- Malaria Parasite Clearance by the Human Spleen
- Random Donor Platelets Often Effective in NAIT
- Unconscious Mind Helps with Complex Decisions
- IV Equipment Without PVC and DEHP
- Clinicians Role in Developing Off-Label Drug Therapies
- Recombinant Factor VIIa Off-Label Use: Use Caution
- Support for Anti-Oxidant Therapy
- FDA Alliance: An Advocacy Voice
- Drug Studies and the Promotional Material Not Always in Sync
MALARIA PARASITE CLEARANCE BY THE HUMAN SPLEEN
It is known that in malaria infections “the spleen serves the useful function of riding the bloodstream of parasitized (harmed) cells and if it (the spleen) is removed, parasitemia levels (level of malaria parasites in the blood) are apt to rise and symptoms worsen.” But how the spleen accomplishes this is not well understood and direct study of the spleen has been difficult for a number of reasons. Some include the sensitivity of the spleen in vivo (inside the body) to probing and biopsy and the difficulty of demonstrating continued splenic function ex vivo (outside the body). Buffet and colleagues solved this problem. They developed an experimental system to study the spleen ex vivo and track the clearance of parasite-infected red blood cells. The article reminds all without a spleen to avoid exposure to malaria but, equally important, the system developed as part of this research may make possible studies that will detail splenic function and better characterize the risks attendant on splenectomy.
Buffet, P.A., et al, “Ex Vivo Perfusion of Human Spleens Maintains Clearing and Processing Functions”, Blood, vol. 107, no. 9, May 1, 2006, pp. 3745 – 3752.
Mohandas, N., “Of Mice and Men: The Voracious Spleen”, Blood, Vol. 107, no. 9, May 1, 2006, p. 3426.
RANDOM DONOR PLATELETS OFTEN EFFECTIVE IN NAIT
A life-threatening emergency exists when a 1- to 2-day-old newborn presents with severe thrombocytopenia due to neonatal alloimmune thrombocytopenia (NAIT). Because of the high incidence of an intracranial hemorrhage (ICH 11% - 21%) in this patient population, treatment to rapidly increase the platelet count is imperative. This has been difficult for a number of reasons including the relatively slow rise in platelets after IVIG, the delay in preparing the mother’s platelets (assuming her health permits), and the difficulty of obtaining matched platelets for transfusion. V. Kiefer and colleagues report in a recent issue of Blood “that random donor platelets are often effective (24 of 27 cases) in severely thrombocytopenic neonates unexpectedly affected by alloimmune thrombocytopenia (AIT).” This work confirms a recent study conducted by J. Bussel and his group “which demonstrated that 11 of 18 random donor platelet transfusions in HPA-1a incompatibility increased the platelet count more than 20 X 109 / L.
Bussel, J.B., “Clinical and Diagnostic Comparison of Neonatal Alloimmune Thrombocytopenia to Non-Immune cases of Thrombocytopenia”, Pediatric Blood Cancer, 2005;45:176-183.
Bussel, J.B., “When are Platelets Just Platelets: Comment on Kiefel et al”, Blood, vol. 107, no. 9, May 1, 2006, pp. 3426 – 3427.
Kiefer, V., et.al., “Antigen-Positive Platelet Transfusion in Neonatal Alloimmune Thrombocytopenia (NAIT)”, Blood, vol. 107, no. 9, May 1, 2006, pp. 3761 – 3763.
UNCONSCIOUS MIND HELPS WITH COMPLEX DECISIONS
The question of the role of the conscious versus the unconscious mind in decision making was addressed by researchers at the University of Amsterdam. They report (Science, February 17, 2006) “that conscious thought may be best for simple decisions. But when things get more complex, two minds—conscious and unconscious—could be better than one.” The capacity of the unconscious mind is far greater than the capacity of the conscious mind; it can accommodate much more information. Getting away from a problem, “sleeping on it”, may permit the unconscious to run through all the options and formulate a gut feeling or “hunch” that improves the decision making process in complex situations. They studied both hypothetical and actual consumer purchases and found similar results in each type of situation. The authors suggest that their conclusions may extend “to other types of choices—political, managerial, or otherwise,” but caution that further research would be needed to ensure that there is no fundamental difference between comparison shopping for consumer items and determining one’s political affiliation—or other life choices.
Harvard Women’s Health Watch, May 2006, pp. 6 – 7.
IV EQUIPMENT WITHOUT PVC AND DEHP
The potential toxicity of PVC (polyvinyl chloride) and DEHP (diethylhexyl phthalate) used in the manufacture of the materials to make intravenous bags and tubes has been a concern for some time. These compounds leach from medical equipment into the blood stream of patients. Studies have shown that DEHP, for instance, can disrupt the body’s hormone system. Recently the two largest manufacturers of this equipment (Baxter Healthcare and Hospira) announced lines of bags and tubes without materials containing PVC or DEHP. These new products are a major equipment improvement and mark the first major overhaul of IV gear in more than 30 years.
Waldman, P., “Intravenous Bags, Tubes Redesigned for Safety”, Wall Street Journal, April 19, 2006, p. D2.
CLINICIANS ROLE IN DEVELOPING OFF-LABEL DRUG THERAPIES
A Boston group identifies a significant role for clinicians in the discovery of off-label drug use. New drug therapies come to market after FDA approval for use in specific treatment situations for which they have been tested in clinical trials. Once approved, clinicians have wide latitude to treat patients with newly approved drugs and biologics in what are referred to as off-label use—situations in which the drug or biologic has not been tested in clinical trials. The clinician must “be well informed about the product, base off-label use on firm scientific rationale and on sound medical evidence, and maintain records of the product’s use and effects.” This study reports on 143 new applications developed for the 29 new drugs considered and approved by the FDA during 1998. Eighty-two of the 143 drug therapy innovations were discovered by practicing clinicians through field discovery.
DeMonaco, H.J., et.al., “The Major Role of Clinicians in the Discovery of Off-Label Drug Therapies”, Pharmacotherapy, 2006;26(3):323-332.
RECOMBINANT FACTOR VIIa OFF-LABEL USE: USE CAUTION
Off-label use of drugs and biologics is important in developing new treatment options for many disease conditions. However, publications of the off-label use of recombinant factor VIIa (RFVIIa) raises some concern for the off-label use of this treatment. RFVIIa “is FDA approved for controlling bleeding associated with inhibitors in patients with hemophilia A or B. It is also approved for treatment of patients with congenital factor VII deficiency.” Case reports and several clinical trials have reported the use of RFVIIa to treat a variety of hemostastic abnormalities. “These publications have created an impression that RFVIIa can function as a universal hemostatic agent, and that it is an appropriate supplement for treating the bleeding patient, regardless of the hemorrhagic etiology.” A randomized placebo-control trial of RFVIIa to treat hemorrhagic strokes published in the NEJM last year was followed, on December 5, 2005, by Novo Nordisk, the manufacturer, issuing a safety alert for the use of RFVIIa in non-hemophilia patients. This report noted that clotting events were increased in patients randomized to receive RFVIIa. “Most of these reported events were arterial, and notably, most were observed in patients who received the highest dose of RFVIIa.” The O'Connell study examined a total of 185 thromboembolic events reported to the FDA through the Adverse Event Reporting System (AERS) from March 25, 1999 through December 31, 2004. The vast majority of these events were associated with off-label use.
Abrams, C., “The Dark Side of Recombinant factor VIIIa”, The Hematologist: ASH News and Reports”, vol. 3, issue 3, May/June 2006, p. 8.
Mayer, S.A., et al, Recombinant Activated Factor VII for Acute Intracerebral hemorrhage”, NEJM, 2005;352:777-785.
O’Connell, K.A., Wood, J.J., Wise, R.P., et al, “Thromboembolic Adverse Events After Use of Recombinant Human Coagulation Factor VIIa”, JAMA, 2006;295:293-298.
SUPPORT FOR ANTI-OXIDANT THERAPY
Recent work strengthens the connection between oxidants and aging by showing that hematopoietic (blood) stem cells (HSCs) respond to oxidants by activating a pathway leading to stem cell exhaustion and bone marrow failure. Liu and Finkel summarize the work of a K. Ito’s group comprised of researchers affiliated with several different centers in Japan. “Whatever the exact sequence of events, it appears that oxidants may contribute to the aging of adult HSCs not as random and nonspecific damaging agents as was originally hypothesized in the free radical theory—but instead, through the redox-dependent activation of a specific MAPK pathway.” The work raises more questions than it answers but just maybe, “the late-night infomercials are on to something.”
Ito, K., et al, “Reactive Oxygen Species Act Through p38 MAPK to Limit the Lifespan of Hematopoietic Stem Cells”, Nature Medicine, vol. 12, no. 4, April 2006, pp. 446-451.
Liu, J, and Finkel, T., “Stem Cell Aging: What Bleach Can Teach”, Nature Medicine, vol. 12, no. 4, April 20206, pp. 383-384.
(Note: We have received letters from people who feel that taking anti-oxidants or reducing oxidative stress in other ways helped increase their platelet count.)
FDA ALLIANCE: AN ADVOCACY VOICE
The FDA has a new friend. A newly-created Maryland non-profit corporation has established the FDA Alliance. This alliance will advocate for increased appropriations, more manpower, and enhanced personnel recruitment for the FDA. This organization fills a gap. While many parts of the government “benefit from independent, private organizations that educate and advocate on their behalf” the FDA did not enjoy support from private sector initiatives. You can learn more about this organization at: www.strengthenFDA.org
DRUG STUDIES AND THE PROMOTIONAL MATERIAL NOT ALWAYS IN SYNC
Three out of 20 promotional brochures developed by pharmaceutical companies to promote their products to physicians were found in a recent study to contain data different from the original study on the effects of the drug. A group at the University of North Texas Health Science Center studied 20 brochures representing 20 different medications. Two reviewers compared the content of each brochure with the data presented in the original study. The group rated 15 of the 20 studies valid. Despite the fact that for the three brochures in which the differences between the data in the brochures and the data in the original study were small, the authors recommended doctors review original studies prior to prescribing new medications.
Hematology and Oncology News and Issues, April 2006, p. 19.