Recognition, Investigation and Management of Acute Transfusion Reactions: Consensus guidelines for Oman.

The recognition and management of transfusion reactions (TRs) are critical to ensure patient safety during and after a blood transfusion. Transfusion reactions are classified into acute transfusion reactions (ATRs) or delayed transfusion reactions, and each category includes different subtypes. Different ATRs share common signs and symptoms which can make categorisation difficult at the beginning of the reaction. Moreover, TRs are often under-recognised and under-reported. To ensure uniform practice and safety, it is necessary to implement a national haemovigilance system and a set of national guidelines establishing policies for blood transfusion and for the detection and management of TRs. In Oman, there are currently no local TR guidelines to guide physicians and hospital blood banks. This paper summarises the available literature and provides consensus guidelines to be used in the recognition, management and reporting of ATRs.

Microdeletion of exon 3 in the HBA2 gene associated with mild α-thalassemia trait.

A mother and son presented with mild symptoms of thalassemia trait. Polymerase chain reaction (PCR) amplification of their globin genes revealed a previously unreported 203 bp microdeletion in the HBA2 gene (NG_000006.1:g.34305_34507del; HBA2:c301-30_*44del). Both mother and son were heterozygous for the deletion which included DNA coding for all of exon 3. DNA sequence analysis revealed a six nucleotide repeat (5'-CGGGCC-3') flanking the breakpoint, suggesting that the microdeletion may have arisen as a result of reciprocal recombination within the HBA2 alleles.

In Utero diagnosis and management of a fetus with homozygous α-Thalassemia in the second trimester: a case report and literature review.

Alpha thalassemia with the absence of 4 α-globin genes leads to fetal hydrops and fetal death from anemia. Historically considered a lethal condition, optimal in utero management of homozygous α-thalassemia is unclear. A fetus of Filipino descent at 26 weeks gestation presented with ultrasound evidence of anemia. Cordocentesis confirmed anemia and homozygous α-thalassemia (--/--). Intrauterine transfusion corrected anemia but fetal growth restriction and oligohydramnios persisted. Intrauterine exchange transfusion improved hemoglobin parameters, fetal growth, and oligohydramnios. The late preterm infant was delivered with classic limb reduction defects. Hemoglobin Bart's is nonfunctional for oxygen transport, and intrauterine exchange transfusion may be effective first-line therapy and further investigation is warranted.

Two new examples of Hb St. Etienne [beta 92(F8)HisGln] in association with venous thrombosis.

Hb St. Etienne [beta92(F8)HisGln] (also known as Hb Istanbul) is a rare unstable beta-globin chain variant that has been described in only three reports involving four patients. We report two individuals in a family of Scottish extraction whose members had been erroneously diagnosed to have hereditary spherocytosis (HS) and have now been shown to be heterozygotes for Hb St. Etienne. They also had venous thrombotic events with minimal provocation. This family illustrates the difficulties in identifying the cause of chronic hemolytic anemia and highlights the possible contribution of chronic hemolysis to increased risk of thrombosis.

Combined neutrophil and erythrocyte agglutination in a 7-year-old boy.

Leukoagglutination is a rare in vitro phenomenon, with demonstration of both temperature and/or ethylenediaminetetraacetic acid dependence. We report a case of combined leukocyte and erythrocyte agglutination in a 7-year-old male with Mycoplasma pneumoniae and Epstein-Barr virus coinfection. To our knowledge, this morphologic finding has not previously been described.

Recognition and management of methemoglobinemia and hemolysis in a G6PD-deficient patient on experimental anticancer drug Triapine.

We report occurrence of severe methemoglobinemia in a patient on novel experimental anti-cancer drug, Triapine. Treatment with methylene blue led to massive hemolysis due to concomitant G6PD deficiency. We recommend that G6PD screening be done in high-risk populations prior to commencement of Triapine therapy.

Severe FVII deficiency caused by a new point mutation combined with a previously undetected gene deletion.

A 3-week-old Caucasian female presented with severe unprovoked parenchymal cerebral haemorrhage. Her plasma factor VII (FVII) activity was <0.01 units/ml. FVII activities for her mother and sister were 0.65 units/ml and 0.51 units/ml, respectively, while her father's level was normal. These results indicated that the mother was heterozygous for a non-functional F7 gene that had also been inherited by the proband's sister. The proband's severe FVII deficiency was caused by a new mutation in her paternal F7 gene coupled with the inheritance of the non-functional maternal F7 gene. DNA sequence analysis revealed that the proband had apparent homozygosity for a novel single point mutation (g.3907G >A) changing the codon for Glu29 to Lys (E29K); neither parent had the E29K mutation. Because of the unlikelihood that the proband was homozygous for two identical new point mutations, the DNA sequence abnormality was more likely to have arisen from a single mutated gene on one allele and a F7 gene deletion on the other allele. Real time polymerase chain reaction (PCR) analysis confirmed that the proband had inherited a gene deletion that was present in the maternal side of the family. Subsequent clotting assays and real time PCR revealed that the maternal deletion also included the closely linked F10 gene.

Utility of anti-xa monitoring in children receiving enoxaparin for therapeutic anticoagulation.

Although enoxaparin is used to treat thromboembolism in children, current treatment guidelines are largely extrapolated from adults. The objectives of this study were to determine: i) correlation between enoxaparin dose and anti-factor Xa (anti-Xa) level, ii) intra-patient variability, and iii) whether dose or anti-Xa level is a predictor of outcomes. A retrospective chart review was conducted on all hospitalized patients receiving enoxaparin in a tertiary care pediatric institution. Simple linear regression, coefficient of variation (CV), and Student's t-test were used to analyze the objectives. Eighty treatment courses with interpretable anti-Xa levels were analyzed. Mean patient age was 6.5 years. Mean enoxaparin dose was 1.10 mg/kg q12h. Correlation between initial dosing and anti-Xa level was poor; R(2) = 0.0307 and 0.0237 for patients > 2 months with and without cardiac or renal diseases, respectively. Four out of seven patients ≤ 2 months of age compared to 4/32 patients > 2 months had a CV > 40%. Similarly, 4/12 cardiac patients compared to 4/27 non-cardiac patients had a CV > 40%. Neither dose nor anti-Xa level predicted treatment success or adverse reactions (P > .05). These results suggest a need to reexamine the use of anti-Xa levels for guiding enoxaparin therapy. Further prospective studies are warranted to clarify whether routine or selective anti-Xa monitoring should be recommended in pediatric patients.

Hyperuricemia and reticulocytopenia in association with autoimmune hemolytic anemia in two children.

Hyperuricemia developed in 2 children with autoimmune hemolytic anemia with reticulocytopenia at a time of hemolytic crisis. One likely cause of hyperuricemia is the destruction of nucleated RBC precursors by autoantibodies. It is advised that patients with autoimmune hemolytic anemia with reticulocytopenia be examined for hyperuricemia. This might explain the reason for reticulocytopenia and might prevent unnecessary bone marrow procedures. When hyperuricemia is present, supportive therapy might be needed to prevent renal damage.

An assessment of published pediatric dosage guidelines for enoxaparin: a retrospective review.

OBJECTIVE: To evaluate the ability of published dosage guidelines for enoxaparin to achieve therapeutic anticoagulation and to determine whether the routine monitoring of anti-Xa levels is still necessary at a tertiary care pediatric institution. METHODS: Consecutive charts and laboratory records were reviewed for all patients receiving treatment doses of enoxaparin for thrombosis in the authors institution over a 4-year period (1998-2002). RESULTS: Sixty-six percent (25/38) of the anti-Xa levels were within the recommended therapeutic range (0.5-1.0 [+/- 10%] U/mL) after two doses. The success rates of achieving therapeutic levels were 1/6, 2/3, 6/9, 10/11, and 6/9, for patients 2 months or younger, more than 2 months to 1 year, more than 1 year to 6 years, more than 6 years to 12 years, and more than 12 years of age, respectively. Patients with cardiac or renal disease were more likely to achieve high anti-Xa levels. Thirty-seven percent of patients reported adverse effects. The most common effects were injection site-related bruising and minor bleeding. One patient experienced a major bleed that was not life-threatening. CONCLUSIONS: Most patients achieved therapeutic anticoagulation when dosed according to the published guidelines. Children with cardiac conditions or renal insufficiency or those younger than 2 months were more likely to require dosage adjustments to achieve the therapeutic range. Routine monitoring of anti-Xa levels is still necessary in these patient populations, particularly when the early establishment of therapeutic anticoagulation may be critical. Enoxaparin appears to be well tolerated in the authors' patient population.

Element of caution: a case of reversible cytopenias associated with excessive zinc supplementation.

Zinc is a common supplement and is widely available as a standard component of many over-the-counter products. A number of reports have identified an association between excessive zinc intake and severe cytopenia. We report a case of zinc-induced copper deficiency in a young adult to illustrate this under-recognized cause of anemia and neutropenia.

Permanent and panerythroid correction of murine beta thalassemia by multiple lentiviral integration in hematopoietic stem cells.

Achieving long-term pancellular expression of a transferred gene at therapeutic level in a given hematopoietic lineage remains an important goal of gene therapy. Advances have recently been made in the genetic correction of the hemoglobinopathies by means of lentiviral vectors and large locus control region (LCR) derivatives. However, panerythroid beta globin gene expression has not yet been achieved in beta thalassemic mice because of incomplete transduction of the hematopoietic stem cell compartment and position effect variegation of proviruses integrated at a single copy per genome. Here, we report the permanent, panerythroid correction of severe beta thalassemia in mice, resulting from a homozygous deletion of the beta major globin gene, by transplantation of syngeneic bone marrow transduced with an HIV-1-derived [beta globin gene/LCR] lentiviral vector also containing the Rev responsive element and the central polypurine tract/DNA flap. The viral titers produced were high enough to achieve transduction of virtually all of the hematopoietic stem cells in the graft with an average of three integrated proviral copies per genome in all transplanted mice; the transduction was sustained for >7 months in both primary and secondary transplants, at which time approximately 95% of the red blood cells in all mice contained human beta globin contributing to 32 +/- 4% of all beta-like globin chains. Hematological parameters approached complete phenotypic correction, as assessed by hemoglobin levels and reticulocyte and red blood cell counts. All circulating red blood cells became and remained normocytic and normochromic, and their density was normalized. Free alpha globin chains were completely cleared from red blood cell membranes, splenomegaly abated, and iron deposit was almost eliminated in liver sections. These findings indicate that virtually complete transduction of the hematopoietic stem cell compartment can be achieved by high-titer lentiviral vectors and that position effect variegation can be mitigated by multiple events of proviral integration to yield balanced, panerythroid expression. These results provide a solid foundation for the initiation of human clinical trials in beta thalassemia patients.