Paroxysmal Cold Hemoglobinuria Treatment & Management: Medical Care, Surgical Care, Consultations
Paroxysmal Cold Hemoglobinuria Treatment & Management: Medical Care, Surgical Care, Consultations
The mainstay of treatment for paroxysmal cold hemoglobinuria is supportive care and the avoidance of cold exposure.
Once hemolysis is suspected, folic acid 1 mg/d orally should be instituted to help with erythropoiesis. Folic acid is lost via the hemolytic process and hence needs to be replenished.
Administer warmed, packed RBC transfusions for life-threatening hemolysis and symptomatic anemia. Utilizing washed RBC units has not been proven to improve transfusion safety, but this can be performed if patient's condition remains refractory to standard warmed products.
As most of the blood supply is P-antigen positive, finding phenotypic p, also called Tj(a-), blood may not be feasible. However, the antibody should not interfere with donor cell survival, nor should it be problematic with pretransfusion and compatibility testing, as the pathogenic immunoresponse does not occur at normal body temperatures. Treat the uncommon chronic form with RBC transfusions only when severe exacerbation occurs.
Plasma exchange therapy with 5% albumin fluid replacement has been successfully employed.Normal use of plasmapheresis for removal of IgG-induced processes is not as effective due to rebound of immunoglobulin as it shifts from the extravascular to the intravascular compartment. However, due to the low titer and limited production period of the D-L antibody, the process can be effectively controlled. Another theory is that the antibody preferentially binds to the RBC, shifting the antibody equilibrium to the intravascular component, allowing for ease in its removal.
Steroids are commonly employed, but these agents have not been shown to shorten the clinical course of paroxysmal cold hemoglobinuria.
Treat underlying secondary conditions with appropriate medical therapy.
Hydration, alkalinization of the urine, and other measures may become necessary to prevent renal failure. Symptoms of cold urticaria may be ameliorated by antihistamines.
Surgery is not indicated in cases of paroxysmal cold hemoglobinuria, other than to aid in the diagnosis of underlying infections or neoplasms.
See the list below:
Folic acid supplements may be useful in the chronic form of paroxysmal cold hemoglobinuria. Encourage patients to eat fresh fruits and vegetables rich in folate.
Patients with paroxysmal cold hemoglobinuria should limit activities while severely anemic or if complications such as renal insufficiency are present. Avoid activities in the outdoors that are likely to result in cold exposure. Patients with the chronic form of the disease must wear proper clothes and garments to protect the extremities from becoming chilled.
Medication
Neetu Radhakrishnan, MD Assistant Professor of Medicine, Division of Hematology/Oncology, University of Cincinnati Medical Center; Lab Director, Hematology Lab, University Point, West Chester
Neetu Radhakrishnan, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology, American Society of Clinical Oncology
Coauthor(s)
Ronald A Sacher, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center
Ronald A Sacher, MB, BCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada, American Clinical and Climatological Association, International Society of Blood Transfusion
Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.
Specialty Editor Board
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Ronald A Sacher, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center
Ronald A Sacher, MB, BCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada, American Clinical and Climatological Association, International Society of Blood Transfusion
Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.
Chief Editor
Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences
Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital
Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology
Acknowledgements
Corinne Goldberg, MD Fellow in Transfusion Medicine/Blood Banking, Transfusion Medicine Department, Hoxworth Blood Center, University of Cincinnati
Disclosure: Nothing to disclose.
Rajalaxmi McKenna, MD, FACP Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.
Harry L Messmore, Jr, MD Professor, Department of Medicine, Division of Hematology/Oncology, Loyola University Stritch School of Medicine
Harry L Messmore, Jr, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Angiology, American College of Physicians, American Heart Assocation, American Society of Hematology, and Phi Beta Kappa
References
A Donath-Landsteiner test result is seen here, showing the appearance of a negative tube (no hemolysis in the supernatant) and a positive tube (red color in the supernate, implying the presence of free hemoglobin).
Workup for hemolytic anemia. Abbreviations: LDH, lactate dehydrogenase; DAT, direct antiglobulin; AIHA, autoimmune hemolytic anemia; WAIHA, warm autoimmune hemolytic anemia; CAIHA, cold autoimmune hemolytic anemia; PCH, paroxysmal cold hemoglobinuria; Ab, antibody.
Medical Care
The mainstay of treatment for paroxysmal cold hemoglobinuria is supportive care and the avoidance of cold exposure.
Once hemolysis is suspected, folic acid 1 mg/d orally should be instituted to help with erythropoiesis. Folic acid is lost via the hemolytic process and hence needs to be replenished.
Administer warmed, packed RBC transfusions for life-threatening hemolysis and symptomatic anemia. Utilizing washed RBC units has not been proven to improve transfusion safety, but this can be performed if patient's condition remains refractory to standard warmed products.
As most of the blood supply is P-antigen positive, finding phenotypic p, also called Tj(a-), blood may not be feasible. However, the antibody should not interfere with donor cell survival, nor should it be problematic with pretransfusion and compatibility testing, as the pathogenic immunoresponse does not occur at normal body temperatures. Treat the uncommon chronic form with RBC transfusions only when severe exacerbation occurs.
Plasma exchange therapy with 5% albumin fluid replacement has been successfully employed.Normal use of plasmapheresis for removal of IgG-induced processes is not as effective due to rebound of immunoglobulin as it shifts from the extravascular to the intravascular compartment. However, due to the low titer and limited production period of the D-L antibody, the process can be effectively controlled. Another theory is that the antibody preferentially binds to the RBC, shifting the antibody equilibrium to the intravascular component, allowing for ease in its removal.
Steroids are commonly employed, but these agents have not been shown to shorten the clinical course of paroxysmal cold hemoglobinuria.
Treat underlying secondary conditions with appropriate medical therapy.
Hydration, alkalinization of the urine, and other measures may become necessary to prevent renal failure. Symptoms of cold urticaria may be ameliorated by antihistamines.
Surgical Care
Surgery is not indicated in cases of paroxysmal cold hemoglobinuria, other than to aid in the diagnosis of underlying infections or neoplasms.
Consultations
See the list below:
- A hematologist-oncologist and an infectious diseases expert may be helpful for the proper diagnosis and treatment of paroxysmal cold hemoglobinuria.
- May also consult a nephrologist as needed to assist in the care of affected patients.
- The support of an experienced laboratory/blood bank is essential for all the serologic testing.
Diet
Folic acid supplements may be useful in the chronic form of paroxysmal cold hemoglobinuria. Encourage patients to eat fresh fruits and vegetables rich in folate.
Activity
Patients with paroxysmal cold hemoglobinuria should limit activities while severely anemic or if complications such as renal insufficiency are present. Avoid activities in the outdoors that are likely to result in cold exposure. Patients with the chronic form of the disease must wear proper clothes and garments to protect the extremities from becoming chilled.
Medication
Neetu Radhakrishnan, MD Assistant Professor of Medicine, Division of Hematology/Oncology, University of Cincinnati Medical Center; Lab Director, Hematology Lab, University Point, West Chester
Neetu Radhakrishnan, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology, American Society of Clinical Oncology
Coauthor(s)
Ronald A Sacher, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center
Ronald A Sacher, MB, BCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada, American Clinical and Climatological Association, International Society of Blood Transfusion
Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.
Specialty Editor Board
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Ronald A Sacher, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center
Ronald A Sacher, MB, BCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada, American Clinical and Climatological Association, International Society of Blood Transfusion
Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.
Chief Editor
Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences
Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital
Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology
Acknowledgements
Corinne Goldberg, MD Fellow in Transfusion Medicine/Blood Banking, Transfusion Medicine Department, Hoxworth Blood Center, University of Cincinnati
Disclosure: Nothing to disclose.
Rajalaxmi McKenna, MD, FACP Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.
Harry L Messmore, Jr, MD Professor, Department of Medicine, Division of Hematology/Oncology, Loyola University Stritch School of Medicine
Harry L Messmore, Jr, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Angiology, American College of Physicians, American Heart Assocation, American Society of Hematology, and Phi Beta Kappa
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A Donath-Landsteiner test result is seen here, showing the appearance of a negative tube (no hemolysis in the supernatant) and a positive tube (red color in the supernate, implying the presence of free hemoglobin).
Workup for hemolytic anemia. Abbreviations: LDH, lactate dehydrogenase; DAT, direct antiglobulin; AIHA, autoimmune hemolytic anemia; WAIHA, warm autoimmune hemolytic anemia; CAIHA, cold autoimmune hemolytic anemia; PCH, paroxysmal cold hemoglobinuria; Ab, antibody.
