31·5). Although the thrombosis rate was low, the significant associations between thrombosis and LA or high aCL level suggest that aPL should be tested at ITP diagnosis.     

Intracranial hemorrhage in children with immune thrombocytopenic purpura

 We sent questionnaires to hospitals in Japan in order to study the incidence and conditions of intracranial hemorrhage (ICH) in children with immune thrombocytopenic purpura (ITP). From 1980 to 1995, 11 cases of ICH were reported in eight patients with ITP at 35 institutions. One patient had ICH four times, but only one patient died of the condition. From 1990 through 1995, ICH occurred in four (0.52%) of 772 patients with ITP. None of the patients died. The platelet count when ICH occurred was 5.2±3.7×10⁹/l (mean±SD) (n=11). Four of the eight patients (1980–1995) had received active treatment [e.g. intravenous immunoglobulin G (i.v. IgG)] immediately before ICH occurred. In seven cases (1980–1995), possible causes of ICH, including menstruation (n=2) and viral infections (n=3), were identified. Systemic lupus erythematosus (SLE) later developed in three patients. Although the incidence of ICH in children with ITP has not decreased compared with the rates in earlier studies, the mortality rate has decreased markedly. Our results suggest that menstruation, infection, and risk factors for progression to SLE may help to predict ICH in children with ITP. Large-scale prospective trials are needed to identify risk factors for ICH. Received: 24 June 1999 / Accepted: 26 May 2000