Potentiation of Oral Anticoagulant Effect by L-thyroxine

Abstract

treatment of congenital dislocation of the knee. J Bone Joint Surg 1967;49-B:112-20. 4. Curtis BH, Fisher RL. Congenital hyperextension with anterior subluxation of the knee. J Bone Joint Surg 1969;51-A:255-69. 5. Laurence M. Genu recurvatum congenitum. J Bone Joint Surg 1967;49-B:121-34. 6. McFarlane AL. A report on four cases of congenital genu recurvatum occurring in one family. Br J Surg 1947;34:388-91. 7. Provenzano RW. Congenital dislocation of the knee. N Engl J Med 1947;236:360-2. 8. Chapple CC, Davidson DT. A study of the relationship between fetal position and certain congenital deformities. J Pediatr 1941; 18:483-93. 9. Browne D. Congenital deformities of mechanical origin. Arch Dis Child 1955;30:37-41. 10. Boorstein SW. Congenital backward dislocation of the knee. Am J Dis Child 1929;38:107-11. 11. Vaughn VC, McKay RJ, eds. Nelson's textbook of pediatrics. Philadelphia : WB Saunders, 1979. 12. Middleton DS. The pathology of congenital genu recurvatum. Br J Surg 1935;22:696-702. 13. Carlson DH, O'Connor J. Congenital dislocation of the knee. AJR 1976:127:465-8. 14. Rao BS, Rao BS, Rao AS. Congenital dislocation of the knee joint. Int Surg 1975;60:32-3. 15. Larsen LJ, Schottstaedt ER, Bost FC. Multiple congenital dislocations associated with characteristic facial abnormality. J Pediatr 1950;37:574-81. 16. Weiss SM, Brooks DB. A simplified method of splinting for congenital dislocation of the knee. Clin Orthop CONCURRENT USE of other medications maỹ~O NCURRENT USE of other medications mayhave an effect on oral anticoagulant therapy (Table 1). We wish to bring to the attention of pediatricians a major clinical problem resulting from simultaneous administration of warfarin sodium (~oumadin~') and L-thyroxine. Case ReportA 13-year-old girl presented at The Hospital for Sick Children, Toronto, with short stature and decreasing height velocity over the previous 5 years. She had undergone total repair of a tetralogy of Fallot at the age of 5 years and was then placed on digoxin and a combination of spironolactone and hydrochlorothiazide (Aldactazide~'). At the age of 1 years, prosthetic pu~monary and aortic valves were implanted. The preoperative coagulation results were as follows: prothrombin time (PT) 11.3 seconds (controls 10-12 seconds), partial thromboplastin time (PTT) 38.5 seconds (controls 25-40 seconds), and platelet count 174,000/Al. There was no family history of a bleeding diathesis. After surgery, the child required warfarin 7.5 mg daily to maintain the PT at 1.5 to 2.0 times baseline values. She continued to take digoxin and Aldactazide but did not receive antiplatelet medication, and the platelet counts remained normai postoperatively. On this current admission 2 years postoperatively, the child's height was 120 cm (<3rd percentile), weight was 36 kg (<10th percentile), and height increment over the preceding 12 months was 2.5 cm. Heart rate was 90/minute and blood pressure 90/60. She appeared hypothyroid with coarse features, dry skin, and dry hair. The relaxation phase of her ankle reflexes...

An evaluation of the potential drug interaction between warfarin and levothyroxine

“…The hypothesized warfarinlevothyroxine interaction described in these reports may be attributable instead to influences of the drug-disease state interaction and comorbidities, rather than an actual drug-drug interaction [11,13,[15][16][17][18]. Additionally, several of the case reports provide insufficient detail for adequate evaluation of potential causation [11][12][13][14][15][16][17][18].…”

“…Other mechanistic theories include levothyroxine-induced changes in the affinity of the warfarin target vitamin Kdependent epoxide reductase [22][23][24]. The conflicting evidence substantiating a warfarin-levothyroxine interaction contributes to the lack of consensus on the clinical significance and practice management of warfarin-receiving patients who start thyroid replacement therapy with levothyroxine [11][12][13][14][15][16][17][18].…”

Possible Effect of Thyroid Function on Anticoagulant Response to Unfractionated Heparin

“…[1][2][3][4][5][6][7][8] The interaction between thyroid function and oral anticoagulation with warfarin has been well described, but no relationship between thyroid function and UFH has been documented in the literature. [9][10][11][12] Thyroid replacement (and/or hyperthyroidism) is associated with increased metabolism of vitamin K-dependent clotting factors, which in turn leads to an enhanced response to oral anticoagulation with warfarin. [9][10][11][12] I describe the case of a patient whose active hyperthyroid disease dramatically affected her UFH requirements.…”

“…[9][10][11][12] Thyroid replacement (and/or hyperthyroidism) is associated with increased metabolism of vitamin K-dependent clotting factors, which in turn leads to an enhanced response to oral anticoagulation with warfarin. [9][10][11][12] I describe the case of a patient whose active hyperthyroid disease dramatically affected her UFH requirements. However, she exhibited a diminished anticoagulant response with UFH when in an actively hyperthyroid state.…”

A Population-Based Assessment of the Drug Interaction Between Levothyroxine and Warfarin

“…Although this potential interaction was first described in animal studies more than half a century ago, 28,29 case reports and small prospective studies have done little to expand our understanding of its frequency and clinical relevance. 19,[22][23][24][25][26][30][31][32][33][34] Increases in the international normalized ratio have been observed in clinical settings after patients receiving warfarin became thyrotoxic for various reasons, including after being given levothyroxine. 30 Similarly, small prospective studies observed increases in prothrombin time of up to 26 s in participants receiving warfarin when they were also given thyroid hormone.…”