Venous thromboembolic events during warm autoimmune hemolytic anemia

Abstract

Thrombotic manifestations are a hallmark of many auto-immune diseases (AID), specially of warm autoimmune hemolytic anemia (wAIHA), as 15 to 33% of adults with wAIHA experience venous thromboembolic events (VTE). However, beyond the presence of positive antiphospholipid antibodies and splenectomy, risk factors for developing a VTE during wAIHA have not been clearly identified. The aim of this retrospective study was to characterize VTEs during wAIHA and to identify risk factors for VTE. Forty-eight patients with wAIHA were included, among whom 26 (54%) had secondary wAIHA. Eleven (23%) patients presented at least one VTE, that occurred during an active phase of the disease for 10/11 patients (90%). The frequency of VTE was not different between primary and secondary AIHA (23.7 vs. 19.2%; p = 0.5). The Padua prediction score based on traditional risk factors was not different between patients with and without VTE. On multivariate analysis, total bilirubin ≥ 40 μmol/L [odds ratio (OR) = 7.4; p = 0.02] and leucocyte count above 7x109/L (OR = 15.7; p = 0.02) were significantly associated with a higher risk of thrombosis. Antiphospholipid antibodies were screened in 9 out the 11 patients who presented a VTE and were negative. Thus, the frequency of VTE is high (23%) during wAIHA and VTE preferentially occur within the first weeks of diagnosis. As no clinically relevant predictive factors of VTE could be identified, the systematic use of a prophylactic anticoagulation should be recommended in case of active hemolysis and its maintenance after hospital discharge should be considered. The benefit of a systematic screening for VTE and its procedure remain to be determined.

Evans syndrome in adults ‐ incidence, prevalence, and survival in a nationwide cohort

“…The risk of thrombosis in patients with AIHA, ITP, or ES was previously reported to be high in absolute terms, and compared to the risk in the general population . Our findings on the causes of death were ambiguous regarding cardiovascular‐related deaths, which included thromboembolic related deaths.…”

“…The incidence and prevalence of ES are unknown, although recent studies in children indicate that it may not be as rare as presumed . Although both AIHA and ITP were found to be associated with elevated risk of thrombosis and increased mortality, we know little about morbidity and mortality in patients with ES . Current knowledge regarding the prognosis and complications in adults with ES is based mostly on single‐case and small case series studies .…”

New Insights in the Pathogenesis and Therapy of Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia

“…In theory, the cross-talk between the complement system, inflammatory processes, and the coagulation cascade (100, 108, 109) might result in an increased frequency of thrombosis in CAD and CAS. Such a risk is definitely present in wAIHA (110,111). In CAD, this risk has been clearly documented in the most severely affected patients (73), and recent registry-based studies have found a slightly increased frequency of thrombosis in unselected CAD cohorts as well (112,113).…”

“…In CAD, this risk has been clearly documented in the most severely affected patients (73), and recent registry-based studies have found a slightly increased frequency of thrombosis in unselected CAD cohorts as well (112,113). According to one AIHA study, leukocytes influenced the risk of thrombosis (111), and the tissue factor expression by granulocytes has been implicated as one of the links between inflammation and thrombosis (114). The role of this interaction is more unclear in CAD, however, due to the different immune pathogenesis and because CAD patients usually do not have elevated leukocyte counts (9).…”

Acute peripheral pulmonary embolism attributed to autoimmune haemolytic anaemia: a case report

“…Transfusion should be treated with caution due to the risk of hemolytic transfusion reactions caused by alloantibodies of AIHA. Given the higher risk of thrombosis, long-term anticoagulation should be advised [8]. Despite the improved safety of Non-vitamin K antagonist oral anticoagulants (NOACs) compared with Vitamin K antagonists (VKAs) for extended anticoagulation of acute PE, treatment with NOACs is not without risk [9].…”