Multiple myeloma and acquired von Willebrand disease: a combined cause of preanalytical interference causing gel formation?

Abstract

We report a patient with acquired von Willebrand disease, associated with multiple myeloma. At one stage in his illness, we were unable to analyse a sample sent in a serum separator tube, due to the presence of a gel within the separated serum layer. We suggest this was due to anomalous position of the gel because of the density of the sample caused by its high total protein concentration, exacerbated by fibrin strand formation because of inhibition of appropriate fibrin clot formation secondary to clotting disorder.

Acquired von Willebrand syndrome associated with plasma cell myeloma – a rare histopathological bone marrow image

“…According to data from the International Registry, 16 out of 186 (9%) AVWS patients were diagnosed with multiple myeloma. Additionally, in the literature there are approximately 30 reported cases of these two disorders in combination [8,9,10,11,12,13,14].…”

An unique encounter with paraprotenemia

“…[5] This suggests that underlying myeloma may be more commonly associated with anomalous gel position than raised total protein alone, and a possible additional mechanism is the known inhibition of myeloma paraprotein with fibrin formation. [3] Van den Ouweland and Church described impaired gel separation in two patients with multiple myeloma. [6] In both of these cases, very high levels of total protein were noted (>130 g/L) along with elevated plasma viscosity.…”

“…Incomplete or delayed fibrin clot formation may result in the presence of latent fibrin in the form of thin strands or gelatinous masses, thus causing interferences in analysis. [3] Abnormal behavior of separator gels…”

“…The gel is thixotropic, i.e., it is semisolid under static conditions, but becomes less viscous if force, such as centrifugation, is applied. [4] The specific gravity of this gel is most often 1.04 g/cm 3 to permit its suitable positioning between serum and cellular constituents of blood upon centrifugation. The density of the liquid (serum/plasma) and cellular components of the blood typically ranges from 1.026-1.031 g/cm 3 and 1.092-1.095 g/cm 3 , respectively.…”

“…Several case reports suggest that multiple myeloma and related disorders are associated with improper gel barrier formation. [3,5,6] In a study of 42,080 patients whose blood was sampled into serum separator containers, only 16 had persistently abnormal separation and of these 14 had multiple myeloma (total protein concentrations 69-141 g/L, median 90 g/L) and two had monoclonal gammopathy of undetermined significance with protein concentrations of 88 and 65 g/L. [5] This suggests that underlying myeloma may be more commonly associated with anomalous gel position than raised total protein alone, and a possible additional mechanism is the known inhibition of myeloma paraprotein with fibrin formation.…”