Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia in Association with Antiphospholipid Syndrome.

Antiphospholipid syndrome and cold agglutinin-mediated autoimmune hemolytic anemia are 2 distinct immune-mediated hematologic disorders. While no clear association exists between these 2 entities, complement activation is known to occur in both of them. Herein, we report a unique case of cold agglutinin hemolytic anemia in a patient with a known primary antiphospholipid syndrome.

Cold Agglutinins and Cardiac Surgey: a Case Report.

Cold agglutinins (CA) are autoantibodies whose clinical significance depends upon titer and thermal amplitude. Patients, which undergo cardio-pulmonary bypass and especially hypothermic cardioplegia myocardial protection, represent a challenge regarding operative management, as tissue temperature should be maintained above the threshold of agglutination. We report on a case in which the presence of CA was discovered during elective aortic valve replacement surgery, and managed with normothermic cardiopulmonary bypass and continuous retrograde warm blood cardioplegia administration.

Severe acrocyanosis precipitated by cold agglutinin secondary to infection with Mycoplasma pneumoniae in a pediatric patient.

This is the first report describing a severe form of cold agglutinin-induced acrocyanosis with cutaneous necrosis after Mycoplasma infection in a 9-year-old patient without any other severe symptoms and laboratory alterations. We also present the results of two non-invasive methods used to determine the viability of tissues, degree of tissue perfusion impairment, and the responsiveness of the microvasculature. Laser Doppler flowmetry and laser speckle contrast imaging, both suitable to measure tissue blood perfusion non-invasively, have been used in the diagnosis and follow-up of various peripheral vascular diseases. In our patient, we demonstrated remarkably reduced microcirculation before the treatment and a significant perfusion increase in the acral regions after pentoxifylline therapy. The investigational techniques were useful tools to assess and quantify the severity of peripheral perfusion disturbances and to monitor the efficacy of the treatment in our patient.

Role of the receptor for the globular domain of C1q protein in the pathogenesis of hepatitis C virus-related cryoglobulin vascular damage.

Mixed cryoglobulinemia (MC) is a lymphoproliferative disorder observed in approximately 10 to 15% of hepatitis C virus (HCV)-infected patients. Circulating, nonenveloped HCV core protein, which has been detected in cryoprecipitable immune complexes, interacts with immunocytes through the receptor for the globular domain of C1q protein (gC1q-R). In this study, we have evaluated circulating gC1q-R levels in chronically HCV-infected patients, with and without MC. These levels were significantly higher in MC patients than in those without MC and in healthy controls and paralleled specific mRNA expression in PBL. Soluble gC1q-R circulates as a complexed form containing both C1q and HCV core proteins. Higher serum gC1q-R levels negatively correlated with circulating concentrations of the C4d fragment. The presence of sequestered C4d in the vascular bed of skin biopsies from MC patients was indicative of in situ complement activation. In vitro studies showed that release of soluble gC1q-R is regulated by HCV core-mediated inhibition of cell proliferation. Our results indicate that up-regulation of gC1q-R expression is a distinctive feature of MC, and that dysregulated shedding of C1q-R molecules contributes to vascular cryoglobulin-induced damage via the classic complement-mediated pathway.

Cold Antibodies in Cardiovascular Surgery: Is Preoperative Screening Necessary?

OBJECTIVES: Cold antibodies (CAs) are rarely significant for transfusion, but they can cause complications under the hypothermic conditions of cardiovascular surgery. The purpose of this study was to determine the incidence of such complications. METHODS: Patients with CAs who underwent cardiovascular surgery were identified, and their records were reviewed for intraoperative complications attributable to CAs. RESULTS: Over 14.5 years, of the 47,373 patients who underwent cardiovascular surgery, 99 had CAs before or within 30 days after surgery. Ninety-seven patients had hypothermic surgery, and intraoperative agglutination was noted in four; two of these cases were never reported to the transfusion service. CONCLUSIONS: The incidence of intraoperative complications among our patients with CAs was only 4%; therefore, the use of special testing protocols for the preoperative identification of CAs is neither necessary nor justified. Patient risk is best managed by preoperative clinical evaluation for potentially pathogenic CAs and intraoperative vigilance for agglutination.

Optimum Conditions for the Efficacy and Safety of Cryofiltration Apheresis: An Analysis of Circuit Temperatures Depending on Plasma Flow Rate and Cooling Coil Lengths/Turns.

A system providing both appropriate cooling and warming are needed for the efficacy and safety of cryofiltration (CF) plasmapheresis. We measured some points of CF circuit temperatures with varying plasma flow rates (QP = 10-40 mL/min) and the numbers of connecting cooling coils (one or two) under the conditions of blood flow rate (QB ) 100 mL/min with 7700-mm coil length, 19 turns, and 50-mL priming volume. We measured the respective temperatures of each point of starting/returning for an extracorporeal circuit (TA /TV ), intracooling coil (TC ), and post-plasma fractionator (PF) (TPF ). The subtraction of TV from TA (ΔT) was used as an indicator of safe return. There were no significant differences in TC , TPF , or ΔT in accordance with each QP between that of one and two coils. All of the Tc values under the condition QP ≤ 20 mL/min achieved <4°C. The TPF under the condition QP ≥ 20 mL/min was not significantly different compared to that of QP 30 mL/min (the lowest condition). Although the ΔT increased depending on the QP increase, the ΔT under the condition QP ≤ 15 mL/min was not significantly different from that of the control (one-way double-filtration plasmapheresis [DFPP]) group. We conclude that (i) one coil is enough for effective cooling in CF, and (ii) an ideal QP that fulfills the required conditions for both effective cooling and sufficient warming of returning fluid does not exist, but QP from 15 to 20 mL/min may be a relevant range.

Cryofibrinogenemia and skin necrosis in a patient with diffuse large cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation.

A 34-year-old woman with diffuse mediastinal B cell large cell lymphoma presented 60 days after high-dose chemotherapy and autologous stem cell transplantation, and post-transplant immunotherapy with interleukin-2, with skin necrosis in the ears and extremities. Extensive work-up revealed the presence of cryofibrinogenemia and associated thrombotic vasculopathy. The patient was successfully treated with corticosteroids and therapeutic plasma exchange. However, she had recurrence of large cell lymphoma a few weeks later and died of progressive disease. Cryfibrinogenemia and skin necrosis may have occurred secondary to the imminent relapse, or as a rare complication of high-dose chemotherapy or treatment with interleukin-2.

Cryofibrinogenemia in a patient with B-cell lymphoma.

Cryofibrinogenemia is an uncommon cause of intravascular coagulation necrosis of the skin and occurs as a result of vascular occlusion from cryoproteins, which reversibly precipitate in cold temperatures. The disease is associated with various conditions, most commonly neoplastic and thromboembolic diseases, and produces cutaneous manifestations such as purpura, ecchymoses, gangrene, and ulcerations. Diagnosis is based on clinical cutaneous manifestations, histopathology, and the laboratory detection of cryofibrinogen precipitation. Treatment is based upon resolution of the underlying disease process or condition, although some interventions have been reported to have therapeutic efficacy. We discuss the presentation, diagnosis, and treatment of a case of cryofibrinogenemia in a patient with underlying B-cell lymphoma.

Cold agglutinin-induced haemolysis in association with antinuclear antibody-negative SLE.

Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease associated with several autoantibodies targeted to nuclear and cytoplasmic antigens. Serum antinuclear antibody (ANA) is considered an important diagnostic marker of SLE. However, 2-3% of patients with typical clinical picture of SLE may have persistently negative ANA tests. Autoimmune haemolytic anaemia (AIHA) in SLE is usually mediated by warm IgG anti-erythrocyte antibodies. Our report describes a female patient who presented with clinical manifestations of SLE including photosensitivity, joint pains and AIHA. Further workup revealed high cold IgM agglutinin titres. A comprehensive workup for infectious aetiologies was negative. Autoimmune studies revealed negative ANA, but positive anti-double-stranded DNA and antiphospholipid antibodies. Lymphoproliferative disorder was excluded by imaging studies. Initial treatment with steroids proved of little benefit; however, rituximab resulted in significant clinical improvement. To the best of our knowledge, this is perhaps the first report of ANA-negative SLE presenting with cold AIHA.

A useful method for the detection of ethylenediaminetetraacetic acid- and cold agglutinin-dependent pseudothrombocytopenia.

INTRODUCTION: Pseudothrombocytopenia (PTCP), caused by platelet (PLT) aggregation, is usually associated with ethylenediaminetetraacetic acid (EDTA)-dependent antibodies and cold aggluti-nins against PLT antigens. The aim of this study was to identify the PTCP and discover the most practical method to distinguish it from real thrombocytopenia. METHODS: This study included 85 patients without hemorrhagic abnormalities and suspected PTCP. Blood samples containing EDTA, citrate and EDTA-kanamycin (KN) were analyzed at room temperature and 37°C. RESULTS: PTCP was detected in 24 of 85 patients. In 23 of 24 patients, EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) was detected; 5 of whom had also the cold agglutinin-dependent PTCP. In only 1 of 24 patients, the cold agglu-tinin-dependent PTCP was found. In this study, no significant difference was observed in leukocyte counts comparing EDTA and citrate blood samples in cases with EDTA-PTCP. CONCLUSION: In clinical laboratories, a significant portion of the cases with low PLT counts was attributable to EDTA-PTCP and, therefore, did not require treatment. Even if these cases can be detected by bringing the blood samples containing EDTA to 37°C or by adding KN to blood samples containing EDTA, the use of blood samples containing citrate taken for erythrocyte sedimentation rate analysis is a more practical priority method.

Enfermedad por crioglobulinas secundaria a infección por Epstein-Barr: una complicación infrecuente de una enfermedad frecuente / Cold agglutinin disease secondary to Epstein-Barr virus infection: a rare complication of a common disease

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Cold agglutinin induced hemolysis in a newly diagnosed systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a well-known autoimmune chronic inflammatory disease, which can virtually affect any organ system in the body. Although hemolytic anemia has been known to occur in <10% of SLE patients, they are usually mediated through warm antibodies. It is extremely rare to see cold antibody-mediated hemolytic anemia in SLE, and only few cases have been reported in literature to our knowledge. This is a unique case report of SLE associated with cold agglutinin hemolytic anemia in a patient presented with generalized tender lymphadenopathy and typical B-symptoms including fever, night sweats, and significant weight loss.