药物性血小板减少症

继发性血小板减少症又称获得性血小板减少症,是继发于其他疾病引起的血小板减少。药物所致血小板减少症一般可分为直接破坏血小板型、骨髓抑制型、免疫性血小板减少症。现对其临床相关内容简述如下。1直接破坏血小板型1.1致病药物及发病机制肝素诱发的血小板减少症(HIT)患者10%~20%应用肝素后1~4天发生型HIT,即轻型HIT,血小板计数一般不低于100×109/L。应用肝素后至少5天出现血小板计数降至50×109/L以下,用灵敏的14C血清素释放试验测定肝素依赖性的抗血小板抗体阳性,称为型HIT。此型多发生在应用肝素治疗后5~10(平均7~8)天。一般足…     

肝素诱导的血小板减少症诊断和治疗进展

肝素诱导的血小板减少症(heparin-inducedthrombocytopenia,HIT)是由肝素类药物引起的一种以血小板减少为特征的并发症,主要表现为血小板减少、血小板激活和血栓形成。HIT可分为两型:最常见的为Ⅰ型,主要发生在初次使用普通肝素(UFH)治疗后的1～3d内。通常认为是由大剂量肝素引起血小板和纤维蛋白原结合而导致的一种轻微的血小板减少症,属非免疫系统介导反应[1],表现为血小板计数一过性轻微减少,随着继续应用肝素治疗,血小板计数将会逐渐上升,预后多较好。Ⅱ型HIT亦称肝素诱导的血小板减少和血栓形成(heparin-induced thrombo-cytopeni…     

肝素引起血小板减少症

血小板减少是肝素治疗的一种罕见并发症。本文根据6例的观察探讨其发生机制,着重于研究肝素对血小板聚集的影响。6例中男2例,女4例,年龄25～71岁,平均57岁。在肝素治疗开始后7～13天出现血小板减少并伴有皮下出血(1例)、血栓性病变(2例)、肢端坏疽     

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     

肝素诱导的血小板减少症诊断与治疗

肝素是临床心血管疾病治疗最常用的抗凝药,所有接受肝素治疗的患者,不管接触的剂量及途径,都有可能发生肝素诱导的血小板减少症(HIT),若伴有血栓形成,则称为肝素诱导的血小板减少症伴血栓形成综合征(HITTS).血小板减少一般发生在应用肝素后的第5～14天内,血小板较基础值下降50%或绝对值降至50×109/L～80×109/L,而停用肝素后血小板计数一般可在1周内恢复正常.其临床表现可为无症状的血小板计数减少或广泛的致死性的血栓栓塞症.一旦怀疑HIT,则应立即停用肝素,且禁输血小板治疗,必要时予直接凝血酶抑制剂治疗.     

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…     

低分子肝素诱导的血小板减少症2例并文献复习

目的 探讨肝素诱导的血小板减少症的诊断和治疗的临床特点.方法 2例低分子肝素诱导的血小板减少症患者,通过血细胞分析、凝血五项等检查,诊断为肝素诱导的血小板减少症.结果 经给予停用低分子肝素及补充凝血因子等治疗,恢复良好.结论 低肝素诱导的血小板减少症是一种少见症,临床医生应充分认识这一疾病的特点,并在临床中注意预防.     

低分子肝素治疗102例肺栓塞发生血小板减少8例报道并文献复习

目的 探讨低分子肝素治疗肺栓塞引起血小板减少的原因.方法 对102例肺栓塞病人应用低分子肝素治疗过程中监测血小板情况并进行分析.结果 102例肺栓塞病人经低分子肝素治疗后有8例患者出现血小板减少.结论 低分子肝素治疗肺栓塞时可诱发血小板减少.     

心脏手术围术期肝素诱导的血小板减少症

肝素诱导的血小板减少症(HIT)是肝素治疗引起的严重并发症之一,是一种免疫介导的血栓形成前疾病,它与血栓形成密切相关,在围术期能及时的诊断和治疗非常有意义.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,实验室抗体检测结合临床有助于早期诊断.而替代性药物抗凝治疗是治疗HIT的有效措施.     

动脉粥样硬化的抗栓和抗凝治疗

在由动脉粥样硬化引起的冠心病、缺血性脑卒中和外周动脉病中,抗血小板和抗凝治疗是主要的措施之一.抗血小板治疗可以减少血小板聚集,防治斑块上形成白色血小板血栓,肝素或低分子量肝素则可以防止白色血栓基础上进一步形成红色血栓完全阻塞动脉.阿司匹林、氯吡格雷是目前最常用的抗血小板药物,而肝素或低分子量肝素是目前最常用的抗凝药物.     

Heparin-induced thrombocytopenia in hemodialysis. Case report and review of the literature

Thrombocytopenia is a potential complication of heparin therapy. There are two forms of heparin-induced thrombocytopenia (HIT). Type-I HIT is characterized by a mild decrease in platelet count that occurs within the first 2-4 days after heparin initiation. The platelet count often returns to normal without stop heparin treatment. The mechanism of thrombocytopenia appears to be due to a direct effect of heparin on platelet activation. The second form (type-II) is an immune-mediated disorder characterized by severe thrombocytopenia, which may include both arterial and venous thrombosis. We present a case of type-II HIT occurred in a hemodialysis patient resulting in acute pulmonary embolism and peripheral venous thrombosis, and review the literature.     

The prothrombotic potential of platelet factor 4

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder initiated by heparin administration. It is caused by the formation of pathogenic antibodies to complexes of platelet factor-4 (PF4) and heparin on platelet surfaces that cause platelet activation, aggregation and thrombosis. There has been intense research on this intriguing, drug-related thrombocytopenia explaining several characteristic aspects of this condition. However, prothrombotic potential of the key player, PF4 has not been investigated in many studies although it has been shown to be critical in monocyte chemotaxis, monocyte–platelet interaction, and megakaryocyte suppression, all of which can contribute to the pathophysiology of HIT. This article explains the important role of PF4 released during platelet activation with the administration of heparin in the pathogenesis of thrombocytopenia and thrombosis in HIT.     

Heparin-induced thrombocytopenia: an overview

Heparin-induced thrombocytopenia (HIT) is the most important immunological drug reaction that patients face today. HIT typically develops in patients 5 days after starting heparin therapy, but can occur sooner with recent heparin exposure or rarely have a delayed onset. The platelet count typically drops below 150 x 10(9)/L (average 60 x 10(9)/L), and patients may experience a thrombotic episode simultaneously or shortly after the onset of thrombocytopenia. The thrombocytopenia and the associated thrombotic episodes are now considered to be overlapping outcomes of the same syndrome. The pathophysiology of HIT has been characterized: immune complexes of IgG and heparin in association with a small platelet peptide, platelet factor 4 (PF4), activate platelets by binding to the Fc receptors (FcR) and releasing procoagulant-active, platelet-derived microparticles. The recognition that HIT is characterized by intense thrombin generation dictates the use of antithrombin agents in HIT therapy. Therapeutic approaches that are currently prevalent in the management of HIT will be discussed.     

Antithrombotic therapy in heparin-induced thrombocytopenia: guidelines translated for the clinician

Heparin-induced thrombocytopenia (HIT) is a clinicopathologic syndrome initiated by heparin exposure and characterized by thrombocytopenia and paradoxical thrombophilia. HIT is mediated by the formation of antibodies against the platelet factor 4/heparin complex, which leads to platelet activation, thrombin generation, and potentially fatal thrombotic sequelae. The clinical presentation of HIT is variable and can be easily overlooked. Although a number of functional and antigen-based immunoassays have been developed to detect the presence of HIT antibodies, initial diagnosis is often based on recognition of thrombocytopenia in the appropriate clinical context and later confirmed with immunologic testing. Given the serious clinical consequences of HIT, immediate cessation of heparin products and administration of non-heparin anticoagulants are crucial components of treatment. We provide a review of the clinical syndrome and practical summary of treatment recommendations from the most recent 2012 American College of Chest Physicians evidence-based guidelines for the treatment and prevention of HIT.     

Heparin-induced thrombocytopenia: a frequent complication after cardiac surgery

Thrombocytopenia is a common problem in cardiovascular patients, and heparin-induced thrombocytopenia (HIT) is therefore frequently suspected. Unfractionated heparin during cardiopulmonary bypass is particularly immunogenic as 25% to 50% post-cardiac surgery patients develop heparin-dependent antibodies but only 1 to 3% will develop HIT. These antibodies recognize a 'self protein', platelet factor 4 (PF4), bound to heparin. Antibodies associated with a high risk of HIT are mainly IgG1 which strongly activate platelets and coagulation, thereby causing thrombocytopenia and thrombosis. A biphasic evolution of platelet count with a secondary decrease after a previous increase following CPB or non-recovery of thrombocytopenia within 6 days post-operatively always requires screening for HIT antibodies. Both functional (platelet activation tests) and immunologic assays (antigen assays) are necessary in every patient to establish the diagnosis of HIT. When the clinical probability of HIT is high, the first requirement is to discontinue heparin, without waiting for results of laboratory investigations. An alternative anticoagulant such as danaparoid sodium (Orgaran) or lepirudin (Refludan) must then be administered since heparin withdrawal alone is insufficient to control the prothrombotic state associated with HIT. The risk of HIT will probably soon decrease due to the wider use of fondaparinux, which does not interact in vitro with PF4, but it could remain significant in patients undergoing cardiac surgery with CPB.     

Delayed-onset HIT caused by low-molecular-weight heparin manifesting during fondaparinux prophylaxis

Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition caused by platelet-activating antibodies that react with platelet factor 4 (PF4)/heparin complexes. Delayed-onset HIT occurs after heparin is stopped. Fondaparinux, a synthetic pentasaccharide, is thought to be a safe alternative anticoagulant in HIT. We describe a patient with delayed-onset HIT triggered by low-molecular-weight heparin (LMWH) which occurred during fondaparinux prophylaxis and which was complicated by microangiopathic hemolytic anemia. Patient serum contained high-titer anti-PF4/heparin antibodies demonstrating heparin-dependent platelet activation with serial dilutions. Confirmed delayed-onset HIT with LMWH has not been previously reported. Low dose fondaparinux does not necessarily prevent thrombotic complications of HIT.     

Bilateral lower extremity gangrene requiring amputation associated with heparin-induced thrombocytopenia: a case report

Heparin is a common cause of thrombocytopenia in hospitalized patients. Between 10% and 15% of patients receiving therapeutic doses of heparin develop thrombocytopenia. Heparin-induced thrombocytopenia (HIT) can cause severe bleeding and thrombosis owing to intravascular platelet aggregation. HIT must be distinguished from other causes of thrombocytopenia. Importantly, heparin use is often associated with an early fall in the platelet count that usually occurs within the first 4 days of initiation and recovers without cessation of heparin treatment. This nonimmune heparin-associated thrombocytopenia has not been found to be associated with thrombosis and does not necessitate discontinuation of heparin. The authors present a case report of a 70-year-old man who received heparin therapy following aortic tissue valve replacement and aortic root repair with graft and developed bilateral lower extremity arterial clots 6 days postoperatively in the setting of positive heparin antibody titers. Ultimately the patient required bilateral above-knee amputations.     

Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications

Heparin-induced thrombocytopenia (HIT) antibodies recognize complexes between heparin and platelet factor 4 (PF4). Heparin and PF4 bind HIT antibodies only over a narrow molar ratio. We explored the involvement of platelet surface-bound PF4 as an antigen in the pathogenesis of experimental HIT. We show that cell-surface PF4 complexes are also antigenic only over a restricted concentration range of PF4. Heparin is not required for HIT antibody binding but shifts the concentration of PF4 needed for optimal surface antigenicity to higher levels. These data are supported by in vitro studies involving both human and murine platelets with exogenous recombinant human (h) PF4 and either an anti-PF4-heparin monoclonal antibody (KKO) or HIT immunoglobulin. Injection of KKO into transgenic mice expressing different levels of hPF4 demonstrates a correlation between the severity of the thrombocytopenia and platelet hPF4 expression. Therapeutic interventions in this model using high-dose heparin or protamine sulfate support the pathogenic role of surface PF4 antigenic complexes in the etiology of HIT. We believe that this focus on surface PF4 advances our understanding of the pathogenesis of HIT, suggests ways to identify patients at high risk to develop HIT upon heparin exposure, and offers new therapeutic strategies.     

Heparin-induced thrombocytopenia

Hemorrhage is the most common and best-recognized complication of heparin treatment. However, a potentially more dangerous complication is the development of heparin-induced thrombocytopenia (HIT). All patients exposed to heparin, irrespective of the dose and route of administration, are at risk of developing HIT. It is due to the formation of antibodies against the heparin-platelet factor 4 complex, which cause secondary activation of platelets, coagulation and, finally, increased thrombin production. The main symptom is the sudden onset of thrombocytopenia involving a drop in the platelet count to less than 50% of the basal level, with or without the appearance of thrombotic complications some 5 to 14 days after the start of heparin therapy. Heparin-induced thrombocytopenia can be detected early in patients receiving heparin by monitoring the platelet count. Demonstration of heparin-dependent platelet activation using an antigen or functional assay confirms the clinical diagnosis. Once the diagnosis of HIT has been confirmed serologically or there is a high level of suspicion of HIT, heparin must be suspended and treatment with an alternative anticoagulant should be considered. This review contains a discussion of the diagnosis and treatment of this syndrome.     

PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI

Heparin-induced thrombocytopenia (HIT) is a potentially devastating form of drug-induced thrombocytopenia that occurs in patients receiving heparin for prevention or treatment of thrombosis. Patients with HIT develop autoantibodies to the platelet factor 4 (PF4)/heparin complex, which is termed the HIT Ab complex. Despite a decrease in the platelet count, the most feared complication of HIT is thrombosis. The mechanism of thrombosis in HIT remains poorly understood. We investigated the effects of the HIT Ab complex on tissue factor (TF) expression and release of TF-positive microparticles in peripheral blood mononuclear cells and monocytes. To model these effects ex vivo, we used a murine mAb specific for the PF4/heparin complex (KKO), as well as plasma from patients with HIT. We found that the HIT Ab complex induced TF expression in monocytes and the release of TF-positive microparticles. Further, we found that induction of TF is mediated via engagement of the FcγRI receptor and activation of the MEK1-ERK1/2 signaling pathway. Our data suggest that monocyte TF may contribute to the development of thrombosis in patients with HIT.