warfarin and Necrosis

Warfarin-induced skin necrosis (WSN) is a rare (0.0.1%-0.1%) and severe adverse reaction. The clinical characteristics of this reaction and its mortality rate have not been explored in a large population. Therefore, we present the case of a Peruvian patient who developed WSN and perform a systematic review of case reports of WSN.. A systematic search was performed using the Pubmed/Medline, Scopus, Web of Science and Embase databases. Patient clinical data were collected and extracted from every case report. Furthermore, we analysed the factors associated with mortality because of WSN using the Poisson regression model with robust variations, obtaining risk ratios (RR) and their respective confidence intervals (95% CI).. We identified 90 case reports that included a total of 111 patients with WSN (mean age 52.5 years), 20.72% of whom died of complications because of WSN. Being male (RR: 2.87; 95% CI 1.21-6.83) and having three or more affected regions (RR: 6.81; 95% CI 2.62-17.74) were associated with an increased risk of death caused by WSN.. This systematic review identified 90 case reports of WSN with three or more affected body regions. Male sex was associated with an increased risk of death. Further studies are needed to analyse and confirm these results.

Topics: Humans; Male; Middle Aged; Necrosis; Warfarin

Breast fat necrosis (BFN) is usually a benign inflammatory response to breast trauma. However, an extremely rare cause of fat necrosis is calciphylaxis, a calcification of small- and medium-sized arteries causing thrombosis and ischemia. It is classified into (A) uremic (B) nonuremic-induced calciphylaxis. Calciphylaxis has been reported to be encountered in different parts of the body. However, to the best of our knowledge there is only one case in the English literature of BFN 2ry to warfarin-induced calciphylaxis. We report a 65-year-old female, known case of atrial fibrillation on warfarin, presented with a left breast mass of 4-month duration. The mass was painful and progressively enlarging. Examination of the left breast showed 7 × 4 cm mass, spanning from 10-2 o'clock, free from surrounding structures, with preserved overlying skin. However, the mass was not visualized on mammogram. Ultrasound showed a left breast lobulated hypoechoic mass containing a hyperechoic component. Biopsy showed fat necrosis. After 1 month, she presented with ulceration of the overlying skin. After wide local excision, histopathology demonstrated a calciphylaxis-induced fat necrosis. Considering the patient's background, the diagnosis was BFN secondary to warfarin-induced calciphylaxis. Hence, the warfarin was shifted to Rivaroxaban, 6 months follow-up showed no evidence of recurrence. In conclusion, the rarity of nonuremic calciphylaxis is reflected on the delay of diagnosis in some of the reported cases and the lack of grading system used to guide the management of such difficult wounds. However, keeping a high index of suspicion is important whenever such wounds are encountered with presence of risk factors other than end-stage kidney disease.

Topics: Aged; Breast Neoplasms; Calciphylaxis; Fat Necrosis; Female; Humans; Necrosis; Neoplasm Recurrence, Local; Warfarin

Hypercoagulable states (HS) are inherited or acquired conditions that predispose an individual to venous and/or arterial thrombosis. The dermatologist can play a vital role in diagnosing a patient's HS by recognizing the associated cutaneous manifestations, such as purpura, purpura fulminans, livedo reticularis, livedo vasculopathy (atrophie blanche), anetoderma, chronic venous ulcers, and superficial venous thrombosis. The cutaneous manifestations of HS are generally nonspecific, but identification of an abnormal finding can warrant a further workup for an underlying thrombophilic disorder. This review will focus on the basic science of hemostasis, the evaluation of HS, the skin manifestations associated with hypercoagulability, and the use of antiplatelet and anticoagulant therapy in dermatology.

Topics: Anetoderma; Anticoagulants; Antiphospholipid Syndrome; Calciphylaxis; Hemostasis; Heparin; Humans; Livedo Reticularis; Necrosis; Platelet Aggregation Inhibitors; Purpura; Skin; Skin Diseases; Thrombophilia; Varicose Ulcer; Venous Thrombosis; Warfarin

A case report of coumadin-induced skin necrosis (CISN) is presented, followed by a topic review of CISN, which reviews presentation, pathophysiology, differential diagnosis, prevention, and management of this disorder. The prevalence of CISN is low (0.01%-0.1% of patients receiving coumadin). However, of those affected, over 50% required some form of surgical debridement or reconstruction. Although skin necrosis secondary to coumadin therapy is rare, it is essential for plastic surgeons to be aware of this clinical entity in order to make the correct diagnosis and provide appropriate treatment.

Topics: Anticoagulants; Breast Diseases; Diagnosis, Differential; Female; Humans; Middle Aged; Necrosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Drug Contamination; Drug Monitoring; Food-Drug Interactions; Hemorrhage; Heparin; Humans; Hypersensitivity; Injections, Subcutaneous; Necrosis; Osteoporosis; Skin Diseases; Subcutaneous Tissue; Thrombocytopenia; Warfarin

Warfarin-induced skin necrosis (WISN) and calciphylaxis share similar early clinical findings and can both lead to significant morbidity and mortality. The authors reviewed the literature on both conditions and describe a case of extensive skin necrosis in a patient with end-stage renal disease who was initially suspected to have calciphylaxis. Further investigation supported a diagnosis of WISN. The pathogenesis, clinical manifestations and treatment of WISN and calciphylaxis are discussed, with emphasis on a diagnostic approach for early recognition.

Topics: Adult; Anticoagulants; Calcinosis; Female; Humans; Necrosis; Skin; Warfarin

Warfarin-induced skin necrosis is a rare complication of anticoagulant therapy with a high associated morbidity and mortality requiring immediate drug cessation. Cutaneous findings include petechiae that progress to ecchymoses and hemorrhagic bullae. Characteristic dermatopathological findings are diffuse dermal microthrombi with endothelial cell damage and red cell extravasation with progression to full-thickness coagulative necrosis. The lesions of warfarin-induced skin necrosis may be difficult to differentiate from mimickers, but skin biopsy in conjunction with careful consideration of the clinical history, including time of onset, cutaneous distribution of the lesions, and laboratory findings, are essential for prompt diagnosis and patient treatment. Herein, we review the clinical and histologic features helpful for differentiating warfarin-induced skin necrosis and report a case illustrative of the diagnostic difficulty that may at times be encountered in clinical practice.

Topics: Aged; Anticoagulants; Biopsy, Needle; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Follow-Up Studies; Humans; Immunohistochemistry; Male; Necrosis; Severity of Illness Index; Skin Diseases; Warfarin

Recommendations for transitioning from therapy with heparin or a low-molecular-weight heparin preparation to therapy with an oral anticoagulant in patients with acute venous or arterial thromboembolism have undergone several changes during the last two decades. Physicians are now comfortable with beginning treatment with an oral anticoagulant once the diagnosis is confirmed, and loading doses are no longer considered to be necessary. Exceptions to early transition may be necessary in patients with an extensive iliofemoral or axillary-subclavian vein thrombosis or pulmonary embolism where thrombolytic agents may be indicated, or in individuals who require surgery or other invasive procedures, or if there are concerns about bleeding. The avoidance of early transition to oral anticoagulants in patients with acute heparin-induced thrombocytopenia also has been advised because of the potential for further thrombotic complications, including venous limb gangrene and warfarin-induced skin necrosis.

Topics: Administration, Oral; Anticoagulants; Arginine; Blood Coagulation; Blood Coagulation Factors; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Gangrene; Heparin; Heparitin Sulfate; Hirudins; Humans; Ischemia; Leg; Necrosis; Pipecolic Acids; Recombinant Proteins; Skin; Sulfonamides; Thrombocytopenia; Thrombosis; Warfarin

Topics: Anticoagulants; Aortic Valve Insufficiency; Arginine; Autoantibodies; Autoimmune Diseases; Female; Fingers; Heart Valve Prosthesis Implantation; Heparin; Hirudins; Humans; Ischemia; Middle Aged; Necrosis; Pipecolic Acids; Platelet Activation; Platelet Factor 4; Postoperative Complications; Raynaud Disease; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Thrombosis; Toes; 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

Warfarin induced skin necrosis is a rare complication with a prevalence of 0.01-0.1 per cent. It was first described in 1943.. A literature review was undertaken using Medline; all relevant papers on this rare compli-cation of warfarin therapy were used.. There are several adverse skin manifestations associated with the use of oral anticoagulants, ranging from ecchymoses and purpura, haemorrhagic necrosis, maculopapular vesicular urticarial eruptions to purple toes. This article concentrates mainly on warfarin induced skin necrosis. The syndrome typically occurs during the first few days of warfarin therapy, often in association with the administration of a large initial loading dose of the drug. Although the precise nature of the disease is still unknown, advances in knowledge about protein C, protein S and antithrombin III anticoagulant pathways have led to a better understanding of the mechanisms involved in pathogenesis. Differential diagnosis between warfarin induced skin necrosis and necrotizing fasciitis, venous gangrene and other causes of skin necrosis may be difficult; the disease may also be confused with other dermatological entities.. Warfarin induced skin necrosis, while rare, is an important complication. All surgeons should be aware of its existence.

Topics: Anticoagulants; Antithrombin III Deficiency; Humans; Necrosis; Protein C Deficiency; Protein S Deficiency; Skin; Warfarin

Topics: Anticoagulants; Drug Monitoring; Female; Gastrointestinal Hemorrhage; Humans; Middle Aged; Necrosis; Patient Education as Topic; Skin Diseases; Warfarin

Breast and nipple skin is commonly affected by various inflammatory and neoplastic processes. Despite this fact, many physicians are unaware of the spectrum of diseases that can involve this area. Because breast and nipple skin represents a cosmetically, sexually, and functionally important entity to most patients, awareness of these disease entities is invaluable. This article reviews the normal anatomy of the breast, cutaneous manifestations of neoplastic processes that can present in these areas, and common inflammatory diseases of the breast and nipple skin.

Topics: Anticoagulants; Breast Diseases; Breast Neoplasms; Dermatitis; Female; Hidradenitis Suppurativa; Humans; Mastitis; Necrosis; Nipples; Panniculitis, Lupus Erythematosus; Scleroderma, Localized; Warfarin

Two patients developed catastrophic multicentric skin necrosis while receiving warfarin to treat venous thromboembolism complicated by immune-mediated heparin-induced thrombocytopenia (HIT). Patient 1 developed skin necrosis involving the breasts, thighs, and face, as well as venous limb gangrene and bilateral hemorrhagic necrosis of the adrenal glands, resulting in death. The second patient developed bilateral mammary necrosis necessitating mastectomies, as well as skin necrosis involving the thigh. Neither patient had an identifiable hypercoagulable syndrome, other than HIT. HIT may represent a risk factor for the development of multicentric warfarin-induced skin necrosis (WISN).

Topics: Adrenal Gland Diseases; Aged; Amputation, Surgical; Anticoagulants; Antigens, Human Platelet; Autoantibodies; Autoimmune Diseases; Databases, Factual; Disseminated Intravascular Coagulation; Ecchymosis; Fatal Outcome; Female; Gangrene; Hemorrhage; Heparin; Humans; Mastectomy; Middle Aged; Multiple Organ Failure; Necrosis; Postoperative Complications; Pulmonary Embolism; Skin; Skin Diseases; Thigh; Thrombin; Thrombocytopenia; Thrombophilia; Thrombophlebitis; Vena Cava Filters; Warfarin

Warfarin-induced skin necrosis is a rare complication of therapy with warfarin or other coumarin derivatives. When it occurs it usually appears 3 to 6 days after initiation of therapy and almost always between days 1 and 10. We report a case of late-onset (16 days after initiation of therapy) warfarin-induced skin necrosis and review the literature on this rarely reported variant of warfarin-induced skin necrosis. The skin lesion in our patient was not associated with either deficiency of protein C or resistance to activated protein C.

Topics: Adult; Anticoagulants; Blood Coagulation Factor Inhibitors; Female; Humans; Male; Middle Aged; Necrosis; Protein C; Skin; Skin Diseases; Thrombosis; Warfarin

Topics: Administration, Oral; Animals; Anticoagulants; Heparin; Humans; Necrosis; Skin; Skin Diseases; Syndrome; Warfarin

Oral anticoagulants are extensively used in everyday medical practice, especially for the prophylaxis of deep vein thrombosis and pulmonary thromboembolism. Bleeding is the major risk of such therapy. Although infrequent, however, non-haemorrhagic complications may also play a considerable role. The purpose of this paper is briefly to review the most important non-haemorrhagic adverse reactions and their clinical signs. Moreover, the pathogenetic hypotheses, the relationships with protein C and S levels, and the possibility of prevention and treatment are also discussed.

Topics: Administration, Oral; Anticoagulants; Drug Eruptions; Ecchymosis; Humans; Necrosis; Peripheral Vascular Diseases; Skin; Warfarin

Warfarin (Coumadin)-induced necrosis of the skin is an unusual condition associated with the administration of warfarin. The necrotic lesions appear suddenly and are extremely painful. Single or multiple lesions develop in a distinct pattern. A hypercoagulable state created early in the course of warfarin administration is most likely responsible for warfarin-associated necrosis. Functional and inherited low levels of proteins C and S are found in some patients. The differential diagnosis of warfarin necrosis is of interest to the plastic surgeon. The condition may mimic purpura fulminans, necrotizing fasciitis, microembolization, breast cancer, and decubitus ulcers. Early recognition and treatment are essential to avoid significant and prolonged morbidity. Mortality has also been reported. We present 2 cases of warfarin-induced necrosis and a review of the literature.

Topics: Diagnosis, Differential; Female; Humans; Male; Middle Aged; Necrosis; Obesity, Morbid; Priapism; Skin; Warfarin

In general, the current recommendations for treating and prophylaxing thrombotic patients with hereditary defects are similar to those for thrombotic individuals without a defect. Determinations as to the need for long-term anticoagulation require that a clinical assessment be made regarding the relative benefit in preventing thrombotic episodes versus the risk of increased bleeding. With our newly found ability to identify genetic risk factors in a substantial fraction of patients with venous thrombosis and pulmonary embolism, it will be possible to perform rigorously designed studies to determine whether they should be managed with more prolonged or intense anticoagulation after a thrombotic event or more aggressive prophylactic regimens in high risk situations such as a total hip replacement.

Topics: Abnormalities, Drug-Induced; Anticoagulants; Antithrombin III; Antithrombin III Deficiency; Blood Proteins; Coumarins; Disease Susceptibility; Drug Eruptions; Factor V Deficiency; Female; Fibrinolytic Agents; Genetic Predisposition to Disease; Humans; Infant, Newborn; Male; Necrosis; Pregnancy; Pregnancy Complications, Hematologic; Prevalence; Protein C; Protein S Deficiency; Puerperal Disorders; Purpura; Recurrence; Risk; Thrombolytic Therapy; Thrombosis; Warfarin

Warfarin-induced skin necrosis is a rare but potentially devastating complication of oral anticoagulation. In this article the historical, clinical, and pathophysiologic features of this hypercoagulable event are reviewed, and recommendations for prevention and treatment are discussed.

Topics: Animals; Humans; Necrosis; Skin Diseases; Warfarin

We describe a 57-year-old woman with homozygous protein C deficiency and mild thrombotic manifestations consisting of three spontaneous distal deep vein thromboses occurring after the age of 45. Previous surgery and pregnancies had been uneventful. Low but detectable protein C antigen and activity levels (both 20%) were discovered on the occasion of skin necrosis induced by oral anticoagulation. This therapy was interrupted because of skin necrosis and several episodes of disseminated intravascular coagulation (DIC) at the initiation of treatment despite a cautious protocol. No recurrent thromboembolic event has occurred in our patient using prophylactic doses of low molecular weight heparin for 24 months. New therapeutic approaches might be the administration of low molecular weight heparin or oral anticoagulation associated with protein C replacement in the induction period. This case reflects the variability of expression of protein C deficiency as well as the potential hazards of antivitamin K anticoagulation in this disorder.

Topics: Acenocoumarol; Administration, Oral; Age Factors; Blood Coagulation Disorders; Contraindications; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Female; Genetic Predisposition to Disease; Heparin; Homozygote; Humans; Middle Aged; Necrosis; Protein C Deficiency; Skin; Skin Diseases; Thrombophlebitis; Warfarin

Skin and subcutaneous tissue necrosis is a rare complication of warfarin therapy. Although the incidence is low, with increased use of warfarin family physicians need to be aware of this potentially catastrophic event. This article reviews the history of warfarin necrosis and discusses its clinical presentation. The histologic findings with necrosed lesions are described, with emphasis on the possible pathogenesis of this disorder. Treatment options based on existing clinical experience as outlined in the literature are discussed.

Topics: Humans; Necrosis; Protein C; Skin Diseases; Warfarin

Warfarin-induced skin necrosis is a rare but serious complication of oral anticoagulant therapy. This condition has been associated with protein C deficiency but only rarely reported in patients with a deficiency of protein S. We have managed 2 patients with a history of warfarin-induced skin necrosis who were diagnosed as being protein-S-deficient. Since both patients were candidates for long-term anticoagulant therapy we elected to reintroduce warfarin using a regimen designed to minimize the risk of recurrent skin necrosis. While they were therapeutically anticoagulated with heparin, warfarin was started at 1 mg/day and the dose was increased gradually. Heparin was not discontinued until the prothrombin times were in the therapeutic range for at least 72 h. Both patients tolerated the reinstitution of warfarin without difficulty and they have now been followed for over 2 years on oral anticoagulants without complication.

Topics: Adult; Combined Modality Therapy; Female; Heparin; Humans; Male; Necrosis; Phenindione; Protein S Deficiency; Skin; Skin Diseases; Skin Transplantation; Thrombophlebitis; Warfarin

Oral anticoagulants are widely used in clinical practice. Hemorrhagic complications are the most frequent adverse reactions, but a rarer complication, coumadin skin necrosis, also can be seen. The recently described association with low levels of protein C and/or free protein S is of importance in the pathophysiology of coumadin skin necrosis. This article describes the case of a patient with a functional protein S deficiency who developed coumadin skin necrosis. The condition is described, and a discussion of theories regarding its pathophysiology is presented. Current treatment recommendations are listed.

Topics: Adult; Blood Proteins; Female; Glycoproteins; Humans; Necrosis; Protein C; Protein S; Skin; Warfarin

Topics: Humans; Necrosis; Protein C Deficiency; Risk Factors; Skin; Warfarin

Several adverse dermatologic effects have been reported with the use of warfarin. Among these is the rare complication of drug-induced necrosis. Approximately 150 cases had been reported by 1976, and a review of the literature since 1943 revealed only 4 reported cases of penile necrosis. We present the fifth case of genital necrosis reported with coumarin anticoagulants and the third such case associated with warfarin.

Topics: Humans; Male; Middle Aged; Necrosis; Penis; Time Factors; Warfarin

Skin and soft tissue necrosis is a rare complication of anticoagulation therapy. Two patients who exhibited the spectrum of this disorder are described. The clinical features, etiology, pathophysiology, and treatment of coumarin skin necrosis are outlined, and the English-language literature is reviewed.

Topics: Adult; Aged; Coumarins; Ecchymosis; Female; Hemorrhage; Humans; Male; Middle Aged; Necrosis; Purpura; Thrombophlebitis; Warfarin

Oral anticoagulants are used extensively, although their risks are not always fully recognized. The prophylaxis of venous thrombosis after hip surgery, the prevention of deep venous thrombosis and pulmonary emboli after an acute episode of these, the prevention of arterial emboli from the heart in patients at risk, and the prophylaxis of thrombosis in patients with congenital deficiency of antithrombin III, protein C, or protein S are some of the indications for oral anticoagulant use. Warfarin sodium is contraindicated in pregnancy, however. The recommended prothrombin time is 1 1/2 to two times control, lower than previously. The major risk of oral anticoagulant therapy, bleeding, is treated with vitamin K or plasma, depending on its severity. Warfarin necrosis and the "purple-toe" syndrome are seen more frequently than realized.

Topics: Absorption; Administration, Oral; Biological Availability; Drug Interactions; Hemorrhage; Hip Fractures; Humans; Myocardial Infarction; Necrosis; Postoperative Complications; Protein Binding; Prothrombin Time; Pulmonary Embolism; Thrombophlebitis; Thrombosis; Vitamin K; Warfarin

Two cases of necrosis of skin and subcutaneous tissues in patients taking oral anticoagulants are reported, and the English literature is reviewed. The mechanism of coumarin necrosis remains unknown. Most patients are women and the lesions are most common on the abdomen, buttocks, thighs, and breasts. Simple mastectomy is the usual treatment for a breast lesion. Although some cases have been reported in which the skin lesion has healed despite continued anticoagulant therapy, curtailing its use is recommended. Heparin has not been associated with skin necrosis, however, and may be desirable if continued anticoagulant treatment is necessary.

Topics: Anticoagulants; Breast Diseases; Coumarins; Female; Heparin; Humans; Male; Mastectomy; Middle Aged; Necrosis; Skin Diseases; Warfarin

Anticoagulant-induced skin necrosis is a rare and potentially life-threatening complication of anticoagulant therapy. The majority of cases of anticoagulant-induced skin necrosis have been attributed to warfarin, known as warfarin-induced skin necrosis (WISN). The use of anticoagulation reversal agents such as Prothrombinex-VF in the development of WISN is not a commonly documented phenomenon. The authors present a case of WISN post-recommencement of warfarin and the use of Prothrombinex-VF.

Topics: Anticoagulants; Anticoagulation Reversal; Drug Eruptions; Humans; Necrosis; Skin; Soft Tissue Injuries; Warfarin

Topics: Anticoagulants; Humans; Necrosis; Skin; Skin Diseases; Warfarin

Dabigatran, a novel oral anticoagulant, is a direct thrombin inhibitor and is being increasingly used owing to the advantage of dosing without the need for laboratory monitoring. While extensive skin necrosis is known to be associated with oral anticoagulants such as warfarin and factor Xa inhibitors, dabigatran toxicity typically manifests with bleeding, especially in the elderly. We describe a 70-year-old woman who was prescribed dabigatran for the treatment of unprovoked deep venous thrombosis. She developed bleeding diathesis along with extensive skin necrosis and acute kidney injury shortly after commencing the drug. Haemodialysis was given in view of dabigatran toxicity and complications of kidney dysfunction which resolved promptly over a week. However, the patient succumbed to severe sepsis from secondary skin infections. It is crucial to closely monitor for signs of dabigatran toxicity, especially in the elderly patients.

Topics: Aged; Anticoagulants; Dabigatran; Factor Xa Inhibitors; Female; Humans; Necrosis; Warfarin

Topics: Ear Auricle; Humans; Necrosis; Warfarin

Calciphylaxis is a rare and severe disease that manifests with painful skin ulceration and necrosis. Herein, we report five patients of hemodialysis patients with skin biopsy-proven calciphylaxis at a single facility. One patient had undergone parathyroidectomy (PTx) due to severe secondary hyperparathyroidism, four had been treated with vitamin D receptor activators, and two were on warfarin therapy. All patients had hyperphosphatemia, and one had hypercalcemia. The intact parathyroid hormone level at diagnosis was 2 pg/ml in the patient after PTx, while three patients were within the target range. The average period after diagnosis of calciphylaxis was 2 months. Skin lesions were present on the thighs and lower legs in two patients, and on the dorsum of the foot in one patient. In skin biopsy, calcification was found in the arteriolar media in four patients, and calcium (Ca) was deposited in the dermal lesion in one patient. All patients received local cures, surgical debridement, antibiotics to control infectious diseases, and strict control of serum Ca and phosphate. Calcimimetics were used in all patients except one who had undergone PTx one month before, sodium thiosulfate was used in 4 patients, and low Ca dialysate was used in three patients. The average follow-up period was 7.4 months. Four patients were cured, and one died due to infection. We suggest that multidisciplinary management for infectious diseases, surgical debridement, strict control of mineral and bone markers from the early stage, and elimination of risk factors may improve the course of calciphylaxis, which is a life-threatening disease.

Topics: Adult; Aged; Calciphylaxis; Combined Modality Therapy; Female; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Hyperphosphatemia; Interdisciplinary Communication; Male; Middle Aged; Necrosis; Parathyroidectomy; Receptors, Calcitriol; Renal Dialysis; Skin Ulcer; Treatment Outcome; Warfarin

Topics: Administration, Topical; Antiphospholipid Syndrome; Humans; Necrosis; Tacrolimus; Warfarin

Topics: Anticoagulants; Coronary Artery Bypass; Coronary Artery Disease; Humans; Leg; Male; Middle Aged; Necrosis; Skin; Warfarin

Warfarin induced skin necrosis is a rare debilitating and, in some cases, life-threatening complication. A 47-year-old male on life-long anticoagulation omits his medication and develops extensive skin necrosis of the left leg complicated by acute renal failure three days after restarting warfarin. Investigations reveal possible Protein S deficiency which is known to be a predisposing condition. Various mechanisms have been proposed as the underlying cause. He was managed on heparin, wound debridement and skin grafting. Warfarin was restarted concurrently with heparin. Knowledge of this complication will enable timely diagnosis and treatment.. None declared.

Topics: Anticoagulants; Combined Modality Therapy; Humans; Male; Middle Aged; Necrosis; Protein C; Protein S; Skin Transplantation; Stroke Volume; Ventricular Function, Left; 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

A myriad of different phenomena exist in the dermatological literature which are based on the concept of locus minores resistentiae. The most commonly described phenomenon is the Koebner phenomenon, which is classically associated with the emergence of psoriatic lesions post trauma. Warfarin-induced skin necrosis (WISN) is a rare but severe side effect that leads to necrosis of the skin, predominantly on areas with increased subcutaneous fat. The presented case reports on WISN within psoriatic plaques.

Topics: Adult; Anticoagulants; Female; Humans; Necrosis; Psoriasis; Purpura; Skin; Warfarin

The incidence of warfarin-induced skin necrosis (WISN) is rare. The majority of WISN cases usually appear between 3 and 6 days after the initiation of warfarin therapy. Here we report a late-onset case of WISN that occurred in a 52-year-old man 4 years after the initiation of therapy. The skin lesions in the patient were associated with acquired deficiency of protein C and protein S and abnormal liver function.

Topics: Anticoagulants; Drug Eruptions; Humans; Liver Diseases; Male; Middle Aged; Necrosis; Protein C Deficiency; Protein S Deficiency; Time Factors; Warfarin

Topics: Adolescent; Female; Humans; Necrosis; Protein C; Protein C Deficiency; Rivaroxaban; Secondary Prevention; Skin Diseases; Thrombin; Thrombomodulin; Warfarin

Patients with protein C deficiency are at increased risk for thrombolic diseases. Non-vitamin K antagonist anticoagulant options should be considered in patients with warfarin-induced skin necrosis (WISN) in the setting of protein C. We report a 41-year-old African American male patient with WISN and protein C deficiency who was treated with rivaroxaban followed by dabigatran. After 1 month on rivaroxaban, he began experiencing blood in his stools, unrelenting pain in his lower extremities, found it difficult to obtain medication despite having insurance and as a result did not maintain compliance. He was then assessed at the hospital, symptomatically treated and discharged on dabigatran. After 6 weeks, he reported symptomatic relief and less side effects. This case involved a head-to-head clinical comparison of rivaroxaban and dabigatran as alternatives to warfarin anticoagulation therapy.

Topics: Adult; Anticoagulants; Diagnosis, Differential; Humans; Male; Necrosis; Protein C Deficiency; Skin Diseases; Venous Thromboembolism; Warfarin

Topics: Anticoagulants; Biopsy, Needle; Disease Progression; Erythema; Female; Humans; Immunohistochemistry; Lower Extremity; Middle Aged; Necrosis; Prednisone; Prognosis; Risk Assessment; Skin; Treatment Outcome; Vasculitis, Leukocytoclastic, Cutaneous; Warfarin

Topics: Administration, Oral; Anticoagulants; Coumarins; Drug Eruptions; Female; Humans; Necrosis; Prognosis; Risk Factors; Skin; Warfarin

Topics: Aged; Anticoagulants; Drug Substitution; Factor Xa Inhibitors; Humans; Kidney Diseases; Male; Necrosis; Rivaroxaban; Skin; Skin Diseases; Warfarin; Wound Healing

Topics: Adult; Anticoagulants; Drug Eruptions; Exanthema; Female; Humans; Necrosis; Purpura; Skin; Warfarin

Skin is the target of both acute and chronic exposure to warfarin, coumarin anticoagulant. Single exposure of rat skin to this agent induces early (24 h following epicutaneous administration) local response which might be part of inflammatory/reparatory homeostatic program or introduction to pathological events in exposed skin.. To examine time-dependent changes in skin of rats exposed to epicutaneously applied warfarin.. The effect of low (10 μg) and high (100 μg) doses of warfarin on histologically evident changes of epidermis (epidermal thickness) and dermis (numbers of mesenchymal cells and dermal capillaries), skin cell proliferative activity (Ki67(+) and PCNA(+) cells) and apoptotic (TUNEL(+)) and necrotic (ultra structural appearance) cells was examined one, three and seven days after the application.. Both warfarin doses affected the majority of skin cell activity, but with differential time-course of skin epidermal and dermal cells state/activity. The occurrence of necrotic/apoptotic epidermal and dermal cells was noted the first day after the application and the activities which point to tissue reparation/remodeling were observed seven days after skin exposure to this agent.. The observed pattern of changes (early evidence of cell/tissue injury which was later followed by signs of cell activity characteristic for tissue reparation/remodeling) implied warfarin-induced toxicity in skin cells as stimulus for subsequent activities relevant for tissue homeostasis.. The data presented provide new and additional information concerning skin responses to warfarin that gains access to this tissue.

Topics: Administration, Cutaneous; Animals; Anticoagulants; Apoptosis; Cell Proliferation; Ki-67 Antigen; Male; Necrosis; Proliferating Cell Nuclear Antigen; Rats; Rodenticides; Skin; Warfarin

Topics: Female; Humans; Middle Aged; Necrosis; Venous Thrombosis; Warfarin

Warfarin-induced skin necrosis (WISN) is a rare complication of anticoagulant therapy associated with a high incidence of  morbidity and mortality requiring immediate drug cessation. At particular risk are those with various thrombophilic abnormalities, especially when warfarinisation is undertaken rapidly with large loading doses of warfarin. Cutaneous findings include petechiae that progress to ecchymosis and hemorrhagic bullae. With the increasing number of patients anticoagulated as out-patients for thromboprophylaxis, we are concerned that the incidence of skin necrosis may increase. We present a case of WISN with low protein C level. He was a 50-year-old male who came to our department because of acute infarction in irrigation area of the superior cerebellar artery. He had intermittent atrial fibrillation and was started on anticoagulant therapy.  After few day of therapy, he developed skin necrosis, and his level of protein C was low. Warfarin-induced skin necrosis is a rare but serious complication that can be prevented by routine screening for protein C, protein S or antithrombin deficiencies or for the presence of antiphospholipid antibodies before beginning warfarin therapy.

Topics: Anticoagulants; Humans; Male; Middle Aged; Necrosis; Protein C Deficiency; Skin Diseases; Warfarin

Topics: Anticoagulants; Aortic Aneurysm, Abdominal; Aortic Rupture; Blood Coagulation Factors; Humans; Male; Middle Aged; Necrosis; Perioperative Care; Skin; Warfarin

Topics: Aged; Anticoagulants; Drug Eruptions; Female; Humans; Leg Dermatoses; Necrosis; Obesity; Skin; Warfarin

A 55-year-old woman presented with an extensive warfarin-induced skin necrosis while an inpatient for treatment of a pulmonary embolism and thromboembolic stroke. She had a background of diabetes mellitus, hypertension and dyslipidaemia. Her warfarin was stopped and she was anticoagulated with low-molecular weight heparin. The wound was successfully treated with a combination of antibiotic, debridement and negative pressure wound therapy.

Topics: Anticoagulants; Drug Eruptions; Female; Humans; Middle Aged; Necrosis; Negative-Pressure Wound Therapy; Remission Induction; Skin; Warfarin

Topics: Adolescent; Female; Humans; Livedo Reticularis; Necrosis; Protein S Deficiency; Skin; Warfarin

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Diagnosis, Differential; Humans; Ischemic Attack, Transient; Male; Middle Aged; Necrosis; Skin; Skin Diseases; Thrombosis; Warfarin

Topics: Aged, 80 and over; Amputation, Surgical; Anticoagulants; Hand; Humans; Leg; Male; Necrosis; Scrotum; Skin Diseases; Warfarin

Topics: Adult; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Humans; International Normalized Ratio; Male; Necrosis; Polymorphism, Genetic; Skin; Warfarin

A patient with a history of deep vein thrombosis presented with painful bruising and blistering on his left leg 7-10 days after warfarin treatment. A complicated 2-month treatment followed, where vasculitis was originally diagnosed from histological findings before the final diagnosis of warfarin-induced skin necrosis (WISN) was made on clinical grounds. Warfarin was stopped, reversed and low molecular weight heparin started but, the lesions had progressed to full thickness necrosis. This was originally treated with conventional surgical debridement before introducing maggot debridement therapy (MDT) in an effort to try to salvage the limb.

Topics: Aged; Animals; Anticoagulants; Debridement; Diagnosis, Differential; Humans; Larva; Male; Necrosis; Skin; Venous Thrombosis; Warfarin

Topics: Adolescent; Anticoagulants; Drug Eruptions; Female; Humans; Necrosis; Protein S Deficiency; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Diagnosis, Differential; Fatal Outcome; Female; Humans; Necrosis; Skin Diseases; Warfarin

Topics: Anticoagulants; Benzimidazoles; Dabigatran; Drug Eruptions; Drug Substitution; Female; Humans; Necrosis; Protein C Deficiency; Pyridines; Severity of Illness Index; Skin; Warfarin; Young Adult

Topics: Aged; Anticoagulants; Atrial Fibrillation; Diagnosis, Differential; Drug Eruptions; Elbow; Heparin; Humans; Male; Necrosis; Skin; Warfarin

A 30-year-old man with a history of bilateral deep vein thromboses and recurrent penile ischemic episodes presented for distal penile amputation and skin graft. Despite suspicion, serologies indicated no hypercoagulable disorder. After surgery, the patient was bridged from enoxaparin to warfarin. Nine days after initiation of warfarin therapy, he developed necrotic arm ulcers, which were subsequently proved to be secondary to warfarin-induced skin necrosis.

Topics: Adult; Anticoagulants; Humans; Ischemia; Male; Necrosis; Penis; Skin; Warfarin

Chronic thromboembolic pulmonary hypertension (CTEPH) is a chronic progressive disease of pulmonary circulation characterised by indistinct ethiopathogenesis. We present a case of a 50 year-old male with thrombophilia of unknown origin leading to the formation of multiple thrombi within venous circulation followed by episodes of acute pulmonary embolism resulting ultimately in acute heart failure in the course of developing CTEPH. Unfortunately, despite the wide range of haemostasis laboratory tests we were not able to define the type of coagulation abnormality. Owing to the efficient cooperation between cardiologists and cardiosurgeons it was possible to save patient's life.

Topics: Acenocoumarol; Anticoagulants; Cardiac Surgical Procedures; Coronary Thrombosis; Echocardiography, Doppler; Humans; Hypertension, Pulmonary; Intestine, Small; Male; Middle Aged; Myocardial Infarction; Necrosis; Pulmonary Embolism; Stroke; Time Factors; Treatment Outcome; Warfarin

Topics: Administration, Oral; Aged; Anticoagulants; Drug Eruptions; Female; Humans; Necrosis; Skin; Warfarin

Few prospective studies have evaluated the safety of dermatologic surgery.. We sought to determine rates of bleeding, infection, flap and graft necrosis, and dehiscence in outpatient dermatologic surgery, and to examine their relationship to type of repair, anatomic location of repair, antibiotic use, antiplatelet use, or anticoagulant use.. Patients presenting to University of Massachusetts Medical School Dermatology Clinic for surgery during a 15-month period were prospectively entered. Medications, procedures, and complications were recorded.. Of the 1911 patients, 38% were on one anticoagulant or antiplatelet medication, and 8.0% were on two or more. Risk of hemorrhage was 0.89%. Complex repair (odds ratio [OR] = 5.80), graft repair (OR = 7.58), flap repair (OR = 11.93), and partial repair (OR = 43.13) were more likely to result in bleeding than intermediate repair. Patients on both clopidogrel and warfarin were 40 times more likely to have bleeding complications than all others (P = .03). Risk of infection was 1.3%, but was greater than 3% on the genitalia, scalp, back, and leg. Partial flap necrosis occurred in 1.7% of flaps, and partial graft necrosis occurred in 8.6% of grafts. Partial graft necrosis occurred in 20% of grafts on the scalp and 10% of grafts on the nose. All complications resolved without sequelae.. The study was limited to one academic dermatology practice.. The rate of complications in dermatologic surgery is low, even when multiple oral anticoagulant and antiplatelet medications are continued, and prophylactic antibiotics are not used. Closure type and use of warfarin or clopidogrel increase bleeding risk. However, these medications should be continued to avoid adverse thrombotic events.

Topics: Aged; Ambulatory Surgical Procedures; Antibiotic Prophylaxis; Anticoagulants; Clopidogrel; Dermatologic Surgical Procedures; Female; Humans; Male; Mohs Surgery; Necrosis; Platelet Aggregation Inhibitors; Postoperative Complications; Postoperative Hemorrhage; Surgical Flaps; Surgical Wound Infection; Ticlopidine; Warfarin

Topics: Acute Kidney Injury; Anti-Inflammatory Agents; Anticoagulants; Biopsy; Cyclophosphamide; Diagnosis, Differential; Female; Heparin, Low-Molecular-Weight; Humans; Immunoglobulin A; Immunosuppressive Agents; Kidney Tubules; Methylprednisolone; Middle Aged; Necrosis; Nephrotic Syndrome; Prednisone; Radiography; Renal Veins; Venous Thrombosis; Warfarin

Necrotic skin lesions are unfortunately common in patients with end stage renal disease undergoing dialysis therapy. We present a case of a necrotic skin lesion in a peritoneal dialysis patient shortly after the initiation of warfarin therapy for atrial fibrillation. We discuss and contrast distinguishing features of two diagnostic possibilities: warfarin skin necrosis (WSN) and calcific uremic arteriopathy (CUA) in terms of clinical presentation, risk factors and pathology. Lastly, we outline the importance of establishing a diagnosis as treatment regimens differ substantially.

Topics: Anticoagulants; Calciphylaxis; Diabetic Nephropathies; Diagnosis, Differential; Humans; Kidney Failure, Chronic; Male; Middle Aged; Necrosis; Skin Diseases; Warfarin

There is a lack of guidelines regarding the selection of patients who need intravenous heparin, duration of intravenous heparin, and future use of warfarin in prevention and treatment of warfarin-induced skin necrosis. This case report emphasizes the challenges in dealing with vitamin K antagonists (VKA) therapy.

Topics: Aged; Anticoagulants; Combined Modality Therapy; Drug Administration Schedule; Heparin; Humans; Male; Necrosis; Skin; Systemic Inflammatory Response Syndrome; Thrombophilia; Vitamin K Deficiency; Warfarin

Topics: Anticoagulants; Humans; Male; Middle Aged; Necrosis; Skin; Warfarin

A case of warfarin-induced skin necrosis (WISN) treated with protein C concentrate (human) is reported.. A 46-year-old Caucasian woman was admitted to the hospital for a herpes viral infection complicated by neutropenic fevers of unknown origin. Broad-spectrum antibiotics were initiated, as well as enoxaparin for prophylaxis of deep venous thrombosis. By hospital day 7, the patient's platelets decreased by 50%; by hospital day 8, they decreased another 50%. A test for heparin antibody was positive, and enoxaparin was stopped. Two days later, the patient developed a clot in her peripherally inserted central catheter, and warfarin and argatroban were initiated. Within 24 hours of warfarin initiation, the patient developed swelling in her feet and new lesions on her inner thigh, buttock, face, feet, fingers, and arms. She was treated with phytonadi-one and fresh frozen plasma, but these treatments failed to slow the progression of her lesions, which had turned to necrotic tissue. WISN was suspected, and warfarin therapy was discontinued after three doses. After a consultation with a hematologist, treatment with protein C concentrate (human) was initiated. Within 24 hours of treatment with this product, progression of necrosis stopped, and the patient's respiratory failure resolved. The patient underwent multiple skin grafts, and the lesions healed without extensive scarring. She experienced no adverse effects with the administration of protein C concentrate (human).. A patient with WISN was treated with protein C concentrate (human) with overall good results and no adverse effects.

Topics: Anticoagulants; Female; Humans; Middle Aged; Necrosis; Protein C; Respiratory Insufficiency; Skin; Skin Diseases; Skin Transplantation; Warfarin

At the turn of the century, only 300 cases of warfarin-induced skin necrosis (WISN) had been reported. WISN is a rare but potentially fatal complication of warfarin therapy. There are no published reports of WISN occurring in patients with HIV-1 infection or tuberculosis (TB).. We retrospectively reviewed cases of WISN presenting from April 2005 to July 2008 at a referral hospital in Cape Town, South Africa.. Six cases of WISN occurred in 973 patients receiving warfarin therapy for venous thrombosis (0.62%, 95% CI 0.25 - 1.37%). All 6 cases occurred in HIV-1-infected women (median age 30 years, range 27 - 42) with microbiologically confirmed TB and venous thrombosis. All were profoundly immunosuppressed (median CD4+ count at TB diagnosis 49 cells/microl, interquartile range 23 - 170). Of the 3 patients receiving combination antiretroviral therapy, 2 had TB-IRIS (immune reconstitution inflammatory syndrome). The median interval from initiation of antituberculosis treatment to venous thrombosis was 37 days (range 0 - 150). The median duration of parallel heparin and warfarin therapy was 2 days (range 1 - 6). WISN manifested 6 days (range 4 - 8) after initiation of warfarin therapy. The international normalised ratio (INR) at WISN onset was supra-therapeutic, median 6.2 (range 3.8 - 6.6). Sites of WISN included breasts, buttocks and thighs. Four of 6 WISN sites were secondarily infected with drug-resistant nosocomial bacteria (methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae) 17 - 37 days after WISN onset. In 4 patients, the median interval from WISN onset to death was 43 days (range 25 - 45). One of the 2 patients who survived underwent bilateral mastectomies and extensive skin grafting at a specialist centre.. This is one of the largest case series of WISN. We report a novel clinical entity: WISN in HIV-1 infected patients with TB and venous thrombosis. The occurrence of 6 WISN cases in a 40-month period may be attributed to (i) hypercoagulability, secondary to HIV-1 and TB: (ii) short concurrent heparin and warfarin therapy; and (iii) high loading doses of warfarin. Active prevention and appropriate management of WISN are likely to improve the dire morbidity and mortality of this unusual condition.

Topics: Adult; Anticoagulants; Comorbidity; Female; HIV Infections; Humans; Necrosis; Retrospective Studies; Skin; Tuberculosis; Tuberculosis, Pulmonary; Venous Thrombosis; Warfarin

Topics: Emergencies; Exanthema; Female; Humans; Leg; Middle Aged; Necrosis; Skin; Venous Thrombosis; Warfarin

A 56-yr-old man with lung adenocarcinoma presented with subsegmental pulmonary thrombosis. Platelet count on presentation was 531 x 10(9)/L. The patient was anticoagulated with subcutaneous low molecular weight heparin (LMWH). Next day, oral anticoagulation was initiated with 5 mg of warfarin once daily with LMWH and LMWH was discontinued at third hospital day. On the third day of oral anticoagulation therapy, he complained of left leg swelling and prolonged painful penile erection of 24 hr-duration. His platelet count reached a nadir 164 x 10(9)/L at that time, and the patient had a deficiency of protein C and S, with an activity level of 16% and 20% of normal value. Warfarin was stopped and he underwent penile aspiration. The next day, left leg edema and penile erection was disappeared, but penile and glans penis necrosis was started. This case illustrates that processes underlying heparin-induced thrombocytopenia (HIT) may also underlie warfarin-induced skin necrosis.

Topics: Adenocarcinoma; Anticoagulants; Heparin; Humans; Lung Neoplasms; Male; Middle Aged; Necrosis; Penile Erection; Penis; Platelet Count; Protein C; Protein S; Pulmonary Artery; Thrombocytopenia; Thrombosis; Warfarin

Warfarin-induced skin necrosis is a rare but recognised complication of this drug. The condition predominantly affects the breasts, buttocks and thighs of obese, peri-menopausal women. We present the case of a patient with the condition in an unusual site, and we discuss the management challenges involved.. An 82-year-old man presented to the ENT department with a diagnosis of pinna haematoma. There was no history of trauma or infection. The patient was taking warfarin long-term for recurrent deep vein thrombosis. Two weeks prior to admission, the patient had had a loading course of warfarin following surgery. Multiple clinical teams were involved in treatment. The only abnormal laboratory investigation was a low protein S level; biopsy showed skin necrosis.. In this case, the unusual presentation created diagnostic confusion, and may have precipitated aggressive surgical debridement. However, a more conservative management strategy was used, which we would recommend in future.

Topics: Aged, 80 and over; Anticoagulants; Ear Auricle; Humans; Male; Necrosis; Skin; Skin Diseases; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Drug Eruptions; Heparin, Low-Molecular-Weight; Humans; Male; Necrosis; Warfarin

Topics: Abdomen, Acute; Aged; Anticoagulants; Atrial Fibrillation; Gallbladder Diseases; Hemorrhage; Humans; Male; Necrosis; Warfarin

A case of heparin-induced thrombocytopenia (HIT) complicated by warfarin-induced skin necrosis (WISN) is reported.. A patient with a history of hypertension, heart failure, and myocardial infarction was admitted to the hospital after complaining of a two-day history of shortness of breath, diaphoresis, and chest pain. The patient underwent a cardiac catheterization and received several medications, including heparin. Suspicions of HIT occurred when her platelets began to decrease severely and she developed a left groin hematoma and a pseudoaneurysm. Lepirudin was initiated and a heparin platelet factor 4 (PF4) antibody test was performed. The results were negative and lepirudin was discontinued. She was rechallenged with unfractionated heparin (UFH) after surgery of the pseudoaneurysm, but her platelets began to decrease again. A second PF4 test was performed, the results of which were positive. The UFH treatment was discontinued. Warfarin was also initiated after surgery and the patient's platelets rapidly increased after heparin was discontinued. She was discharged one week later. Three days after discharge, she was readmitted after complaining of severe pain and swelling of the fatty tissue of her right flank that began the day after she was discharged. Some blistering and necrosis were noted on the lesion. Histological sections showed focal thrombosis of vessels in the deep reticular dermis consistent with WISN. Local wound care was given to manage the WISN, lepirudin was initiated, and warfarin was discontinued and reinstated one week later at a low dosage.. A patient with HIT developed severe skin necrosis after initiation of warfarin therapy.

Topics: Anticoagulants; Female; Heparin; Humans; Middle Aged; Necrosis; Skin; Thrombocytopenia; Warfarin

A 64-year-old woman with colon carcinoma presented with subsegmental pulmonary emboli. Platelet count on presentation was 598 x10(9)/l. The patient was anticoagulated with intravenous heparin. By hospital day 3, heparin was replaced with enoxaparin and warfarin. On hospital day 6, the patient developed a 20 x 15 cm area of necrotic skin on her left hip and a 1 x 3 cm area of necrosis on her right hip. By that time, her platelet count had fallen to 433 x 10(9)/l. Three days later (hospital day 9), anticoagulation was switched from the combination of enoxaparin and warfarin to argatroban. Her platelet count reached a nadir of 82 x 10(9)/l by the 12th hospital day. The areas of skin necrosis had never been sites of heparin injection. Heparin/platelet factor 4 antibody, sent on hospital day 9, returned positive and (14)C-serotonin release assay was also positive. This case illustrates that processes underlying heparin-induced thrombocytopenia (HIT) may also underlie warfarin-induced skin necrosis. Skin necrosis may be the earliest manifestation of HIT and need not be accompanied by thrombocytopenia. This patient's course illustrates that HIT should be considered in all patients presenting with skin necrosis while receiving anticoagulation with heparin or a combination of heparin and warfarin.

Topics: Colonic Neoplasms; Female; Heparin; Humans; Middle Aged; Necrosis; Pulmonary Embolism; Skin Diseases; Thrombocytopenia; Warfarin

Hemodialysis complicated by heparin-induced thrombocytopenia (HIT) is a rare event requiring anticoagulation with direct-thrombin inhibitors. Contaminant calcific uremic arteriolopathy (calciphylaxis) further complicates this situation due to the possibility that warfarin anticoagulation may exacerbate skin necrosis. The authors report a patient with renal failure and calciphylaxis who developed HIT after starting hemodialysis. She was successfully treated with Argatroban.

Topics: Adult; Anticoagulants; Arginine; Calciphylaxis; Drug Contamination; Female; Heparin; Humans; Necrosis; Pipecolic Acids; Renal Dialysis; Renal Insufficiency; Skin Diseases; Sulfonamides; Thrombocytopenia; Warfarin

Topics: Aged; Anticoagulants; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Necrosis; Outpatients; Patient Discharge; Pulmonary Embolism; Skin; Skin Diseases; Warfarin

Topics: Antibodies, Anticardiolipin; Anticoagulants; Cryoglobulinemia; Debridement; Enoxaparin; Hepatitis C; Humans; Male; Middle Aged; Necrosis; Penis; Plastic Surgery Procedures; Vasculitis, Leukocytoclastic, Cutaneous; Venous Thrombosis; Warfarin

Topics: Aged; Anticoagulants; Female; Humans; Necrosis; Skin Diseases; Warfarin

Warfarin-induced skin necrosis is the rare but potentially devastating complication of anticoagulant therapy and commonly occurs in previously undetected C- and S-protein deficient patients. Because routine preoperative examination does not include protein C and S level measurement, detection of these patients preoperatively is generally not possible, which increases the risk of occurrence of this important complication. In this report we present and discuss such a patient, who died from warfarin-induced skin necrosis after coronary artery bypass surgery.

Topics: Aged; Anticoagulants; Comorbidity; Coronary Artery Bypass; Coronary Vessels; Endarterectomy; Fatal Outcome; Female; Humans; Myocardial Ischemia; Necrosis; Protein C Deficiency; Protein S Deficiency; Skin; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Drug Eruptions; Eyelid Diseases; Female; Heart Valve Prosthesis Implantation; Humans; Necrosis; Skin; Warfarin

Warfarin-induced skin necrosis is an unusual complication of anticoagulation therapy associated with high morbidity. A patient is presented who had protein C deficiency and in whom this complication developed twice within a short time as a result of delayed diagnosis. Early recognition of this syndrome has important implications in the treatment of such patients and may reduce the severity of complications.

Topics: Adult; Arterial Occlusive Diseases; Humans; Male; Necrosis; Protein C Deficiency; Skin Diseases; Thrombosis; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Cardiac Surgical Procedures; Coumarins; Extremities; Gangrene; Heparin; Humans; International Normalized Ratio; Male; Middle Aged; Necrosis; Thrombocytopenia; Vitamin K; Warfarin

Topics: Anticoagulants; Carcinoma, Signet Ring Cell; Female; Gangrene; Heparin, Low-Molecular-Weight; Humans; Lower Extremity; Lymphatic Metastasis; Middle Aged; Necrosis; Neoplasms, Unknown Primary; Purpura, Thrombotic Thrombocytopenic; Skin; Venous Thrombosis; Warfarin

Warfarin-induced skin necrosis (WISN) is a disorder of unclear etiology that predominantly affects obese women. Although WISN typically occurs within the first 10 days of warfarin therapy, some patients develop the complication several years after warfarin exposure. We describe the case of a 43-year-old Caucasian woman with a history of recurrent thromboembolic disorders, protein S deficiency, and multiple exposures to warfarin who came to the emergency room with complaints of worsening dermatitis that had progressed over a 15-hour period. Examination revealed multiple, diffuse "lace-like" erythematous eruptions with superimposed lesions that were tender, ulcerated, and crusted. A biopsy was performed, and histopathologic findings were consistent with WISN. Based on the Naranjo adverse drug reaction probability scale, a probable causal relationship existed between warfarin and skin necrosis in this patient. Since treatment is generally supportive, prompt and prudent evaluation of suspicious skin lesions is necessary to prevent the serious sequelae associated with WISN.

Topics: Adult; Anticoagulants; Fatal Outcome; Female; Humans; Necrosis; Skin; Skin Diseases; Warfarin

The anticoagulant warfarin can produce a skin necrosis that is clinically indistinguishable from the skin necrosis caused by purpura fulminans associated with disseminated intravascular coagulation (DIC) and heparin-induced thrombocytopenia (HIT). The similar clinical and histologic findings observed in each of these skin necroses create a challenge for diagnosis and eventual treatment. The authors report a patient with significant risk factors for warfarin-induced skin necrosis, DIC, and HIT presenting with painful, purpuric patches beginning on her feet and extending proximally before becoming hemorrhagic bullae on her lower extremities.

Topics: Aged; Anticoagulants; Biopsy; Carcinoma, Non-Small-Cell Lung; Diagnosis, Differential; Disseminated Intravascular Coagulation; Fatal Outcome; Female; Humans; IgA Vasculitis; Lung Neoplasms; Mediastinal Neoplasms; Necrosis; Pulmonary Embolism; Warfarin

Hemostatic physiology involves a complex interlinking of blood and endothelial factors. Its pharmacological manipulation invariably impacts at multiple molecular sites. Herein is reported an unusual case of coexistent warfarin-induced skin necrosis and heparin-induced thrombocytopenia following mitral valve replacement for thromboembolic phenomena associated with marantic endocarditis and bronchial adenocarcinoma. Thrombophilia in the face of endocarditis should be treated with a suspicion of underlying cancer.

Topics: Adenocarcinoma; Anticoagulants; Bronchial Neoplasms; Endocarditis; Fatal Outcome; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Heparin; Humans; Intracranial Embolism; Male; Middle Aged; Mitral Valve; Necrosis; Postoperative Complications; Skin; Thrombocytopenia; Warfarin

The presence of antiphospholipid antibodies is associated with thromboembolic events, thrombocytopenia and numerous pregnancy complications such as recurrent miscarriage, preeclampsia and HELLP syndrome. This condition is known as the antiphospholipid syndrome (APS). We describe a rare case of recurrent liver necrosis postpartum in two consecutive pregnancies of woman with systemic lupus erythematosus (SLE) and positive antiphospholipid antibodies (aPL) who underwent complete recovery.

Topics: Adult; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Female; Heparin, Low-Molecular-Weight; Humans; Liver Diseases; Magnetic Resonance Imaging; Necrosis; Pregnancy; Pregnancy Complications; Recurrence; Warfarin

Topics: Anticoagulants; Humans; Male; Middle Aged; Necrosis; Priapism; Protein C Deficiency; Risk Factors; Skin Diseases; Warfarin

Necrosis of the digits is a rare complication of warfarin therapy of obscure pathogenesis. We report a 61-year-old woman with a 12-month history of Raynaud's phenomenon who developed multiple digital necrosis following aortic valve replacement with mechanical prosthesis for aortic insufficiency caused by nonbacterial thrombotic endocarditis. Exacerbation of Raynaud's phenomenon occurred during the postoperative period, with daily episodes of ischemia of the fingers and toes that improved with local warming. However, coincident with the occurrence of immune heparin-induced thrombocytopenia, and while undergoing routine warfarin anticoagulation because of the mechanical valve prosthesis, the patient abruptly developed progression of digital ischemia to multiple digital necrosis on postoperative day 8, at the time the international normalized ratio reached its peak value of 4.3. All limb pulses were readily palpable, and vascular imaging studies showed thrombosis only in the superficial femoral and popliteal veins of the right leg. Coagulation studies showed greatly elevated levels of thrombin-antithrombin complexes and prothrombin fragment F1.2 levels, consistent with uncontrolled thrombin generation. After vitamin K administration, no abnormalities of the protein C anticoagulant pathway were identified, consistent with previous studies of other patients with warfarin-induced necrosis complicating heparin-induced thrombocytopenia. Subsequently, the patient was shown to have metastatic breast adenocarcinoma, which explained the patient's initial presentation with nonbacterial thrombotic endocarditis. This patient case suggests that multiple digital gangrene can result from the interaction of various localizing and systemic factors, including compromised microvascular blood flow (Raynaud's phenomenon), increased thrombin generation (heparin-induced thrombocytopenia, adenocarcinoma), and warfarin-induced failure of the protein C natural anticoagulant pathway.

Topics: Adenocarcinoma; Anticoagulants; Aortic Valve; Endocarditis; Female; Fingers; Heart Valve Prosthesis Implantation; Heparin; Humans; Ischemia; Middle Aged; Necrosis; Postoperative Period; Raynaud Disease; Thrombocytopenia; Thrombosis; Toes; Warfarin

Heparin-induced thrombocytopenia (HIT) is a common, often catastrophic, syndrome that produces the most hypercoagulable of states. Emerging therapeutic strategies use alternative anticoagulants; warfarin's place is being reexamined. Early in the course of warfarin therapy, there may be net procoagulant effects because of the inhibition of protein C. With HIT, it has been suggested that unopposed warfarin can precipitate venous limb gangrene. There are also reports of warfarin-induced skin necrosis. We seek to confirm and increase awareness of the risks of warfarin with HIT.. We describe 6 patients with HIT seen at 3 medical centers in whom frank or impending venous limb gangrene, central skin necrosis, or both were temporally related to warfarin initiation.. At warfarin initiation, 5 patients had recognized HIT and 1 had it recognized later. Complications emerged after 2 to 7 days, and consisted of warfarin-induced skin necrosis (n = 5) and venous limb gangrene (n = 2); 1 patient had both. This emerged with unopposed warfarin in 4 patients and as a direct thrombin inhibitor was being withdrawn in 2. All had supratherapeutic international normalized ratios. One patient required leg and breast amputations, and another one died.. Because of the early effects on protein C, warfarin can precipitate venous limb gangrene and/or skin necrosis in the extreme hypercoagulable milieu of HIT. With HIT, unopposed warfarin should be avoided and caution is needed during transition from a direct thrombin inhibitor. Warfarin should be initiated at modest doses in patients with HIT after platelet recovery. Implications extend to warfarin initiation with other thrombotic diatheses.

Topics: Adult; Aged; Anticoagulants; Drug Eruptions; Female; Gangrene; Heparin; Humans; Leg; Male; Middle Aged; Necrosis; Thrombocytopenia; Warfarin

The use of warfarin is rarely complicated by skin necrosis. We describe a 50-year-old woman who presented with a left leg deep venous thrombosis and subsequent pulmonary embolism. She was initially anticoagulated with low-molecular weight heparin and subsequently warfarin. Within 4 days abdominal skin necrosis developed. Investigations revealed the presence of protein S deficiency and in addition, a mutation in the methylenetetrahydrofolate reductase gene (MTHFR). We present, to our best knowledge, the first case of warfarin skin necrosis associated with a methylenetetrahydrofolate reductase mutation.

Topics: Anticoagulants; Drug Eruptions; Female; Humans; Leg; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Necrosis; Protein S Deficiency; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Female; Heparin; Humans; Middle Aged; Necrosis; Skin; Thrombocytopenia; Warfarin

Warfarin-induced skin necrosis is a rare complication associated with the use of oral anticoagulants. Most patients develop this at the initiation of therapy, often while still receiving intravenous unfractionated heparin (UFH). Recently, low-molecular-weight heparins (LMWHs) have gained wider use, providing an option for outpatient treatment of deep-vein thrombosis. The treatment protocols are similar to UFH, including the early initiation of oral anticoagulation with warfarin. A Medline search failed to reveal any cases of warfarin-induced skin necrosis while using a LMWH. We present a patient with protein S deficiency who developed warfarin skin necrosis despite appropriate anticoagulation with enoxaparin, and review the chemical and clinical difference between UFH and LMWH.

Topics: Anticoagulants; Arterial Occlusive Diseases; Enoxaparin; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Necrosis; Popliteal Artery; Postoperative Complications; Protein S Deficiency; Skin Diseases; Subclavian Vein; Tibial Arteries; Treatment Failure; Vascular Surgical Procedures; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Breast; Dermatologic Surgical Procedures; Factor V; Female; Heparin; Humans; Necrosis; Pulmonary Embolism; Skin; Warfarin

Topics: Anticoagulants; Contraindications; Heparin; Humans; Necrosis; Skin; Thrombocytopenia; Warfarin

A 36-year-old woman developed skin necrosis of the inner thighs following the re-introduction of warfarin after a laparoscopic cholecystectomy. She had a history of liver disease and cardiomyopathy and was on warfarin for 10 years. Warfarin-induced skin necrosis secondary to protein C deficiency was diagnosed. Although warfarin was ceased immediately, the prothrombin time measurements remained prolonged and warfarin levels remained therapeutic. Our patient, who had attached great significance to warfarin therapy, had continued the ingestion of warfarin despite our advice. She required three surgical debridements. Protein C levels, as measured 1 year later, were within normal limits, confirming the transient nature of the acquired deficiency during the acute event. This is the second reported case of warfarin necrosis associated with acquired protein C deficiency.

Topics: Adult; Anticoagulants; Cardiomyopathy, Dilated; Cholelithiasis; Diagnosis, Differential; Drug Eruptions; Female; Humans; Leg; Necrosis; Protein C Deficiency; Warfarin

Topics: Anticoagulants; Female; Humans; Middle Aged; Necrosis; Skin Diseases; Venous Thrombosis; Warfarin

Portal vein thrombosis (PVT) is a complication of hepatic disease and a potentially lethal complication of splenectomy. The reported incidence of this complication is low (approximately 1%). However, its true incidence may have been underestimated due to difficulty in making the diagnosis. Herein we report the case of a 19 year-old woman who presented with a 2-year history of idiopathic thrombocytopenic purpura (ITP). Because she had become refractory to medical therapy, she underwent laparoscopic splenectomy. She was discharged on postoperative day 2 after an uncomplicated procedure. She did well, complaining only of mild backache, until postoperative day 21, when she presented with nausea, vomiting, and leukocytosis. CT showed PVT and superior mesenteric vein thrombosis. Despite heparin and fluid administration, her condition worsened. At laparotomy, she had diffuse small bowel edema and congestion. At a second-look procedure 24 h later, nearly all her jejunum and ileum were necrotic. After three procedures, she was left with 45 cm of proximal and 10 cm of distal small bowel. Bowel continuity was restored 8 weeks later. She continued on warfarin anticoagulation therapy for 1 year. Postsplenectomy PVT is most often seen following splenectomy for myeloproliferative disorders and almost never after trauma. The large splenic vein stump and the hypercoagulable state in patients with splenomegaly are thought to be contributory. The presentation of PVT is vague, without defining signs or symptoms. Color-flow Doppler and contrast-enhanced CT scans are the best methods for the nonoperative diagnosis of PVT. Aggressive thrombolysis offers the best hope for clot lysis and maintenance of bowel viability. Even vague symptoms must be considered seriously following splenectomy.

Topics: Adult; Anastomosis, Surgical; Anticoagulants; Back Pain; Combined Modality Therapy; Crystalloid Solutions; Diagnostic Errors; Female; Fluid Therapy; Heparin; Humans; Ileum; Immunosuppressive Agents; Ischemia; Isotonic Solutions; Jejunum; Laparoscopy; Mesenteric Veins; Muscular Diseases; Necrosis; Parenteral Nutrition; Plasma Substitutes; Plasmapheresis; Platelet Transfusion; Portal Vein; Postoperative Complications; Purpura, Thrombocytopenic, Idiopathic; Splenectomy; Splenomegaly; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Child; Dermatan Sulfate; Heparin; Humans; Male; Necrosis; Protein C; Protein C Deficiency; Skin; Thrombocytopenia; Warfarin

A 43-year-old woman developed tenderness and induration of her thighs and lower abdomen, 56 days after commencing warfarin for aortic and mitral valve replacements. Investigations showed elevated inflammatory markers, mild renal impairment, normal echocardiogram and low protein C and S levels consistent with warfarin therapy. Three weeks later, purpuric areas evolved into large tender haemoserous bullae, which broke down to form ulcers. Histology confirmed the clinical impression of warfarin-induced skin necrosis with dermal and subcutaneous venular thrombi. Despite cessation of warfarin and commencement of heparin, the lesions progressed. When the patient became febrile, blood cultures grew Pseudomonas aeruginosa, which was treated with intravenous imipenem and vancomycin. Wound swabs grew methycillin-resistant Staphylococcus aureus and the antibiotics were changed. The patient developed septic shock and, despite intensive care management, her condition deteriorated and she died 9 weeks after the onset of the skin symptoms.

Topics: Adult; Aortic Valve; Biopsy, Needle; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatal Outcome; Female; Heart Valve Prosthesis; Humans; Mitral Valve; Necrosis; Postoperative Care; Rheumatic Heart Disease; Severity of Illness Index; Skin Ulcer; Time Factors; Warfarin

A 34-year-old woman with systemic lupus erythematosus and high titres of antiphospholipid antibodies was admitted to hospital suffering a viral illness but developed haemorrhagic and necrotic areas on the neck and anterior chest 7 days following cessation of warfarin. Anticoagulation had been initiated following a retinal vein thrombosis, but was ceased on day 4 of admission when she was found to be excessively anticoagulated (international normalized ratio (INR) > 10). However, at the time of developing the cutaneous lesions, the INR was sub-therapeutic. Histology of a skin biopsy from the neck revealed thrombosis of upper dermal blood vessels without vasculitis, consistent with antiphospholipid antibody-related skin necrosis. This case illustrates one of the cutaneous features that can occur in patients with elevated titres of antiphospholipid antibodies and the importance of closely monitoring anticoagulation in such patients.

Topics: Adult; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Biopsy, Needle; Drug Therapy, Combination; Female; Follow-Up Studies; Heparin; Humans; Immunohistochemistry; Lupus Erythematosus, Systemic; Neck; Necrosis; Risk Assessment; Severity of Illness Index; Skin Diseases; Treatment Outcome; Warfarin

We report two patients with deep-vein thrombosis complicating immune heparin-induced thrombocytopenia who developed venous limb gangrene during overlapping therapy with a direct thrombin inhibitor (lepirudin or argatroban) and warfarin. In both patients, therapy with the direct thrombin inhibitor was interrupted during persisting severe athrombocytopenia while warfarin administration continued. Both patients exhibited the typical feature of a supratherapeutic international normalized ratio (INRs, 5.9 and 7.3) that has been linked previously with warfarin-associated venous limb gangrene. These data suggest that warfarin anticoagulation be postponed in patients with acute heparin-induced thrombocytopenia until substantial recovery of the platelet count has occurred.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Anticoagulants; Arginine; Autoimmune Diseases; Catheterization, Central Venous; Contraindications; Drug Administration Schedule; Drug Therapy, Combination; Female; Gangrene; Heparin; Hirudin Therapy; Hirudins; Humans; International Normalized Ratio; Leg; Male; Middle Aged; Necrosis; Pipecolic Acids; Protein C Deficiency; Recombinant Proteins; Sulfonamides; Surgical Wound Infection; Thrombin; Thrombocytopenia; Thrombophlebitis; Warfarin

Vascular complications are frequent in long-term dialysis patients. The differential diagnosis is complex and includes immunological derangement (underlying disease, uremia), vasculopathic-atheroembolic diseases, calciphylaxis, infections, neoplasm, coagulation disorders, and adverse drug effects.. We report on a 50-year-old male patient with a long follow-up on renal replacement therapy (20 years), currently on daily hemodialysis. The patient's history of kidney transplantation was complicated by seven acute rejection episodes and by Kaposi sarcoma; comorbidity included HLA-B27 positive ankylosing spondylitis, diffuse vascular disease, recurrent atrial fibrillation, chronic hypotension, HCV positivity. Ten days after the start of warfarin for an atrial fibrillation episode, the patient developed digital necrotising ulcerations, rapidly evolving into partial symmetric digital gangrene at distal phalanxes. The timing and evolution of the lesions and the finding of protein S deficiency were the clues for diagnosing warfarin-induced skin necrosis (WISN); the drug was discontinued and therapy with low-molecular weight heparin, plasma and prostacyclin achieved slow resolution of lesions.. According to a combined MEDLINE and EMBASE search, this is the first report of WISN in a hemodialysis patient: underlining the clinical relevance of this uncommon problem, this case exemplifies the difficult differential diagnosis of acute vascular skin lesions in dialysis

Topics: Anticoagulants; Databases as Topic; Diagnosis, Differential; Dialysis; Fingers; Gangrene; HLA-B27 Antigen; Humans; Male; Middle Aged; Necrosis; Renal Replacement Therapy; Skin; Spondylitis, Ankylosing; Vascular Diseases; Warfarin

Skin necrosis associated with warfarin anticoagulation is a rare but serious complication. Few cases of warfarin-induced skin necrosis are found in the orthopaedic literature. We report a fatal case of warfarin-induced skin necrosis after total hip arthroplasty.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Fatal Outcome; Female; Humans; Necrosis; Postoperative Complications; Skin; Warfarin

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

Thrombotic events are rare complications during anticoagulation therapy. The thrombosis varies from localized cutaneous involvement to catastrophic thromboembolism and is usually associated with an underlying thrombophilia. We describe a patient who developed skin necrosis during warfarin treatment for a pulmonary thromboembolism. The management was complicated by the development of heparin-induced thrombocytopenia and further thrombotic events. Thrombophilia screen demonstrated the presence of protein S deficiency and Factor V Leiden as the prothrombotic factors, together with the demonstration of antiplatelet factor 4 antibodies, which confirms the diagnosis of heparin-induced thrombocytopenia (type II). Reinstitution of warfarin at a low loading dose was successful without the recurrence of skin lesions nor any further thrombosis.

Topics: Adult; Anticoagulants; Autoantibodies; Factor V; Female; Humans; Necrosis; Platelet Count; Platelet Factor 4; Protein S Deficiency; Purpura, Thrombocytopenic; Skin; Skin Diseases; Thrombophilia; Warfarin

Topics: Aged; Anticoagulants; Factor V; Female; Humans; Mutation; Necrosis; Skin; Warfarin

Skin necrosis and priapism are unusual complications of warfarin therapy. We report a teenager with warfarin-associated skin necrosis and priapism who was subsequently found to be a compound heterozygote for protein C deficiency and a heterozygote for the factor V Leiden mutation.

Topics: Adolescent; Anticoagulants; Drug Eruptions; Factor V; Humans; Male; Necrosis; Priapism; Protein C Deficiency; Thrombophilia; Warfarin

Warfarin induced skin necrosis occurs in 0.01-0.1% of warfarin treated patients. The usual presentation is that of painful lesions developing in obese women after the initiation of warfarin treatment. The lesions usually evolve into full thickness skin necrosis within a few days. Although the exact mechanism is not totally clear, low levels of Protein C or S, either functional or inherited, are associated with many of the cases. We report the case of a 17-year-old patient treated with warfarin because of iliofemoral deep vein thrombosis post abortion. The patient developed several huge haemorrhagic blisters on the affected leg. The condition rapidly developed into full thickness skin and fat necrosis. The necrotic lesions were excised and eventually covered with skin graft. The combination of the patient tendency towards hyper-coagulation and the local factors is discussed.

Topics: Adolescent; Anticoagulants; Female; Humans; Necrosis; Skin; Warfarin

Topics: Aged; Female; Humans; Necrosis; Point Mutation; Prothrombin; Skin; Warfarin

Topics: Adult; Anticoagulants; Female; Humans; Necrosis; Puerperal Disorders; Skin; Skin Diseases; Thrombophlebitis; Treatment Refusal; Warfarin

Topics: Anticoagulants; Buttocks; Drug Eruptions; Emergencies; Female; Humans; Middle Aged; Necrosis; Pain; Skin; Venous Thrombosis; Warfarin

Skin necrosis is a rare but serious side-effect of treatment with warfarin. At particular risk are those with various thrombophilic abnormalities, especially when warfarinization is undertaken rapidly with large loading doses of warfarin. With the increasing number of patients anticoagulated as out-patients for thromboprophylaxis, we are concerned that the incidence of skin necrosis may increase. If skin necrosis does occur, prompt remedial action may be of benefit in preventing permanent tissue damage.

Topics: Adult; Anticoagulants; Drug Eruptions; Female; Humans; Necrosis; Skin; Warfarin

We present a kindred with a new mutation of the protein C gene, in which the proband had an unusual clinical presentation. The relationship between warfarin induced skin necrosis and level of anticoagulation was investigated. The pharmacokinetics of protein C concentrate was assessed to determine frequency of replacement therapy. The clinical and biochemical efficacy of therapy with low molecular weight heparin (LMWH) was assessed. The effect of long-term LMWH on bone density in the growing child was monitored using whole body densitometry. Warfarin therapy required an INR of greater than 3.5 to avoid skin necrosis. If protein C replacement was to be used, doses of 100 U/kg/day would have been required to maintain protein C levels consistently at or above 0.20 U/ml. While receiving prophylactic therapy with LMWH for almost 3 years, there were no episodes of recurrent thrombosis, no skin necrosis and no bleeding. Biochemical markers of in vivo thrombin generation were suppressed and within the normal range. Bone density continued to increase at the normal rate throughout the treatment period. LMWH is an effective form of long-term therapy for homozygous protein C deficient patients with measurable protein C levels.

Topics: Adult; Anticoagulants; Biomarkers; Bone Density; Child; Drug Eruptions; Enoxaparin; Female; Heparin; Heparin, Low-Molecular-Weight; Homozygote; Humans; Necrosis; Pedigree; Point Mutation; Protein C; Protein C Deficiency; Skin; Thrombophilia; Warfarin

Skin necrosis is an uncommon complication of warfarin (Coumadin; Dupont Pharma, Wilmington, DE) therapy. The presentation may mimic other disorders. This article reports a case of a 72-year-old woman who presented to the emergency department complaining of swelling and ecchymosis to her left breast and right foot. The patient had been hospitalized for coronary artery bypass grafting, and had been discharged from the hospital earlier that day. This article reviews the pathophysiology and clinical features of warfarin-induced skin necrosis.

Topics: Aged; Anticoagulants; Breast Diseases; Diagnosis, Differential; Emergency Medical Services; Female; Foot Dermatoses; Humans; Necrosis; Skin; Warfarin

Warfarin-induced skin necrosis is a rare and dangerous complication affecting 0.01-0.1% of patients on warfarin. Deficiencies in protein C or protein S in association with other factors have been implicated in its etiology. No report has described this disorder in the immediate postpartum period in patients with protein S deficiency.. A 1-week postpartum woman with known protein S deficiency presented with skin necrosis after a previously uneventful course of warfarin.. Reduced levels of free protein S during the antepartum and immediate postpartum periods predispose protein S-deficient women to warfarin skin necrosis. Previously uncomplicated courses of warfarin do not obviate the possibility of skin necrosis with future warfarin administrations. Initiation of low-dose warfarin with heparin can reduce the likelihood of this disorder.

Topics: Adult; Anticoagulants; Female; Humans; Necrosis; Postpartum Period; Pregnancy; Protein S Deficiency; Skin; Skin Diseases; Warfarin

Skin necrosis is a rare but serious complication of oral anticoagulation with coumarin derivatives. Frequently, the necrosis can be extensive and may result in major morbidity and mortality. The majority of these patients require prolonged anticoagulation for life-threatening conditions such as deep various thrombosis and pulmonary embolism. Resuming oral anticoagulants in the face of skin necrosis is a difficult decision for both the patient and the physician. Because long-term heparin therapy is inconvenient and is associated with significant side effects, we reviewed the literature to find alternative treatment strategies. A Medline search was done, and all papers published in English since 1967 were reviewed. Of 58 cases with skin necrosis attributed to oral anticoagulants, oral anticoagulation was resumed in 7 patients with no resulting adverse effects. Warfarin is the most widely used coumarin derivative in the United States. Based on our review, we make recommendations for resuming warfarin in patients who have developed skin necrosis when the clinical condition absolutely requires prolonged anticoagulation.

Topics: Adult; Anticoagulants; Female; Humans; Male; Middle Aged; Necrosis; Skin Diseases; Warfarin

Topics: Adult; Anticoagulants; Drug Resistance; Female; Humans; Necrosis; Pregnancy; Protein C; Skin; Warfarin

Necrosis of skin and soft tissue as a complication of oral anticoagulation therapy is a rare condition with approximately 200 cases documented in the world. Coumadin-induced skin necrosis is a painful skin lesion, sudden, localized, initially erythematous or hemorrhagic, that becomes bullous and eventually culminates in gangrenous necrosis. It develops mainly in women around 50 years of age who are usually obese and have been treated for thrombophlebitis or pulmonary embolism. There seems to be a marked predilection for areas with increased subcutaneous fat content, such as breasts, thighs, and buttocks. The injury is so significant that plastic surgery is frequently required to repair the damaged tissue. The authors present four clinical cases of Coumadin necrosis, observed in two different institutions, and perform a literature review on the mechanisms that trigger the development of the disease. This condition still remains a diagnostic-therapeutic challenge.

Topics: Adult; Anticoagulants; Female; Humans; Middle Aged; Necrosis; Pulmonary Embolism; Renal Insufficiency; Skin; Thrombophlebitis; Warfarin

Skin necrosis is a rare complication of treatment with coumarin derivatives. Since it was first identified by Verhagen in 1952, approximately 200 cases of skin necrosis have been reported worldwide, but only 73 have been reported in the English language literature. A telltale clinical scenario of pain and petechiae progressing to sharply demarcated ecchymosis, bullae formation, and gangrenous necrosis manifests most often in the adipose tissues of middle-aged women. Necrosis usually appears within 3 to 6 days of the initiation of warfarin sodium therapy. We report a case of cutaneous necrosis that began 46 days after warfarin sodium therapy was begun.

Topics: Adipose Tissue; Female; Humans; Middle Aged; Necrosis; Skin; Warfarin

Topics: Drug Eruptions; Fibrinolytic Agents; Humans; Necrosis; Warfarin

When radiation is used to treat nervous system cancer, exposure of adjacent normal nervous system tissue is unavoidable, and radiation-induced injury may occur. Acute injury is usually mild and transient, but late forms of radiation-induced nervous system injury are usually progressive and debilitating. Treatment with corticosteroids, surgery, and antioxidants is often ineffective. We treated 11 patients with late radiation-induced nervous system injuries (eight with cerebral radionecrosis, one with a myelopathy, and two with plexopathies, all unresponsive to dexamethasone and prednisone) with full anticoagulation. Some recovery of function occurred in five of the eight patients with cerebral radionecrosis, and all the patients with myelopathy or plexopathy. Anticoagulation was continued for 3 to 6 months. In one patient with cerebral radionecrosis, symptoms recurred after discontinuation of anticoagulation and disappeared again after reinstitution of treatment. We hypothesize that anticoagulation may arrest and reverse small-vessel endothelial injury--the fundamental lesion of radiation necrosis--and produce clinical improvement in some patients.

Topics: Adult; Aged; Brain; Brain Neoplasms; Female; Glioblastoma; Heparin; Humans; Male; Middle Aged; Necrosis; Radiation Injuries; Spinal Cord Diseases; Warfarin

Topics: Acenocoumarol; Combined Modality Therapy; Female; Heparin; Humans; Middle Aged; Necrosis; Partial Thromboplastin Time; Plasma; Protein C; Protein C Deficiency; Skin; Thrombophlebitis; Warfarin

Topics: Administration, Oral; Female; Humans; Infant; Male; Milk, Human; Necrosis; Peritoneal Dialysis; Skin; Warfarin

Topics: Aged; Female; Fracture Fixation, Internal; Hip Fractures; Humans; Necrosis; Postoperative Complications; Skin; Thromboembolism; Warfarin

A 62-year-old woman with a 8-month-history of recurrent deep and superficial vein thrombosis developed multiple areas of skin necrosis during warfarin treatment initiation. Routine coagulation tests did not revealed any abnormalities. Protein C plasma activity and concentration were significantly decreased (59.9% and 63.3% of the normal value, respectively). Antithrombin III and protein S (total and free) content were in the normal range. Initially, the adjusted dosage of standard heparin and fresh frozen plasma was administered. Thereafter, the treatment with low doses of oral anticoagulant (acenocoumarol) was reinstalled simultaneously with Protein C Concentrate (Immuno, Vienna) intravenous administration. After six days of the oral anticoagulation the therapeutic value of prothrombin time was obtained and administration of Protein C Concentrate could have been discontinued. No adverse reactions and post-transfusions complications were observed.

Topics: Female; Humans; Middle Aged; Necrosis; Protein C Deficiency; Recurrence; Skin; Thrombophlebitis; Warfarin

Topics: Administration, Oral; Adult; Female; Humans; Necrosis; Skin; Skin Diseases; Warfarin

Topics: Aged; Female; Hip Prosthesis; Humans; Necrosis; Osteoarthritis, Hip; Postoperative Complications; Skin; Warfarin

A female patient with a history of both arterial and venous thrombosis developed extensive skin necrosis following warfarin treatment. When protein C deficiency was diagnosed, successful anticoagulation with warfarin was achieved by prolonging the course of intravenous heparin and introducing warfarin therapy with a low initial dose which was gradually increased. Aspects of the pathogenic mechanism are discussed.

Topics: Adult; Female; Humans; Necrosis; Protein C Deficiency; Skin; Thrombosis; Warfarin

A 58-year-old woman developed Coumadin-induced necrosis of the left breast, resulting in a mastectomy. This patient had experienced an earlier episode of coumadin-induced necrosis that resolved spontaneously. The etiology of this rare complication is unknown. The literature has suggested that patients can be restarted on Coumadin without difficulty. This case and others in the literature suggest that this may not be true. Patients requiring long-term anticoagulation should be considered for other treatment modalities if they develop Coumadin-induced skin necrosis.

Topics: Breast; Female; Humans; Mastectomy, Simple; Middle Aged; Necrosis; Recurrence; Warfarin

The idiosyncratic dermatologic reaction to coumarin-like agents, most notably, Coumadin (warfarin sodium) has been well described in the world's literature. Although the incidence is reported to be less than 0.1% of patients treated with Coumadin, pedal cases tend to be striking and their treatment seemingly tenuous.

Topics: Aged; Female; Foot; Heparin; Humans; Middle Aged; Necrosis; Obesity; Skin; Warfarin

Topics: Aged; Female; Heparin; Humans; Middle Aged; Necrosis; Skin Diseases; Thrombophlebitis; Warfarin

Thromboembolic events occur with a frequency of 3-5% in children with nephrotic syndrome (NS). Although numerous abnormalities in all phases of coagulation have been described in NS, the pathogenesis of clotting abnormalities remains poorly understood in this group of patients. We describe a child with long-standing NS in whom a severe deep venous thrombosis and pulmonary embolism secondary to acquired protein S deficiency and a strong lupus-type circulating anticoagulant developed. In addition, this patient had a markedly decreased plasma level of C4b binding protein. Although acquired protein S deficiency has been described in various clinical disorders including NS, our patient is unusual in having C4bBP deficiency, and his is the only reported pediatric case of NS complicated by thromboembolism in which a circulating anticoagulant has been implicated, to our knowledge.

Topics: Autoimmune Diseases; Carrier Proteins; Child; Complement Inactivator Proteins; Drug Eruptions; Drug Therapy, Combination; Glomerulonephritis, Membranous; Glycoproteins; Heparin; Humans; Lupus Coagulation Inhibitor; Male; Methylprednisolone; Necrosis; Nephrotic Syndrome; Phospholipids; Prednisone; Protein S; Pulmonary Embolism; Thrombolytic Therapy; Thrombophlebitis; Urokinase-Type Plasminogen Activator; Warfarin

Skin necrosis is a well-known yet rare complication of oral anticoagulant therapy. We report the unusual recurrence of lesions typical of warfarin skin necrosis in the absence of anticoagulant therapy. A 59-year-old woman developed skin necrosis while receiving prophylactic warfarin following the detection of a large left ventricular thrombus. The warfarin was discontinued and the lesions improved. One month later new areas of skin necrosis developed although the patient had received no further warfarin. Progressive congestive heart failure, poor nutrition, and prolonged oral antibiotic therapy preceded the recurrence. Vitamin K deficiency was present on admission. The potential role of vitamin K-dependent coagulation factors in the pathogenesis of anticoagulant-associated skin necrosis is discussed.

Topics: Female; Humans; Middle Aged; Necrosis; Skin Diseases; Vitamin K Deficiency; Warfarin

Coumarin skin necrosis is a rare and usually unpredictable complication of coumarin therapy, occasionally leading to death. Onset is usually between the third and sixth day of coumarin therapy. The patient most commonly complains of pain in a region of abundant subcutaneous fat, with progression to erythema, petechiae, and gangrenous necrosis. Thrombosis of the dermal and the subcutaneous veins is demonstrated pathologically. We describe a case and review the pathogenesis, treatment, and prevention of this lesion.

Topics: Aged; Aged, 80 and over; Biopsy; Diagnosis, Differential; Female; Humans; Necrosis; Skin Diseases; Thrombosis; Warfarin

Topics: Aged; Foot; Humans; Knee Prosthesis; Male; Necrosis; Postoperative Complications; Skin; Warfarin

Topics: Aged; Autoantibodies; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Proteins; Female; Glycoproteins; Humans; Infarction; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Necrosis; Phospholipids; Protein C Deficiency; Protein S; Skin; Warfarin

Although the association of coagulopathy and neoplastic disease is well documented, there have been few reports of patients with primary central nervous system tumors who exhibited hypercoagulable states. We report the case of a 58-year-old woman with a recurrent falcine meningioma and repeated episodes of venous thrombosis who developed warfarin-associated breast necrosis on the fifth day of coumadin therapy. Laboratory evaluation at that time demonstrated an elevated prothrombin time and normal activated partial thromboplastin time. Of the 24 cases of warfarin-associated massive necrosis of the breast described in the literature, only one other case was associated with a neoplasm, a resected craniopharyngioma.

Topics: Blood Coagulation Disorders; Breast; Humans; Male; Mastectomy; Meningeal Neoplasms; Meningioma; Middle Aged; Necrosis; Neoplasm Recurrence, Local; Warfarin

Topics: Humans; Male; Middle Aged; Necrosis; Protein C Deficiency; Skin; Warfarin

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Necrosis; Skin; Thrombophlebitis; Thrombosis; Warfarin

A family is described in which venous thromboembolic disease is associated with reduced plasma protein C activity and normal levels of protein C antigen. Immunoelectrophoretic analysis of protein C antigen gave an abnormal pattern in all affected members, suggesting that the disorder is related to the presence of a structurally and functionally abnormal form of protein C. The propositus developed simultaneous warfarin-induced skin necrosis and bilateral adrenal hemorrhage. This is the first reported instance of warfarin-induced skin necrosis associated with a dysfunctional protein C molecule and the first reported instance of simultaneous warfarin-induced skin necrosis and bilateral adrenal hemorrhage.

Topics: Adrenal Gland Diseases; Hemorrhage; Humans; Immunoelectrophoresis, Two-Dimensional; Male; Middle Aged; Necrosis; Protein C; Protein C Deficiency; Protein Deficiency; Skin; Warfarin

We describe a severe case of warfarin-induced skin necrosis with extensive full-thickness tissue loss involving approximately 12 per cent of the body surface area. The early management was conservative, with wound observation only, and no aggressive débridement was attempted. Wound and associated systemic sepsis followed, and the patient was transferred to our burn unit. The wounds were then managed with aggressive therapy including surgical excision, temporary coverage with allograft, and final closure with split-thickness autograft. This case illustrates important principles of appropriate surgical management of extensive skin lesions of this type.

Topics: Burn Units; Critical Care; Debridement; Female; Humans; Middle Aged; Necrosis; Sepsis; Skin; Skin Transplantation; Warfarin; Wound Infection

In cases of ischemic extremities and diabetes mellitus, the trauma on finger and toe is very intractable. For such injuries amputation of extremity is indicated very often because of severe necrosis. The number of such cases has been increasing recently because many cases of these patients have arteriosclerotic arterial occlusion and diabetes mellitus, and these are correlated with the changes of aging. The number of cases of Buerger's disease has been also increasing and it is another etiology of intractable trauma in ischemic extremity. The repeated hyperbaric oxygenation, sympathetic block, warfarin therapy and insulin bath with bubbling of hyperbaric oxygen, were applied to has been of such necrosis. By these procedures, the rate of amputation of extremity decreasing. It was concluded that the surgical reconstruction of artery for ischemic extremity has never any meaning as the therapy of such intractable injuries, if blood flow in the peripheral tissue is not kept physiologically, before vascular reconstruction. In order to increase peripheral tissue circulation, the hyperbaric oxygenation, sympathetic block and warfarin therapy wer performed in many cases and these methods were very effective for intractable injuries with severe necrosis.

Topics: Adult; Aged; Arteriosclerosis Obliterans; Diabetic Angiopathies; Female; Finger Injuries; Humans; Hyperbaric Oxygenation; Ischemia; Male; Middle Aged; Necrosis; Raynaud Disease; Thromboangiitis Obliterans; Toes; Warfarin

Topics: Aged; Epoprostenol; Female; Humans; Necrosis; Skin; Skin Diseases; Warfarin

Topics: Diagnosis, Differential; Gangrene; Humans; Necrosis; Skin; Warfarin

Topics: Acquired Immunodeficiency Syndrome; Adult; Breast; Female; Humans; Necrosis; Warfarin

Topics: Adult; Heparin; Humans; Male; Necrosis; Skin; Skin Diseases; Warfarin

Patchy necrosis of the skin is a rare and unpredictable complication of oral anticoagulant therapy. Of the four patients that we have seen with this disorder, three had metastatic adenocarcinoma; in two, this was an unexpected finding. The association of a malignant neoplasm with warfarin-induced skin necrosis has not been emphasized previously. Whether such necrosis represents a clue to the presence of cancer or occurs only coincidentally in patients requiring anticoagulant therapy because of adenocarcinoma-associated thrombophlebitis must await further experience. A congenital or acquired deficiency of protein C may be the primary initiating factor.

Topics: Adenocarcinoma; Aged; Drug Eruptions; Female; Foot; Glycoproteins; Humans; Leg; Male; Necrosis; Neoplasm Metastasis; Pancreatic Neoplasms; Protein C; Sigmoid Neoplasms; Skin Diseases, Vesiculobullous; Warfarin

Topics: Drug Eruptions; Female; Humans; Middle Aged; Necrosis; Protein C Deficiency; Warfarin

Topics: Adult; Aged; Drug Eruptions; Female; Humans; Male; Middle Aged; Necrosis; Skin; Warfarin

Coumarin necrosis, a rare complication of coumarin anticoagulation, typically presents with well-defined purpuric patches that progress to bullae formation and necrosis. The vast majority of those affected are women, and most commonly affected sites are the breasts, buttocks, thighs, and abdomen. We present a male patient who manifested a unique reticulated purpura that progressed to bullae formation on the toes of one foot in addition to more classic lesions on the thigh and calf.

Topics: Coumarins; Humans; Male; Middle Aged; Necrosis; Purpura; Skin; Toes; Warfarin

Topics: Female; Femoral Vein; Humans; Middle Aged; Necrosis; Skin; Thrombosis; Warfarin

Topics: Adult; Blood Transfusion; Drug Therapy, Combination; Glycoproteins; Hemorrhage; Heparin; Humans; Male; Necrosis; Plasma; Protein C; Skin Diseases; Thromboembolism; Warfarin

Severe and recurrent purpura fulminans developed in a Chinese boy at one day of age. Results of coagulation studies performed on the patient during attacks were compatible with the diagnosis of disseminated intravascular coagulation. Subsequent investigations have revealed that the patient is homozygous and that his parents are heterozygous for protein C deficiency. Cryoprecipitate and fresh frozen plasma induced a remission, and administration of warfarin has been successful in preventing recurrence of attacks for as long as 8 months without infusion of any plasma components. None of the family members who are heterozygous for protein C deficiency have had thrombotic episodes.

Topics: Combined Modality Therapy; Cryoglobulins; Glycoproteins; Heparin; Homozygote; Humans; Infant, Newborn; Male; Necrosis; Plasma; Protein C; Protein Deficiency; Purpura; Skin; Warfarin

Recent reports have suggested a correlation between congenital protein C deficiency and tissue necrosis complicating oral anticoagulants (warfarin necrosis). The authors studied blood samples of 13 patients, obtained two weeks to more than six months after warfarin necrosis. Protein C antigen levels were assayed by an enzyme-linked immunosorbent assay method (Diagnostica Stago, France). Factors II, VII, IX, and X were assayed by functional methods, and IX and X additionally by immunologic methods. The results show that 11 of 13 patients with a history of tissue necrosis had low protein C levels, ranging from 23 to 69%, with the normal range being 70-140%. These results confirm that low protein C antigen levels are implicated in the pathogenesis of warfarin necrosis.

Topics: Administration, Oral; Blood Coagulation Factors; Enzyme-Linked Immunosorbent Assay; Humans; Necrosis; Protein C; Protein C Deficiency; Warfarin

Topics: Adult; Humans; IgA Vasculitis; Leg; Male; Necrosis; Warfarin

Topics: Adolescent; Adult; Female; Glycoproteins; Humans; Infant, Newborn; Male; Necrosis; Protein C; Skin; Warfarin

Sodium warfarin is one of the most commonly used oral anticoagulants. It is not without complications. A case is presented of a 56-year-old woman on well-regulated sodium warfarin therapy who suffered unexplained necrosis and gangrene of the breast. She underwent total mastectomy for debridement because of the extensive nature of the infarction. Possible pathophysiological mechanisms for this process are discussed.

Topics: Breast; Female; Gangrene; Humans; Mastectomy; Middle Aged; Necrosis; Warfarin

We report a 55-year-old man with coumarin necrosis. This drug eruption is sometimes a devastating gangrenous process in sites with abundant underlying adipose tissue. In our patient, however, it assumed an evanescent limited linear distribution on the skin, prompting this report.

Topics: Drug Eruptions; Humans; Male; Middle Aged; Necrosis; Pulmonary Embolism; Skin; Warfarin

Two women developed coumadin-induced skin necrosis. A 16-year-old woman sustained necrosis on the leg after a single dose of the drug, and a 59-year-old woman developed gangrene of most of her left breast.

Topics: Adolescent; Dose-Response Relationship, Drug; Drug Eruptions; Female; Humans; Middle Aged; Necrosis; Skin; Warfarin

A 25-year-old man with Klinefelter's syndrome and recurrent thromboplebitis , for which he had been receiving long-term warfarin sodium therapy, had bilateral ecchymoses on the hips coincident with serologically confirmed Epstein-Barr virus-caused mononucleosis. Biopsy specimens taken from the hip lesions showed microscopic findings consistent with a diagnosis of warfarin necrosis. Direct immunofluorescence microscopy disclosed vessel-wall deposition of IgM and heavy upper-dermal deposition of IgG. Electron microscopy disclosed nonspecific endothelial cell blebs that projected into the vessel lumen. The temporal association of mononucleosis with the onset of warfarin necrosis suggests that the viral illness may have precipitated an immunologic endothelial surface reaction, leading to thrombosis and secondary hemorrhage with infarction. To our knowledge, the appearance of warfarin necrosis in a patient receiving long-term, stable anticoagulation therapy has not been previously reported.

Topics: Adult; Herpesvirus 4, Human; Humans; Immunoglobulin G; Immunoglobulin M; Infectious Mononucleosis; Klinefelter Syndrome; Male; Microscopy, Fluorescence; Necrosis; Skin; Thrombophlebitis; Time Factors; Warfarin

Topics: Adult; Antigens; Blood Proteins; Factor X; Female; Glycoproteins; Heterozygote; Humans; Male; Necrosis; Penile Diseases; Protein C; Skin Diseases; Vitamin K 1; Warfarin

The authors report two cases of delayed radiation necrosis of the brain. In these cases a dramatic clinical and computerized tomographic improvement was noted after the institution of anticoagulant therapy. Based on a review of the literature, a possible causal mechanism is suggested. It was believed from both the clinical observation and the literature review that the anticoagulant agents had a direct effect upon the improvement in these patients. Laboratory data are needed to determine the role of anticoagulant therapy in the treatment of delayed radiation necrosis of the brain.

Topics: Adult; Brain Diseases; Brain Neoplasms; Carcinoma; Female; Glioma; Heparin; Humans; Male; Necrosis; Radiation Injuries; Thyroid Neoplasms; Tomography, X-Ray Computed; Warfarin

Two patients had breast necrosis after sodium warfarin (Coumadin) therapy. This well recognized, but rare, complication of anticoagulation therapy also occurs in other areas of the body. The cause is not known. We present these cases and discuss the literature.

Topics: Aged; Breast; Breast Diseases; Dose-Response Relationship, Drug; Female; Humans; Lung Diseases, Obstructive; Middle Aged; Necrosis; Prothrombin Time; Pulmonary Embolism; Warfarin

Topics: Aged; Female; Humans; Leg; Male; Middle Aged; Necrosis; Purpura; Skin Diseases; Warfarin

Topics: Adult; Female; Humans; Necrosis; Skin Diseases; Warfarin

Gangrene of the male external genitalia is an uncommon urologic problem with a limited differential diagnosis. To the etiologic spectrum we add warfarin-induced penile gangrene. Pathophysiology, diagnosis and treatment are discussed.

Topics: Adult; Humans; Male; Necrosis; Penile Diseases; Skin Diseases; Thrombophlebitis; Warfarin

Skin necrosis secondary to Coumadin-congener therapy is a rare, unpredictable complication. A case is reported of a patient given sodium warfarin therapy following coronary artery bypass who developed skin necrosis of the trochanteric region, bilaterally, and the right breast on the fourth day following administration of Coumadin. The Coumadin therapy was discontinued, and the areas of skin necrosis went on to slow, spontaneous healing. However, significant subcutaneous induration persisted, although the areas were no longer painful.

Topics: Breast; Diagnosis, Differential; Female; Hemorrhage; Hip; Humans; Middle Aged; Necrosis; Skin; Skin Diseases; Warfarin

A rare complication of warfarin treatment is described. In two patients an extensive skin necrosis of the breast developed during anticoagulant treatment for thromboembolic disease. In both cases conservative treatment was successful. The cases are discussed in the light of previous reports in the literature.

Topics: Aged; Breast; Female; Humans; Middle Aged; Necrosis; Skin; Warfarin

Four cases of warfarin-induced skin necrosis are reported, and previous reports of this adverse drug reaction are summarized. A 53-year-old man experienced two episodes of skin necrosis on his left flank and buttock, following the initiation of warfarin therapy for acute thrombophlebitis and after a dose adjustment. The lesion formed multiple hemorrhagic bullae that ruptured, and an eschar formed that did not heal and eventually required skin grafting. Seven days after the initiation of warfarin therapy, an area of erythema surrounded by a halo was noted on the left thigh of a 79-year-old woman. Following the typical pattern, the erythematic area turned to a blue-black color and rapidly formed an eschar deep into the subcutaneous tissue that required debridement. A 70-year-old man was given a warfarin dose of 10 mg daily that was reduced to 2.5 mg daily. It was discontinued when bullous violaceous lesions were discovered on his lower left leg and foot. His prothrombin times never exceeded 20 seconds with a control of 10.6 seconds. A 37-year-old woman was admitted with an erythematous area on her right thigh that turned blue-black and subsequently formed an eschar. Her prothrombin time was 21 seconds with a control of 10.6 seconds. Of the 50 reports of warfarin-induced skin necrosis in the literature (including the four here), 74% of the cases involved women. The mean age of the patients was 54 years, and 60% of the lesions occurred on the thigh, breast, or buttock. Usually the onset of the lesion was noted on days 3--5 of warfarin therapy. Sixty percent of the patients were hypocoagulated. The etiology of warfarin-induced skin necrosis has not been definitively established. In the event of this unusual complication, warfarin therapy should be discontinued, vitamin K should be administered to reverse the effects of warfarin, and heparin should be used to provide anticoagulation.

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Necrosis; Prothrombin Time; Skin Diseases; Skin Transplantation; Warfarin

A case of coumadin necrosis of the breast is presented. Most patients with this entity are obese, middle-aged females who have been treated with oral anticoagulants for three to five days for thrombophlebitis or peripheral arterial embolization. The key to therapy is early diagnosis and clinical differentiation from subcutaneous hemorrhage--a disease which is self-limited, nonprogressive, and treatable when anticoagulant therapy is either discontinued or reversed with vitamin K. Surgical debridement or simple mastectomy is generally necessary in those cases where necrosis is present.

Topics: Breast Diseases; Female; Humans; Middle Aged; Necrosis; Thromboembolism; Warfarin

Two patients with dermal necrosis due to anticoagulation therapy with warfarin are reported. Both patients demonstrated some disturbance in immunological function. It appears possible that warfarin may act as a hapten in the induction of hypersensitivity to the drug. It is recommended that future cases should be studied to determine whether there is a defect in immunoregulation, and whether circulating immune complexes are responsible for the typical skin lesions.

Topics: Aged; Complement C3; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Lymphocyte Activation; Middle Aged; Necrosis; Phytohemagglutinins; Skin; Skin Diseases; Warfarin

A case of ovarian carcinoma with bilateral metastases to the breasts is presented. This is the first report of simultaneous involvement of both breasts presenting as an inflammatory tumor. Axillary lymph node enlargement preceded breast involvement. The related literature is reviewed briefly, and the unpredictable invasiveness of malignant neoplasms is emphasized.

Topics: Adenocarcinoma, Papillary; Breast Diseases; Breast Neoplasms; Diagnosis, Differential; Female; Humans; Middle Aged; Necrosis; Ovarian Neoplasms; Warfarin

Necrosis of the skin developed soon after the initiation of coumarin therapy in an elderly woman. Inadvertent rechallenge resulted in similar lesions. Coumarin necrosis is a poorly understood phenomenon unlikely to respond to therapy. Fortunately, its incidence is quite rare, considering the widespread use of this anticoagulant.

Topics: Aged; Female; Humans; Necrosis; Skin; Warfarin

Skin and soft tissue necrosis is an uncommon but increasingly recognized complication of coumarin anticoagulant therapy. A patient is described with extensive involvement of all four extremities and the nose, requiring amputation of three extremities. The characteristic clinical features of the disorder are reviewed, with a discussion of the pathology, pathogenesis, and possible treatment modalities.

Topics: Aged; Connective Tissue; Extremities; Female; Gangrene; Humans; Necrosis; Nose; Skin; Warfarin

Necrosis of cutaneous and subcutaneous tissue is a rare complication of therapy of with oral anticoagulants, and is related to the use of loading-dose regimes. Three cases are reported, and demonstrate that the principal histopathological feature is thrombosis within the subcutaneous vasculature. The effect of large doses of anticoagulant on the levels of the vitamin K dependent clotting factors provides a satisfactory model for the temporal sequence of events in this syndrome. The occurrence of intravascular thrombosis with low or absent levels of Factor VII indicates that the intrinsic clotting system is of primary importance in venous thrombosis. This complication of anticoagulant therapy is not seen if loading-dose regimes are avoided.

Topics: Aged; Drug Administration Schedule; Drug Eruptions; Factor VII; Female; Humans; Middle Aged; Necrosis; Skin; Veins; Warfarin

Topics: Adult; Female; Heparin; Humans; Necrosis; Skin Diseases; Warfarin

Topics: Drug Eruptions; Humans; Necrosis; Vitamin K; Warfarin

A rare but potentially lethal complication of coumarin and its congeners is skin necrosis. A case of skin necrosis due to warfarin is reported and the literature is reviewed. It is suggested that if necrosis develops, the coumarin therapy should be terminated, and the patient should immediately be heparinized. Heparin, which never causes necrosis, can be used freely if further anticoagulation therapy is required, and may well prevent necrosis due to the thrombotic process.

Topics: Adolescent; Female; Humans; Necrosis; Pregnancy; Pregnancy Complications, Hematologic; Skin Diseases, Vesiculobullous; Warfarin

Necrosis of the skin is a rare complication of oral anticoagulation therapy by coumarin congeners. Three males receiving prophylactic warfarin anticoagulation therapy following cardiac valve replacement and one female similarly receiving anticoagulation drugs because of bilateral deep thrombophlebitis associated with carcinoma of the pancreas had typical skin necrosis develop. The lesions passed rapidly through stages beginning with pain, edema, erythema and petechiae. Ecchymoses followed in the localized area with a large bullae containing deep red fluid. Biopsy of the skin revealed involvement of the dermovascular loops with localized necrosis from extensive occlusion of dermal capillaries and venulae by fibrin thrombi. There was red cell extravasation, but inflammatory changes were inconstant. In the patients, in our study, the involvement ranged from small localized lesions of the trunk to extreme extensive skin involvement of both legs with full thickness necrosis in areas. This condition is not dose related nor the result of simple hypoprothrombinemia. It appears to be a conditioned and localized toxicity, although hypersensitivity has not been excluded. Once the diagnosis is made, orally administered anticoagulant drugs must be stopped immediately, and heparinization may be beneficial in confining the process.

Topics: Aged; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Necrosis; Skin; Thrombophlebitis; Warfarin

A 67-year-old woman with a history of thrombophlebitis had been taking warfarin sodium for 1 1/2 years when she developed multiple skin lesions resembling warfarin-induced skin necrosis or purpura fulminans. Despite discontinuing the warfarin and administering prednisone, the lesions increased in size. Disseminated intravascular coagulation (DIC) was found and resolved with heparin sodium therapy, and her skin lesions healed. This patient was believed to have an atypical form of purpura fulminans rather than warfarin-induced skin necrosis because of the duration of warfarin therapy and the dramatic resolution with heparin. A monoclonal (IgG) gammopathy was found, which stabilized as the skin lesions resolved, and fulfilled the criteria for a benign (asymptomatic) monoclonal gammopathy.

Topics: Aged; Diagnosis, Differential; Disseminated Intravascular Coagulation; Female; Humans; Hypergammaglobulinemia; Immunoglobulin G; Necrosis; Purpura; Skin Diseases; Warfarin

Topics: Adipose Tissue; Coumarins; Gangrene; Humans; Leg; Necrosis; Skin; Skin Diseases; Thrombophlebitis; Warfarin

Skin and soft tissue necrosis, in association with the coumarin derivatives, characteristically afflicts females between the third and tenth days of treatment. Anatomic regions abundant in subcutaneous fat are most commonly affected. Many of these patients have underlying serious medical problems. Three additional patients with tissue infarction complicating coumadin therapy are presented. Possible etiologic mechanisms are discussed, but the basic physiopathologic condition remains an enigma. Venous thrombosis can be a related clinical phenomenon. Treatment perspectives are outlined.

Topics: Adult; Coumarins; Female; Gangrene; Heparin; Humans; Infarction; Middle Aged; Necrosis; Pulmonary Embolism; Thrombophlebitis; Time Factors; Warfarin

Necrotizing skin lesions developed in a man with chronic ulcerative colitis. No evidence of intrinsic disease of medium or small-sized vessels was found. A circulating cryofibrinogen was thought to be responsible for in situ thrombosis leading to skin infarctions. Sodium warfarin in a daily dose of 2.5 to 5 mg appears to have thwarted progression of developing lesions and the occurrence of new ones.

Topics: Blood Protein Disorders; Chronic Disease; Cold Temperature; Colitis, Ulcerative; Fibrinogen; Humans; Male; Middle Aged; Necrosis; Skin Diseases; Warfarin

Topics: Breast Diseases; Female; Heparin; Humans; Middle Aged; Necrosis; Phenindione; Warfarin

A typical case of skin necrosis following anticoagulant therapy with warfarin is described.

Topics: Female; Heparin; Humans; Necrosis; Pulmonary Embolism; Skin Diseases; Warfarin

Topics: Female; Humans; Middle Aged; Necrosis; Skin Diseases; Warfarin

Topics: Anemia, Hemolytic; Breast Diseases; Disseminated Intravascular Coagulation; Female; Fibrin; Gangrene; Humans; Middle Aged; Necrosis; Thrombophlebitis; Warfarin

Topics: Humans; Necrosis; Warfarin

Although venous thrombosis (thrombophlebitis) is well known, there are uncommon manifestations which are seen infrequently, discussed rarely, and documented poorly. Experiences with 38 patients in seven categories are discussed in terms of our results and the pertinent reports of others. Pulmonary necrosis after embolic pulmonary infarction (six patients) may require tube thoracotomy and/or lung resection and contraindicate further heparin therapy. Iliac and/or femoral vein thrombosis occasionally fails to recanalize. Long-standing occlusion (18 patients) may be benefited by a cross-over saphenous vein graft. Left iliac venous occlusion secondary to pressure from the crossing right iliac artery (four patients) may indicate repair or bypass. Budd-Chiari syndrome (thrombosis of the hepatic venous outflow) was, in a single patient, carried past a critical period by a long Dacron tube shunt graft from the umbilical vein to the azygos vein. Subclavian and axillary venous thrombosis due to thoracic outlet pressure syndrome (three patients) often responds to heparin but may require thrombectomy; later resection of the first rib is indicated. Phlegmasia cerulea dolens (blue phlebitis) with tissue gangrene (three patients) requires immediate venous thrombectomy and subsequent heparinization. The occluded inferior vena cava (three patients) remains a challenging unsolved problem.

Topics: Adult; Aged; Arteries; Blood Pressure; Blood Vessel Prosthesis; Budd-Chiari Syndrome; Child; Female; Femoral Vein; Gangrene; Heparin; Humans; Iliac Vein; Male; Middle Aged; Necrosis; Pulmonary Embolism; Subclavian Vein; Thoracic Outlet Syndrome; Thrombophlebitis; Transplantation, Autologous; Veins; Vena Cava, Inferior; Warfarin

Topics: Aged; Breast Diseases; Female; Humans; Necrosis; Pulmonary Embolism; Warfarin

Topics: Aged; Breast Diseases; Buttocks; Female; Humans; Necrosis; Thrombophlebitis; Warfarin

Topics: Aged; Drug Hypersensitivity; Female; Humans; Necrosis; Purpura; Thrombophlebitis; Warfarin

Topics: Aged; Gastrointestinal Hemorrhage; Hematoma; Humans; Intestinal Obstruction; Intestine, Small; Laparotomy; Male; Necrosis; Postoperative Complications; Warfarin

Topics: Aged; Anticoagulants; Arteriosclerosis; Arthritis; Breast Diseases; Female; Gangrene; Humans; Hypertension; Mastectomy; Middle Aged; Necrosis; Penicillins; Postoperative Complications; Thrombophlebitis; Warfarin

Topics: Adult; Coumarins; Female; Heparin; Humans; Injections, Subcutaneous; Necrosis; Skin Diseases; Warfarin

Topics: Breast Diseases; Female; Humans; Middle Aged; Necrosis; Warfarin

Topics: Aged; Anticoagulants; Blood Transfusion; Breast Diseases; Buttocks; Coumarins; Diagnosis, Differential; Female; Hemorrhage; Humans; Male; Middle Aged; Necrosis; Thrombophlebitis; Vitamin K; Warfarin

Topics: Adult; Humans; Male; Middle Aged; Necrosis; Skin Diseases; Thrombophlebitis; Warfarin

Topics: Adolescent; Carcinoma, Hepatocellular; Diagnosis, Differential; Female; Humans; Hypersensitivity; Liver Neoplasms; Necrosis; Skin Diseases; Thigh; Thrombophlebitis; Warfarin

Topics: Aged; Anticoagulants; Female; Heart Failure; Hemorrhage; Humans; Infarction; Necrosis; Skin; Skin Diseases; Warfarin

Topics: Adult; Humans; Male; Necrosis; Penile Diseases; Skin; Warfarin

Topics: Aged; Humans; Male; Myocardial Infarction; Necrosis; Skin Diseases; Warfarin

Topics: Acenocoumarol; Anticoagulants; Coumarins; Dicumarol; Drug Therapy; Ecchymosis; Ethyl Biscoumacetate; Gangrene; Necrosis; Phenindione; Pulmonary Embolism; Purpura; Skin Diseases; Thrombophlebitis; Toxicology; Warfarin

Using intravenous sodium warfarin, rabbits were rendered hypoprothrombinemic and subjected to two intravenous injections of Shear's polysaccharide. None of the 9 animals surviving the required period of time developed bilateral renal cortical necrosis or histologic thrombi in the kidney, liver, spleen, or lungs. In a control group of 7 animals treated only with endotoxin, 6 developed bilateral renal cortical necrosis. It is concluded that the prothrombin complex is necessary for the production of the generalized Shwartzman reaction by bacterial endotoxins and that this phenomenon is essentially a process of disseminated intravascular coagulation.

Topics: Animals; Coumarins; Disseminated Intravascular Coagulation; Endotoxins; Hypersensitivity; Kidney; Necrosis; Rabbits; Shwartzman Phenomenon; Sodium; Thrombosis; Warfarin