First report of human immunodeficiency virus transmission via an RNA-screened blood donation.

BACKGROUND AND OBJECTIVES: Blood banks in the USA have recently introduced minipool nucleic acid amplification testing (MP-NAT) of blood products to reduce the transmission of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) by transfusions. However, MP-NAT is limited in its ability to detect preseroconversion samples with very low viral RNA loads. MATERIALS AND METHODS: To determine whether a red blood cell unit, from an MP-NAT-negative donation, transmitted HIV when transfused to a patient, we compared the viral sequences from the blood donor and recipient. The implicated donation was also tested by commercially available NAT assays at a range of dilution factors to determine whether the infectious unit could have been detected using individual-donation NAT (ID-NAT). RESULTS: Phylogenetic linkage of HIV sequences in the blood donor and recipient confirmed the transmission of HIV by blood transfusion, the first such case identified since introduction of MP-NAT screening in 1999. Viral RNA was reliably detected by ID-NAT, but only inconsistently detected by MP-NAT. CONCLUSIONS: Even following the introduction of MP-NAT, a preseroconversion donation with a viral load of

Acute intravascular hemolysis secondaryto out-of-group platelet transfusion.

BACKGROUND: Acute intravascular hemolysis is rarely associated with platelet transfusion. Out-of-group single-donor platelets may cause hemolysis if the donor has high-titer ABO hemagglutinins. CASE REPORT: A 44-year-old woman, blood group A, was recently diagnosed with acute myeloid leukemia and was receiving chemotherapy. After the transfusion of apheresis platelets from a group O donor, back pain, hemoglobinuria, and hemoglobinemia developed, and her Hb dropped by 2.3 g per dL, despite the transfusion of 2 units of RBCs. RESULTS: Investigation revealed acute intravascular hemolysis with a positive DAT due to anti-A(1) on her RBCs. The donor's titer of anti-A(1) was greater than 16,000. CONCLUSION: Review of published cases raises the possibility that hemolytic reactions to out-of-group platelets may be more frequent since the use of apheresis platelets has increased.

A mouse model of human familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.

Mice lacking the calcium-sensing receptor (Casr) were created to examine the receptor's role in calcium homeostasis and to elucidate the mechanism by which inherited human Casr gene defects cause diseases. Casr+/- mice, analogous to humans with familial hypocalciuric hypercalcemia, had benign and modest elevations of serum calcium, magnesium and parathyroid hormone levels as well as hypocalciuria. In contrast, Casr-/- mice, like humans with neonatal severe hyperparathyroidism, had markedly elevated serum calcium and parathyroid hormone levels, parathyroid hyperplasia, bone abnormalities, retarded growth and premature death. Our findings suggest that Casr mutations cause these human disorders by reducing the number of functional receptor molecules on the cell surface.

Altered hepatic transport of immunoglobulin A in mice lacking the J chain.

We have created J chain knockout mice to define the physiologic role of the J chain in immunoglobulin synthesis and transport. The J chain is covalently associated with pentameric immunoglobulin (Ig) M and dimeric IgA and is also expressed in most IgG-secreting cells. J chain-deficient mice have normal serum IgM and IgG levels but markedly elevated serum IgA. Although polymeric IgA was present in the mutant mice, a larger proportion of their serum IgA was monomeric than was found in wild-type mouse serum. Bile and fecal IgA levels were decreased in J chain-deficient mice compared with wild-type mice, suggesting inefficient transport of J chain-deficient IgA by hepatic polymeric immunoglobulin receptors (pIgR). The pIgR-mediated transport of serum-derived IgA from wild-type and mutant mice was assessed in Madin-Darby canine kidney (MDCK) cells transfected with the pIgR. These studies revealed selective transport by pIgR-expressing MDCK cells of wild-type IgA but not J chain-deficient IgA. We conclude that although the J chain is not required for IgA dimerization, it does affect the efficiency of polymerization or have a role in maintaining IgA dimer stability. Furthermore, the J chain is essential for efficient hepatic pIgR transport of IgA.

Emergency transport of AS-1 red cell units by pneumatic tube system.

We present a study in which 14 units of AS-1 red blood cells (AS-1RBC) were transported by the Trans-Logic 620 (Denver, CO) pneumatic tube system to determine whether the system could be used without risk of significant hemolysis. Using standard hematologic parameters we detected negligible hemolysis and conclude that the Trans-Logic 620 system can be used to transport AS-1RBC. This may provide time- and labor-saving benefits generalizable to more than 250 U.S. hospitals which presently operate the Trans-Logic 620.

Myelodysplastic syndrome: identification in the routine hematology laboratory.

The Coulter S+IV electronically generates an automated white blood cell differential which counts 10,000+ cells per sample, separating lymphocytes, mononuclear cells, and granulocytes. In patients with preleukemic or so-called myelodysplastic syndromes, the histograms are consistently abnormal. CBCs of five patients demonstrate the variable features of myelodysplasia involving abnormal monocytosis, neutropenia, thrombocytopenia, and macro-ovalocytic anemias. The histogram analysis of white blood cells is a rapid, economic way of alerting the hematologist to a possible diagnostic problem in the elderly patient population.

A new method for evaluating the hepatitis risk of the multiply-implicated donor.

The usual method of estimating probability of infectivity for donors implicated in more than one case of post-transfusion hepatitis fails to take adequate account of the donor's past history and underestimates the risk of infectivity. A corrected method of calculation is presented and shown to give substantially different results.

Effect of centrifugation and subsequent storage on red blood cells.

Blood drawn into CPD solution from 33 normal donors was divided into four groups: (I) centrifuged (at 5,000 g for 7 min) after 7 days of storage, (II) centrifuged after 14 days storage, (III) centrifuged after 21 days storage and (IV) uncentrifuged. After 21 days of storage, aliquots of all units were labeled with chromium-51, reinjected into the donor from which they were drawn and erythrocyte survival was measured. Red blood cell recovery and survival for all four groups was essentially the same; 24-hour recovery was 85%; T 1/2 was 28.2--31.6 days. Our results suggest that blood can be centrifuged and stored at any time during its 21-day shelf life without detrimental effect on erythrocyte survival.