Transfusion-associated graft-vs-host disease. A fatal case caused by blood from an unrelated HLA homozygous donor.

Transfusion-associated graft-vs-host disease (TA-GVHD) is a rare complication of transfusion. We report fatal TA-GVHD in a 63-year-old coronary artery bypass patient of European descent after an RBC transfusion from an unrelated donor. The patient had mild lymphocytopenia and received 2 80-mg doses of methylprednisolone and 7 units of RBCs. On day 14 after the transfusion, he had fever, elevated liver enzyme levels, and a macular rash. Pancytopenia and bone marrow aplasia developed. On day 26, he had a massive gastrointestinal hemorrhage and died. At autopsy, histopathologic findings of the skin, liver, bone marrow, and gastrointestinal tract were consistent with TA-GVHD. One donor of the transfused RBCs (3 days old at transfusion) had a 1-way HLA match with the patient. A method using multiplex polymerase chain reaction is presented. This patient with TA-GVHD and mild immune suppression suggests that blood component irradiation guidelines may need to be reevaluated.

Pulmonary alveolar proteinosis. A report of two cases with diagnostic features in bronchoalveolar lavage specimens.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare condition that has been associated with myriad diseases and disorders. Alveolar spaces are progressively filled with a phospholipoproteinaceous material, presumably related to a derangement of surfactant production and/or catabolism. The cytologic features of PAP in bronchoalveolar lavage (BAL) sediments are unique, and recognition of these characteristics can help guide clinical intervention. CASES: A 47-year-old male with a history of progressive dyspnea and recent pneumonia presented with a five-lobe alveolar infiltrate and subsequently underwent bronchoscopic examination. A 31-year-old female with chronic myelogenous leukemia in blast transformation developed unresponsive pulmonary infiltrates necessitating bronchoscopy with lavage. Both BAL lavage fluid sediments contained a homogeneous, basophilic, granular material typical of PAP. The material was composed of extracellular, multilamellated bodies when viewed by electron microscopy. Both patients required repeated therapeutic whole lung lavage, and one died of the disease eight months after the diagnosis. CONCLUSION: Clinical presentation, grossly milky BAL fluid and fluid sediment with light microscopic findings of basophilic, periodic acid-Schiff-positive, granular debris with cholesterol crystals and a few alveolar macrophages suggest this process. The light microscopic findings can be confirmed by ultramicroscopic demonstration of extracellular multilamellated bodies. BAL with appropriate examination of the effluent sediment facilitates the diagnosis of PAP.

Common variable immunodeficiency: diagnosis by absent ABO reverse type.

Many causes for ABO discrepancy between red blood cell and serum testing have been cited in the literature. ABO discrepancy due to weak or absent reverse type is most often seen at the extremes of age. We report a case of ABO discrepancy in a 25-year-old woman who presented for wisdom teeth extraction. Initial serologic workup revealed total absence of isohemagglutinin anti-B in this group A, D+ individual. Further evaluation revealed decreased levels of all classes of immunoglobulins and a medical history significant for multiple episodes of infection. Based on the patient's history and laboratory data, she was diagnosed with common variable immunodeficiency (CVID). CVID can cause ABO discrepancy in an adult patient because of an absent ABO reverse type.

The mechanism of platelet aggregation induced by HLA-related antibodies.

Immune-mediated platelet activation is emerging as an important pathogenic mechanism of thrombosis. In vitro studies have suggested two distinct pathways for immune-mediated platelet activation; one involving clustering of platelet Fc gamma RIIa, the other involving platelet-associated complement activation. HLA-related antibodies have been shown to cause platelet aggregation, but the mechanism has not been clarified. We evaluated the mechanism of platelet aggregation induced by HLA-related antibodies from nine patients. Antibody to platelet Fc gamma RIIa failed to block platelet aggregation with 8/9 samples, indicating that engagement of platelet Fc gamma RIIa is not necessary for the platelet aggregation induced by HLA-related antibodies. In contrast, platelet aggregation was blocked by antibodies to human C8 (5/7) or C9 (7/7). F(ab')2 fragments of patient IgG failed to induce platelet activation although they bound to HLA antigen on platelets. Intact patient IgG failed to aggregate washed platelets unless aged serum was added. The activating IgG could be adsorbed by incubation with lymphocytes and eluted from the lymphocytes. These results indicate that complement activation is involved in the aggregation response to HLA-related antibodies. This is the first demonstration of complement-mediated platelet aggregation by clinical samples. Five of the patients developed thrombocytopenia in relationship to blood transfusion and two patients developed acute thromboembolic disease, suggesting that these antibodies and the complement-dependent pathway of platelet aggregation may be of clinical significance.

Patterns of autologous blood use in elective orthopedic surgery: does the availability of autologous blood change transfusion behavior?

We studied the orthopedic surgery service at our institution to determine whether the mere availability of autologous blood (AB) affected transfusion practice. As a group, patients who had AB available received an average of 1.11 fewer red cell units per hospitalization than did patients with only homologous blood (HB) available. At every transfusion episode, those patients having AB available received fewer red cell units than did patients without AB available. Predeposit of autologous red cells was effective in protecting 77.6% of patients from HB exposure. The availability of autologous red cells resulted in an overall more conservative approach to transfusion.

HELLP syndrome: laboratory parameters and clinical course in four patients treated with plasma exchange.

We report our apheresis department's experience with four patients with HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. The average age of the patients was 23.25 years (range 19-27). Three were in their second pregnancy while one was a primigravida. All had symptoms of pre-eclampsia prior to delivery. All experienced the syndrome postpartum. Plasma exchange was instituted an average of 3.25 days postpartum (range 1.08-7.33 days). All underwent plasmapheresis with fresh frozen plasma replacement. The average number of plasma exchange treatments was four (range 1-8). The first laboratory parameter to reach its peak/nadir was the aspartate aminotransferase (AST), followed by the lactate dehydrogenase (LDH) enzyme level, followed by the hemoglobin (HGB) level, and, finally, the platelet count (PLT). The AST was the first parameter to peak and the first to normalize. In the three cases in which more than one plasmapheresis procedure was performed, plasmapheresis was required for an average of 98 hours (range 39-206 hours) after a normal AST level was obtained in order to achieve a self-sustaining platelet count of > or = 100 x 10(9)/L. No additional exchanges were required to maintain the PLT once a PLT of over 100 x 10(9)/L was attained. The laboratory values normalized in the following order: AST, HGB, PLT, and LDH. Three patients were discharged anemic. One was discharged with a normal LDH level. By our experience, awaiting normal LDH levels as an indicator for cessation of plasma exchange therapy would mean subjecting the patients to many unnecessary procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of demographics and motivations of highly committed whole blood and platelet donors.

To compare donor demographics and motivations for donation, we surveyed 159 consecutive whole blood donors (WD) and 146 consecutive plateletpheresis donors. All donors had donation experiences of at least 2 gallons (i.e., 16 previous donations). Evaluation of answers to fixed-response and open-ended questions revealed no difference between the two groups in age, type of wages, compensation by employer, "time off" for donation, and church or volunteer organization memberships. The two groups differed in that the platelet donor (PD) group had a higher percentage of males than females (PD group 72.6% males and 27.4% females versus WD group 59% males and 41% females [chi-square = .01]). PDs most often began donating platelets because they were asked (22.6%), demonstrating the importance of active recruitment. When asked why they do not donate platelet products by apheresis, highly committed WDs reported lack of time (25%), lack of knowledge ("Don't know about it," 21%), lack of recruitment ("No one asked," 18.5%), or lack of awareness ("Never though about it," 5%) as reasons. Factors centering on time constraints, lack of knowledge or awareness about platelet donation by apheresis, and lack of active recruitment prohibit highly committed WDs from entering into plateletpheresis programs.

Lymphoproliferative disorders associated with carbamazepine.

Carbamazepine-induced lymphoproliferative disorders are relatively rare. A 32-year-old woman developed cervical lymphadenopathy while taking carbamazepine. Histologic evaluation of the lymph node biopsy specimen demonstrated near-total effacement of the nodal architecture by a population of pleomorphic immunoblasts. The predominant cell population expressed CD3, CD2, CD5, and CD4, while results of testing for CD8 were negative. On the basis of the morphologic and immunohistologic features, a diagnosis of high-grade, non-Hodgkin's lymphoma, T-cell immunoblastic type, was made. Despite the fact that aggressive behavior is usually associated with immunoblastic lymphomas, the patient has done well for 33 months after cessation of carbamazepine in the absence of chemotherapeutic treatment. The clinical features of this patient's illness, therefore, suggest that it is best regarded as a so-called pseudolymphoma.

The safety of intraosseous infusions: risks of fat and bone marrow emboli to the lungs.

The technique of intraosseous infusion is a life-saving emergency alternative when IV access is impossible or will be critically delayed. Concerns about its safety remain, especially concerning the risk of bone marrow and fat emboli to the lungs. We examined autopsy pulmonary specimens on two children who had received intraosseous infusions during resuscitation attempts and found an average of 0.23 to 0.71 bone marrow and fat emboli per mm2 of lung. We studied normotensive dogs with intraosseous infusions of emergency drugs and solutions into the distal femur. Three dogs were studied with each of the following emergency drugs or solutions: controls with normal saline (0.9% NaCl), epinephrine 0.01 mg/kg, NaHCO3 1 mEq/kg, CaCl 10 mg/kg, atropine 0.01 mg/kg, hydroxyethyl starch 6% in normal saline 10 mL/kg, 50% dextrose in water 0.25 g/kg, and lidocaine 1 mg/kg. Four hours after infusion, the animals were killed, and representative sections of the lung were examined with oil red-0 and hematoxylin and eosin stains for the presence of fat and bone marrow emboli. Fat and bone marrow emboli were found in all lung sections, varying from 0.11 to 4.48 emboli/mm2 lung (mean, 0.91 emboli/mm2 lung) for the emergency drugs and solutions and 0.06 to 0.53 emboli/mm2 (mean, 0.29 emboli/mm2 lung) for the controls. Analysis of variance revealed no significant difference (P = .07) in mean number of fat and bone marrow emboli per square millimeter of lung among the emergency drugs and compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)