vitamin-k-semiquinone-radical and Leg-Ulcer

Venous insufficiency following deep venous thrombosis is known as the post thrombotic syndrome. Whilst its presentation and symptoms can vary slightly between individuals, it can have a profound effect on quality of life. Symptoms range from mild limb swelling to severe intractable ulceration. A number of scoring systems have been developed to help monitor the disease progression, response to treatment as well as to classify patients for research purposes.Treatment involves a combination of therapies, including compression stockings, venous stenting for out flow obstruction and in some instances deep venous bypass. A considerable effort is made in preventing post thrombotic syndrome with a number of trials looking into the effect of prompt and stable anticoagulation, the effect of compression stockings, the effect of exercise and the outcomes following early thrombus removal strategies such as catheter directed and pharmacomechanical thrombolysis.

Topics: Anticoagulants; Disease Progression; Edema; Heparin, Low-Molecular-Weight; Humans; Leg Ulcer; Mechanical Thrombolysis; Postthrombotic Syndrome; Quality of Life; Severity of Illness Index; Stents; Stockings, Compression; Treatment Outcome; Venous Thrombosis; Vitamin K

This review presents a closer look at four diseases which are probably closely related to one another pathophysiologically: (a) calciphylaxis (distal pattern); (b) calciphylaxis (proximal pattern); (c) Martorell hypertensive ischemic leg ulcer; (d) calciphylaxis with normal renal and parathyroid function (synonym: eutrophication). The four diseases have largely the same risk factors: (1) arterial hypertension, (2) diabetes mellitus (types 1 and 2), (3) secondary or tertiary hyperparathyroidism (in end-stage kidney disease) and (4) oral anticoagulation with vitamin K antagonists. They share the same clinical patterns: necrotizing livedo, skin infarctions at typical locations and acral gangrene in calciphylaxis. They also share the same histopathology: ischemic subcutaneous arteriolosclerosis and small-artery disease and 'miniaturizing' Mönckeberg medial calcinosis. The treatment concept for the acute phase of the diseases is also broadly similar. In addition to an optimized control of the cardiovascular risk factors, a proactive wound approach (necrosectomy, negative pressure wound treatment with vacuum dressings, and early skin grafts supported by systemic antibiotic therapy) leads most rapidly and effectively to a reduction of the initially severe wound pain, and finally to complete healing of the wound. Oral anticoagulation with vitamin K antagonists should be stopped. In extensive cases, the use of intravenous sodium thiosulfate is recommended. All four diagnoses are little known in the medical schools of most countries. The need to improve familiarity with these four closely related disorders is therefore great. In particular, the risk of confusion with pyoderma gangrenosum is a major diagnostic problem which can lead to false and even damaging treatment.

Topics: Anticoagulants; Calciphylaxis; Diabetes Complications; Humans; Hyperparathyroidism, Secondary; Hypertension; Infarction; Leg Ulcer; Skin; Vitamin K

Calcific arteriolopathy (CA), also known as " Calciphylaxis " describes a phenomenon of necrosis, mainly cutaneous and sometimes systemic, due to the obliteration of the arteriole's lumen. Initially there are under-intimal calcium deposits, and then the thrombosis occurs leading to the necrosis. CA affects mainly the renal insufficient hemodialysed patient, but not exclusively. We present 4 cases which illustrate well the etiologic spectrum of CA: terminal renal insufficiency, neoplasia, primary hyperparathyroidism, proteinuria, vitamin K inhibitors. We describe the AC's epidemiology, its cutaneous and systemic clinical presentations, its treatment. We make the hypothesis that CA is a strong risk marker in matter of cardiac mortality and we discuss this point.. In this article we describe the numerous breakthroughs that have been made in matter of research about calcification over the past few years: inhibitors of calcium phosphate deposition, vitamin D and PTH1R, protein-calcium complexes, cell death, induction of bone formation. These data are analysed from a clinical point of view with practical purposes. We present CA not only as a cutaneous disease but as a systemic pathology.. The CA epidemiology is an incentive to more diagnosis suspicion in front of organ infarct involving a patient likely to be concerned by CA. The scientific and therapeutic breakthroughs in matter of calcification enable a better prevention of the disease. Nevertheless it remains very difficult to cure when installed.

Topics: Aged; Arterioles; Biopsy; Calciphylaxis; Calcium; Coronary Artery Disease; Fatal Outcome; Female; Humans; Hyperparathyroidism; Kidney Failure, Chronic; Leg Ulcer; Male; Middle Aged; Neoplasms; Phosphates; Proteinuria; Skin; Vitamin K

Genetically, Klinefelter's syndrome is characterized by a super-numerary chromosome X in male subjects presenting with clinical and biochemical hypoandrogenism and relative hyperoestrogenism. The association of Klinefelter's syndrome with chronic leg ulcer has given rise to numerous publications. The cause of the trophic disorders is unclear. We report two cases of this syndrome associated with chronic leg ulcers and anomalies of haemostasis. One of these two patients had platelet hyperaggregability followed by disorders of fibrinolysis, while the other had disorders of fibrinolysis. We reviewed the literature concerning the various aetiopathogenic hypotheses put forward to explain the cause of these leg ulcers, as well as their interactions and relationship with the hormonal anomalies. The position occupied by disorders of haemostasis is particularly developed.

Topics: Adult; Aspirin; Blood Coagulation Disorders; Gonadal Steroid Hormones; Humans; Klinefelter Syndrome; Leg Ulcer; Male; Platelet Aggregation; Vitamin K

Topics: Administration, Intravenous; Humans; Leg Ulcer; Male; Middle Aged; Peripheral Vascular Diseases; Plasma; Vitamin K

Patients treated by vitamin K antagonists (VKA) represent 1% of the population in France. We report a case of atypical necrotic leg ulcers induced by VKA.. A 84-year-old woman was referred to our dermatology department because of necrotic leg ulcers that developed for the past 5weeks, and appeared spontaneously after the introduction of a VKA, fluindione. The etiological assessment was non contributive, in particular the search for thrombophilic factors. The skin biopsy found an aspect compatible with pyoderma gangrenosum. The outcome was favorable after discontinuing the fluindione and the switch to apixaban. A complete healing was obtained in 5months.. We report an original case of necrotic leg ulcers induced by VKA without deficit of protein C or S, with a pyoderma like histology. Reported cases of ulcers induced by VKA are uncommon and the physiopathology is not well known. The involvement of VKA should be evoked in case of necrotic leg ulcer without specific etiology found.

Topics: 4-Hydroxycoumarins; Aged, 80 and over; Female; Humans; Indenes; Leg Ulcer; Necrosis; Protein C Deficiency; Protein S Deficiency; Pyoderma Gangrenosum; Vitamin K

Hypertensive leg ulcers (HLU) are a form of necrotic leg ulcer. Their physiopathology is not well known and in these patients, no venous or arterial insufficiency is detected. The primary objective of this study was to evaluate the association between HLU severity and the presence or absence of concomitant vitamin K antagonist (VKA) medication. We furthermore aimed to describe the epidemiology of this entity and the prevalence of thrombophilia factors in this population.. This was a retrospective study in 54 patients hospitalized in the dermatology department of Reims University Hospital between 01/01/2007 and 31/12/2013: 23 patients were included in the "without VKA" group, and 30 were included in the "with VKA" group. Clinical and laboratory data were collected.. The average HLU surface was higher in the "with VKA" group i.e. 35.00cm. Our study shows no obvious differences between patients with HLU with or without VKA medication. A prospective, comparative study is necessary to further evaluate this hypothesis, with particular emphasis on routine thrombophilia factor analysis.

Topics: Aged; Aged, 80 and over; Anticoagulants; Dermatology; Diabetes Complications; Disease Progression; Female; France; Hospitals, University; Humans; Hypertension; Leg Ulcer; Male; Middle Aged; Retrospective Studies; Risk Factors; Smoking; Treatment Outcome; Vitamin K

Vitamin K antagonists are widely used in thromboembolic diseases. Hemorrhagic complications related to drug overdose represent their main side effect. We report a rare side effect, a severe and unexpected type of skin vasculitis - necrotic leg ulcer - induced by vitamin K antagonist.. A 63-year-old female with a history of diabetes developed hyperalgesic necrotic ulcerations on the lower limbs one month after starting an acenocoumarol-based treatment for ischemic heart disease. Histological examination revealed lymphocytic vasculitis with fibrinoid necrosis. Etiological explorations searching for vasculitis were negative. In the absence of a precise etiology, drug-induced ulcer was suspected. Low molecular weight heparin was prescribed to replace acenocoumarol. The lesions slowly resolved with topical treatment.. The chronological criteria and the negativity of etiological explorations allowed the diagnosis of vitamin K antagonist-induced necrotic skin ulcer. Clinicians should be aware of this rare complication induced by oral anticoagulants because of its practical therapeutic implications. This is the first case of necrotic leg ulcer induced by acenocoumarol corresponding histologically to necrotising lymphocytic vasculitis.

Topics: Acenocoumarol; Anticoagulants; Diabetes Mellitus, Type 2; Drug Substitution; Female; Heparin, Low-Molecular-Weight; Humans; Hyperalgesia; Leg Ulcer; Middle Aged; Necrosis; Vasculitis; Vitamin K

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

Vitamin K antagonists (VKAs) are widely used in thromboembolic diseases. We report five cases of necrotic leg ulcers having a particularly severe course and in which withdrawal of VKA treatment alone enabled healing.. Five patients presented with necrotic leg ulcers clinically evocative of necrotic angiodermatitis or vasculitis. Histological features were variable, including inconstantly inflammatory lesions (leukocytoclastic vasculitis) and microthrombosis. None of the patients had laboratory signs of autoimmune disease. Healing occurred in all patients only after withdrawal of VKA therapy (fluindione or acenocoumarol). Associated vascular diseases included superficial venous, distal arterial insufficiency and postphlebitic disease. In three cases, thrombotic factors were observed: hyperhomocysteinaemia or heterozygous Factor V Leiden mutation.. Although the causative role of VKAs is based solely on chronological criteria, this potential side effect deserves publication because of its practical therapeutic consequences. The physiopathological mechanisms accounting for the role of VKAs, including immunoallergic phenomena and, above all, microcirculatory thrombotic processes, are hypothetical and not universally accepted.

Topics: Acenocoumarol; Activated Protein C Resistance; Aged; Aged, 80 and over; Anticoagulants; Diabetic Angiopathies; Factor V; Female; Humans; Hyperhomocysteinemia; Leg Ulcer; Male; Necrosis; Phenindione; Polyarteritis Nodosa; Postoperative Complications; Purpura; Thrombophilia; Varicose Ulcer; Vasculitis, Leukocytoclastic, Cutaneous; Vitamin K

Topics: Drug Eruptions; Fatal Outcome; Female; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Injections, Intramuscular; Leg Ulcer; Male; Necrosis; Syndrome; Treatment Outcome; Vitamin K

Topics: Adolescent; Adult; Aged; Female; France; Heparin, Low-Molecular-Weight; Humans; Leg Ulcer; Male; Middle Aged; Platelet Aggregation Inhibitors; Skin Diseases, Vascular; Vitamin K

Calciphylaxis is a rare disorder of small-vessel calcification and cutaneous infarction associated with chronic renal failure. Rare cases of calciphylaxis not associated with chronic renal failure have been reported with breast cancer, hyperparathyroidism, and alcoholic cirrhosis. To our knowledge, we report the first case of calciphylaxis without chronic renal failure associated with cholangiocarcinoma and the first attempt to treat calciphylaxis with vitamin K. A 56-year-old woman presented with necrotic leg ulceration. She was treated initially with low-molecular-weight heparin, with no effect. A coagulation work-up showed vitamin K deficiency. During vitamin K therapy, the patient had fulminant progression of the calciphylaxis. She died, and an autopsy showed metastatic cholangiocarcinoma. Thrombosis and protein C deficiency have been implicated in the pathophysiology of calciphylaxis. Functional protein C deficiency may be one of several factors contributing to the development of calciphylaxis. Vitamin K therapy was ineffective in our patient and may have been detrimental.

Topics: Adenocarcinoma; Anticoagulants; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biopsy; Calciphylaxis; Cholangiocarcinoma; Fatal Outcome; Female; Heparin, Low-Molecular-Weight; Humans; Leg Ulcer; Liver Neoplasms; Lung Neoplasms; Middle Aged; Necrosis; Neoplasms, Multiple Primary; Prognosis; Sepsis; Vitamin K; Vitamin K Deficiency