Blood products risks from

Infection risk On 10 April 2009, during a routine record review in connection with a subsequent blood drive, a blood bank supervisor learned of a breach in the deferral protocol for blood products collected from trainees [52 ]. Further investigation showed that the blood that had been obtained during the previous drive had been from trainees who had been immunized with yellow fever vaccine 4 days before the drive. All of those blood products had already been processed and incorporated into the inventory at the hospital s blood bank. The blood bank supervisor reviewed the blood bank s records and identified 87 units of whole blood and three units of platelet that had been obtained from the recently immunized trainees. Blood products that had been released for transfusion were tracked forward to identify the patients who had received the implicated blood products. Unused blood products were identified and destroyed. Five patients had received six blood products (three units of platelets, two units of fresh frozen plasmas, and one unit of packed erythrocytes) from six of the trainees, who had no previous history of immunization or travel consistent with... 

In 1983 the move to develop red cell substitutes intensified when it was recognized that the acquired immune deficiency syndrome (AIDS) could be transmitted by the blood-bome human immunodeficiency vims (HIV). Concern for the nation s blood supply followed. Since that time other retrovimses have been identified, efforts to screen blood not only for these agents but also for vimses that cause hepatitis have intensified, the indications for transfusion have been reevaluated, and the use of blood products has become much more efficient. More carehil screening of donors, testing of all donated units, and a general awareness in the donor population have all contributed to a decreased risk from transfusion-contracted AIDS. 

Biopharmaceutical products are also subjected to screening for the presence of viral particles prior to final product release. Although viruses could be introduced, for example, via infected personnel during downstream processing, proper implementation of GMP minimizes such risk. Any viral particles found in the finished product are most likely derived from raw material sources. Examples could include HIV or hepatitis viruses present in blood used in the manufacture of blood products. Such raw materials must be screened before processing for the presence of likely viral contaminants. 

Risks associated with infusion of blood products include transfusion-related reactions, virus transmission (rare), hypocalcemia resulting from added citrate, elevations in serum potassium and phosphorus concentrations from use of stored blood that has hemolyzed, increased blood viscosity from supranormal hematocrit elevations, and hypothermia from failure to appropriately warm solutions before administration. 

Receiving a transfusion of HIV-infected blood. Since transfusion involves placing foreign blood or blood products directly into the recipient s bloodstream, the necessary conditions for HIV transmission are present. After screening of the blood supply by antibody tests began in 1985, the risk was low that the blood or blood product involved in transfusion was infected, except for hemophiliacs, who require a clotting factor extracted from the blood of many different donors. 

Better methods for preparing clotting factors from blood and the development of recombinant clotting factors provided the solutions. Methods of detecting, inactivating, and removing viruses were improved, and none of the hemophilia replacement products— conventional or recombinant—has transmitted either HIV or hepatitis since 1987. As an alternative, recombinant clotting factors 8 and 9, produced in animal cells, were approved in 1992 and 1997, without the risk associated with human blood products. 

Human plasma has a colloid osmotic pressure of 3.6 kPa, of which 2.8 kPa is contributed by albumin. Volume-for-volume, 4.5% albumin is approximately four times more effective in expanding the plasma volume than crystalloid solutions, and the effect lasts 6-8 hours, compared to only 15-20 min with crystalloids. Although popular in the past as volume expanders, albumin solutions have fallen into disfavour. They are prepared from pooled human plasma, with all the inherent risks of pooled blood products. Albumin can cause adverse reactions, similar to other transfusion reactions, such as chills, urticaria, and vasodilatation. These may be caused by organic or inorganic substances formed during the processing... 

Precautionary Measures to Reduce the Possible Risk of Transmission of Zoonoses by Blood and Blood Products from Xenotransplantation Product Recipients and Their Contacts. DHHS/FDA/CBER, Bethesda, MD Dec. 1999. 

The norms for medicinal production are particularly stringent. Biological products are composed of complex molecules, produced by cell lines with a relatively recent history, and difficult to characterize. Tests performed only on the final product do not guarantee consistency of production. The purification procedures should be planned and validated for the removal of potential contaminants from diverse sources cells, culture media, equipment, and reagents used in the purification or even degradation products derived from the protein itself. There are examples of products with unexpected risks that have caused serious problems such as blood contamination by HIV-1 virus between 1980 and 1985 (Bloom, 1984) or the presence of residual infectious viruses in the poliomyelitis vaccine due to inefficient inactivation (Lubiniecki et al., 1990). 

Fractionation techniques have made it possible to recover active o -antitrypsin from blood. Use of this product for intravenous replacement therapy in deficient individuals has shown that it is possible to increase levels in the serum to those of PISZ heterozygotes who experience no increase in pulmonary disease over the general population. Pulmonary lavage of patients transfused with this product showed that functional (Xj-antitrypsin reaches the alveolar structures. The Food and Drug Administration has approved weekly administration of purified serum-derived oq-antitrypsin to PIZZ and PI null individuals with pulmonary disease. Although serum levels of oq-antitrypsin increase to those believed to be protective, it has not been possible to show clinical improvement. Furthermore, viral transmission via blood products is a significant risk factor. 

In 2005, a study appeared in Cancer Letters that would have evoked widespread media coverage if it had been about an illegal drug, rather than about a pharmaceutical company product (El-Zein, 2005). Researchers from the University of Texas examined 12 children treated with therapeutic effects of Ritalin to determine whether this central nervous system stimulant produces cytogenetic abnormalities in pediatric patients at therapeutic doses. Using peripheral blood lymphocytes taken from the children, they found a 2.4-fold increase in chromosome aberrations and similar defects. They concluded, These findings warrant further investigations of the possible health effects of methylphenidate in humans, especially in view of the well-documented relationship between elevated frequencies of chromosome aberrations and increased cancer risk. ... 

Long-term exposure to benzene increases the risks of getting cancer however, cancer linked to benzene has been discovered in people exposed for less than 5 years. Workers exposed for decades are at increased risk for these rare forms of leukemia and long-term exposure may also adversely impact bone marrow and blood production. Still other workers have been diagnosed with aplastic anemia, a group of disorders that prevent bone marrow from producing all three types of blood cells red blood cells, white blood cells, and platelets. ... 

ACE inhibitors and AT -receptor blockers are most useful in hypertension when the raised blood pressure results from excess renin production (e.g. renovascular hypertension), or where concurrent use of another drug (diuretic or calcium blocker) renders the blood pressure renin-dependent. The fall in blood pressure can be rapid, especially with short-acting ACE inhibitors, and low initial doses of these should be used in patients at risk those with impaired renal function, or suspected cerebrovascular disease. These patients may be advised to omit any concurrent diuretic treatment for a few days before the first dose. The antihypertensive effect increases progressively over weeks with continued adminis-... 

In principle, a certificate can be granted for any substance (active substances, excipients) such as organic or inorganic substances, substances produced by fermentation as indirect gene products, and products with risk of TSE for which a monograph published in the European Pharmacopeia exists. Excluded, however, are biological substances such as proteins, products obtained from human tissues, vaccines, blood products, and preparations. 

As in several other countries, the Health Council of the Netherlands has prepared recommendations on the need for routine leukodepletion by filtration of blood. The presence of leukocytes in blood products has no beneficial effect for the recipient, except in special cases, such as patients undergoing organ transplantation (41). Apart from preventing the adverse effects associated with leukocyte transfusion, it has been postulated that the risk of transmission of new variant Creutzfeldt-Jakob disease can be prevented by using leukodepleted blood products. 

To date studies have shown that patients who develop Creutzfeldt-Jakob disease do not have a history of a higher rate of transfusion or treatment with blood products. Likewise, those who have received blood from donors who subsequently prove to have Creutzfeldt-Jakob disease do not acquire an increased risk. Furthermore, animal experiments have shown that blood and blood products are very low risk materials in transfer experiments from diseased to healthy animals. AH the same, certain authorities are now considering the exclusion of donors from families with known cases of classic Creutzfeldt-Jakob disease. 

However, the emergence of variant Creutzfeldt-Jakob disease (vCJD) in the UK and France has raised concern about a new theoretical risk of infection in patients treated with blood and blood products (198). Animal experiments in which blood from sheep infected with bovine spongiform encephalopathy and natural scrapie-infected sheep into scrapie-free recipient animals have suggested disease transmission by the blood transfusion route in 2 of 24 sheep with bovine spongiform encephalopathy and in 4 of 21 sheep with scrapie (199). Many European countries have incorporated leukodepletion of all blood products, as leukocytes are believed to play a key role in the pathogenesis of variant Creutzfeldt-Jakob disease (198). In some countries, people who have lived in the UK for a period longer than 6 months between 1980 and 1996 are excluded from blood donation (13). Furthermore, it has been shown that various steps used in the manufacture of plasma-derived products also contribute to reduced infectivity by bovine spongiform encephalopathy (198). 

CPMP report. Risk of transmission of Creutzfeldt-Jakob disease via medicinal products derived from human blood or plasma. CPMP report 1995 846/95. 

The treatment of ACD is somewhat less specific than the treatment of other anemias. Focus should be on treating the underlying disorder and correcting reversible causes of anemia. Direct approaches to correction of anemia may not be needed. During inflammation, oral or parenteral iron therapy is ineffective. Transfusions of RBCs are effective, but should be limited to situations in which oxygen transport is inadequate due to concomitant medical problems. The Hgb level necessitating a RBC transfusion varies from 8 to 10 g/dL based on factors such as cost, convenience, and risk of infectious complications. Assessment of the symptomatic state should always be considered before blood products are administered. 

In addition to transmission from donor organs, primary CMV disease also may be transmitted from seropositive blood products, although this is a much less common mode of transmission. Risk of such transmission increases with the administration of large numbers of blood products. 

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