warfarin and Autoimmune-Diseases

Glucocorticosteroids are still very important part of the treatment of chronic inflammatory disorders. Their use is often accompanied by unpleasant adverse effects, problems associated with withdrawal during their long-term use and interactions with concomitantly administered drugs. One of the important interactions that may often occur in clinical practice is interaction with warfarin. Despite the fact that as glucocorticosteroids so warfarin are used for many years and seem to be completely known, their co-administration is still accompanied by uncertainties. The interaction may have pharmacodynamic or pharmacokinetic character and both types result in increased risk of bleeding. The pharmacodynamic interaction can be expected to increase a risk of gastrointestinal bleeding to which a gastrotoxicity of glucocorticosteroids contributes. A pharmacokinetic interaction is considered to influence a hepatic metabolism of warfarin and to increase its availability. The exact mechanism is still not fully understood. Manifestations of both types of interactions are taken up with a delay. Co-administration requires increased attention and close monitoring of international normalized ratio. At higher doses of glucocorticosteroids proton pump inhibitors are also effective in prevention of gastrotoxicity.

Topics: Anti-Inflammatory Agents; Anticoagulants; Autoimmune Diseases; Drug Interactions; Gastrointestinal Hemorrhage; Glucocorticoids; Humans; 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

Several counterintuitive treatment paradoxes complicate the management of immune heparin-induced thrombocytopenia (HIT). For example, simple discontinuation of heparin often fails to prevent subsequent HIT-associated thrombosis. Thus, current treatment guidelines recommend substituting heparin with a rapidly acting alternative anticoagulant (eg, danaparoid, lepirudin, or argatroban) even when HIT is suspected on the basis of thrombocytopenia alone ("isolated HIT"). Another paradox-coumarin (warfarin) anticoagulation-can lead to venous limb gangrene in a patient with HIT-associated deep-vein thrombosis. Thus, warfarin is not recommended during acute thrombocytopenia secondary to HIT. However, warfarin can be given as overlapping therapy with an alternative anticoagulant, provided that (1) initiation of warfarin is delayed until substantial platelet count recovery has occurred (to at least above 100 x 10(9)/L); (2) low initial doses of warfarin are used; (3) at least 5 days of overlapping therapy are given; and (4) the alternative agent is maintained until the platelet count has normalized. It has recently been recognized that HIT antibodies are transient and usually do not recur upon subsequent re-exposure to heparin. This leads to a further paradox-patients with previous HIT can be considered for a brief re-exposure to heparin under exceptional circumstances; for example, heart surgery requiring cardiopulmonary bypass, if HIT antibodies are no longer detectable using sensitive assays. For patients with acute or recent HIT who require urgent heart surgery, other approaches include use of alternative anticoagulants (eg, lepirudin or danaparoid) for cardiopulmonary bypass or antiplatelet agents (eg, tirofiban or epoprostenol) to permit intraoperative use of heparin.

Topics: Anticoagulants; Antithrombins; Arginine; Autoimmune Diseases; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparin; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Pipecolic Acids; Recombinant Proteins; Sulfonamides; Thrombocytopenia; 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

More than a decade has gone by since the detailed clinical description of the Antiphospholipid (Hughes) Syndrome. Because of the wide spectrum of manifestations, virtually any physician may encounter patients with this potentially treatable condition. Because of limited controlled, prospective data, current therapy remains empirical and directed at coagulation mechanisms, immune mechanisms, or both. There is now good evidence that patients with antiphospholipid-associated thrombosis will be subject to recurrences and require prophylactic therapy. Although most authorities agree about the efficacy of warfarin alone or warfarin plus low-dose aspirin in preventing recurrences of venous and arterial thrombosis, there is still doubt regarding the intensity and duration of warfarin therapy. Steroids and immunosuppressive drugs have not provided long-term benefit. Controlled clinical trials of the treatment of pregnant women with antiphospholipid antibody demonstrated that prednisolone is ineffective, and possibly detrimental, in treatment of recurrent pregnancy loss and that heparin plus low-dose aspirin is beneficial.

Topics: Abortion, Habitual; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Autoimmune Diseases; Contraindications; Drug Therapy, Combination; Female; Heparin; Humans; Iloprost; Immunoglobulins, Intravenous; Immunosuppressive Agents; Male; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies; Recurrence; Thrombophilia; Thrombosis; Warfarin

The objectives of this study are to examine the efficacy and safety of low-dose aspirin (LDA) vs LDA plus low-intensity warfarin (LDA + W) in the primary thrombosis prevention of aPL-positive patients with SLE and/or obstetric morbidity and the role of clinical and serological markers in the development of thrombosis.. In this 5-year prospective, randomized, open, controlled trial, 166 patients with aPL were randomly assigned using a minimization protocol to receive treatment with LDA (n = 82) or LDA + W [international normalized ratio (INR) = 1.5] (n = 84). Sixty-six patients who declined randomization were followed up in an observational arm. Clinical and laboratory characteristics and medication side effects were recorded.. There were no differences in the number of thromboses between patients treated with LDA (4/82) or LDA + W (4/84) [hazard ratio (HR) 1.07, 95% CI 0.27, 4.3]. The incidence of thrombosis in the randomized patients was 8/166 (1.8 events/100 person-years) (HR 1.07, 95% CI 0.27, 4.3) and in the observational arm was 7/66 (4.9 events/100 person-years) (HR 2.43, 95% CI 0.87, 6.79). Sixty-five of 66 patients included in the observational arm received LDA. None of the examined clinical or serological factors appeared to predict thrombosis. Medication side effects included mild gastrointestinal symptoms in the LDA group (n = 2) and bleeding in the LDA + W group (n = 11; 1 nasal and 10 menorrhagia). The risk difference for bleeding was 13% (CI 6, 20).. No differences in the number of thromboses were observed between patients treated with LDA vs those treated with LDA + W. More episodes of bleeding were detected in the LDA + W group. The LDA + W regime was significantly less safe and not as acceptable as LDA alone.. ISRCTN81818945; http://isrctn.org/.

Topics: Adult; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Autoimmune Diseases; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Lupus Erythematosus, Systemic; Male; Middle Aged; Outcome Assessment, Health Care; Pregnancy; Pregnancy Complications; Prospective Studies; Thrombosis; Treatment Outcome; Warfarin

Fifty-seven pregnancies in women with antiphospholipid syndrome (APS) are presented. These were treated with s.c. enoxaparin and low dose aspirin. In fourteen pregnancies warfarin was prescribed between weeks 15-34 (warfarin group). The decision to switch to warfarin depended on a morbidity score, and the patient's consent. Neither teratogenicity nor significant maternal, fetal or neonatal hemorrhage was observed. Despite the higher pretreatment morbidity score of the warfarin group, the live birth rate was high in both groups: 86% in the warfarin group and 87% in the non-warfarin group. There was no significant difference in week of delivery, birth weight, or incidence of thrombosis between the groups. The study demonstrates the efficacy and safety of anticoagulants during pregnancy. The use of LMWH in pregnant women with APS not being moot, warfarin might be justified in selected patients.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Autoimmune Diseases; Enoxaparin; Female; Hemorrhage; Humans; Infant, Newborn; Lupus Erythematosus, Systemic; Nervous System Diseases; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnancy, Multiple; Safety; Thrombosis; Warfarin

Topics: Antibodies, Antiphospholipid; Anticoagulants; Aspirin; Autoimmune Diseases; Female; Humans; Male; Pregnancy; Pregnancy Complications; Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Antithrombin III; Antithrombin III Deficiency; Autoimmune Diseases; Humans; Inflammatory Bowel Diseases; Intracranial Thrombosis; Magnetic Resonance Imaging; Male; Warfarin

Acquired haemophilia is a rare phenomenon and prompt diagnosis is essential for successful treatment. Early laboratory detection could minimize its potentially devastating consequences and reduce mortality but when a masking element such as anticoagulant therapy is present, delay in diagnosis is not uncommon. A prolonged activated partial thromboplastin time (APTT) may be falsely attributed to warfarin alone, particularly when it is associated with oral anticoagulant overdose. We describe two patients on treatment with warfarin who presented with a bleeding diathesis and disproportionately prolonged APTT, which led to the diagnosis of antibodies directed against factor VIII.

Topics: Aged; Anticoagulants; Autoantibodies; Autoimmune Diseases; Factor VIII; Female; Hemophilia A; Hemorrhage; Humans; Partial Thromboplastin Time; Radiography; Warfarin

Topics: Adenocarcinoma; Adult; Anticoagulants; Arterial Occlusive Diseases; Autoimmune Diseases; Drug Resistance; Female; Heparin; Heparin, Low-Molecular-Weight; Hepatitis C, Chronic; Hirudins; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Neoplasms, Unknown Primary; Platelet Aggregation Inhibitors; Portal Vein; Pulmonary Embolism; Recombinant Proteins; Recurrence; Thrombocytopenia; Vena Cava, Inferior; Venous Thrombosis; 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

Pulmonary hypertension (PH) sometimes occurs in patients with systemic lupus erythematosus (SLE). We report a case of 51-year-old-woman with PH associated with SLE. She had been diagnosed as SLE on the basis of pericardial effusion, hematological disorder, positive antinuclear antibody, and hypocomplementemia. Despite minimal lupus activity, she had marked elevation of pulmonary arterial pressure (101/53 mmHg) and decreased cardiac index (1.5 l/min/m2). Symptoms related to PH were progressive under treatment with oral corticosteroids, oxygen, calcium antagonists, and warfarin. After 17 months of epoprostenol treatment, she died of pulmonary infarction. SLE-associated PH is often severe and progressive even in association with minimal activity.

Topics: Anticoagulants; Autoimmune Diseases; Calcium Channel Blockers; Disease Progression; Epoprostenol; Fatal Outcome; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Lupus Erythematosus, Systemic; Middle Aged; Oxygen; Prednisolone; Pulmonary Embolism; Warfarin

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Autoimmune Diseases; Enoxaparin; Female; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Pulmonary Embolism; Sagittal Sinus Thrombosis; Thrombophlebitis; Warfarin

The dilute Russell viper venom time and kaolin clotting time (KCT) are very sensitive screening tests for lupus anticoagulant activity. However, due to the high turbidity of the kaolin reagent it is difficult to accommodate the KCT on the optical end point automation of today. We evaluated five recently reported screening tests (the silica clotting time, the Textarin/Ecarin ratio, the Taipan venom time, the factor V ratio, and a kaolin clotting time using low-turbidity kaolin) as potential alternatives to the KCT. The sensitivity and specificity of the silica clotting time compared well to KCT, detecting 10/12 KCT positive samples and showing equal sensitivity to dilution of lupus positive plasma. In addition, the silica clotting time allows for a confirmatory phospholipid correction procedure. False-positive results were seen in 2 of 15 warfarinised samples. A second assay utilising the ratio of extrinsic/intrinsic factor V assays was not affected by either warfarin or heparin. This assay also gave positive results with 3 of 23 samples previously screened as lupus negative but exhibiting anticardiolipin positivity. It was therefore concluded that a combination of the silica clotting time and dilute Russell viper venom time met the requirements of lupus sensitivity with demonstration of phospholipid dependence and optical end point compatibility. The factor V ratio is a useful second-line screen for both anticoagulated patients and anticardiolipin antibody-positive samples.

Topics: Anticoagulants; Antiphospholipid Syndrome; Autoimmune Diseases; Automation; Blood Coagulation Tests; Elapid Venoms; Endopeptidases; Evaluation Studies as Topic; Factor V; False Positive Reactions; Heparin; Humans; Kaolin; Liver Diseases; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Nephelometry and Turbidimetry; Partial Thromboplastin Time; Peptide Hydrolases; Postoperative Period; Prothrombin; Prothrombin Time; Silicon Dioxide; Warfarin

Topics: Abortion, Habitual; Adult; Animals; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Autoimmune Diseases; Drug Monitoring; Female; Humans; International Normalized Ratio; Intracranial Embolism; Intracranial Thrombosis; Male; Middle Aged; Pregnancy; Recombinant Proteins; Recurrence; Risk; Seizures; Thromboembolism; Thrombophilia; Thrombophlebitis; Thromboplastin; Warfarin

We reported a 61% morbidity rate and a 23% mortality rate for the heparin-induced thrombocytopenia (HIT) syndrome in 1983. We subsequently reported in 1987 that with early recognition, immediate cessation of the administration of heparin, and platelet function inhibition, the morbidity rate could be reduced to 23% and the mortality rate to 12%. One hundred recent cases of patients with heparin-associated antiplatelet antibodies (HAAb) have been reviewed to determine whether aggressive screening, early diagnosis, and alternate management could further reduce morbidity and mortality rates.. The consecutive records of 100 patients with positive platelet aggregation tests were reviewed. Sixty-six patients were male. The patients' ages ranged from 23 days to 92 years. The patients were from vascular (28), cardiothoracic (42), and other (30) services. HIT was suspected in patients who received heparin and had falling platelet counts, platelet counts less than 100,000/mm3, or new thromboembolic or hemorrhagic events.. Heparin was not offered to six patients with known HAAb. Twelve patients were successfully treated with antiplatelet therapy and limited reexposure to heparin, and 75 patients were successfully treated with early diagnosis and prompt cessation of heparin. Alternate forms of anticoagulation therapy were used selectively. Seven patients had 11 complications. Three of the seven patients were treated successfully with warfarin anticoagulation and aspirin (2) or with aspirin alone (1). A fourth patient was treated with thrombectomy, hematoma evacuation, and aspirin. A fifth patient underwent thrombolysis and coronary angioplasty in addition to receiving warfarin and aspirin. The sixth patient required two thrombectomies and warfarin. A seventh patient required two thrombectomies and aspirin. HIT was responsible for one of 17 deaths.. A 7.4% morbidity rate and a 1.1% mortality rate have been achieved in patients with HAAb by aggressive screening, early recognition of HIT, and prompt cessation of the administration of heparin. Platelet function inhibitors and other anticoagulants, including nonreacting low molecular weight heparin, are important adjuncts in the management of the thromboembolic disorders associated with HIT.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Autoimmune Diseases; Blood Platelets; Child; Child, Preschool; Female; Heparin; Humans; Infant; Infant, Newborn; Male; Middle Aged; Morbidity; Platelet Aggregation; Platelet Aggregation Inhibitors; Retrospective Studies; Syndrome; Thrombocytopenia; Warfarin

A 27 year old woman presented with recurrent cerebrovascular strokes in the setting of an ill defined auto-immune disease responsive to corticosteroid therapy. Investigation for a hypercoagulable state revealed activated protein C resistance in the absence of protein C, protein S, or antithrombin III deficiency or anticardiolipin antibodies. Her parents and sibling did not demonstrate APC resistance. This case suggests that activated protein C resistance may be associated with arterial as well as venous thrombotic events and implies that resistance to activated protein C should also be considered in the evaluation of young adults with strokes.

Topics: Adult; Antithrombin III; Autoimmune Diseases; Blood Coagulation Disorders; Brain Ischemia; Drug Resistance; Female; Humans; Intracranial Embolism and Thrombosis; Partial Thromboplastin Time; Prednisone; Protein C; Protein S; Warfarin

The clinical relevance of antiphospholipid antibodies (APLA) in patients without systemic lupus erythematosus who have venous thromboembolism (VTE) in unknown. Limited evidence suggests that there is an association between the presence of APLA and both initial and recurrent episodes of VTE and that patients with APLA and VTE are resistant to warfarin therapy. Unselected patients with a first episode of clinically suspected deep vein thrombosis or pulmonary embolism were evaluated with objective tests for VTE and with laboratory tests for APLA; the latter included tests for the lupus anticoagulant (LA) and anticardiolipin antibodies (ACLA). Patients with VTE were treated with anticoagulant therapy and observed during and after discontinuation of anticoagulants for symptomatic recurrence of VTE. There was a strong association between LA and VTE (odds ratio, 9.4; 95% confidence interval [CI], 2.1 to 46.2) and 9 to 65 (14%; 95% CI, 7% to 25%) patients with VTE had LA. There was no association between the presence of ACLA and VTE (odds ratio, 0.7; 95%CI, 0.3 to 1.7) because of the high frequency of positive ACLA assays in patients without VTE. None of the 16 patients with VTE and APLA developed recurrent VTE while receiving warfarin therapy. There was no difference in rates of recurrent VTE in patients with or without APLA after anticoagulant therapy was discontinued. The strong association between LA and VTE suggests that testing for LA in patients with VTE is useful. The measurement of ACLA in patients with VTE has no clinical usefulness because the results are abnormal in a high proportion of patients without VTE. Although the presence of APLA in patients with VTE was not associated with resistance to a conventional intensity of warfarin or an increased risk of recurrent VTE after discontinuation of warfarin, a larger study should address these issues in a subgroup of patients with VTE and LA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Autoimmune Diseases; Female; Humans; Lupus Coagulation Inhibitor; Male; Middle Aged; Ontario; Predictive Value of Tests; Prospective Studies; Pulmonary Embolism; 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

Antibodies to cardiolipin, closely related to the 'lupus anticoagulant', are strongly implicated in the pathogenesis of thrombosis. We record six patients, all with high titres of these antibodies (greater than SD) in serum, who developed recurrent vascular occlusions six to 12 weeks after warfarin withdrawal. Five of the six had deep vein thrombosis, while the sixth suffered a myocardial infarction. To minimise the risk of 'recurrent' thrombosis it is strongly suggested that such patients remain on long-term anticoagulation, pending the reduction of high antibody levels.

Topics: Adolescent; Adult; Antibodies; Autoimmune Diseases; Cardiolipins; Female; Humans; Lupus Erythematosus, Systemic; Male; Myocardial Infarction; Recurrence; Thrombophlebitis; Warfarin

Topics: Autoimmune Diseases; Betamethasone; Dexamethasone; Digoxin; Humans; Myocardial Infarction; Radiography, Thoracic; Syndrome; Warfarin