Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis

Abstract

P atients with immunoglobulin light chain amyloidosis are at risk for both thrombotic and bleeding complications. While the hemostatic defects have been extensively studied, less is known about thrombotic complications in this disease. This retrospective study examined the frequency of venous thromboembolism in 929 patients with immunoglobulin light chain amyloidosis presenting to a single referral center, correlated risk of venous thromboembolism with clinical and laboratory factors, and examined complications of anticoagulation in this population. Sixty-five patients (7%) were documented as having at least one venous thromboembolic event. Eighty percent of these patients had events within one year prior to or following diagnosis. Lower serum albumin was associated with increased risk of VTE, with a hazard ratio of 4.30 (CI 1.60-11.55; P=0.0038) for serum albumin less than 3 g/dL compared to serum albumin greater than 4 g/dL. Severe bleeding complications were observed in 5 out of 57 patients with venous thromboembolism undergoing treatment with anticoagulation. Prospective investigation should be undertaken to better risk stratify these patients and to determine the optimal strategies for prophylaxis against and management of venous thromboembolism. Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis

Venous thromboembolism in multiple myeloma – choice of prophylaxis, role of direct oral anticoagulants and special considerations

“…In patients with myeloma, and especially those with AL amyloidosis, proteinuria can contribute to increased thrombotic tendency, and this is most marked in those with nephrotic‐grade proteinuria. Bever et al () reviewed 929 patients with AL amyloidosis presenting to a single‐centre over a 10‐year period, of whom 7% had documented VTE. A non‐significant increase in VTE risk was observed if serum albumin was 3–4 g/l (HR 2·16, CI 0·80–5·81).…”

“…This is of additional relevance due to the haemorrhagic deficiencies seen in amyloidosis. These have been more extensively studied than the thrombotic issues, and involve defective vascular integrity, acquired factor X deficiency and acquired von Willebrand syndrome (Bever et al , ), and clearly have to be borne in mind when managing thrombotic risk in affected individuals.…”

“…This is of additional relevance due to the haemorrhagic deficiencies seen in amyloidosis. These have been more extensively studied than the thrombotic issues, and involve defective vascular integrity, acquired factor X deficiency and acquired von Willebrand syndrome (Bever et al, 2016), and clearly have to be borne in mind when managing thrombotic risk in affected individuals. Separate to proteinuria and the nephrotic syndrome, chronic renal impairment is not only a risk factor for thrombosis, but subsequent anticoagulation also poses challenges in this demographic, who are at greater risk of haemorrhagic complications (Parker et al, 2018).…”

Echocardiography as the first diagnostic clue to rapidly progressive systemic AL amyloidosis associated with multiple site thrombosis. A case report

“…The evaluation of cardiac amyloidosis has crucial prognostic importance because the presence of heart failure in these patients reduces the average survival period in the lack of specific treatment from 24 months to under 9 months [2]. Hemostasis is frequently affected by AL-amyloidosis, which predisposes to both bleeding and thrombotic complications [3].…”

Identification of a new potential mechanism responsible for severe bleeding in myeloma: immunoglobulins bind the heparin binding domain of antithrombin activating this endogenous anticoagulant

“…The binding of certain IgGs to the heparin binding domain of antithrombin might impair the activation of antithrombin by physiological co-factors when it is required, thus also contributing to the risk of thrombosis, which is also a relatively frequent complication in these disorders. 13 Purification following our procedure and analysis of the IgG of patients with myeloma and related plasma cell disorders who develop thrombosis may help to answer this question. …”