Which antibody is associated with paroxysmal cold hemoglobinuria PCH?

Clinical Features

Paroxysmal cold hemoglobinuria was historically associated with tertiary syphilis, which is rarely seen today. PCH is now more commonly seen primarily in children after a viral or, much less commonly, bacterial illness.124 Most commonly, the viral etiology is not known but is associated with an upper respiratory tract infection. However, case reports in both adults and children have reported an association of PCH with varicella.

Although the Donath-Landsteiner antibody often occurs in tertiary or congenital syphilis, it generally does not cause hemolytic disease in this situation. On exposure to cold, an occasional patient experiences paroxysms of hemoglobinuria and constitutional symptoms (fever, back pain, leg pain, abdominal cramps, and rigors) followed by hemoglobinuria. In contrast, the postviral form of PCH125–127 is characterized by constitutional symptoms with fulminant intravascular hemolysis and its associated signs of hemoglobinemia, hemoglobinuria, jaundice, severe anemia, and sometimes renal failure. The disease is self-limited, usually lasting 2 to 3 weeks, although it can be life threatening because of the severity of the hemolysis and consequent anemia.

Clinical Manifestations

PNH is a rare disorder in children. Approximately 60% of pediatric patients have marrow failure, and the remainder have either intermittent or chronic anemia, often with prominent intravascular hemolysis (Table 488.2). Nocturnal and morning hemoglobinuria is the classic finding in adults, but only a minority of PNH patients have this manifestation. Most patients experience chronic hemolysis, often with thrombocytopenia and leukopenia. Hemoglobinuria is rarely seen in children compared to adults with PNH.Thrombosis andthromboembolic phenomena are serious complications that may be related to altered glycoproteins on the platelet surface and resultant platelet activation and production of procoagulant microparticles. Abdominal venous thrombosis presents as recurrent episodes of abdominal pain, Budd-Chiari syndrome (hepatic veins), or splenomegaly (splenic vein). Furthermore, released free hemoglobin results in depletion of nitric oxide, fostering vasoconstriction, thrombosis, and pain. Back and head pain may also be prominent. Hypoplastic or aplastic pancytopenia can precede or follow the diagnosis of PNH; rarely, PNH may progress to acute myelogenous leukemia. At the time of presentation, >90% of patients with PNH have some cell line abnormality (including approximately 35% with anemia alone, 15% with anemia and thrombocytopenia, 7% with anemia and neutropenia, and 30% with pancytopenia), >10% have abdominal pain, and >5% have thrombosis. The mortality in PNH is related primarily to the development of aplastic anemia or thrombotic complications. The predicted survival rate for children before the development of eculizumab was 80% at 5 yr, 60% at 10 yr, and 28% at 20 yr.

Paroxysmal Cold Hemoglobinuria

PCH is rare in adults, but accounts for 32% of cases of immune hemolytic anemia in children. It is a disorder that occurs due to the formation and activity of the DL antibody, which is a weak-affinity “biphasic” IgG cold-reactive, complement-binding autoantibody most frequently shown to have P specificity. This biphasic antibody binds to autologous P-positive RBCs at low temperature and initiates complement activation, but intravascular hemolysis does not occur until the RBCs with the antigen–antibody complex warm to 37°C. Patients with DL antibodies generally have a negative antibody screen because the antibodies do not react with RBCs under usual laboratory testing conditions. Because the DL antibody does not cause RBC agglutination above 20°C, it does not interfere with pretransfusion testing. PCH may be idiopathic or secondary to viral infections or syphilis. The clinical manifestation of PCH is an acute intravascular hemolytic anemia. In severe cases, shaking chills, abdominal pain, and high fever may be observed. It is predominantly a pediatric disease, typically occurring after a viral illness, such as an upper respiratory or gastrointestinal infection; however, rare causes may include vaccination, autoimmune disorders, and hematopoietic malignancies. Usually, it is self-limited, resolving completely within several weeks. There are only rare reported cases of chronic PCH, which were more common historically with advanced syphilis. The DAT is usually positive with complement only (Table 51.1). Along with the clinical presentation, the diagnosis is supported by a positive DL test and the absence of warm autoantibodies or CAs. Spherocytosis or rouleaux may be seen in up to 50% of patients on the peripheral blood smear. Although erythrophagocytosis by neutrophils is a pathognomonic finding, this is observed in less than 10% of cases. Treatment for PCH is primarily supportive, including cold avoidance. Corticosteroids have not been shown to improve outcome. Rare cases with severe or recurrent hemolysis have been treated with IVIG, azathioprine, or rituximab. Syphilis treatment usually eliminates syphilis-associated PCH.

There is some suggestion that transfused p or Pk RBCs will have better in vivo survival, but the patient is likely to require transfusion before these RBC products becoming available. Therefore, the use of crossmatch-compatible RBCs of common P types should be provided, which usually provides adequate RBC support. In addition, RBCs should be transfused through a blood warmer, and the patient should be maintained at a warm temperature.

Paroxysmal Cold Hemoglobinuria

PCH is a rare condition. It is usually seen in children following a viral infection. In adults it was classically associated with syphilis but is now more commonly associated with malignancies.

The autoantibody is directed against the blood group antigen P. It is an IgG that is usually active at temperatures below normal core temperatures; some however are active at 37 °C. The antibody binds to the red cells when the blood is cooler, at the peripheries, and then binds the complement which then causes red cell intravascular hemolysis when the blood returns to normal temperature in the core; as the blood temperature increases, the antibody dissociates from the red cell. The complement-mediated hemolysis leads to anemia and hemoglobinuria. The DAT is usually only positive for complement. It is diagnosed by performing a Donath–Landsteiner test (Figure 9).

In children most cases are transient and usually only need treatment with blood transfusions if there is symptomatic anemia. The patient should be kept warm. In adults the course may be more chronic but it is important to warm the patient, treat the underlying cause, and transfuse if the anemia is symptomatic. Steroids and plasma exchange may be beneficial.

Paroxysmal cold hemoglobinuria

Paroxysmal cold hemoglobinuria (PCH) is the rarest of all autoimmune hemolytic anemias, accounting for less than 2% of these disorders. It is also quite unique from the standpoint of immunohematology in that the disease process is based upon an IgG-class autoantibody which demonstrates the strongest RBC avidity at cold temperatures. Moreover, the IgG autoantibodies of PCH primarily fix complement and thus mediate a severe form of intravascular hemolysis. Like the autoantibodies of CAS, the IgG autoantibodies associated with PCH show wide thermal amplitude, fixing to RBCs at temperatures around 27–30 °C. Once the PCH autoantibody has bound, complement fixation occurs, resulting in subsequent intravascular hemolysis. As such, individuals with PCH present with fatigue, severe anemia, fever, and frequently red colored urine resulting from the accumulation of free hemoglobin.

Similar to both CAS and WAIHA, the mechanisms leading to induction of the IgG cold autoantibody of PCH remain poorly understood, although the epidemiology of associated disorders has been well documented. In the past, PCH was a common complication of tertiary syphilis in adults. However, the vast majority of cases of PCH in the modern era are seen in children after infection or vaccination. EBV and M. pneumoniae are among the most common causes of infection-associated PCH, while vaccines for measles, polio, and even Haemophilus influenza have been reported to be associated with PCH.

DAT testing is a first-line approach in the assessment of PCH. Since the IgG antibodies in this disorder are cold reactive and primarily fix complement, agglutination of RBCs is typically only seen with anti-C3. If a diagnosis of PCH is suspected based on the clinical picture and initial DAT testing, then the Donath–Landsteiner test may subsequently be performed to confirm this condition. As shown in Figure 4, the Donath–Landsteiner test involves collecting the patient sample into a prewarmed tube and letting the plasma separate at a warm temperature. The patient's plasma is then incubated with reagent RBCs at a variety of temperatures. Since the IgG autoantibody fixes at cold temperatures, but causes hemolysis by complement activity at a core body temperature of 37 °C, a positive Donath–Landsteiner test occurs when in vitro hemolysis is associated with a specimen that is incubated at cold temperatures and then warmed to 37 °C (controls maintained persistently at cold and warm temperatures should be negative). Notably, most PCH cold autoantibodies show specific reactivity against the P blood group antigen. Such findings may be helpful in confirming a diagnosis of PCH.

Treatment of PCH is largely supportive, since resolution of the initiating cause is typically associated with the disappearance of the cold-reactive IgG autoantibody. Supportive care for PCH is similar to that of CAS and may include transfusion therapy, monitoring of end-organ function, and maintenance of warm temperatures in patient extremities. Immunosuppression may also be beneficial in some cases.

Bacillary Hemoglobinuria

Bacillary hemoglobinuria is an acute and highly fatal disease of cattle and sheep that occurs in various areas of the world and can be endemic in those regions in which liver fluke, particularly Fasciola hepatica, infection also occurs. Spores of Clostridium haemolyticum, the causative agent of bacillary hemoglobinuria, are ingested and come to reside within Kupffer cells, but they proliferate only in areas of low oxygen tension. Migration of immature liver flukes, or less commonly other parasites, or an event such as liver biopsy produces a nidus of necrotic hepatic parenchyma in which bacterial spores can germinate. Bacteria proliferate and release exotoxins, including the beta toxin phospholipase C, which induces the hepatocellular necrosis, intravascular hemolysis, anemia, and hemoglobinuria that characterize the disease. Grossly, these foci (or often a large single lesion), which have been misnamed infarcts, are sharply delineated from the adjacent parenchyma and usually are pale and surrounded by an intensely hyperemic zone (Fig. 8-73). The causative organisms, Gram-positive spore-containing rods, may be visible in histologic sections. Migration tracts of the immature flukes that typically precipitate the disease may be present. Serous cavities (pleura, peritoneum, and pericardium) can be flecked with fibrin.

Paroxysmal Cold Hemoglobinuria

Paroxysmal cold hemoglobinuria is a rare form of immune-mediated hemolytic anemia in which C1q bound to an IgG autoantibody attaches to red cells at low temperatures. The target antigens are globoside and a glycosphingolipid. The antibody dissociates from red cells at 37° C, but C1q remains on the membrane; at the warmer temperature it triggers progression of the complement cascade to its lytic components. The result is intravascular hemolysis.

An unsolved problem is how the lytic components of complement are generated on the red cell surface in paroxysmal cold hemoglobinuria but not in cold agglutinin disease. With the waning of late syphilis in modern times, the so-called Donath-Landsteiner antibody of paroxysmal cold hemoglobinuria is encountered most often during convalescence from a viral infection, usually a childhood exanthem.

The Donath-Landsteiner autoantibody has no clinical effects unless the patient is exposed to cold temperatures. With cold exposure, even of just an arm or a leg, intravascular hemolysis begins soon after the return to a warm temperature. Chills, fever, back pain, abdominal cramps, and hemoglobinuria are typical. Urticaria is common, acute renal failure is rare, and anemia is an inevitable consequence of severe intravascular hemolysis. The attack is self-limited, lasting only 1 or 2 days.

A positive Donath-Landsteiner test is diagnostic, but the test is relatively insensitive. The procedure should demonstrate hemolysis in the test tube when the patient's blood is chilled and then warmed to 37° C. Addition of normal serum as a source of complement is often necessary to bring out the hemolytic phase of the reaction.

Treatment is generally unnecessary, and spontaneous recovery can be expected within weeks or a few months.

What antibody is associated with PCH?

Which of the following is associated with paroxysmal cold hemoglobinuria?

Which antibody is associated with paroxysmal cold hemoglobinuria quizlet?

Is PCH IgG?