Development of a method to analyze the complexes of enoxaparin and platelet factor 4 with size-exclusion chromatography

Publication date: Available online 16 November 2018Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Fangxia Wu, Kai Dong, Meng Zhu, Qinghua Zhang, Bingying Xie, Duxin Li, Hao Gan, Robert J. Linhardt, Zhenqing ZhangAbstractHeparin, a highly sulfated glycosaminoglycan, has been used as a clinical anticoagulant over 80 years. However, heparin-induced thrombocytopenia and thrombosis (HITT) is a serious side effect of heparin therapy, resulting in relatively high risk of amputation and even death. HITT is caused by forming of complexes between heparin and platelet factor 4 (PF4). Enoxaparin, one of the most commonly used low molecular weight heparin (LMWH), were developed in 1980’s. The lower molecular weight of enoxaparin reduces the risk of HITT by binding to less PF4. To detect the binding capacity between enoxaparin and PF4 could be an effect way to control this risk before it goes to patients. In this work, a size exclusion chromatography (SEC) method was developed to analyze the patterns of complexes formed between PF4 and enoxaparin. The chromatographic condition was optimized to separate PF4, enoxaparin, ultra-large complexes and small complexes. The linearity and stability of this method were confirmed. The impacts of PF4/enoxaparin mixture ratios and incubation time on the forming complexes were investigated. Four enoxaparin samples were analyzed with this method to verify its practicability. It is a robust, accurate and practicable method, and p...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research

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Whereas the utility of washed platelet assays such as the heparin-induced platelet activation test (HIPA) for the diagnosis of heparin-induced thrombocytopenia (HIT) is regarded as high, the performance of simpler assays such as the heparin-induced platelet aggregation test (PAT) is still elusive. Using well-characterized samples of a large cohort study, we aimed to assess the diagnostic accuracy of PAT for the diagnosis of HIT.
Source: Thrombosis Research - Category: Hematology Authors: Tags: Full Length Article Source Type: research
The objective of the present study was to review the pathophysiology of APS and its association with female infertility. A bibliographic review of articles of the past 20 yearswas performed at the PubMed, Scielo, and Bireme databases. Antiphospholipid antibody syndrome may be associated with primary infertility, interfering with endometrial decidualization and with decreased ovarian reserve. Antiphospholipid antibodies also have direct negative effects on placentation, when they bind to the trophoblast, reducing their capacity for invasion, and proinflammatory effects, such as complement activation and neutrophil recruitme...
Source: Revista Brasileira de Ginecologia e Obstetricia - Category: OBGYN Source Type: research
CONCLUSION: The αIIb(R990W) KI mice developed macrothrombocytopenia, which was primarily attributed to impaired proplatelet formation. In addition, Homo KI mice showed marked downregulation in αIIbβ3 expression in platelets with severe impaired platelet function, similar to Glanzmann thrombasthenia. PMID: 31691484 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Tags: J Thromb Haemost Source Type: research
We describe a case as an example to illustrate how we balanced the risk of serious bleeding versus the risk of stent thrombosis successfully according to evolution of the disease process, by temporary withholding of antiplatelets in such a patient. PMID: 31701855 [PubMed - as supplied by publisher]
Source: The American Journal of Tropical Medicine and Hygiene - Category: Tropical Medicine Authors: Tags: Am J Trop Med Hyg Source Type: research
CONCLUSIONS: TREM-1 inhibition decreases thrombin generation and could be an interesting target for the development of new inhibitors of leukocyte-associated thrombotic activity. PMID: 31680426 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Tags: J Thromb Haemost Source Type: research
This study aims to evaluate the effect of thalidomide on ITP mouse model. ITP mouse model was established through intraperitoneal injection of rat anti-mouse integrin GPIIb/CD41 immunoglobulin.
Source: Thrombosis Research - Category: Hematology Authors: Tags: Full Length Article Source Type: research
Heparin is commonly used in the renal transplant setting but heparin-induced thrombocytopenia (HIT) a serious adverse reaction to heparin appears to be infrequent in this patient population [1 –3]. A subset of HIT antibodies considered “pathogenic” activate platelets in functional assays like the serotonin release assay (SRA) and can be distinguished from “benign” antibodies commonly seen in clinical practice that are positive in PF4/Polyanion ELISAs (PF4 ELISA) but are not plat elet-activating [4].
Source: Thrombosis Research - Category: Hematology Authors: Tags: Letter to the Editors-in-Chief Source Type: research
CONCLUSIONS: In addition to arterial and venous thrombosis, antiphospholipid syndrome can affect the microvasculature of select organs. It is thus important for clinicians to be aware that antiphospholipid syndrome-associated microvascular involvement has a unique pathogenesis and can be a life-threatening condition. PMID: 31635555 [PubMed - as supplied by publisher]
Source: Lupus - Category: Rheumatology Authors: Tags: Lupus Source Type: research
AbstractVery limited but promising experiences with the use of direct factor Xa inhibitors for the treatment of heparin-induced thrombocytopenia (HIT) have been reported. This contribution features our first experience with the use of apixaban (without a pre-treatment with parenteral anticoagulant) to treat a case of HIT which developed in a patient after multiple heart replacement surgery. Apixaban was effective, well tolerated and safe. An apixaban-calibrated chromogenic anti-Xa activity assessment was used to monitor apixaban activity throughout the therapy. Patient continued on apixaban for the prevention of thrombosis...
Source: Journal of Thrombosis and Thrombolysis - Category: Hematology Source Type: research
This study evaluated the roles of subgroup lymphocytes from peripheral blood in ITP adults with different treatment response.
Source: Thrombosis Research - Category: Hematology Authors: Tags: Full Length Article Source Type: research
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