Successful Use of Glycoprotein IIb/IIIa Inhibitor Involving Severely Ill COVID-19 Patient


Patrick Joseph Merrill, MD, FACP1; R Mark Bradburne, MD, FACCP2

Perm J 2021;25:21.125

This case report describes a successful outcome involving a patient with severe COVID-19 viral pneumonia utilizing a novel therapeutic approach with the glycoprotein IIb/IIIa inhibitor, eptifibatide.


COVID-19–infected patients commonly are afflicted with thromboembolic complications due to direct and indirect effects of the virus.1 The objective of this case report is to consider an alternative therapeutic approach to reduce morbidity/mortality from intravascular thromboembolic events utilizing glycoprotein (GP) IIb/IIIa inhibition. Here, we report a case of successful outcome involving a patient with severe COVID-19 viral pneumonia utilizing a novel therapeutic approach with the GP IIb/IIIa inhibitor, eptifibatide.


A 34-year-old female correctional officer presented with 1 week of symptoms including diarrhea and cough. Five days prior to admission, she had a fever of 102.9°F and headache. Two days prior to admission she lost her sense of taste and smell.

Her past medical history included poorly controlled type 2 diabetes (on insulin), hypothyroidism (on replacement therapy), longstanding microcytic anemia, and morbid obesity.

At admission on August 27, 2020, her symptoms included nonproductive cough, fatigue, chest pains with palpitations, pleuritic pain, shortness of breath, and nausea with occasional vomiting. Her vital signs were temperature 102.3°F, BP 137/83 mmHg, pulse 132 BPM, respiratory rate 35 breaths per minute with O2 saturation of 84% on 3 liters per minute of nasal cannula O2. Her weight was 259 pounds (BMI 41.77). Physical examination showed an anxious young woman in moderate respiratory distress. Lung fields were clear bilaterally on auscultation.

Laboratory studies (for normal value range and units see Table 1) showed Hgb 12.4, Hct 38.5, MCV 75.4, WBC 6.5, platelets 154. Na+ 134, K+ 3.5, Cl- 98, HCO3- 21. Lactate was 1.8 , Alk phos 135, ALT 194, AST 151, LDH 254, CRP 224.2, D-dimer 0.99, HgbA1c 15.3%, ferritin 164, and lymphocyte count of 0.95. Procalcitonin was 0.28; UA was positive for ketones. The CXR showed bilateral hazy infiltrates.

Table 1.

Test Normal range Units
Hemoglobin (Hgb) 12.0-16.0 g/dL
Hematocrit (Hct) 37.0-47.0 %
Mean corpuscular volume (MCV) 81.0-99.0 femtoliters (fL)
White blood count (WBC) 4.0-11.0 ´ 1,000/mcL
Platelets 130-400 ´ 1,000/mcL
Na+ 135-145 mEq/L
K+ 3.5-5.0 mEq/L
Cl- 101-111 mEq/L
HCO3- 21-31 mEq/L
Serum lactate 0.5-1.9 mmol/L
Alkaline phosphatase (Alk phos) < 125 u/L
ALT < 54 u/L
AST < 30 u/L
LDH < 180 IU/L
C-reactive protein (CRP) < 7.4 mg/L
D-dimer < 0.49 mcgFEU/ml
HgbA1c 4.6-6.9 %
Ferritin 13-126 ng/ml
Procalcitonin < 0.05 ng/ml
Fibrinogen 218-441 mg/dL
Lymphocyte count 1.00-3.60 ´ 1,000/mcL
Troponin I < 0.03 ng/ml

The patient was admitted for diabetic ketoacidosis and “patient under investigation” for COVID-19 pneumonia. The COVID-19 test returned as positive the following day.

She was initially on a nasal cannula at 3 liters per minute of O2, which was increased to 40 liters per minute with a high-flow nasal cannula. An Infectious Disease consult on August 28, 2020 recommended standard remdesivir and Decadron therapy, and she was placed on an anti-DVT prophylactic dose of enoxaparin (40 mg subcutaneously twice a day) and insulin NPH with regular insulin sliding scale as necessary to resolve diabetic ketoacidosis and control blood sugars. Due to desaturating episodes, she was transferred to the Intensive Care Unit anticipating impending intubation on August 28, 2020. The patient continued with progressive dyspnea but was maintained on high-flow nasal cannula O2. A troponin I test done on August 30, 2020 was 0.05.

By August 30, 2020, her CBC showed Hgb 10.8, Hct 34.3, WBC 4.9, and platelets 176. CRP rose to 264.4, ferritin 190, D-dimer 1.60, fibrinogen 779, LDH 307, ALT 143, Alk phos 139, and lymphocyte count 0.82. Due to elevated TNI, diabetic ketoacidosis, and symptoms of chest discomfort, eptifibatide for NSTEMI protocol as well as anti-thrombotic therapy were initiated and 0.25 inch of nitroglycerin topical ointment 2% was applied every 6 hours. The patient was deemed to be an appropriate candidate for GP IIb/IIIa therapy, and the risks and benefits of that treatment were discussed. After being informed, the patient consented to the use of eptifibatide. She received a loading dose of 180 mcg/kg of intravenous eptifibatide and continued with 2 mcg/kg/min shortly after noon on August 30, 2020. Her enoxaparin was held the following morning due to onset of menses during the early hours of August 31, 2020. CRP dropped to 50.5, ferritin to 163, D-dimer to 1.29, fibrinogen to 611, LDH to 272, ALT to 119, and Alk phos to 118. Enoxaparin was restarted that afternoon, but during the early hours of September 1, 2020, the eptifibatide and enoxaparin were held due to nasal sinus bleeding. Within 1 hour, the patient’s O2 saturation decreased, and she was placed on a bilevel positive airway pressure mask. CRP rose again to 162.3, ferritin to 175, D-dimer to 3.9, fibrinogen to 800, LDH to 368, ALT to 164,  and Alk phos to 161. The eptifibatide and enoxaparin were restarted 6 hours after interruption and by September 4, 2020, CRP reduced to 53.4, ferritin to 157, D-dimer to 2.08, fibrinogen to 735, and lymphocyte count to 1.39. Subsequent troponin tests were normal, and ECGs showed no evidence of injury. She returned to high-flow nasal cannula O2, yet LFTs remained moderately elevated. A repeat COVID-19 test was positive on September 3, 2020. The remdesivir 6 day treatment had expired on September 3, 2020, and hydroxychloroquine was started at 200 mg orally twice a day on September 4, 2020. The patient’s eptifibatide was discontinued on September 4, 2020. She was placed on dual antiplatelet therapy with ECASA 81 mg daily and ticagrelor 90 mg twice a day. Repeat CRP by September 5, 2020 was 38.6, ferritin 175, D-dimer 1.47, and lymphocyte count 1.57. Her symptoms had significantly abated and O2 supplementation was able to be reduced. She will continue on dual antiplatelet therapy until inflammatory markers normalize.


Endothelial cells are known to have ACE2 receptors,2 and they are also known to be adversely affected by COVID-19 viral infection.3 Despite anticoagulation therapies, which have shown some promise, morbidity and mortality due to hypercoagulation complications remain the remain one of the most challenging aspects in the management of severely and critically ill COVID-19–infected patients.

Antiplatelet therapy with dipyridamole had been shown to be promising early on in the pandemic,4 but no large-scale randomized controlled trial has been reported to suggest this as a mainstay of treatment. Many features of severely and critically ill COVID-19–infected patients mimic microangiopathic hemolytic anemia. Recent research suggests possible benefits by treating patients with plasma exchange therapy similar to management of thrombotic thrombocytopenic purpura patients.5

An alternative approach may be to use GP IIb/IIIa inhibition to decrease thrombosis due to platelet activation from denuded microvascular beds. This may prevent downstream end organ necrosis while endothelial cell repair may take place. Our case presentation demonstrates rather immediate improvement in all measured inflammatory markers, only to worsen significantly within 2 hours of interruption. Slow improvement occurred with re-initiation (without re-bolus) suggesting that GP IIb/IIIa inhibition had a substantial effect in reducing inflammatory markers and patient symptoms within 5 days of therapy. Of note, the patient’s lymphocyte count began to normalize within 48 hours of initiation of therapy. Our success with this case will hopefully lead to more robust randomized controlled trials utilizing GP IIb/IIIa inhibition in an effort to augment antithrombotic treatment in severely/critically ill COVID-19–infected patients as well as other scenarios where microangiopathic hemolytic anemia due to endothelial denuding processes occurs.

Disclosure Statement

The author(s) have no conflicts of interest to disclose.

Funding Statement

No funding was received for this work.


The authors wish to thank Dr. Virgil Nielsen for graciously reviewing the manuscript and making editorial improvements.

Author Affiliations

1 Department of Cardiology, Riverside Kaiser Hospital, Southern California Permanente Medical Group, Riverside, CA

2 Department of Pulmonology, Riverside Kaiser Hospital, Southern California Permanente Medical Group, Riverside, CA

Corresponding Author

Patrick Joseph Merrill, MD, FACP (;

Author Contributions

Patrick Joseph Merrill, MD, FACP, was the investigator and wrote the report; R Mark Bradburne MD, FACCP, verified the therapy and the integrity of the report.


1. Bikdeli M, Madhavan M, Jimenez D, et al. COVID-19 and thrombotic or thromboembolic disease: Implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol 2020 Jun;75(23):2950–73. DOI:

2. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004 Jun;203(2):631–7. DOI:

3. Guervilly C, Burtey S, Sabatier F, et al. Circulating endothelial cells as a marker of endothelial injury in severe COVID-19. J Infect Dis 2020 Nov;222(11):1789–93. DOI:

4. Liu X, Li Z, Liu S, et al. Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19. Acta Pharm Sin B 2020 Jul;10(7):1205–15. DOI:

5. Tabibi S, Tabibi T, Conic RRZ, Banisaeed N, Streiff MB. Therapeutic plasma exchange: A potential management strategy for critically ill COVID-19 patients. J Intensive Care Med 2020 Sep;35(9):827–35. DOI:

Keywords: COVID-19, eptifibatide, platelets, glycoprotein IIb/IIIa, case report

AbbreviationsGP = glycoprotein


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