Case studies anticoagulant

DuVall, M.D., Murphy, M.J., Ray, A.C., Reagor, J.C. (1989). Case studies on second-generation anticoagulant rodenticide toxicities in non-target species. J. Vet. Diagn. Invest. 1(1) 66-8. 

B. Superwarfarins are extremely potent and can have prolonged effects even after a single small ingestion (ie, as little as 1 mg in an adult). However, in a large study of accidental superwarfarin ingestions in children, no serious cases of anticoagulation occurred. 

In single-dose and steady-state studies in a total of 16 healthy subjects, tenoxicam 20 mg daily for 14 days had no significant effect on the anticoagulant effects of warfarin or on bleeding times. This report also mentions case studies in a small number of patients and healthy subjects, which similarly found that tenoxicam had no significant effect on the anticoagulant effects of phenprocoumon. ... 

Routledge PA, Shetty HG, White JP, Collins P (1998) Case studies in therapeutics warfarin resistance and inefficacy in a man with recurrent thromboembolism, and anticoagulant-associated priapism. Br J Clin Pharmacol 46 343-346... 

For patients who demonstrate continued neurological deterioration despite anticoagulation, local intrathrombus thrombolysis may be beneficial. In case series in which most patients received urokinase, favorable outcome with no major therapeutic morbidity has been described.In one study, 29 patients with angiogram-proven CVST were reviewed retrospectively. Of the 18 who received local urokinase, 17 recovered completely, and 1 was left with a mild neurological deficit. Heparin was given to four patients, three of whom made a complete recovery. Six presented in a comatose state with severe CVST and only supportive measures were used. It is difficult to draw conclusions from these data, as only patients with mild or moderately severe disease were selected for thrombolytic treatment. 

Anticoagulants and continuous intravenous infusion of epoprostenol are the standard treatments for primary pulmonary hypertension. However, their combined use increases the likelihood of hemorrhagic complications, as demonstrated in a retrospective study of 31 consecutive patients with primary pulmonary hypertension (mean age, 29 years, 10 men, 21 women), nine of whom had 11 bleeding episodes nine episodes were cases of alveolar hemorrhage and two patients had severe respiratory distress (9). The mean dose of epoprostenol at the time of the first bleeding episode was 89 ng/kg/minute. More of the patients who had a bleeding episode died (67% versus 41%). 

In one case the concomitant use of P. ginseng and warfarin resulted in loss of anticoagulant activity (17). However, in an open, crossover, randomized study in 12 healthy men ginseng did not affect the pharmacokinetics or pharmacodynamics of. S -warfarin or 1 -warfarin (18). 

In contrast to heparin, coumarins are secreted into the breast milk, but it has long been known that prothrombin activity in the plasma of neonates whose mothers take coumarins is not significantly reduced (88-90) and that warfarin does not have anticoagulant effects in breast-fed infants when given to nursing mothers (89,91). These conclusions are subject to the reservation that in some of the studies the dose of anticoagulant was low (89). Acenocoumarol-treated breastfeeding mothers can as a rule safely breastfeed their infants (92,93) nevertheless, it is prudent to check the infant s prothrombin time in such cases. 

In a prospective, case-control study, designed to determine causes of INRs over 6.0 in an outpatient anticoagulant unit, there was a clear dose-dependent association between the use of paracetamol (acetaminophen) and having an INR greater than 6.0 (212). The authors studied 93 patients with INRs over 6.0 (cases) and 196 patients with INRs of 1.7-3.3 (controls) during warfarin therapy. The likelihood of an INR greater than 6.0 increased from an odds ratio of 3.5 for doses of 2275 549 mg per week, to 6.9 for doses of 4550-9099 mg per week, to a 10-fold increase at a dose of over 9100 mg per week. 

Animal studies and case reports have suggested that recombinant factor Vila should reduce the INR in patients taking oral anticoagulants and also has a hemostatic effect (8). 

Neither patient was taking NSAIDs, aspirin, or anticoagulants. Catheters were removed immediately on diagnosis of hematoma formation. There was no neurological or sympathetic fiber damage to the upper limb in either patient, as tested by electroneuromyography and sympathetic skin response. Remission in both cases occurred within 1 year. There has been one previous report of prolonged Homer s syndrome in the absence of any obvious technical comphcation (67). Further studies into the use of interscalene catheters are needed to assess their propensity to cause this rare comphcation. 

However, in a case-control study of the risk factors for excessive warfarin anticoagulation the investigators studied 289 patients prospectively, 93 with an International Normalized Ratio (INR) over 6.0 and 196 with an INR of 1.7-3.3 during warfarin therapy (125). Paracetamol intake was independently associated with a high INR and the effect was dose-related. At a dosage of about 2-4 g/week the adjusted odds ratio (OR) for having an INR over 6 was 3.5 (95% Cl = 1.2, 10) compared with no intake of paracetamol. At an intake of 4-9 g/week the adjusted OR was 6.9 (95% Cl = 2.2, 22), and at an intake over 10 g/week the OR was 10 (95% Cl = 2.6, 38). 

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