Letters to the Editor - September 1, 1999 - American Academy of Family Physicians

Letters to the Editor

The Potential Postfertilization Effect with Use of the IUD

TO THE EDITOR: Dr. Canavan's article on the appropriate use of the intrauterine device (IUD)¹ may have misled physicians and, indirectly, their female patients. In the article, Dr. Canavan stated, "It is important for the patient to understand that the IUD does not appear to be an abortifacient but, rather, prevents conception."¹ Of interest, he cited studies that have been interpreted as not supporting his premise.²

In addition, Dr. Canavan said, "women who use IUDs have fewer ectopic pregnancies than noncontraceptive-using control subjects."¹ If, as he asserts, the exclusive action of the IUD is to prevent fertilization (and then there would be no possible postfertilization effect), then any reduction in the percentage of intrauterine pregnancies should be matched by an equal reduction in the percentage of ectopic pregnancies. However, several studies that were not mentioned by Dr. Canavan have shown an excess risk of ectopic pregnancy versus intrauterine pregnancy among patients who use IUDs.^3-6

Dr. Canavan's failure to discuss these studies is critically important. Why? Because the results of these studies, which clearly show an increased risk of ectopic pregnancy, can only be explained by greater success in preventing implantation than in blocking fertilization and/or by excess ectopic pregnancies caused by the IUD. Both possible explanations represent postfertilization effects; the mechanism that Dr. Canavan feels is "important for the patient to understand" does not occur.¹

In a systematic review² of the mechanisms of action of the IUD, published in 1997 in the American Journal of Obstetrics and Gynecology, Dr. Spinnato wrote, "Several important conclusions can be drawn from the available literature regarding the mechanism of action in IUDs: (1) The available evidence supports a continued significant role for a postfertilization mechanism of action of IUDs. (2) There is little compelling evidence to suggest that . . . IUDs reliably eliminate the likelihood of fertilization." Dr. Spinnato concluded, "the analysis of the evidence strongly suggests that the contraceptive effectiveness of [IUDs] is achieved by both a prefertilization spermicidal action and a postfertilization inhibition of uterine implantation."²

It seems obvious that, in order to accurately reflect the medical literature, complete and accurate informed consent about the use of IUDs should include explanation of the possible postfertilization action of the IUD. This information would be especially important for patients with a moral objection to this effect. Because it would be difficult to predict which patients might object, the possible effect should be disclosed to all patients. Therefore, any patient education handout that lacks information on this potential effect represents, at the very least, a failure to provide the patient with complete informed consent. If the potential effect violates the moral requirements of a woman and she is not informed of the possibility, then this failure of disclosure seriously jeopardizes her autonomy. Further, I believe that conscious withholding of such information constitutes unethical deception.

Unfortunately, the patient education handout that was published with Dr. Canavan's article is incomplete, inaccurate and potentially misleading when it says, "The IUD prevents sperm from joining with an egg."¹ Even if Dr. Canavan rejects Dr. Spinnato's conclusions, I feel that Dr. Canavan has failed the readers of American Family Physician. Furthermore, AFP was potentially remiss in not letting its readers and their patients (via the patient education handout) know of the potential postfertilization effect of the IUD. Hopefully, the handout will be revised to sensitively and accurately address the potential postfertilization effect of the IUD, which is recognized in the medical literature but not discussed in Dr. Canavan's article.

WALTER L. LARIMORE, M.D.
825 E. Oak St.
Kissimmee, FL 34744

REFERENCES

Canavan TP. Appropriate use of the intrauterine device. Am Fam Physician 1998;58:2077-88.

Spinnato JA 2d. Mechanism of action of intrauterine contraceptive devices and its relation to informed consent. Am J Obstet Gynecol 1997; 176:503-6.

Ory HW. Ectopic pregnancy and intrauterine contraceptive devices: new perspectives. The Women's Health Study. Obstet Gynecol 1981;57:137-44.

Marchbanks PA, Annegers JF, Coulam CB, Strathy JH, Kurland LT. Risk factors for ectopic pregnancy. A population-based study. JAMA 1988;259:1823-7.

UK Family Planning Research Network. Pregnancy outcome associated with the use of IUDs. Br J Fam Plann 1989;15:7-10.

Rossing MA, Daling JR, Voigt LF, Stergachis AS, Weiss NS. Current use of an intrauterine device and risk of tubal pregnancy. Epidemiology 1993; 4:252-8.

IN REPLY: I am pleased to respond to Dr. Larimore's letter, as I am very sensitive to his concerns about the mechanisms of action of the intrauterine device (IUD). A large volume of data exists on the mechanisms of action of the IUD. However, after weighing the evidence, I felt that the preponderance of data supports the conclusion that the IUD works by preventing fertilization. Dr. Larimore's evaluation of similar data with an alternative conclusion clearly shows that the data are open to different interpretations. A study with absolutely irrefutable evidence and unquestionable statistical power is presently unavailable and is unlikely to become available.

Dr. Larimore asserts that, "any reduction in the percentage of intrauterine pregnancies should be matched by an equal reduction in the percentage of ectopic pregnancies," and discusses several studies that have found an increase in the ratio of ectopic pregnancies to intrauterine pregnancies in IUD users. These studies are unreliable. They present data on IUDs that are not available in the United States. The IUD that is used in the United States and discussed in my article is the TCu 380 (ParaGard), which may act differently than other IUDs because of its high copper content.

Moreover, no attempt was made in these studies to compensate for the age-related increase in ectopic pregnancies. The study findings may be affected by sample bias because other risk factors for ectopic pregnancy were not known, such as vaginal douching, cigarette smoking and number of sexual partners.¹ Also, the number of pregnancies in patients using an IUD is so low that statistical power is poor. Although the Marchbanks study¹ reported an 11.9 percent relative risk for ectopic pregnancy in IUD users, the 95 percent confidence interval was 2.3 to 62.0 percent.

In the Marchbanks study,¹ an increased risk of ectopic pregnancy with current use of an IUD was noted, but the researchers admitted that "any condition that prevents or retards migration of the fertilized ovum to the uterus could predispose a woman to ectopic gestation." A study by Cramer and associates² found that patients who have used an IUD in the past have an increased rate of tubal infertility, which suggests that tubal function is affected by the IUD through an inflammatory or infectious etiology. Because these factors are both associated with ectopic pregnancy, the increased ratio of ectopic pregnancies reported in some studies may reflect these effects.

Sivin³ found that the rate of pregnancy (and the rate of ectopic pregnancy) varied inversely with the copper surface area of the IUD. These findings would support the dose-related spermicidal effect of copper. If we assume that an implantation effect is related to the presence of a foreign body, it would be highly unlikely that increasing the copper content of the IUD would decrease the number of pregnancy failures and ectopic pregnancies.

Dr. Spinnato's article,⁴ quoted by Dr. Larimore, was published after my article was written; time did not permit me the opportunity to present his opinions. Dr. Spinnato repeatedly points out the limited value of available clinical trials but leaves out numerous studies that contradict an implantation effect of IUDs. Sivin reviewed this same information and their data, which showed strong support for an exclusive contraceptive effect.⁵

It is often difficult and, sometimes, harmful to present to a patient all of the extremely rare risks of any device or procedure. The possibility that the IUD may cause an implantation failure seems remote enough to make it unreasonable and inconsistent with present standards to place it on patient information material. Many medical procedures carry severe risks that are not disclosed to the patient because the risks are so remote. Patients who seek preconception counseling are rarely informed of the risk of death from childbirth, just as mothers who are considering cesarean section are not informed of the risk of death from such surgery. These discussions should come directly from the physician to those patients who wish to know about these extremely rare risks.

My opinion remains that the TCu 380 IUD represents a very safe and effective form of contraception for selected patients.

TIMOTHY P. CANAVAN, M.D., F.A.C.O.G.
Department of Family and Community Medicine
Lancaster General Hospital
555 N. Duke St.
Lancaster, PA 17604-3555

REFERENCES

Marchbanks PA, Annegers JF, Coulam CB, Strathy JH, Kurland LT. Risk factors for ectopic pregnancy. A population-based study. JAMA 1988;259:1823-7.

Cramer DW, Schiff I, Schoenbaum SC, Gibson M, Belisle S, Albrecht B, et. al. Tubal infertility and the intrauterine device. N Engl J Med 1985;312:941-7.

Sivin I. Dose and age-dependent ectopic pregnancy risks with intrauterine contraception. Obstet Gynecol 1991;78:291-8.

Spinnato JA 2d. Mechanism of action of intrauterine contraceptive devices and its relation to informed consent. Am J Obstet Gynecol 1997; 176:503-6.

Sivin I. IUDs are contraceptives, not abortifacients: a comment on research and belief. Stud Fam Plann 1989;20:355-9.

EDITOR'S NOTE: Since this issue is so emotionally charged, upon review of both sides of the argument, I believe it is prudent to acknowledge the controversy regarding whether IUDs exert an implantation/abortifacient effect. For this reason, we have modified the electronic/Web-based version of the patient education handout on IUDs that accompanied this article to acknowledge both viewpoints.

Sarcoidosis and Vasculitis

TO THE EDITOR: We read with great interest the excellent review article on sarcoidosis by Drs. Belfer and Stevens.¹ The authors reviewed the epidemiology, clinical spectrum, diagnosis, treatment and prognosis of sarcoidosis. We would like to comment on vasculitis as another possible presentation of sarcoidosis.

Vasculitis associated with sarcoidosis is rare, but it has been reported in both adults² and children.³ In adults, reported cases have included involvement of the abdominal aorta, pulmonary granulomatous angiitis, cutaneous vasculitis and granulomatous glomerulonephritis.^2,4,5 A review of the literature reveals a wide spectrum of vasculitis in childhood sarcoidosis, including leukocytoclastic vasculitis, systemic vasculitis of small- to medium-sized vessels and large-vessel vasculitis.⁶

We suggest that all patients with sarcoidosis be followed carefully for the development of vessel wall disease.

AVINASH K. SHETTY, M.D.
Pediatric Infectious Diseases
Stanford University School of Medicine
300 Pasteur Dr.
Palo Alto CA 94305-5208

ABRAHAM GEDALIA, M.D.
Louisiana State University
New Orleans, LA

REFERENCES

Belfer MH, Stevens RW. Sarcoidosis: a primary care review. Am Fam Physician 1998;58:2041-50.

Thompson JR. Vascular changes in sarcoidosis. Dis Chest 1966;50:357-61.

Gross KR, Malleson PN, Culham G, Lirenman DS, McCormick AQ, Petty RE. Vasculopathy with renal artery stenosis in a child with sarcoidosis. J Pediatr 1986;108(5 pt 1):724-6.

Maeda S, Murao S, Sugiyama T, Utaka I, Okamoto R. Generalized sarcoidosis with "sarcoid aortitis." Acta Pathol Jpn 1983;33:183-8.

Muther RS, McCarron DA, Bennett WM. Renal manifestations of sarcoidosis. Arch Intern Med 1981;141:643-5.

Shetty AK, Gedalia A. Sarcoidosis: a pediatric perspective. Clin Pediatr 1998;37:707-17.

Monitoring Warfarin Therapy

TO THE EDITOR: We appreciate the recent article by Drs. Horton and Bushwick on warfarin therapy.¹ We would like to add our comments based on a recent case we shared.

A 52-year-old man presented with severe epistaxis of two hours' duration. In 1996, he had undergone surgery to replace a congenital bicuspid aortic valve. The patient's medication included warfarin, in a dosage of 12.5 mg per day. He denied taking any other medication or herbal remedies, receiving direct trauma to the nose, or having hematuria, back pain or hematochezia. On physical examination, he was hemodynamically stable and neurologically intact, although he had bleeding from the left nostril.

Laboratory studies demonstrated a prothrombin time (PT) of 24.0, an International Normalized Ratio (INR) of 4.65 and a hemoglobin level of 150 g per L (15.0 g per dL). Local measures to control the bleeding failed. Hemostasis was ultimately achieved by placing anteroposterior packing soaked in bacitracin, oxymetazoline and 4 percent cocaine solution. Anticoagulation was reversed with vitamin K, 2.5 mg subcutaneously, and 2 U of fresh frozen plasma. By the next morning, the PT had nearly normalized to 15.0 and the INR was 1.71.

The patient declined readmission for heparin anticoagulation therapy and was followed daily in our clinic. The lowest hemoglobin level was 102 g per L (10.2 g per dL). Nasal packing was removed after five days without incident, and the patient was restarted on his usual dosage of warfarin. His response was still subtherapeutic (PT = 14.8; INR = 1.67) when he returned home five days later.

We identified two major teaching points in this case. The first was that the reversal of anticoagulation with fresh frozen plasma and vitamin K was overly aggressive, since the bleeding was controlled. Patients with prosthetic valves are at high risk for systemic embolism, necessitating higher INR values (2.5 to 3.5). By administering vitamin K and plasma, coagulopathy was corrected at the cost of increasing the risk of systemic embolism. The cost of fresh frozen plasma and the risk of infection are factors to consider. A more elegant solution, as outlined by Drs. Horton and Bushwick, would have been to hold off the warfarin therapy, follow the PT and INR values, and restart warfarin therapy at a lower dosage while watching for bleeding.

The second point is that it is essential to obtain a comprehensive history to identify the cause of the elevated INR. Our patient revealed that he had been eating 1 to 2 lb of carrots a day as a substitute for smoking. He had abruptly stopped eating the carrots one week before admission, when he had flown out to visit his daughter. This history explains the high maintenance dose of warfarin, as well as the development of a supratherapeutic INR. The patient is currently doing well taking 12.5 mg of warfarin and eating 1 lb of carrots per day.

DAVID R. BEANLAND, MAJ, DC, USA
DAVID A. DORSEY, MAJ, MC, USA
Weed Army Community Hospital
Fort Irwin, CA 92310

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Army Medical Department or the Army Service at large.

REFERENCE

Horton JD, Bushwick BM. Warfarin therapy: evolving strategies in anticoagulation. Am Fam Physician 1999;59:635-46.

IN REPLY: Bleeding complications related to anticoagulation are a source of concern. The case presented by Drs. Beanland and Dorsey refers to the key discussion points of reversal and dietary education regarding vitamin K.

In the case presented, the patient experienced epistaxis at an International Normalized Ratio (INR) of 4.65 that required treatment with nasal packing. Recent literature suggests that if rapid reversal were necessary, the administration of intravenous vitamin K, fresh frozen plasma and prothrombin complex concentrate (depending on urgency) would be indicated. Rapid reversal with intravenous vitamin K via slow infusion is safe, effective and more rapid than reversal with subcutaneous vitamin K; a minimum of six to 12 hours is necessary to evaluate responsiveness.¹ The physician should also consider that maximal response to vitamin K may not be noted until 24 to 48 hours after administration.

Administration of oral vitamin K (in doses of 2 to 4 mg) would have been an appropriate choice in this case, as the patient was hemodynamically stable and did not require either complete reversal to an INR of 1.0 or a rapid reduction to an INR of less than 1.5 (i.e., to go to surgery).¹ Based on our experience, we believe administering 2.5 mg of oral vitamin K and holding two doses of warfarin would have resulted in an INR of less than 2.0 in this patient (baseline INR of 4.65) within 48 hours (unpublished data). Our experience suggests that this patient might have had an INR in the 2.0 to 3.0 range at 24 hours with this treatment approach and would not have been resistant to the effects of warfarin administration. INRs greater than 9.0 require treatment with larger doses of oral vitamin K (5 mg) for adequate INR reduction by 24 to 48 hours.

The second point in this case relates to dietary intake of vitamin K. This patient's daily warfarin dose was significantly higher than that used in a typical patient between 50 and 59 years of age. The normal warfarin dose in this age group is approximately 5 mg per day.² When evaluating such patients, it is helpful to identify possible reasons for this finding so that adverse events can be avoided.³ In this case, initial education and evaluation would have identified the confounding dietary factors. Unfortunately, we often stress "green leafy vegetables" and minimize discussions relating to other sources of vitamin K (cabbage, cauliflower, tuna, etc.).

While there are no cases reported in the medical literature of the interaction between carrots and warfarin, carrots are a recognized source of vitamin K. The normal serving size of carrots is approximately 78 g, which contains 12 mg of vitamin K.⁴ The patient reported eating 1 to 2 lb of carrots daily or approximately 339 mg of vitamin K (339 mg vitamin K per 1 lb of carrots). This alone exceeds the total recommended daily allowance for men (80 mg) by a factor of 4. It also demonstrates that if any diet is maintained consistently, an appropriate dosage of warfarin can be identified and is safe, as long as the patient is warned to (1) avoid major dietary changes or (2) notify those responsible for warfarin monitoring when dietary changes are anticipated.

JON D. HORTON, PHARM.D.
BRUCE M. BUSHWICK, M.D.
Department of Pharmacy
York Hospital
1001 S. George St.
York, PA 17405

REFERENCES

Hirsh J, Dalen JE, Anderson DR, Poller L, Bussey H, Ansell J, et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 1998;114(5 suppl):445S-69S.

Gurwitz JH, Avorn J, Ross-Degnan D, Choodnovskiy I, Ansell J. Aging and the anticoagulant response to warfarin therapy. Ann Intern Med 1992;116:901-4.

Wells PS, Holbrook AM, Crowther NR, Hirsh J. Interactions of warfarin with drugs and food. Ann Intern Med 1994;121:676-83.

Booth SL, Pennington JA, Sadowski JA. Food sources and dietary intakes of vitamin K-1 (phylloquinone) in the American diet: data from the FDA Total Diet Study. J Am Diet Assoc 1996; 96:149-54.

Send letters to Jay Siwek, M.D., Editor, American Family Physician, 8880 Ward Pkwy., Kansas City, MO 64114; fax: 816-333-0303; e-mail: afplet@aafp.org. Please include your complete address, telephone number and fax number. Letters should be double-spaced, fewer than 500 words and limited to one table or figure and six references. Please submit a word count. Letters submitted for publication in AFP must not be submitted to any other publication. Possible conflicts of interest must be disclosed at time of submission. Submission of a letter constitutes transfer of copyright to the American Academy of Family Physicians. The editors may edit letters to meet style and space requirements.

The editors of AFP welcome input concerning topics of current medical interest and feedback in response to articles and other material published in AFP. Send letters to Jay Siwek, M.D., Editor, American Family Physician, 8880 Ward Pkwy., Kansas City, MO 64114; fax: 816-333-0303; e-mail: afplet@aafp.org. Please include your complete address, telephone number and fax number. Letters should be double-spaced, fewer than 500 words and limited to one table or figure and six references. Letters submitted for publication in AFP must not be submitted to any other publication. Letters pertaining to AFP subject matter must be received within two months of publication. Any financial associations or other possible conflicts of interest must be disclosed at time of submission. Submission of a letter constitutes transfer of copyright to the American Academy of Family Physicians. The editors reserve the right to edit correspondence to meet style and space requirements.

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