Smear Examination: The Clue to the Diagnosis of Rare Disorder Mixed Cryoglobulinemia - An Interesting Case Report

Cryoglobulins are circulating immunoglobulins or immunoglobulin complexes that precipitate under cold conditions and resolubilize on rewarming. Persistant presence of cryoglobulins in serum is known as Cryoglobulinemia. It is of three types- Type I, II, III. Type II and III are known as Mixed cryoglobulinemia. We recently encontered special case during routine examination of complete blood cell count of a 67 years old male patient which showed pseudoleucocytosis on Coulter DXH 800 automatic haematology analyzer and WBC histogram showed decreasing trend. We examined peripheral blood smear to rule out other causes of psuedoleucocytosis like platelet clumps or nRBCs which were absent on smears studied. However large ammount of lumpy grey-blue deposits were observed. On warming blood at 370C lumpy grey blue deposits reduced on smear but did not disappear. With these findings we suspected cryoglobulinemia and took detailed patient history which revealed triad of weakness, arthralgia and purpuric rash suggesting possibility of cryoglobulinemia. For quick confirmation RA factor and complement levels were analyzed. RA factor was positive and C4 was reduced with normal C3 levels characteristically indicating mixed cryoglobulinemia. Finally for confirmation blood sample was recollected in pre warmed syringe and under temperature control plasma was separated and kept for cold incubation at 4-80 C which showed cryoprecipitate at bottom of tube after 12 hrs. It confirmed mixed cryoglobulinemia. Further Serum Protein electrophoresis revealed distorted gamma region but no monoclonal band was seen. This confirmed polyclonal nature of cryoglobulin indicating mixed cryoglobulinemia. Hence though rare disorder (Incidence 1 in 100000) simple clue of erroneous leucocyte count, and WBC histogram pattern followed by blood smear examination can help easily identify unsuspected cases of cryoglobulinemia.