Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparin-induced thrombocytopenia type II is a serious, immune-mediated complication of heparin therapy. Due to its low cross-reactivity with heparin-associated antibodies (10-20%), danaparoid has successfully been administered in these patients. In recent studies, r-hirudin as a potent and specific thrombin inhibitor, was demonstrated to be a safe and effective anticoagulant. We report a pregnant woman with systemic lupus erythematosus and recurrent venous thromboembolism who suffered from heparin-induced thrombocytopenia type II while treated with dalteparin sodium. Positive cross-reactivities with danaparoid were found. Anticoagulation with 15 mg subcutaneous r-hirudin was performed twice daily from the 25th week of pregnancy until delivery. No thromboembolism or bleeding or fetal toxicity of r-hirudin was detected. Recombinant hirudin is a potent and specific thrombin inhibitor that can be used as a safe and effective anticoagulant in pregnancy.
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PMID:Management of heparin-associated thrombocytopenia in pregnancy with subcutaneous r-hirudin. 1062 77

Venous thromboembolism is a chronic disease with an annual incidence of recurrence of 5 to 10%. Patients with venous thrombosis should be treated with anticoagulants for at least 3 months. The optimal duration of anticoagulation entails balancing the risk of recurrence against the risk of treatment-associated bleeding. Candidates for extended anticoagulation are patients with a high risk of recurrence. The risk of recurrence is increased in patients with antithrombin deficiency, the lupus anticoagulant, homozygous F V Leiden, combined defects, high F VIII, high F IX, high TAFI, hyperhomocysteinemia or more than one episode of thrombosis. The risk of recurrence is low in patients with venous thrombosis secondary to surgery or trauma. Routine thrombophilia screening is aimed at identifying patients who could benefit from extended anticoagulation. This population consists of patients with venous thrombosis at a young age, an unprovoked episode of venous thrombosis, patients with a strong positive family history or patients with recurrent venous thrombosis. Screening should comprise antithrombin determination and the search for the lupus anticoagulant. Patients harbouring one of these defects are at high risk of recurrence and most likely will profit from prolonged anticoagulation. The clinical relevance of new treatment strategies such as extended low-intensity warfarin or administration of the direct thrombin inhibitor (xi-)melagatran is at present unclear.
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PMID:The optimal duration of secondary thromboprophylaxis in patients with venous thromboembolism. The importance of thrombophilia screening. 1577 39

Although patients undergoing cardiac surgery often present with diverse comorbidities, those with coagulation derangements are especially challenging. The present report describes the management of a patient who presented with a Factor V Leiden mutation, lupus anticoagulant, and acquired activated protein C resistance. A 42-year-old female presented with acute shortness of breath and chest pain. She was otherwise healthy 1 month prior to admission when she presented with dysfunctional uterine bleeding, resulting in the transfusion of three units of packed red blood cells. Coagulation evaluation revealed that the patient had lupus anticoagulant, factor V Leiden mutation and an activated protein C resistance. The patient presented with an acute myocardial infarction and was found to have 90% stenosis of her left main coronary artery, moderate mitral and tricuspid regurgitation, and a left ventricular ejection fraction of 25%. An emergent off-pump coronary artery bypass procedure with placement of a vein graft to the left anterior descending artery was completed. Intraoperative thrombophilia was encountered as evidenced by both an elevated thromboelastograph coagulation index (+3.6) and an acquired antithrombin-III deficiency. Postoperatively, the patient was placed on low molecular weight heparin, but developed heparin-induced thrombocytopenia and was switched to a direct thrombin inhibitor, argatroban. The following case report describes the coagulation management of this patient from the time of admission to discharge 43 days later, and the unique challenges this combination of hemostatic defects present to the clinicians.
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PMID:Coagulation management of a patient with factor V Leiden mutation, lupus anticoagulant, and activated protein C resistance: a case report. 1591 49

Vascular complications remain the most common cause of early renal allograft loss in patients with end-stage renal failure. Underlying thrombophilic disorders increase the risk of early graft thrombosis. A male adolescent with high-risk thrombophilia because of combined heterozygous factor V Leiden (G1691A) and prothrombin gene (G20210A) mutation developed HIT II. Hemodialysis and subsequent renal transplantation were undertaken using recombinant hirudin, a direct and selective thrombin inhibitor, as an anticoagulant. Primary function in the transplanted kidney was excellent. No thrombotic or hemorrhagic events have occurred and follow-up showed excellent long-term graft survival. Patients on HD have an increased risk for the development of HIT, and therefore, they need repetitive screening for the development of acquired thrombotic risk factors (e.g. HIT II or lupus anticoagulant). R-hirudin is efficacious and safe on both HD and following renal transplantation.
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PMID:Successful renal transplantation in a patient with heterozygous prothrombin gene, factor V Leiden mutation and heparin-induced thrombocytopenia using r-hirudin as anticoagulant. 1649

Unfractionated heparin has been a near universal anticoagulant for cardiac surgery; however it is contraindicated in heparin-induced thrombocytopenia type II. Alternative anticoagulants such as bivalirudin (a direct thrombin inhibitor) are being utilized. Bivalirudin was successfully used in an immunologically complex patient (diagnoses of heparin-induced thrombocytopenia type II, systemic lupus erythematosus, antiphospholipid syndrome, and dialysis-dependent renal failure) requiring cardiopulmonary bypass. Thrombotic events are common in antiphospholipid syndrome patients undergoing cardiac surgery utilizing high-dose heparin. This may represent unrecognized heparin-induced thrombocytopenia type II. Our patient did not experience perioperative thrombotic or bleeding complications. The possible cross-reactivity between heparin induced thrombocytopenia type II and antiphospholipid syndrome has not been investigated.
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PMID:Bivalirudin anticoagulation for a patient with hypercoagulable immune syndromes undergoing mitral valve surgery. 1673 Nov 83

We previously described a simplified quantitative hemolytic assay for classical pathway (CP) hemolytic function in serum that has been shown to correlate with the 50% hemolytic complement (CH50) assay. In the present study, we used this assay to compare CP functions; plasma levels of C3, C4, and C3dg; and ratios of C3dg to C3 in healthy individuals and patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) with different degrees of complement activation. A significant depression in CP function and levels of C4 and C3 and increased C3dg levels and C3dg/C3 ratios were observed in the SLE patients. In patients with RA, CP function was normal, whereas C3, C4, and C3dg levels and the C3dg/C3 ratio were elevated. The SLE results are compatible with systemic complement consumption, whereas the RA data suggest an acute-phase reaction with a normal C3 catabolic rate. To facilitate the handling of patient samples, we also developed a method to restore the hemolytic function of EDTA-plasma by transferring it to Veronal-buffered saline containing the thrombin inhibitor lepirudin. This process inhibits coagulation and enables complement activation, allowing a longer time lag between sample harvesting and testing. These results, combined with previous correlation studies, suggest that the CP hemolytic assay can effectively replace the CH50 assay for routine SLE differential diagnosis and monitoring of disease activity.
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PMID:Use of serum or buffer-changed EDTA-plasma in a rapid, inexpensive, and easy-to-perform hemolytic complement assay for differential diagnosis of systemic lupus erythematosus and monitoring of patients with the disease. 1734 43

Argatroban is a direct thrombin inhibitor approved for the treatment of heparin-induced thrombocytopenia (HIT) type II. Argatroban is predominantly metabolized in the liver. It is widely believed that no dosage adjustment is required in patients with renal insufficiency, making it a preferred agent in patients on renal replacement therapy (Reddy and Grossman, Ann Pharm 2005;39:1601-1605). The elimination half-life of argatroban is approximately 50 min. Lupus anticoagulants can cause baseline elevation of the PTT and hence it is difficult to monitor the effects of anticoagulants such as heparin, lepirudin, or argatroban in patients with antiphospholipid antibody syndrome. Heparin levels may be used as an alternative for heparin monitoring but plasma levels of argatroban are not commercially available. A chromogenic antifactor IIa assay could be useful for monitoring argatroban in the presence of a lupus anticoagulant, but it is not widely available at present. We report a patient with end-stage renal disease, maintained on peritoneal dialysis with HIT, who demonstrated a markedly prolonged half-life when treated with argatroban despite the discontinuation of therapy. This case also demonstrates the lack of guidelines for the monitoring of argatroban therapy in the presence of an underlying lupus anticoagulant.
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PMID:Prolonged half-life of argatroban in patients with renal dysfunction and antiphospholipid antibody syndrome being treated for heparin-induced thrombocytopenia. 1791 40

Anticoagulation with oral vitamin K antagonists (VKA) is the mainstay of the treatment of venous and/or arterial thromboembolism in patients with antiphospholipid syndrome (APS), although the optimal intensity of anticoagulation remains controversial. The limitations of existing anticoagulants have driven a search for novel agents. Dabigatran etexilate (Pradaxa), a direct thrombin inhibitor (DTI), and rivaroxaban (Xarelto), the first in a new class of drugs, the oral direct factor Xa (FXa) inhibitors, are both fixed-dose orally administered agents. They are now licensed in the UK and Europe for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective total hip replacement (THR) or total knee replacement (TKR). Prospective randomized clinical trials suggest that these agents, and also apixaban, a further oral direct anti-Xa inhibitor, may have potential in other areas including the treatment of acute VTE, prevention of stroke or systemic embolism in patients with atrial fibrillation (AF) and acute coronary syndromes. Here, we summarize current indications for these agents and address the potential for their use in patients with thrombotic APS.
Lupus 2010 Apr
PMID:Antithrombotic treatment failures in antiphospholipid syndrome: the new anticoagulants? 2035 92

A 48-year-old woman presented with bilateral lower extremity critical limb ischemia. In addition to this, her work-up revealed multiple other thromboembolic insults including cerebral and visceral emboli. Initial laboratory findings were significant for an indeterminate platelet count, secondary to platelet clumping. After appropriate emergent surgical treatment including bilateral lower extremity embolectomy, the patient was empirically anticoagulated with a direct thrombin inhibitor. Further embolic work-up discovered bilateral renal and splenic infarctions as well as a large mobile mitral vegetation. Finally, an upper extremity duplex revealed left axillary, left subclavian, and right internal jugular acute deep vein thromboses. Mitral valve replacement was performed to remove the septic source. A series of hypercoagulability studies was done, and results were positive for lupus anticoagulants. Months after her recovery, the patient was tested and found to be positive for sticky platelet syndrome.
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PMID:Sticky platelet syndrome: an unusual presentation of arterial ischemia. 2036 2

Anti-CD40L immunotherapy in systemic lupus erythematosus patients was associated with thromboembolism of unknown cause. We previously showed that monoclonal anti-CD40L immune complexes (ICs) activated platelets in vitro via the IgG receptor (FcgammaRIIa). In this study, we examined the prothrombotic effects of anti-CD40L ICs in vivo. Because mouse platelets lack FcgammaRIIa, we used FCGR2A transgenic mice. FCGR2A mice were injected i.v. with preformed ICs consisting of either anti-human CD40L mAb (M90) plus human CD40L, or a chimerized anti-mouse CD40L mAb (hMR1) plus mouse CD40L. ICs containing an aglycosylated form of hMR1, which does not bind FcgammaRIIa, were also injected. M90 IC caused shock and thrombocytopenia in FCGR2A but not in wild-type mice. Animals injected with hMR1 IC also experienced these effects, whereas those injected with aglycosylated-hMR1 IC did not, demonstrating that anti-CD40L IC-induced platelet activation in vivo is FcgammaRIIa-dependent. Sequential injections of individual IC components caused similar effects, suggesting that ICs were able to assemble in circulation. Analysis of IC-injected mice revealed pulmonary thrombi consisting of platelet aggregates and fibrin. Mice pretreated with a thrombin inhibitor became moderately thrombocytopenic in response to anti-CD40L ICs and had pulmonary platelet-thrombi devoid of fibrin. In conclusion, we have shown for the first time that anti-CD40L IC-induced thrombosis can be replicated in mice transgenic for FcgammaRIIa. This molecular mechanism may be important for understanding thrombosis associated with CD40L immunotherapy. The FCGR2A mouse model may also be useful for assessing the hemostatic safety of other therapeutic Abs.
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PMID:Anti-CD40L immune complexes potently activate platelets in vitro and cause thrombosis in FCGR2A transgenic mice. 2058 32


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