Autoimmune hemolytic anemia (AIHA) is the clinical condition in which IgG antibodies bind to RBC surface antigens and initiate RBC destruction via the complement and reticuloendothelial system. AIHA is commonly treated with transfusions, corticosteroids, and splenectomy. We present a ease of an adult with life-threatening AIHA secondary to ulcerative colitis emergently managed with neuromuscular paralysis, induced hypothermia, and splenic embolization.
Key words: autoimmune hemolytic anemia; hypothermia; liver transplantation; splenic embolization; ulcerative colitis
Abbreviations: AIHA = autoimmune hemolytic anemia; LDH = lactate dehydrogenase; OPSI = overwhelming postsplenectomy infection; PRBC = packed RBC; V[O.sub.2] = oxygen uptake
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Autoimmune hemolytic anemia (AIHA) is the clinical condition in which IgG antibodies bind to BBC surface antigens and initiate RBC destruction via the complement and reticuloendothelial system. (1,2) Since the autoantibodies are usually directed against high-incidence antigens, they often exhibit reactivity against allogenic RBCs as well. AIHA is an uncommon disease, with an incidence of approximately 10 cases per million population. (1,2) AIHA occurs more commonly in women than in men and usually occurs in midlife. Approximately 50% of cases are primary AIHA, the remaining 50% being associated with an underlying disease, most commonly lymphoproliferative and connective tissue disease. AIHA can also be induced by drags. AIHA is rarely associated with ulcerative colitis, occurring in approximately 0.6 to 1.7% of cases. (1,3,4) Because the severity of AIHA may range from indolent to acutely life threatening, the impetus to initiate treatment must begin with a thorough appraisal of symptoms and the severity of hemolysis. Rapidly developing anemia with a hematocrit of < 20 requires urgent management. AIHA is commonly treated with transfusion, corticosteroids, and splenectomy. Treatments for refractory anemia include immunosuppressive agents, IV Ig, plasma exchange, and danazol, which may have limited efficacy and delayed onset of action. (1,2,5) We present a case of an adult with life-threatening AIHA secondary to ulcerative colitis emergently managed with neuromuscular paralysis, induced hypothermia, and splenic embolization.
CASE REPORT
A 43-year-old woman, status-post total colectomy in 1991 for ulcerative colitis and orthotopic liver transplant in 1999 for sclerosing cholangitis, was transferred from an outside hospital with a 2-day history of nausea and vomiting and 1-day history of jaundice. Physical examination revealed intact mental status, jaundice, and pallor. CBC count revealed a hemoglobin of 4.6 g/dL with a reticulocyte count of 42.5%, a WBC count of 17.2 x [10.sup.9]/L, with 68% neutrophils and 12% bands, and a platelet count of 368 x [10.sup.9]/L. Spherocytes were present on peripheral smear. Blood chemistry revealed increased total bilirubin of 5.5 mg/dL (<0.1 mg/dL conjugated bilirubin) and lactate dehydrogenase (LDH) of 922 IU/L. Serum haptoglobin was <5.0 mg/dL. The direct antiglobulin test (direct Coombs test) was positive for C3 and IgG. A diagnosis of severe AIHA was made. The patient was started on oral corticosteroids (prednisolone, 60 mg/d), and cross-matched blood was ordered. Due to the presence of alloantibodies and antoantibodies, it was extremely difficult to find blood for the patient.
On the second clay of hospitalization, the patient became symptomatic secondary to tissue hypoxia. Physical examination revealed tachycardia (120 to 130 beats/min), tachypnea (20 to 26 breaths/min), mild hypotension (100/53 mm Hg), temperature of 37.4[degrees]C, and a markedly depressed level of consciousness. CBC count showed hemoglobin of 3.3 g/dL, and blood chemistry revealed a lactate level of 6.2 mg/dL. At this time, the patient was urgently admitted to the liver transplant ICU. She was intubated and placed on mechanical ventilation (fraction of inspired oxygen, 100%.) In order to decrease oxygen uptake (V[O.sub.2]), the patient was sedated and paralyzed (with propofol and vecuronium) and actively cooled with a cooling blanket and cooled IV crystalloids. In addition, the patient received 1 g of methylprednisolone IV. Secondary to these interventions, the patient's pulse rate decreased to the upper 80s, temperature decreased to 33.8[degrees]C, BP decreased slightly to 90/53 mm Hg, and lactate level decreased to 1.0 mg/dL. The patient was then slowly transfused with 1 U of blood, crossed-matched as closely as possible, when it became available later in the day. The hemoglobin level subsequently increased to 3.9 g/dL, and LDH further increased to 1,058 IU/L. Given the severity of the AIHA an d the paucity of blood available for transfusion, it was decided that the patient would likely benefit from splenic embolization.
Embolization of the splenic artery, with polyvinyl alcohol particles, was performed the following day in the interventional radiology suite. The patient tolerated the procedure well. On the day of the splenic embolization, the patient subsequently received three more units of packed RBCs (PRBCs). The hemoglobin level increased to 9.4 g/dL (hematocrit 26.5), and LDH increased to 2,333 IU/L. Following the blood transfusion, the neuromuscular blocking agent was discontinued and the propofol gradually weaned off The patient was extubated the following day. The patient's temperature, hemoglobin concentration, LDH, and lactate levels over this time period are illustrated in Figure 1. After extubation, the patient complained of abdominal pain, which was managed with oral narcotics. The pain subsided over the course of 3 days. An abdominal CT performed 2 days after the embolization demonstrated marked splenic heterogeneity with multiple central and peripheral hypodense regions consistent with multifocal infarctions (Fig 2). Two accessory spleens within the splenic hilum also demonstrated heterogeneity, indicating multiple infarcts. The LDH level remained stable for 3 to 4 days and began to steadily decrease approximately 4 days after splenic embolization until it fell into the normal range. Although there was no evidence of further hemolysis, the hematocrit continued to decrease secondary to GI bleeding from an antral ulcer, which subsequently necessitated antrectomy. While in surgery, the patient also underwent a prophylactic splenectomy. There has been no recurrence of the AIHA.
[FIGURES 1-2 OMITTED]
DISCUSSION
The treatment of life-threatening AIHA must be based on the severity of the patient's presentation. In the setting of an altered mental status and rising lactate level, the patient must be managed very aggressively in order to optimize oxygen delivery and minimize V[O.sub.2]. For this reason, our patient was sedated, paralyzed, intubated, and cooled. With these initial interventions, the patient's lactate decreased significantly and rapidly, demonstrating almost immediate efficacy. Although controlled mechanical ventilation reduces V[O.sub.2], neuromuscular paralysis has been demonstrated to further reduce V[O.sub.2] and improve tissue oxygenation in patients with evidence of tissue hypoxia. (6) Furthermore, neuromuscular paralysis is required to facilitate induced hypothermia. Moderate hypothermia decreases V[O.sub.2] by decreasing the basal metabolic rate. In patients with acute ischemic stroke, Bardutzky and colleagues (7) demonstrated that the ratio of total energy expenditure to predicted basal energy expenditure declined from 1.01 before induction of hypothermia (to 33[degrees]C) to an average of 0.74 during steady state of hypothermia.
AIHA is commonly treated with transfusion, corticosteroids, and splenectomy. Management of AIHA in the setting of ulcerative colitis is generally the same as in other diseases with the exception of the role of colectomy. Colectomy results in a short-term remission in most patients; treatment that does not include colectomy results in a remission rate of approximately 50%. (3,4.8,9) However, as in our case, hemolysis can occur years after total colectomy, indicating that colectomy is not necessarily protective.
In our patient, transfusion with PRBCs was made difficult due to the presence of alloantibodies and autoantibodies, and was of only limited efficacy due to the ongoing hemolysis. The patient received high-dose methylprednisolone to blunt the ongoing immune response. (1,2) Although the onset of the response to corticosteroids is usually rapid and significant hematologic improvement can become evident within a few days, (5) a more aggressive course was desirable in our patient due to the life-threatening nature of the anemia.
Splenectomy is usually considered the second-line treatment in surgical candidates in whom glucocorticoid therapy is unsuccessful. (1,2,5) Removal of the spleen theoretically has a twofold effect. First, because IgG antibodies predominantly mediate AIHA, it removes the primary site of extravascular hemolysis. Less importantly, the spleen is a site of antibody production. Splenectomy in patients with AIHA and underlying systemic diseases has decreased efficacy and increased surgical morbidity compared to patients with idiopathic AIHA, with only 19% of patients having a complete response and 37% a partial response. This compares to an 82% complete response and 18% partial responses in patients with idiopathic AIHA. (10) Furthermore, patients with underlying disease have an increased incidence of postoperative complications mostly in the form of bacterial infections. (10) The most serious adverse effect of splenectomy is overwhelming postsplenectomy infection (OPSI). Although published estimates of the incidence of OPSI vary, (11-13) and most of the published data antedate the widespread availability of the pneumococcal and Haemophilus influenzae vaccines, OPSI remains an important consideration when contemplating splenectomy. Laproscopic splenectomy, though associated with decreased incidence of postoperative complications, (14) may not be a safe option in critically ill patients.
Surgical morbidity was expected to be high in our patient, preventing urgent splenectomy. An alternative approach to decrease the function of the spleen in a critically ill patient is splenic embolization. Partial splenic embolization has been shown to be a safe and effective alternative to splenectomy or partial splenectomy for alleviating hypersplenism in the treatment of hereditary spherocytosis, (15) and in children with thalassemia. (16.17) Partial splenic embolization has also been successfully used in an infant with autoimmune hemolytic anemia. (18) Described complications of splenic embolization include postembolization syndrome (ie, pain, fever, vomiting), spontaneous rupture, and splenic abscess. (19,20) In two studies (21,22) of patients undergoing postembolization CT scans to identify complications secondary to embolization, only 2 of 96 patients and 1 of 53 patients, respectively, were found to have a splenic abscess. Furthermore, while partial splenic embolization will decrease the hemolytic rate, it does not destroy the phagocytic function of the spleen, thereby avoiding the risk of OPSI. In our patient, the LDH level rapidly stabilized following splenic embolization, reflecting decreased hemolysis.
Other therapies available for the treatment of AIHA include immunosuppressive drugs such as cyclophosphamide and azathioprine, danazol, and high-dose IV [gamma]-globulin. (1,2,5,9) However, these therapies may require days to weeks to become effective. (1,5) Plasma exchange may be indicated for acute reversal of severe hemolysis while other therapies are taking effect. However, due to the continuous antibody production and large extravascular distribution of IgG, it is of limited efficacy. (23) In conclusion, this case report highlights the potential for induced hypothermia and splenic embolization as useful rescue therapy in the management of life-threatening AIHA, especially in the setting of secondary AIHA, and a safe alternative to splenectomy in an unstable patient.
* From the Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA.
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Manuscript received June 1, 2004; revision accepted August 16, 2004.
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions@chestnet.org).
Correspondence to: Paul Marik, MD, FCCP, Professor of Critical Care and Medicine, Department of Critical Care, University of Pittsburgh, 640A Scaife Hall, 3550 Terrace St, Pittsburgh, PA 15261; e-mail: maripe@ccm.upmc.edu
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