warfarin and Leg-Ulcer

Classic calciphylaxis associated with renal failure is a life-threatening disease. Warfarin-associated calciphylaxis without renal injury has been described, but whether it is a subset of classic calciphylaxis or a different entity remains unknown. We describe 1 case of warfarin-associated calciphylaxis, present data from 2 others from our institution, and review all cases of warfarin-associated calciphylaxis available in the literature. Our review indicates that warfarin-associated calciphylaxis is clinically and pathophysiologically distinct from classic calciphylaxis.. To review warfarin-associated calciphylaxis and determine its relationship to classic calciphylaxis.. We searched MEDLINE and Ovid without language or date restrictions for case reports of calciphylaxis from the inpatient setting using the terms "calciphylaxis and warfarin," "non-uremic calciphylaxis," and "nonuremic calciphylaxis." We defined nonuremic calciphylaxis as a histopathologic diagnosis of calciphylaxis without severe kidney disease (serum creatinine level >3 mg/dL; glomerular filtration rate <15 mL/min; acute kidney injury requiring dialysis; and renal transplantation).. Each patient had been exposed to warfarin before the onset of calciphylaxis.. Patient data were abstracted from published reports. Original patient medical records were requested and reviewed when possible.. We identified 18 patients with nonuremic calciphylaxis, 15 from the literature, and 3 from our institution. Patients were predominantly female (15 of 18 [83%]) with ages ranging from 19 to 86 years. Duration of warfarin therapy prior to calciphylaxis onset averaged 32 months. Lesions were usually located below the knees (in 12 of 18 [67%]). No cases reported elevated calcium-phosphate products (0 of 17 [0%]). Calcifications were most often noted in the tunica media (n = 8 [44%]) or in the vessel lumen and tunica intima (n = 7 [39%]). The most common treatments included substitution of heparin or low-molecular weight heparin for warfarin (n = 13 [72%]), intravenous sodium thiosulfate (n = 9 [50%]), and hyperbaric oxygen (n = 3 [17%]). The survival rate on hospital discharge was remarkably high, with 15 cases (83%) reporting full recovery and 3 cases ending in death.. Warfarin-associated calciphylaxis is distinct from classic calciphylaxis in pathogenesis, course, and, particularly, outcome. This finding should influence clinical management of the disease and informs targeted treatment of the disease.

Topics: Anticoagulants; Calciphylaxis; Female; Humans; Leg Ulcer; Livedo Reticularis; Purpura; Warfarin

Osteonecrosis is a relatively common comorbidity in systemic lupus erythematosus (SLE), but avascular necrosis in multiple sites is unusual. Multifocal osteonecrosis is defined as osteonecrotic lesions affecting three or more separate anatomic sites. We report a case of a 24-year-old woman diagnosed with SLE when she presented with mucocutaneous, haematological and mild renal manifestations. Initially, she was treated with prednisone and hydroxychloroquine and her condition remained stable. Two years later, she developed severe bilateral pretibial ulcers intractable to immunosuppressive therapy and broad-spectrum antibiotics. MRI of both legs disclosed osteonecrosis of the distal tibia, proximal tibia, distal fibula and talus bilaterally. She had elevated anticardiolipin antibodies for which she was treated with chronic anticoagulation resulting in complete healing of the leg ulcers and no further episodes of osteonecrosis. In addition to this case, we review the demographic, clinical and pharmacological features of 14 cases reported in the literature.

Topics: Adult; Antibodies, Anticardiolipin; Anticoagulants; Antiphospholipid Syndrome; Female; Fibula; Humans; Leg Ulcer; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Osteonecrosis; Talus; Tibia; Warfarin; Young Adult

Severe peripheral artery disease (PAD) is the predominant cause of ischemic ulcerations involving the lower extremities. PAD-associated ulcerations are typically distally located involving the feet, toes, and sometimes the calves. In contradistinction, atypical ischemic ulcerations of the lower extremity are often non-atherosclerotic in etiology, involve the proximal leg (thigh/buttocks), can evolve despite palpable distal pulses, and may coexist with other cutaneous aberrations (e.g. macules, purpura, nodules, and livedo reticularis). A differential diagnosis of atypical ischemic ulcerations involving the legs is presented.

Topics: Anticoagulants; Antiphospholipid Syndrome; Calciphylaxis; Diagnosis, Differential; Drug Eruptions; Embolism, Cholesterol; Heparin; Humans; Ischemia; Leg Ulcer; Lower Extremity; Peripheral Vascular Diseases; Spider Bites; Vasculitis; Warfarin

Calciphylaxis is a relatively rare, but horribly disfiguring, skin condition that is most often associated with end-stage renal disease and long-term dialysis. Unfortunately, calciphylaxis-related morbidity and mortality are significant. The case study presented demonstrates many of the findings associated with the typical calciphylaxis patient; end-stage renal disease and an extensive, painful ulcer. The complexity of the patient s history and medical/surgical interventions, especially medication therapy with coumadin and heparin, complicated initial diagnostic processes. Close scrutiny of multiple physical assessment findings, historical factors, and test results was required for correct diagnosis. Crucial components of differential diagnosis of calciphylaxis versus coumadin-induced skin necrosis or heparin-induced thrombocytopenia necrosis include: patient history and characteristics, clinical presentation, and diagnostic test results.

Topics: Amputation, Surgical; Anticoagulants; Calciphylaxis; Diagnosis, Differential; Disease Progression; Fatal Outcome; Heparin; Humans; Kidney Failure, Chronic; Leg Ulcer; Male; Middle Aged; Necrosis; Skin Care; Thrombocytopenia; Warfarin

Calcific uremic arteriolopathy (CUA) is a highly morbid condition usually found in ESRD patients that has rarely been reported after renal transplantation and renal function restoration. Furthermore, little is known about the optimal management of CUA in this setting. Herein, we report on the clinical case of AB, a 70-year-old woman who developed CUA after renal transplantation and renal function restoration. However, other risk factors for CUA such as diabetes and warfarin treatment, due to mechanical aortic valve implantation, were present. Thirty-eight months after renal transplantation she developed erythema and livedo reticularis in both legs and a gradually enlarging skin ulcer in the right leg. A skin biopsy of the ulcer showed features compatible with the CUA, such as sub-intimal calcification and luminal obstruction of the small dermal arterioles, tissue ischemia and signs of adipocytes degeneration. A multidisciplinary approach was adopted, including medical and non-medical treatments such as surgical debridement and vacuum-assisted closure therapy. Medical treatments included a five weeks course of once a week intravenous infusion of pamidronate and intravenous sodium thiosulfate (STS) at increasing doses. Four months after beginning the therapy with STS, a complete healing of the ulcer on the right leg and the disappearance of the livedo reticularis on the left leg was noted. In conclusion, although rare CUA may develop also in renal transplanted patients, a timely and combined therapeutic approach is essential for its resolutive treatment. Sodium thiosulfate therapy has proven to be effective and tolerated.

Topics: Aged; Anticoagulants; Bone Density Conservation Agents; Calciphylaxis; Chelating Agents; Combined Modality Therapy; Diabetes Mellitus; Female; Humans; Kidney Transplantation; Leg Ulcer; Livedo Reticularis; Pamidronate; Rare Diseases; Risk Factors; Thiosulfates; Warfarin

Calciphylaxis is a complex dermatological lesion of micro vascular calcification that is typically presented as panniculitis with gangrenous painful lesions having uremic and non-uremic causes.. We present a case of a 48-year old male with a history of paroxysmal atrial fibrillation and hypertension taking amlodipine 5 mg and warfarin 5 mg daily for the last 26 months. The patient had a 6- months history of painful swelling followed by necrotic skin ulcer over the right leg. His remarkable examination findings were right leg tender ulcer with surrounding erythema and secondary sepsis. His hemogram, metabolic profile and connective tissue diseases work up were unremarkable except leucocytosis and raised inflammatory markers. His local part radiological and skin biopsy findings were suggestive of calciphylaxis.. In our case, warfarin and amlodipine were culprit drugs for the lesion, but Naranjo score (warfarin 7and amlodipine 1) speculate warfarin as a probable adverse reaction of warfarin. The lesion was cured with local wound treatment after discontinuation of warfarin. The physician should be aware of this rare cutaneous disorder of systemic origin for proper management.

Topics: Anticoagulants; Calciphylaxis; Humans; Leg Ulcer; Male; Middle Aged; Necrosis; Warfarin

Topics: Adult; Aneurysm, False; Aneurysm, Ruptured; Drug Overdose; Dyspnea; Echocardiography, Doppler, Color; Humans; Leg Ulcer; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Male; Treatment Outcome; Venous Thrombosis; Ventricular Dysfunction, Left; Warfarin

Calciphylaxis or calciphic uremic arteriolopathy (CUA) is a rare syndrome characterized by the deposition of calcium within the walls of small and medium size vessels in the dermis and in the subcutaneous tissue. The disease mainly affects patients with end-stage renal disease. We report here our experience with 4 cases of calciphylaxis in dialysis patients. The main predisposing factor observed in our 4 patients was warfarin use (2 patients, 50%), while local traumas and diabetes were respectively present in only one patient. None of our patients was obese. Lower legs were the most frequently involved site of CUA (3/4 patients, 75%). In our experience biopsy was crucial to achieve a correct diagnosis and did not cause aggravation of the ulcers. Therapeutic approach was multimodal: mainly hyperbaric oxygen therapy, cinacalcet and sodium thiosulphate. Although many recent case reports have shown exceptional results and healing with the use of sodium thiosulphate, we did not experience any change in the poor prognosis of our patients with the use of this drug, at a dosage of 5 g thrice weekly endovenously.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Biopsy; Calciphylaxis; Cinacalcet; Combined Modality Therapy; Fatal Outcome; Female; Hemodialysis Solutions; Heparin; Humans; Hyperbaric Oxygenation; Kidney Failure, Chronic; Leg Ulcer; Male; Middle Aged; Naphthalenes; Prognosis; Renal Dialysis; Skin Ulcer; Thiosulfates; Warfarin

Topics: Aged; Anticoagulants; Arterial Occlusive Diseases; Humans; Leg Ulcer; Male; Thrombosis; Venous Insufficiency; Vitamin K; Warfarin

Low molecular weight heparin is used in the treatment of patients with antiphospholipid syndrome, who develop thrombosis while being managed on oral anticoagulants. Although laboratory monitoring of this agent is not widely performed, it has been suggested to be useful in selected situations of high-risk thrombosis and bleeding. It is however not entirely clear, whether the dose should be altered on the basis of anti-Xa results in asymptomatic individuals.

Topics: Adult; Anti-Bacterial Agents; Antibodies, Anticardiolipin; Anticoagulants; Antiphospholipid Syndrome; Asymptomatic Diseases; Dalteparin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Factor Xa Inhibitors; Humans; International Normalized Ratio; Leg Ulcer; Lupus Coagulation Inhibitor; Male; Recurrence; Thrombophilia; Thrombophlebitis; Ultrasonography; Warfarin

Topics: Adrenal Cortex Hormones; Aged; Anticoagulants; Cryoglobulinemia; Drug Therapy, Combination; Humans; Leg Ulcer; Male; Treatment Outcome; Warfarin

Calciphylaxis is a rare, usually fatal vasculopathic disorder characterized by cutaneous ischemia and necrosis due to calcification of arterioles. Although calciphylaxis is most frequently associated with end-stage renal disease (ESRD) and secondary hyperparathyroidism, it has been reported infrequently among patients on warfarin. No standard treatment has been established for atypical calciphylaxis; however, a potentially beneficial treatment is hyperbaric oxygen therapy (HBOT). A high degree of clinical suspicion, early diagnosis, and understanding the pathophysiology of this disease promotes the optimal management of this extremely morbid and often fatal condition.. We present a 63-year-old Polynesian woman with biopsy-proven calciphylaxis in the absence of ESRD or elevated serum calcium levels while taking warfarin. Therapeutic dose enoxaparin was substituted for warfarin and she received 40 sessions of HBOT during which lower extremity ulcers resolved.. Warfarin has been implicated when calciphylaxis presents in an atypical fashion. No guidelines exist for treatment of atypical calciphylaxis in the setting of concomitant warfarin therapy. Up to 80% of calciphylaxis patients die within 1 year of diagnosis. Our patient was changed to low-molecular-weight heparin and received HBOT.. We present what we believe is the first case of atypical calciphylaxis thought to be attributable to warfarin treated with a therapeutic substitution of anticoagulant and HBOT leading to resolution of cutaneous lesions.

Topics: Anti-Bacterial Agents; Anticoagulants; Calciphylaxis; Calcium-Binding Proteins; Cellulitis; Combined Modality Therapy; Debridement; Diabetes Mellitus, Type 2; Extracellular Matrix Proteins; Female; Humans; Hyperbaric Oxygenation; Leg Ulcer; Matrix Gla Protein; Middle Aged; Obesity, Morbid; Risk Factors; Thrombophilia; Warfarin

We report herein a case of a 28-year-old woman with persistent livedo racemosa and recurrent ulcerations on the lower extremities. The clinical presentation, together with histopathological findings of vascular occlusion without overt vasculitis in the dermis, led to the diagnosis of livedoid vasculopathy. The patient experienced recurrence of ulcerations and developed peripheral neuropathy affecting the distal extremities during the course of treatment with sarpogrelate hydrochloride. The skin lesions and neurological symptoms improved dramatically after adding low-dose warfarin potassium to the treatment regimen. This case suggests that administration of low-dose warfarin is an effective therapy of choice for patients with livedoid vasculopathy.

Topics: Adult; Anticoagulants; Female; Humans; Leg; Leg Ulcer; Livedo Reticularis; Mononeuropathies; Succinates; Vasculitis; Warfarin

Leg ulcers are a manifestation of antiphospholipid syndrome (APS), and characteristically respond poorly to treatment. Because the similar findings both clinical and pathological to pyoderma gangrenosum (PG), we treated these patients with a combination of immunosuppression (steroids, azathioprine or cyclosporine), acetylsalicylic acid and anticoagulation. We evaluated the response to the combined treatment with steroids, immunosuppression, acetylsalicylic acid, anticoagulation and local measures in patients with APS and leg ulcers resembling PG. We studied 8 women with leg ulcers of a cohort of 53 patients with APS (15%). Pathological findings of PG were observed in all patients. Seven patients (87.5%) received cyclosporine as usual for the treatment of PG, and all patients received steroids and anticoagulation with warfarin. Cicatrisation was present in all patients in 7 months. Leg ulcers in patients with APS may be resemble to PG, and their treatment with immunosuppression, acetylsalicylic acid and anticoagulation is effective for this severe and poorly responding condition.

Topics: Adult; Antiphospholipid Syndrome; Cohort Studies; Cyclosporine; Dosage Forms; Female; Follow-Up Studies; Humans; Immunosuppression Therapy; Leg Ulcer; Middle Aged; Pyoderma Gangrenosum; Time Factors; Treatment Outcome; Warfarin

Cutaneous polyarteritis nodosa (CPN) is an uncommon disorder that can be difficult to manage effectively. We have previously suggested that CPN might be associated with the presence of anti-phosphatidylserine-prothrombin complex (anti-PS/PT) antibodies, members of the antiphospholipid antibody family.. To evaluate clinical manifestations and effective treatments of CPN.. We conducted a retrospective analysis of three patients with CPN who responded to warfarin therapy. IgG and IgM anti-PS/PT antibodies were measured with a specific enzyme-linked immunosorbent assay.. There was a dramatic improvement in our three CPN patients following warfarin therapy adjusted to a target international normalized ratio (INR) of about 3.0. Active disease progression was halted by sustained warfarin therapy during which the patients experienced resolution of their skin manifestations.. A small number of cases were studied and the study design was retrospective.. We propose that warfarin therapy at a target INR of roughly 3.0 could be effective for treating patients with CPN. We further believe that treatment with warfarin led to the effective attenuation of anti-PS/PT antibodies related to prothrombin, and improved the symptoms in our CPN patients.

Topics: Adult; Anticoagulants; Biopsy, Needle; Dose-Response Relationship, Drug; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Immunohistochemistry; International Normalized Ratio; Leg Ulcer; Middle Aged; Polyarteritis Nodosa; Prothrombin; Retrospective Studies; Sampling Studies; Severity of Illness Index; Treatment Outcome; Warfarin; Wound Healing; Young Adult

A 50-year-old woman had a lifelong history of painful ulcerations as a result of livedoid vasculopathy. She was a heterozygous carrier of factor V Leiden and prothrombin gene mutations and was receiving hormone replacement therapy. The ulcers healed after warfarin therapy, which has been reported to be effective in only one previous patient with this condition.

Topics: Anticoagulants; Factor V; Female; Heterozygote; Humans; Leg Ulcer; Livedo Reticularis; Middle Aged; Mutation; Prothrombin; Skin Diseases, Vascular; Thrombophilia; Warfarin

Livedoid vasculopathy is characterized by painful purpuric lesions on the extremities which frequently ulcerate and heal with atrophic scarring. It has been considered to be a vasculitic process but now there has been increasing evidence that abnormal coagulation plays a major role in the pathogenesis of this rare disorder. We report the case of a 19-year-old male who had been suffering from recurrent painful ulcerations on both lower legs with atrophic scars for 4 years. A biopsy specimen revealed vasculopathy, and laboratory studies showed resistance to activated protein C with factor V Leiden mutation. Treatment with oral warfarin led to rapid improvement of the lesions.

Topics: Administration, Oral; Adult; Anticoagulants; Factor V; Humans; Leg Ulcer; Male; Mutation; Skin Diseases, Vascular; Warfarin

A 53-year-old woman presented with a chronic history of recurrent, painful ulcers, predominantly involving her lower legs. Both her clinical picture and histopathological findings were consistent with a diagnosis of livedoid vasculopathy, although she did have unusual findings of deep tender nodules and the presence of lesions over her elbows. Multiple investigations were undertaken, the only abnormality being a heterozygous mutation of the prothrombin G2021A gene. Although various coagulopathic states have been associated with livedoid vasculopathy, the finding of an associated prothrombin gene mutation is quite rare. Warfarin has ameliorated the clinical course when anti-inflammatory drugs and other anticoagulants were unhelpful.

Topics: Anticoagulants; Female; Heterozygote; Humans; Leg Ulcer; Middle Aged; Point Mutation; Prothrombin; Skin Diseases, Vascular; Warfarin

Topics: Adult; Aspirin; Disease Management; Female; Humans; Hydroxyurea; Interferon-alpha; Leg Ulcer; Male; Middle Aged; Pipobroman; Platelet Count; Pregnancy; Pregnancy Complications, Hematologic; Quinazolines; Thrombocythemia, Essential; Warfarin

Topics: Antibodies, Anticardiolipin; Anticoagulants; Factor V; Female; Heterozygote; Humans; Leg Ulcer; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Prothrombin; Thrombophilia; Warfarin

Topics: Aged; Anemia; Anticoagulants; Diagnosis, Differential; Erythropoietin; Granulomatosis with Polyangiitis; Humans; Leg Ulcer; Male; Recombinant Proteins; Renal Insufficiency; Thrombosis; Treatment Outcome; Warfarin

Antiphospholipid syndrome (APS) has been well defined in adults; however, primary nontraumatic arterial thrombosis owing to this entity is unusual in the pediatric population. The authors report a case of APS with lower extremity arterial thrombosis who had discolored feet since delivery.

Topics: Antibodies, Anticardiolipin; Anticoagulants; Antiphospholipid Syndrome; Arterial Occlusive Diseases; Aspirin; Child, Preschool; Collateral Circulation; Heparin, Low-Molecular-Weight; Humans; Immunoglobulin G; Immunosuppressive Agents; Intermittent Claudication; Leg Ulcer; Male; Prednisolone; Skin Diseases, Vascular; Thrombophilia; Warfarin

Topics: Anticoagulants; Antithrombin III Deficiency; Bandages; Debridement; Female; Humans; Leg Ulcer; Middle Aged; Necrosis; Skin Care; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Humans; Leg Ulcer; Male; Middle Aged; Protein S Deficiency; Venous Thrombosis; Warfarin

Topics: Aged; Animals; Cattle; Diabetic Angiopathies; Female; Femoral Artery; Humans; Intermittent Claudication; Knee; Leg Ulcer; Male; Middle Aged; Pain; Popliteal Artery; Postoperative Complications; Radiography; Rest; Thrombosis; Transplantation, Heterologous; Warfarin

Topics: Adolescent; Adult; Aged; Female; Heparin; Humans; Leg; Leg Ulcer; Ligation; Male; Middle Aged; Phlebitis; Pulmonary Embolism; Recurrence; Regional Blood Flow; Suture Techniques; Thromboembolism; Vena Cava, Inferior; Venous Pressure; Warfarin