Incidence of bleeding and thromboembolism and impact on overall survival in adult patients with hemophagocytic lymphohistiocytosis: A 20‐year provincial retrospective cohort study

Abstract

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by uncontrolled immune activation and high risk of death. There is scarce data on the incidence of bleeding and thromboembolism in HLH. Objectives To determine the cumulative incidence of bleeding and thromboembolism and impact on survival in adults with HLH. Patients/Methods We conducted a multicenter retrospective cohort study of adults with HLH in Alberta, Canada (1999–2019). The cumulative incidence of bleeding and thromboembolism were calculated, accounting for competing risks. Cox proportional hazards models were used to assess the impact of bleeding and thromboembolism on overall survival (OS). Results We identified 97 adults with HLH (median age 46 years). Venous thromboembolism (VTE) occurred in 11 (11%) patients at a median of 9 days from admission. ISTH major bleeding and clinically relevant non‐major bleeding occurred in 39 (40%) patients, at a median of 16 days after admission. Nadir platelet count (adjusted odds ratio [aOR] 1.8 per log decrease, 95% confidence interval [CI] 1.2–2.8) and mechanical ventilation (aOR 4.9, 95% CI 1.8–14.8) were independent predictors of bleeding on multivariable analysis. Adjusting for competing risks, the 90‐day cumulative incidences of bleeding and thromboembolism were 39% and 13%, respectively. The median OS was 18.8 months. VTE, but not bleeding, was significantly associated with adverse OS (adjusted hazard ratio 2.5, 95% CI 1.1–5.7). Conclusions In adults with HLH, VTE appears more common than previously described and is a predictor of mortality, although this may be due to unadjusted confounding. VTE prevention and treatment are challenging due to high bleeding rates.

Management of haemostatic complications of chimaeric antigen receptor T‐cell therapy

“…70 Another recent review reported VTE in 11% and bleeding in 40%. 71 This contrasts with the CAR-T studies, where bleeding has been reported less frequently. 11 CAR-T patients may also develop toxicities resembling HLH, sometimes referred to as carHLH in the literature.…”

“…Hypofibrinogenaemia was significantly associated with bleeding, which occurred in 22% (4.3% fatal) 70 . Another recent review reported VTE in 11% and bleeding in 40% 71 . This contrasts with the CAR‐T studies, where bleeding has been reported less frequently 11 …”

Kidney Dysfunction and Pathology in the Setting of Hemophagocytic Lymphohistiocytosis

“… 18 Endothelial or vascular injury and a procoagulant state leading to acute features of TMA are also likely mediated by abnormal activation of the immune system in HLH: TMA has been variably reported (13%–70%) to occur in HLH. 19 , 20 Gloude et al. 19 describe resolution of TMA and survival after treatment that included eculizumab and emapalumab (an interferon gamma blocker) in a small group of patients developing TMA in HLH.…”

A Study on Early Death Prognosis Model in Adult Patients with Secondary Hemophagocytic Lymphohistiocytosis

“…e selection of effective firstline induction therapy can to a large extent improve the serious and bad basic condition of patients in the early stage of treatment and create conditions for survival and further clear diagnosis of potential diseases and targeted treatment. Bleeding in deep organs is the main risk of acute death before treatment takes effect [17,18]. As a coagulation factor, serum calcium is a risk factor for bleeding events in patients.…”