Гепарин-индуцированная тромбоцитопения

Есть два типа гепарин-индуцированной тромбоцитопении (ГИТ). В общей медицинской практике термин гепарин-индуцированная тромбоцитопения (ГИТ) относится к ГИТ 2-го типа, которая является иммунной реакцией организма на введение гепарина и проявляется через 4-10 дней от начала терапии. ГИТ 1-го типа является неиммунным состоянием, которое возникает в результате прямого воздействия гепарина на активацию тромбоцитов. ГИТ 1-го типа проявляется в течение первых двух дней после начала терапии и количество тромбоцитов в дальнейшем нормализуется без отмены препарата.

Источники: Platelets. 2019 Jan 29:1-5. doi: 10.1080/09537104.2018.1562169. [Epub ahead of print]

                    Cureus. 2018 Oct 31;10(10):e3532. doi: 10.7759/cureus.3532.

                     J Thromb Haemost. 2019 Mar;17(3):525-531. doi: 10.1111/jth.14383. Epub 2019 Feb 20.

A platelet viability assay (PVA) for the diagnosis of heparin-induced thrombocytopenia.

Ivetic N et al

Diagnosing heparin-induced thrombocytopenia (HIT) requires functional assays measuring platelet activation as they are highly specific and sensitive. A useful functional test for diagnosing HIT is the serotonin release assay (SRA), but this assay is technically demanding and requires a radioactive marker. We describe an alternate functional HIT assay, the platelet viability assay (PVA), that overcomes the need for a radioactive marker by using a viability dye endpoint to measure platelet activation. We compared the performance characteristics of the PVA to the SRA. Serum samples from 76 patients with suspected HIT were tested in both the PVA and the SRA. The PVA uses calcein-AM as a marker of platelet viability, with decreases in fluorescence and cell size as surrogate markers for platelet activation. A significant linear correlation (Spearman correlation, r = -0.78, P < 0.0001) was observed between the PVA and SRA. Calcein-AM fluorescence decreased in a negative linear relationship with platelet activation as measured by 14C-serotonin release. The PVA detected all positive SRA samples, with an overall sensitivity of 100% and a specificity of 97% in comparison to the SRA. The measurement of platelet viability using the PVA provided similar results to the SRA when testing suspected HIT patient samples.


The Appropriateness of Testing Platelet Factor 4/Heparin Antibody in Patients Suspected of Heparin-induced Thrombocytopenia.

Jindal V et al

Heparin-induced thrombocytopenia (HIT) is an adverse reaction to the administration of heparin due to the activation of the platelets by the immunoglobulin G (IgG) antibody-platelet factor 4 (PF4)/heparin immune complex. Since the clinical outcome is uncertain (as it could be associated with significant morbidity and sometimes death), an early diagnosis and appropriate treatment are necessary. The 4Ts pretest clinical scoring system and testing for all anti-PF4/heparin antibodies can markedly improve the diagnosis and prompt adequate treatment. Our study was undertaken to retrospectively evaluate the appropriateness of ordering the PF4 enzyme-linked immunosorbent assay (ELISA) test by using the 4Ts scoring system in a tertiary institution. We examined a database of 118 patients who had the PF4 ELISA test and calculated their 4Ts scores retrospectively. A total of 107 patients were evaluated; 95 patients (88.79%) had a negative PF4 ELISA assay and 12 patients tested positive (11.21%). Only one patient tested weakly positive in the low probability group (negative predictive value 98%). In the intermediate group, six patients were strongly positive (optical density (OD) > 1.0). In this latter group, further confirmatory testing using serotonin release assays (SRAs) could have been done. We also evaluated the setting where the tests were performed and found that the majority of patients (63.55%) were tested in the intensive care unit (ICU) where thrombocytopenia is multifactorial. We concluded that the large majority of patients were not appropriately evaluated prior to testing, which incurred unnecessary expense and patient distress. For the proper identification of patients suspected of HIT who should undergo PF4/heparin antibody testing, further education of the ordering physicians is recommended.


An international external quality assessment for laboratory diagnosis of heparin-induced thrombocytopenia.

Eekels JJM et al

Essentials A pilot study for External Quality Assessment for testing of HIT is described. The qualitative accordance for the PF4/heparin IgG test was 97.6%. The qualitative accordance for functional HIT tests was considerably lower. External Quality Assessment for functional HIT tests is required. SUMMARY: Objective Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening complication of heparin exposure. Diagnosis is most reliable using a combination of an enzyme immunoassay (EIA) that detects antibodies against platelet factor 4 (PF4)/heparin complexes ("antigen" assay) and a "functional" assay that detects platelet-activating properties of the pathogenic HIT antibodies. No External Quality Assessment (EQA) is available for a combination of the tests. Here we report on the results of the first international EQA. Methods The pilot EQA was organized by the Department of Transfusion Medicine, Universitätsmedizin Greifswald, Germany. Six serum samples of patients, which were referred to Greifswald for HIT diagnosis, and one negative control sample were distributed to seven participants in Germany, Canada, and Singapore. Participants were asked to report the optical density (OD) values of their local EIA test for IgG-specific antibodies against the PF4/heparin complexes and the results for a functional assay (HIPA or SRA). Consensus was defined as a minimum 70% agreement, i.e., agreement among at least five of the seven participating laboratories. Results and conclusion Six out of seven participants reported results for EIA, with a high quantitative accordance (97.6%). For the functional assay, consensus was reached for all samples except the negative control, for which some participants reported nonspecific reactivity. All HIT-negative samples were correctly diagnosed by all participants; for HIT-positive samples, consensus of 70% was reached. Although the limited availability of sample material is an obstacle to overcome, an EQA combining both EIA and functional testing is feasible.


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