REPORT ON COLD AGGLUTININ DISEASE PATIENTS CLINICAL CHARACRERISTICS.
Author(s): ,
Aspasia Koudouna
Affiliations:
Haematology Section of First Department Of Propaedeutic Internal Medicine,National and Kapodistrian University of Athens,Athens,Greece
,
Ioannis Grafakos
Affiliations:
Haematology Section of First Department Of Propaedeutic Internal Medicine,National and Kapodistrian University of Athens,Athens,Greece
,
Aikaterini Bitsani
Affiliations:
Haematology Section of First Department Of Propaedeutic Internal Medicine,National and Kapodistrian University of Athens,Athens,Greece
,
Annita-Ioanna Gkioka
Affiliations:
Haematology Section of First Department Of Propaedeutic Internal Medicine,National and Kapodistrian University of Athens,Athens,Greece
,
Vasiliki Bartzi
Affiliations:
Haematology Section of First Department Of Propaedeutic Internal Medicine,National and Kapodistrian University of Athens,Athens,Greece
,
George Karamanakos
Affiliations:
Haematology Section of First Department Of Propaedeutic Internal Medicine,National and Kapodistrian University of Athens,Athens,Greece
,
Maria Dimou
Affiliations:
Haematology Section of First Department Of Propaedeutic Internal Medicine,National and Kapodistrian University of Athens,Athens,Greece
,
Theodoros Iliakis
Affiliations:
Haematology Section of First Department Of Propaedeutic Internal Medicine,National and Kapodistrian University of Athens,Athens,Greece
,
Vassilis Pardalis
Affiliations:
Haematology Section of First Department Of Propaedeutic Internal Medicine,National and Kapodistrian University of Athens,Athens,Greece
,
Panayiotis Panayiotidis
Affiliations:
Haematology Section of First Department Of Propaedeutic Internal Medicine,National and Kapodistrian University of Athens,Athens,Greece
Marie-Christine Kyrtsonis
Affiliations:
Haematology Section of First Department Of Propaedeutic Internal Medicine,National and Kapodistrian University of Athens,Athens,Greece
(Abstract release date: 05/14/20) EHA Library. Koudouna A. 06/12/20; 294169; EP1688
Dr. Aspasia Koudouna
Dr. Aspasia Koudouna
Contributions
Abstract

Abstract: EP1688

Type: e-Poster

Background
Cold agglutinin disease (CAD) is a rare entity. There are three types of cold-sensitive antibodies that can cause clinical manifestations: (1) Cold agglutinins, which are IgM autoantibodies that recognize antigens (I or i) on red blood cells (RBCs) surface at low temperatures. They can cause agglutination of RBCs and extravascular hemolysis.  Cold agglutinins classified into Primary and Secondary CAD .(2) Donath-Landsteiner antibodies that are IgG autoantibodies that recognize RBC P antigens at cold temperatures, but unlike cold agglutinins, these antibodies fix complement and cause intravascular hemolysis. (3)Cryoglobulins are autoantibodies forming immune complexes in the cold but generally do not interact with RBCs. Cryoglobulins  subclassified into 3 types (Type I, IgG or IgM, frequently associated with hematological malignancies; Type II  mixed cryoglobulins including monoclonal IgM with rheumatoid factor activity and polyclonal IgG  and type III mixed cryoglobulins involving polyclonal IgM and IgG).

Aims
To study the clinical and laboratory characteristics of a series of CAD patients.

Methods
Eight CAD patients diagnosed and followed in our section were retrospectively studied after their consent. Demographic, clinical as well as laboratory features were analyzed. They were diagnosed with cold-sensitive antibodies (while 1 also had cryoglobulins).

Results
Median age at diagnosis was 62 years, most patients had middle socio-economic status and females were affected more often (5 versus 3). All female patients were retired. Presenting symptoms in patients with cold-agglutinins ranged from none to extreme fatigue; pallor and jaundice with no lymph node enlargement or splenomegaly. The patient with cryoglobulinemia presented with skin necrosis – vascular occlusion. Five patients had at list one synchronous medical condition (hematologic malignancies, hepatitis, SEL) which was diagnosed during the workup, and one patient diagnosed CD5 positive BNHL 14 years later. Three patients had hepatitis. Cold agglutinins titers were disproportionate to the degree of hemolysis in 4 patients with underlying lymphoproliferative disorders. Median haemoglobin at presentation was 8,9 g/dL. Direct Coombs test was positive, usually IgM, C3d positive. Low serum monoclonal IgM was observed in 4 patients although most patients presented hypogammaglobulinemia. Slightly elevated serum CRP and ferritin were common findings. All patients received corticosteroids initially. Response to treatment, complete or partial, was seen in three primary CAD patients with corticosteroids, splenectomy and mycophenolate mofetil. Additional treatment included plasma exchange and anti-CD20 therapy. Five patients additionally received therapy for the underlying disease. During a median follow-up time of 42,5 months, two patients deceased from infections and sepsis, 2 others completely recovered, while the others presented relapses and remissions.

Conclusion
Although it is a small series, it highlights the wide range of CAD clinical behavior. Further and larger studies are needed to better understand and manage this rare entity.

Session topic: 33. Bleeding disorders (congenital and acquired)

Abstract: EP1688

Type: e-Poster

Background
Cold agglutinin disease (CAD) is a rare entity. There are three types of cold-sensitive antibodies that can cause clinical manifestations: (1) Cold agglutinins, which are IgM autoantibodies that recognize antigens (I or i) on red blood cells (RBCs) surface at low temperatures. They can cause agglutination of RBCs and extravascular hemolysis.  Cold agglutinins classified into Primary and Secondary CAD .(2) Donath-Landsteiner antibodies that are IgG autoantibodies that recognize RBC P antigens at cold temperatures, but unlike cold agglutinins, these antibodies fix complement and cause intravascular hemolysis. (3)Cryoglobulins are autoantibodies forming immune complexes in the cold but generally do not interact with RBCs. Cryoglobulins  subclassified into 3 types (Type I, IgG or IgM, frequently associated with hematological malignancies; Type II  mixed cryoglobulins including monoclonal IgM with rheumatoid factor activity and polyclonal IgG  and type III mixed cryoglobulins involving polyclonal IgM and IgG).

Aims
To study the clinical and laboratory characteristics of a series of CAD patients.

Methods
Eight CAD patients diagnosed and followed in our section were retrospectively studied after their consent. Demographic, clinical as well as laboratory features were analyzed. They were diagnosed with cold-sensitive antibodies (while 1 also had cryoglobulins).

Results
Median age at diagnosis was 62 years, most patients had middle socio-economic status and females were affected more often (5 versus 3). All female patients were retired. Presenting symptoms in patients with cold-agglutinins ranged from none to extreme fatigue; pallor and jaundice with no lymph node enlargement or splenomegaly. The patient with cryoglobulinemia presented with skin necrosis – vascular occlusion. Five patients had at list one synchronous medical condition (hematologic malignancies, hepatitis, SEL) which was diagnosed during the workup, and one patient diagnosed CD5 positive BNHL 14 years later. Three patients had hepatitis. Cold agglutinins titers were disproportionate to the degree of hemolysis in 4 patients with underlying lymphoproliferative disorders. Median haemoglobin at presentation was 8,9 g/dL. Direct Coombs test was positive, usually IgM, C3d positive. Low serum monoclonal IgM was observed in 4 patients although most patients presented hypogammaglobulinemia. Slightly elevated serum CRP and ferritin were common findings. All patients received corticosteroids initially. Response to treatment, complete or partial, was seen in three primary CAD patients with corticosteroids, splenectomy and mycophenolate mofetil. Additional treatment included plasma exchange and anti-CD20 therapy. Five patients additionally received therapy for the underlying disease. During a median follow-up time of 42,5 months, two patients deceased from infections and sepsis, 2 others completely recovered, while the others presented relapses and remissions.

Conclusion
Although it is a small series, it highlights the wide range of CAD clinical behavior. Further and larger studies are needed to better understand and manage this rare entity.

Session topic: 33. Bleeding disorders (congenital and acquired)

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