Page 2037 - Hematology_ Basic Principles and Practice ( PDFDrive )

1808 Part XI Transfusion Medicine

50 years among intravenous drug users in the United States, Brazil,
Pathogen Reduction
and Europe. Transmission of both HTLV-1 and HTLV-2 occurs by
Pathogen-reduction technology (PRT) offers a proactive strategy to parenteral exposures, sexual contact, and by vertical transmission
address new threats; these technologies involve physical, chemical, from mother to child during pregnancy and breastfeeding.
and photochemical treatments of blood components to inactivate or Diseases associated with HTLV-1 infection include adult T-cell
decrease viral, bacterial, and parasite infectivity. 23,25 leukemia/lymphoma (ATL), HTLV-associated myelopathy/tropical
Beginning in the 1980s, heat treatment, nanofiltration, and solvent/ spastic paraparesis (HAM/TSP), lymphocytic pneumonitis, uveitis,
detergent treatment eliminated or reduced viral transmission in prod- polymyositis, and arthritis. HTLV-2 does not appear to cause hema-
ucts derived from large-scale plasma fractionation such as albumin, tologic malignancy but has been associated with HAM/TSP and
immunoglobulin, and hemostatic factor concentrates. linked to a higher rate of common infections such as acute bronchitis,
In the past two decades, attention turned to whole blood–derived pneumonia, and urinary tract infections, suggesting a subtle immu-
components: frozen plasma, platelets, and red cells. For these, PRT 29
utilizes solvent-detergent, ultraviolet (UV) and methylene blue and nomodulatory effect of the virus.
visible light treatment for plasma; amotosalen (psoralen) and UVA ATL occurs in only 1% to 5% of infected persons following a latent
light, and riboflavin (vitamin B 2 ) and UVB and UVA light for plasma period of decades. The illness is characterized by malignant lymphocy-
and platelets; and riboflavin/UV light and S303 (a labile alkylating tosis and leukemia, lymphadenopathy, hepatomegaly, abnormal liver
compound) for whole blood or red cells. Many European countries use function test results, splenomegaly, skin lesions, bone lesions, and
PRT for platelets and plasma. Amotosalen/UVA-treated plasma and hypercalcemia. HAM/TSP occurs in approximately 2% of individuals
platelets (Intercept, Cerus Corporation) and solvent-detergent plasma infected with HTLV-1 and HTLV-2. Patients with transfusion-
(OctaPlas, OctaPharma) are FDA-approved and available in the United associated HAM/TSP develop neurologic symptoms rather more
States. Because solvent-detergent does not inactivate nonenveloped rapidly, at a median of 3.3 years after transfusion. This illness is char-
viruses, OctaPharma screens all incoming units in pools to prevent the
introduction of HAV, HEV and B19. Breakthough HEV infections have acterized by slowly progressive chronic spastic paraparesis, lower limb
been described with Intercept-treated plasma in France. weakness, urinary incontinence, impotence, sensory disturbances, low
Amotosalen/UVA (Intercept, Cerus) and riboflavin/UV (TerumoBCT) back pain, hyperreflexia, and impaired vibration sense.
have advanced furthest in investigation in North America. They provide Blood donor screening for HTLV-1 antibodies began in 1988,
significant antiviral activity against all agents for which tests are per- and more sensitive combination HTLV-1/2 assays that detect close
formed currently, human immunodeficiency virus (HIV), hepatitis B to 100% of HTLV-2 infections were introduced in 1998. The preva-
and C viruses (HBV and HCV), human T-lymphotropic virus (HTLV), lence of HTLV confirmed-positive donors decreased approximately
West Nile virus (WNV), the parasite, Trypanosoma cruzi, and cyto- 10-fold during the 1990s to the current value of 0.004%. The rate
megalovirus, but the two methods appear to differ in their inactivation is threefold higher in female compared with male donors. Incident
capacity. PRT also inactivates agents causing bacterial contamination of
platelets; inactivates white blood cells to prevent transfusion-associated infections are rare in repeat donors, an observation that has led
graft-versus-host disease; decreases formation and release of cytokines to one-time testing of donors in some European countries, but an
during storage, reducing febrile, nonhemolytic transfusion reactions; incidence of 3 per million donor years of follow up is felt by some to
and abrogates white blood cell–induced alloantibody (e.g., human be too high for adoption of this strategy in the United States. Cell-free
leukocyte antigen [HLA] antibody) formation mitigating alloimmune components such as plasma and cryoprecipitate do not transmit
platelet refractoriness. Intercept-treated plasma (as mentioned) and HTLV, and less than 30% of infected cellular components transmit.
platelets are FDA approved and available in the United States; clinical The residual risk for transfusion-associated HTLV infection using
studies on pathogen-inactivated red cells (Cerus) and whole blood contemporary serologic testing is approximately 1 per 2.4 million
(TerumoBCT) are ongoing. donations, but since the initiation of testing using these contem-
Methylene blue and visible light inactivate pathogens in plasma
by targeting nucleic acids. However, this alters fibrinogen structure. porary tests, there has not been a breakthrough HTLV infection
Because it damages cell membranes, methylene blue is not used for by transfusion. The contribution of blood-donor serologic testing
platelets or red cells. It is not effective against hepatitis A or parvovirus to this low residual risk is confounded by the effect of effective
and is not recommend for use in the treatment of thrombotic throm- leukoreduction that reduces HTLV-1 copy numbers in red blood
bocytopenic purpura. cell (RBC) concentrates by up to 6 logs, to below the infectious
Amotosalen/UVA targets nucleic acids. Platelets treated with these dose of 10 to 10 infected cells per unit (one of a number of
7
8
technologies have somewhat lower 1-hour post-transfusion corrected- arguments used in support of universal leukoreduction of blood
count counts. In clinical trials, mild and moderate bleeding frequency components).
26
is increased, but not severe bleeding complications; the time between The deferral, notification, and counseling of healthy blood donors
transfusions and the total number of platelet transfusions have not gen-
erally been different. Pulmonary toxicity similar to transfusion-related after a repeatedly reactive screening test for HTLVs has been prob-
acute lung injury (TRALI) has been reported in clinical trials and in lematic, and tens of thousands have been affected since screening
animal model experiments in which UV light has been implicated. started. The vast majority of such tests are false positive, a licensed
Previous clinical trials in red blood cells (RBCs) were halted because confirmatory test is now available and will greatly improve this
of asymptomatic immunoreactivity against the red cell neoantigens situation.
believed to be the result of treatment, and are being resumed with a
reformulated process. Preliminary reports suggest riboflavin/UV causes
functional impairment in red cells stored nearest the 42-day expiration HUMAN HERPESVIRUS INFECTIONS
Although, there have been discussions about the potential for adverse
reactions to treated products, extensive reviews of European data do
not support the additional concern. Nevertheless, initial implementa- Human herpesviruses (HHVs) are enveloped, structurally complex
tion of the Intercept platelet technology will be accompanied by Phase double-stranded DNA viruses that cause common infectious diseases.
4 studies in the United States. Primary infection is followed by lifelong carrier states and the pos-
Interest in PRT remains high because it reduces sepsis-related plate- sibility of reactivation. They are classified in three subfamilies,
let transfusion complications and will eliminate the need for complex Alphaherpesvirinae, Betaherpesvirinae, and Gammaherpesvirinae, of
testing procedures to reduce bacterial risk related to contaminated which the latter two contain the herpesviruses that are of greatest
platelets; inactivates parasites such as Babesia microti, and Plasmo- concern from a transfusion medicine standpoint. Members of the
dium falciparum; mitigates risks associated with recognized emerging Alphaherpesvirinae subfamily, herpes simplex viruses (HSVs) and
pathogens such as dengue, chikungunya, and Zika viruses; and varicella-zoster virus (VZV), are rarely, if ever, associated with
proactively decreases threats from unknown, emerging pathogens. It
should be noted that inactivation capabilities differ greatly between the transfusion-transmitted infections. Transfusion-transmitted cyto-
various technologies, and each must be evaluated for its intended use. megalovirus (CMV) is well recognized. Transmissions of Epstein-Barr
virus (EBV) and HHVs 6–8 by blood are virtually nonexistent in the
United States because of the use of primarily leukocyte-depleted
(leukoreduced) blood products.