Jonathan Wallis

Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency

The human syndrome of dendritic cell, monocyte, B and natural killer lymphoid deficiency presents as a sporadic or autosomal dominant trait causing susceptibility to mycobacterial and other infections, predisposition to myelodysplasia and leukemia, and, in some cases, pulmonary alveolar proteinosis. Seeking a genetic cause, we sequenced the exomes of 4 unrelated persons, 3 with sporadic disease, looking for novel, heterozygous, and probably deleterious variants. A number of genes harbored novel variants in person, but only one gene, GATA2, was mutated in all 4 persons. Each person harbored a different mutation, but all were predicted to be highly deleterious and to cause loss or mutation of the C-terminal zinc finger domain. Because GATA2 is the only common mutated gene in 4 unrelated persons, it is highly probable to be the cause of dendritic cell, monocyte, B, and natural killer lymphoid deficiency. This disorder therefore constitutes a new genetic form of heritable immunodeficiency and leukemic transformation.

The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency

Human immunodeficiency syndrome with loss of DCs, monocytes, and T reg cells; preservation of Langerhans cells; associated loss of BM multilymphoid progenitors; and overproduction of Flt3 ligand.

Single hospital experience of TRALI

BACKGROUND: TRALI is a serious adverse effect of blood transfusion. There is evidence that the condition is underrecognized and underreported.

Effect of WBC reduction of transfused RBCs on postoperative infection rates in cardiac surgery

BACKGROUND : WBC‐replete blood transfusion has been suggested as an independent cause of increased postoperative infection.

Acute lung injury after ruptured abdominal aortic aneurysm repair : The effect of excluding donations from females from the production of fresh frozen plasma

Objectives:Transfusion-related acute lung injury may contribute to the development of acute lung injury in the critically ill, due to plasma from female donors containing antileukocyte antibodies. In July 2003, the U.K. National Blood Service stopped using female donor plasma for the production of fresh frozen plasma. Patients undergoing repair of a ruptured abdominal aortic aneurysm receive large amounts of fresh frozen plasma and often develop acute lung injury. We investigated whether the change to male fresh frozen plasma was associated with a change in the frequency of acute lung injury in these patients. Design:A retrospective, before and after, observational, single-center study. Setting:Tertiary care center and a regional blood center. Patients:The study included 211 patients undergoing open repair of a ruptured abdominal aortic aneurysm between 1998 and 2006. Interventions:None. Measurements and Main Results:Primary outcome was the development of acute lung injury in the first 6 hrs after surgery. Secondary outcomes were significant hypoxia (Pao2/Fio2 ratio <300), time to extubation, and survival at 30 days. Groups were well matched and received similar volumes of intravenous fluids and blood components. There was significantly less acute lung injury following the change to male fresh frozen plasma (36% before vs. 21% after, p = .04). At 6 hrs after surgery, fewer patients were hypoxic (87% before vs. 62% after, p < .01). In multivariate analysis, the change in donor policy was associated with a decreased risk of developing acute lung injury (odds ratio 0.39; 95% confidence interval, 0.16–0.90). Time to extubation and survival at 30 days were not statistically different between groups. Conclusions:The policy to exclude female donors from the production of fresh frozen plasma was associated with a decrease in the frequency of acute lung injury in patients undergoing repair of a ruptured abdominal aortic aneurysm.

Transfusion‐related acute lung injury caused by two donors with anti‐human leucocyte antigen class II antibodies: a look‐back investigation

Summary.  Transfusion‐related acute lung injury (TRALI) is considered as one of the most important complications of blood transfusion. Previous look‐back investigations have revealed unrecognized cases.

Long‐term survival after blood transfusion: a population based study in the North of England

BACKGROUND:  Blood transfusion may transmit infec‐tious diseases with long incubation periods. Estimation of the risks of transmission of such disease requires know‐ledge of long‐term survival of transfused patients. No such information is available in the UK, where there is particular concern about possible transmission by trans‐fusion of variant CJD.

Nitric oxide and blood: a review

Summary.  Nitric oxide (NO) was identified as a physiological mediator of vascular tone in 1987. NO produced by endothelial cells causes vasodilatation and also inhibits platelet aggregation and leucocyte adhesion. Red cells metabolize NO to nitrate but may possibly carry and release, or even produce, NO in hypoxic conditions. NO physiology may have important implications for transfusion medicine, ranging from adverse effects of haemoglobin substitutes to preservation of stored platelets and to detrimental effects of stored red cells.

Female donors and transfusion-related acute lung injury: A case-referent study from the International TRALI Unisex Research Group

BACKGROUND: Although quantitative evidence is lacking, it is generally believed that the majority of cases of transfusion‐related acute lung injury (TRALI) are caused by female blood donors. We aimed to examine the relation between female donors and the occurrence of TRALI.

Transfusion-related acute lung injury (TRALI): presentation, epidemiology and treatment

Transfusion-related acute lung injury (TRALI) was clearly described in a paper by Brittingham [1] in 1957. Numerous case reports have been published since, but the condition drew wider attention in 1985 following a prospective observational study at the Mayo clinic where Popovsky and Moore documented an incidence of acute respiratory distress of 1 per 5000 units of blood components transfused [2]. Despite this, knowledge of TRALI remained poor in many medical specialities. The advent of systematic haemovigilance reporting systems has led to better education and to greater recognition of TRALI.