Investigation of the Etiology of Anemia in Thromboangiitis Obliterans

Abstract

During a review of patients admitted with thromboangiitis obliterans (TAO), there was evidence of normochromic normocytic anemia and abrupt changes in hemoglobin (Hgb) levels in patients with several hospital admissions. Therefore, the evidence of hemolytic anemia was evaluated based on 37 banked plasma samples taken from Caucasian male TAO patients during disease exacerbation between 2012 and 2014. The patients' hospital records, including clinical manifestations and complete blood count, were evaluated. The following tests were performed on all samples: indirect antiglobulin test (IAT), C-reactive protein (CRP), high-sensitivity CRP (hsCRP), lactate dehydrogenase (LDH), haptoglobin, indirect bilirubin, D-aspartate aminotransferase (AST), and D-alanine aminotransferase (ALT). The mean age of the patients was 40 ± 7 years. Two patients underwent below-knee amputation. The mean hospital-documented Hgb of the patients was 12.9 ± 2.6 g/dL. CRP and IAT were positive in 75.6 and 70.2% of the samples, respectively. The tests and corresponding results were as follows: hsCRP, 14.07 ± 2.37 µg/mL; LDH, 2,552 ± 315 u/ L; haptoglobin, 2.27 ± 1.1 g/L; indirect bilirubin, 0.09 ± 0.04 mg/dL; AST, 67 ± 7 u/L; and ALT, 26 ± 3 u/L. There was a significant inverse correlation between hsCRP and hospitaldocumented Hgb level (p = 0.03). Anemia with the positive IAT in most of the samples, high LDH and AST, and normal ALT are suggestive of hemolytic anemia. Normal indirect bilirubin is consistent with intravascular hemolysis. The positive CRP and elevated haptoglobin levels could be due to systemic inflammation in TAO. However, it is not known if an autoantigen or an infectious antigen is responsible for TAO systemic inflammation and induction hemolytic anemia. As such, the underlying mechanism of anemia in TAO could be part of the footprint of its main etiology.

The Imbalance among Oxidative Biomarkers and Antioxidant Defense Systems in Thromboangiitis Obliterans (Winiwarter-Buerger Disease)

“…Despite the studies on pathophysiology (reviewed in [29,51], actually, the detailed etiopathogenesis and molecular mechanisms are still unknown. Among the possible biomolecular hypotheses [10,12,14,18,[20][21][22][23]27,50,[54][55][56], oxidative stress has been crucially indicated as an important factor for both the initiation and progression of WBD [30,31,51,54].…”

“…Among the immunologic and inflammatory biomolecular hypotheses for the WBD disease, some biomarkers and biochemical mechanisms have been identified. Among them, crucial roles are played by cytokines and chemokines [10][11][12], adhesion molecules [13][14][15], Rickettsia rickettsii and Porphyromonas gingivalis (through toll-like receptors) [16][17][18][19], angiogenic factors [20], catecholamines [21], inflammation on sympathetic ganglia [22], T cells/macrophages/dendritic cells (intima infiltration of vessels) [23], accumulation of immunoglobulins, immune complexes and complement factors on sub-endothelial elastic lamina [24], urinary cotinine [25], circulating auto-antibodies [26], heme oxygenase 1 and the inducible isozyme of nitric oxide synthase [27], and matrix metalloproteinases [28] (as reviewed in [29]).…”

Recent Updates and Advances in Winiwarter-Buerger Disease (Thromboangiitis Obliterans): Biomolecular Mechanisms, Diagnostics and Clinical Consequences

“…In another study, although the indirect Coombs test was positive in 70% of the TAO patients with high levels of LDH (Lactate dehydrogenase) and AST (Aspartate aminotransferase) and normal levels of ALT (Alanine aminotransferase), the definitive diagnosis of hemolytic anaemia was not confirmed, because of the normal level of bilirubin as well as the normal or high level of haptoglobin [10].…”

“…Several studies reported anaemia, most commonly normochromic and normocytic type, in about 40% of TAO patients, particularly during the acute exacerbation of the disease [9,10]. Notably, a significant inverse correlation between haemoglobin (Hb) level and duration of smoking has been reported in TAO patients, which is not anticipated because a high Hb level would be expected in long-term, heavy smokers [9].…”

Secondary Infertility: A Neglected Aspect of Buerger’s Disease

“…BD usually is diagnosed in young men, and it appears that tobacco use is a risk factor for disease development and prognosis [2]. Until recently, the trigger for developing BD was unknown, and it is not yet known if BD is an autoimmune vasculitis or a peripheral vascular disease induced by an unknown aetiological factor besides smoking [3].…”