Margem de Segurança para Hiperviscosidade Plasmática para Prevenção de Trombose em Pacientes com Doença Cardiovascular após Vacinação contra COVID-19

High-dose intravenous immunoglobulin (IVIg) can increase blood viscosity in vitro and has been associated with cardiovascular or cerebrovascular thromboembolism. Because thromboembolic events were observed in two (3%) of 65 patients we treated with IVIg, we measured serum viscosity serially in 13 patients (five with amyotrophic lateral sclerosis [ALS], eight with IgM paraproteinemic polyneuropathy) before and immediately after each of three consecutive monthly infusions of IVIg. We correlated changes in viscosity with serial determinations of the total serum IgG, IgM, and IgA before and after each infusion. Serum viscosity increased after IVIg in all the patients by 0.1 to 1.0 centipoise (cp) (mean, 0.55 cp). In three ALS patients and in all the patients with paraproteinemic polyneuropathy, serum viscosity exceeded the upper limit of normal (normal, 1.5 to 1.9 cp) and increased as high as 2.6 cp. The increase in viscosity occurred immediately after completion of the infusion, declined over 1 month, and appeared to correlate best with the serum IgG level, which after the infusions was as high as 6,160 mg/dl (normal, 545 to 1,560 mg/dl). I conclude that IVIg increases serum viscosity and in many patients can cross the symptomatic threshold level. Because increased serum viscosity can impair blood flow and trigger a cardiovascular or cerebrovascular thromboembolic event, IVIg should be used judiciously and with concurrent monitoring of serum viscosity in elderly patients and patients with cryoglobulinemia, monoclonal gammopathies, high lipoproteins, or preexisting vascular disease.

Hypergammaglobulinemia increases serum viscosity and is the most common cause of hyperviscosity syndrome. Monoclonal hypergammaglobulinemia resulting in hyperviscosity syndrome is seen in multiple myeloma and Waldenström's macroglobulinemia. The reasons for elevated viscosity are increased protein content and large molecular size, abnormal polymerization, and abnormal shape of immunoglobulin molecules. Other hematologic and metabolic abnormalities seen in patients with plasma cell dyscrasias also contribute to hyperviscosity. Symptomatic hyperviscosity is much more common in Waldenström's macroglobulinemia (10 to 30%) than it is in myeloma (2 to 6%). Symptoms of hyperviscosity usually appear when the normal serum viscosity of 1.4 to 1.8 cp reaches 4 to 5 cp, corresponding to a serum immunoglobulin M (IgM) level of at least 3 g/dL, an IgG level of 4 g/dL, and an IgA level of 6 g/dL. Symptoms of hyperviscosity include constitutional symptoms; bleeding; and ocular, neurological, and cardiovascular manifestations. Immediate therapy of symptomatic hyperviscosity is directed at reduction of blood viscosity by plasmapheresis to control symptoms. Long-term management is directed at control of the underlying disease to prevent production of the monoclonal protein. There may be a small proportion of individuals, usually old or with severely compromised performance status, who undergo plasma exchange as the sole symptomatic therapy of hyperviscosity secondary to plasma cell dyscrasia.