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Chapter 10 : Cryoglobulins, Cryofibrinogenemia, and Pyroglobulins

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Cryoglobulins, Cryofibrinogenemia, and Pyroglobulins, Page 1 of 2

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Abstract:

Cryoglobulinemia is one of a group of syndromes characterized by the induction of clinical and/or laboratory abnormalities by cold. Cryoglobulins are immunoglobulins (Igs) that precipitate out of solution below core body temperatures, either as a single isotype (simple cryoglobulins) or as immune complexes in which both antibody and antigen are Igs (mixed cryoglobulins). In some instances, cryoglobulinemia may coexist with other related but usually distinct forms of cold hypersensitivity, such as Raynaud's phenomenon, cold agglutinin activity, or cold-dependent activation of complement (CDAC) (1).

Citation: Gorevic P, Galanakis D. 2016. Cryoglobulins, Cryofibrinogenemia, and Pyroglobulins, p 101-111. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch10
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Figures

Image of FIGURE 1
FIGURE 1

(A) Cryoglobulinemia was initially missed in a patient with cutaneous vasculitis documented by biopsy of a purpuric lesion on the right second digit (left). Because of deteriorating status, including renal failure, she was treated with high doses of steroids and then cytotoxic agents, with an apparently poor response in terms of an expected drop in white blood cell (WBC) counts. One weekend, while still in the intensive care unit, she was noted to have developed nasal purpura in the distribution of a cold-air oxygen mask (right). (B) The Coulter histograms obtained at 4°C, 25°C, and 37°C each display the leukocyte (top), erythrocyte (middle), and platelet (bottom) panels. The leukocyte panel shows small lymphocytes to the left (thin arrow) and larger polymorphonuclear leukocytes and monocytes to the right (thick arrow), with the ordinate displaying percentages of total cells; the platelet panels at 4°C and 25°C are unusual in having a long tail (*) after the expected narrow peak. Pseudoleukocytosis and pseudothrombocytosis are revealed at 37°C, which shows (i) all the leukocytes to be polymorphonuclear, with few lymphocytes, as expected in a patient on high-dose corticosteroids, and (ii) a narrow platelet peak. Both findings are reflected in the manual counts (right). Recognition of this artifact led to identification of a type II cryoglobulin with RF activity, with restricted IgM and kappa arcs by immunoelectrophoresis (C, arrowheads) and a high thermal amplitude of cryoprecipitation (D). OD@280, optical density at 280 nm.

Citation: Gorevic P, Galanakis D. 2016. Cryoglobulins, Cryofibrinogenemia, and Pyroglobulins, p 101-111. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch10
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Image of FIGURE 2
FIGURE 2

Kinetics of cryoprecipitation, assessed by turbimetric analysis, for a type II cryoglobulin, comparing serum and isolated cryoglobulin (A), different concentrations of isolated cryoglobulin (B), and different temperatures of cryoprecipitation (C). OD, optical density.

Citation: Gorevic P, Galanakis D. 2016. Cryoglobulins, Cryofibrinogenemia, and Pyroglobulins, p 101-111. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch10
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Image of FIGURE 3
FIGURE 3

Isolated washed cryofibrinogen (arrows) visualized by agarose gel electrophoresis (left) and immunofixation (right). Gel electrophoresis reveals some residual albumin toward the anode, fibronectin in the beta region, an origin artifact, and fibrinogen, compared to serum samples in the upper and lower lanes. In the immunofixation on the right, an origin artifact is seen in all lanes due to precipitation on the cold gel. However, the antifibrinogen lane shows increased precipitate, thereby characterizing this as fibrinogen. SPE, serum protein electrophoresis. Courtesy of D. Keren, reproduced with permission.

Citation: Gorevic P, Galanakis D. 2016. Cryoglobulins, Cryofibrinogenemia, and Pyroglobulins, p 101-111. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch10
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Image of FIGURE 4
FIGURE 4

Reversible cryogel formation at 4°C (tube inverted) and 37°C (liquid).

Citation: Gorevic P, Galanakis D. 2016. Cryoglobulins, Cryofibrinogenemia, and Pyroglobulins, p 101-111. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch10
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Image of FIGURE 5
FIGURE 5

EDTA inhibition of fibrin polymerization abolished by albumin. Clotting was initiated by thrombin (final concentration, 0.2 U/ml) in a solution containing isolated (>96% pure) fibrinogen (1 µM in 0.15 NaCl, 0.01 M Tris-HCl, pH 7.4). Clots shown are the control (C), that containing EDTA (1 mM), and that containing EDTA plus human albumin (200 µM).

Citation: Gorevic P, Galanakis D. 2016. Cryoglobulins, Cryofibrinogenemia, and Pyroglobulins, p 101-111. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch10
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Image of FIGURE 6
FIGURE 6

Higher cryoprecipitate contents in EDTA-collected than in citrate-collected plasma. Plasma from duplicate pairs of blood specimens from each of four normal donors was collected in tubes containing EDTA or citrate, frozen (−30°C) within an hour, and thawed overnight (4°C) to harvest cryoprecipitate. The cryoprecipitate was then washed and measured (280 nm) as detailed in the text. The protein content of cryoprecipitate from each donor is shown as a percentage of C, its citrate counterpart.

Citation: Gorevic P, Galanakis D. 2016. Cryoglobulins, Cryofibrinogenemia, and Pyroglobulins, p 101-111. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch10
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References

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Tables

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TABLE 1

Classification of cryoglobulins

Citation: Gorevic P, Galanakis D. 2016. Cryoglobulins, Cryofibrinogenemia, and Pyroglobulins, p 101-111. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch10
Generic image for table
TABLE 2

Disease, clinical, and laboratory associations

Citation: Gorevic P, Galanakis D. 2016. Cryoglobulins, Cryofibrinogenemia, and Pyroglobulins, p 101-111. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch10
Generic image for table
TABLE 3

Laboratory abnormalities in cryoglobulinemia

Citation: Gorevic P, Galanakis D. 2016. Cryoglobulins, Cryofibrinogenemia, and Pyroglobulins, p 101-111. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch10

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