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Biomedical subjects

Douglas P Blackall

Publications and source records attributed to Douglas P Blackall.

13 recordsLinked to original sources
PubMed2006

Severe neonatal hemolysis due to a maternal antibody to the low-frequency Rh antigen C(w).

C(w) is a low-frequency antigen in the Rh blood group system with a prevalence of approximately 2% in whites. Although anti-C(w) is not an uncommon antibody in pregnancy (0.1% incidence), clinically significant hemolytic disease of the newborn is highly unusual. We report the case of an infant with severe hyperbilirubinemia and persistent anemia due to a high-titer maternal C(w) antibody. The medical literature relating to maternal C(w) alloimmunization and neonatal outcome is also reviewed. In addition, recommendations are made regarding the management of pregnancies and newborns complicated by antibodies to C(w).

Adult↗
PubMed2005

Transfusion-associated graft-versus-host disease: a serious residual risk of blood transfusion.

Transfusion-associated graft-versus-host disease (TA-GVHD) is well recognized as an uncommon, but frequently fatal, adverse effect of blood component therapy. In this disorder, viable donor lymphocytes transfused to a vulnerable patient orchestrate a devastating attack on the recipient's tissues. In contrast to the striking reduction in infectious risks of blood transfusion, a significant residual risk of TA-GVHD remains. This article reviews the pathogenesis and mechanism of TA-GVHD, which provide the foundation for a prevention strategy. A review of selected recent cases illustrates the challenges faced in the identification, prevention, and treatment of this frustrating disorder.

Female↗
PubMed2004

Clinical significance of anti-Jra: report of two cases and review of the literature.

BACKGROUND: Jra is a high-frequency antigen seen in all populations, but the clinical significance of Jra antibodies is incompletely understood. Two cases are reported in which patients with anti-Jra received incompatible transfusions. CASE REPORTS: A 69-year-old Japanese man had anti-K and anti-Jra. Despite multiple transfusions of Jr(a+), K- RBCs, his clinical course remained stable without evidence of hemolysis. A 45-year-old Japanese woman with anti-Jra was transfused with two units of Jr(a+) RBCs without clinical evidence of hemolysis. However, the same patient received an additional unit of Jr(a+) RBCs 1 week after the initial transfusions and, within 6 hours of transfusion, developed signs and symptoms of an acute hemolytic transfusion reaction. STUDY DESIGN AND METHODS: Routine serologic methods were used to study the patients' RBCs and plasma. A monocyte monolayer assay (MMA) was used to determine the potential clinical significance of the anti-Jra, where reactivity (R) greater than 5 percent indicates potential clinical significance. RESULTS: The anti-Jra in the first case had a pretransfusion titer of 32 with a MMA result of 3.3 percent R. No clinical or laboratory evidence of hemolysis was seen after transfusion of 4 units of Jr(a+), K- RBCs. The anti-Jra in the second case had a pretransfusion titer of 32 with a MMA result of 24.5 percent R. This patient developed an acute hemolytic reaction after transfusion of Jr(a+) RBCs. CONCLUSION: Anti-Jra can be clinically significant as demonstrated by acute hemolysis in the second case. The MMA accurately predicted the clinical outcome of each case and appears to be a useful tool in predicting the biologic behavior of anti-Jra.

Acute Disease↗
PubMed2004

Hemolytic uremic syndrome revisited: Shiga toxin, factor H, and fibrin generation.

The hemolytic uremic syndrome (HUS) is a disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. These features reflect the underlying histopathologic lesion: fibrin-rich thrombi that predominate in the renal microvasculature. HUS most commonly affects children younger than 5 years and is associated with Shiga toxin-producing enteric bacteria, the most important of which is Escherichia coli O157:H7. In this setting, HUS is epidemic and also might affect adults, particularly elderly people. Sporadic cases of HUS more commonly occur in adults and are associated with a wide variety of inciting agents and conditions. Although the disease manifestations might be similar and endothelial activation or injury likely represents a common etiologic event, differing responses to therapy suggest different pathogenic mechanisms. As more is understood about the underlying pathogenesis of the diseases that we now lump together as HUS, more efficacious and rational treatment and prevention strategies are likely to follow.

Complement Factor H↗
PubMed2004

Warm reactive autoantibodies: clinical and serologic correlations.

Warm reactive autoantibodies are encountered relatively frequently in tertiary care hospitals. We studied 100 consecutive patients with warm autoantibodies to correlate their clinical and serologic features. Study patients (56 male, 44 female) had various diagnoses and a mean age of 53.5 years (range, 3-90 years). Autoimmune hemolysis was documented in 29 patients; 20 patients (69%) in this subset had diseases classically associated with warm autoimmune hemolytic anemia (hematologic and autoimmune disorders). All study patients demonstrated IgG on their RBCs (direct antiglobulin test [DAT] reactivity range, microscopic to 4+); 49 also demonstrated C3 (reactivity range, microscopic to 3+). The DAT for IgG was 2+ or more in 25 (86%) of 29 patients with hemolysis; the DAT for IgG was 1+ or less in 45 (63%) of 71 patients without hemolysis. In patients with hemolysis, 21 (72%) of 29 had a DAT reactive for C3. These findings may be useful in determining the clinical significance of warm autoantibodies and the extent to which patients should be followed up for hemolysis.

Adolescent↗
PubMed2004

Thrombotic thrombocytopenic purpura: from platelet aggregates to plasma.

Thrombotic thrombocytopenic purpura (TTP) is a syndrome of severe thrombocytopenia and microangiopathic hemolytic anemia without an alternative explanation. Although some patients also have a combination of fever and neurologic and/or renal manifestations, these are not required for the diagnosis. Thus, plasmapheresis should start as soon as TTP is placed high in the differential diagnosis to prevent significant mortality. Histopathologically, TTP is characterized by widespread platelet thrombi in the microcirculation. Ultralarge von Willebrand factor (vWf) multimers found in the patient's plasma are the basis for the platelet thrombi. Recent evidence has linked the abnormal fragments of vWf with deficiency of a plasma enzyme named vWf-cleaving protease, or ADAMTS-13. While a small percentage of patients with TTP have a constitutional defect in this enzyme, many with the acute idiopathic form have an antibody to ADAMTS-13, affecting its ability to cleave vWf. The determination of the enzyme activity and the presence of its inhibitor have emerged as a potential tool in the diagnosis and prognosis of TTP. Furthermore, it helps to differentiate TTP from the hemolytic uremic syndrome, in which the level of ADAMTS-13 is expected to be normal or only slightly decreased.

ADAM Proteins↗
PubMed2003

Amelioration of graft versus host disease by galectin-1.

Graft versus host disease is a significant cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Galectin-1, a mammalian lectin that modulates T cell function and apoptosis, has been shown to be immunomodulatory in animal models of autoimmune disease. We investigated the efficacy of galectin-1 in a murine model of graft versus host disease and found that 68% of galectin-1-treated mice survived, compared to 3% of vehicle-treated mice. Galectin-1-treated animals also had reduced inflammatory infiltrates in tissues compared to animals treated with vehicle alone. Galectin-1 did not affect engraftment of donor hematopoietic cells. However, galectin-1-treated animals demonstrated increased cellularity in bone marrow and spleen with increased numbers of splenic B cells and CD4 T cells compared to those animals treated with vehicle alone. Galectin-1 treatment also significantly improved reconstitution of normal splenic architecture following transplant. Production of type I cytokines interleukin-2 (IL-2) and interferon-gamma was reduced in splenocytes derived from galectin-1-treated transplanted mice when compared to animals treated with vehicle alone, while production of the type II cytokines, IL-4 and IL-10, was similar between the two groups of animals. Although splenocytes from galectin-1-treated transplanted animals responded to both third party antigens and leukemic challenge, host alloreactivity was significantly reduced when compared to cells from vehicle-treated animals. These results demonstrate that galectin-1 therapy is capable of increasing survival and suppressing the graft versus host immune response without compromising engraftment or immune reconstitution following allogeneic hematopoietic stem cell transplant.

Adjuvants, Immunologic↗
PubMed2002

In utero development of a warm-reactive autoantibody in a severely jaundiced neonate.

BACKGROUND: The fetus and neonate are widely considered to be immunologically immature. However, there are rare case reports of RBC alloantibody and autoantibody development. STUDY DESIGN AND METHODS: This report describes the case of a severely jaundiced full-term boy neonate presenting at birth with an IgG warm-reactive autoantibody. RESULTS: Mother and neonate were both blood group A, D+. The mother had a negative antibody screen at 18 weeks' gestation and a negative DAT and antibody screen at the time of delivery. The neonate was born with a strongly reactive DAT (IgG) and a panreactive eluate. The serum also contained a panreactive antibody, and all crossmatches were incompatible. The neonate had a bilirubin of 12.5 mg per dL at birth, which peaked at 22.5 mg per dL. However, there was no overt evidence of hemolysis, as evidenced by normal serial Hct levels and reticulocyte counts. The neonate responded well to phototherapy and did not require either simple or exchange transfusion. The neonate's warm-reactive autoantibody maintained its original strength of reactivity on follow-up testing performed at 2 weeks and 2 months of age. CONCLUSIONS: This report describes a rare case of apparent in utero RBC autoantibody development. The fetal/neonatal immune response to blood group antigens is reviewed.

Autoantibodies↗