Clinical analysis of critically ill children with heparin-induced thrombocytopenia during extracorporeal membrane oxygenation / 中国小儿急救医学

Objective:To prospectively investigate the prevalence of heparin-induced thrombocytopenia (HIT) in critically ill children during extracorporeal membrane oxygenation(ECMO) and explore the clinical characteristics and prognosis of HIT during ECMO.Methods:A total of 22 critically ill children, who had received ECMO support for more than 96 hours in the Intensive Care Unit at the Children′s Hospital of Fudan University from March 2019 to December 2020, were enrolled.According to the 4T score and the heparin/platelet factor 4(PF4) antibody, children whose 4T scores were not less than 6 and heparin/ PF4 antibodies were positive, were classified into HIT group ( n=6), and non-HIT group ( n=16). The clinical outcomes and the incidence of thrombotic events were compared between two groups. Results:The incidence of HIT during ECMO in critically ill children was 27% in this study.The incidence of thrombosis in the ECMO circuit in the HIT group was higher (100% vs.63%, P=0.133), and the average time to the first thrombosis in ECMO circuit in the HIT group was shorter than that in the non-HIT group (3.70 d vs.5.44 d, P=0.06). During the first 14 days of ECMO, the proportion of children with thrombotic events no less than twice was higher in the HIT group (67% vs.19%, P=0.054). There was no significant difference regarding the survival rate at 28 days after ECMO withdrawal between two groups (33% vs.50%, P=0.664). Conclusion:The prevalence of HIT during ECMO in critically ill children is high.Thrombosis events tend to occur earlier and more extensively in children with HIT during ECMO.No significant effect of HIT on the survival rate of children during ECMO is found.Whether HIT has effect on the survival rate of children with ECMO requires a prospective and large clinical study.

Acute renal failure due to bilateral renal vein thromboses: A rare complication of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia type II is a rare but devastating complication of heparin exposure. We review a case of a 66-year-old female who underwent aortic valve surgery requiring venoarterial extracorporeal membranous oxygenation (ECMO) support postoperatively. She subsequently developed acute renal failure due to bilateral renal vein thromboses and thrombocytopenia and was found to have platelet factor 4/heparin antibodies and was diagnosed with heparin-induced thrombocytopenia (HIT). She was transitioned to nonheparin anticoagulation and her thrombocytopenia improved. Although a rare complication of anticoagulation, diagnosing HIT in a patient on ECMO requires a high index of suspicion and should be considered.

Diagnostic value of two immunoassays for detecting heparin/PF4 complex antibodies in heparin-induced thrombocytopenia / 中华血液学杂志

Objectives@#To assess the diagnostic values of latex immunoturbidimetric assay (LIA) and particle immunofiltration assay (PIFA) for heparin-induced thrombocytopenia (HIT) .@*Methods@#Samples from 94 patients with suspected HIT from May 2016 to July 2018 in our hospital were prospectively analyzed by the two immunoassays. Their medical records and further follow-up data were also collected and analyzed by our hematologists to make the 4Ts scores and confirm the diagnosis of HIT, respectively. Performance characteristics of the two immunoassays were assessed, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) . Their post-test probabilities (PTP) were also calculated based on the 4Ts score.@*Results@#Among 94 cases, 15 (16.0%) had a positive HIT, including 6 of 37 (16.2%) with an intermediate, and 9 of 15 (60.0%) with a high 4Ts score. PIFA operating characteristics were: sensitivity 100.0% (15/15) , specificity 51.9% (41/80) , PPV 28.3% (15/53) , NPV 100.0% (41/41) . The positive PTP in intermediate and high 4Ts score group were 28.7% and 75.7%, respectively, while negative PTP were all 0. At manufacturers’ cutoffs, LIA operating characteristics were: sensitivity 66.7% (10/15) , specificity 94.9% (75/79) , PPV 71.4% (10/14) and NPV 93.8% (75/80) . The positive and negative PTP in intermediate 4Ts score group were 71.8% and 6.3%, while 95.2% and 34.4% in high 4Ts score group, respectively. Receiver operating characteristic (ROC) analysis manifested that LIA was preferable than PIFA, and combining the 2 assays together was significantly better than single test.@*Conclusions@#4Ts score is still an important tool for the diagnosis of HIT. Combining clinical score with heparin/PF4 antibody assay can increase the accuracy of confirming or excluding HIT. Although PIFA is inferior to LIA in the diagnostic value, its user friendliness and 100% NPV have major advantages. Combining the 2 assays together can achieve a higher diagnostic value.

Prospective evaluation of heparin-induced thrombocytopenia expert probability and 4T scores in Chinese patients with suspected heparin-induced thrombocytopenia / 中华医学杂志(英文版)

Background@#Diagnosis of heparin-induced thrombocytopenia (HIT) is challenging. This study aimed to compare the diagnostic performance of HIT expert probability (HEP) and 4T scores, and to evaluate the inter-observer reliability for the 4T score in a clinical setting.@*Methods@#This prospective study included HIT-suspected patients between 2016 and 2018. Three hematologists assessed the HEP and 4T scores. Correlations between scores and anti-platelet factor 4 (anti-PF4)/heparin antibodies were evaluated. Receiver operating characteristic curves and area under the curve (AUC) were used to assess the predictive accuracy of these two scoring models. The intraclass correlation coefficient (ICC) was used to assess the inter-observer agreement of 4T scores between residents and hematologists.@*Results@#Of the 89 subjects included, 22 (24.7%) were positive for anti-PF4/heparin antibody. The correlations between antibody titer and either HEP or 4T scores were similar (r = 0.392, P < 0.01 for the HEP score; r = 0.444, P < 0.01 for the 4T score). No significant difference in the diagnostic performance was displayed between these two scores (AUC for the HEP score: 0.778 vs. AUC for the 4T score: 0.741, P = 0.357). Only 72 4T scores were collected from the residents, with a surprisingly low percentage of observers (43.1%) presenting the four individual item scores which made up their 4T score. The AUC of 4T score assessed by residents and hematologists was 0.657 (95% confidence interval [CI]: 536–0.765) and 0.780 (95% CI: 0.667–0.869, P < 0.05), respectively. The ICC of 4T score between residents and hematologists was 0.49 (95% CI: 0.29–0.65, P < 0.01), demonstrating a fair inter-observer agreement.@*Conclusions@#The HEP score does not display a better performance for predicting HIT than the 4T score. With the unsatisfactory completion rate, the inter-observer agreement of 4T score in a tertiary hospital is fair, underscoring the necessity for continuing education for physicians.

Anticoagulant Therapy for an Acute Pulmonary Embolism Patient with Renal Insufficiency and Thrombo-cytopenia / 中国药师

The article analyzed an anticoagulant treatment regimen for a patient with acute pulmonary embolism and discussed the drug treatment strategy when the patient had renal insufficiency and thrombocytopenia. After fully evaluating the advantages and disad-vantages, unfractionated heparin was firstly applied under the monitoring of activate partial thrombin time, platelet counts and hemor-rhage. When the renal function was improved, low molecular weight heparin replaced unfractionated heparin. Finally, long-term warfa-rin therapy was conducted. The efficacy monitoring included symptoms, thrombosis,respiratory cycle indicators and indicators of extra-pulmonary organ function, such as serum creatinine, transaminases and pro-brain natriuretic peptides. Adverse reaction monitoring in-cluded bleeding and assessing the risk of heparin-related thrombocytopenia based on the characteristics of reduced platelet counts. After the adequate anticoagulant therapy, the patient's symptoms were relieved, liver and kidney functions were improved without significant bleeding and heparin-related thrombocytopenia. When patients have a variety of complications resulting in increased risk of drug treat-ment, the treatment regimen should be based on drug efficacy and adverse reaction characteristics. Assessing patients' prognosis and choosing a controllable treatment regimen are the keys to reducing treatment risk.

A Case of Surgical Ventricular Restoration with Heparin-Induced Thrombocytopenia Type II / 日本心臓血管外科学会雑誌

A 67-year-old man with dilated cardiomyopathy was admitted to our hospital for treatment of cardiac failure. After using heparin because cerebral infarction developed during hospitalization, in acknowledgment of thrombocytopenia, we reach the diagnosis of HIT. We judged surgery to be necessary because heart failure had difficulty with catecholamine secession and the left ventricular dilation progressed rapidly, and performed left ventriculoplasty, mitral valve plasty. There were no complications such as the thrombosis during cardiopulmonary bypass, and the postoperative course was good without leading to re-thoracotomy due to bleeding. He passes without a heart failure symptom by the follow of one year 6 months after surgery at home.

A Surgery Case of Heparin-Induced Thrombocytopenia as a Complication of Ventricular Septal Perforation after Acute Myocardial Infarction / 日本心臓血管外科学会雑誌

<p>A 66-year-old man with an unknown medical history developed chest pain and a diagnosis of acute myocardial infarction (AMI) was given by his physician. Percutaneous coronary intervention was performed in the left anterior descending artery. Echocardiography revealed ventricular septal perforation (VSP) ; therefore, the patient was transferred to our hospital. After admission, his platelet count dropped rapidly during heparin administration, and left ventricular thrombosis and deep vein thrombosis were noted, raising a suspicion of heparin-induced thrombocytopenia (HIT). To establish cardiopulmonary bypass, argatroban alone was insufficient to prolong the Powered by Editorial Manager^® and ProduXion Manager^® from the Aries Systems Corporation activated clotting time (ACT) ; thus, nafamostat mesilate was also used for coronary artery bypass grafting and surgical repair of VSP. It took many hours to normalize the ACT, requiring re-exploration for excessive bleeding. On the 37th postoperative day, the patient was transferred to another hospital. We performed cardiac surgical procedures using argatroban in a patient who developed HIT during the course of VSP following AMI ; however, we had difficulty in controlling the ACT. Since, to the best of our knowledge, there are no previous studies reporting surgical case of VSP complicated by HIT, we present this case with a review of the relevant literature.</p>

Research advances in heparin-induced thrombocytopenia / 介入放射学杂志

Clinically,heparin-induced thrombocytopenia (HIT) is an uncommon but serious disease,which is induced by the use of immune unfractionated heparin or low-molecular-weight heparin.The overall incidence of HIT is about 0.6％-5.0％.Nevertheless,in clinical practice it is profoundly dangerous,especially for patients who are receiving cardiovascular surgery or interventional therapy.At present,HIT is a hot clinical research subject.This paper aims to make a brief review about HIT pathogenesis,epidemiology,clinical evaluation and treatment,etc.

Assessment on antibody test for diagnosis performance of heparin induced thrombocytopenia / 临床检验杂志

Objective To assess the antibody test for the diagnosis performance of heparin induced thrombocytopenia(HIT).Methods 52 plasma samples of patients with HIT,126 plasma samples of heparin treated patients without HIT and 50 plasma samples of healthy individuals were collected from 2014 September to 2016 November.According to thrombosis,the patients were further divided into two groups:isolated HIT group without thrombosis (30 cases) and heparin induced thrombocytopenia with thrombosis (HITY) group (22 cases).The whole HIT antibody in plasma was assayed by using ACL-TOP 700 coagulation analyzer and reagent (HemosIL HIT-AbPF4-H).The IgG-specific HIT antibody in plasma was assayed by using ACL AcuStar chemiluminescent analyzer and reagent (HemosIL AcuStar HIT-IgGPF4-H).Results The levels of whole antibody and IgG-specific antibody in the patients of heparin control group was higher than those in healthy control (U value was 1 644.0 and 1 911.0,respectively,P ＜ 0.01).The levels of two HIT antibodies in HIT patients group were higher than those in the patients of heparin control group (U value was 550.0 and 4.7,respectively,P ＜ 0.01).ROC curve showed that the sensitivities of both whole antibody and IgG-specific antibody were 100％,and up-regulating the cut-off value could improve the specificity of both tests.The positive incidence of the whole antibody was 27.8％ in the heparin control group and 100％ in HIT patients group while the cut-off value was 1.50 U/mL.The positive incidence of IgG-specific antibody was 0 in the heparin control group and 100％ in the HIT patients group while the cut-off value was 1.51 U/mL.While the cut-off value of IgG-specific antibody was 2.32 U/mL,the diagnosis sensitivity of thrombosis assessment was 90.9％ and the specificity was 80.0％.In case the cut-off value exceeded 2.32 U/mL,the accumulating risk of HIT increased significantly in HIT patients within 15 days (Log-rank x2 =56.577,P ＜ 0.01).Conclusion The whole antibody and IgG-specific antibody could contribute to excluding diagnosis,diagnosis or risk assessment for the suspected HIT patients.

Perfil de seguridad de bemiparina como tromboprofilaxis en pacientes crítico / Safety profile of bemiparin thromboprofilaxis in critically III patients / Perfil de segurança da bemiparina como tromboprofilaxia em pacientes en estado crítico

Resumen: Introducción: La enfermedad tromboembólica es una causa prevenible de mortalidad en pacientes críticamente enfermos. La estrategia de tromboprofilaxis más utilizada es el uso de heparinas de bajo peso molecular; sin embargo, no se conoce cuál es superior. La bemiparina presenta características farmacológicas favorables. Objetivo: Evaluar el perfil de seguridad de la tromboprofilaxis con bemiparina en pacientes críticos. Material y métodos: Se trata de un estudio retrospectivo y observacional. Se incluyeron pacientes hospitalizados en la Unidad de Cuidados Intensivos de Adultos entre diciembre de 2013 y junio de 2015 que recibieron bemiparina. Se evaluó la presencia de sangrado mayor, trombocitopenia y correlaciones entre la dosis administrada y la presencia de eventos adversos. Resultados: 111 pacientes críticos recibieron bemiparina como tromboprofilaxis. No hubo episodios de enfermedad tromboembólica. Seis punto tres por ciento de los pacientes presentaron sangrado mayor durante su estancia. La incidencia de trombocitopenia severa fue de 1.8%, 8.6% presentó descenso en la cuenta plaquetaria sugerente de trombocitopenia inducida por heparina; no obstante, no se documentó ningún caso. Los efectos adversos no se asociaron a mayores dosis de bemiparina. Conclusiones: La seguridad de la tromboprofilaxis con bemiparina es comparable con el resto de las heparinas de bajo peso molecular (HBPM) en pacientes críticamente enfermos.

Abstract: Introduction: Venous thromboembolism is a preventable cause of death in critically ill patients. The most common thromboprophylaxis strategy is the use of low molecular weight heparins, however it is not known which is superior. Bemiparin shows a favorable pharmacologic profile. Objective: Evaluate the safety profile of bemiparin thromboprophylaxis in the critically ill. Materials and methods: This retrospective observational trail was carried out in an adult intensive care unit. Patients hospitalized between December 2013 and June 2015 receiving bemiparin throboprophylaxis were included. The presence of major bleeding, thrombocytopenia and the correlation between dose and adverse events was noted. Results: 111 critically ill patients received bemiparin thromboprophylaxis No episodes of venous thromboembolism were recorded. 6.3% of patients had a major bleeding episode during their intensive care unit stay. The incidence of severe thrombocytopenia was 1.8%, while 8.6% of patients had a platelet count decrease typical of heparin induced thrombocytopenia, no cases were recorded. Adverse events were not associated with bemiparin dose. Conclusions: The safety of bemiparin thromboprofilaxis is similar to that of other Low Molecular Weight Heparins (LMWH) in critically ill patients.

Resumo: Antecedentes: A doença tromboembólica é uma causa evitável de morte em pacientes em estado crítico. A estratégia tromboprofiláxica mais utilizada é o uso de heparinas de baixo peso molecular, no entanto, não é conhecido qual é superior. A bemiparina apresenta características farmacológicas favoráveis. Objetivo: Avaliar o perfil de segurança da tromboprofilaxia com bemiparina em pacientes em estado crítico. Material e métodos: Estudo retrospectivo observacional na unidade de terapia intensiva de adultos. Foram incluídos pacientes hospitalizados na unidade de terapia intensiva que receberam bemiparina entre dezembro de 2013 e junho 2015. Avaliou-se a presença de hemorragia grave, trombocitopenia e correlações entre doses administrada e a presença de eventos adversos. Resultados: 111 pacientes em estado crítico receberam bemiparina como tromboprofilaxia. Não houve episódios de tromboembolismo. 6.3% dos pacientes apresentaram sangramento maior durante a sua estadia. A incidência de trombocitopenia grave foi de 1.8%, 8.6% apresentaram uma diminuição na contagem de plaquetas sugestivos de trombocitopenia induzida pela heparina, porém não se documentou nenhum caso. Os efeitos adversos não se associaram com a doses mais elevadas de bemiparina. Conclusão: A segurança de tromboprofilaxia bemiparina é comparável com o resto do Heparina de baixo peso molecular (HBPM) em pacientes em estado critico.

Anticoagulants in dermatology.

Anticoagulants are the cornerstone of treatment of venous thromboembolism associated with various medical conditions and surgical procedures. They act on different steps of the coagulation pathway and are broadly categorized into heparins, vitamin K antagonists, and inhibitors of thrombin and factor Xa. The classification is evolving as newer and better oral and parenteral anticoagulants are being added. Anticoagulants in dermatology are important not only for their therapeutic application in cutaneous thrombotic dermatoses such as livedoid vasculitis, purpura fulminans, superficial and deep venous thrombosis and others but also for their use in non‑thrombotic dermatoses such as lichen planus, recurrent oral aphthosis, chronic urticaria and several others. Further, the use of anticoagulants for any indication is associated with various adverse effects with dermatologic manifestations including specific reactions such as warfarin‑induced skin necrosis, heparin‑induced thrombocytopenia and anticoagulant‑associated cholesterol embolization syndrome.

Trombocitopenia inducida por heparina: Nuevas opciones terapéuticas / Heparin-induced thrombocytopenia. New therapeutical options

La trombocitopenia inducida por heparina (TIH) es una reacción adversa inmunológica mediada por la formación de anticuerpos contra el complejo heparina-factor plaquetario 4 (FP4), caracterizada por la presencia de trombocitopenia y la asociación paradojal de trombosis arterial o venosa. Es una complicación poco frecuente pero grave del uso de cualquier tipo de heparina. En tratados con procedimientos cardiovasculares como intervención coronaria percutánea y cirugía de revascularización cardiaca, la prevalencia de anticuerpos es significativamente mayor que en otros escenarios clínicos. El reconocimiento de las características clínicas y de laboratorio permite la suspensión inmediata de la heparina y la instauración de tratamiento anticoagulante alternativo, para evitar la progresión y formación de nuevos trombos y sus complicaciones. En la presente revisión se resumen las diferentes alternativas terapéuticas para la TIH, en particular los anticoagulantes orales directos (DOACS) como el dabigatran, rivaroxaban y apixaban que pueden proporcionar una nueva opción para el tratamiento de TIH.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.

The role of side stream dark field microvasculature imaging in a rare case of vancomycin‑resistant enterococcal endocarditis complicated by heparin‑induced thrombocytopenia.

Sidestream dark field (SDF) imaging allows direct visualization of microvascular architecture and function. We examine the role of an SDF imaging device in visualizing the sub‑lingual microvasculature as a surrogate for splanchnic microperfusion. We demonstrate good correlation between current monitoring techniques and the SDF imaging device in a rare case of vancomycin‑resistant enterococcal (VRE) sepsis along with heparin‑induced thrombocytopenia (HIT). To the best of our knowledge, VRE endocarditis with concurrent HIT has not been described in literature. The role of SDF imaging may predict the earlier need for escalation of care, improving morbidity and mortality.

Dabigatran approaching the realm of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a serious, immune mediated complication of exposure to unfractionated or low-molecular-weight heparin. Though rare, it is a condition associated with high morbidity and mortality that requires immediate change to alternative anticoagulants for the prevention of life-threatening thrombosis. The direct thrombin inhibitors lepirudin and argatroban are currently licensed for the treatment of HIT. Dabigatran, a novel oral anticoagulant (NOAC) with a similar mechanism of action and effective use in other indications, has recently been proposed as another therapeutic option in cases of HIT. This review serves as an introduction to using dabigatran for this purpose, detailing the clinical aspects of its administration, evidence of its performance compared to other anticoagulants, and the preliminary reports of HIT successfully treated with dabigatran. As the literature on this develops, it will need to include clinical trials that directly evaluate dabigatran against the other NOACs and current treatment options.

Off-Pump Coronary Artery Bypass Grafting for an Unstable Angina Pectoris Complicated by Heparin-Induced Thrombocytopenia Diagnosed after Introducing Hemodialysis / 日本心臓血管外科学会雑誌

<p>A 53-year-old man was urgently hospitalized with chronic renal failure, congestive heart failure, pulmonary edema, and pneumonia. He received respiratory support and dialysis after hospitalization in the intensive care unit. Coronary arteriography revealed an old myocardial infarction and unstable angina (triple vessel disease). Surgery was planned. However, after dialysis under heparin administration, clot formation was noted in the dialyzer. Serological tests confirmed the presence of antibodies to heparin-platelet factor 4 complex ; accordingly, heparin-induced thrombocytopenia (HIT) was diagnosed. Coronary artery bypass surgery should preferably be performed early in the case of coronary artery disease. However, surgery during the acute phase of HIT when antibodies to heparin-platelet factor 4 complex (HIT antibodies) are present is associated with a very high risk of developing thromboembolism. There is no criterion regarding the optimal timing for surgery when HIT antibodies are present. Therefore, clinicians are often confused about this. In cases where the platelet count, D-dimer level, fibrinogen degradation product (FDP) level, and fibrinogen level improve, thrombin production due to HIT antibodies is thought to decrease. We considered that the improvement in these values suggests that the number of HIT antibodies decreases and thus HIT antibody activity would be reduced. We evaluated the platelet count, D-dimer level, FDP level, and fibrinogen level over time and accordingly determined the optimal timing for surgery. In the present case, argatroban administration was started after HIT developed, and the platelet counts increased gradually ; the D-dimer and FDP levels decreased, whereas there were no significant changes in the fibrinogen levels. Although HIT antibodies were still present, we performed off-pump coronary artery bypass grafting under the administration of argatroban when the platelet count, D-dimer, and FDP values improved. The patency of coronary bypass grafts was confirmed postoperatively ; the patient did not develop thromboembolism during the perioperative period and was discharged without complications. When HIT antibodies are present, an improvement in platelet count, D-dimer, and FDP values is thought to be useful in determining the optimal timing of surgery.</p>

Diagnosis and treatment of heparin-induced thrombocytopenia / 国际外科学杂志

Heparin-induced thrombocytopenia is a profoundly dangerous,potentially lethal,immunologically mediated adverse drug reaction to unfractionated heparin or low-molecular weight heparin.Clinical vigilance of this disease process is important to ensure its recognition,diagnosis,and treatment.Misdiagnosis of the syndrome,as well as misunderstanding of the disease process,continues to contribute to its morbidity and mortality.In this comprehensive review,the authors highlight heparin-induced thrombocytopenia's clinical presentation,diagnostic principles,and treatment.

Tratamiento exitoso con fondaparinux en trombocitopenia inducida por heparina y trombosis / Successful treatment with fondaparinux in heparin-induced thrombocytopenia and thrombosis

La trombocitopenia inducida por heparina (TIH) es una reacción adversa inmunológica caracterizada por trombocitopenia y la asociación paradojal de trombosis arterial o venosa. Es causada por la formación de anticuerpos IgG contra el complejo multimolecular de heparina-factor plaquetario 4 (FP4). Fondaparinux es un inhibidor selectivo del factor Xa que tiene escasa afinidad por el FP4 y posee un menor potencial para inducir una respuesta inmunológica, haciendo del mismo un agente potencialmente útil en el tratamiento de la TIH. Se presenta el caso de una mujer de 73 años con TIH asociada a fenómenos trombóticos arteriales y venosos, que recibió exitosamente fondaparinux, con normalización del recuento plaquetario y sin progresión trombótica.

Heparin induced thrombocytopenia (HIT) is an immune-mediated adverse reaction characterized by thrombocytopenia and paradoxical arterial or venous thrombosis, due to the formation IgG antibodies directed to a multimolecular complex of heparin-platelet factor 4 (PF4). Fondaparinux is a selective factor Xa inhibitor with little affinity for PF4 and thus less likely to induce an immune response, making fondaparinux a potentially useful drug for the treatment of HIT. Herein we report the case of a 73 years old woman with HIT associated with arterial and venous thrombosis that was successfully treated with fondaparinux, with normalization of the platelet countand without progression of thrombosis.

Performance of Four Anti-Heparin/Platelet Factor 4 Immunoassays for the Diagnosis of Heparin-Induced Thrombocytopenia

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a significant complication of heparin therapy induced by antibodies to heparin/platelet factor 4 (PF4) complexes. We investigated the diagnostic performance of four commercial immunoassays that detect the anti-heparin/PF4 antibody. METHODS: Four different anti-heparin/PF4 antibody assays were performed in 39 patients with suspected HIT: HemosIL AcuStar HIT-IgG, HemosIL AcuStar HIT-total antibody (Ab) (Instrumentation Laboratory, USA), STic Expert HIT (Diagnostica Stago, France), and PF4 Enhanced (Immucor GTI Diagnostics, USA). Patients were diagnosed with HIT when the Chong score was > or =5. RESULTS: The estimated sensitivity and specificity for diagnosis of HIT were 33.3% and 80.0% for AcuStar HIT-IgG, 55.6% and 53.3% for AcuStar HIT-total Ab, 100.0% and 37.9% for STic Expert HIT, and 33.3% and 66.7% for PF4 Enhanced. All specificities significantly increased when 4Ts scores were included in the diagnosis. The areas under the curves (AUCs) for predicting thrombosis in the AcuStar HIT-IgG, AcuStar HIT-total Ab, and PF4 Enhanced assays were 0.639, 0.522, and 0.681, respectively. When the results of each assay were analysed along with 4Ts scores, the AUC increased to 0.927 in the AcuStar HIT-IgG assay and 0.944 in the AcuStar HIT-total Ab and PF4 Enhanced assays. CONCLUSIONS: The STic Expert HIT assay had high sensitivity but low specificity for diagnosis of HIT. The performances of the three other immunoassays were comparable to each other. Specificity significantly increased when assay data were combined with 4Ts scores. Differences in the diagnostic performance of the four immunoassays were not evident, and simultaneous consideration of clinical scoring systems improved performance.

Low molecular weight heparin: a promising anticoagulant in pregnancy.

Venous thromboembolism (VTE) is a leading cause of maternal mortality and morbidity during pregnancy in developed countries. The incidence of VTE increases about 4-fold during pregnancy and at least 14-fold during the puerperium. Risk factors include a personal history of VTE, presence of inherited or acquired thrombophilia, a family history of VTE and general medical conditions, such as immobilisation, overweight, varicose veins, some haematological diseases and inflammatory disorders. VTE is considered potentially preventable with the prophylactic administration of anticoagulants. Low molecular weight heparin has emerged as choice of anticoagulant in the present day obstetric and infertility practice. It has many advantages over unfractionated heparin and warfarin. Longer duration of action, less frequent dosing schedule, better safety profile are few of the advantages. Higher cost as compared to warfarin and unfractionated heparin is the main limiting factor for its use.

Application of ELISA in Detecting Heparin-Induced Thrombocytopenia Antibodies / 现代检验医学杂志

Objective To develop an ELISA method for determination of heparin-induced thrombocytopenia (HIT)antibody. Methods The compound formed between human platelet factor 4 (PF4)and heparin was used as the coating antigen,incu-bating the patients plasma with the coating antigen in the well,after washing,the second antibody labeled HRP was added in the well to incubate and washing again,the chromogenic substrates was added in the well to incubate,when the stop reaction was finished,the absorbance A450/A630 was detected,and the test results were judged according to standard,this method was compared with IBL method and was optimized and evaluated the performance.Results An indirect ELISA method was de-velop with the purified human PF4,the optimal dilution of sample and second antibody were 1∶100 and 1∶1 500 which de-tected by the orthogonal test,the intra-and inter-assay average coefficients of variation were 7.66% and 7.76%(<10%) respectively that detected by repeated measurement the three positive standard plasma.Through measureing the 100 healthy human plasm with no history of using heparin,the positive and negative predictive reference values were 0.304 and 0.456. IBL and this method detected 100 hemodialysis patients samples at the same time,and the result of statistical analysis was that,the sensitivity,speciality and accuracy of this method were 90%,97.78% and 90%,respectively.The negative and posi-tive predictive value were 81.8% and 98.88% respectively,and the difference was statistically significant [K=0.84(0.81~1)and Pexac=0.012<0.05].The difference was statistically significant,consistency was optimal,95% confidence interval was 92.59%~92.59%.Conclusion Comparing with the IBL,the method reported by this article had the similar perform-ance and good consistency,and it could satisfy the clinical detection and diagnosis of HIT patients.