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Doruk Erkan

Publications and source records attributed to Doruk Erkan.

At least 19 recordsLinked to original sources
PubMed2025

A proteomic map of thromboinflammatory signatures in antiphospholipid syndrome: results from antiphospholipid syndrome alliance for clinical trials and international networking (APS ACTION) registry.

INTRODUCTION: Antiphospholipid syndrome (APS) is an autoimmune disease with thromboembolic and obstetric morbidity arising via a model of immunothrombosis. Individuals with APS may present with thrombotic (TAPS), obstetric (OAPS), or microvascular (MAPS) disease, while many have circulating antiphospholipid antibodies (aPL) without APS classification (NoAPS). Multiple pathophysiologic mechanisms have been proposed in APS, including activation by aPL of platelets, endothelial and immune cells, as well as complement and coagulation pathways; however, the pathophysiology of APS, particularly transition of clinical APS from aPL remains unclear. METHODS: Seeking to define the inflammatory signature of APS, we carried out an unbiased proteomic screen of persistently aPL-positive patients with different clinical phenotypes from the international APS Alliance for Clinical Trials and International Networking (ACTION) Registry and compared them to 10 healthy controls. 6398 unique proteins were estimated using an DNA aptamer-based assay. Subsequently, we validated our findings in 34 additional patients. RESULTS: Our data show that the mere presence of aPL confers a distinct thromboinflammatory signature characterized by the activation of coagulation, complement, innate and adaptive immune response pathways shared by all APS subtypes. Pathway enrichment analysis revealed increasing enrichment with rising statistical significance of thrombosis, complement, neutrophil and other innate and adaptive immune activation, as well as extracellular matrix (ECM) organization with increasing clinical severity, suggesting a model of progressive thromboinflammation in evolution of APS from NoAPS to TAPS and MAPS. CONCLUSIONS: Our findings provide novel insights into the pathogenesis of APS and identify potential novel targets for diagnostic and therapeutic intervention in APS across its entire spectrum.

Humans↗
PubMed2007

Tumor-induced osteomalacia.

Tumor-induced osteomalacia, also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome in which vitamin D resistant osteomalacia occurs due to the presence of a tumor. The following case report describes a young woman who seeks a second opinion from a rheumatologist and is found to have oncogenic osteomalacia. Not often discussed in the rheumatology literature, oncogenic osteomalacia is a rare and interesting disease entity in which diagnosis is often more challenging than treatment.

Adult↗
PubMed2006

Therapeutic and prognostic considerations in catastrophic antiphospholipid syndrome.

Catastrophic antiphospholipid syndrome (CAPS) is a rapidly progressive life-threatening disease that causes multiple organ thromboses in the presence of antiphospholipid antibodies. High index of clinical suspicion and careful investigation are required to make an early diagnosis so that treatment with anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins can be initiated. Despite this multi-modal treatment, CAPS is associated with high mortality; evidence-based management recommendations do not exist due to the rarity of the condition and the lack of controlled studies. This article reviews the therapeutic and prognostic controversies that were addressed during the 1st International Symposium on CAPS.

Animals↗
PubMed2006

Mortality in the catastrophic antiphospholipid syndrome: causes of death and prognostic factors in a series of 250 patients.

OBJECTIVE: To assess the main causes of death and the prognostic factors that influence mortality in patients with the catastrophic antiphospholipid syndrome (CAPS). METHODS: We analyzed the case reports of 250 patients included in the CAPS Registry up to February 2005. To identify prognostic factors for CAPS, we compared the main clinical and immunologic features and the types of treatment in the patients who died with those features in the patients who survived. RESULTS: Recovery occurred in 56% of the episodes of CAPS and death occurred in 44%. Cerebral involvement, consisting mainly of stroke, cerebral hemorrhage, and encephalopathy, was considered the main cause of death, being present in 27.2% of patients, followed by cardiac involvement (19.8%) and infection (19.8%). The only factor we identified that was prognostic of a higher mortality rate was the presence of systemic lupus erythematosus (SLE). A higher recovery rate was associated with combined treatment with anticoagulants (ACs) plus corticosteroids (CS) plus plasma exchange (PE) (77.8%), followed by ACs plus CS plus PE and/or intravenous immunoglobulins (69%). In contrast, concomitant treatment with cyclophosphamide did not demonstrate additional benefit. CONCLUSION: Cerebral involvement (mainly consisting of stroke), cardiac involvement, and infections were considered the main causes of death in patients with CAPS. The presence of SLE was related to a higher mortality rate. According to the results of the present study, ACs plus CS plus PE should be the first line of therapy in patients with CAPS.

Adult↗
PubMed2006

New treatments for antiphospholipid syndrome.

Challenges in new drug development for APS include the controversy about the strength of association between aPL and thrombotic events, and unknown mechanism of aPL-induced thrombosis. In the long-term management of patients who have APS, controlled studies with warfarin alternatives (such as antiplatelet agents), the new anticoagulant agents (such as direct and indirect thrombin inhibitors), and newer therapeutic agents are vital. It is highly possible that the current "antithrombotic" approach to patients who are aPL-positive will be replaced by a "more specifically targeted, anti-inflammatory or immunomodulatory" approach in the future.

Antiphospholipid Syndrome↗
PubMed2006

Cardiac manifestations in the antiphospholipid syndrome.

Experimental evidence reveals that aPL are not only markers of APS, but also may play a causative role in the development of vascular thrombosis and pregnancy morbidity. The pathogenic mechanisms of aPL seem to be heterogeneous, including endothelial cell activation, the direct inhibition of the activated protein C pathway, abnormalities in platelet function, and in complement activation. aPLs induce proadhesive, proinflammatory, and procoagulant molecules that provide a persuasive explanation for induction of thrombosis in APS. Cardiac manifestations in APS include valve abnormalities (valve thickening and vegetations), occlusive arterial disease (atherosclerosis and myocardial infarction), intracardiac emboli, ventricular dysfunction, and pulmonary hypertension. aPL may be associated with accelerated atherosclerosis in APS patients. Valve disease is the most important and most common cardiac manifestation of APS. The precise mechanism by which valves become deformed is not yet fully known.

Antibodies, Antiphospholipid↗
PubMed2006

Antiphospholipid syndrome.

PURPOSE OF REVIEW: To review the recently published studies that can guide physicians in the management of persistently antiphospholipid antibody (aPL)-positive patients. RECENT FINDINGS: Two recent prospective randomized controlled trials of two intensities of warfarin concluded that both moderate and high-intensity anticoagulation are similarly protective in antiphospholipid syndrome patients after the first thrombosis. Despite lack of controlled studies, there is experimental evidence that hydroxychloroquine and statins may play a role in the management of aPL-positive patients. In the mouse model of antiphospholipid syndrome that involves the injection of high-titer antiphospholipid syndrome human serum, complement activation is essential in aPL-mediated fetal loss and heparin prevents aPL-induced complement activation. SUMMARY: Primary thrombosis prevention in persistently aPL-positive individuals lacks an evidence-based approach; elimination of reversible thrombosis risk factors and prophylaxis during high-risk periods is crucial. Secondary thrombosis prevention in persistently aPL-positive individuals lacks a risk-stratified approach; although the current recommendation is life-long warfarin, the necessity, duration, and the intensity of warfarin are still debated. Catastrophic antiphospholipid syndrome patients usually receive a combination of anticoagulation, corticosteroids, intravenous immunoglobulin, and plasma exchange; there is a clear need to test new agents. A common strategy to prevent fetal loss in aPL-positive patients with history of pregnancy morbidities is low-dose aspirin and heparin; if patients fail this regimen, the next step is the addition of intravenous immunoglobulin although this is not supported by controlled studies. Currently, there is no evidence that anticoagulation is effective for nonthrombotic manifestations of antiphospholipid antibodies.

Adult↗
PubMed2006

Lupus and thrombosis.

Explore the source record for details and available documents.

Antiphospholipid Syndrome↗
PubMed2004

What is antiphospholipid syndrome?

The description of antiphospholipid syndrome (APS) is vascular thrombosis and/or pregnancy morbidity occurring in persons with antiphospholipid antibodies (aPL). However, because of an unclear etiopathogenesis and the heterogeneous nature of aPL and of aPL-related clinical manifestations, a single, unambiguous definition of APS does not exist. In this paper, we describe a structured approach to APS, discuss the controversies, and offer descriptions of APS that include: an autoimmune systemic disease with a spectrum of (mostly thrombotic) clinical manifestations, an overdiagnosed disease when aPL is present but has no proven direct causative role in the clinical manifestations, and a disease of controversies that requires clarification of etiology and mechanisms and risk-stratified controlled clinical studies.

Antiphospholipid Syndrome↗
PubMed2004

How much warfarin is enough in APS related thrombosis?

Warfarin is the best available, most effective treatment for the secondary prevention of recurrent thrombosis in antiphospholipid syndrome (APS) patients. However, warfarin is cumbersome for both patients and physicians because of risk for bleeding and the need for frequent monitoring. Much detail regarding optimal management of APS patients still lacks an evidence-based approach. Asymptomatic patients should not receive warfarin. An optimal treatment for patients with livedo, cardiac valve disease, leg ulcers or microangiopathic nephropathy is unknown; it is likely that warfarin is ineffective for these manifestations of the APS. In low risk patients who have not previously failed warfarin, moderate intensity anticoagulation (target international normalized ratio [INR] 2.5) is as effective as, and safer than, high intensity anticoagulation (INR 3.5), at least for patients with venous thrombosis. Current recommendations, based on the opinion rather than on documentation, state that warfarin should be prescribed for the APS patient's life; studies that challenge this conclusion for carefully defined low risk patients whose thromboses occurred with trigger events will be welcome, as will be studies examining alternatives to warfarin, including antiplatelet drugs.

Antibodies, Antiphospholipid↗
PubMed2004

Challenges in bringing the bench to bedside in drug development for SLE.

It is now widely accepted that the current standard of care for systemic lupus erythematosus (SLE) patients is inadequate. There has not been a new medication approved for this disease in thirty years. Attempts to develop and test new drugs have been ongoing since the mid-1990s, but have encountered formidable obstacles. Current models for lupus pathogenesis have provided a theoretical framework for understanding how heterogeneous genetic defects might combine in various ways to increase susceptibility to SLE in different individuals, and could have important implications for new drug development. With the current burst of drug discovery and increased public awareness of SLE, the impetus to overcome these obstacles has never been greater.

Animals↗
PubMed2003

Monitoring by rheumatologists for methotrexate-, etanercept-, infliximab-, and anakinra-associated adverse events.

OBJECTIVE: To determine what monitoring protocols rheumatologists use to identify adverse events in rheumatoid arthritis (RA) patients treated with methotrexate (methotrexate), etanercept (etanercept), infliximab (infliximab), and anakinra (anakinra), how often rheumatologists encounter treatment-altering adverse events in their RA patients receiving these treatments, and how they feel about and comply with the current monitoring guidelines. METHODS: Three hundred ten physician members of the American College of Rheumatology (ACR) were notified by e-mail of a survey that was posted on our rheumatology Web site. Questions were closed-ended and multiple choice in format. RESULTS: One hundred twenty-three responses were received (40%). Most rheumatologists reported that they utilize the ACR recommended screening tests at baseline before methotrexate treatment is initiated. Seventy-nine percent reported that treatment-altering abnormalities had occurred in <5% of their methotrexate-treated RA patients, and 88% reported that such abnormalities had occurred in <10% of such patients, in the previous 3 years. Forty-one percent believed liver function monitoring guidelines need to be changed; 59% said they would agree with new guidelines that would include a recommendation for liver function monitoring every 3-4 months. Most rheumatologists were not aware of any guidelines for monitoring by blood tests in RA patients treated with biologic agents, yet the majority reported that they order blood tests before patients start these therapies and on followup. CONCLUSION: Our survey indicates that treatment-altering liver function abnormalities in methotrexate-treated RA patients are rare, and more than half of rheumatologists agree that a less stringent monitoring regimen should be considered. Rheumatologists and pharmaceutical companies might work together to develop guidelines for monitoring of patients treated with biologic agents.

Adverse Drug Reaction Reporting Systems↗