Purple toes syndrome associated with warfarin therapy in a patient with antiphospholipid syndrome

Purple toes syndrome is an extremely uncommon, nonhemorrhagic, cutaneous complication associated with warfarin therapy. It is characterized by the sudden appearance of bilateral, painful, purple lesions on the toes and sides of the feet that blanch with pressure. The syndrome usually develops 3-8 weeks after the start of warfarin therapy. A 47-year-old man with a history of purple toes syndrome that resolved after discontinuing warfarin--prescribed for a deep vein thrombosis (DVT) in his right lower leg--experienced an acute, proximal DVT in his other leg. Warfarin again was prescribed; 1 week later, purple toes syndrome developed in that extremity. Warfarin therapy again was discontinued, and intravenous unfractionated heparin was started; the patient's clinical picture indicated a possible pulmonary embolism, and laboratory analysis suggested antiphospholipid syndrome. The patient's toe pain resolved, but the purple discoloration persisted. Follow-up laboratory analysis confirmed antiphospholipid syndrome, and warfarin was restarted with close monitoring. No further complications occurred with long-term therapy. Although a rare complication of therapy, clinicians should monitor for the development of purple toes syndrome in patients taking warfarin.     

临床药师对1例下肢深静脉血栓患者应用华法林抗凝的药学监护

目的:探讨临床药师在下肢深静脉血栓患者个体化抗凝治疗方案的制订与用药监护中的工作要点。方法:参与血管外科1例下肢深静脉血栓患者华法林抗凝治疗用药方案的制订与用药监护。根据该患者HAS-BLED评分为1分,为出血低危患者,且无使用华法林禁忌证,确定使用华法林抗凝;目标国际标准化比值(INR)确定在2.0³.0之间,以2.5为宜。结果:确定符合患者特点的抗凝强度,提高其长期抗凝治疗和INR监测的依从性,使患者注意影响华法林疗效的因素。结论:抗凝药物个体化方案的参与制订及用药监护是临床药师开展药学服务工作的切入点。     

临床药师参与1例下肢深静脉血栓患者抗凝方案调整分析

摘 要 目的：探讨临床药师在抗凝药物治疗中的作用。方法: 临床药师参与1例下肢深静脉血栓患者抗凝方案的调整。药师评估了深静脉血栓的危险因素和抗凝的出血风险,出现华法林抗凝过度时提出合理的治疗建议,治疗过程中发现患者的不依从性并提供充分的用药教育。结果: 医生采纳治疗建议,INR控制在合理范围内,患者病情平稳出院。结论:临床药师参与华法林的抗凝治疗,可有效减少用药风险,提高治疗的安全性和有效性。     

孟鲁司特钠片致皮疹

1例51岁女性患者，有过敏史，因支气管哮喘，在吸入布地奈德的同时，口服孟鲁司特钠10mg／d。服药第3天，四肢出现皮疹，伴瘙瘁，立即停服孟鲁司特钠，继续使用布地奈德，给予氯雷他定10mg／d口服。3d后，皮疹减轻，1周后皮疹消退。     

Possible cross-sensitivity between sertraline and paroxetine in a panic disorder patient

Cross-sensitivity due to paroxetine and sertraline, the SSRIs, is rarely reported in the literature. We report an adverse drug reaction to paroxetine and sertraline in a patient of panic disorder, who initially developed a maculopapular, erythematous, pruritic rash in the third week with sertraline 50 mg/day. The rash resolved within 2 days of its discontinuation and oral supplementation of diphenhydramine and betamethasone. 10 days following discontinuation of sertraline, the patient was shifted on sustain release paroxetine 12.5 mg/day when another skin reaction with the same appearance and distribution appeared on day 4 of it, suggesting a possibility of cross-sensitivity, a drug class effect. This case report intends to improve the awareness among clinicians to use caution when choosing an alternative SSRIs.     

克罗恩病伴下肢深静脉血栓应用华法林致出血1例的药学监护

目的 通过临床药师全程参与1例克罗恩病伴下肢深静脉血栓病人应用华法林致出血的抗凝治疗过程,探讨临床药师在临床治疗中发挥的作用.方法 对病人全程进行药学监护,分析评估病人应用华法林致出血的可能原因,协助医师制定和调整用药方案,并对病人进行用药教育以加强自我抗凝管理.结果 病人出血停止.结论 临床药师通过参与临床实践,可协助医师提高药物治疗的安全性和有效性,使病人获得优良的药学服务.     

临床药师参与1例人工肝术后下肢深静脉血栓病例的临床实践

摘要：目的 通过临床药师参与1例人工肝术后下肢深静脉血栓病例的临床治疗实践,探讨临床药师在治疗中所起的作用。方法 临床药师通过查阅指南、专家共识、文献资料,分析人工肝术后下肢深静脉血栓形成的原因,预防措施以及参与制定个体化抗凝治疗方案、药学监护及用药教育。结果 临床医师与药师共同制定华法林抗凝治疗方案,临床药师对患者进行药学监护、用药教育,用药过程未发生不良反应,患者熟练掌握华法林治疗注意事项,依从性良好。结论 临床药师协助临床医师制定个体化的抗凝治疗方案,做好药学监护、用药教育,保障治疗的安全性、有效性。     

Warfarin Resistance in a Patient with Short Bowel Syndrome

Drug therapy in short bowel syndrome can be complicated by inadequate or incomplete absorption of drugs in the small intestine. Many case reports claim that warfarin absorption is not affected by the syndrome. We treated a patient with oral warfarin for recurring deep vein thrombosis; up to 20 mg/day was administered with no increase in the international normalized ratio. Drug-drug interactions that may prevent absorption, increase metabolism, or antagonize the effects of warfarin were ruled out. Intravenous lipid administration, which is anecdotally reported to precipitate warfarin resistance, may have contributed to the condition, but dosing was less frequent than in published reports. The most probable explanation of warfarin resistance is the reduced surface area for drug absorption secondary to surgical removal of the patient's duodenum and gastrojejunostomy.     

Temozolomide-induced desquamative skin rash in a patient with metastatic melanoma

Temozolomide is an oral alkylating agent used in the treatment of metastatic melanoma. Commonly reported adverse effects of the drug include nausea and vomiting, constipation, headache, and fatigue, as well as myelosuppression, which may be dose limiting. Few reports have described dermatologic adverse effects such as rash and pruritus, and, to our knowledge, none have discussed the seriousness or extensiveness of the rash. We describe a 37-year-old woman who was receiving temozolomide for treatment of metastatic melanoma. After 6 weeks of therapy, the patient developed an unexplained fever. The drug was discontinued, and the fever resolved within 2 days. Temozolomide was restarted 2 months later; the patient again developed a fever. This time the fever was accompanied by a diffuse erythematous skin rash that progressed to an extensive, full-body, desquamative skin rash. The rash was treated with moisturizing cream along with intravenous and topical corticosteroids and antibiotics. Due to the severity of the rash, temozolomide was permanently discontinued. Even after its discontinuation, the patient experienced the rash on a long-term basis, with periodic exacerbations. However, none were as severe as the first rash. The patient's metastatic disease remained stable for the next 2 years. According to the Naranjo adverse drug reaction probability scale, the likelihood that temozolomide was responsible for the adverse drug reaction of fever was probable (score of 6). Clinicians should be aware that an erythematous and exfoliative rash may be induced by temozolomide, and be familiar with the pharmacologic and supportive measures necessary for its treatment.     

Thrombotic complications after intravenous immunoglobulin therapy in two patients

Although intravenous immunoglobulin (IVIg) generally is considered a safe treatment for various autoimmune and inflammatory disorders, rare cases of thrombosis may occur. We describe two patients who experienced thrombotic complications associated with IVIg therapy. A 54-year-old woman with idiopathic thrombocytopenia received IVIg 1 g/kg/day for 2 days. While receiving her infusion on day 2, she had an ischemic stroke with hemiparesis; 3 days later she developed deep vein thrombosis. A 33-year-old woman with Evans' syndrome received IVIg 400 mg/kg/day for 5 days and developed deep vein thrombosis 1 week after therapy was completed; she then received warfarin. Six months later, she received an additional course of IVIg for recurrent hemolytic anemia; 1 day later she died of pulmonary thromboembolism. We suggest that IVIg may promote thrombosis by increasing blood viscosity, activating platelets, or causing vasospasm and should be administered with caution.     

Selective serotonin reuptake inhibitor-induced rash: case report and review of the literature

Selective serotonin reuptake inhibitors (SSRIs) are one of the most frequently prescribed classes of drugs. Rashes induced by SSRIs seldom have been reported in the literature. Computerized MEDLINE and Current Contents searches yielded a report of two cases of rash induced specifically by paroxetine. We describe a patient who developed a rash that appeared on day 3 of treatment with oral paroxetine 20 mg/day. Her rash was morbilliform, pruritic, and generalized over the trunk and limbs, with some facial involvement. There was no palm or sole involvement. The patient reported that she had experienced a similar reaction to fluoxetine, which may suggest a drug class effect. The rash resolved within 2 days of drug discontinuation and treatment with oral diphenhydramine and topical hydrocortisone cream.     

Angioedema and Photosensitive Rash Induced by Valsartan

A 71-year-old woman experienced an acute onset of angioedema and a photosensitive pruritic rash after 3 months of therapy with valsartan, an angiotensin II receptor antagonist. After discontinuing valsartan and treatment with subcutaneous epinephrine, intravenous methylprednisolone, diphenhydramine, and Eucerin cream, her symptoms dissipated and the rash resolved. Rash and angioedema have been reported with angiotensin-converting enzyme inhibitors and, very rarely, with losartan, the other currently marketed angiotensin II receptor antagonist. To our knowledge, this is the first report of such a reaction with valsartan.     

Effect of carbamazepine initiation and discontinuation on antithrombotic control in a patient receiving warfarin: case report and review of the literature

A 72-year-old Caucasian woman with paroxysmal atrial fibrillation had been taking warfarin therapy for 5 years with a stable international normalized ratio (INR). Her dentist then prescribed carbamazepine 200 mg/day to control facial nerve pain. At her next physician visit about 2 weeks after the start of the carbamazepine, the patient's INR had dropped from 3.3 to 1.3; she reported no contributing changes in her diet or warfarin dosage, nor had she taken other interacting drugs. Her warfarin dosage was increased, and the INR returned to the target range of 2.0-3.0 approximately 2 months later. The patient's INR remained stable for approximately 6 more months, until she had facial surgery. During that time, her warfarin was discontinued for 5 days, and the patient had stopped taking the carbamazepine because she had no pain. One month later, her INR increased from 2.2 to 3.6. She did not experience any thrombotic or hemorrhagic episodes. Warfarin undergoes hepatic metabolism through cytochrome P450 2C9, and carbamazepine induces this isoenzyme. Inducing warfarin metabolism necessitates an increase in the warfarin dosage to maintain the INR in the therapeutic target range. To our knowledge, this is the first report documenting the effect of the carbamazepine initiation and discontinuation in a patient receiving anticoagulation therapy with warfarin. In patients taking warfarin, clinicians should monitor the INR closely when carbamazepine is started or discontinued, or when either dosage is changed.     

1例深静脉血栓形成多次复发患者抗凝治疗的药学监护

目的:探讨临床药师为深静脉血栓形成(DVT)患者提供药学监护的工作要点。方法:参与1例DVT多次复发患者的华法林抗凝治疗用药方案的制订、抗凝疗效的评估、药物相互作用分析以及患者教育。结果:确定了符合患者特点的抗凝强度,提高了患者的依从性以及自我管理能力。结论:临床药师对抗凝患者的药学监护、长期随访降低了DVT复发以及出血风险。     

Ximelagatran

Despite the significant advances over the last 50 years with regard to anticoagulant therapy, warfarin remains the definitive standard for the long-term prevention of thromboembolic events in at-risk patients, except those with acute coronary syndromes, in which antiplatelets are preferred. Ximelagatran, a prodrug of melagatran, is an orally administered direct thrombin inhibitor whose therapeutic potential has been investigated in venous thromboembolism, acute coronary syndromes and prevention of stroke in atrial fibrillation. Clinical studies have demonstrated ximelagatran to be comparable in efficacy to the oral vitamin K antagonist warfarin and low molecular weight heparin for prophylaxis of venous thromboembolism, comparable to warfarin for stroke prevention in the setting of atrial fibrillation, and, when combined with aspirin, more effective than aspirin alone at preventing major adverse cardiovascular events in patients with a recent myocardial infarction. Double-blind trials have also revealed the efficacy of ximelagatran in the secondary prevention of venous thromboembolism and shown the agent to be as effective as enoxaparin/warfarin in treating patients with acute deep vein thrombosis. Adverse effects with ximelagatran include elevations in alanine transaminase (ALT), which may require monitoring, and bleeding complications. Bleeding complications appear to be less than or at least comparable to those occurring with standard anticoagulant treatments like warfarin or low molecular weight heparin. In addition to its favorable efficacy and safety profile in comparison with standard anticoagulant therapy, the convenience of its oral, fixed-dose administration without the need for anticoagulation monitoring might help encourage a wider use of appropriate anticoagulation using ximelagatran across the population at risk, reducing the incidence of thromboembolic events.     

Management of Stevens-Johnson syndrome

A patient with Stevens-Johnson syndrome is described, and the literature concerning the etiology, pathophysiology, clinical manifestations, and management of Stevens-Johnson syndrome is reviewed. A 2 1/2-year-old girl was treated with phenobarbital and i.v. ampicillin, followed by oral amoxicillin, for an upper-airway infection, otitis media, and febrile seizures. The fever returned, and she was treated unsuccessfully with penicillin and cefaclor. She was admitted to the hospital and treated with i.v. ampicillin. Within 24 hours an erythematous maculopapular rash developed. Phenobarbital was discontinued and phenytoin was begun. Four days later bullous lesions developed; ampicillin and phenytoin were discontinued, and cefazolin and phenobarbital were given. By the eighth day severe sloughing of the skin occurred over 75% of her body, and mucosal sloughing was apparent. The patient's condition was diagnosed as Stevens-Johnson syndrome. Porcine xenografts were immediately grafted to 75% of her total body surface. Severe lesions of the mouth and pharynx made parenteral nutrient therapy necessary, and ocular complications required the care of an ophthalmologist. Although the skin had healed by 14 days after grafting, another 14 days of treatment for respiratory complications was required. Stevens-Johnson syndrome is a severe exfoliative dermatitis accompanied by fever, inflammation of the gastrointestinal mucosa, and severe purulent conjunctivitis. It is associated with high morbidity and mortality. The etiologic factors may be iatrogenic (e.g., various antibiotics and anticonvulsants), infectious, or idiopathic. Respiratory complications, leukopenia, infections, erosion of the gastrointestinal mucosa, fluid and electrolyte disturbances, and chronic ocular complications may occur.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oral anticoagulant drug interactions with statins: case report of fluvastatin and review of the literature

A 67-year-old man receiving a stable maintenance dosage of warfarin experienced an increased international normalized ratio (INR) without bleeding when his atorvastatin therapy was switched to fluvastatin. His warfarin dosage was reduced and his INR stabilized. The fluvastatin was switched back to atorvastatin, and the warfarin dosage was increased to maintain the patient's goal INR. The literature supports a drug interaction between warfarin and fluvastatin due to the strong affinity of fluvastatin for the cytochrome P450 enzyme 2D6. This interaction has not been seen with atorvastatin. Lovastatin also reportedly has caused increases in INR when coadministered with warfarin. It is unclear whether simvastatin interacts with warfarin, but it may increase INRs slightly or increase serum simvastatin levels. One case report describes an interaction between simvastatin and the anticoagulant acenocoumarol, which resulted in an elevated INR. Pravastatin does not appear to interact with warfarin but has caused an increased INR when combined with the anticoagulant fluindione. Thus, until more definitive data are available, clinicians should monitor the INR closely after starting statin therapy in any patient receiving anticoagulation therapy.     

一例抗磷脂综合征伴克罗恩病并发下肢深静脉血栓患者抗栓治疗分析

目的:分析1例抗磷脂综合征伴克罗恩病并发下肢深静脉血栓病例的治疗过程,探讨抗栓药物选择的合理性,为临床合理用药提供参考.方法:临床药师协助医师依据患者自身疾病特点及实验室指标评估血栓及出血风险,并制订最优的抗栓治疗方案.结果 和结论:患者初始抗栓药物为利伐沙班.临床药师根据循证医学证据建议换用华法林进行抗栓治疗,并针对...     

A case report of warfarin resistance due to azathioprine and review of the literature

A 32-year-old woman with a history of deep vein thrombosis (DVT), steroid-dependent ulcerative colitis, and osteoporosis was prescribed azathioprine for a steroid-sparing effect. Stable, therapeutic international normalized ratios (INRs) were obtained with warfarin 35 mg/week during a 6-week postpartum course to treat an initial DVT. Ten days after completing warfarin therapy, azathioprine was begun. A recurrent DVT occurred 9 days later, and an increase in warfarin dosage to 120 mg/week was necessary to achieve an INR of 2.0-3.0. The patient denied changes in warfarin adherence, dietary vitamin K intake, or medical conditions. The addition of azathioprine was the only change in her regimen. Review of the literature found only limited reports of an interaction between warfarin and azathioprine, with increases in warfarin requirements of 3-4 times. Careful monitoring and caution are recommended when administering these two drugs concomitantly.     

A pilot study of home treatment of deep vein thrombosis with subcutaneous once-daily enoxaparin plus warfarin

OBJECTIVE: To evaluate patient satisfaction, effectiveness, and safety of at-home treatment of acute deep vein thrombosis (DVT) with subcutaneous enoxaparin dosed at 1.5 mg/kg once daily plus oral warfarin. METHODS: Patients with acute DVT and no more than 1 previous episode of DVT received enoxaparin plus oral warfarin until their international normalized ratio (INR) was >2 on 2 consecutive days. Patients were recruited between November 2000 and June 2003, and a home-care nurse visited the patient daily to administer the enoxaparin and to perform a fingerstick INR test. Patients received warfarin at doses adjusted to maintain an INR in the range of 2 to 3. Efficacy and safety were assessed daily by a home-care nurse and then by telephone interview conducted by a pharmacist at 14, 30, and 90 days during follow-up. Patient satisfaction with treatment was assessed by a verbal questionnaire. RESULTS: There were 52 patients enrolled. The mean duration of enoxaparin home treatment was 4.5 days, and the mean INR on discontinuation of enoxaparin was 2.73. Most patients (84.6%) had INRs within the desired therapeutic range (INR value 2-3); no patient had a subtherapeutic INR. There were no symptoms of recurrent venous thromboembolism reported. Major bleeding occurred 7 days after discontinuation of enoxaparin in one patient with impending surgery for removal of a uterine tumor. There were 2 cases of minor bleeding. The patient satisfaction questionnaire revealed that patients considered home treatment to be acceptable. The average cost savings was $2,925 per patient compared with typical inpatient treatment with unfractionated heparin. CONCLUSION: The results of this pilot study suggest that home treatment with initial once-daily enoxaparin in conjunction with long-term oral warfarin is a safe and effective alternative to inpatient therapy with once-daily enoxaparin or unfractionated heparin for select patients with acute DVT. Cost savings are derived from the substitution of inpatient care with home care.