- Splenectomy: The Long Run
- Disclosing New Data for Medications and Treatments
- Hemophilia Drug Lowers Risk of Death for Bleeding Stroke
- Splenectomized Patients at Greater Risk of Contracting Babesiosis
- Scar Prevention Polymers May Help Those with Inflammatory Conditions
- Take Charge of Your Care: Some Suggestions
SPLENECTOMY: THE LONG RUN
Two recent articles in the journal “Blood” address several long term aspects of splenectomy outcome for ITP. The first article examines the outcome for ITP patients refractory to splenectomy. The second addresses three questions: How durable are the responses to splenectomy? Is it possible to predict who will respond to splenectomy? What is the frequency of surgical complications with splenectomy as a treatment for ITP?
The first article by Robert McMillan and Carol Durette reports on long-term follow-up of 105 patients who failed splenectomy and required additional therapy. Seventy-five of these patients attained a stable partial (platelet count 30,000/mm3) or complete (normal platelet count) remission. Of these 75 patients, 51 maintained their remission after stopping therapy while 24 required continued treatment. Thirty of the 105 patients in the study remained unresponsive to treatment. Thirty-one of the 105 patients died 17 due to ITP (11 – bleeding, 6 – therapy complications) and 14 of unrelated causes. Five of these deaths were from the group of 51 who maintained remission after stopping therapy, 8 from the group of 24 who achieved remission but required continued treatment, and 18 from the 30 patients who remained unresponsive to treatments. The authors conclude “that most refractory ITP patients attain a stable remission although, on average, this occurs slowly. However, a subpopulation with severe, resistant disease has significant morbidity and mortality.”
McMillan, Robert and Durette, Carol, “The Long Term Outcome of Adult Chronic ITP Patients Who Fail Splenectomy,” Blood, August 2004, 104:956-960.
The second article by James George and colleagues poses three very important questions regarding the durability, predictability, and complications associated with splenectomy. The study reviewed 135 case series reporting over 6,000 splenectomized ITP patients. They report a complete response in 1731 of 2623 (66%) patients with a median follow-up of 29 months (2.4 years). This series included adults and children. In another set of case series that included only adults 456 of 707 (64%) patients were reported to have had complete remission with a median follow-up of 87 months (7.25 years). Among the variables available prior to splenectomy, age at the time of splenectomy most often correlated with response. Six case series studies used different radioisotope techniques to determine the site of platelet destruction and found that patients who had predominately splenic destruction had a better response than patients who had predominately non-splenic destruction. However 10 other case series did not support the site of platelet destruction as a good predictor of response. The authors caution that “the decision for splenectomy must be carefully balanced by consideration of the potential risks, since the rate of complications following splenectomy is relatively great. Mortality rates of 0.2% and 1.0%, with laparoscopy and open laparotomy, respectively.” The authors go on to warn that “the risks of splenectomy may be greater than described in this systematic review, since we did not evaluate long-term risks of sepsis and thrombosis.”
Kojouri, K., Vesely, S.K., Terrell, D.R., George, J.N., “Splenectomy for Adult Patients with ITP: A Systematic Review to Assess Long Term Platelet Count Responses, Prediction of Responses, and Surgical Complications,” Blood (prepublished online), June 24, 2004, DOI 10.1182/blood-2004-03-1168.
DISCLOSING NEW DATA FOR MEDICATIONS AND TREATMENTS
The July 2004 Bulletin of The National Organization for Rare Disorders (NORD) brought attention to the difficulty in updating drug labels to reflect the results of clinical trials completed after a drug has been approved by the FDA. Even if a company submits clinical trial data showing that a drug is not effective after a drug has received FDA approval, the information cannot be added to a drug’s label unless the manufacturer agrees. Triggered by recent disclosure of the ineffectiveness of some and the adverse effect of other medications, “medical societies, and especially pediatricians, are telling FDA it is unethical not to add information to drug labels if the FDA knows about it, even if the manufacturers object.”
NORD On-Line Bulletin, “Keeping Negative Clinical Trial Results Secret,” July 2004, pp2,3. http://www.rarediseases.org
HEMOPHILIA DRUG LOWERS RISK OF DEATH FOR BLEEDING STROKE
NovoSeven, a drug used to prevent hemophilia patients from bleeding to death, shows promise of lowering the risk of disability and death for victims of bleeding stroke. The drug is a clotting agent called factor VIIa, a protein that causes blood clots to form. It was administered to bleeding stroke patients at Columbia Medical Center in New York. The study was designed to test the drug’s safety and potential for reducing bleeding. The patients in the study received an intravenous infusion of the drug, in one of three doses, or a placebo. Twenty-four hour follow-up revealed that any of the three doses reduced bleeding in the brain by about half. At three month follow-up those receiving the drug were approximately 30% less likely to die or be left severely disabled (paralyzed or in a coma). Close to 70% of those receiving the placebo either died or were severely disabled. On the downside, those receiving the drug were about 6% more likely to suffer heart attacks or blood clot caused strokes. The study was funded by the manufacturer and most comments suggested more testing to determine the relative risks and benefits of the treatment.
Stein, R, “Possible Therapy for Bleeding Strokes,” The Washington Post, June 27, 2004, p. A14.
(NovoSeven has also been used off-label to help stop internal bleeding in patients with ITP)
SPLENECTOMIZED PATIENTS AT GREATER RISK OF CONTRACTING BABESIOSIS
The spleen is important in protecting humans from babesiosis, a rare tick-transmitted disease. In the United States it is found mainly in New England (especially the coastal islands) and the Great Lakes Region. It takes from one to six weeks (in some cases up to three months) for symptoms of this disease to appear. Symptoms vary widely from a mild case without visible symptoms, to more severe cases where the flu-like symptoms include tiredness, loss of appetite, fever, drenching sweats, and muscle pain that may be accompanied by nausea, anemia, and weight loss. Humans who have had a splenectomy, the elderly, and those who have had a serious disease, such as cancer or AIDS, are at a higher risk of infection. Stained blood smears are the most common diagnostic tool in conjunction with patient history. In more serious cases clindamycin and quinine are the standard treatment. Best prevention is to stay away from the New England and the Great Lakes Region between May and September. In these areas wear protective clothing and use tick repellant.
Talsky, J, “Babesiosis in Humans,” Science Education, July 30, 2003, http://www.bact.wisc.edu:8080/scienceed/stories/storyReader$115
Note: Babesiosis is a life threatening infection for splenectomized patients and for all patients when treatment is delayed. Splenectomized patients have an additional hurdle in that an important part of treatment is quinine which has been associated with (some suggest causes) low platelet counts.
SCAR PREVENTION POLYMERS MAY HELP THOSE WITH INFLAMMATORY CONDITIONS
Some promise for treating inflammatory diseases comes from an unlikely source. Treating glaucoma, a buildup of fluid that causes pressure in the eye, involves surgically implanting an artificial tube to drain the fluid. In one-third of all patients the treatment is not effective due to the formation of scar tissue that blocks the surgically implanted tube. To prevent the formation of this scar tissue, researchers turned to protein-sized polymers called dendrimers. Sugar molecules were added to the outer tips of the polymer chains. These sugar molecules were known to bind to the immune cells involved in the inflammation and the scaring. Injecting a solution containing these dendrimers into the eyes of rabbits that had undergone glaucoma surgery reduced the scaring significantly. The success rate of the surgery increased from 30% to 80%. Donald Tomalia, of Dendritic Nano Technologies, suspects that this strategy could be important in developing therapies for inflammatory diseases like rheumatoid arthritis.
Goho, A, “Velcro Therapy,” Science News, July 31, 2004, vol 166, p70.
TAKE CHARGE OF YOUR CARE: SOME SUGGESTIONS
Gone are the days of going to the hospital and relinquishing full control of your care to the hospital staff of nurses, physicians and administrators. For example, in 2002 approximately 500 hospitals and health care facilities across the country reported nearly 200,000 mistakes in prescribing and dispensing medicine. In February new FDA regulations required bar codes on commonly used prescription drugs. About 2% of hospitals have such a system in place today. (The FDA has given institutions 2 years to implement this change.) In the mean time we suggest you know the purpose and appearance of all medications and monitor your care closely.
Another alarming statistic is the fact that 2 million patients acquire an infection while in the hospital each year. The best that you can do in this area is to be sure you as the patient as well as your caregivers and guests wash their hands at the start and the end of their visit.
Also avoid hospitals from mid-December through the end of the first week of January. In teaching hospitals avoid the period mid-June through the middle of July when new residents begin training.
Simon, N., “Good Medicine,” Time Bonus Section, September 2004.