Rituximab can be combined with daily plasma exchange to achieve effective B-cell depletion and clinical improvement in acute autoimmune TTP.

Much of idiopathic thrombotic thrombocytopenic purpura (TTP) is attributed to the presence of an autoantibody to ADAMTS13, the metalloprotease that degrades ultralarge von Willebrand protein multimers. Most patients respond to treatment with therapeutic plasma exchange (TPE), which replaces the missing protease and removes the circulating inhibitor. However, a substantial fraction of idiopathic TTP cases (10%-20%) might not respond to TPE alone, and, therefore, interest has been gathering around the use of the novel immunosuppressive anti-B-cell antibody, rituximab. We report 2 cases of refractory TTP in which the combined use of plasma exchange and rituximab was associated with clinical resolution of active TTP, and we discuss the benefits and possible timing of combined therapy.

Acute hemolysis of transfused A2 red cells by an auto-HI antibody.

BACKGROUND: Anti-HI is a common cold autoantibody that complicates serologic testing for underlying alloantibodies and has only rarely been associated with hemolysis. An unusual case of an acute hemolytic transfusion reaction (AHTR) due to an anti-HI autoantibody in a subgroup A1 patient transfused with A2 red blood cells (RBCs) is reported. CASE REPORT: A 56-year-old man presented to the hospital with anemia and gastrointestinal tract bleeding. His medical history was significant for congestive heart failure, obesity, and pulmonary hypertension. On admission, he was noted to have a hemoglobin level of 7.7 g per dL and therefore transfusion of RBCs was ordered. The patient was group A, D- with a reactive antibody screen due to a cold autoantibody with HI specificity. Further serologic investigation did not detect any alloantibodies. The patient was issued an electronically cross-matched group A, D- unit of RBCs. Several hours after the transfusion, he was found to be producing "Coca-cola"-colored urine with gross hemoglobinemia visible in a posttransfusion specimen, indicating an AHTR. A transfusion reaction investigation excluded mistransfusion or a missed alloantibody and instead revealed that the patient's anti-HI had a high thermal amplitude and that the implicated unit of RBCs was from the A2 subgroup. The patient subsequently tolerated transfusion of a unit of group A1 RBCs through a blood warmer without any signs or symptoms of hemolysis. CONCLUSION: This case illustrates that anti-HI autoantibodies rarely may behave like alloantibodies and cause AHTRs. Subsequent RBC transfusion with an appropriate ABO group or subgroup through a blood warmer is well tolerated.

Current usage of intravenous immune globulin and the rationale behind it: the Massachusetts General Hospital data and a review of the literature.

BACKGROUND: Intravenous immune globulin (IVIG) has been approved by the Food and Drug Administration (FDA) for use in 6 conditions: immune thrombocytopenic purpura (ITP), primary immunodeficiency, secondary immunodeficiency, pediatric HIV infection, Kawasaki disease, prevention of graft versus host disease (GVHD) and infection in bone marrow transplant recipients. However, most usage is for off-label indications, and for some of these comprehensive guidelines have been published. STUDY DESIGN AND METHODS: We retrospectively reviewed all approved IVIG transfusions at Massachusetts General Hospital in 2004 to identify the current usage pattern and completed a literature review. RESULTS: IVIG was most commonly used in the treatment of chronic neuropathy, which included chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy. For such patients, the annual cost of IVIG can exceed 50,000 dollars per patient. Other common indications were the treatment of hypogammaglobulinemia, ITP, renal transplant rejection, myasthenia gravis, Guillain-Barre syndrome, necrotizing fasciitis, autoimmune hemolytic anemia, and Kawasaki disease. IVIG was administered in a variety of other indications each representing <3% of the total treated patients. CONCLUSION: Only a few indications account for most of the usage for IVIG. Reports concerning IVIG continue to grow at a tremendous pace but few high-quality randomized controlled trials have been reported. Randomized trials are especially needed for conditions such as CIDP, which consume large quantities of product.

Hyperhemolysis syndrome in anemia of chronic disease.

BACKGROUND: Occasional cases of delayed hemolytic transfusion reaction (DHTR) demonstrate severe and persistent hemolysis and are referred to as hyperhemolysis syndrome. This syndrome usually occurs in patients with sickle cell disease and possibly thalassemia who receive multiple transfusions. There are few such clinical reports in patients without hemoglobinopathies. CASE REPORT: A 67-year-old woman with anemia and a history of four previous transfusions was admitted with shortness of breath and a hematocrit (Hct) level of 27 percent. The patient was group O with a negative antibody screen. She received 1 unit of electronically cross-matched red blood cells (RBCs) and was discharged. Thirteen days later she returned to hospital with weakness and a Hct level of 23 percent. The antibody screen now demonstrated anti-K alloantibody. The direct antigloblulin test (DAT) was positive with both anti-immunoglobulin G and anti-complement (C3). Anti-K was recovered in the eluate. The previously transfused RBC unit was positive for presence of the K antigen. The patient's RBCs were negative for the presence of K antigen. Other laboratory data confirmed ongoing hemolysis, and a diagnosis of DHTR was made. She continued to display findings of active hemolysis for 9 more weeks requiring 19 units of RBCs. Thirty-four days after the original transfusion, her DAT remained positive and both the plasma sample and a RBC eluate demonstrated anti-K. CONCLUSION: The delayed hemolytic transfusion reaction with hyperhemolysis can occur among patients without hemoglobinopathies.

Nephrolithiasis as primary symptom in sarcoidosis.

A 30-year-old black woman presented with a 1-year history of repeated episodes of worsening weight loss and fatigue. Physical examination showed no skin lesions and a chest roentgenogram was normal. Workup showed no obvious cause of recurrent renal stones. Finally, the detection of lymphadenopathy led to the diagnosis of extrapulmonary sarcoidosis. Up to 4% of all cases of sarcoidosis may present with urolithiasis only. Renal stones may be more common in severe cases of sarcoidosis, which affect blacks most frequently. Although not generally recommended for diagnostic purposes in sarcoidosis, in this case determination of the angiotensin-converting enzyme level was helpful in making the correct diagnosis. It is important that physicians are aware of the possibility that sarcoidosis may present as urolithiasis, even in the presence of a negative chest roentgenogram.