Heparin-induced thrombocytopenia in patients with COVID-19: a systematic review and meta-analysis

Abstract

Heparin thromboprophylaxis is routinely administered during hospitalization for coronavirus disease 2019 (COVID-19). Due to the immune stimulation related to COVID-19, there is ongoing concern regarding a heightened incidence of heparin-induced thrombocytopenia (HIT). We performed a literature search using PubMed, EMBASE, Cochrane and, medRxiv database to identify studies that reported clinical and laboratory characteristics and/or the incidence of HIT in COVID-19 patients. The primary aim was to systematically review the clinical features and outcomes of COVID-19 patients with confirmed HIT. The secondary objective was to perform a meta-analysis to estimate the incidence of HIT in hospitalized COVID-19 patients. A meta-analysis of 7 studies including 5,849 patients revealed the pooled incidence of HIT in COVID-19 of 0.8% (95% confidence interval [CI], 0.2-3.2%; I2 = 89%). The estimated incidences were 1.2% (95%CI, 0.3-3.9%; I2 = 65%) versus 0.1% (95%CI, 0.0-0.4%; I2 = 0%) in therapeutic versus prophylactic heparin subgroups, respectively. The pooled incidences of HIT were higher in critically ill COVID-19 patients (2.2%, 95%CI, 0.6-8.3%; I2 = 72.5%) compared to non-critically ill patients (0.1%, 95%CI, 0.0-0.4%: I2 = 0%). There were 19 cases of confirmed HIT and one with autoimmune HIT for clinical and laboratory characterization. The median time from heparin initiation to HIT diagnosis was 13.5 (interquartile range [IQR], 10.75, 16.25) days. Twelve (63%) developed thromboembolism after heparin therapy. In conclusion, the incidence of HIT in COVID-19 patients was comparable to non-COVID-19 medical patients, with higher incidences with therapeutic anticoagulation and in critically ill patients.

A case of severe COVID-19 with pulmonary thromboembolism related to heparin-induced thrombocytopenia during prophylactic anticoagulation therapy

“…Consequently, the 4Ts pre-test clinical scoring system for HIT is used in clinical practice to make a semiquantitative diagnosis [ 17 ]. Reported confirmed cases of HIT in COVID-19 showed intermediate or high scores, with a median of 5 points in the 4Ts score [ 6 , 18 ], as in our case, which was as high as 7 points. It is important to promptly discontinue heparin and initiate non-heparin anticoagulation therapy when HIT is suspected with a 4Ts score of 4 points or greater.…”

“…Recent findings suggest that critically ill patients with COVID-19 are prone to complications with HIT [ 5 , 6 ]. A systemic review and meta-analysis on HIT in hospitalized COVID-19 patients reported that the incidence was higher in critically ill patients compared with non-critically ill patients (2.2% and 1.2%, respectively), although the incidence of 0.8% HIT in hospitalized patients with COVID-19 was comparable to that in patients without COVID-19 [ 6 ]. Clinical characteristics among the 19 confirmed cases of HIT in patients with COVID-19 in a systemic review [ 6 ] showed the following results: the median age was 62 years, and all but one patient were critically ill.…”

“…According to the American Society of Hematology guidelines, discontinuation of heparin and initiation of non-heparin anticoagulants such as argatroban, bivalirudin, danaparoid, and fondaparinux or DOACs is recommended when HIT is suspected [ 19 ]. For the treatment of reported HIT cases in COVID-19, parenteral anticoagulants such as argatroban are frequently used, and most oral anticoagulants such as DOACs are used after bridging with the parenteral anticoagulants as necessary [ 6 , 18 , 20 ]. The use of DOACs as alternative anticoagulants in HIT has been increasingly reported during recent years [ 21 ].…”

“…COVID-19 with HIT has been reported relatively frequently in Europe and the United States [ 5 , 6 ], but very few cases have been reported in Japan. Here, we report a case of COVID-19 in a Japanese patient with complications related to HIT during prophylactic anticoagulation therapy.…”

Mechanisms of Immunothrombosis by SARS-CoV-2

“…Considering that one of the main characteristics of COVID-19 is hypercoagulability, and therefore the increased risk of venous and arterial thrombosis, it is necessary to differentiate from Heparin-induced thrombocytopenia (HIT) [ 67 , 68 , 69 ], particularly secondary to the use of vaccines [ 70 ]. Uaprasert et al [ 71 ], in a systematic review and meta-analysis, found a pooled incidence of HIT of 0.8%, being slightly higher in critically ill COVID-19 patients.…”