To the editor,
We read the article by Parvizi et al. with great interest [8].
Parvizi and colleagues identified the preoperative comorbidities associated with an increased risk of symptomatic pulmonary embolism (PE) after total joint arthroplasty (TJA) in a large group of patients. The authors concluded that patients with obesity, chronic obstructive pulmonary disease, atrial fibrillation, anemia, depression, or postoperative deep vein thrombosis, as well as those patients who undergo knee procedures, or have a high Charlson Comorbidity Index, are at an increased risk of having a postoperative PE development. Those risk factors should be considered when deciding on postoperative anticoagulation prophylaxis. According to Parvizi and colleagues, the reasons why preoperative anemia is a risk factor for PE development remains unclear.
Several studies from internal medicine [2–4, 6, 7] suggest some possible mechanisms for PE development in iron deficiency anemia (IDA). We reviewed and summarized the mechanisms to explain the association between IDA and thrombosis. First, iron is a crucial regulator of thrombopoiesis due to its negative feedback effect on platelet production and lower levels of iron disinhibit megakaryocyte activity [2]. These characteristics promote secondary thrombocytosis, which lead to a hypercoagulable state [4]. Additionally, when erythropoietin increases to stimulate the red cell production, it also stimulates the megakaryocyte production [3]. Second, in IDA, microcytosis causes lower red cell deformability, which increases the blood viscosity [7]. Third, when the oxygen-carrying capacity of erythrocytes decreases, anemic hypoxia may occur, especially in situations where the metabolic demands are increased. The vessels undergo autoregulatory dilatation, which can lead to a turbulent blood flow, causing more frequent contact of the platelets with the endothelial lining of the vessels [3, 6]. Fourth, platelets may become hyperresponsive in anemic states due to the increased levels of erythropoietin. The abnormal platelet count and function observed in IDA can promote thrombus formation, especially in the setting of an underlying atherosclerotic disease [2, 3]. Fifth, the decrease in antioxidant defense may cause increased oxidant stress, which could result in platelet aggregation [2]. And finally, acute bleeding raises platelet adhesiveness and lowers fibrinolytic activity, which leads to intravascular thrombogenesis [7].
As would be expected, other forms of anemia such as sickle cell disease, thalassemia or autoimmune hemolytic anemia may also cause both arterial and venous thrombosis [1, 5, 9]. After considering the possible mechanisms, the question, “Should we better detect the cause of anemia and treat it firstly prior to TJA?” emerges and needs further investigation.
Footnotes
(RE: Parvizi J, Huang R, Raphael IJ, Arnold WV, Rothman RH. Symptomatic pulmonary embolus after joint arthroplasty: stratification of risk factors. Clin Orthop Relat Res. 2014;472:903–912.)
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