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Soluble glycoprotein VI is a predictor of major bleeding in patients with suspected heparin-induced thrombocytopenia.

ABSTRACT: We have shown that patients with suspected heparin-induced thrombocytopenia (HIT) have a high incidence of major bleeding. Recent studies have implicated elevated soluble glycoprotein VI (sGPVI) levels as a potential risk factor for bleeding. We sought to determine if elevated sGPVI plasma levels are associated with major bleeding events in patients with suspected HIT. We used a cohort of 310 hospitalized adult patients with suspected HIT who had a blood sample collected at the time HIT was suspected. Plasma sGPVI levels were measured by using enzyme-linked immunosorbent assay. Patients were excluded who had received a platelet transfusion within 1 day of sample collection because of the high levels of sGPVI in platelet concentrates. We assessed the association of sGPVI (high vs low) with International Society on Thrombosis and Haemostasis major bleeding events by multivariable logistic regression, adjusting for other known risk factors for bleeding. Fifty-four patients were excluded due to recent platelet transfusion, leaving 256 patients for analysis. Eighty-nine (34.8%) patients had a major bleeding event. Median sGPVI levels were significantly elevated in patients with major bleeding events compared with those without major bleeding events (49.09 vs 31.93 ng/mL; P < .001). An sGPVI level >43 ng/mL was independently associated with major bleeding after adjustment for critical illness, sepsis, cardiopulmonary bypass surgery, and degree of thrombocytopenia (adjusted odds ratio, 2.81; 95% confidence interval, 1.51-5.23). Our findings suggest that sGPVI is associated with major bleeding in hospitalized patients with suspected HIT. sGPVI may be a novel biomarker to predict bleeding risk in patients with suspected HIT.

SUBMITTER: Pishko AM

PROVIDER: S-EPMC7509866 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Soluble glycoprotein VI is a predictor of major bleeding in patients with suspected heparin-induced thrombocytopenia.

Pishko Allyson M AM Andrews Robert K RK Gardiner Elizabeth E EE Lefler Daniel S DS Cuker Adam A

Blood advances 20200901 18

We have shown that patients with suspected heparin-induced thrombocytopenia (HIT) have a high incidence of major bleeding. Recent studies have implicated elevated soluble glycoprotein VI (sGPVI) levels as a potential risk factor for bleeding. We sought to determine if elevated sGPVI plasma levels are associated with major bleeding events in patients with suspected HIT. We used a cohort of 310 hospitalized adult patients with suspected HIT who had a blood sample collected at the time HIT was susp ...[more]

PMID: 32915974

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Project description:BackgroundDiagnosis 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.MethodsThis 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.ResultsOf 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.ConclusionsThe 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.

Project description:BackgroundThis is a review article on heparin-induced thrombocytopenia, an adverse effect of heparin therapy, and vaccine-induced immune thrombotic thrombocytopenia, occurring in some patients administered certain coronavirus vaccines.Main body/textImmune-mediated thrombocytopenia occurs when specific antibodies bind to platelet factor 4 /heparin complexes. Platelet factor 4 is a naturally occurring chemokine, and under certain conditions, may complex with negatively charged molecules and polyanions, including heparin. The antibody-platelet factor 4/heparin complex may lead to platelet activation, accompanied by other cascading reactions, resulting in cerebral sinus thrombosis, deep vein thrombosis, lower limb arterial thrombosis, myocardial infarction, pulmonary embolism, skin necrosis, and thrombotic stroke. If untreated, heparin-induced thrombocytopenia can be life threatening. In parallel, rare incidents of spontaneous vaccine-induced immune thrombotic thrombocytopenia can also occur in some patients administered certain coronavirus vaccines. The role of platelet factor 4 in vaccine-induced thrombosis with thrombocytopenia syndrome further reinforces the importance the platelet factor 4/polyanion immune complexes and the complications that this might pose to susceptible individuals. These findings demonstrate, how auxiliary factors can complicate heparin therapy and drug development. An increasing interest in biomanufacturing heparins from non-animal sources has driven a growing interest in understanding the biology of immune-mediated heparin-induced thrombocytopenia, and therefore, the development of safe and effective biosynthetic heparins.Short conclusionIn conclusion, these findings further reinforce the importance of the binding of platelet factor 4 with known and unknown polyanions, and the complications that these might pose to susceptible patients. In parallel, these findings also demonstrate how auxiliary factors can complicate the heparin drug development.

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Soluble glycoprotein VI is a predictor of major bleeding in patients with suspected heparin-induced thrombocytopenia.

Publications

Soluble glycoprotein VI is a predictor of major bleeding in patients with suspected heparin-induced thrombocytopenia.

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