Overcoming blood shortages: red blood cell and platelet substitutes and membrane modifications

Blood shortages are increasingly common as the donor base declines and extensive restrictions on blood donation disqualify many donors. Red blood cell (RBC) and platelet substitutes have long been anticipated as alternatives to standard transfusions. However, difficulties in manufacturing, efficacy, and safety have slowed the development of these products. New understanding of the relationship between blood viscosity, oxygen transport, and vasoactivity have led to more effective RBC substitutes, several of which are in advanced clinical trials. In addition, creative approaches to RBC membrane modification, such as the enzymatic cleavage of ABH glycoproteins, may lead to a universal RBC. Advances in the understanding of platelet membrane behavior at low temperatures may lead to extended platelet storage at refrigerator temperatures. Standard transfusions of human RBCs and platelets will not be replaced soon. However, these new products will be a useful alternative for selected clinical applications and will lessen our dependence on our marginally adequate blood supply.     

Impact of stem cell donation modality on normal donor quality of life: a prospective randomized study

As part of a previously reported trial comparing granulocyte-colony stimulating factor (G-CSF) stimulated bone marrow and peripheral blood stem cells (PBSCs) in allogeneic stem cell transplantation, we included a questionnaire to compare donor morbidity and long-term complications between the two donation procedures. Bone marrow donation was associated with significantly more donors experiencing localized pain at the donation site compared to PBSC collection. However, this was not associated with any increased delay in returning to normal activity. Although a minority of bone marrow donors suffered chronic pain at the donation site, no serious long-term side effects relating to G-CSF stimulated stem cell donation were identified.     

Donating umbilical cord blood to a public bank or storing it in a private bank: knowledge and preference of blood donors and of pregnant women

Background.

Umbilical cord blood (UCB) is a source of stem cells for allogeneic haematopoietic transplantation in paediatric and adult patients with haematological malignancies and other indications. Voluntary donation is the basis for the success of unrelated UCB transplantation programmes. In the last few years a growing number of private banks offer their services to expectant parents, to store UCB for future use. The debate concerning UCB donation and private preservation has been ongoing for several years. The aims of this single centre study were to explore knowledge about UCB stem cells and attitudes towards voluntary UCB donation or private UCB preservation among both blood donors and pregnant women.

Materials and methods.

This study was conducted at the “Sapienza” University of Rome. Two types of anonymous questionnaires were prepared: one type was administered to 1,000 blood donors while the other type was distributed to 300 pregnant women.

Results.

Most blood donors as well as the majority of pregnant women had some general knowledge about UCB (89% and 93%, respectively) and were aware of the possibility of donating it (82% and 95%). However, the level of knowledge regarding current therapeutic use resulted generally low, only 91 (10%) among informed blood donors and 69 (31%) among informed pregnant women gave a correct answer. The survey revealed a preference for voluntary donation both among blood donors (76%) and among pregnant woman (55%). Indeed, a minority of blood donors (6.5%) and of pregnant women (9%) would opt to store UCB for private use.

Discussion.

The study raises the following considerations: (i) the large support for UCB donation expressed by blood donors and by pregnant women suggests that UCB preservation does not represent an obstacle to the expansion of UCB donation and to development of unrelated transplantation programmes; (ii) information about UCB donation and preservation should be carefully given by professionals and institutions.     

Liver transplantation: Issues for the next 20 years

The growing numbers of potential transplant recipients on waiting lists is increasingly disproportionate to the supply of cadaveric donor organs. The hope for the next 20 years is that supply will satisfy demand. This requires both a reduction in indications for the procedure and an increase in the transplants performed. A multi-pronged approach is needed to increase cadaveric organ donation, generating enthusiasm for donation among both the general public and hospital staff. Accurate assessment of marginal grafts with stringent criteria known to predict graft function will diminish wastage of organs. Methods of rehabilitating marginal grafts during extracorporeal perfusion will increase organ availability. Supply of non-heart beating donors can be greatly expanded and protocols developed with ethical consent to optimize their initial function despite warm ischemia. Splitting livers that fulfill selection criteria, thus providing for two recipients, should be universally applied with acceptable incentives to those units who do not directly benefit. A proportion of recipients, though not those transplanted for autoimmune disease, will be spared the side-effects of immunosuppression thanks to immune tolerance. Protocols for close monitoring of those patients for rejection during treatment withdrawal must be carefully observed. In addition to gene therapy, it is highly likely that hepatocyte transplantation will replace orthotopic grafting in patients without cirrhosis, especially for inherited metabolic diseases. It is much more difficult to envisage that heterologous stem cell transplantation or xenotransplantation will have clinical impact in the next 20 years, although research in those areas has obvious long-term potential.     

Benefit and risk perceptions in transfusion medicine: blood and blood substitutes

Blood transfusion is a remarkably safe, routine procedure in clinical medicine. However, little attention has focused on the perceptions of risk associated with the receipt of blood, blood products or 'blood substitutes'. It is pertinent to ask (i) what key stakeholder groups know about transfusion, (ii) how safe they perceive blood/blood products to be, (iii) how the latter information might influence their own and others' perceptions of risk linked to transfusion, and (iv) the extent to which approved blood substitutes might be preferred over autologous or donor blood. An appreciation of what stakeholders perceive to be the benefits and risks of the receipt of blood and blood substitutes will inform future transfusion strategies. To obtain such information, a programme of research has been initiated at Nottingham. Surveys have targeted key stakeholder groups, namely, UK adult blood donors and nondonors, anaesthetists, general practitioners and health care journalists. Experimental studies examining message framing and cueing have also been conducted with undergraduate students. Such research will improve misunderstandings about current issues associated with blood donation and transfusion against the backdrop of changing public trust of health care professionals and attitudes and expectations on blood safety and benefits of blood substitutes.     

Haemophilia therapy: assessing the cumulative risk of HIV exposure by cryoprecipitate

Most of the world's haemophilia population live in countries with developing or emerging economies. As such, they do not have access to viral inactivated clotting product. Many are treated with cryoprecipitate made from locally supplied blood. The rationale for using cryoprecipitate instead of viral inactivated products is based on an implicit belief that because blood banks can provide reasonably safe products by using modern testing procedures, transmission of HIV and other blood-borne viruses is rare. However, the risk of acquiring a blood-borne infection is cumulative, and haemophilia patients treated with cryoprecipitate or fresh-frozen plasma are exposed to hundreds or thousands of donors during their lifetime. The risk that an HIV-infected person will be a donor during the 'window period' is directly related to the incidence of HIV in the country where the donation occurs. To illustrate the extent of this problem, we devise a model for estimating the risk that a person with haemophilia will encounter HIV-contaminated cryoprecipitate as a function of years of treatment and the underlying incidence rate of HIV among blood donors. We apply the model to two countries with different incidence rates of HIV, Venezuela and the USA. Over a lifetime of treatment (60 years), the cumulative risk of HIV exposure for a person with haemophilia receiving monthly infusion of cryoprecipitate prepared from plasma of 15 donors is significant, 2% in the USA and 40% in Venezuela. Considering the cumulative risk for transmitting HIV to patients with haemophilia through cryoprecipitate treatment, medical care providers should carefully evaluate the use of cryoprecipitate in any but emergency conditions or when no virally inactivated products are available.     

Organtransplantation in Deutschland

Organ transplantation over the last 40 years has developed into a standardized successful procedure for the replacement of heart, kidney liver, lung, and pancreas. During this time, treatment strategies have greatly improved and novel procedures such as living related organ donation have been introduced. Despite these improvements, the number of organ transplants has stalled in recent years. In the face of increasing numbers of patients on the waiting list for organ transplantation, this situation is unacceptable and ways to improve the situation of organ transplantation have to be found.     

Cell adhesion to fibronectin down-regulates the expression of Spy1 and contributes to drug resistance in multiple myeloma cells

Allogeneic hematopoietic stem cell transplantation is now an important treatment for numerous diseases. Donation of hematopoietic stem cells, either through bone marrow (BM) harvesting or peripheral blood stem cell (PBSC) collection, is a well-established and generally accepted procedure. The BM is aspirated from the posterior iliac crest under spinal or general anesthesia, and common side effects include fatigue and local pain. PBSC collection requires 4–6 days of G-CSF injections and leukapheresis 1–2 times. Common side effects of these procedures include bone pain, fatigue, and headache. The side effects of BM and PBSC collections are mostly transient and well tolerated. Severe adverse events are uncommon in healthy donors. At present, there is no definitive evidence to show that the stem cell donation increases the risk of marrow failure or cancer development. Nevertheless, all donors must be carefully evaluated and fully informed before donation. Donors must be able to provide informed consent without being coerced or pressured. Donors and graft products must be examined for potential agents to avoid transmitting infections and other diseases that may jeopardize donor’s health during stem cell collection or recipient’s well being after transplantation. Understanding the potential physical and psychological complications of stem cell donation and factors that may increase risks is very important to ensure that transplantation physicians maintain positive attitude in conducting this benevolent practice.     

Umbilical cord blood: biology and transplantation

Umbilical cord blood transplantation is becoming an acceptable alternative source of hematopoietic stem cells for patients with malignant diseases. Cord blood differs from bone marrow and peripheral blood progenitors in its immune tolerance and kinetics of engraftment. In this article, we will review the biology of cord blood stem cells and clinical studies of cord blood transplants in pediatric and adult populations. We will also discuss potential uses of cord blood stem cells in regenerative medicine and novel methods for ex vivo expansion of hematopoietic stem cells. As we learn more about cord blood transplants, there is the potential to overcome the limitations of cord blood transplants so that they can become more widely available.     

Barriers and motivators to blood and cord blood donations in young African-American women

The primary aim of this study was to assess potential barriers and motivators to blood and cord blood donation among African-American women. A telephone survey of African-American women, ages 18-30 years, in the St. Louis metropolitan area was performed. The survey was administered by trained telemarketing personnel using a Computer-Assisted Direct Interview (CADI) system. One hundred sixty-two women were surveyed. Common barriers to blood donation were inconvenience of donor sites (19%), fear of needles (16%), and too much time required to donate (15%). Potential motivators were increasing awareness of need for blood (43%), increasing the number of convenient donor locations (19%), and encouragement by spiritual leaders to have blood drives at their church (17%). Lack of awareness was the only identified barrier to cord blood donation. Most women surveyed (88%) indicated that they definitely or probably would donate cord blood. Strategies to increase the proportion of African-American blood and cord blood donations may include educating potential donors about the process and benefits of donation to particular patient populations and engaging church leadership in supporting blood and cord blood donations.