Intravascular hemolysis and multitreatment predict thrombosis in patients with autoimmune hemolytic anemia

Abstract

Background Thrombosis may complicate autoimmune hemolytic anemia (AIHA), but its predictors are still lacking, and no clear‐cut indications for anticoagulant prophylaxis are available. Objectives To characterize frequency and severity of thromboses in AIHA patients and identify risk factors for thrombosis that may advise primary anticoagulant prophylaxis. Patients/Methods A total of 287 consecutive AIHA patients diagnosed and followed from 1978 at a tertiary Italian center were retrospectively studied; 174 of them were prospectively evaluated from January 2020 until December 2021. AIHA relapse, thrombosis occurrence, and primary anticoagulant prophylaxis were evaluated. Results Thirty‐three AIHA patients (11.4%) experienced thrombosis, 70% of whom hospitalized. The cumulative thrombosis incidence was higher in patients with lactate dehydrogenase (LDH) ≥ 1.5 (hazard ratio [HR] 3.22), in those experiencing infections (HR 3.57), receiving transfusions (HR 3.06), rituximab (HR 3.3), or cyclophosphamide (HR 2.67). By multivariable analysis, LDH, transfusions, rituximab, and cyclophosphamide treatment emerged as independent factors associated with thrombosis. Among 174 patients prospectively followed in the past 2 years, we observed 70 acute hemolytic episodes in 45 patients; 33/45 displayed LDH ≥1.5 × upper limit of normal, and 17 received anticoagulant prophylaxis with low molecular weight heparin for a median of 70 days (30–300). In those receiving prophylaxis no thrombotic complications occurred, whereas five thrombotic episodes were registered in the remaining 16 cases. Conclusions Thrombosis was observed in about 11% of AIHA patients, mainly grade 3, and associated with intravascular hemolysis, need of transfusions, multitreatment, and infections, advising primary anticoagulant prophylaxis in these settings.

Successful outcome of pregnancy post‐allogeneic stem cell transplant despite severe RH1 alloimmunization: A case report

“…18 Furthermore, even with IUT, the fetus may be anaemic, and major organs hypo-oxygenated, for prolonged periods of fetal development, causing neurodevelopmental delays and motor defects in some infants. 19 In addition, active haemolysis constitutes a prothrombotic factor 20 ; repetitive thrombosis may have accounted for the placenta hypoperfusion and low weight in the present case.…”

Thromboembolism Early After Glucocorticoid Administration in Patients with Autoimmune Hemolytic Anemia

“…Active hemolysis markers such as higher LDH levels, lower hemoglobin levels, and splenectomy have been identified as risk factors for thrombosis [ 7 , 9 , 10 ]. As seen in Case 2, some patients with AIHA and thrombosis were reported to be positive for LA; however, its association with AIHA remains controversial [ 7 , 10 , 17 ]. Intravascular hemolysis has also been reported as a risk factor for thrombosis [ 7 , 9 , 10 ], but other studies have not supported this finding [ 13 ].…”

“…As seen in Case 2, some patients with AIHA and thrombosis were reported to be positive for LA; however, its association with AIHA remains controversial [ 7 , 10 , 17 ]. Intravascular hemolysis has also been reported as a risk factor for thrombosis [ 7 , 9 , 10 ], but other studies have not supported this finding [ 13 ]. This discrepancy may be explained by the differences in the study design, sample size, and availability of patient information.…”

“…Hendrick reported that thrombotic events were lower in the prophylaxis than in the non-prophylactic group [ 11 ]. Fattizzo et al also reported the efficacy of prophylaxis [ 7 ]. Other studies recommended anticoagulant therapy for active or severe hemolysis [ 6 , 9 , 15 ].…”

The choice of new treatments in autoimmune hemolytic anemia: how to pick from the basket?

“…This is probably explained by autoantibody activity against erythroid precursors (40), but T-cell mediated suppression or inflammatory mechanisms may also contribute. WAIHA carries an increased risk of thrombosis, which, in addition to a risk of infection and other treatment complications, probably contributes to increased mortality (41)(42)(43)(44)(45)(46)(47)(48). In most cases, wAIHA is a chronic relapsing rather than a chronic disease.…”