Patricia M. Kopko

HLA class II antibodies in transfusion‐related acute lung injury

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is a serious, sometimes fatal, complication of transfusion. Granulocyte and HLA class I antibodies present in blood donors have been associated with TRALI. HLA class II antibodies have recently been described in a few cases of TRALI.

TRALI: correlation of antigen-antibody and monocyte activation in donor-recipient pairs.

BACKGROUND : TRALI may be a severe reaction associated with transfusion of plasma‐containing blood components. TRALI has usually been associated with antibodies against granulocytes and HLA class I antigens, but more recently with antibodies against HLA class II and monocytes. TRALI cases were investigated to determine correlation between antigen and antibody. Additionally, activation of monocytes by TRALI serums was studied.

Transfusion-related acute lung injury

A 77-year-old man was diagnosed with acute lymphoblastic leukaemia and started induction chemotherapy with vincristine, daunorubicin and prednisolone. His haemoglobin was 7Æ1 g/dl, total white cell count 2Æ1 · 10/l and platelet count 14 · 10/l, so he was given his first transfusion of a single pool of apheresis platelets. One hour after platelet-transfusion, he became acutely unwell with severe shortness of breath. On physical examination, he had become hypotensive (blood pressure 68/40 mmHg) with tachycardia (heart rate 120 beats/ min) and tachypnoea (respiratory rate 30 breaths/min), but remained apyrexial. There was no evidence of volume-overload but lung ausculatation revealed bilateral crepitations to the midzones. The oxygen saturation in room air was 67% and a chest X-ray showed extensive pulmonary oedema (left) in comparison with his X-ray on admission (right). His clinical condition deteriorated rapidly and he died from cardiac arrest. There was no previous history of cardiovascular or respiratory disease and postmortem examination showed gross pulmonary oedema, but no significant coronary artery disease or evidence of recent myocardial ischaemia. The transfused platelets were an apheresis pool from a female donor. She was subsequently found to have anti-human leucocyte antigen class I immunoglobulin G antibodies and was retired from the donor panel. Transfusion-related acute lung injury remains an important cause of transfusion-related morbidity and mortality and should be considered in the differential diagnosis when a patient becomes acutely unwell in the first 24 h following transfusion with plasma-containing blood products.

A national survey of transfusion-related acute lung injury risk reduction policies for platelets and plasma in the United States

BACKGROUND: Little information exists on the specific transfusion‐related acute lung injury (TRALI) risk reduction practices used by multiple blood collecting institutions in the United States.

Mechanisms of severe transfusion reactions

Serious adverse effects of transfusion may be immunologically or non-immunologically mediated. Currently, bacterial contamination of blood products, particularly platelets, is one of the most significant causes of transfusion-related morbidity and mortality. Septic transfusion reactions can present with clinical symptoms similar to immune-mediated hemolytic transfusion reactions and transfusion-related acute lung injury. Extremely high fever and/or gastrointestinal symptoms, in a transfusion recipient, may be indicative of sepsis. The diagnosis is based upon culturing the same organism from both the patient and the transfused blood component. Numerous organisms have been implicated as the cause of septic transfusion reactions. Due to different storage conditions, gram negative organisms are more often isolated from red blood cell components; gram positive organisms are more often isolated from platelets. Prevention of septic transfusion reactions is primarily dependent on an adequate donor history and meticulous preparation of the donor phlebotomy site. Visual inspection of blood components prior to transfusion is also vital to preventing these reactions. Several methods of detection of bacterial contamination and inactivation of pathogens are currently under active investigation.

Pulmonary injury from transfusion-related acute lung injury.

Transfusion-related acute lung injury (TRALI) can be a life-threatening complication of transfusion. In its severe form, it is clinically indistinguishable from acute respiratory distress syndrome. Symptoms typically begin within 4 hours of transfusion. TRALI has been reported after transfusion of all plasma-containing blood components. TRALI is associated with antibodies to white blood cells and biologically active lipids in trans-fused blood components.

Early diagnosis and successful treatment of a patient with transfusion-associated GVHD with autologous peripheral blood progenitor cell transplantation.

BACKGROUND : Transfusion‐associated GVHD (TA‐GVHD) is an uncommon complication of blood transfusion. Diagnosis of TA‐GVHD is difficult, and it is usually rapidly fatal. There are few documented sur‐ vivors of TA‐GVHD.

AABB survey of transfusion-related acute lung injury policies and practices in the United States

BACKGROUND: Policies and practices with regard to transfusion‐related acute lung injury (TRALI) diagnosis, laboratory investigation of TRALI cases, and donor deferral and donor management are not standardized.

Methods for the selection of platelet products for alloimmune‐refractory patients

The ability to efficiently and accurately diagnose the cause(s) of platelet (PLT) refractoriness is paramount in providing effective PLT products for transfusion. Recent advances in methods for detecting and identifying alloantibodies against human leukocyte antigens (HLAs) and human PLT antigens, combined with accurate molecular techniques for HLA typing, have provided a framework for the development of clinical algorithms to support such patients. Alloantibodies may be detected and/or identified by several methods, including complement‐dependent cytotoxicity, enzyme‐linked immunosorbent assays (ELISA), and microbead‐based assays using Luminex or flow cytometry. The primary difference in these assays is the sensitivity of detection and the range of antibody specificities that may be reliably identified. Direct PLT cross‐matching to identify compatible PLTs can be accomplished by several methods, including solid‐phase red cell adherence, modified antigen capture ELISA, and flow cytometry. A survey of blood centers and laboratories providing transfusion support has identified the heterogeneity of testing options available, areas of concern and need for improvement, and common obstacles in providing appropriate and timely support to immune‐refractory PLT patients. Depending on the testing methods and the pool of HLA‐typed PLT donors available, there are numerous options for developing suitable algorithms to provide effective support to immune‐refractory PLT patients.

HIV Transmissions From a Window-Period Platelet Donation

Recently, blood centers began investigational testing for HIV RNA by pooled nucleic acid testing (NAT). A 35-year-old frequent platelet donor tested HIV p24 antigen positive, antibody negative before implementation of NAT. He made 2 platelet donations (day -4 and -11) immediately before testing positive for HIV. The donors HIV seroconversion was monitored, and stored samples were tested retrospectively for HIV RNA. Platelet recipients were tested for HIV infection. The day -4 sample tested positive for HIV RNA by pooled and individual sample NAT. The day -11 sample tested negative for HIV RNA by both NAT tests. The 2 recipients of the day -4 platelets tested HIV RNA and p24 antigen positive. The recipient of the day -11 platelets could not be tested because he had died. HIV NAT would have prevented transmission of HIV had it been available at the time of this donors HIV seroconversion.