肝素诱导性血小板减少症诊疗策略

<正>肝素诱导性血小板减少症(heparin-induced thrombocytopenia,HIT)是指临床使用肝素类药物治疗后出现血小板计数降低,且机体处于易栓状态,不伴或伴有新发血栓的一类患者。如未经治疗,高于50%患者将在数天或数周内发生血栓,及时治疗将明显降低血栓并发症[1,2]。因此,临床早期诊断极为重要。本文主要介绍HIT的临床表现及早期诊断策略的新进展。发病机制与流行病学HIT是肝素治疗的严重并发症之一。肝素在体内与血小板4因子结合形成血小板4因子-肝素     

二尖瓣置换术后肝素诱导性血小板减少症的诊治体会

<正>肝素诱导性血小板减少症(heparin induced thrombocytopenia,HIT)是临床使用肝素治疗的不良反应之一,由抗血小板4因子-肝素复合物(PF4-H)抗体所介导的高血栓风险性疾病[1,2]。约占所有接受肝素患者的0.5%~5.0%,HIT相关性病死率高达5%~10%[2]。对于HIT患者,一方面血小板计数较低,出血风险较高;另一方面处于高凝高血栓风险状态,需要积极抗凝,预防血栓形成[3],这给临床医生带来极大诊疗困惑。现将我院诊治HIT1例报道如下。     

肝素诱导血小板减少导致下肢、脑、肝、脾、肾多器官栓塞

肝素诱导血小板减少症(heparin induced thrombocytopenia, HIT)是一种由肝素引起的并发症。HIT 可以导致血栓形成,出现动脉和/或静脉栓塞。我们报道一例少见的HIT伴血栓栓塞病例。患者,男性,48岁,因急性心肌梗死接受肝素治疗后并发肝素诱导的血小板减少,随后并发下肢、脑、肝、脾、肾等多个部位和器官血栓栓塞。经过及时调整治疗方案,停用肝素,改为阿加曲班和华法林抗凝治疗,逆转了病情,避免了病情进一步的恶化。     

肝素诱导的血小板减少症

接受抗凝剂治疗或预防栓塞的病人,最常使用肝素,而肝素诱导的血小板减少症(heparin-inducedthrombocytopenia,HIT)是肝素治疗的并发症,此并发症与肝素预期的治疗效果相反。1什么是HIT?通常,肝素预防血栓栓塞,不影响血小板,由于肝素触发免疫系统,HIT导致血小板数降低(血小板减少症)。HIT可出现2种明显的类型:非免疫和免疫介导。非免役介导HIT:最常出现,血小板数轻微减少,对身体无害。免疫介导HIT:较少出现,但很危险。免疫介导HIT引起血小板数明显降低,但尽管血小板数很低,HIT病人仍有栓塞的危险。病人使用肝素后,在肝素和特殊的血…     

肝素诱导血小板减少导致多器官栓塞

正肝素诱导血小板减少症(heparin-induced thrombocytopenia,HIT)是由肝素引起、免疫介导的并发症。以血小板减少和血栓形成为主要特征。HIT通常出现一过性高凝状态,增加了动脉和静脉血栓栓塞的风险~([1])。本文报道1例HIT导致的下肢、脑、肝、脾、肾等多个部位和器官血栓栓塞病例。患者男,48岁。因"胸闷、喘气6 d,加重8 h"入院。患者6天前突发胸闷,伴全身乏力、出汗,持续     

肝素引起的血小板减少症

肝素引起的血小板减少症 ( HIT)曾有多个名称 ,包括 型 HIT、HIT/血栓栓塞综合征( HITTS)、肝素相关的血小板减少 ( HAT)以及白色血栓综合征。对于非免疫机制的肝素相关性血小板减少则称为非免疫性肝素相关性血小板减少症。1　发病机制HIT由肝素依赖性抗体 (常为 Ig G1 ,或 Ig G、Ig M共有或 Ig M型 )通过其 Fcγ a受体激活血小板。血小板 Fc受体的单克隆抗体可抑制血小板的激活 ,这就使 HIT与其他 Ig G介导的、药物诱发的免疫性血小板减少性紫癜区分开来 (如奎宁、磺胺类抗生素 )。后者起因于 Ig G Fab和药物 /血小板膜糖…     

心脏外科围术期肝素诱导血小板减少症的诊治进展

肝素诱导血小板减少症(HIT)是应用肝素后由抗体介导的不良反应,以血小板减少,伴或不伴血栓形成为主要临床表现。由于HIT发病率低、诊断结果时效长以及诊断技术要求高,大大降低了HIT的诊出率。治疗上非肝素抗凝剂种类繁多且适用阶段不同,临床上并无规范诊疗策略。部分研究已涉及新型口服抗凝剂（NOACs）、血浆置换及免疫抑制治疗,但未得到临床上广泛应用。心脏手术后HIT发病率较其他手术或内科疾病高,其围术期治疗也有特殊性。本文就近几年心脏手术围术期HIT的诊治进展进行综述,以期为临床医生提供参考。     

急性冠脉综合征伴发肝素诱导的血小板减少症4例

肝素是临床上常用的抗凝剂,广泛应用于心血管介入、血管外科和血液透析等方面,并发症也被大家所熟知,包括出血、骨质疏松、过敏反应和血小板减少。但肝素诱导的血小板减少症（HIT）还未引起人们的重视。HIT是由肝素类物质诱导的免疫反应,临床表现为自相矛盾的血小板减少和血栓栓塞并发症,是一种后果严重的药物不良反应。我院2010年～2012年心血管内科收治了急性冠脉综合征伴发HIT患者4例。     

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肝素诱导的血小板减少症(HIT)的常见表现包括轻中度血小板减少和静脉或动脉的血栓栓塞,后者是HIT的主要死亡原因。及时诊断和正确治疗HIT可明显降低不良预后的危险。目前我们亟待提高对HIT的认识,改善HIT的诊断方法。     

肝素诱导的血小板减少症研究进展

肝素诱导的血小板减少（HIT）是一种由肝素诱导、免疫介导的以血小板减少和血栓形成为主要特征的药物不良反应,具有一定的致残和致死风险,死亡发生率约为5％～10％.临床研究发现,约1％～5％接受肝素治疗的患者会在应用肝素5～10天后出现HIT[1].目前临床上尚未得到充分重视,极易漏诊、误诊.我们对近年来HIT的发生机制、临床表现、诊断和治疗进展作一综述.     

Plasma thrombopoietin concentrations in thrombocytopenic and non-thrombocytopenic patients in a neonatal intensive care unit

Thrombocytopenia is a frequent occurrence in the neonatal intensive care unit (NICU), but the role of thrombopoietin (Tpo) in the pathophysiology is unknown. We obtained serial plasma Tpo concentrations in 20 thrombocytopenic neonates in our NICU, and performed bone marrow studies in 15. The initial Tpo levels ranged from undetectable (<41 pg/ml) to 1112 pg/ml and did not correlate with gestational age or platelet count. Neonates with decreased marrow megakaryocytes did not have plasma Tpo levels as high as those reported in adults, particularly in small for gestational age infants (Tpo < 300 pg/ml). In 14/15 neonates followed until resolution, the Tpo concentration decreased as the platelet count increased.     

Unstable signal of aequorin-indicated free (Ca2+)i in EGTA-permeabilized human platelets

We present a case of eptifibatide-induced acute profound thrombocytopenia in a 64-year-old male receiving eptifibatide for the second time during percutaneous coronary intervention. Although rare, short and self-limited episodes of acute and profound thrombocytopenia have been associated with eptifibatide exposure. The thrombocytopenia is thought to be immune mediated, and assays are available to test for eptifibatide-induced platelet antibodies.     

Twenty‐year mortality of adult patients with primary immune thrombocytopenia: a Danish population‐based cohort study

Studies have reported a 1·3‐ to 2·2‐fold higher mortality rate among patients with primary immune thrombocytopenia (ITP) compared to the general population. However, long‐term mortality estimates as well as cause‐specific mortality data are sparse. In our population‐based cohort of adult patients with newly diagnosed ITP and up to 37 years of follow‐up, the 5‐year, 10‐year and 20‐year mortality among the ITP patients was 22%, 34% and 49%, respectively. The mortality in the ITP cohort was consistently higher than in the in the general population cohort yielding an adjusted hazard ratio (HR) of 1·5 [95% confidence interval (CI): 1·2–1·8]. The adjusted HRs of mortality due to cardiovascular disease, infection, bleeding and haematological cancer were 1·5 (95% CI: 1·1–1·5), 2·4 (95% CI: 1·0–5·7), 6·2 (95% CI: 2·8–13·5) and 5·7 (95% CI: 2·1–15·7), respectively, whereas mortality due to solid cancer and other causes were similar in ITP patients and the general population. We conclude that mortality rates among ITP patients are higher than in the general population, predominantly as a result of increased cardiovascular disease, infection, bleeding and haematological cancer cause‐specific mortalities.     

New Concepts in Heparin-Induced Thrombocytopenia: Diagnosis and Management

Heparin-induced thrombocytopenia (HIT) is a clinicopathologic condition and adverse drug reaction caused by immunoglobulin G (IgG) antibodies directed against the heparin-platelet factor 4 complex. In most patients, the onset of thrombocytopenia begins while the patient is receiving heparin. In less than 5% of patients, the onset of thrombocytopenia begins several days following heparin discontinuation and has been termed “delayed-onset” HIT. This review summarizes the presentation and clinical course of published reports of delayed-onset HIT occurring in 30 patients. The diagnosis of delayed-onset HIT should be considered in all patients presenting with venous thromboembolism (VTE) and all patients with recent heparin exposure (within the past 14 days) who present with a low platelet count. Most patients with HIT are treated with direct thrombin inhibitors and transitioned to warfarin oral anticoagulation. Administration of direct thrombin inhibitors requires close monitoring for bleeding, dose adjustments based upon coagulation monitoring and is costly. Fondaparinux, a synthetic pentasaccharide and indirect-acting factor-Xa inhibitor, has little to no cross-reactivity with the heparin-platelet factor 4 antibody in in vitro testing. This review summarizes dosing, monitoring and outcomes of preliminary reports of fondaparinux successfully administered to 13 patients with subacute HIT and 22 patients with acute HIT. While several reports have described the treatment and prophylaxis of thrombosis in patients with HIT using fondaparinux, clinical trials should be conducted and reported before fondaparinux becomes a therapy of choice for HIT.     

Dysfunctional alpha-globin genes in hemoglobin H disease in blacks: variation in restriction fragment size permits the detection of the -alpha/-alpha T genotype

Hemoglobin H (HbH) disease is most often due to deletion of three of the four alpha-globin genes (genotype --/--alpha). In black subjects although the -alpha/chromosome is common, the --/haplotype is very rare and few examples of HbH disease have been detected. We have studied three black siblings with HbH by restriction endonuclease mapping of the alpha-like gene complex (5'-zeta-psi zeta-psi alpha 2-psi alpha 1-alpha 2-alpha 1-3') using zeta- and alpha- specific probes. The presence of size differences in the previously described hypervariable region between the zeta and psi zeta genes results in a restriction fragment length polymorphism which permitted the detection of single alpha genes on both number 16 chromosomes in these subjects. Quantitative DNA hybridization by a slot-blot technique confirmed that their genomes contained two alpha-globin genes. The results establish that in these black subjects HbH disease is associated with dysfunctional alpha-globin genes (genotype: -alpha/-alpha T).     

Effect of pregnancy on the course of immune thrombocytopenia: a retrospective study of 118 pregnancies in 82 women

In women with pre‐existing immune thrombocytopenic purpura (ITP), the effect of pregnancy on the course of the disease is poorly known. We performed a dual‐centre retrospective cohort study of 118 pregnancies in 82 women with primary ITP. In early pregnancy, the platelet count was <100 × 10⁹/l in 35·6% of pregnancies. During pregnancy the median platelet count nadir was 66 × 10⁹/l (25th–75th percentile: 42–117), with platelet count <30 × 10⁹/l for 26 pregnancies (22%). In 49% of pregnancies, a significant decrease of the platelet count required treatment at least transiently in preparation for delivery. At the time of delivery, the median platelet count was 110 × 10⁹/l (77–155). Compared to before pregnancy, at 3 months post‐partum, only 11% of pregnancies [95% confidence interval (95% CI): 6·8–20·2] showed disease worsening. Previous splenectomy was the only factor significantly associated with ITP worsening after pregnancy (53·9% vs. 10·3%, P < 0·001). For 8·3% of the pregnancies (95% CI: 3·8–15·1), neonatal thrombocytopenia required treatment, especially in case of previous maternal splenectomy (adjusted odds ratio 16·7, 95% CI: 2·61–106). The overall risk of exacerbation of ITP and severe thrombocytopenia during pregnancy is acceptable.     

Relationships between severe neonatal thrombocytopenia and maternal characteristics in pregnancies associated with autoimmune thrombocytopenia

In pregnant women with antecedents of autoimmune thrombocytopenia (AITP), no predictive factor for severe fetal thrombocytopenia has been identified. We evaluated the relationships between the course of the maternal disease before and during pregnancy and the risk of severe fetal thrombocytopenia, in 64 pregnant women with known chronic AITP antecedents, over a 12-year period. 28 pregnant women had undergone splenectomy before pregnancy and 17 experienced severe thrombocytopenia (< 50 × 10⁹/l) during pregnancy (monthly determination). Eight infants presented with severe thrombocytopenia at birth (12.5%), and four in the following days (6.25%). No severe haemorrhage was observed. Severe thrombocytopenia at birth was present in 57% (CI 95% 18–90%) of the infants born to mothers with severe pregnancy-associated thrombocytopenia and splenectomy antecedents, and in 0% (CI 95% 0–15%) of the infants born to mothers who presented none of these antecedents ( P  = 0.001). In thrombocytopenic mothers the infant platelet counts at birth were positively correlated to the nadir maternal platelet count during the index pregnancy ( r  = 0.42, P  = 0.0075).
These results suggest that severe autoimmune disease is a risk factor for severe fetal thrombocytopenia, and that pregnant women with no antecedent of splenectomy nor severe thrombocytopenia during pregnancy have a very low risk of severe fetal thrombocytopenia.     

How I manage neonatal thrombocytopenia

Although neonatal thrombocytopenia (platelet count < 150×10(9) /l) is a common finding in hospital practice, a careful clinical history and examination of the blood film is often sufficient to establish the diagnosis and guide management without the need for further investigations. In preterm neonates, early-onset thrombocytopenia (<72h) is usually secondary to antenatal causes, has a characteristic pattern and resolves without complications or the need for treatment. By contrast, late-onset thrombocytopenia in preterm neonates (>72h) is nearly always due to post-natally acquired bacterial infection and/or necrotizing enterocolitis, which rapidly leads to severe thrombocytopenia (platelet count<50×10(9) /l). Thrombocytopenia is much less common in term neonates and the most important cause is neonatal alloimmune thrombocytopenia (NAIT), which confers a high risk of perinatal intracranial haemorrhage and long-term neurological disability. Prompt diagnosis and transfusion of human platelet antigen-compatible platelets is key to the successful management of NAIT. Recent studies suggest that more than half of neonates with severe thrombocytopenia receive platelet transfusion(s) based on consensus national or local guidelines despite little evidence of benefit. The most pressing problem in management of neonatal thrombocytopenia is identification of safe, effective platelet transfusion therapy and controlled trials are urgently needed.     

Automated counting of platelets on the Bayer ADVIATTMM 120 analyser

Precise counting of platelets is difficult particularly in the low thrombocytopenic range or when large platelets exist. The recently available Bayer ADVIA^TM 120 analyser uses a method of counting platelets based on two dimensional laser light scatter. We have evaluated this technique on an analysis of 217 peripheral blood samples and found significant differences in platelet counts compared with values obtained by impedance technology, when the causes of thrombocytopenia were due to peripheral platelet consumption. Moreover, such differences were more marked in those samples from severely thrombocytopenic individuals with large platelets on the blood film. These differences, which warrant further study, may have significant implications for the management of patients with very low platelet counts.