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Dipyridamole Added to Anticoagulant Prophylaxis: Decline in Poor Outcome of Clinically Severe Ill COVID-2019 Patients

S. Kalayoglu Besisik, M. Ozbalak, Y.B. Tor, A. Alibeyoglu, M. Kose, N. Şenkal, A. Cagatay, M. Erelel, A. Gul, F. Esen, S. Umman, U. Isoglu Alkoclar, T. Tukek

Istanbul University Istanbul Medical Faculty, Istanbul, Turkey

Abstract Number: PB/CO01

Meeting: ISTH 2020 Congress

Theme: Coagulation and Natural Anticoagulants » Regulation of Coagulation

Background: Initial reports suggest a coagulopathy mimicking DIC and thrombotic microangiopathy associates Coronavirus disease 2019 (COVID-2019). The outcome was with thrombotic complications related morbidity which was found to be the main contributor to death in patients with severe COVID-2019. The guidelines are established and anticoagulant therapy became the standard of care.

Aims: We here present our experience with hospitalized COVID-2019 patients, in whom we added dipyridamole to anticoagulant prophylaxis.

Methods: All hospitalized COVID-2019 adult patients were stratified as moderate, severe or critically ill disease according to radiology and clinical findings. The data was collected retrospectively by screening the medical records from electronic files. The treatment protocol included favipravir and anticytokine treatment when patients deteriorating under treatment hydroxychlorakine and azytromycin. All patients had received anticoagulant treatment with low molecular weight heparins and dypridamole as bid 75mg orally.

Results: A total of 510 patients were hospitalized with a diagnosis of COVID-2019 between March 11th and May 5th of 2020(Table1). A total of 48 patients were excluded from the analysis. 462 patients were included in the final analysis. The median age was 56 and 61.5% were male. About 30% were above the age of 65. About 62% had SARS-CoV2 positivity in nose and throat swab polymerase chain reaction analysis. 93 patients did not receive dypridamol. The administration of dypiridamol independently decreased the risk of both demonstrated coagulopathy (HR:0.62;p=0.018; 95%CI:0.0062-0.62) and highly suspected coagulopathy (HR:0.12;p=0.001, 95%CI:0.032-0.41)(Table2). Dypiridamol administration did not have an impact on the survival and severity progression in the short-term follow-up.

Conclusions: Dipyridamole is an antiplatelet agent and acts as a phosphodiesterase inhibitor that increases intracellular cAMP/cGMP. Its probable antiviral activity, antinflammatory and mucosal healing and inhibitory propert against acute injury and progressive fibrosis. We advocate further trials for DIP adjunctive therapy for patients with COVID-2019, particularly for those with early signs of elevated concentrations of D-dimer.

Median Age (range) 56 (23-98) Initial vital signs   Comorbid conditions   Anti-hypertensive exposure 177 (38%)
Sex   Median saturation on pulse oximetry (range) 96% (70-100) Hypertension 182 (40%) ACE inh 35 (8%)
Female (%) Male (%) 178 (38.5%) 284 (61.5%) Median systolic blood pressure (range) 130 (80-250) Diabetes mellitus 100 (22%) ARB 83 (18%)
Initial symptoms   Median diastolic blood pressure (range) 75 (50-136) COPD or Asthma 56 (12%) Acute conditions at the time of initial presentation  
Fatigue and myalgia 432 (94%) Median pulse rate (range) 93 (66-190) Coronary artery disease 51 (11%) Acut kidney failure 10
Cough 389 (84%) Median respiratory rate (range) 18 (12-36) Congestive heart failure 30 (6.5%) Increase in creatinine kinase 4
Fever 224 (72%) COVID RT-PCR positive vs negative 285 vs 177 Solid malignancy 22 (5) Acute myocardial infarction 1
Dyspnea 198 (43%) Initial computerized tomography feature   Hematologic malignancy 13 (3%) Deep venous thrombosis 1
Nausea Diarrhea 71 (15%) 54 (12%) Mild pneumonia 218 (49%) Median number of comorbidities (range) 1 (0-6) Hypertensive pulmonary edema 1
Ansomia Sputum 38 (8%) 14 (3%) Mild pneumonia 230 (51%)     Cerebrovascular accident 1

[Table 1: Demographic characteristics, initial signs and symptomatology]

  Variable HR p 95% CI
Independent risk factors affecting coagulopathy Peak D-dimer >15.000 U/ml 29.53 0.012 2.08-417
  Dipiridamol administration 0.062 0.018 0.0062-0.62
Independent risk factors affecting highly suspected coagulopathy Moderate or severe CT findings 69.198 0.001 6.11-761.02
  Initial SpO2 ≤85% 23.23 0.003 2.85-189.11
  Peak Hgb <8.5 g/dl 7.52    
  Peak direct bilirubin >1.3 mg/dl 472 0.001 9.46-23632
  Peak ferritin >20.000ng/ml 15.82 0.033 1.25-199.25
  Progresive severity 86.57 0.012 2.62-2856.54
  Dipiridamol administration 0.12 0.001 0.032-0.41

[Table 2: Independent risk factors affectng coagulopathy and highly suspected coagulopathy]

To cite this abstract in AMA style:

Kalayoglu Besisik S, Ozbalak M, Tor YB, Alibeyoglu A, Kose M, Şenkal N, Cagatay A, Erelel M, Gul A, Esen F, Umman S, Isoglu Alkoclar U, Tukek T. Dipyridamole Added to Anticoagulant Prophylaxis: Decline in Poor Outcome of Clinically Severe Ill COVID-2019 Patients [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/dipyridamole-added-to-anticoagulant-prophylaxis-decline-in-poor-outcome-of-clinically-severe-ill-covid-2019-patients/. Accessed October 1, 2023.

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