phenprocoumon and Necrosis

We report the case of a 28-year old woman with extensive red-black colored lesions of the skin on the left thigh, which appeared without trauma. The disease arrived during longterm coumarin therapy because of a deep vein thrombosis and an antiphospholipid syndrome. After consideration of the differential diagnoses and due to the typical clinical picture we made the diagnosis of coumarin necrosis. We review the clinical and therapeutic features for this rare complication.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation Tests; Coumarins; Diagnosis, Differential; Drug Administration Schedule; Drug Eruptions; Drug Therapy, Combination; Female; Humans; Leg Dermatoses; Long-Term Care; Necrosis; Phenprocoumon; Skin; Venous Thrombosis; Vitamin K Deficiency

Coumarin necrosis is a rare but clinical very important complication of therapy with coumarin derivatives. We report a patient with congenital protein S deficiency type II, who developed coumarin necrosis during stabilization of phenprocoumon. Diagnostic problems and therapeutic alternatives are discussed considering the recent literature.

Topics: Adult; Diagnosis, Differential; Heterozygote; Humans; Male; Necrosis; Phenprocoumon; Protein S Deficiency; Skin; Thrombophlebitis

A 52-year-old female patient presented at our hospital with right upper abdominal pain and impaired general condition. During the previous 7 months, the patient had received anticoagulation treatment with phenprocoumon due to a prosthetic aortic valve replacement.. Serological tests for virologic, autoimmune or metabolic causes of hepatitis were negative. The histologic examination of liver biopsies showed necrotizing hepatocellular injury in zone 3 of the acinus without relevant fibrosis. Initially, a lymphocyte transformation test with phenprocoumon was negative. A second test after one week turned out to be positive. DIAGNOSIS AND CLINICAL COURSE: After withdrawal from phenprocoumon therapy and switching to anticoagulation with a low molecular weight heparin, liver tests gradually became normal. Aminotransferase levels rapidly increased when phenprocoumon treatment was resumed. Phenprocoumon-associated necrotizing hepatitis was diagnosed by clinical course, liver histology and the positive lymphocyte transformation test. After immunosuppressive treatment with prednisolone was started again, liver enzymes gradually normalized. Anticoagulation was further performed with low molecular weight heparin.. This case stresses the fact that an adequate and detailed history on concomitant medication is mandatory in patients who present with cryptic hepatitis. Though severe hepatic adverse effects of phenprocoumon are rare, physicians should consider coumarin derivatives as a potential source of hepatitis.

Topics: Anti-Inflammatory Agents; Anticoagulants; Biopsy; Chemical and Drug Induced Liver Injury; Clinical Enzyme Tests; Female; Fibrinolytic Agents; Heart Valve Prosthesis Implantation; Heparin, Low-Molecular-Weight; Humans; Immunosuppressive Agents; Liver; Middle Aged; Necrosis; Phenprocoumon; Prednisolone; Time Factors; Transaminases

Topics: Anticoagulants; Chemical and Drug Induced Liver Injury; Female; Heparin; Humans; Necrosis; Phenprocoumon

We report the case of a severe relapsing phenprocoumon-induced hepatitis. The first episode of hepatitis was thought to be caused by another drug (Verapamil). The anticoagulation with Phenprocoumon was therefore continued after healing of liver inflammation. The relapse typically developed after a shorter exposition-time supporting the hypothesis of an allergic etiology. Fortunately we didn't find any cross-reaction between Phenprocoumon and Acenocoumarol. The patient could thus be anticoagulated orally without complications. If long term anticoagulation is absolutely essential, it is reasonable to prescribe a different Coumarin-derivate. In the case of a cross-reaction, the therapy should be continued with low-molecular weight heparin.

Topics: Administration, Oral; Aged; Anticoagulants; Biopsy; Chemical and Drug Induced Liver Injury; Drug Hypersensitivity; Female; Humans; Liver; Necrosis; Phenprocoumon; Recurrence

A 52-year-old woman was admitted because of pain for several days in the lower left leg and increasing pretibial swelling with livid discoloration. Six months before she had undergone a bilateral adnexectomy with removal of the omentum and subsequent chemotherapy for ovarian cancer.. Duplex sonography on the day of admission revealed thrombosis of the left popliteal vein with an unobstructed femoral vein. Both the quick value (89%) and partial thromboplastin time (PTT, 35.9 s) were within normal limits. Computed tomography and sonography were highly suspicious of a local recurrence of the ovarian cancer with peritoneal carcinomatosis.. PTT-effective heparinization (heparin-Na) was initiated together with overlapping anticoagulation with phenprocoumon (thromboplastin time 20-30%). On the 9th day after starting phenprocoumon painful, black necrotic changes began to appear on the skin of the left first to fourth toes. Assuming these to be due to phenprocoumon, anticoagulation was switched to low-molecular heparin (Enoxaparin), and antithrombin III and protein C were administered. A few days later thrombosis of the right iliac vein occurred, probably caused by local recurrence of the ovarian cancer. No palliative chemotherapy was undertaken in view of the thrombotic complications. The patient died a few months later from the cancer.. If there is an underlying malignancy, chemotherapy and therapeutic vitamin-K antagonism in the presence of thromboembolic complications increases the risk of lowering protein C activity and may cause the rare complication of skin necrosis, induced by phenprocoumon.

Topics: Anticoagulants; Chemotherapy, Adjuvant; Fatal Outcome; Female; Humans; Iliac Vein; Middle Aged; Necrosis; Neoplasm Recurrence, Local; Ovarian Neoplasms; Phenprocoumon; Popliteal Vein; Skin; Venous Thrombosis

Topics: Anticoagulants; Chemical and Drug Induced Liver Injury; Female; Humans; Liver; Middle Aged; Necrosis; Phenprocoumon

An 81 year old male patient treated by sulfonylurea and diet was known to have type II diabetes for three years. Because of pulmonary embolism phenprocoumon had been administered for four months. Painful livedo racemosa developed acutely on both lateral sides of the feet and the left knee. A necrosis of the skin over the base of the left small toe developed within a few days. On the basis of the clinical picture cholesterol-embolism was diagnosed. Since anticoagulation is known to promote cholesterol-embolism it was discontinued. Prostaglandin E1 infusions into both legs were administered. Within 3 months the cutaneous lesions healed completely.

Topics: Aged; Aged, 80 and over; Cholesterol; Diabetes Mellitus, Type 2; Embolism; Foot; Humans; Male; Necrosis; Phenprocoumon; Pulmonary Embolism

Topics: Female; Humans; Middle Aged; Necrosis; Phenprocoumon; Pulmonary Embolism; Skin; Streptokinase; Thrombolytic Therapy; Thrombophlebitis; Urokinase-Type Plasminogen Activator

Topics: 4-Hydroxycoumarins; Coronary Artery Bypass; Coumarins; Estrogens; Female; Humans; Middle Aged; Necrosis; Phenprocoumon; Terminology as Topic

In three patients painful reddening of a well-circumscribed area of the skin occurred within five days of starting anticoagulant treatment with phenprocoumon (Marcumar), and within a short time it developed into a full-blown picture of coumarin necrosis. The indication for phenprocoumon was, in the first patient (a 29-year-old mother lying-in after her second child had been born) an increased platelet count and the presence of high risk factors for thromboembolism. In the second patient (25-year-old man) and the third one (45-year-old woman) it was secondary prophylaxis after pulmonary embolus and deep-vein thrombosis, respectively. All three patients were very obese and had a drug allergy, as well as other allergies (bronchial asthma in Cases 1 and 2; allergic rhinitis in Case 3). Phenprocoumon was at once discontinued in all three patients and low-dose heparin administration (Cases 1 and 3) or dextran infusion (Case 2: heparin intolerance) started. All three needed excision of the necrotic tissue with grafting to the skin defect. The coexistence of obesity and allergic diathesis may thus present an especially high risk for coumarin necrosis.

Topics: Adult; Coumarins; Drug Hypersensitivity; Drug Therapy, Combination; Female; Heparin; Humans; Middle Aged; Necrosis; Obesity; Phenprocoumon; Pulmonary Embolism; Risk Factors; Skin Diseases; Thrombophlebitis; Time Factors

Topics: 4-Hydroxycoumarins; Aged; Female; Forefoot, Human; Humans; Necrosis; Phenprocoumon; Pulmonary Embolism

Topics: 4-Hydroxycoumarins; Adult; Antithrombin III Deficiency; Female; Hemorrhage; Humans; Necrosis; Phenprocoumon; Skin Diseases; Thrombophlebitis; Toes

A case of hemorrhagic necrosis of the breast is reported in a thirty-four year old woman who received Cumarin treatment for deep leg vein thrombosis and pulmonary embolism. It was necessary to remove the breast. The microscopic examination showed complete blockage of the vessels by fibrin thrombi in almost all veins. The cause of this venous thrombosis was explained as a Shwartzman-Sanarelli-Phenomenon.

Topics: 4-Hydroxycoumarins; Adult; Breast Diseases; Female; Humans; Necrosis; Phenprocoumon; Shwartzman Phenomenon

In a 62-year-old female patient petechial haemorrhages of the right breast were observed after the 4th day of treatment with phenprocoumon. Within a few hours large cutaneous necroses developed. Histology showed lymphocytic vasculitis with vessel wall destruction and erythrocytic extravasates as well as necrobiotic changes of the middle and lower corium. High-dosage treatment with prednisolone was started after withdrawal of phenprocoumon. Progression of the necrosis to the left breast could be prevented. However, necrosis of the haemorrhagic area of the right breast could not be arrested. Aetiology and pathomechanisms of coumarin-induced necrosis have to date not been ascertained. Allergic precipitating mechanisms probably were of no importance in our patient.

Topics: 4-Hydroxycoumarins; Breast Diseases; Bromhexine; Cimetidine; Female; Furosemide; Humans; Middle Aged; Necrosis; Phenprocoumon; Prednisolone; Pulmonary Embolism; Urticaria; Vasculitis

Successful prevention of the progression of incipient hemorrhagic skin necrosis by timely administration of vitamin K1 in a woman treated with phenprocoumon is presented. From a critical review of the literature strong evidence emerges that coumarin necrosis does only occur in cases with severe initial drug induced hypocoagulability. Non- recognition thusfar of its importance is due to insufficient knowledge of the biological activities of thromboplastin preparations presently used in the laboratory control of oral anticoagulation. All well documented cases with apparently adequate Quick values were monitored with Faktor VIII insensitive thromboplastin. Therefore, such preparations should no longer be used in anticoagulant control.

Topics: 4-Hydroxycoumarins; Female; Hemorrhage; Humans; Middle Aged; Necrosis; Phenprocoumon; Skin; Skin Diseases; Thromboplastin; Vitamin K 1

Topics: Aged; Cauda Equina; Coumarins; Ependymoma; Humans; Infarction; Male; Myocardial Infarction; Necrosis; Paralysis; Phenprocoumon; Spinal Cord Neoplasms; Subarachnoid Hemorrhage