Histologic findings in the 2 skin biopsy specimens were similar. Multiple thrombi were seen within blood vessels in the superficial and deep dermis; several of the thrombi had a hyalinized appearance. There were also scattered neutrophils in and around the vessels, with hemorrhage and proliferation of capillaries in small lobules. The dermatopathologist raised the possibility of monoclonal cryoglobulinemia.
When a serum sample was cooled to 4掳C, a gelatinous cryoprecipitate formed (Figure 4, from left to right: positive control, patient's serum, and negative control samples, all at 4掳C) and disappeared when the sample was rewarmed. A cryocrit could not be determined because the sample became completely gelled. The results of additional laboratory investigations were negative or within normal limits: anticardiolipin antibody, lupus anticoagulant, Russell viper venom clotting time, serum viscosity at 37掳C, rheumatoid factor, and serologic tests for hepatitis A, B, and C. There was a transient decrease of 10 to 30 U below reference ranges in the levels of fibrinogen, protein C, protein S, antithrombin III, CH50, C3, and C4. There was also a slight activated protein C resistance, and subsequent DNA analysis demonstrated heterozygosity for the factor V Leiden mutation. Serum and urine protein electrophoresis indicated the presence of a monoclonal IgG 位 protein. Flow cytometry immunophenotyping of the bone marrow identified a CD38+, 位 chain鈥搑estricted population of cells, compatible with multiple myeloma.