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

Heparin thromboprophylaxis is routinely administered during hospitalization for COVID-19. Because of 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 patients with COVID-19. The primary aim was to systematically review the clinical features and outcomes of patients with COVID-19 with confirmed HIT. The secondary objective was to perform a meta-analysis to estimate the incidence of HIT in hospitalized patients with COVID-19. A meta-analysis of 7 studies including 5849 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%) vs 0.1% (95% CI, 0.0%-0.4%; I2 = 0%) in therapeutic vs prophylactic heparin subgroups, respectively. The pooled incidences of HIT were higher in critically ill patients with COVID-19 (2.2%; 95% CI, 0.6%-8.3%; I2 = 72.5%) compared with noncritically ill patients (0.1%; 95% CI, 0.0%-0.4%: I2 = 0%). There were 19 cases of confirmed HIT and 1 with autoimmune HIT for clinical and laboratory characterization. The median time from heparin initiation to HIT diagnosis was 13.5 days (interquartile range, 10.75-16.25 days). Twelve (63%) developed thromboembolism after heparin therapy. In conclusion, the incidence of HIT in patients with COVID-19 was comparable to patients without COVID-19, with higher incidences with therapeutic anticoagulation and in critically ill patients.

Pharmacologic Thromboprophylaxis and Thrombosis in Hospitalized Patients with COVID-19: A Pooled Analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) increases thrombosis in hospitalized patients prompting adoption of different thromboprophylaxis strategies. Safety and efficacy of escalated-dose pharmacologic thromboprophylaxis are not established. OBJECTIVES: To determine the pooled incidence of thrombosis/bleeding in hospitalized patients with COVID-19 for standard-dose, intermediate-dose, therapeutic anticoagulation, and no pharmacologic thromboprophylaxis. METHODS: MEDLINE, EMBASE, and Cochrane CENTRAL were searched up to August 29, 2020 for studies reporting pharmacologic thromboprophylaxis and thrombosis or bleeding. Pooled event rates were calculated using a random-effects model. RESULTS: Thirty-five observational studies were included. The pooled incidence rates of total venous thromboembolism (N = 4,685) were: no prophylaxis 41.9% (95% confidence interval [CI]: 28.1-57.2, I 2 = 76%), standard-dose prophylaxis 19.8% (95% CI: 13.2-28.6, I 2 = 95%), intermediate-dose prophylaxis 11.9% (95% CI: 4.3-28.6, I 2 = 91%), and therapeutic-dose anticoagulants 10.5% (95% CI: 4.2-23.8, I 2 = 82%, p = 0.003). The pooled incidence rates of arterial thrombosis (N = 1,464) were: no prophylaxis 11.3% (95% CI: 5.2-23.0, I 2 = 0%), standard-dose prophylaxis 2.5% (95% CI: 1.4-4.3, I 2 = 45%), intermediate-dose prophylaxis 2.1% (95% CI: 0.5-7.7, I 2 = 45%), and therapeutic-dose anticoagulants 1.3% (95% CI: 0.2-8.8, I 2 = 0, p = 0.009). The pooled bleeding event rates (N = 6,393) were nonsignificantly higher in therapeutic-dose anticoagulants compared with standard-dose prophylaxis, (6.3 vs. 1.7%, p = 0.083). CONCLUSION: Thrombosis rates were lower in hospitalized COVID-19 patients who received pharmacologic thromboprophylaxis. Thrombosis and bleeding rates for patients receiving intermediate-dose thromboprophylaxis or therapeutic anticoagulation were similar to those who received standard-dose pharmacologic thromboprophylaxis.

Postdischarge thrombosis and hemorrhage in patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is associated with a prothrombotic state with a high incidence of thrombotic events during hospitalization; however, data examining rates of thrombosis after discharge are limited. We conducted a retrospective observational cohort study of discharged patients with confirmed COVID-19 not receiving anticoagulation. The cohort included 163 patients with median time from discharge to last recorded follow-up of 30 days (interquartile range [IQR], 17-46 days). The median duration of index hospitalization was 6 days (IQR, 3-12 days) and 26% required intensive care. The cumulative incidence of thrombosis (including arterial and venous events) at day 30 following discharge was 2.5% (95% confidence interval [CI], 0.8-7.6); the cumulative incidence of venous thromboembolism alone at day 30 postdischarge was 0.6% (95% CI, 0.1-4.6). The 30-day cumulative incidence of major hemorrhage was 0.7% (95% CI, 0.1-5.1) and of clinically relevant nonmajor bleeds was 2.9% (95% CI, 1.0-9.1). We conclude that the rates of thrombosis and hemorrhage appear to be similar following hospital discharge for COVID-19, emphasizing the need for randomized data to inform recommendations for universal postdischarge thromboprophylaxis.

Incidence of thrombosis and hemorrhage in hospitalized cancer patients with COVID-19.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a recognized prothrombotic state. Patients hospitalized with active cancer are predisposed to thrombosis but whether active cancer further amplifies thrombotic risk with COVID-19 is not known. OBJECTIVES: To evaluate cumulative incidences of thrombotic and hemorrhagic events in hospitalized COVID-19 patients with and without active cancer at 28 days. METHODS: A retrospective cohort analysis of consecutive adults hospitalized with COVID-19 was performed. Active cancer required cancer-directed therapy within previous 6 months. The cumulative incidences of thrombosis or hemorrhage were estimated considering death as a competing risk. RESULTS: Patients without cancer (n = 353) and active cancer (n = 45) were comparable in terms of age, sex, antibiotics administered, length of hospitalization, and critical care. The most common malignancies were lymphoid (17.8%), gastrointestinal (15.6%), lung (13.3%), and genitourinary (13.3%). At day 28, the cumulative incidence of thrombotic events was 18.2% (95% confidence interval [CI], 10.2%-27.9%) in the non-cancer cohort and 14.2% (95% CI, 4.7%-28.7%) in the cancer cohort. The cumulative incidence of major and fatal bleeding at day 28 was 20.8% (95% CI, 12.1%-31.0%) in the non-cancer group and 19.5% (95% CI, 5.5%-39.8%) in the cancer cohort. Three patients experienced fatal bleeds, all of whom were in the non-cancer cohort. Survival was significantly shorter in the group with active cancer (P = .038). CONCLUSIONS: We observed a similarly high incidence of thrombosis and bleeding among patients admitted with COVID-19 with or without active cancer.