Predicting risk of peripartum blood transfusion during vaginal and cesarean delivery: A risk prediction model.

OBJECTIVE: The objective of this study is to develop a model that will help predict the risk of blood transfusion using information available prior to delivery. STUDY DESIGN: The study is a secondary analysis of the Consortium on Safe Labor registry. Women who had a delivery from 2002 to 2008 were included. Pre-delivery variables that had significant associations with transfusion were included in a multivariable logistic regression model predicting transfusion. The prediction model was internally validated using randomly selected samples from the same population of women. RESULTS: Of 156,572 deliveries, 5,463 deliveries (3.5%) required transfusion. Women who had deliveries requiring transfusion were more likely to have a number of comorbidities such as preeclampsia (6.3% versus 4.1%, OR 1.21, 95% CI 1.08-1.36), placenta previa (1.8% versus 0.4%, OR 4.11, 95% CI 3.25-5.21) and anemia (10.6% versus 5.4%, OR 1.30, 95% CI 1.21-1.41). Transfusion was least likely to occur in university teaching hospitals compared to community hospitals. The c statistic was 0.71 (95% CI 0.70-0.72) in the derivation sample. The most salient predictors of transfusion included type of hospital, placenta previa, multiple gestations, diabetes mellitus, anemia, asthma, previous births, preeclampsia, type of insurance, age, gestational age, and vertex presentation. The model was well-calibrated and showed strong internal validation. CONCLUSION: The model identified independent risk factors that can help predict the risk of transfusion prior to delivery. If externally validated in another dataset, this model can assist health care professionals counsel patients and prepare facilities/resources to reduce maternal morbidity.

Unusual serological findings associated with ceftriaxone-induced immune hemolytic anemia in a child with disseminated low-grade glioma.

Ceftriaxone-induced immune hemolytic anemia (CIHA) is the second most common cause of drug-induced hemolytic anemia. Prompt recognition of this drug reaction is essential because brisk hemolysis can be deadly. The extent to which ceftriaxone antibodies persist after CIHA is unknown; rechallenging patients who have experienced CIHA is not recommended. We report a case of CIHA in a neurooncology patient, which is the first to show anticeftriaxone antibodies with Rh specificity and persisted for 8 months after the drug reaction. These findings have implications for understanding the mechanism of CIHA.

An unusual presentation of perinatally transmitted hepatitis C.

A unique presentation of perinatally acquired hepatitis C (HCV) with acute jaundice and chronic aggressive liver disease in a previously asymptomatic preadolescent is described. The difficulties in establishing the diagnosis and the importance of confirmatory testing for HCV in cryptogenic liver disease are discussed.

Prevention of transfusion-associated graft-versus-host disease by inactivation of T cells in platelet components.

Patients with hematological malignancies and infants with congenital immunodeficiencies who received blood are two of many populations at risk for transfusion-associated graft-versus-host disease (TA-GVHD). Of the methodologies (eg, photoinactivation, peglyation, ultraviolet light, and irradiation) that can be used to prevent TA-GVHD, only irradiation of whole blood and cellular components is currently accepted practice of the US Food and Drug Administration (FDA). Among the newer methods that have been developed to reduce the risks of bacterial and viral contaminants of platelet transfusions, photochemical treatment (PCT) using psoralens and long-wavelength ultraviolet (UVA) irradiation modifies bacterial and viral genomes sufficiently to inhibit replication. Among a broad group of compounds, the synthetic psoralen compound amotosalen hydrochloride (HCl) (S-59) has been shown to be particularly effective in inactivating bacteria and viruses, without adversely affecting in vitro and in vivo platelet function.

Prospective RBC phenotype matching in a stroke-prevention trial in sickle cell anemia: a multicenter transfusion trial.

BACKGROUND: Most sickle cell anemia patients undergo transfusion therapy to prevent complications. The Stroke Prevention Trial in Sickle Cell Anemia showed that transfusion therapy is effective in the primary prevention of stroke. Despite its efficacy, transfusion therapy is limited by alloimmunization. The purpose of this study was to determine if a multicenter trial could implement a transfusion program utilizing phenotypically matched blood to reduce alloimmunization. STUDY DESIGN AND METHODS: One hundred thirty children underwent RBC phenotyping and antibody screening with review of blood bank records. The protocol required use of WBC-reduced RBCs, which were matched for E, C, and Kell. Monthly alloantibody testing and review of transfusion forms were performed to determine compliance and the occurrence of any adverse events. RESULTS: Patient RBCs expressed a low frequency of Kell (2%), E (20%), and C (25%) antigens. Sixty-one patients received 1830 units. Ninety-seven percent of all units were WBC reduced. Only 29 units were inadvertently not matched for E, C, and Kell. Five patients (8%) developed a clinically significant alloantibody. Four developed a single antibody to E or Kell. Three patients (5%) developed a warm autoantibody. There were 11 transfusion reactions and 8 transfusion-associated events. Transfusion reactions included 6 febrile reactions (0.33%/unit), 3 allergic (0.16%/unit), and 2 hemolytic (0.11%/unit). Associated events included 4 episodes of hypertension (0.22%/unit), 3 crises (0.16%/unit), and 1 transient ischemic attack (0.05%/unit). CONCLUSION: This is the first multicenter study to show that extended RBC phenotyping can be implemented nationwide. Compared to studies, the alloimmunization rate dropped from 3 percent to 0.5 percent per unit, and hemolytic transfusion reactions dropped by 90 percent. It is recommended that all transfused sickle cell anemia patients be antigen matched for E, C, and Kell. Patients should be closely monitored during transfusions to avoid preventable risks.

Low factor VIII recovery in haemophilia A patients without inhibitor titre is not due to the presence of anti-factor VIII antibodies undetectable by the Bethesda assay.

Measurements of factor VIII (FVIII) recovery in previously untreated patients with haemophilia A were done as part of the clinical trial of safety and efficacy of the recombinant FVIII, Recombinate. In 22 of 72 assessable patients, positive inhibitor titres > or = 0.6 Bethesda units mL-1 were detected by the Bethesda assay in one or more plasma samples, and the remaining 50 patients were negative at all timepoints. Of the latter group, 16 individuals without inhibitors unexpectedly had both normal (111) and low (52) recoveries during the study. We investigated the possibility that other antibodies not detectable in the Bethesda assay were responsible for the low recovery, by using a highly sensitive immunopreciptation (IP) assay for detection of all antiFVIII antibodies. Eight of the 16 patients with low and normal recoveries did indeed have antibodies detected by the IP assay, and the remaining eight were negative. Four antibody-positive individuals had insignificantly low titres, and the other four had modest to high titres. In the latter group, antibodies were found with similar frequencies and titre in plasmas from patients with low or normal recovery. Low recovery in haemophilia A patients without inhibitor titres must therefore be attributed to factors other than antiFVIII.

Clinical heterogeneity in mitochondrial DNA deletion disorders: a diagnostic challenge of Pearson syndrome.

The clinical presentation of mitochondrial DNA (mtDNA) disorders is quite diverse. Very often, the initial symptoms do not fit a specific disease, and diagnosis is difficult to make. We describe a patient who presented with macrocytic anemia. Extensive biochemical and clinical work-up failed to provide an etiology for the macrocytic anemia. The patient over the course of 6 years developed gait problems, exercise intolerance, episodic vomiting, short stature, dermatological problems, and recurrent infection. At age 8 years she had encephalopathy with ataxia and dysphagia. The presence of elevated lactate, bilateral basal ganglia calcification, and ragged red fibers led to mtDNA mutational analysis. A novel 4.4-kb deletion from nucleotide position 10,560 to nucleotide position 14, 980 was identified in muscle biopsy. The same heteroplasmic mtDNA deletion was present in blood, buccal cells, and hair follicles, but not in mother's blood, consistent with sporadic mutation in the patient. This case emphasizes the importance of considering mtDNA disorder in patients with multisystemic symptoms that cannot be explained by a specific diagnosis.

Influence of human immunodeficiency virus-infected maternal environment on development of infant interleukin-12 production.

Monocyte-derived cytokine production by cord blood mononuclear cells (CBMC) from infants born to human immunodeficiency virus (HIV)-positive and -negative women was measured to determine whether monocyte dysfunction could contribute to the accelerated HIV disease of pediatric patients. Production of interleukin (IL)-12, but not that of tumor necrosis factor-alpha and IL-10, was reduced, compared with adult peripheral blood mononuclear cells (PBMC). This deficiency was more pronounced in infants of HIV-positive women, whose IL-12 production was also deficient. CBMC IL-12 levels were increased by interferon-gamma and CD40 ligand but remained deficient, compared with PBMC. IL-12 production was undetectable in 7 of 8 HIV-positive infants, in contrast to 21 of 26 uninfected infants. Uninfected infants of infected women exhibited an intermediate profile. These findings suggest that the maternal environment and/or exposure in utero to HIV products influence the newborn's immune response and that the differences between infants born to HIV-positive and -negative women may persist.

Retention of coagulation factors in plasma frozen after extended holding at 1-6 degrees C.

BACKGROUND AND OBJECTIVES: The ability to use plasma, isolated from units of whole blood and frozen within 24 h of phlebotomy, as a substitute for plasma frozen within 8 h of phlebotomy would have several advantages for blood centers. It should provide increased flexibility pertaining to the freezing of plasma for clinical use. We have conducted studies to assess the influence of an extended holding time for separated plasma, prior to freezing, on the retention of coagulation factor activity. STUDY DESIGN AND METHODS: Freshly harvested plasma from each of 10 units of CPD-whole blood was divided into four equal aliquots. These aliquots were held in plastic packs at 1-6 degrees C for a total of 0, 8, 15 and 24 h. Subsequently, the plasma aliquots were frozen rapidly and stored at -20 degrees C for 4 months. The thawed plasma was tested for coagulant factors V and IX, factor VIII coagulant activity (factor VIII:C), von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor of von Willebrand factor. RESULTS: The levels of factor V, factor vWF:Ag, factor IX and ristocetin cofactor were not influenced by holding the plasma for up to 24 h prior to freezing. Factor VIII:C activity was reduced with extended holding at 1-6 degrees C; the percentage at time zero activity was 75.9+/-2.4% for samples frozen immediately after a 24-hour period. CONCLUSIONS: The data indicate that coagulation factor properties of harvested plasma are retained except for factor VIII for at least 24 h prior to freezing.

Irradiation of platelet components: inhibition of lymphocyte proliferation assessed by limiting-dilution analysis.

BACKGROUND: Using a limiting-dilution analysis (LDA) assay that measures clonigenic T cells, it has been demonstrated that, with 2500 cGy, there is no T-cell growth in red cell components irradiated in blood bags. In the current study, the LDA assay was used to investigate the effect of gamma radiation on the proliferative capacity of T cells in plateletpheresis components. STUDY DESIGN AND METHODS: Platelets were collected by using an apheresis instrument and settings that provided sufficient mononuclear cells for the LDA assay. Platelet components (n = 8) were irradiated in 1-L plastic bags 24 hours after collection with 500, 1500, and 2500 cGy of gamma radiation in a stepwise manner. Mononuclear cells were isolated after each irradiation dose by the use of ficoll-hypaque. A density separation medium was used to reduce the platelet numbers. T cells were enumerated by fluorescence-activated cell sorter and functionally assessed by LDA assay, which quantified T cells proliferating in the presence of polyclonal stimuli and cytokines. The frequency of T-cell growth (f) was visually scored after 4 weeks of incubation at 37 degrees C. Data were calculated as f(experimental)/f(control) and expressed as log(10) reduction. RESULTS: The T-cell content of the mononuclear cell population was 17 +/- 10.5 percent, which was unaltered by irradiation. After 500-cGy irradiation, functional T cells were reduced by 2.09 log(10). Irradiation with 1500 cGy resulted in a 3. 96 log(10) reduction, but viable clonable T cells were detected in all experiments. With 2500-cGy irradiation, no T-cell growth was detected; this represented a greater than 4.86 log(10) reduction. CONCLUSION: As the dose of gamma radiation delivered to plateletpheresis components increased, the number of residual functional T cells decreased exponentially. Irradiation with 2500 cGy inactivates T cells in apheresis platelets, as measured by an LDA assay.