从血液透析的角度看肝素诱导的血小板减少症

肝素诱导的血小板减少症(heparin-induced thrombocytopenia,HIT)是使用普通肝素或低分子肝素的副反应,其特征是血小板减少同时伴有动静脉血栓形成的高风险。临床上HIT并不少见,而被诊断并得到治疗的却很少。HIT的发生与HIT抗体的产生密切相关,而血液透析患者中HIT抗体阳性是否会导致患者死亡率增加仍存在争议。HIT的诊断基于临床表现和实验室检查。HIT的实验室检查主要包括监测血小板计数和血清学检查方法2大类,4T临床评分系统对诊断HIT有一定的指导意义。对于临床高度怀疑HIT的患者,应立即停所有肝素制剂、转换抗凝剂、进行相应的实验室检查、仔细监测血栓事件、避免预防性输注血小板。     

肝素诱导的血小板减少症

肝素诱导的血小板减少症是一种药物诱导的血小板减少症，是肝素治疗中的一种严重并发症，近年来，有关本病的发生率，发病机理及诊断方法等方面的研究取得了较大进展，并且意见渐趋于一致；而有关本病的治疗则尚无较一致的看法，本文拟阐述本病在发病机理，实验室检查，诊断，治疗及预后等方面的最新进展。     

肝素诱导的血小板减少症并发血栓形成的治疗进展

给予肝素治疗患者中,在肝素诱导的血小板减少症(HIT)的发生率约为1％,而HIT常可致灾难性血栓形成和血栓栓塞并发症(HITT),包括肺栓塞、缺血性肢体坏死、急性心肌梗死(AMI)和中风.此文对HITT的最佳治疗策略给予讨论.有证据表明,肾功能正常的HITT患者应给予阿加曲班或来匹卢定或达那肝素治疗,而肾功能不全的HITT患者应给予阿加曲班治疗.虽然有给HITT患者输注血小板无疑是“火上加油”和增加血栓形成危险的广泛报道,但并没有直接证据能够证明HITT患者输注血小板后可增加血栓形成的风险.     

肝素诱导的血小板减少症

肝素诱导的血小板减少症是一种药物诱导的血小板减少症,是肝素治疗中的一种严重并发症。近年来,有关本病的发生率、发病机理及诊断方法等方面的研究取得了较大进展,并且意见渐趋一致;而有关本病的治疗则尚无较一致的看法。本文拟阐述本病在发病机理、实验室检查、诊断、治疗及预后等方面的最新进展。     

肝素诱导的血小板减少症诊治进展

肝素是临床应用最广泛的抗凝药物之一。肝素诱导的血小板减少症(heparin-induced thrombocytopenia,HIT)是使用肝素所引起的一种严重并发症。概述既往将HIT分为2种类型,即Ⅰ型HIT和Ⅱ型HIT。Ⅰ型HIT,即非免疫介导的肝素相关性血小板减少症,是由肝素与循环血小板直接相互作用,引起血小板聚集和活化,造成的一过性轻度血小板减少,患者常无明显的临床症状,且血小板计数下降时间较短,无需停用肝素即可恢复,是一种良性过程,并不增加使用者的血栓栓塞危险。Ⅱ型HIT,即免疫介导肝素诱导的血小板减少症,其是由于使用肝素     

肝素诱导的血小板减少症抗体试验的诊断性能评价

目的评价肝素诱导的血小板减少症(HIT)抗体试验的诊断性能。方法收集2014年9月至2016年11月HIT患者血浆标本52例,未发生HIT的用肝素治疗患者的血浆标本126例和体检健康者血浆标本50例。根据是否伴有血栓形成,将HIT患者进一步分为未伴血栓形成的孤立性HIT组30例和伴血栓形成的HIT(HITT)组22例。用ACL-TOP 700型血液凝固仪及其相关试剂(Hemos IL HIT-Ab PF4-H)测定血浆HIT混合抗体;用ACL Acu Star发光分析仪及其相关试剂(Hemos IL Acu Star HIT-IgGPF4-H)测定血浆IgG特异性抗体。结果肝素对照患者组的混合抗体和IgG特异性抗体水平高于健康人对照组,差异有统计学意义(U值分别为1 644.0、1 191.0,P均0.01);HIT患者组的两种抗体水平均高于肝素对照患者组(U值分别为550.0和4.7,P均0.01)。ROC曲线结果显示,混合抗体和IgG特异性抗体诊断HIT的敏感性均为100%,上调临界值可提高两个试验的诊断特异性。混合抗体以1.50 U/m L为临界值时,肝素对照患者组的阳性率为27.8%,HIT患者组为100%。IgG特异性抗体以1.51 U/m L为临界值时,在肝素对照患者组的阳性率为0,在HIT患者中为100%。IgG特异性抗体临界值为2.32 U/m L时,评估HIT患者血栓形成风险的诊断敏感性为90.9%,特异性为80.0%;高于此临界值的HIT患者在15 d内的血栓形成累积概率显著增加(Log-rankχ2=56.577,P0.01)。结论 HIT混合抗体试验与IgG特异性抗体试验有助于对HIT患者进行排除诊断、诊断或风险评估。     

肝素／血小板因子4抗体与肝素诱导的血小板减少症

肝素诱导的血小板减少症（heparin—induced thrombocytopenia，HIT）是肝素治疗引起的严重并发症，可导致血栓形成和栓塞。HIT的发病机制主要与肝素／血小板因子4抗体介导的免疫反应有关，IgG类是主要的致病抗体，能与肝素和血小板因子4结合形成复合物，引起血小板凝集和凝血反应增强，同时抗体还通过作用于血管内皮细胞和单核细胞参与HIT的形成。抗体相关的实验室检测包括功能性血小板试验和免疫学试验，临床表现结合实验室检测有助于本病的早期诊断和治疗，但是在检测方面目前尚没有理想的方法。本文就AHPF4抗体、HIT发病机制、临床实验室检测和免疫学试验检测等问题进行了综述。     

肝素诱导的血小板减少症诊治进展

肝素诱导的血小板减少症是一种药物诱导的血小板减少症,伴有抗体反应和血栓形成,是临床使用肝素所引起的一种严重的并发症。本文综述该疾病的发病率及诊断、高凝状态的原因及防治进展。     

肝素诱导血小板减少症的致病性及其实验？…

肝素作为抗凝剂广泛应用于临床。但是，由于肝素的血小板前聚效应（Ｉ型）或者通过免疫机制产生肝素依赖性抗体的损害作用（Ⅱ型）可导致肝素诱导血小板减少症（ＨＩＴ）发生。ＨＩＴ实验诊断除了经典的血小板计数，血小板聚集试验和血小板＾１４Ｃ－５羟色胺释放等试验外，近来ＥＬＩＳＡ也应用于ＨＩＴ的诊断。但国内对ＨＩＴ尚缺乏清醒的认识。本文就ＨＩＴ的致病性实验诊断进展作一简要综述。     

警惕肝素诱导的血小板减少症

肝素目前仍然是临床上应用最广泛抗凝药物之一,肝素诱导的血小板减少症(heparin-induced thrombocytopenia,HIT)是肝素治疗的常见并发症,由于有着很高的病死率,越来越引起人们的重视.     

Intravenous immunoglobulin as an adjunct therapy in persisting heparin-induced thrombocytopenia

Heparin induced thrombocytopenia (HIT) is a serious adverse drug reaction caused by transient antibodies against platelet factor 4 (PF4)/heparin complexes, resulting in platelet activation and potentially fatal arterial and/or venous thrombosis. Most cases of HIT respond to cessation of heparin and administration of an alternative non-heparin anticoagulant, but there are cases of persisting HIT, defined as thrombocytopenia due to platelet activation/consumption for greater than seven days despite standard therapy. These patients remain at high risk for thrombotic events, which may result in limb-loss and mortality. Intravenous immunoglobulin (IVIg) has been proposed as an adjunct therapy for these refractory cases based on its ability to saturate FcγRIIa receptors on platelets, thus preventing HIT antibody binding and platelet activation. We describe 2 cases of persisting HIT (strongly positive antigen and functional assays, and persisting thrombocytopenia >7 days) with rapid clinical response to IVIg. We performed in-vitro experiments to support IVIg response. Healthy donor platelets (1?×?10e6) were treated with PF4 (3.75?μg/mL) for 20?min followed by 1-hour incubation with patients’ sera. Platelet activation with and without addition of IVIg (levels equivalent to those reached in a patient after treatment with 2?gm/Kg) was evaluated in the PF4-dependent P-selectin expression assay (PEA). A significantly decreased platelet activation was demonstrated after the addition of IVIg to both patient samples, which correlated well with the rapid clinical response that each patient experienced. Thus, our study supports the use of IVIg as an adjunct therapy for persisting HIT.     

Catastrophic heparin-induced thrombocytopenia/thrombosis syndrome related to the use of a Port-A-Cath in a breast cancer patient receiving chemotherapy

Heparin-induced thrombocytopenia and thrombosis (HIT/T) syndrome is usually triggered by an immune response after repeated administration of heparin. The syndrome is strongly associated with limb deep vein thrombosis and is potentially life-threatening if unrecognized. We describe the case of a patient with compartment syndrome of the left forearm complicated by HIT/T that developed after Port-A-Cath implantation through the left subclavian vein. Prompt recognition of HIT/T, immediate withdrawal of heparin, and timely institution of thrombolytic therapy successfully prevented limb loss.     

Assays for heparin-induced thrombocytopenia

Tests for the presence of heparin-dependent antibodies (heparin-Ig) have evolved in parallel with improved understanding of the pathophysiology of heparin-induced thrombocytopenia (HIT). The first group of tests relied upon platelet aggregation or activation. Among tests in this group, the serotonin release assay has been reported to demonstrate the best performance characteristics. However, this test has not been widely adopted outside a few specialized laboratories owing to its complexity and need for radioactive materials. As a result, the less sensitive and specific platelet aggregation test is more commonly used for the diagnosis of heparin-Ig. The literature suggests that test sensitivity can be improved by the use of the patient’s own platelets, platelets from selected donors known to be reactive in the assay, or washed platelets. Test specificity has been enhanced by the use of two point assays that include neutralization of the reaction by a high dose of heparin. A second group of assays have focused on detection of heparin-dependent binding of immunoglobulins to the platelet membrane. Most of these tests are hampered by the fact that platelets in patients with suspected HIT and in conditions that are in the differential diagnosis of HIT frequently express high levels of platelet-associated immunoglobulin. The most recent tests for heparin-Ig are based on the recognition that patient antibodies are directed against the heparin-PF4 complex. This has led to the development of the PF4/heparin EIA assay. Because whole platelets are not used in this assay, problems related to under-reactivity or nonspecific reactivity are avoided. In addition, the ability of the test to predict clinical complications may be improved because the test can distinguish IgM from IgG heparin-Ig. Currently the laboratory diagnosis of heparin-Ig remains inexact. The sensitivity and specificity of laboratory assays cannot be firmly established. Much like the diagnosis of the phospholipid syndrome — where use of both the cardiolipin EIA and the lupus anticoagulant test offer overlapping advantages — the combination of the heparin-PF4 EIA plus either a test of platelet activation or a heparin-dependent antibody binding assay may prove to be a more sensitive and specific approach to the diagnosis of heparin-Ig. Despite the progress that has been made in the area of laboratory diagnosis of heparin-Ig, further improvement is needed. Heparin-induced thrombocytopenia is not rare and may be associated with devastating morbidity as well as mortality. Low-molecular-weight heparins usually cross-react with heparin-Ig. Therapy with Org 10172 appears to be the most promising alternative for patients with HIT. Because the clinical diagnosis is uncertain in sick hospitalized patients, further improvements in laboratory assays for heparin-Ig allowing earlier and more accurate diagnosis of patients at risk for HIT will be welcome.     

Prospective evaluation of PF4/heparin immunoassays for the diagnosis of heparin-induced thrombocytopenia

Summary.  Background:  Heparin-induced thrombocytopenia (HIT) is an adverse complication of heparin caused by HIT antibodies that recognize platelet factor 4-heparin (PF4/hep) complexes leading to platelet activation. Several methods are available for the identification of HIT antibodies. Objectives:  To evaluate the clinical usefulness of different antigen-binding assays for detection of antibodies against PF4/hep complexes in a prospective study. Patients/methods:  A prospective cohort of 500 surgical and medical patients suspected of having HIT was evaluated. The laboratory assessment included particle gel immunoassay (PaGIA), polyspecific ELISA recognizing IgG, IgM and IgA antibodies (Poly-ELISA), IgG-specific ELISA (IgG-ELISA) and the HIPA test. The pretest probability of HIT was determined using the 4T's model. Positive and negative predictive values (PPV, NPV) of each immunoassay were determined depending upon the heparin-induced platelet activation (HIPA) results and the clinical scoring. The operating characteristics of each immunoassay were determined using the receiver-operation characteristic (ROC) curve. Results:  Platelet-activating antibodies were identified in 35/500 patients, all of whom had intermediate to high clinical probability. PF4/hep antibodies were detected in 124, 86 and 90 sera using Poly-ELISA (PPV = 28), IgG-ELISA (PPV = 40.6) and PaGIA (PPV = 36.6). NPV was 100% for Poly- and IgG-ELISA, but only 99.5% for PaGIA. ROC analysis revealed that PaGIA is less informative than ELISA. The IgG-ELISA provides better diagnostic information than the other assays. In addition, there is a clear correlation between optical density (OD) value and the probability of having HIT. Conclusions:  Our observation indicates that an IgG-ELISA provides the best diagnostic information of all antigen-binding assays.     

A case of severe COVID-19 with pulmonary thromboembolism related to heparin-induced thrombocytopenia during prophylactic anticoagulation therapy

A 53-year-old male Japanese patient with COVID-19 was admitted to our hospital after his respiratory condition worsened on day 9 of the disease. With the diagnosis of severe COVID-19, treatment with remdesivir, dexamethasone, and unfractionated heparin was started for the prevention of thrombosis. Although the patient's respiratory status data improved after treatment, severe respiratory failure persisted. Thrombocytopenia and D-dimer elevation were observed on day 8 after heparin therapy initiation. Heparin-induced thrombocytopenia (HIT) antibody measured by immunological assay was positive, and contrast computed tomography showed pulmonary artery thrombus. The patient was diagnosed with HIT because the pre-test probability score (4Ts score) for HIT was 7 points. Heparin was changed to apixaban, a direct oral anticoagulant, which resulted in a reduction of the pulmonary thrombus and improvement of the respiratory failure. In patients with COVID-19, anticoagulant therapy with heparin requires careful monitoring of thrombocytopenia and elevated D-dimer as possible complications related to HIT. (151/250 words).     

Thrombosis and ELISA optical density values in hospitalized patients with heparin-induced thrombocytopenia

The natural history of heparin-induced thrombocytopenia (HIT) in the absence of thrombosis was previously established using functional assays for confirmation of diagnosis (e.g. 14C serotonin release assay). An enzyme-linked immunosorbent assay (ELISA) that detects the presence of antibodies directed against the heparin-platelet factor-4 (PF4) complex has largely replaced functional assays in many medical centers. Although the ELISA is highly sensitive for detecting HIT antibodies, its usefulness for predicting thrombotic outcomes has not been clearly established. We performed a retrospective chart review of all hospitalized patients at a university hospital who tested seropositive for HIT by a commercial ELISA during 2001 and 2002. A total of 63 inpatients were identified as HIT positive by ELISA. Forty-eight patients had no apparent HIT-associated thrombosis at the time of HIT seropositivity (i.e. isolated HIT) and only one was treated prophylactically with a direct thrombin inhibitor. The 30-day thrombosis rate for patients with isolated HIT was 17% (eight of 48). Higher ELISA optical density (OD) measurements correlated significantly with thrombosis (1.41 +/- 0.87 vs. 0.79 +/- 0.46, P <0.001). Patients with isolated HIT and an OD measurement of > or = 1.0 demonstrated nearly a 6-fold increased risk of thrombosis compared with those with OD values between 0.4 and 0.99 (odds ratio 5.74, 95% confidence interval 1.73, 19.0; absolute rate of thrombosis, 36% vs. 9%, respectively, P=0.07). We conclude that in hospitalized patients with isolated HIT, the presence of heparin-PF4 antibodies detected by ELISA was associated with a significant risk of subsequent thrombosis and higher ELISA values were observed among patients suffering thrombotic events.     

Treatment of heparin-induced thrombocytopenia

OBJECTIVE: To describe heparin-induced thrombocytopenia (HIT or HIT-2), an immune-mediated adverse reaction to heparin or low-molecular-weight heparin. Available treatment options and considerations in developing a therapy approach are discussed. DATA SOURCES: A search of the National Library of Medicine (1992-June 2001) was done to identify pertinent literature. Additional references were reviewed from selected articles. STUDY SELECTION: Articles related to laboratory recognition and treatment options of HIT, including the use of agents in selected clinical conditions, were reviewed and included. CONCLUSIONS: HIT is a rare but potentially severe adverse reaction to heparin that was, until recently, poorly understood and had limited treatment options. Recent advances describing the recognition and clinical manifestations of immune-mediated HIT, including recently available antithrombotic treatment options, have dramatically changed outcomes for patients having this syndrome.     

Diagnostic score for heparin-induced thrombocytopenia after cardiopulmonary bypass.

Heparin-induced thrombocytopenia (HIT) occurs in nearly 3% of patients treated with heparin after cardiopulmonary bypass (CPB). HIT carries a risk of severe thrombotic complications, and must be diagnosed rapidly. To identify simple criteria for estimating the probability of HIT after CPB, we retrospectively analyzed the files of 84 patients with suspected HIT after CPB and we analyzed the usefulness of several variables collected at the time of HIT suspicion to estimate HIT probability. HIT was confirmed in 35 cases and ruled out in 49 cases, on the basis of a platelet increment after heparin withdrawal, detection of heparin-dependent antibodies, and absence of other clear cause of thrombocytopenia. A biphasic platelet count from CPB to the first day of suspected HIT, an interval of >/= 5 days from CPB to the first day of suspected HIT, and a CPB duration of 相似文献   

Absolute immature platelet counts in the setting of suspected heparin-induced thrombocytopenia may predict anti-PF4-heparin immunoassay testing results

Background

Heparin-induced-thrombocytopenia (HIT) is a disease mediated by antibodies to platelet factor 4 (PF4)-heparin complexes. Immature platelet fraction (%-IPF) and absolute immature platelet count (A-IPC) measure newly-released platelets into circulation and can prove useful in differentiating patients with thrombocytopenic presentations due to consumptive or hypoproduction processes. Therefore, we evaluated utility of A-IPC in a cohort of thrombocytopenic patients suspected of HIT.