warfarin and Hypothyroidism

Whether patients with atrial fibrillation (AF) and thyroid disease are clinically distinct from those with AF and no thyroid disease is unknown. Furthermore, the effectiveness of anticoagulation for prevention of AF-related thromboembolic events in patients with thyroid disease has not been adequately studied. Patients enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation, which compared apixaban with warfarin in patients with AF (n = 18,201), were categorized by thyroid disease history at randomization (hypothyroidism, hyperthyroidism, and no thyroid disease). Adjusted hazard ratios derived from Cox models were used to compare outcomes by thyroid disease history. Associations between randomized treatment and outcomes by thyroid disease history were examined using Cox models with interaction terms. A total of 18,021/18,201 (99%) patients had available thyroid disease history at randomization: 1,656 (9%) had hypothyroidism, 321 (2%) had hyperthyroidism, and 16,044 (89%) had no thyroid disease. When compared with those without a history of thyroid disease, patients with hypo- or hyperthyroidism were more likely to be female (60.4% vs 32.1%; 52.0% vs 32.1%; both p <0.0001). Patients with hypothyroidism were older (73 vs 70 years, p <0.0001) and more likely to have had previous falls (8.7% vs 4.3%, p <0.0001). There was no difference in clinical outcomes by thyroid disease history. The benefit of apixaban compared with warfarin was similar regardless of thyroid disease history (interaction p >0.10). In conclusion, despite differences in baseline characteristics of patients with and without thyroid disease, their clinical outcomes were similar. The benefit of apixban compared with warfarin was preserved regardless of thyroid disease history.

Topics: Age Distribution; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comorbidity; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Proportional Hazards Models; Pyrazoles; Pyridones; Sex Distribution; Stroke; Treatment Outcome; Warfarin

Hypothyroidism is a procoagulant state; hypothyroid females have greater risk of DVT than hypothyroid males. We present a case of primary hypothyroidism who presented with euvolemic hyponatremia and DVT that required thyroxine replacement and correction of hyponatremia. This highlights that hypothyroidism can present as euvolemic hyponatremia and deep vein thrombosis.

Topics: Diagnosis, Differential; Female; Fibrinolytic Agents; Heparin; Humans; Hyponatremia; Hypothyroidism; Leg; Lost to Follow-Up; Middle Aged; Thyroxine; Treatment Outcome; Ultrasonography, Doppler, Duplex; Venous Thrombosis; Warfarin

Unlike hyperthyroidism, few data exist regarding the impact of hypothyroidism on systemic anticoagulation with coumarin derivates. Therefore, we evaluated a potential impact of short-term hypothyroid conditions on systemic anticoagulation with coumarin derivates in patients after complete thyroidectomy for treatment of thyroid cancer. Fifteen patients with differentiated thyroid cancers and continued international normalized ratio (INR)-adjusted therapy with coumarin derivates were included in this retrospective analysis. A total of 88 laboratory tests was analyzed. INR values were compared between thyroid-stimulating hormone (TSH) values greater than 10 and 10 mU/L or less. An INR value of less than 2.0 was defined as being out of the therapeutic range. Analysis of significant differences between categorized TSH and INR values were performed by using X(2) analysis, correlation of continuous TSH and INR values by using the Pearson's analysis. When TSH was greater than 10 mU/L (n = 50) the INR value was less than 2.0 in 76.0% (n = 38) cases. In contrast, the INR value was less than 2.0 in only 21.1% (n = 8; p < 0.0001) of patients with TSH of 10 mU/L or less (n = 38). Correlation between continuous TSH and INR values was r = -0.589 (p < 0.0001). Based on the results of the present study, it seems to be necessary to monitor the anticoagulation parameters more often in patients with hypothyroidism and either to correct the hypothyroid state, or in cases of desired hypothyroid conditions, to adjust the therapy with coumarin derivates in order to ensure a sufficient anticoagulation.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Coumarins; Female; Humans; Hypothyroidism; Male; Middle Aged; Retrospective Studies; Thyroid Neoplasms; Thyroidectomy; Thyrotropin; Venous Thrombosis; Warfarin

The optimal dose of warfarin varies among individuals, and the prediction of a maintenance dose is difficult. Ethnicity has been reported to influence warfarin dosing.. To quantitate the influence of ethnicity on warfarin dose requirement.. We conducted a retrospective cohort study at a university anticoagulation clinic to evaluate the influence of ethnicity on warfarin dose. Inclusion criteria included age > or = 18 years, target international normalized ratio (INR) 2-3, and warfarin management within the clinic for > or = 3 months with a minimum of 5 clinic visits. We collected clinical and demographic data including age, gender, weight, ethnicity, disease states, concomitant medications, indication, weekly warfarin dosage, and INR. To assess potential confounders, multivariate, repeated-measures regression analysis was used to identify and adjust for variables that may influence the maintenance dose of warfarin.. Of the 345 patients who met the inclusion criteria, 27% were Asian American, 6% Hispanic, 54% white, and 14% African American. The adjusted mean (95% CI) weekly warfarin doses for patients with an INR goal of 2 to 3 were Asian Americans 24 mg (21 to 27), Hispanics 31 mg (25 to 37), whites 36 mg (34 to 39), and African Americans 43 mg (39 to 47) (p < 0.001). Additional factors found to influence warfarin dose requirement included age, weight, concomitant use of amiodarone, and diagnosis of venous thromboembolism.. Warfarin dose requirements vary across ethnic groups even when adjusted for confounding factors, suggesting that genetic variation contributes to interpatient variability.

Topics: Aged; Asian People; Atrial Fibrillation; Black or African American; Cohort Studies; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Hispanic or Latino; Humans; Hypothyroidism; International Normalized Ratio; Ischemic Attack, Transient; Male; Middle Aged; Retrospective Studies; Stroke Volume; Venous Thrombosis; Ventricular Function, Left; Warfarin; White People

Topics: Aged; Anemia; Anticoagulants; Antifungal Agents; Atrial Fibrillation; Drug Interactions; Ecchymosis; Female; Hemorrhage; Humans; Hypothyroidism; Melena; Miconazole; Stomatitis; Thyroxine; Warfarin

Radiation-induced optic neuropathy is a rare complication (prevalence less than 1%) following radiotherapy of the sellar region. However, the vasculopathy in Cushing's disease predisposes to radiation-induced injury. We report the case of a 24-year-old man with Cushing's disease since he was 16. The hormonal study including bilateral inferior petrosal sinus catheterization diagnosed a pituitary right lesion, but imagiology was always negative. He underwent a transsphenoidal microadenomectomy and the pathological study showed the presence of corticotrophic hyperplasia but no adenoma. Secondary hypothyroidism and hypogonadism as well as permanent diabetes insipidus were diagnosed and because the patient was not cured he underwent a second transsphenoidal total hypophysectomy. After that and because he was still hypercortisolemic, pituitary external irradiation was given in a total dose of 6000 rad. Six months later he developed progressive bilateral visual loss. Cerebral MR revealed focal enhancement of the enlarged optic nerves and chiasm, associated with demyelination areas of the posterior visual pathways. Treatment was tried first with high doses of corticosteroids and later with anticoagulants-heparin EV. 1000 U/h during 7 days followed by warfarin, but unsuccessfully, probably because the patient was already amaurotic at the beginning of the last treatment.

Topics: Adolescent; Adult; Anticoagulants; Combined Modality Therapy; Cushing Syndrome; Glucocorticoids; Heparin; Humans; Hypogonadism; Hypophysectomy; Hypothyroidism; Male; Optic Nerve Diseases; Radiotherapy; Treatment Failure; Warfarin

Although our observation is not the first case of reduced PT response to oral anticoagulants associated with hypothyroidism, it is the only such interaction reported since 1963, and the first case involving warfarin therapy in a human being. We submit this case as a reminder of a potentially forgotten interaction, and to stress the importance of close monitoring in patients receiving warfarin therapy who have concomitant changes in thyroid function.

Topics: Administration, Oral; Female; Humans; Hypothyroidism; Middle Aged; Prothrombin Time; Thyroid Function Tests; Thyroxine; Time Factors; Warfarin

The influence of the thyroid function on the metabolic rate of prothrombin, factor VII, and X was studied in the rat. Disappearance rates of the three coagulation factors were measured after synthesis had been blocked with appropriate doses of warfarin, and reappearance rates were assessed upon induction of synthesis by high doses of vitamin K1 injected into rats displaying coumarin induced hypocoagulability. No statistically significant difference in the disappearance and production rates of any of the factors could be found between normal euthyroid rats and thyroxin-treated hypothyroid rats proven to be euthyroid. The differences between the two euthyroid groups and the hypothyroid group were highly significant, however: hypothyroidism results in an approximately 50% decrease of the metabolic rates of the three coagulation factors under study. The reappearance of the three factors, under euthyroid as well as hypothyroid conditions, showed a biphasic pattern: in the first two hours after vitamin K1 administration to warfarin treated rats, a rapid reappearance was observed, to the same extent for all three factors, in hypo- as well as euthyroid rats. This finding suggests that in vitamin K1 deficiency an intracellular accumulation of precursor proteins (PIVKAs) occurs, which after rapid conversion into biologically active coagulation factors by vitamin K1 are shed into circulation. The subsequent phase of reappearance is much slower and reflects the synthesis rate of coagulation enzymes. It is characteristic for each factor and clearly slower in hypothyroid rats than in euthyroid rats. From this an influence of thyroid function on the synthesis rate of the protein moiety of coagulation factors can be inferred. An apparent difference between disappearance and reappearance rate of the coagulation factors in the plasma, particularly pronounced for factors VII and X in euthyroid rats, could theoretically be explained as the consequence of the model used for derivation of these rates.

Topics: Animals; Factor VII; Factor X; Hypothyroidism; Male; Prothrombin; Rats; Thyroid Gland; Vitamin K 1; Warfarin

Topics: Animals; Blood Proteins; Body Weight; Half-Life; Hypothyroidism; Male; Protein Binding; Prothrombin Time; Rats; Rats, Inbred Strains; Serum Albumin; Thyroidectomy; Time Factors; Warfarin

Topics: Anticoagulants; Asphyxia Neonatorum; Female; Hemorrhage; Humans; Hypothyroidism; Iatrogenic Disease; Infant, Newborn; Infant, Newborn, Diseases; Iodides; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Toxicology; Warfarin

Topics: Animals; Coumarins; Hyperthyroidism; Hypothyroidism; Prothrombin; Prothrombin Time; Rats; Warfarin