Cross-reactivity study of low molecular weight heparins and heparinoid in heparin-induced thrombocytopenia (original) (raw)
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Heparin-Induced Thrombocytopenia (HIT)
Anticoagulant Drugs, 2018
Heparin-induced thrombocytopenia (HIT I) is a severe, life-threatening, and immunological drug reaction. According to the clinical-laboratory characteristics, there are two types of HIT: type I (HIT I) and type II (HIT II). HIT I is the result of non-immunologic, direct interaction of heparin with the platelet surface. Contrary, HIT II is immunologically induced (antibody-mediated) and life-threatening side effect of heparin therapy, often associated with thromboembolic complications. All patients receiving heparin are exposed to the development of anti-heparin antibodies, irrespective of the heparin dosage, type, and method of administration. HIT most commonly develops in intensive care patients, dialyzed patients, and cardiosurgical and orthopedic patients. It commonly develops after 5-10 days of heparin therapy. Platelet count decreases by more than 50% from the baseline and ranges from 20 × 10 9 /L to 100 × 10 9 /L. In HIT II, thromboembolic complications usually include deep-vein thrombosis and pulmonary embolism, but they also include arterial occlusion of the extremities, myocardial infarction, stroke, and necrosis and organ damage. Clinical assessment of the HIT probability using 4T´s score system, systematic monitoring of platelet number in heparin-receiving patients, and specific laboratory diagnosis of anti-heparin antibodies substantially contribute to the final confirmation of the diagnosis, enable timely administration of direct non-heparin thrombin antagonists, and reduce mortality from thromboembolic complications.
Heparin-induced thrombocytopenia: studies with a new low molecular weight heparinoid, Org 10172
Blood, 1989
Studies were performed to determine the cross-reaction rate of the heparin-dependent antibody with Org 10172, a new low molecular weight heparinoid, and to investigate the effect of Org 10172 on platelet activation induced by the antibody. The plasmas of 17 patients with thrombocytopenia induced by standard heparin were shown, by platelet aggregation studies, to contain the heparin-dependent antibody. Of these 17 patient plasmas, only three cross-reacted with the heparinoid, producing a cross-reaction rate of 18%. When Org 10172 was added to a reaction mixture containing normal platelet-rich plasma, patient plasma, and standard heparin with non-cross-reacting plasmas, it inhibited platelet aggregation and thromboxane B2 production induced by the antibody, provided that the ratio of Org 10172 concentration (anti-Xa U/mL) to standard heparin concentration (IU/mL) exceeded 2.5 to 5.0. This inhibitory effect was observed only with platelet activation mediated by the antibody, but not by...
Mediterranean Journal of Hematology and Infectious Diseases, 2015
Background: The increasing trend of using low-molecular-weight-heparin (LMWH) versus unfractionated heparin (UFH) in hospitalized adult patients is raising concerns about the incidence of heparin-induced thrombocytopenia (HIT). Method: A retrospective study analyzed the requests for heparin-induced antibodies by enzyme-linked immunosorbent assay (ELISA) among adult hospitalized patients during the period from January 2011 to December 2013. These patients received either UFH or LMWH for prevention or therapeutic indications. Those with positive immune-mediated HIT were identified and considered as case patients. Result: The usage of LMWH and UFH and development of HIT was determined during the study period. The incidence of HIT in patients receiving UFH and those receiving LMWH was 4.09 per thousand patients and 0.48 per thousand patients, respectively, (p<0.0001) with an overall incidence of 2.49 per thousand patients. Conclusion: The increased trend of using LMWH over UFH among ...
2011
The current study compares the anticoagulant effects of a reference heparin product, heparin Leo ® USA to a test product, heparin Hikma, Jordan. Both products are usually administered intravenous (IV) or subcutaneous (SC) and bioequivalence requirements are typically waived. Hence, it is pivotal to compare the therapeutic equivalency of the two products without jeopardizing the health of human volunteers. We have compared the anticoagulant effects of the two products in male albino rats by comparing the aPTT values 2 h following a single subcutaneous dose of either Hikma or Leo heparins. The average aPTT values for both Hikma and Leo heparins were 101.2 and 102.8 s, respectively. Further, the USP heparin assay test was performed to determine the ID50 of the Hikma and Leo heparins. The average volume of heparin that caused 50% inhibition of plasma in vitro was 0.431 and 0.439 ml for Hikma and Leo heparins, respectively. There was no statistically significant difference between the tw...
Obstacles in the diagnostics and therapy of heparin-induced thrombocytopenia
Srpski arhiv za celokupno lekarstvo, 2010
An immune-mediated, severe, acquired prothrombotic disorder, heparin-induced thrombocytopenia type II (HIT II) occurs in 0.5-5% of patients exposed to unfractionated heparin longer than 5-7 days. Arterial and venous thromboses are induced by HIT II in about 35-50% of patients. Typical death rate for HIT is about 29%, while 21% of HIT patients result in amputation of a limb. The trend towards the occurrence of HIT due to the administration of low molecular weight heparins (LMWH) taking ever conspicuous place in the standard venous thromboembolism (VTE) prophylaxis has been more frequently observed recently. It is considered that LMWH may cause HIT II in about 0.25-1%. The need for further modification of HIPA assays with LMWH has been imposed in the HIT laboratory diagnostics, heretofore overburdened with complexity. There are several constantly opposing problems arising in HIT laboratory diagnostics, one of which is that in a certain number of patients immunologic assays detect nonp...
Heparins: Clinical use and laboratory monitoring
Laboratory Medicine, 2010
Heparin has long been used as an antithrombotic to treat and prevent thromboembolic events, as well as for systemic anti-coagulation during cardiopulmonary bypass and dialysis. Heparin continues to have distinct advantages when intense anti-coagulation is needed, but newer low molecular weight derivatives of heparin (LMWH) have advantages in the management of thromboembolism. One advantage of LMWH is that they often do not require laboratory monitoring; when monitoring is indicated it can be done with an anti-factor Xa activity assay. Monitoring is recommended for heparin because the patient response to a given dose is highly variable. The aPTT and anti-Xa assays are used for monitoring. However, the therapeutic ranges have not been rigorously validated, and current monitoring is not highly predictive of patient outcome.