scholarly journals Heparin Induced Thrombocytopenia in Patients with COVID-19

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
Surbhi Warrior ◽  
Elizabeth Behrens ◽  
Sefer Gezer ◽  
Parameswaran Venugopal ◽  
Shivi Jain
Keyword(s):  
Risk Factors ◽  
Mechanical Ventilation ◽  
Platelet Factor 4 ◽  
Thromboembolic Events ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Increased Risk ◽  
The Impact ◽  
4T Score ◽  
Immune Assay

Background The Coronavirus disease-2019 (COVID-19) is a global pandemic caused by novel coronavirus SARS-CoV-2. Acute respiratory and renal failure as well as systemic coagulopathy are critical aspects of the morbidity and mortality in patients with COVID-19. Heparin Induced Thrombocytopenia (HIT) occurs when IgG antibodies form against platelet factor 4-Heparin complex, resulting in platelet activation and removal, leading to a prothrombotic state. HIT is suspected when there is a platelet count decrease of more than 50% after exposure to heparin, along with hypercoagulability. Clinical Scoring systems like 4T Score (Thrombocytopenia, Timing, Thrombosis, no other cause of Thrombocytopenia) have been developed to assess the pretest probability of HIT. The use of unfractionated heparin, post-orthopedic and post-cardiac surgery state, female gender, and old age are recognized as risk factors for HIT. There is a nine-fold increased risk of developing HIT in patients requiring hemodialysis. ICU patients and patients with VTE without thrombocytopenia are considered to have low pre-test probability for HIT. Studies have shown that only 6% who are investigated serologically for HIT actually have the diagnosis. We conducted this study to assess the incidence and risk factors for HIT in COVID-19 positive patients and its impact on mortality. Methods A retrospective analysis was performed on all patients who were COVID-19 positive and hospitalized between March 1, 2020 and June 26, 2020 at our institution. Patients with intermediate or high suspicion for HIT, based on 4T score of 4 or higher, underwent IgG-specific platelet factor 4(PF4)-dependent enzyme immune assay (EIA). Washed platelet assays such as serotonin release assay (SRA) and heparin-induced platelet aggregation (HIPA) were used as confirmatory tests in cases with intermediate or low optical density (OD) with EIA. The incidence of HIT, its impact on mortality, and positivity of IgG-specific PF4-EIA in COVID-19 patients were studied, and statistical analysis was done with X2 testing. Subgroup analysis was performed based on demographic factors and risk factors for HIT, including exposure to heparin or low molecular weight heparin (LMWH), history of or cancer, recent orthopedic or cardiac surgery, exposure to renal replacement therapy (RRT), and severity of disease (D-dimer >6 ULN, Acute Kidney Injury, ICU admission, and mechanical ventilation requirement). These factors were analyzed by Fisher's exact test to determine their impact on mortality. The hospital course for HIT antibody-positive patients was further analyzed to study the impact of COVID-19 related therapy, such as Remdesivir, Tocilizumab, Hydroxychloroquine, Steroids, and anticoagulation after diagnosis of HIT. Results WEight out of 1265 hospitalized COVID-19 positive patients tested positive for IgG-specific platelet factor 4(PF4)-dependent enzyme immune assay (EIA+). Incidence of EIA+ in COVID-19 patients was 0.6%, which is significantly higher than in the general population 0.2% (p<.0001, 95% CI 0.25-1.20%). The incidence of thromboembolic events in EIA+ patients was 87.5%, significantly higher than the rate of 10.90% in all COVID-19 patients (p<.0001, CI 41.96- 86.98%). The mortality rate in EIA+ patients was 50%, significantly greater than the mortality rate of 12% in all hospitalized COVID-19 patients (p=.0011, CI 9.46-66.53). Serological confirmation of HIT diagnosis was 37.5% (2 had OD>1, 1 was SRA positive) which is significantly higher than confirmation of HIT in nonCOVID-19 patients 6% (p<.0001, 95% CI 29.57-85.32%). All 3 confirmed HIT patients (100%) had severe disease (3/3 required ICU admission, 2/3 required mechanical ventilation, the one not requiring mechanical ventilation required RRT). Conclusion Our study indicates incidence of HIT is higher in the COVID-19 population. The incidence of positive EIA for patients with intermediate to high 4T scores is also higher in COVID-19 positive patients. This can be attributed to the cytokine storm and severe sepsis seen in critically ill COVID-19 patients. Our study also suggests that development of HIT can contribute to increased risk for thromboembolic events as well as mortality of COVID-19 patients, however, our study is limited due to small sample size. Therefore, prospective studies are needed to analyze the impact of HIT on morbidity, mortality and long-term outcomes in COVID-19 patients. Table Disclosures No relevant conflicts of interest to declare.

scholarly journals Heparin Induced Thrombocytopenia in Patients with COVID-19

2021 ◽  
Author(s):  
Surbhi Warrior ◽  
Elizabeth Behrens ◽  
Sefer Gezer ◽  
Parameswaran Venugopal ◽  
Shivi Jain
Keyword(s):  
Mortality Rate ◽  
General Population ◽  
Small Sample Size ◽  
Small Sample ◽  
Platelet Factor 4 ◽  
Thromboembolic Events ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Confirmatory Testing ◽  
Increased Risk

Abstract Background Acute respiratory and renal failure as well as systemic coagulopathy are critical aspects of the morbidity and mortality in patients with COVID-19. Heparin Induced Thrombocytopenia (HIT) occurs when IgG antibodies form against platelet factor 4-Heparin complex, resulting in platelet activation and removal, leading to a prothrombotic state. Studies have shown that only 6% who are investigated serologically for HIT actually have the diagnosis. Methods A retrospective analysis was performed on all COVID-19 positive patients hospitalized between March and June 2020. Patients with suspicion for HIT were tested for HIT antibodies with IgG-specific platelet factor 4(PF4)-dependent enzyme immunoassay (EIA). Confirmatory testing with serotonin release assay (SRA) and heparin-induced platelet aggregation were used in cases with intermediate or low optical density (OD) with EIA positivity (EIA+). Due to rarity of disease, a through literature review on HIT in COVID-19 patients was also analyzed. Results Incidence of EIA + in COVID-19 patients was 0.6%, significantly higher than in the general population 0.2% (p < 0.0001). The incidence of thromboembolic events in EIA + patients was 87.5%, significantly higher than the rate of 10.90% in all COVID-19 patients (p < 0.0001). The mortality rate in EIA + patients was 50%, significantly greater than the mortality rate of 12% in all hospitalized COVID-19 patients (p = 0.0011). Serological confirmation of HIT diagnosis was 37.5% which is significantly higher than confirmation of HIT in nonCOVID-19 patients 6% (p < 0.0001). Of 39 HIT antibody positive patients in the literature, 23.07% had positive confirmatory testing (6 SRA, 3 HIPAA) which is significantly higher than 5.6% in the general population (p = 0.00001). The incidence of thrombosis in EIA + COVID-19 patients in the literature was 56.4% which is significantly higher than reported rates of thrombotic events in in all COVID-19 patients in the literature at 4.8%1 (p = 0.00001). Conclusion Our study indicates incidence of HIT is higher in the COVID-19 population. This can be attributed to the cytokine storm and severe sepsis seen in critically ill COVID-19 patients. Our study also suggests that development of HIT can contribute to increased risk for thromboembolic events as well as mortality of COVID-19 patients, however, our study is limited due to small sample size.

Is prolonged immobilization a risk factor for symptomatic venous thromboembolism in elderly bedridden patients?

2004 ◽  
Vol 91 (03) ◽  
pp. 538-543 ◽  
Author(s):  
Ora Paltiel ◽  
Michael Bursztyn ◽  
Moshe Gatt
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Early Period ◽  
Thromboembolic Events ◽  
Historical Cohort ◽  
Increased Risk ◽  
Venous Thromboembolic Events ◽  
Venous Thromboembolic ◽  
Prolonged Immobilization ◽  
The Impact

SummaryProlonged immobilization and advanced age are considered to be important risk factors for venous thromboembolism (VTE). Nevertheless, the need for VTE prophylaxis in long-term bedridden patients is not known. To assess whether very prolonged immobilization (i.e. over three months) carries an increased risk for clinically apparent VTE, we performed a historical-cohort study of nursing home residents during a ten-year period. Data concerning patient’s mobility and incidence of overt deep vein thrombosis or pulmonary embolism were registered. The mean resident age was 85 ± 8.4 years. Eighteen mobile and eight immobile patients were diagnosed with clinically significant thromboembolic events, during 1137 and 573 patient-years of follow up, respectively. The incidence of venous thromboembolic events was similar in both chronically immobilized and mobile patient groups, 13.9 and 15.8 per thousand patient years, respectively (p = 0.77). The rate ratio for having a VTE event in the immobilized patient group as compared with the mobile group was 0.88 (95% Confidence Interval (CI) 0.33 to 2.13). When taking into account baseline characteristics, risk factors and death rates by various causes, no differences were found between the two groups. In conclusion, chronically immobile bedridden patients are no more prone to clinically overt venous thromboembolic events than institutionalized mobile patients. Until further studies are performed concerning the impact of very prolonged immobilization on the risk of VTE, there is no evidence to support primary prevention after the first three months of immobilization. Evidence for efficacy or cost effectiveness beyond this early period is not available.

Performance of 4T score and heparin–platelet factor 4 antibody in the diagnosis of heparin-induced thrombocytopenia (HIT) in cancer

2017 ◽  
Vol 44 (2) ◽  
pp. 261-266 ◽  
Author(s):  
Myra Wong ◽  
Thein Hlaing Oo ◽  
Wei Qiao ◽  
Naveen Garg ◽  
Cristhiam M. Rojas-Hernandez
Keyword(s):  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
4T Score

Utility of Optical Density Values from Heparin-Platelet Factor 4 Antibody Testing and Probability Scoring Models To Diagnose Patients with Heparin Induced Thrombocytopenia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1475-1475
Author(s):  
Kim A. Janatpour ◽  
Robert C. Gosselin ◽  
William E. Dager ◽  
Andrew Lee ◽  
John T. Owings ◽  
...  
Keyword(s):  
High Risk ◽  
Optical Density ◽  
Predictive Value ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Predictive Values ◽  
Heparin Induced Thrombocytopenia ◽  
Sensitivity Specificity ◽  
Test Probability ◽  
4T Score

Abstract Background: Heparin induced thrombocytopenia (HIT) is a potentially life threatening complication of heparin administration caused by antibodies directed to the heparin-platelet factor 4 (PF4) complex and characterized by thrombocytopenia with a seemingly paradoxical high risk of thrombosis. Diagnosis is challenging, and is based on both clinical suspicion and laboratory detection of heparin-PF4 antibodies. The Warkentin 4 T’s “pre-test” probability and Chong’s “post-test” probability models have been developed to aid the diagnosis of HIT. Enzyme-linked immunoabosorbant assay (ELISA) laboratory measurement of heparin-PF4 antibodies is commonly used but has a low positive predictive value for thrombosis. Recent reports suggest that using an ELISA optical density (OD) value of ≥ 1 may improve the predictive value for thrombosis. Methods: We performed a retrospective analysis of 105 patients with suspected HIT who were treated with a direct thrombin inhibitor and evaluated the anti-heparin-PF4 ELISA OD values and Warkentin 4 T’s scores for sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) using the Chong’s score to define HITBoth the manufacturer’s OD threshold of 0.4 and ≥ 1 were evaluated. Table 1. Comparison of sensitivity, specificity, and predictive values for 4 T’s and OD levels, alone and in combination Sensitivity (%) Specificity (%) NPV (%) PPV (%) For calculations, Chong’s categories of definite/probable and unlikely were used to define presence or absence of HIT. 4T’s score (high and low) 81 100 80 100 OD level 0.4 69 75 65 78 OD level ≥1 38 85 52 77 4T’s + OD 0.4 94 100 94 100 4T’s +OD ≥1 69 85 81 75 Results: The sensitivity, specificity and predictive value of ELISA alone were inferior to the 4 T’s clinical scorings system. The sensitivity and negative predictive values of the 4T’s score were improved by considering positive or negative ELISA test results. Conclusions: Consistent with previous reports, the PPV of a high probability 4T score alone was 100%. Thus, ELISA results might not change clinical decisions in this situation. Alternative anticoagulation might be inappropriately withheld in 20% of patients if a low probability 4T score alone were to be used for decision-making. The addition of ELISA data using an OD level of 0.4 increased the NPV to a threshold that might be considered clinically acceptable (94%) to withhold therapy. Addition of an OD level of ≥ 1 did not improve the PV of the 4 T’s. However, in contrast to other studies that found better predictive value to using this higher OD threshold, our study group was limited to people considered high risk for HIT. Validation of this strategy in a prospective trial with clinical endpoints should be considered.

scholarly journals The Impact of Intervention-Related Risk Factors on the Risk of Ventilator-Associated Pneumonia Is High in a Neurosurgical Intensive Care Unit

2020 ◽  
Vol 41 (S1) ◽  
pp. s407-s409
Author(s):  
Ksenia Ershova ◽  
Oleg Khomenko ◽  
Olga Ershova ◽  
Ivan Savin ◽  
Natalia Kurdumova ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mechanical Ventilation ◽  
Negative Slope ◽  
Infection Prevention And Control ◽  
Ventilator Associated Pneumonia ◽  
Related Factors ◽  
Icu Patients ◽  
The Impact ◽  
Adf Test ◽  
Over Time

Background: Ventilator-associated pneumonia (VAP) represents the highest burden among all healthcare-associated infections (HAIs), with a particularly high rate in patients in neurosurgical ICUs. Numerous VAP risk factors have been identified to provide a basis for preventive measures. However, the impact of individual factors on the risk of VAP is unclear. The goal of this study was to evaluate the dynamics of various VAP risk factors given the continuously declining prevalence of VAP in our neurosurgical ICU. Methods: This prospective cohort unit-based study included neurosurgical patients who stayed in the ICU >48 consecutive hours in 2011 through 2018. The infection prevention and control (IPC) program was implemented in 2010 and underwent changes to adopt best practices over time. We used a 2008 CDC definition for VAP. The dynamics of VAP risk factors was considered a time series and was checked for stationarity using theAugmented Dickey-Fuller test (ADF) test. The data were censored when a risk factor was present during and after VAP episodes. Results: In total, 2,957 ICU patients were included in the study, 476 of whom had VAP. Average annual prevalence of VAP decreased from 15.8 per 100 ICU patients in 2011 to 9.5 per 100 ICU patients in 2018 (Welch t test P value = 7.7e-16). The fitted linear model showed negative slope (Fig. 1). During a study period we observed substantial changes in some risk factors and no changes in others. Namely, we detected a decrease in the use of anxiolytics and antibiotics, decreased days on mechanical ventilation, and a lower rate of intestinal dysfunction, all of which were nonstationary processes with a declining trend (ADF testP > .05) (Fig. 2). However, there were no changes over time in such factors as average age, comorbidity index, level of consciousness, gender, and proportion of patients with brain trauma (Fig. 2). Conclusions: Our evidence-based IPC program was effective in lowering the prevalence of VAP and demonstrated which individual measures contributed to this improvement. By following the dynamics of known VAP risk factors over time, we found that their association with declining VAP prevalence varies significantly. Intervention-related factors (ie, use of antibiotics, anxiolytics and mechanical ventilation, and a rate of intestinal dysfunction) demonstrated significant reduction, and patient-related factors (ie, age, sex, comorbidity, etc) remained unchanged. Thus, according to the discriminative model, the intervention-related factors contributed more to the overall risk of VAP than did patient-related factors, and their reduction was associated with a decrease in VAP prevalence in our neurosurgical ICU.Funding: NoneDisclosures: None

Prevalence, isotype, and functionality of antiheparin–platelet factor 4 antibodies in patients treated with heparin and clinically suspected for heparin-induced thrombocytopenia

2002 ◽  
Vol 105 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Brian Untch ◽  
Sarfraz Ahmad ◽  
Walter P. Jeske ◽  
Harry L. Messmore ◽  
Debra A. Hoppensteadt ◽  
...  
Keyword(s):  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia

Abstract T P136: Potential Contributors to the Declining Impact of Stroke Risk Factors with Age: Implications for Stroke Epidemiology in the Elderly

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
George Howard ◽  
Mary Cushman ◽  
Maciej Banach ◽  
Brett M Kissela ◽  
David C Goff ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Stroke Risk ◽  
Multivariable Analysis ◽  
The Elderly ◽  
Stroke Risk Factors ◽  
Age Related ◽  
Increased Risk ◽  
The Impact ◽  
Age Related Changes

Purpose: The importance of stroke research in the elderly is increasing as America is “graying.” For most risk factors for most diseases (including stroke), the magnitude of association with incident events decreases at older ages. Potential changes in the impact of risk factors could be a “true” effect, or could be due to methodological issues such as age-related changes in residual confounding. Methods: REGARDS followed 27,748 stroke-free participants age 45 and over for an average of 5.3 years, during which 715 incident strokes occurred. The association of the “Framingham” risk factors (hypertension [HTN], diabetes, smoking, AFib, LVH and heart disease) with incident stroke risk was assessed in age strata of 45-64 (Young), 65-74 (Middle), and 75+ (Old). For those with and without an “index” risk factor (e.g., HTN), the average number of “other” risk factors was calculated. Results: With the exception of AFib, there was a monotonic decrease in the magnitude of the impact across the age strata, with HTN, diabetes, smoking and LVH even becoming non-significant in the elderly (Figure 1). However, for most factors, the increasing prevalence of other risk factors with age impacts primarily those with the index risk factor absent (Figure 2, example HTN as the “index” risk factor). Discussion: The impact of stroke risk factors substantially declined at older ages. However, this decrease is partially attributable to increases in the prevalence of other risk factors among those without the index risk factor, as there was little change in the prevalence of other risk factors in those with the index risk factor. Hence, the impact of the index risk factor is attenuated by increased risk in the comparison group. If this phenomenon is active with latent risk factors, estimates from multivariable analysis will also decrease with age. A deeper understanding of age-related changes in the impact of risk factors is needed.

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