Paroxysmal Cold Hemoglobinuria Research Articles

Paroxysmal cold haemoglobinuria caused by non‐Hodgkin's lymphoma

Paroxysmal cold haemoglobinuria is an autoimmune haemolytic anaemia characterized by a biphasic polyclonal IgG autoantibody, the Donath-Landsteiner (D-L) antibody. Although classically described in association with chronic syphilis, it is most commonly seen after acute viral infections in children. We describe a case of high-grade B-cell non-Hodgkin's lymphoma which presented with paroxysmal cold haemoglobinuria. The lymphoma responded promptly to combination chemotherapy whilst, at the same time, the haemolytic process rapidly resolved. Subsequent investigations showed that the D-L antibody originated from the lymphoma cells.

Paroxysmal cold haemoglobinuria caused by non-Hodgkin's lymphoma

Paroxysmal cold haemoglobinuria caused by non-Hodgkin's lymphoma

Paroxysmal cold hemoglobinuria and the elusive Donath- Landsteiner antibody

Abstract Four patients with paroxysmal cold hemoglobinuria (PCH) illustrate some of the difficulties in making the diagnosis. A 46-year-old male presented with anemia, a weakly positive direct antiglobulin test (DAT) with anti-IgG, a haptoglobin < 0.1 g/L, and a cold autoagglutinin showing anti-P specificity. A 9-year-old female had a 4-day coryzal illness, a 20 g/L fall in hemoglobin over 24 hours, and a haptoglobin < 0.1 g/L; the DAT was positive with anti-C3d. A 3-year-old female was referred following a rapid drop in hemoglobin of 30 g/L; the DAT was positive with anti-C3d. A 17-month-old female, unwell for 2 weeks, had a hemoglobin of 41 g/L; the DAT was strongly positive with anti-C3d and weakly positive with anti-IgG and -C3c. In all patients, PCH was confirmed by positive indirect Donath- Landsteiner tests, and the autoantibodies demonstrated P specificity. In two patients, the test was strongly positive; in the third patient, it was only positive using papainized red cells; and in the fourth patient, a two-stage papainized procedure was needed before a positive result was obtained. PCH must always be considered in a child with a rapid drop in hemoglobin, even if initial tests are negative.

Delayed hemolytic transfusion reaction and paroxysmal cold hemoglobinuria: an unusual association

An 80-year-old female presented with melena and anemia due to bleeding from a benign gastric ulcer. Her blood group was O, D+. The serum contained anti-B and a weak anti-A (titer 2 at 18°C). She was inadvertently transfused with approximately 3.5 units of group A red blood cells with no initial ill effects. One week later, the antiA titer increased to 8 and the direct antiglobulin test (DAT) was weakly positive (IgG and C3d). The next day, intravascular hemolysis became evident. The DAT was still weakly positive and the serum contained a weak cold autoagglutinin, which did not correlate with the severity of the hemolysis. A Donath-Landsteiner test was performed and found to be strongly positive. The antibody showed P specificity, confirming a diagnosis of paroxysmal cold hemoglobinuria (PCH). Exchange transfusion was followed by rapid recovery even though the Donath-Landsteiner test remained positive for at least a month. The patient was well when last seen 11 months after presentation. It was thought that the original low titer of anti-A reflected compromised immune homeostasis in an elderly patient and that stimulation by incompatible blood in those circumstances resulted in a delayed hemolytic transfusion reaction that triggered, exacerbated, or was accompanied by an autoimmune response manifesting as PCH.

Case report: rapid onset of severe anemia in childhood. A systematic approach to laboratory diagnosis

Abstract Evaluation of a patient prompted the systematic review of causes of abrupt onset anemia in children and the development of a protocol for the immunohematologic workup of such cases. The patient, a 3-year-old boy, presented to our institution two weeks following a viral illness with gross hematuria, jaundice, and severe anemia (hematocrit 14.5%). He was found to have a positive direct antiglobulin test (DAT) due to primarily complement sensitization (2+) with smaller amounts of IgG (weak). A nonspecific cold agglutinin, anti-P1, and a hemolytic biphasic Donath-Landsteiner antibody were demonstrated in his serum, and he was diagnosed with paroxysmal cold hemoglobinuria (PCH). The hemolytic anemia resolved with packed red cell transfusions, intravenous immune globulin, and steroid treatment. It was concluded that a complete immunohematologic evaluation, including a DAT, cold agglutinin, and Donath-Landsteiner antibody tests, is pivotal to prompt and accurate assessment of the cause of an abrupt onset of severe anemia in children.

Hemophagocytosis in a Child with Paroxysmal Cold Hemoglobinuria

Hemophagocytosis in a Child with Paroxysmal Cold Hemoglobinuria

Transfusion Therapy in Autoimmune Hemolytic Anemia

Autoimmune hemolytic anemias include warm and cold reactive autoimmune hemolytic anemias (WAIHA and CAD), paroxysmal cold hemoglobinuria (PCH), and drug-induced hemolytic anemias. If autoimmune hemolytic anemia is suspected, the clinical history should be communicated to the transfusion service, because specific tests to confirm these diagnoses are not routinely performed. This includes evaluation of the patient's RBCs for bound IgG and complement (direct antiglobulin test) and evaluation of the patient's serum for antibodies with RBC specificity. For warm or cold autoimmune hemolytic anemia, special procedures including autoabsorption may be necessary to identify underlying RBC alloantibodies prior to transfusion. Transfused RBCs may not have normal survival in patients with RBC autoantibodies. The decision to transfuse should consider the patient's need for oxygen-carrying capacity, the risk of withholding transfusion, and the potential benefit of alternative therapy.

Case report: serologic confirmation of paroxysmal cold hemoglobinuria

A child with a history of recent viral infection entered the hospital with severe anemia, hemoglobinuria, and suspected autoimmune disease, Serologic findings included a positive direct antiglobulin test and incompatible crossmatches. Extensive studies, including a Donath-Landsteiner test, confirmed paroxysmal cold hemoglobinuria. The child was transfused several times with washed red blood cells compatible by prewarm technique. Although hemolysis continued after each transfusion, he stabilized and went home 5 days after his hospital admission. He reportedly made a complete recovery. Immunohematology 1992;8: 19–21.

Two cases of paroxysmal cold hemoglobinuria with a Donath‐Landsteiner antibody reactive by the indirect antiglobulin test using anti‐IgG

Two cases of paroxysmal cold hemoglobinuria with a Donath‐Landsteiner antibody reactive by the indirect antiglobulin test using anti‐IgG

Donath-Landsteiner Antibody of the IgM Class with Anti-I Specificity and Possible Efficacy of Azathioprine Therapy in Paroxysmal Cold Hemoglobinuria: A Case Report

Donath-Landsteiner Antibody of the IgM Class with Anti-I Specificity and Possible Efficacy of Azathioprine Therapy in Paroxysmal Cold Hemoglobinuria: A Case Report

Transient donath landsteiner haemolytic anaemia in children

The majority of patients with the syndrome of paroxysmal cold haemoglobinuria in whom Donath and Landsteiner described their classical biphasic haemolysin test suffered from tertiary syphilis. In the last two decades acute haemolytic anaemias associated with a positive Donath Landsteiner test (DLT) have been reported also In young children following upper respiratory tract infections (URTI). Between 1975 and 1988, 7 patients (6 boys, 1 girl) between 15 and 30 months of age presented at this hospital with acute haemoglobinuria and an associated positive DLT. An URTI had been noted 3-10 days earlier. Haemoglobin nadir values were in the range 4.1 to 9.3 G/dl (Two children required transfusion). All children had negative serological tests for syphilis. Viral antibody tests failed to document a specific viral cause of the URTI. All children showed spontaneous recovery to normal haemoglobin levels. In the 4 patients with continued outpatient follow-up at this hospital the DLT became negative within 1-6 weeks of presentation. Because of the transient nature of the Donath Landsteiner haemolysin associated with viral infection a DLT is indicated early in the investigation of children with acute haemoglobinuria.

Human Organ Specific Autoimmunity: Personal Memories

Many stratagems exist that bring about tolerance to endogenous body components to allow self-nonself discrimination and avoid potentially embarrassing autoimmune responses. At the turn of the century, the great Erlich recognized the necessity to establish the mechanisms that prevented self-reactivity and suggested that this could be mediated by the lymphoid system. However, these protective mechanisms against autoreactivity were not always successful; for example, Donath and Landsteiner’ described an antibody in paroxysmal cold haemoglobinuria that bound to red cells in the cold and then in the presence of complement would cause lysis as the temperature was raised. Interestingly, evidence for thyroid autoimmunity in human disease had been obtained as long ago as 19 1 1, when a young Romanian lady named Alexandrina Papazolu found that a third of the serum samples from patients with thyrotoxicosis gave positive complement fixation tests (CFT) with thyroid extracts. The audience, of course, was quite unmoved by these revelations because at that time they did not have the background knowledge to appreciate their significance. Also, in the aftermath of the discovery of the Wasserman reaction for syphilis, the studies were carried out as part of a popular vogue, looking at CFT with various organs rather than deliberately attempting to examine the hypothesis that autoimmunity was responsible for the disease. In fact, direct links between autoimmunity and disease were not really recognized until well after the Coombs’ test had been introduced in 1946 when the role of autoantibodies to red cells in the pathogenesis of acquired haemolytic anaemia was proposed. That deliberate induction of autoimmunity could cause tissue damage was well known from animal studies. Autolysed preparations of monkey brain, when injected back into the same species, were known to produce encephalomyelitis’. The introduction of the water in oil emulsion with killed TB by Dr Freund provided immunologists with a powerful way to provoke autoimmune lesions by incorporating autoantigens in an emulsion with that adjuvant. Freund himself showed quite unequivocally that sperm in Freund adjuvant could readily induce aspermat~genesis~. many other examples of autoantigen-induced tissue lesions were described, but particularly relevant in the present context were the experiments of Rose and Witebsky4 described elsewhere in this issue, who showed that extracts of an animal’s own thyroid incorporated in Freund adjuvant would induce both thyroid antibodies and a damaging invasive lymphocytic infiltration of the residual thyroid gland. In other words, the induction of autoimmunity to components of the thyroid gland resulted in an attack by the immunologically sensitized cells on the thyroid, with the autoantigen itself providing the target.

Evans' syndrome as a presenting manifestation of atypical paroxysmal cold hemoglobinuria

Paroxysmal cold hemoglobinuria is a rare and potentially life-threatening acquired hemolytic anemia occurring either as an acute transient anemia following several different viral syndromes, or in a chronic idiopathic form. Episodic hemolysis in paroxysmal cold hemoglobinuria is usually associated with a biphasic (Donath-Landsteiner) IgG cold-reactive complement-fixing autohemolysin with anti-P specificity. Paroxysmal cold hemoglobinuria has not previously been associated with malignancy nor has it been clearly shown to be steroid-responsive. This report describes a patient with steroid-responsive autoimmune hemolytic anemia and immune thrombocytopenia (Evans' syndrome) associated with oat cell carcinoma of the lung and a unique biphasic anti-I IgM autohemolysin. This case extends the spectrum of biphasic antibody-mediated immune cytopenias and widens both the clinical and the serologic definition of paroxysmal cold hemoglobinuria.

A Case of Paroxysmal Cold Hemoglobinuria with Thrombocytopenia (Evans' Syndrome), and without Anti-P Specificity of Biphasic Hemolysin

A Case of Paroxysmal Cold Hemoglobinuria with Thrombocytopenia (Evans' Syndrome), and without Anti-P Specificity of Biphasic Hemolysin

Cardiac Surgery in Patients with Cold Autoimmune Diseases

Cold-reactive autoantibodies may occur normally in humans at 4°C but, in the primary cold autoimmune diseases such as cold hemagglutinin disease and paroxysmal cold hemoglobinuria (1,2), cold-reactive autoantibodies occur at temperatures as high as 29–32°C. These autoantibodies or cold agglutinins may agglutinate erythrocytes at cold temperatures and cause hemolysis on rewarming (1,2). Perioperative myocardial infarction, hemolytic anemia with cardiac failure, persistent postoperative hemolysis, and immune-complex nephritis with azotemia may occur during systemic hypothermia and infusion of cold cardioplegic solutions in patients with cold autoimmune diseases (3–5). The differential diagnosis, anesthetic implications, and methods for myocardial preservation in patients with cold autoimmune diseases undergoing cardiac surgery are described.

Transfusing the Patient with Autoimmune Hemolytic Anemia

Because the problems relating to blood transfusion in patients with autoimmune hemolytic anemia vary depending on the specific type of disease (warm antibody AHA, cold agglutinin syndrome, or paroxysmal cold hemoglobinuria), definitive diagnosis is crucial. Blood should never be considered to be contraindicated, even though the compatibility test may be strongly incompatible, without also considering such critical factors as the progression of the anemia.

Autoimmune haemolysis associated with Donath-Landsteiner antibodies.

The clinical pattern of haemolysis associated with Donath-Landsteiner antibodies has undergone a change over the years. In the current study 13 patients developed the acute form of the disease whilst only 1 presented with the classical picture of chronic paroxysmal cold haemoglobinuria. The acute illness typically occurred in young children with a male predominance of about 2.5:1; 10 patients were less than 5 years old. There was often a history of a preceding infection, the onset was sudden, prostration, haemoglobinuria and pallor were prominent. The patients were very ill but rapid and complete recovery usually occurred within a few days; however, 1 patient died. Treatment consisted of rest and warmth; in addition blood transfusion was needed in 7 patients. The chronic disease (which was non-syphilitic in origin) followed a benign course, warmth and avoidance of cold being all that were necessary to maintain the patient's well-being. It is felt that the general term for this disorder should be Donath-Landsteiner haemolysis rather than the traditional paroxysmal cold haemoglobinuria.

Reaction of Antibodies That Cause Paroxysmal Cold Hemoglobinuria (PCH) With Globoside and Forssman Glycosphingolipids

Many antibodies that cause paroxysmal cold hemoglobinuria (Donath-Landsteiner antibodies) appear to be directed against the blood group P antigen. We recently identified this antigen as the glycosphingolipid globoside GalNAc(β, 1-3)Gal(α, 1-4)Gal(β,1-4)Glc-Cer, and we examined the reaction of four Donath-Landsteiner antibodies with anti-P specificity, and an anti-P acid autoagglutinin, with globoside and Forssman glycolipids. Forssman glycolipid, GalNAc(α, 1-3) GalNAc(β, 1-3)Gal(α, 1-4)Gal(β,1-4)Glc-Cer, contains the globoside structure plus an additional terminal nonreducing α-GalNAc residue. All five antibodies were inhibited effectively by globoside. Two of the Donath-Landsteiner antibodies were inhibited much more effectively by globoside than Forssman glycolipid, and the other two antibodies were inhibited more effectively by Forssman glycolipid. The two glycolipids were approximately equally effective in inhibiting the acid anti-P agglutinin. We suggest that the populations of antibodies that react with both glycolipids are directed against an aspect of the globoside structure that is accessible in the Forssman compound, whereas the antibodies that react best with globoside are probably directed against the terminal β-GalNAc residue of this glycolipid. Some human “anti-P“ antibodies are probably elicited by immunization against Forssman antigens that are widespread in animal tissues and in microorganisms.

Reaction of antibodies that cause paroxysmal cold hemoglobinuria (PCH) with globoside and Forssman glycosphingolipids

Reaction of antibodies that cause paroxysmal cold hemoglobinuria (PCH) with globoside and Forssman glycosphingolipids

Measurement of Donath-Landsteiner antibody-producing cells in idiopathic nonsyphilitic paroxysmal cold hemoglobinuria (PCH) in children

2-yr-old girl with a nonsyphilitic type of paroxysmal cold hemoglobinuria (PCH) is reported. We applied the plaque-forming cell (PFC) assay to the measurement of Donath-Landsteiner (DL) antibody- producing cells in the patient. Some of the circulating B lymphocytes formed plaques in our assay system. Initially the number of PFC was 1442 +/- 225/10(6) lymphocytes and DL titer was 1:16. Thereafter the PFC decreased in number as the DL titer decreased. Eight weeks later circulating PFC were not found but the DL titer was still 1:1 positive. The PFC assay appears to be useful as a new method for obtaining rapid imformation as to the disease status of PCH.