The role of funduscopy in severe thrombocytopenia: A prospective study

PurposePlatelet transfusions for patients suffering from severe thrombocytopenia are regulated by clinical bleedings and platelet counts. The aim of this study was to assess the prevalence of retinal hemorrhage in patients with hematologic and oncologic malignancies and severe thrombocytopenia, and to determine the benefit of systematic funduscopic examination in this setting.Materials and methodsHospitalized patients with hematologic and oncologic malignancies having a platelet count less than 25,000 per μL underwent indirect ophthalmoscopy. The prevalence of retinal hemorrhage and its correlation with different patients’ characteristics were determined. The decision to transfuse platelets or not following bedside indirect ophthalmoscopy was left at the discretion of the treating physician.ResultsA total of 34 severe thrombocytopenic patients were included in the study. The prevalence of retinal hemorrhage was detected in 10 patients (29.4%). No significant correlation was found between the occurrence of retinal hemorrhage and age, platelet count or thrombocytopenia etiology (P > 0.05). No significant difference was found concerning the rate of transfusion between those with and without retinal hemorrhage.ConclusionAccording to our statistical results, retinal hemorrhage is a frequent finding in severely thrombocytopenic patients. Early detection may lead to an increase in the platelet transfusion threshold from to 30,000 per μL offering additional protection against spontaneous bleedings. Funduscopy is a safe and easy exam to perform systematically in patients with severe thrombocytopenia.     

The Myelodepletive Phenotype in Myelofibrosis: Clinical Relevance and Therapeutic Implication

Myelofibrosis (MF) is a BCR-ABL1⁻ myeloproliferative neoplasm that arises from hematopoietic stem and progenitor cells frequently harboring a somatic driver mutation in 1 of 3 genes: JAK2, CALR, or MPL. The pathologic features of this hematologic malignancy include myeloproliferation, diffuse bone marrow fibrosis, and overactivation of the JAK-STAT pathway, resulting in enhanced inflammatory cytokine release. The common clinical manifestations of MF include systemic symptoms, abnormal peripheral blood count levels, and splenomegaly. However, it has become increasingly appreciated that significant clinical heterogeneity exists among patients with MF. Two distinct MF clinical phenotypes include the myeloproliferative and myelodepletive phenotype, with peripheral blood counts being the main discerning feature. Patients with the myeloproliferative phenotype will present with elevated peripheral blood counts and often experience significant constitutional symptoms and progressive splenomegaly. In contrast, patients with the myelodepletive phenotype will have low peripheral blood counts and will frequently require transfusion support. Current frontline therapies for MF, include ruxolitinib and fedratinib, which can exacerbate cytopenias and thereby pose an impediment to effective treatment of the myelodepletive patient. The present review discusses the clinical and prognostic implications of the myelodepletive phenotype and the therapeutic options and limitations for this subset of patients, representing an unmet clinical need.     

Thrombocytopenia after therapeutic hypothermia in severe traumatic brain injury

Objective: To investigate the clinical characteristics and significance of thrombocytopenia after therapeutic hypothermia in severe traumatic brain injury (TBI). Methods:Ninety-six inpatients with severe brain injury were randomized into three groups: SBC (selective brain cooling) group (n=24), MSH (mild systemic hypothermia ) group (n=30), and control (normothermia) group (n=42). The platelet counts and prognosis were retrospectively analyzed. Results: Thrombocytopenia was present in 18 (75%), 23 (77%) and 15 (36%) patients in SBC group, MSH group and control group, respectively (P<0. 01). Thrombocytopenia, in which the minimum platelet count was seen 3 days after hypothermia, showed no significant difference between SBC and MSH group (P>0.05). Most platelet counts (37 cases, 90 %) in hypothermia group were returned to normal level after 1 to 2 days of natural rewarming. The platelet count in SBC group reduced by 16%, 27% and 29% at day 1, 3 and 5 respectively compared with the baseline value. Good recovery ( GOS score 4-5) rate of thrombocytopenia 1 year after injury for hypothermia group (17 cases, 37%) was significantly lower than that of control group (P < 0.01). Conclusions: Therapeutic hypothermia increases the incidence of thrombocytopenia in severe TBI, and patients with thrombocytopenia after therapeutic hypothermia are associated with unfavorable neurological prognosis.     

Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer

Rhenium-186 hydroxyethylidene diphosphonate (¹⁸⁶Re-HEDP) has been used for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using ¹⁸⁶Re-HEDP Twenty-four patients with hormone-resistant prostate cancer entered the study. Each patient had at least four bone metastases and adequate haematological function. Groups of at least three consecutive patients were treated with doses starting at 1295 MBq and increasing to 3515 MBq (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose-limiting toxicity, while leucopenia played a minor role. Early death occurred in one patient (10 days after administration) without clear relationship to the ¹⁸⁶Re-HEDP therapy. Transient neurological dysfunction was seen in two cases. Two patients who received 3515 MBq ¹⁸⁶Re-HEDP showed grade 3 toxicity (thrombocytes 25–50 × 10⁹/1), defined as unacceptable toxicity. After treatment alkaline phosphatase levels showed a transient decrease in all patients (mean: 26% ± 10% IUA; range: 11%–44%). Prostate-specific antigen values showed a decline in eight patients, preceded by a temporary increase in three patients. From this study we conclude that the maximally tolerated dose of ¹⁸⁶Re-HEDP is 2960 MBq. A placebo-controlled comparative study on the efficacy of ¹⁸⁶Re-HEDP has been initiated.     

The heparin-induced thrombocytopenia and thrombosis syndrome: Treatment with intraarterial urokinase and systemic platelet aggregation inhibitors

We report a case of the heparin-induced thrombocy-topenia and thrombosis syndrome presenting with acute ischemia of a lower limb. The patient was successfully treated by withdrawal of heparin products, intraarterial urokinase, and platelet anti-aggregation therapy consisting of Dextran and aspirin.     

细菌性肝脓肿患者发生血小板减少影响因素研究

背景细菌性肝脓肿(PLA)是临床常见的内脏器官感染性疾病,既往PLA发生血小板减少的临床研究较少。目的 分析PLA患者发生血小板减少的流行病学和临床特征,并探讨发生血小板减少的影响因素。方法 纳入北京大学人民医院2011年1月至2020年12月161例因PLA住院的患者为研究对象。收集患者资料,包括年龄、性别、体质指数(BMI)、发病症状(发热、腹痛、恶心、呕吐)、既往病史信息(高血压、糖尿病、冠心病、肝胆疾病、恶性肿瘤);收集患者入院时辅助检查结果,包括白细胞计数、中性粒细胞绝对值、淋巴细胞绝对值(ALC)、单核细胞绝对值、血红蛋白、C反应蛋白(CRP)、降钙素原(PCT)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBiL)、尿素氮(BUN)、肌酐(Scr)、白蛋白(ALB)、凝血酶原时间(PT)、活化部分凝血活酶时间、纤维蛋白原、D-二聚体(D-Dimer)、血小板计数(PLT);收集患者肝脓肿影像学检查(腹部CT或超声)结果(是否多个脓肿)、病原学检查结果(血培养、培养出肺炎克雷伯菌比例);收集患者的并发症情况及预后情况。根据外周血PLT是否<1...     

Treatment of septic thrombocytopenia with immune globulin

Thrombocytopenia frequently complicates systemic infection and results from multiple possible mechanisms. We and others have demonstrated that platelet-associated IgG (PAIgG) levels are elevated in the majority of patients with septic thrombocytopenia. Corticosteroids may be undesirable as a treatment for thrombocytopenia for patients with severe infection because of their potential for suppressing the immune response. We hypothesized that septic thrombocytopenia is, in most cases, an immune disorder analogous to idiopathic thrombocytopenic purpura (ITP) which might respond to intravenous gamma-globulin as a treatment for increasing the platelet count in this disorder. Intravenous immune globulin (IVIG), 400 mg/kg daily for 3 days, was administered in a randomized double-blind placebo-controlled trial. Twenty-nine patients who developed thrombocytopenia during a documented, septic episode were studied. Patients with disseminated intravascular coagulation (DIC), hypersplenism, or drugs known to cause thrombocytopenia were excluded. Elevated PAIgG levels were documented in 52% of evaluable patients. Mean platelet counts in the IVIG group rose from 43K at study entry to 178K (411% rise) by Day 9. In the placebo group platelets rose from 51K to 125K (261% rise;P = 0.02). Seventy-seven percent of the IVIG group had a minimum peak rise of 35K, vs 56% of the placebo group. Three patients in the placebo group had a serious bleeding episode, vs one in the IVIG group. The use of IVIG to treat septic thrombocytopenia not associated with DIC leads to a more rapid, more sustained, and greater increase in platelet count than placebo. Its use is recommended in the septic patient who is bleeding or is likely to need invasive or surgical procedures.     

Successful treatment of refractory thrombocytopenia with mycophenolate mofetil in a patient with systemic lupus erythematosus

While mild thrombocytopenia in systemic lupus erythematosus (SLE) is frequently seen in the context of active disease, severe thrombocytopenia causing significant bleeding is not that common. Corticosteroids are considered the first line therapy for severe thrombocytopenia in SLE. Second-line therapeutic agents or splenectomy have been reported to be effective for patients who fail to respond to steroids or those who require moderate doses of steroids to maintain the platelet counts. Recent randomized controlled studies have shown that mycophenolate mofetil (MMF) is an efficacious and safe therapeutic agent in patients with proliferative forms of lupus nephritis. However, little information has been available regarding the role of MMF in the treatment of immune thrombocytopenia complicated with SLE. Hereby I describe a patient with SLE in whom thrombocytopenia was refractory to corticosteroids, intermittent intravenous cyclophosphamide, azathioprine, cyclosporine, intravenous gamma globulin, danazol, and splenectomy, and whose platelet counts eventually normalized during therapy with MMF. In this patient, thrombocytopenia is initially thought to be associated with active SLE involving major organ. However, after immunosuppressive agents were given, the refractory nature of thrombocytopenia seems to be an isolated phenomenon, independently of SLE activity.     

妊娠合并血小板减少的病因及对母儿结局的影响

目的探讨妊娠合并血小板减少的病因及对母儿结局的影响。方法回顾性分析2010年1月1日至2017年8月31日北京妇产医院收治的妊娠合并血小板减少病例617例,分析血小板减少的不同病因和血小板降低的不同程度对母儿结局的影响。结果妊娠合并血小板减少的病因主要为妊娠期血小板减少症(GT)、免疫性血小板减少性紫癜(ITP)、先兆子痫(PE)、HELLP综合征及弥散性血管内凝血(DIC)。按照上述五种病因分为五组患者,其年龄、住院天数、分娩孕周、孕次、产次及孕前BMI、血小板最低值、首次出现血小板减少的孕周及血小板最低值出现孕周的差异均存在统计学意义(P<0.05),五组患者的早产率、胎死宫内发生率、产后出血发生率、胎儿生长受限发生率、出生5分钟Apgar评分及新生儿体重等妊娠结局存在组间差异(P<0.05)。依血小板降低程度分为轻、中、重三组,随血小板减少程度的增加,三组间剖宫产率、早产率、死产率、产后出血率、贫血率、输血小板治疗率、肝功能异常发生率均存在统计学差异(P<0.05)。结论相比妊娠期血小板减少症,其余病理性血小板减少均在不同程度上影响着母婴的安全,尤其HELLP综合征及DIC。血小板计数<50×109/L对不良妊娠结局有重要的提示作用。