COVID-19-Related Thrombosis in Japan: Final Report of a Questionnaire-Based Survey in 2020

Abstract

A questionnaire on COVID-19-related thrombosis in patients hospitalized before Aug 31, 2020, was sent to 399 hospitals throughout Japan. Responses were received from 111 (27.8%) with information on 6,202 COVID-19 patients. Of these, 333 and 56 required ventilation or extracorporeal membrane oxygenation (ECMO), respectively, and 212 died (3.4%). D-dimer levels were measured in 75.0% of the patients, revealing that 9.2% and 7.6% exhibited D-dimer increases of 3-8-fold and ≥8-fold the reference value, respectively. Thrombotic events occurred in 108 patients (1.86% of the 5,807 patients with available data) including symptomatic cerebral infarction in 24, myocardial infarction in 7, deep vein thrombosis in 41, pulmonary thromboembolism in 30, and other thrombotic events in 22. Some patients developed multiple thrombotic events. Thrombosis occurred in 32 patients with mild or moderate COVID-19 severity (0.59% of those with data available) and in 52 patients on ventilation or ECMO (13.5% of severe patients for whom data were available). Thrombosis occurred in 67 patients during worsening clinical condition and in 26 during recovery. Anticoagulant therapy was provided to 893 patients (14.6% of the 6,119 patients with available data), the main reasons being provided as elevated D-dimer levels and worsening clinical condition.

Keywords: COVID-19; Cerebral infarction; D-dimer; Thrombosis; Venous thromboembolism.

Fig. 1.

Severity of COVID-19 in 6,068 patients according to the response to the questionnaire on COVID-19-related thrombosis

Fig. 2.

Distribution of D-dimer and FDP values The proportion of patients with D-dimer assessments (A) and maximal values of D-dimer (B) and FDP (C) during hospitalization.

Fig. 3.

Patients with D-dimer or FDP levels > 100-fold the reference value Thirty-nine patients had D-dimer or FDP levels > 100 times the reference value

Fig. 4.

Numbers of patients developing each thrombotic disease Thrombotic disease developed in 108 patients (1.86% of the 5,807 patients for whom responses to questions about thrombosis were provided). Multiple answers were permitted when one patient developed multiple thrombotic events.

Fig. 5.

Incidence of thrombotic events in patients with mild and moderate COVID-19 and in those during ventilation and ECMO therapy

Fig. 6.

Clinical conditions of the 108 patients developing thrombosis Multiple answers were permitted

Fig. 7.

Methods used for the diagnosis of pulmonary thromboembolism Methods used for the diagnosis of pulmonary thromboembolism were requested to hospitals that made this diagnosis for mild and moderate COVID-19 patients, and separately for severe patients. Responses were received from 12 hospitals for mild and moderate COVID-19 patients and 9 hospitals for severe patients. Multiple answers were permitted.

Fig. 8.

Incidence of (A) and drugs used (B) for anticoagulant therapy (A) Anticoagulant therapy was given to 893 of the 6,119 patients with available data. (B) Drugs used for the anticoagulant therapy. Multiple answers were permitted.

Fig. 9.

The reasons for initiating anticoagulant therapy in the 893 COVID-19 patients Multiple answers were permitted.

Fig. 10.

The reasons for initiating prophylactic anticoagulant therapy Answers were obtained from 51 hospitals that performed prophylactic anticoagulant therapy. Multiple answers were permitted.

Fig. 11.

The reasons for discontinuation of anticoagulant therapy Information on the reasons for discontinuation of anticoagulant therapy was provided for 606 patients in 50 hospitals. Multiple answers were permitted.