Cryoglobulins are not essential

[...]the blood collected must be maintained at 37°C from the start so as not to lose cryoglobulins, which precipitate as soon as the temperature falls below 37°C. Once the blood has coagulated the serum is separated by centrifugation at 37°C. The serum should then be freed of fibrinogen, which could, like several other plasma proteins, precipitate in the cold. From our experience these parameters can completely modify the results.\n In conclusion, cryoglobulins are often found in patients with HCV infection and a necessary step for their development seems to be long standing infection with liver disease and hypergammaglobulinaemia. Because chronic HCV infection often progresses without any clinical or laboratory abnormality, only a liver biopsy will show the presence of hepatitis in many patients. 26 The absence of hepatitis on liver biopsy in a patient with cryoglobulinaemia and HCV infection (tested by the presence of HCV RNA and a positive serology) is rare enough to merit publication. 27 However, it may be possible that chronic liver disease is not an obligatory step in the progression towards cryoglobulinaemia.