Skip to main content
NCBI home page
North Carolina Medical Journal logoLink to North Carolina Medical Journal
. 2023 Mar 6;84(2):73024. doi: 10.18043/001c.73024

Retrospective Study of Thrombosis in Hospitalized Patients with COVID-19 in Rural North Carolina

Amanda Brechko 1, Michael R Jiroutek 2, Kyla Jones 3, Bonnie Brenseke 3, Donald C Maharty 3, James Cappola 3, Stephen P Holly 2
PMCID: PMC13368123  PMID: 39302334

Abstract

Background

Some patients with COVID-19 develop life-threatening thrombotic complications including myocardial infarction, deep vein thrombosis, pulmonary embolism, disseminated intravascular coagulation, and ischemic stroke. These inflammatory and hypercoagulable states have been well documented in patient cohorts from metropolitan areas, but not in more rural populations, nor has a data-driven treatment plan been developed for thrombotic COVID-19 patients.

Methods

We undertook a retrospective case-control study of COVID-19-positive patients to analyze the impact of thrombosis on various clinical endpoints including terminal diagnosis and disease severity. Prevalence and impact of thrombosis were determined using medical records from 2237 COVID-19-positive patients hospitalized in Cumberland County, North Carolina. Odds ratios for terminal diagnosis, death, ICU admission, and ventilation were calculated based on thrombosis status, D-dimer level, or type of antithrombotic treatment.

Results

Terminal diagnosis [OR 1.81; 95% CI (1.10, 2.98)], ICU admission [2.25; (1.33, 3.81)], and ventilation [2.46; (1.45, 4.18)] were all more likely in thrombotic patients (N = 97) compared to nonthrombotic patients (N = 2140) after adjusting for age. D-dimer levels were associated with death overall, but not among thrombotic patients. Treatments that combined antiplatelet and anticoagulant drugs appeared to be more efficacious than anticoagulants alone in preventing death and severe disease.

Limitations

Patient medical history prior to hospitalization was not evaluated.

Conclusion

In this cohort, those with thrombosis are at increased risk for adverse outcomes including death and severe disease. Antithrombotic therapy that includes antiplatelet drugs provides improved outcomes. Higher-powered prospective trials will be necessary to confirm any potential merits of antiplatelet therapy.

Keywords: original research, thrombosis, covid-19, Amanda Brechko, Campbell University

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with a high incidence of thrombotic complications.1–3 The pathogenesis of SARS-CoV-2 leading to thrombosis involves an aggressive inflammatory response known as the cytokine storm, endothelial cell injury, and activation of platelets and clotting factors, resulting in a hypercoagulable state.3 An autopsy study of patients who died of acute respiratory distress syndrome (ARDS) in the setting of COVID-19 early in the pandemic revealed that COVID-19 patients had a 9-fold greater prevalence of alveolar capillary microthrombi compared to patients who died of ARDS in the setting of influenza.4 An indicator of this inflammatory and hypercoagulable state is thought to be elevated levels of D-dimer, a degradation product of cross-linked fibrin.1,5,6

In response to the potential for thrombosis in patients with COVID-19, both prophylactic (low) and therapeutic (high) doses of antithrombotic drugs have been administered. Antithrombotic drugs are divided into 3 classes— anticoagulants, antiplatelets, and fibrinolytics—each having a distinct mechanism of action. Fibrinolytics act to dissolve existing clots, whereas anticoagulants and antiplatelets prevent thrombosis by inhibiting clotting factors of the coagulation cascade or platelet aggregation, respectively.7,8 Recent guidelines recommend prophylactic doses of anticoagulants such as heparin for the management of COVID-19 based on trials with both prophylactic and therapeutic anticoagulation treatment arms.9,10 For example, a recent trial of therapeutic anticoagulation with heparin in non-critically ill patients with COVID-19 showed that therapeutic anticoagulation with heparin is associated with a greater probability of survival, hospital discharge, and a greater number of days free of cardiovascular or respiratory organ support compared to prophylactic anticoagulation with heparin.11 In contrast, trials using similar treatments (therapeutic anticoagulation with heparin) in critically ill patients with COVID-19 did not demonstrate a survival benefit.12,13 The role of fibrinolytics and antiplatelet agents as treatments for COVID-19 is not yet clear, but several clinical trials with antiplatelet drugs, such as aspirin and clopidogrel are ongoing (NCT04409834, NCT04424901, and NCT04505774).14

Minority and rural populations experience greater risk for severe COVID-19 illness and mortality and appear underrepresented in COVID-19 research.15 In the context of these findings, we sought to analyze the incidence of thrombotic complications among the largely rural population of Cumberland County, North Carolina, and surrounding area, which is home to few major urban centers.16 Fayetteville is the largest city within this region and is home to Cape Fear Valley Medical Center, a 678-bed tertiary care hospital. Therefore, the goal of this study was to analyze patient records from the Cape Fear Valley Medical Center to: 1) determine the prevalence and impact of thrombosis in patients with COVID-19 in rural areas of North Carolina and 2) identify potential interventions associated with improved outcomes in this patient population.

Methods

This retrospective case-control study utilized deidentified records collected from 2237 patients at the Cape Fear Valley Medical Center in Fayetteville, North Carolina, from March 2020 to January 2021. This research was approved as an exempt protocol by the IRB of the Cape Fear Valley Medical Center (protocol #326-20) prior to data collection. Data included demographic characteristics, discharge disposition, thrombosis, antithrombotic drug treatment, ICU admission, ventilation, and terminal diagnosis, which was defined as either death or hospice care utilization. We created binary (yes/no) variables for the primary endpoints of terminal diagnosis, death, ICU admission, ventilation, and receipt of any medication (heparin, enoxaparin, warfarin, apixaban, rivaroxaban, clopidogrel, ticagrelor, and prasugrel), anticoagulant medication (heparin, enoxaparin, warfarin, apixaban, and rivaroxaban), and antiplatelet medication (clopidogrel, ticagrelor, and prasugrel). Based on literature values, we defined a high/low D-dimer variable (2 μg/mL).

A number of patients had multiple records in the dataset (corresponding to multiple hospital visits within the study period). Out of the 2727 records in the original data from 2237 patients, 490 visits were distributed across 375 patients with a range of 2–7 records per patient. In an attempt to eliminate bias and make those with multiple records comparable to those with just a single record, we created a set of rules (without inspecting the data). For each patient with multiple records: 1) any incidence of death, hospice care, ICU admission, or thrombosis was counted and retained; 2) medications from only the most recent admission date were counted in the single row, which was retained (medications from all other rows were excluded); and 3) D-dimer values from a patient’s initial (oldest) visit were retained (D-dimer values from all other rows were excluded).

Multivariable logistic regression models were constructed to evaluate the relationship between thrombosis and each outcome of terminal diagnosis, ICU admission, and ventilation. Age was included as a predictor variable in each model to account for concerns over any confounding between thrombosis and age. Odds ratios (OR) and associated 95% confidence intervals (CIs), adjusted for the inclusion of age in each model, were reported.

Computation of unadjusted ORs and 95% CIs permitted an assessment of the strength of the relationship between 1) terminal diagnosis and various medication use as well as ICU admission and various medication use (any medication, anticoagulant medication, and antiplatelet medication); 2) death or ICU admission and D-dimer level (low versus high) overall as well as amongst those with only thrombosis; and 3) death or ICU admission and (combined) thrombosis and high D-dimer level (both versus not both).

We conducted 2 sample independent group t-tests to compare the mean D-dimer values for those with and without thrombosis. Subjects missing data were excluded only from analyses for which the data were missing. As this was an exploratory, hypothesis-generating type of study, no adjustments for multiple comparisons were made. In addition, following current thinking regarding best practices for significance testing, P-values were reported as appropriate, but statistical significance was not evaluated for any results.17 All analyses were generated using SAS version 9.4 or JMP version 14.

Results

The purpose of this retrospective single-site study was to identify potential associations between COVID-19 and thrombosis with respect to patient outcome, antithrombotic strategies, and disease severity in a hospitalized population from a rural demographic. To evaluate the association of thrombosis with these factors, 2237 patients were divided into 2 groups for further analysis: case (COVID + thrombosis, n = 97) and control (COVID-19 alone, n = 2140). All 2237 patients were SARS-CoV-2 positive, predominantly female (52.9%), and mostly identified as either African American (52.1%) or White (32.7%, Table 1). The Cape Fear Valley ICU admitted a relatively low number of patients (8.6%) from our cohort and a similar number received ventilation treatment (7.8%). Only 97 COVID-19-positive patients were diagnosed with cardiovascular or cerebrovascular thrombosis (4.3%) as defined by clinical evaluation and diagnosis-related group (DRG) codes. However, 20.6% of those needing intensive care were diagnosed with thrombosis (Table 1. Overall, patients experienced a variety of outcomes, with the vast majority surviving and discharged to home (1611, 72.0%), whereas 247 patients (11.1%) expired or received hospice care. Patients who left against medical advice or were discharged to long-term care collectively represented 2.0% of the total population studied (Table 1).

Table 1. Patient Demographics and Selected Thrombosis Parameters.

COVID only
n = 2140 (%)		 COVID+thrombosis
n = 97 (%)		 Total
N = 2237 (%)
Age in years (Mean ± SD) 52.5 ± 23.8 70.2 ± 16.1 53.2 ± 23.8
Gender
Female 1144 (53.5) 40 (41.2) 1184 (52.9)
Male 996 (46.5) 57 (58.8) 1053 (47.1)
Ethnicity
African American 1117 (52.3) 46 (47.9) 1163 (52.1)
White 698 (32.7) 33 (34.4) 731 (32.7)
Remaining 323 (15.1) 17 (17.7) 340 (15.2)
ICU admission 173 (8.1) 20 (20.6) 193 (8.6)
Ventilator treatment 154 (7.2) 20 (20.6) 174 (7.8)
Terminal diagnosis* 220 (10.3) 27 (27.8) 247 (11.1)
Discharged to home 1572 (73.5) 39 (40.2) 1611 (72.0)
Left against medical advice 29 (1.4) 3 (3.0) 32 (1.4)
Discharged to long-term care 9 (0.4) 4 (4.1) 13 (0.6)
Open in a new tab

SD: Standard Deviation; ICU: Intensive Care Unit

*Terminal diagnosis includes death and discharged to hospice.

Impact of Thrombosis

To evaluate the impact of thrombosis on patient outcomes and epidemiology, odds of terminal diagnosis (death or hospice), ICU admission, and initial D-dimer levels in thrombotic (case) and nonthrombotic COVID-19 patients (control) were analyzed. Over 80% of thrombotic patients were aged 56 years or over, with the highest fraction of thrombosis occurring in patients over age 75, at 45.4% (Figure 1A). Reflective of the total COVID-19-positive patient population in this study, 47.9% of thrombotic patients were African American, followed by 34.4% who were White, with the remaining 17.7% of other ethnicities (Figure 1B).

Figure 1. Distribution of Patients with Thrombosis According to Age (A) or (B) Ethnicity.

Figure 1.

Open in a new tab

Thrombosis incidence was calculated as a percentage of patients within the indicated age ranges (A) or ethnicity (B). Only data for thrombotic patients are shown for both panels (n = 97). Thrombosis across ethnicity closely mimicked the racial distribution of the entire patient population (N = 2237).

Thrombosis in combination with COVID-19 was associated with a higher risk of terminal diagnosis compared to patients with COVID-19 alone after adjusting for age (OR 1.81, 95% CI 1.10–2.97, Table 2). In addition, patients with thrombosis were more likely to be admitted to the ICU (OR 2.25, 95% CI 1.33–3.81, Table 2) or placed on a ventilator (OR 2.46, 95% CI 1.45–4.18, Table 2). These data indicate that a combination of thrombosis and SARS-CoV-2 infection greatly influences patient outcome with respect to increased probability of mortality and severity of disease, even after accounting for age in each model.

Table 2. Odds Ratios (95% CI) of Terminal Diagnosis or Death, ICU Admission, or Ventilation by Thrombosis or D-dimer Value.

Endpoint Thrombosis* D-dimer† D-dimer‡
Terminal diagnosis§ 1.81 (1.10–2.97) ND ND
Death - 2.92 (2.09–4.01) 0.88 (0.28–2.78)
ICU 2.25 (1.33–3.81) 2.40 (1.69–3.42) 1.97 (0.63–6.17)
Ventilation 2.46 (1.45–4.18) - -
Open in a new tab

OR: Odds Ratio; CI: Confidence Interval; ND: not determined

*OR (95% CI) from multivariable logistic regression models to compare each endpoint for those with thrombosis to those with no thrombosis, adjusting for patient age, while using the entire patient population, N = 2237.

†OR (95% CI) comparing death for all those with high D-dimer levels to all those with low D-dimer levels, n = 1176.

‡OR (95% CI) comparing death for those with high D-dimer levels to those with low D-dimer levels in thrombotic patients only, n = 62.

§Terminal diagnosis includes death and discharged to hospice.

D-dimer

Despite this strong correlation between thrombosis and adverse outcomes, levels of the clot biomarker D-dimer only weakly correlated with thrombosis. As shown in Figure 2, among 1176 patients who underwent laboratory-confirmed D-dimer testing, the mean D-dimer value for 62 thrombotic patients was 4.0 ± 6.52 μg/mL compared to 2.24 ± 3.82 μg/ mL for 1114 patients without thrombosis (Figure 2, P = .04).

Figure 2. Distribution of D-dimer Values in Thrombotic and Nonthrombotic COVID-19 Patients.

Figure 2.

Open in a new tab

Lab-confirmed D-dimer tests for 1114 nonthrombotic patients (mean ± SD, 2.24 ± 3.82 μg/mL) and for 62 patients diagnosed with thrombosis (mean ± SD, 4.0 ± 6.52 μg/mL) were plotted. The limited number of patients with thrombosis makes comparisons of the 2 distributions of D-dimer values potentially spurious.

To further analyze D-dimer levels, a “high” D-dimer value was derived from the literature (≥ 2 μg/mL) and used as a threshold value to assess the association between D-dimer level (high, ≥ 2 μg/mL versus low, < 2 μg/mL) and death. High D-dimer was associated with an increased risk of death irrespective of thrombosis (OR 2.92, 95% CI 2.09–4.10, Table 2).

Thrombosis incidence was calculated as a percentage of patients within the indicated age ranges (A) or ethnicity (B). Only data for thrombotic patients are shown for both panels (n = 97). Thrombosis across ethnicity closely mimicked the racial distribution of the entire patient population (N = 2237).

However, the risk of death within the thrombotic case population alone was not found to be associated with D-dimer level (OR 0.88, 95% CI 0.28–2.78, n = 62, Table 2) nor did the combination of thrombosis and high D-dimer level associate with increased risk of death within the total population (data not shown). Collectively, our data show a weak correlation between thrombosis and high D-dimer level despite the similar maximum D-dimer values for thrombotic and nonthrombotic COVID-19 patients. High D-dimer value correlates more strongly with death in the total population, which is driven by the higher number of nonthrombotic COVID-19 patients in this cohort.

Antithrombotic Treatment

In an effort to determine which anticoagulant treatment strategies were associated with positive outcomes, odds of terminal diagnosis and ICU admission were calculated in patients given anticoagulant medications. Antithrombotics were broadly defined as either anticoagulant (heparin, enoxaparin, warfarin, apixaban, and rivaroxaban) or antiplatelet (P2Y12 antagonists: cIopidogrel, ticagrelor, and prasugrel) medications. Over 61% of all patients and 91.8% of thrombotic patients received at least 1 anticoagulant or antiplatelet medication. The majority of thrombotic patients received anticoagulants (55.7%) as opposed to antiplatelet drugs alone (1.0%) or a combination of both (35.1%).

Admission to the ICU indicated disease severity. Patients receiving at least 1 antithrombotic drug were more likely to be admitted to the ICU (OR 10.54, 95% CI 5.84–19.04, Table 3). Patients receiving an antiplatelet drug (as compared to those who received none) were also more likely to arrive in the ICU (OR 1.88, 95% CI 1.17–3.03, N = 2237, Table 3) but with relatively lower odds.

Table 3. Odds Ratios (95% CI) of Terminal Diagnosis or ICU Admission by Type of Antithrombotic Treatment.

Endpoint All meds* Anticoagulant† Antiplatelet‡
Terminal diagnosis 12.13 (7.02–20.96) 12.33 (7.14–21.30) 2.30 (1.52–3.48)
ICU 10.54 (5.84–19.04) 10.70 (5.94–19.30) 1.88 (1.17–3.03)
Open in a new tab

OR: Odds Ratio; CI: Confidence Interval

*OR (95% CI) comparing each endpoint for those treated with any medication to those treated with none, N = 2237.

†OR (95% CI) comparing each endpoint for those treated with at least one anticoagulant to those treated with none (see Methods), N = 2237.

‡OR (95% CI) comparing each endpoint for those treated with at least one antiplatelet to those treated with none (see Methods), N = 2237.

Similarly, odds of terminal diagnosis (defined as in-hospital death or discharged to hospice care) for patients receiving at least 1 type of antithrombotic medication as compared to those receiving none, regardless of thrombotic status, was very high (OR 12.13, 95% CI 7.02–20.96, Table 3). Patients receiving at least 1 anticoagulant (as compared to those receiving none) experienced high odds of terminal diagnosis (OR 12.33, 95% CI 7.14–21.30, Table 3). Interestingly, the odds of terminal diagnosis in patients receiving at least 1 antiplatelet medication compared to patients receiving no antiplatelet medications (anticoagulants alone) was relatively low (OR 2.30, 95% CI 1.52–3.48, Table 3). Furthermore, of the 23 thrombotic patients who died, 60.9% were treated only with anticoagulants, whereas 39.1% were treated with both anticoagulant and antiplatelet drugs, and none were treated with antiplatelet drugs alone. These outcomes likely reflect severity of disease, as we have no reason to believe medication(s) directly contributed to morbidity or mortality.

Discussion

Patients with COVID-19 hospitalized at Cape Fear Valley Medical Center had a 4.3% incidence of thrombosis. Compared to other studies focused on thrombosis in COVID-19 patients, this incidence appears low. Among COVID-19 patients hospitalized at the nearby Duke University Health System, 12.0% experienced a thromboembolic event,18 and among 3334 hospitalized COVID-19 patients in New York, the thrombosis incidence was 16.0%.1 Thrombotic events in COVID-19 patients in the ICU setting, however, were comparable between our cohort (20.6%) and populations from large urban areas or multicenter studies, which ranged from 6.3% to 31%.5,13,19–21

Over 80% of thrombotic patients in our study were aged 56 years or over, with the highest fraction of thrombosis occurring in patients aged over 75, which is consistent with existing data.22 This increased risk for severe disease in older patients could be due to increased susceptibility to the virus, the presence of comorbidities, and naturally waning immunity.23,24 Comparing census data for Cumberland County to our study cohort, a disproportionately large percentage of the patients were African American.25 Other studies have observed a disproportionate incidence of COVID-19 among racial minority groups, which may reflect differences in housing, work environments, or underlying medical comorbidities.15,26

While patients in this study had a relatively low incidence of thrombosis, patients with thrombosis were more likely to have severe disease (ICU admission) or require ventilation treatment. Additionally, those with documented thrombotic events were at higher risk of terminal diagnosis (death or hospice) compared to patients with COVID-19 alone. These data indicate that COVID-19-associated thrombosis greatly influences patient outcome with respect to increased probability of mortality and severity of disease and are consistent with other studies.21,27

Although considered a feature of COVID-19-associated coagulopathy, an elevated D-dimer level in our patient population only weakly correlated with thrombosis. In fact, both case and control populations in our study exhibited “high” (≥ 2 μg/mL) mean D-dimer concentrations and were not statistically different. It is well known that elevated D-dimer concentrations are observed in many thrombotic disease states, such as pulmonary embolism and deep vein thrombosis, but do not always indicate thrombosis since D-dimer values may be elevated in nonthrombotic conditions, such as pregnancy, trauma, infection, liver disease, and malignancy.28,29 However, an extremely elevated D-dimer is uniquely associated with severe disease including venous thromboembolism, sepsis, cancer, and now COVID-19.1,5,30,31 Elevated D-dimer levels also correlated with severe disease in our patient cohort, manifested by increased odds of death, which suggests that abnormally elevated D-dimer levels serve more as a general predictor of a negative patient outcome than as a specific marker for thrombosis.30,32,33

Despite patient demographics, disease severity, or a clear diagnosis of thrombosis, initiation of antithrombotic medications is becoming the standard of care for hospitalized COVID-19 patients. Heparin is the prototypical prophylactic anticoagulant used for most hospitalized patients and has been globally recommended as a treatment for COVID-19; however, some studies show therapeutic doses of heparin are insufficient for reversing the hypercoagulable state induced by COVID-19.12,13

In addition to coagulation, platelet hyperreactivity contributes to the thrombotic sequelae of COVID-19. For example, multiple groups have shown that platelets isolated from COVID-19 patients have a procoagulant or hyperreactive phenotype in which platelets secrete higher levels of activation markers such as P-selectin, aggregate more intensely in response to agonists, and generate more leukocyte-containing aggregates compared to controls.34–38 Other studies have revealed that platelet development, secretion, and regulation of normal blood clotting (hemostasis) are critical pathways affected by COVID-19.39–41 Consistent with these data, the use of antiplatelet drugs in COVID-19 patients appears to improve patient outcomes and respiratory symptoms. For example, aspirin treatment correlates with reduced all-cause mortality and severity of COVID-19 symptoms42 and fondaparinux treatment in combination with aspirin, clopidogrel, and tirofiban leads to increased arterial oxygen partial pressure and reduced hypoxemia.43

Despite these encouraging results, data regarding efficacy of antiplatelet strategies in COVID-19 remain scarce. Interestingly, patients in our study who received at least 1 antiplatelet medication compared to those receiving no antiplatelet medications (anticoagulants alone or no medications) experienced a lower risk of death and discharge to hospice care. These data indicate that anticoagulants used in this patient population only partially mitigated the odds of death or severe disease and suggest that antiplatelet drugs or a combination of anticoagulant and antiplatelet medications may be more effective treatment options compared to anticoagulants alone. Furthermore, of the thrombotic patients who died, 60.9% were treated only with anticoagulants, whereas 39.1% were treated with both anticoagulants and antiplatelet drugs, suggesting that targeting platelet activation may be beneficial for certain COVID-19 patients. In fact, another group recently identified prior antiplatelet therapy as a beneficial factor for COVID-19 outcome.44 As of this writing, there are several ongoing clinical trials investigating efficacy of anticoagulant, antiplatelet, and combinations of both in patients with COVID-19 (e.g., NCT04324463, NCT04359277, NCT04409834, NCT04424901, and NCT04505774).

A limitation of this study is the lack of medication and health history prior to hospitalization, as antithrombotic treatments and comorbidities could potentially impact outcomes and interpretation of the data. Due to the retrospective design of this study, however, it is not possible to demonstrate causal relationships between disease states and mortality, nor between therapeutic interventions and improved patient outcomes; retrospective analysis can only identify association, not causation. However, our results are consistent with another recently published retrospective antiplatelet analysis, which suggests that retrospective study designs may be valuable for identifying associations in COVID-19 patient populations.44

In conclusion, our study addresses an unmet need by evaluating the impact of thrombosis in patients with COVID-19 from rural communities and by identifying potential interventions that may benefit this patient population. The overall incidence of thrombotic complications in this cohort is relatively low, but as with other populations in more urban settings, thrombosis was associated with increased mortality and COVID-19 disease severity. Importantly, the combination of anticoagulant and antiplatelet drugs greatly lowered the odds of death and severe disease, suggesting that the addition of antiplatelet drugs to an antithrombotic treatment regimen for hospitalized COVID-19 patients may be an effective therapeutic option. Higher-powered prospective trials will be necessary to confirm our observations and the potential merits of antiplatelet therapy in these patients.

Author Bios

Swarna Reddy, MS planner and evaluator, North Carolina Division of Aging and Adult Services, Raleigh, North Carolina.

Divya Venkataganesan, MPH planner and evaluator, North Carolina Division of Aging and Adult Services, Raleigh, North Carolina.

Acknowledgments

All authors contributed to the writing of the manuscript. AB, BB, DCM, JC, and SPH created the experimental design. MRJ performed statistical analysis. AB, SPH, and DCM wrote the IRB. DCM acquired medical records. MRJ and SPH made figures.

This work was supported by the Honors College of Campbell University (AB), College of Pharmacy and Health Sciences, Department of Pharmaceutical Sciences and Clinical Research at Campbell University (MRJ, SPH), and the School of Osteopathic Medicine at Campbell University (KJ, BB, DCM, JC).

The authors declare no conflicts of interest.

References

  • 1.Thrombosis in hospitalized patients with COVID-19 in a New York City health system. Bilaloglu Seda, Aphinyanaphongs Yin, Jones Simon, Iturrate Eduardo, Hochman Judith, Berger Jeffrey S. Aug 25;2020 JAMA. 324(8):799–801. doi: 10.1001/jama.2020.13372. https://doi.org/10.1001/jama.2020.13372 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.The emerging threat of (micro) thrombosis in COVID-19 and its therapeutic implications. McFadyen James D., Stevens Hannah, Peter Karlheinz. Jul 31;2020 Circulation Research. 127(4):571–587. doi: 10.1161/circresaha.120.317447. https://doi.org/10.1161/circresaha.120.317447 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Ragab Dina, Salah Eldin Haitham, Taeimah Mohamed, Khattab Rasha, Salem Ramy. Frontiers in Immunology. 1446. Vol. 11. Frontiers Media SA; The COVID-19 cytokine storm; what we know so far.https://doi.org/10.3389/fimmu.2020.01446 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Ackermann Maximilian, Verleden Stijn E., Kuehnel Mark, Haverich Axel, Welte Tobias, Laenger Florian, Vanstapel Arno, Werlein Christopher, Stark Helge, Tzankov Alexandar, Li William W., Li Vincent W., Mentzer Steven J., Jonigk Danny. New England Journal of Medicine. 2. Vol. 383. Massachusetts Medical Society; Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19; pp. 120–128.https://doi.org/10.1056/nejmoa2015432 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Prevalence and outcomes of D-dimer elevation in hospitalized patients with COVID-19. Berger Jeffrey S., Kunichoff Dennis, Adhikari Samrachana, Ahuja Tania, Amoroso Nancy, Aphinyanaphongs Yindalon, Cao Meng, Goldenberg Ronald, Hindenburg Alexander, Horowitz James, Parnia Sam, Petrilli Christopher, Reynolds Harmony, Simon Emma, Slater James, Yaghi Shadi, Yuriditsky Eugene, Hochman Judith, Horwitz Leora I. Oct;2020 Arteriosclerosis, Thrombosis, and Vascular Biology. 40(10):2539–2547. doi: 10.1161/atvbaha.120.314872. https://doi.org/10.1161/atvbaha.120.314872 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.D-dimer level is associated with the severity of COVID-19. Yu Hai-Han, Qin Chuan, Chen Man, Wang Wei, Tian Dai-Shi. Nov;2020 Thrombosis Research. 195:219–225. doi: 10.1016/j.thromres.2020.07.047. https://doi.org/10.1016/j.thromres.2020.07.047 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Platelet receptors as therapeutic targets: past, present and future. Jamasbi Janina, Ayabe Keng, Goto Shinya, Nieswandt Bernhard, Peter Karlheinz, Siess Wolfgang. 2017Thrombosis and Haemostasis. 117(7):1249–1257. doi: 10.1160/th16-12-0911. https://doi.org/10.1160/th16-12-0911 [DOI] [PubMed] [Google Scholar]
  • 8.Gross P L, Weitz J I. Clinical Pharmacology & Therapeutics. 2. Vol. 86. Springer Science and Business Media LLC; New antithrombotic drugs; pp. 139–146.https://doi.org/10.1038/clpt.2009.98 [DOI] [PubMed] [Google Scholar]
  • 9.ISTH DIC subcommittee communication on anticoagulation in COVID-19. Thachil Jecko, Juffermans Nicole P., Ranucci Marco, Connors Jean M., Warkentin Theodore E., Ortel Thomas L., Levi Marcel, Iba Toshiaki, Levy Jerrold H. Sep;2020 Journal of Thrombosis and Haemostasis. 18(9):2138–2144. doi: 10.1111/jth.15004. https://doi.org/10.1111/jth.15004 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19. Cuker Adam, Tseng Eric K., Nieuwlaat Robby, Angchaisuksiri Pantep, Blair Clifton, Dane Kathryn, Davila Jennifer, DeSancho Maria T., Diuguid David, Griffin Daniel O., Kahn Susan R., Klok Frederikus A., Lee Alfred Ian, Neumann Ignacio, Pai Ashok, Pai Menaka, Righini Marc, Sanfilippo Kristen M., Siegal Deborah, Skara Mike, Touri Kamshad, A. Akl Elie, Bou Akl Imad, Boulos Mary, Brignardello-Petersen Romina, Charide Rana, Chan Matthew, Dearness Karin, Darzi Andrea J., Kolb Philipp, Colunga-Lozano Luis E., Mansour Razan, Morgano Gian Paolo, Morsi Rami Z., Noori Atefeh, Piggott Thomas, Qiu Yuan, Roldan Yetiani, Schünemann Finn, Stevens Adrienne, Solo Karla, Ventresca Matthew, Wiercioch Wojtek, Mustafa Reem A., Schünemann Holger J. Feb 8;2021 Blood Adv. 5(3):872–888. doi: 10.1182/bloodadvances.2020003763. https://doi.org/10.1182/bloodadvances.2020003763 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.The ATTACC, ACTIV-4a, and REMAP-CAP Investigators . New England Journal of Medicine. 9. Vol. 385. Massachusetts Medical Society; Therapeutic anticoagulation with heparin in noncritically ill patients with Covid-19; pp. 790–802.https://doi.org/10.1056/nejmoa2105911 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.The REMAP-CAP, ACTIV-4a, and ATTACC Investigators . New England Journal of Medicine. 9. Vol. 385. Massachusetts Medical Society; Therapeutic anticoagulation with heparin in critically ill patients with Covid-19; pp. 777–789.https://doi.org/10.1056/nejmoa2103417 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Al-Samkari Hanny, Karp Leaf Rebecca S., Dzik Walter H., Carlson Jonathan C. T., Fogerty Annemarie E., Waheed Anem, Goodarzi Katayoon, Bendapudi Pavan K., Bornikova Larissa, Gupta Shruti, Leaf David E., Kuter David J., Rosovsky Rachel P. Blood. 4. Vol. 136. American Society of Hematology; COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection; pp. 489–500.https://doi.org/10.1182/blood.2020006520 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Matli Kamal, Farah Raymond, Maalouf Mario, Chamoun Nibal, Costanian Christy, Ghanem Georges. Open Heart. 1. Vol. 8. BMJ; Role of combining anticoagulant and antiplatelet agents in COVID-19 treatment: a rapid review; p. e001628.https://doi.org/10.1136/openhrt-2021-001628 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.COVID-19 death rates are higher in rural counties with larger shares of Blacks and Hispanics. Cheng Kent Jason G., Sun Yue, Monnat Shannon M. Sep;2020 The Journal of Rural Health. 36(4):602–608. doi: 10.1111/jrh.12511. https://doi.org/10.1111/jrh.12511 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Health Statistics and Data. [2021-11-1]. https://www.ncdhhs.gov/divisions/office-rural-health/office-rural-health-programs/analytics-and-innovations-program/health-statistics-and-data Accessed November 1, 2021.
  • 17.Moving to a world beyond “p0.05”. Wasserstein Ronald L., Schirm Allen L., Lazar Nicole A. Mar 20;2019 The American Statistician. 73(Suppl1):1–19. doi: 10.1080/00031305.2019.1583913. https://doi.org/10.1080/00031305.2019.1583913 [DOI] [Google Scholar]
  • 18.COVID-19 associated coagulopathy: thrombosis, hemorrhage and mortality rates with an escalated-dose thromboprophylaxis strategy. Daughety Molly M., Morgan Andrew, Frost Erin, Kao Chester, Hwang Joyce, Tobin Rachel, Patel Bhavik, Fuller Matthew, Welsby Ian, Ortel Thomas L. Dec;2020 Thrombosis Research. 196:483–485. doi: 10.1016/j.thromres.2020.10.004. https://doi.org/10.1016/j.thromres.2020.10.004 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Al-Samkari Hanny, Gupta Shruti, Leaf Rebecca Karp, Wang Wei, Rosovsky Rachel P., Brenner Samantha K., Hayek Salim S., Berlin Hanna, Kapoor Rajat, Shaefi Shahzad, Melamed Michal L., Sutherland Anne, Radbel Jared, Green Adam, Garibaldi Brian T., Srivastava Anand, Leonberg-Yoo Amanda, Shehata Alexandre M., Flythe Jennifer E., Rashidi Arash, Goyal Nitender, Chan Lili, Mathews Kusum S., Hedayati S. Susan, Dy Rajany, Toth-Manikowski Stephanie M., Zhang Jingjing, Mallappallil Mary, Redfern Roberta E., Bansal Amar D., Short Samuel A.P., Vangel Mark G., Admon Andrew J., Semler Matthew W., Bauer Kenneth A., Hernán Miguel A., Leaf David E., Walther Carl P., Anumudu Samaya J., Arunthamakun Justin, Kopecky Kathleen F., Milligan Gregory P., McCullough Peter A., Nguyen Thuy-Duyen, Shaefi Shahzad, Krajewski Megan L., Shankar Sidharth, Pannu Ameeka, Valencia Juan D., Bauer Kenneth A., Waikar Sushrut S., Kibbelaar Zoe A., Athavale Ambarish M., Hart Peter, Upadhyay Shristi, Vohra Ishaan, Oyintayo Ajiboye, Green Adam, Rachoin Jean-Sebastien, Schorr Christa A., Shea Lisa, Edmonston Daniel L., Mosher Christopher L., Shehata Alexandre M., Cohen Zaza, Allusson Valerie, Bambrick-Santoyo Gabriela, aain Bhatti Noor ul, Mehta Bijal, Williams Aquino, Brenner Samantha K., Walters Patricia, Go Ronaldo C., Rose Keith M., Hernán Miguel A., Zhou Amy M., Kim Ethan C., Lisk Rebecca, Chan Lili, Mathews Kusum S., Coca Steven G., Altman Deena R., Saha Aparna, Soh Howard, Wen Huei Hsun, Bose Sonali, Leven Emily A., Wang Jing G., Mosoyan Gohar, Pattharanitima Pattharawin, Gallagher Emily J., Friedman Allon N., Guirguis John, Kapoor Rajat, Meshberger Christopher, Kelly Katherine J., Parikh Chirag R., Garibaldi Brian T., Corona-Villalobos Celia P., Wen Yumeng, Menez Steven, Malik Rubab F., Cervantes Carmen Elena, Gautam Samir C., Mallappallil Mary C., Ouyang Jie, John Sabu, Yap Ernie, Melaku Yohannes, Mohamed Ibrahim, Bajracharya Siddhartha, Puri Isha, Thaxton Mariah, Bhattacharya Jyotsna, Wagner John, Boudourakis Leon, Nguyen H. Bryant, Ahoubim Afshin, Thomas Leslie F., Sirganagari Dheeraj Reddy, Guru Pramod K., Zhou Yan, Bergl Paul A., Rodriguez Jesus, Shah Jatan A., Gupta Mrigank S., Kumar Princy N., Lazarous Deepa G., Kassaye Seble G., Melamed Michal L., Johns Tanya S., Mocerino Ryan, Prudhvi Kalyan, Zhu Denzel, Levy Rebecca V., Azzi Yorg, Fisher Molly, Yunes Milagros, Sedaliu Kaltrina, Golestaneh Ladan, Brogan Maureen, Thakkar Jyotsana, Kumar Neelja, Ross Michael J., Chang Michael, Raichoudhury Ritesh, Athreya Akshay, Farag Mohamed, Schenck Edward J., Cho Soo Jung, Plataki Maria, Alvarez-Mulett Sergio L., Gomez-Escobar Luis G., Pan Di, Lee Stefi, Krishnan Jamuna, Whalen William, Charytan David, Macina Ashley, Srivastava Anand, Leidner Alexander S., Martinez Carlos, Kruser Jacqueline M., Wunderink Richard G., Hodakowski Alexander J., Q. Velez Juan Carlos, Price-Haywood Eboni G., Matute-Trochez Luis A., Hasty Anna E., Mohamed Muner M.B., Avasare Rupali S., Zonies David, Leaf David E., Gupta Shruti, Al-Samkari Hanny, Leaf Rebecca Karp, Rosovsky Rachel, Sise Meghan E., Newman Erik T., Omar Samah Abu, Pokharel Kapil K., Sharma Shreyak, Singh Harkarandeep, Correa Simon, Shaukat Tanveer, Kamal Omer, Wang Wei, Lee Meghan, Strohbehn Ian A., Li Jiahua, Mueller Ariel L., Redfern Roberta E., Cairl Nicholas S., Naimy Gabriel, Abu-Saif Abeer, Hall Danyell, Bickley Laura, Rowan Chris, Madhani-Lovely Farah, Peev Vasil, Reiser Jochen, Byun John J., Vissing Andrew, Kapania Esha M., Post Zoe, Patel Nilam P., Hermes Joy-Marie, Sutherland Anne K., Patrawalla Amee, Finkel Diana G., Danek Barbara A., Arikapudi Sowminya, Paer Jeffrey M., Cangialosi Peter, Liotta Mark, Radbel Jared, Puri Sonika, Sunderram Jag, Scharf Matthew T., Ahmed Ayesha, Berim Ilya, Vatson Jayanth S., Karp George, Anand Shuchi, Levitt Joseph E., Garcia Pablo, Boyle Suzanne M., Song Rui, Zhang Jingjing, Woo Sang Hoon, Deng Xiaoying, Katz-Greenberg Goni, Sharshir Moh'd A., Rusnak Vadym V., Ali Muhammad Imran, Bansal Anip, Podoll Amber S., Chonchol Michel, Sharma Sunita, Burnham Ellen L., Rashidi Arash, Hejal Rana, Judd Eric, Latta Laura, Tolwani Ashita, Albertson Timothy E., Adams Jason Y., Chang Steven Y., Beutler Rebecca M., Schulze Carl E., Macedo Etienne, Rhee Harin, Liu Kathleen D., Jotwani Vasantha K., Koyner Jay L., Shah Chintan V., Jaikaransingh Vishal, Toth-Manikowski Stephanie M., Joo Min J., Lash James P., Neyra Javier A., Chaaban Nourhan, Elias Madona, Ahmad Yahya, Dy Rajany, Iardino Alfredo, Au Elizabeth H., Sharma Jill H., Sosa Marie Anne, Taldone Sabrina, Contreras Gabriel, De La Zerda David, Gershengorn Hayley B., Fornoni Alessia, Hayek Salim S., Blakely Pennelope, Berlin Hanna, Azam Tariq U., Shadid Husam, Pan Michael, O’Hayer Patrick, Meloche Chelsea, Feroze Rafey, Padalia Kishan J., Leya Jeff, Donnelly John P., Admon Andrew J., Flythe Jennifer E., Tugman Matthew J., Chang Emily H., Brown Brent R., Leonberg-Yoo Amanda K., Spiardi Ryan C., Miano Todd A., Roche Meaghan S., Vasquez Charles R., Bansal Amar D., Ernecoff Natalie C., Kapoor Sanjana, Verma Siddharth, Chen Huiwen, Kovesdy Csaba P., Molnar Miklos Z., Azhar Ambreen, Hedayati S. Susan, Nadamuni Mridula V., Shastri Shani, Willett Duwayne L., Short Samuel A.P., Renaghan Amanda D., Enfield Kyle B., Bhatraju Pavan K., Malik A. Bilal, Semler Matthew W., Vijayan Anitha, Joy Christina Mariyam, Li Tingting, Goldberg Seth, Kao Patricia F., Schumaker Greg L., Goyal Nitender, Faugno Anthony J., Schumaker Greg L., Hsu Caroline M., Tariq Asma, Meyer Leah, Kshirsagar Ravi K., Weiner Daniel E., Christov Marta, Griffiths Jennifer, Gupta Sanjeev, Kapoor Aromma, Chugh Savneek, Wilson Perry, Arora Tanima, Ugwuowo Ugochukwu. Annals of Internal Medicine. 5. Vol. 174. American College of Physicians; Thrombosis, bleeding, and the observational effect of early therapeutic anticoagulation on survival in critically ill patients with COVID-19; pp. 622–632.https://doi.org/10.7326/m20-6739 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. Cui Songping, Chen Shuo, Li Xiunan, Liu Shi, Wang Feng. Jun;2020 Journal of Thrombosis and Haemostasis. 18(6):1421–1424. doi: 10.1111/jth.14830. https://doi.org/10.1111/jth.14830 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Klok F.A., Kruip M.J.H.A., van der Meer N.J.M., Arbous M.S., Gommers D.A.M.P.J., Kant K.M., Kaptein F.H.J., van Paassen J., Stals M.A.M., Huisman M.V., Endeman H. Jul;2020 Thrombosis Research. 191:145–147. doi: 10.1016/j.thromres.2020.04.013. https://doi.org/10.1016/j.thromres.2020.04.013 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Garg Shikha, Kim Lindsay, Whitaker Michael, O’Halloran Alissa, Cummings Charisse, Holstein Rachel, Prill Mila, Chai Shua J., Kirley Pam D., Alden Nisha B., Kawasaki Breanna, Yousey-Hindes Kimberly, Niccolai Linda, Anderson Evan J., Openo Kyle P., Weigel Andrew, Monroe Maya L., Ryan Patricia, Henderson Justin, Kim Sue, Como-Sabetti Kathy, Lynfield Ruth, Sosin Daniel, Torres Salina, Muse Alison, Bennett Nancy M., Billing Laurie, Sutton Melissa, West Nicole, Schaffner William, Talbot H. Keipp, Aquino Clarissa, George Andrea, Budd Alicia, Brammer Lynnette, Langley Gayle, Hall Aron J., Fry Alicia. MMWR. Morbidity and Mortality Weekly Report. 15. Vol. 69. Centers for Disease Control MMWR Office; Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 — COVID-NET, 14 States, March 1–30, 2020; pp. 458–464.https://doi.org/10.15585/mmwr.mm6915e3 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: A systematic review and meta-analysis. Fu L., Wang B., Yuan T.., et al. 2020J Infect. 80(6):656–665. doi: 10.1016/j.jinf.2020.03.041. https://doi.org/10.1016/j.jinf.2020.03.041 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.The coronavirus pandemic has forced rapid changes in care protocols for cystic fibrosis. Davies Jane. Jul 29;2020 Nature. 583(7818):S15. doi: 10.1038/d41586-020-02112-y. https://doi.org/10.1038/d41586-020-02112-y [DOI] [PubMed] [Google Scholar]
  • 25.QuickFacts: Cumberland County, North Carolina. Jul 1;2021 [2021-9-20];US Census Bureau website. https://www.census.gov/quickfacts/cumberlandcountynorthcarolina Accessed September 20, 2021.
  • 26.Characteristics associated with hospitalization among patients with COVID-19 – metropolitan Atlanta, Georgia, March – April 2020. Killerby Marie E., Link-Gelles Ruth, Haight Sarah C., Schrodt Caroline A., England Lucinda, Gomes Danica J., Shamout Mays, Pettrone Kristen, O'Laughlin Kevin, Kimball Anne, Blau Erin F., Burnett Eleanor, Ladva Chandresh N., Szablewski Christine M., Tobin-D’Angelo Melissa, Oosmanally Nadine, Drenzek Cherie, Murphy David J., Blum James M., Hollberg Julie, Lefkove Benjamin, Brown Frank W., Shimabukuro Tom, Midgley Claire M., Tate Jacqueline E., Browning Sean D., Bruce Beau B., da Silva Juliana, Gold Jeremy A.W., Jackson Brendan R., Bamrah Morris Sapna, Natarajan Pavithra, Neblett Fanfair Robyn, Patel Priti R., Rogers-Brown Jessica, Rossow John, Wong Karen K., CDC COVID-19 Response Clinical Team. CDC COVID-19 Response Clinical Team Jun 26;2020 MMWR. Morbidity and Mortality Weekly Report. 69(25):790–794. doi: 10.15585/mmwr.mm6925e1. https://doi.org/10.15585/mmwr.mm6925e1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Goshua George, Pine Alexander B, Meizlish Matthew L, Chang C-Hong, Zhang Hanming, Bahel Parveen, Baluha Audrey, Bar Noffar, Bona Robert D, Burns Adrienne J, Dela Cruz Charles S, Dumont Anne, Halene Stephanie, Hwa John, Koff Jonathan, Menninger Hope, Neparidze Natalia, Price Christina, Siner Jonathan M, Tormey Christopher, Rinder Henry M, Chun Hyung J, Lee Alfred I. Aug;2020 The Lancet Haematology. 7(8):e575–e582. doi: 10.1016/s2352-3026(20)30216-7. https://doi.org/10.1016/s2352-3026(20)30216-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Causes of elevated D-dimer in patients admitted to a large urban emergency department. Lippi Giuseppe, Bonfanti Laura, Saccenti Carlotta, Cervellin Gianfranco. Jan;2014 European Journal of Internal Medicine. 25(1):45–48. doi: 10.1016/j.ejim.2013.07.012. https://doi.org/10.1016/j.ejim.2013.07.012 [DOI] [PubMed] [Google Scholar]
  • 29.Help me, Doctor! My D-dimer is raised. Lippi Giuseppe, Franchini Massimo, Targher Giovanni, Favaloro Emmanuel J. Jan;2008 Annals of Medicine. 40(8):594–605. doi: 10.1080/07853890802161015. https://doi.org/10.1080/07853890802161015 [DOI] [PubMed] [Google Scholar]
  • 30.Never ignore extremely elevated D-dimer levels: they are specific for serious illness. Schutte T., Thijs A., Smulders Y.M. 2016Neth J Med. 74(10):443–448. [PubMed] [Google Scholar]
  • 31.Elevated D-dimer levels are associated with increased risk of mortality in Coronavirus Disease 2019: a systematic review and meta-analysis. Shah Siddharth, Shah Kuldeep, Patel Siddharth B., Patel Foram S., Osman Mohammed, Velagapudi Poonam, Turagam Mohit K., Lakkireddy Dhanunjaya, Garg Jalaj. Jul 2;2020 Cardiol Rev. 28(6):295–302. doi: 10.1097/crd.0000000000000330. https://doi.org/10.1097/crd.0000000000000330 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Harper P. L, Theakston E., Ahmed J., Ockelford P. Internal Medicine Journal. 9. Vol. 37. Wiley; D-dimer concentration increases with age reducing the clinical value of the D-dimer assay in the elderly; pp. 607–613.https://doi.org/10.1111/j.1445-5994.2007.01388.x [DOI] [PubMed] [Google Scholar]
  • 33.Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. Schouten H. J., Geersing G. J., Koek H. L., Zuithoff N. P. A., Janssen K. J. M., Douma R. A., van Delden J. J. M., Moons K. G. M., Reitsma J. B. May 3;2013 BMJ. 346(1):f2492–f2492. doi: 10.1136/bmj.f2492. https://doi.org/10.1136/bmj.f2492 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Antibody-mediated platelet activation in COVID-19: a coincidence or a new mechanism of the dysregulated coagulation system? Althaus Karina, Zlamal Jan, Bakchoul Tamam. May;2021 Journal of Thrombosis and Haemostasis. 19(5):1171–1173. doi: 10.1111/jth.15275. https://doi.org/10.1111/jth.15275 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Hottz Eugenio D., Azevedo-Quintanilha Isaclaudia G., Palhinha Lohanna, Teixeira Lívia, Barreto Ester A., Pão Camila R. R., Righy Cassia, Franco Sérgio, Souza Thiago M. L., Kurtz Pedro, Bozza Fernando A., Bozza Patrícia T. Blood. 11. Vol. 136. American Society of Hematology; Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19; pp. 1330–1341.https://doi.org/10.1182/blood.2020007252 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Manne Bhanu Kanth, Denorme Frederik, Middleton Elizabeth A., Portier Irina, Rowley Jesse W., Stubben Chris, Petrey Aaron C., Tolley Neal D., Guo Li, Cody Mark, Weyrich Andrew S., Yost Christian C., Rondina Matthew T., Campbell Robert A. Blood. 11. Vol. 136. American Society of Hematology; Platelet gene expression and function in patients with COVID-19; pp. 1317–1329.https://doi.org/10.1182/blood.2020007214 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Platelet activation in critically ill COVID-19 patients. Yatim Nader, Boussier Jeremy, Chocron Richard, Hadjadj Jérôme, Philippe Aurélien, Gendron Nicolas, Barnabei Laura, Charbit Bruno, Szwebel Tali-Anne, Carlier Nicolas, Pène Frédéric, Azoulay Célia, Khider Lina, Mirault Tristan, Diehl Jean-Luc, Guerin Coralie L., Rieux-Laucat Frédéric, Duffy Darragh, Kernéis Solen, Smadja David M., Terrier Benjamin. Jul 17;2021 Annals of Intensive Care. 11(1):113. doi: 10.1186/s13613-021-00899-1. https://doi.org/10.1186/s13613-021-00899-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Platelet reactivity to thrombin differs between patients with COVID-19 and those with ARDS unrelated to COVID-19. Zaid Younes, Guessous Fadila, Puhm Florian, Elhamdani Wail, Chentoufi Lamyae, Morris Andrew Conway, Cheikh Amine, Jalali Farid, Boilard Eric, Flamand Louis. Jan 29;2021 Blood Adv. 5(3):635–639. doi: 10.1182/bloodadvances.2020003513. https://doi.org/10.1182/bloodadvances.2020003513 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Platelets contribute to disease severity in COVID-19. Barrett Tessa J., Bilaloglu Seda, Cornwell Macintosh, Burgess Hannah M., Virginio Vitor W., Drenkova Kamelia, Ibrahim Homam, Yuriditsky Eugene, Aphinyanaphongs Yin, Lifshitz Mark, Xia Liang Feng, Alejo Julie, Smith Grace, Pittaluga Stefania, Rapkiewicz Amy V., Wang Jun, Iancu-Rubin Camelia, Mohr Ian, Ruggles Kelly, Stapleford Kenneth A., Hochman Judith, Berger Jeffrey S. Dec;2021 Journal of Thrombosis and Haemostasis. 19(12):3139–3153. doi: 10.1111/jth.15534. https://doi.org/10.1111/jth.15534 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Plasma proteomics identify biomarkers and pathogenesis of COVID-19. Shu Ting, Ning Wanshan, Wu Di, Xu Jiqian, Han Qiangqiang, Huang Muhan, Zou Xiaojing, Yang Qingyu, Yuan Yang, Bie Yuanyuan, Pan Shangwen, Mu Jingfang, Han Yang, Yang Xiaobo, Zhou Hong, Li Ruiting, Ren Yujie, Chen Xi, Yao Shanglong, Qiu Yang, Zhang Ding-Yu, Xue Yu, Shang You, Zhou Xi. Nov;2020 Immunity. 53(5):1108–1122.e1105. doi: 10.1016/j.immuni.2020.10.008. https://doi.org/10.1016/j.immuni.2020.10.008 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Platelet and haemostasis are the main targets in severe cases of COVID-19 infection; a system biology study. Zamanian-Azodi M., Arjmand B., Razzaghi M., Rezaei Tavirani M., Ahmadzadeh A., Rostaminejad M. 2021Arch Acad Emerg Med. 9(1):e27. doi: 10.22037/aaem.v9i1.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Aspirin use is associated with decreased mechanical ventilation, intensive care unit admission, and in-hospital mortality in hospitalized patients with Coronavirus Disease 2019. Chow Jonathan H., Khanna Ashish K., Kethireddy Shravan, Yamane David, Levine Andrea, Jackson Amanda M., McCurdy Michael T., Tabatabai Ali, Kumar Gagan, Park Paul, Benjenk Ivy, Menaker Jay, Ahmed Nayab, Glidewell Evan, Presutto Elizabeth, Cain Shannon, Haridasa Naeha, Field Wesley, Fowler Jacob G., Trinh Duy, Johnson Kathleen N., Kaur Aman, Lee Amanda, Sebastian Kyle, Ulrich Allison, Peña Salvador, Carpenter Ross, Sudhakar Shruti, Uppal Pushpinder, Fedeles Benjamin T., Sachs Aaron, Dahbour Layth, Teeter William, Tanaka Kenichi, Galvagno Samuel M., Herr Daniel L., Scalea Thomas M., Mazzeffi Michael A. 2021Anesth Analg. 132(4):930–941. doi: 10.1213/ane.0000000000005292. https://doi.org/10.1213/ane.0000000000005292 [DOI] [PubMed] [Google Scholar]
  • 43.Enhanced platelet inhibition treatment improves hypoxemia in patients with severe Covid-19 and hypercoagulability. A case control, proof of concept study. Viecca Maurizio, Radovanovic Dejan, Forleo Giovanni Battista, Santus Pierachille. Aug;2020 Pharmacological Research. 158:104950. doi: 10.1016/j.phrs.2020.104950. https://doi.org/10.1016/j.phrs.2020.104950 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Association of prehospital antiplatelet therapy with survival in patients hospitalized with COVID-19: a propensity score-matched analysis. Chow Jonathan H., Yin Ying, Yamane David P., Davison Danielle, Keneally Ryan J., Hawkins Katrina, Parr K. Gage, Al-Mashat Mustafa, Berger Jeffery S., Bushardt Reamer L., Mazzeffi Michael A., Nelson Stuart J. Nov;2021 Journal of Thrombosis and Haemostasis. 19(11):2814–2824. doi: 10.1111/jth.15517. https://doi.org/10.1111/jth.15517 [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from North Carolina Medical Journal are provided here courtesy of North Carolina Institute of Medicine

RESOURCES