Heparin-induced thrombocytopenia

Warkentin, Theodore E.

doi:10.1097/mcc.0000000000000259

Cited by 51 publications

(29 citation statements)

References 79 publications

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“…Heparin is widely given to prevent or treat thrombosis. After receiving heparin, some patients suffer from the serious adverse drug effect heparin‐induced thrombocytopenia (HIT) . Heparin forms through electrostatic attraction large complexes with platelet factor 4 (PF4), a positively charged protein belonging to CXC chemokine family released from human platelet α‐granules .…”

Section: Introductionmentioning

confidence: 99%

Reactivity of platelet‐activating and nonplatelet‐activating anti‐PF4/heparin antibodies in enzyme immunosorbent assays under different conditions

Nguyen

Wesche

Raschke

et al. 2019

Journal of Thrombosis and Haemostasis

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Background: Enzyme immunosorbent assays (EIA) are widely used to detect human antiplatelet factor 4/heparin antibodies (aPF4/H Abs) to rule out heparin-induced thrombocytopenia. EIAs cannot differentiate between clinically relevant, plateletactivating, and nonrelevant, nonplatelet-activating Abs and only ~50% of patients' sera testing positive by EIA contain antibodies that activate platelets. Recently, we have shown platelet-activating aPF4/H Abs bind more strongly to PF4/H complexes than nonplatelet-activating antibodies. Antigen-antibody interactions are known to depend on electrostatic interactions governed by pH, heat, and ionic strength. We tested whether changes in pH and ionic strength can improve the specificity of EIAs detecting aPF4/H Abs. Methods:We investigated first the conformational change of PF4 when binding to heparin under various pH and salt conditions using circular dichroism spectroscopy, and then the binding of aPF4/H Abs to PF4/H complexes by EIA. Results:Maximal conformational change of PF4 on complexation with heparin was identified at low pH and low salt concentrations. EIA tested with a large number of sera at 50 mmol/L NaCl, pH 6.0 shows a potential to increase the specificity for the detection of platelet-activating aPF4/H Abs. Conclusion:Changing physicochemical conditions may become an approach to better discriminate the signal of platelet-activating and nonactivating PF4/H Abs in antigen tests. K E Y W O R D SaPF4/H antibody, CD spectroscopy, enzyme immunosorbent assays, human PF4, ionic strength, pH

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Section: Introductionmentioning

confidence: 99%

Reactivity of platelet‐activating and nonplatelet‐activating anti‐PF4/heparin antibodies in enzyme immunosorbent assays under different conditions

Nguyen

Wesche

Raschke

et al. 2019

Journal of Thrombosis and Haemostasis

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“…HIT is a clinical paradox, where an immune response to the heparin/platelet factor 4 (PF4) complex during heparin anticoagulation in some patients gives rise to increased arterial or venous thrombotic (or even both) risk rather than bleeding risk. [40][41][42] The test is recommended in conjunction with assessing the patient's pretest probability, the most commonly applied being the 4T score, but other scoring methods have also been described (e.g., Chang score, HIT expert probability score). 42 Failure to recognize HIT in patients may lead to severe morbidity (e.g., limb loss) or mortality.…”

Section: Rationale For Heparin-induced Thrombocytopenia Assay Designamentioning

confidence: 99%

International Council for Standardization in Haematology Recommendations for Hemostasis Critical Values, Tests, and Reporting

Gosselin

Adcock²,

Dorgalaleh

et al. 2019

Semin Thromb Hemost

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This guidance document was prepared on behalf of the International Council for Standardization in Haematology (ICSH), the aim of which is to provide hemostasis-related guidance documents for clinical laboratories. The current ICSH document was developed by an ad hoc committee, comprising an international collection of both clinical and laboratory experts. The purpose of this ICSH document is to provide laboratory guidance for (1) identifying hemostasis (coagulation) tests that have potential patient risk based on analysis, test result, and patient presentations, (2) critical result thresholds, (3) acceptable reporting and documenting mechanisms, and (4) developing laboratory policies. The basis for these recommendations was derived from published data, expert opinion, and good laboratory practice. The committee realizes that regional and local regulations, institutional stakeholders (e.g., physicians, laboratory personnel, hospital managers), and patient types (e.g., adults, pediatric, surgical) will be additional confounders for a given laboratory in generating a critical test list, critical value thresholds, and policy. Nevertheless, we expect this guidance document will be helpful as a framework for local practice.

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“…[6][7][8] For example, heparin, a commonly administered anticoagulant, can induce major bleeding complications 9 and heparin-induced thrombocytopenia. 10 Similarly, the antiplatelet drug aspirin can also induce bleeding complications. 11 Meanwhile, studies have shown that the administration of the commonly used thrombolytic agent tissue plasminogen activator (tPA) can lead to neurotoxicity.…”

Section: Thrombosis and Current Clinical Treatmentsmentioning

confidence: 99%

Targeting Nanotechnologies for the Treatment of Thrombosis and Cardiovascular Disease

Palazzolo

Westein

Hagemeyer

et al. 2019

Semin Thromb Hemost

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Thrombosis is characterized by the formation of in vivo blood clots that are localized within arterial or venous blood vessels. These thrombi form beyond the need for physiologically healthy hemostatic responses and can lead to significant medical issues for affected individuals. Unfortunately, the existing standard-of-care therapies for treating thrombosis are systemic in their therapeutic design; therefore, they interfere with the patient's physiological hemostasis. Examples of the severe clinical side effects commonly associated with currently available therapies include, but are not limited to, bleeding complications. Therefore, there is a profound demand for novel therapeutic interventions that can circumvent these debilitating complications, while offering improved therapeutic efficacy. Recent advancements in nanotechnology present an opportunity to develop novel and improved drug delivery systems to meet this clinical demand. Preclinical investigations have begun to uncover the potential of nanotechnology, particularly in the treatment of thrombosis and also in nonhemostatic cardiovascular diseases. This article reviews recent preclinical studies aimed at developing a diverse array of different nanotechnologies for treating thrombosis as well as heart diseases. This review will also outline the limitations with current nanotechnologies and what challenges need to be overcome to translate these novel therapies to the clinic.

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Heparin-induced thrombocytopenia

Abstract: Greater understanding of the various clinical and laboratory features that distinguish HIT from non-HIT thrombocytopenia could help improve outcomes in patients who develop thrombocytopenia and coagulopathies in the ICU.

Cited by 51 publications

References 79 publications

Reactivity of platelet‐activating and nonplatelet‐activating anti‐PF4/heparin antibodies in enzyme immunosorbent assays under different conditions

Reactivity of platelet‐activating and nonplatelet‐activating anti‐PF4/heparin antibodies in enzyme immunosorbent assays under different conditions

International Council for Standardization in Haematology Recommendations for Hemostasis Critical Values, Tests, and Reporting

Targeting Nanotechnologies for the Treatment of Thrombosis and Cardiovascular Disease

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