Biomedical subjects

Syma Iqbal

Publications and source records attributed to Syma Iqbal.

17 recordsLinked to original sources

PubMed2006

Molecular determinants of irinotecan efficacy.

Molecular markers predicting the efficacy of CPT-11 based chemotherapies in patients with colorectal cancer (CRC) are unknown. Therefore, we investigated whether mRNA levels of drug targets (Topoisomerase I, TS), enzymes involved in 5-FU metabolism (DPD), in angiogenesis (EGFR, IL-8, VEGF) and in DNA-repair/drug detoxification (ERCC1, GST-P1) are associated with the clinical outcome of patients with CRC treated with first-line CPT-11 based chemotherapy. Thirty three patients with metastatic CRC were included in the study. Intratumoral gene expression levels were assessed from paraffin-embedded tissue samples, using laser capture microdissection and quantitative Real-Time PCR. Complete response was observed in 1 patient, partial response in 12 patients, stable disease in 13 patients and progressive disease in 6 patients. Response was inevaluable for 1 patient. Patients with complete response or partial response were classified as responders, while patients with stable disease or progressive disease were classified as nonresponders. High intratumoral mRNA levels of EGFR, ERCC1 and GSPT-P1 were each significantly associated with response to CPT-11 based chemotherapy. Recursive partitioning analysis showed that mRNA levels of EGFR and ERCC1 are primarily responsible for delineating responders from nonresponders. Also, the combination of high intratumoral gene expression levels of both EGFR and ERCC1 was significantly associated with progression-free survival. The mRNA levels of EGFR had a significant correlation with expression levels of ERCC1, GST-P1 and VEGF. This small retrospective study suggests that gene expression levels of EGFR, ERCC1 and GST-P1 may be useful in predicting the clinical outcome of patients with metastatic CRC treated with first-line CPT-11 based chemotherapy.

Adult↗

PubMed2006

Phase I clinical trial of weekly docetaxel and exisulind, a novel inducer of apoptosis.

BACKGROUND: The objective of this phase I study was to determine the maximal tolerated dose (MTD) of the combination of weekly docetaxel and exisulind in patients with advanced solid tumors. PATIENTS AND METHODS: Patients with advanced or refractory solid tumors were treated with intravenous weekly docetaxel with daily oral exisulind. The following dose levels (docetaxel/exisulind) were explored: 30-mg/m2/200 mg po bid, 35/200, 35/250 and 40/250. Docetaxel was administered weekly for 6 weeks followed by 2 weeks off, and exisulind was taken twice daily. Each cycle was 8 weeks. RESULTS: Eighteen patients were enrolled in the study. All of them had received prior systemic therapy. Most patients had either melanoma or carcinomas of the upper gastrointestinal tract. A total of 31 cycles of therapy were administered. DLTs were grade 3 diarrhea, anorexia and fatigue and grade 3 cutaneous toxicity at dose level 4 (40/250). Myelosuppression was mild. Fatigue and gastrointestinal toxicity (anorexia, dyspepsia, nausea, abdominal pain and diarrhea) represented the most common toxicities. However, grade 3 and grade 4 toxicities were uncommon. There were no treatment related deaths. No objective responses were observed and five patients achieved stable disease. CONCLUSIONS: The recommended dose for phase II studies is weekly docetaxel 35 mg/m2 for 6 weeks followed by 2 weeks off in combination with oral exisulind 250 mg po bid. This combination is feasible and well-tolerated at these doses.

Adult↗

PubMed2006

Cyclin D1 and epidermal growth factor polymorphisms associated with survival in patients with advanced colorectal cancer treated with Cetuximab.

The study aimed to investigate whether polymorphisms in genes of the EGFR signaling pathway are associated with clinical outcome in advanced colorectal cancer (CRC) patients treated with single-agent Cetuximab. Polymorphisms of interest in the EGFR pathway include: cyclin D1 (CCND1) A870G, cyclooxygenase 2 (Cox-2) G-765C, epidermal growth factor (EGF) A61G, epidermal growth factor receptor (EGFR) codon R497 K, EGFR CA dinucleotide repeat in intron 1, interleukin (IL)-8 T-251A and vascular endothelial growth factor (VEGF) C936 T gene polymorphisms. Thirty-nine metastatic CRC patients were enrolled in the IMCL-0144 trial and treated with single-agent Cetuximab. Using the polymerase chain reaction-restriction fragment length polymorphism method, gene polymorphisms of CCND1, COX-2, EGF, EGFR, IL-8 and VEGF were assessed from genomic DNA extracted from blood samples. A significant association was found between the CCND1 A870G polymorphism and overall survival in our 39 CRC subjects. Patients with the AA homozygous genotype survived for a median of 2.3 months [95% confidence interval (CI)=2.1-5.7], whereas those with any G allele (AG, GG genotype) survived for a median of 8.7 months (95% CI=4.4-13.5) (P=0.019, log-rank test). When we analysed the cyclin D1 and EGF polymorphisms together, patients with favourable genotypes (EGF any A allele and CCND1 any G allele) showed a median survival time of 12 months (95% CI=4.8-15.2), whereas patients with any two unfavourable genotypes (EGF GG or CCND1 AA) showed a median survived time of 4.4 months (95% CI=2.1-5.7) (P=0.004, log-rank test). The findings of this pilot study suggest that the cyclin D1 A870G and the EGF A61G polymorphisms may be useful molecular markers for predicting clinical outcome in CRC patients treated with single-agent Cetuximab.

Adult↗

PubMed2006

Gene expression in tumor-adjacent normal tissue is associated with recurrence in patients with rectal cancer treated with adjuvant chemoradiation.

Recurrence is a significant clinical problem for patients with rectal cancer treated with adjuvant chemoradiation. Previous studies have suggested that determining intratumoral gene expression of key genes may be helpful in predicting clinical outcome of patients with gastrointestinal malignancies undergoing chemotherapy. The role of molecular predictors for prediction of recurrence in the setting of adjuvant chemoradiotherapy is not well established. The present study was designed to identify a genetic profile that would be associated with recurrence in patients with rectal cancer treated with adjuvant chemoradiation therapy. A retrospective study with a longitudinal cohort and a cross-sectional cohort of 67 patients with locally advanced rectal cancer who underwent cancer resection, followed by 5-fluorouracil (5-FU) plus pelvic radiation was conducted. Total RNA was extracted from formalin-fixed, paraffin-embedded, laser-captured-microdissected tissue. We determined mRNA levels of genes involved in the 5-FU pathway (thymidylate synthase, dihydropyrimidine dehydrogenase), DNA-repair (excision-repair cross-complementing factor 1, Rad51), angiogenesis/radiation sensitivity [vascular endothelial growth factor (VEGF)] and radio-sensitivity [epidermal growth factor receptor (EGFR)] in tumor tissue and tumor-adjacent normal tissue by quantitative reverse transcriptase-polymerase chain reaction. In univariate analysis, only intratumoral gene expression level of VEGF (P = 0.055) was associated with recurrence, whereas elevated mRNA expression levels of thymidylate synthase (P = 0.008), VEGF (P = 0.023) and EGFR (P = 0.004) in tumor-adjacent normal tissue were significantly associated with recurrence. Multivariate analysis using recursive partitioning indicated that distinct groups of recurrence could be defined by elevated mRNA expression levels of VEGF, EGFR in tumor-adjacent normal tissue, and Rad51 in tumor tissue. These data suggest that the genetic profile of the tumor-adjacent normal tissue may be associated with treatment failure, indicating that tumor microenvironment may be more important in the development of recurrence of rectal tumors than formerly expected.

Adult↗

PubMed2006

Genomic profiling associated with recurrence in patients with rectal cancer treated with chemoradiation.

PURPOSE: Stage II and III adenocarcinoma of the rectum has an overall 5-year survival rate of approximately 50%, and tumor recurrence remains a major problem despite an improvement in local control through chemotherapy and radiation. The efficacy of chemoradiation therapy may be significantly compromised as a result of interindividual variations in clinical response and host toxicity. Therefore, it is imperative to identify those patients who will benefit from chemoradiation therapy and those who will develop recurrent disease. In this study, we tested whether a specific pattern of 21 polymorphisms in 18 genes involved in the critical pathways of cancer progression (i.e., drug metabolism, tumor microenvironment, cell cycle regulation, and DNA repair) will predict the risk of tumor recurrence in rectal cancer patients treated with chemoradiation. PATIENTS AND METHODS: A total of 90 patients with Stage II or III rectal cancer treated with chemoradiation were genotyped using polymerase chain reaction (PCR)-based techniques for 21 polymorphisms. RESULTS: A polymorphism in interleukin (IL)-8 was individually associated with risk of recurrence. Classification and regression tree analysis of all polymorphisms and clinical variables developed a risk tree including the following variables: node status, IL-8, intracellular adhesion molecule-1, transforming growth factor-beta, and fibroblast growth factor receptor 4. CONCLUSION: Genomic profiling may help to identify patients who are at high risk for developing tumor recurrence, and those who are more likely to benefit from chemoradiation therapy. A larger prospective study is needed to validate these preliminary data using germline polymorphisms on tumor recurrences in rectal cancer patients treated with chemoradiation.

Antineoplastic Agents↗

PubMed2006

Epidermal growth factor receptor and epidermal growth factor receptor variant III gene expression in metastatic colorectal cancer.

PURPOSE: The epidermal growth factor receptor (EGFR) variant type III (variously called EGFRvIII, de2-7 EGFR, or triangle upEGFR) has an in-frame deletion of the extracellular domain and is found in numerous types of human tumors. Because EGFRvIII has been reported to be tumor specific and has oncogenic potential, it is being investigated as a potential therapeutic target, but to our knowledge, there is only 1 previous report about EGFRvIII by immunohistochemistry in colorectal cancer. Our aim was to indicate the frequency of gene expressions of EGFRvIII and EGFR in metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Forty-five patients with mCRC who received the chemotherapy for metastatic disease were analyzed for the EGFRvIII variant. Paraffin-embedded tumor tissues were dissected using laser-captured microdissection and analyzed for the EGFR and EGFRvIII messenger RNA expression using a quantitative real-time reverse-transcriptase polymerase chain reaction method. Gene expression values (relative messenger RNA levels) are expressed as ratios (differences from the cycle threshold values) between the target gene and internal reference gene (beta-actin). Twenty-five women and 20 men with a median age of 55 years (range, 25-76 years) were included in this study. RESULTS: We did not find any expression of EGFRvIII in these 45 patients except for control cell lines as U87.EGFRvIII. However, EGFR gene expression was found in 43 of 45 (95.6%) with a range of 0.38-2.83. CONCLUSION: Our results demonstrate that the expression of EGFRvIII is rare, but most colon cancer demonstrates EGFR gene expression. We conclude that EGFRvIII does not play an important role in mCRC.

Adult↗

PubMed2005

Molecular determinants of cetuximab efficacy.

PURPOSE: To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF), all members of the EGFR signaling pathway, are associated with clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab. PATIENTS AND METHODS: Thirty-nine patients with metastatic CRC, refractory to both irinotecan and oxaliplatin, were enrolled on IMCL-0144 and treated with single-agent cetuximab. The intratumoral mRNA levels of CCND1, Cox-2, EGFR, IL-8, and VEGF were assessed from paraffin-embedded tissue samples using laser-capture microdissection and quantitative real-time polymerase chain reaction. RESULTS: There were 21 women and 18 men with a median age of 64 years (range, 35 to 83 years). Higher gene expression levels of VEGF were associated with resistance to cetuximab (P = .038; Kruskal-Wallis test). The combination of low gene expression levels of Cox-2, EGFR, and IL-8 was significantly associated with overall survival (13.5 v 2.3 months; P = .028; log-rank test). Both findings were independent of skin toxicity that was itself significantly correlated to survival. Patients with a lower mRNA amount of EGFR had a longer overall survival compared with patients that had a higher mRNA amount (7.3 v 2.2 months; P = .09; log-rank test). Patients with lower expression of Cox-2 had a significantly higher rate of grade 2 to 3 skin reactions under cetuximab treatment. CONCLUSION: This pilot study suggests that gene expression levels of Cox-2, EGFR, IL-8, and VEGF in patients with metastatic CRC may be useful markers of clinical outcome in single-agent cetuximab treatment.

Adult↗

PubMed2005

Phase I clinical and pharmacokinetic trial of docetaxel and irinotecan administered on a weekly schedule.

BACKGROUND: Docetaxel and irinotecan are synergistic agents with a broad spectrum of activity but overlapping myelosuppression. The study was designed to maintain dose intensity while limiting myelosuppression. The objectives of this study were to determine the maximal tolerated dose (MTD) of the combination of docetaxel and irinotecan administered weekly for four consecutive weeks every 42 days, to describe toxicities of this regimen, and to perform a pharmacokinetic analysis to evaluate changes in drug disposition as a function of dose as well as repeated dosing. METHODS: Adult patients with advanced solid tumors were treated with docetaxel followed by irinotecan. Doses of 30/50, 35/50, 35/66, 30/57, 30/65, 30/80 mg/m(2), respectively, were studied. Pharmacokinetics of docetaxel, irinotecan and SN-38 in plasma were determined on days 1 and 22 by a high-performance liquid chromatography (HPLC) assay. RESULTS: A total of 35 patients were treated. The MTD was docetaxel 30 mg/m(2) plus irinotecan 65 mg/m(2). Diarrhea was the dose-limiting toxicity; myelosuppression and other non-hematological toxicities were uncommon and mild. There were no significant differences in pharmacokinetic parameters between day 1 and day 22 (n=20). Five objective responses (breast, stomach and unknown primary) were observed among 30 evaluable patients. In addition, eight patients achieved stable disease. CONCLUSIONS: The combination of weekly docetaxel and irinotecan is a well tolerated regimen and should be explored in phase II trials. This schedule maintains dose intensity and has limited myelosuppression.

Adult↗

PubMed2005

A phase II study of farnesyl transferase inhibitor R115777 in pancreatic cancer: a Southwest oncology group (SWOG 9924) study.

Ninety per cent of pancreatic adenocarcinomas (PC) contain mutations of the K-Ras proto-oncogene resulting in constitutively activated Ras protein. A critical step in Ras activation is farnesylation of Ras protein. Farnesyl transferase inhibitors are compounds that inhibit farnesylation. We report the results of a phase II trial of R115777, an oral farnesyl transferase inhibitor, in patients with surgically incurable locally advanced or metastatic PC. Between 6/1/2000 and 11/20/2001, 58 cases were accrued, 53 of whom were eligible and analyzable. Patients were required to have a performance status (PS) 0 to 1, be able to take oral medications, and to have adequate renal, hepatic, and hematologic functions. Fifty-five percent were male. Median age was 64.7 years (38.9 to 80.6), and patients had no previous systemic therapy for advanced PC. Treatment consisted of R115777 300 mg po bid given for 3 out of every 4 weeks. Toxicities were as follows: Grade 3 in 19/53 (36%), grade 4 in 53 (173%), and grade 5 in 53 (8%). Most frequent toxicities were: anemia 35/53 (66%), fatigue and malaise 33/53 (62%), nausea 31/53 (58%). Grade 5 toxicities included: thromboembolism 1, infection 2, other 1. Median survival was 2.6 months (mo) (95% CI 2.1-3.6), 6-mo survival is 19% (95% CI, 8-29%), median time to treatment failure was 1.4 mo (95% GI 1.1-1.6). R115777 is ineffective as monotherapy in advanced pancreatic cancer.

Adenocarcinoma↗

PubMed2004

Integration of novel agents in the treatment of colorectal cancer.

Two of the most promising new targets in the treatment of colorectal cancer are the epithelial growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF). Agents that inhibit the EGFR or bind to VEGF have demonstrated clinical activity as single agents and in combination with chemotherapy in phase II and phase III clinical trials. The most promising of these agents are cetuximab, which blocks the binding of EGF and transforming growth factor alpha (TGF-alpha) to EGFR, and bevacizumab, which binds free VEGF. Cetuximab and irinotecan have been evaluated in two clinical studies in the USA (IMCL CP02-0141 and IMCL CP02-9923). Study IMCL CP02-0141 evaluated the antitumor activity of single-agent cetuximab in patients with irinotecan-refractory, EGFR-positive metastatic colorectal carcinoma. There were 6 partial responses in 57 treated patients, for a response rate of 10.5%. Study IMCL CP02-9923 evaluated the combination of cetuximab and irinotecan in a total of 139 patients enrolled at 27 study sites. In this trial 22.5% of patients with progressive disease on irinotecan achieved an objective response (19% by investigator assessment) showing that the combination of cetuximab and irinotecan has antitumor activity in this population. A large randomized phase II trial evaluating similar study populations in Europe confirmed these findings, demonstrating response rates for cetuximab/irinotecan and cetuximab alone of 22.9% and 10.8%, respectively. The other promising agent bevacizumab is a humanized variant of the anti-VEGF monoclonal antibody. VEGF is produced by healthy and neoplastic cells. Its activities are mediated by two receptor tyrosine kinases. VEGF signaling is often a rate-limiting step in physiologic and pathologic angiogenesis. Bevacizumab has been studied as an antiangiogenic cancer therapeutic as a single agent and in combination with chemotherapy in patients with stage III and IV colon cancer. In addition to its direct antiangiogenic effects, bevacizumab may allow more efficient delivery of chemotherapy by altering tumor vasculature and decreasing the elevated interstitial pressure common in tumors. In this regard, some of the most robust phase II data using bevacizumab are from a randomized study of chemotherapy [fluorouracil (5-FU) and leucovorin (LV)] with or without bevacizumab in metastatic colorectal cancer. In this study, treatment with bevacizumab plus 5-FU/LV resulted in higher response rates, longer median time to disease progression, and longer median survival. Recently, a phase III, multicenter, double-blind, randomized, placebo-controlled trial was designed to investigate the addition of bevacizumab to first-line irinotecan, 5-FU, and LV chemotherapy (IFL). The trial showed a higher response rate, longer time to tumor progression, and prolonged overall survival in patients with metastatic colorectal cancer. It was the first large, randomized, phase III survival trial to assess the importance of targeting VEGF and tumor angiogenesis for the treatment of human cancer. Integration of novel agents targeting VEGF and EGFR with irinotecan-based chemotherapy has shown clinical activity in patients with metastatic colorectal cancer. The goal in the future will be to predict which specific chemotherapy and targeted agent combination will most likely benefit individual patients.

Antibodies, Monoclonal↗

PubMed2004

Angiogenesis inhibitors in the treatment of colorectal cancer.

Angiogenesis is critical for normal and pathologic processes in new blood vessel formation. A recent significant advance in the treatment of metastatic colorectal cancer has occurred by the development of agents targeting key regulatory molecules involved in this process, specifically vascular endothelial growth factor (VEGF). These angiogenesis inhibitors, include bevacizumab (Avastin, Genentech, Inc, South San Francisco, CA), which binds free VEGF. Recently, a phase III, multicenter, double-blind, randomized, placebo-controlled trial was designed to determine whether or not the addition of bevacizumab to first-line irinotecan, 5-fluorouracil, and leucovorin chemotherapy was completed in patients with metastatic colorectal cancer. The trial showed a higher response rate, longer time to tumor progression, and prolonged overall survival in patients with metastatic colorectal cancer. Of note, this was the first large, randomized, phase III study to show the importance of targeting VEGF and tumor angiogenesis for the treatment of human cancer. Other potential targets of angiogenesis, such as the VEGF receptor and multi-targeted agents, are undergoing evaluation in clinical trials.

Angiogenesis Inhibitors↗

PubMed2004

Tailored chemotherapy for colorectal cancer: a new approach to therapy.

The treatment of colorectal cancer has advanced over the past several years with the introduction of several active agents. Determining which patients to treat with chemotherapy and choosing optimal treatment would allow practioners to maximize the benefit of chemotherapy. Several prognostic and predictive markers have been identified and include oncogenes, tumor suppressor genes, genes involved in angiogenic and apoptotic pathways and cell proliferation, and those encoding targets of chemotherapy. Specifically, prognostic markers include deletion of 18q (DCC), p27 and microsatellite instability. Predictive markers are those that may determine efficacy of drugs used in colorectal cancer such as fluropyrimidines and oxaliplatin. Alterations in gene expression, protein expression and polymorphic variants in genes encoding thymidylate synthase, dihydropyrimidine dehydrogenase, and thymidine phosphorylase and excision repair cross-complementing genes (ERCC1) may be useful as markers for clinical drug response, survival and host toxicity. The integration of these prognostic and predictive markers would allow individualized treatment for patients, maximizing therapeutic effect and minimizing exposure to toxicity.

Antineoplastic Agents↗

PubMed2004

A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels.

OBJECTIVE: A 6 bp deletion polymorphism in the thymidylate synthase (TS) gene was investigated in order to determine its function. METHODS: A luciferase system was used to investigate the function of the 6 bp/1494 polymorphism in vitro. A group of 43 patients with colorectal carcinoma were evaluated for the 6 bp/1494 polymorphism and for intratumoral TS mRNA levels in vivo. RESULTS: The 3'UTR of TS containing the +6 bp polymorphism resulted in an approximate 35% decrease in luciferase activity and mRNA levels, while the TS-3'UTR bearing the -6 bp deletion resulted in an approximate 70% decrease in luciferase activity and mRNA levels. The TS-3'UTR construct containing the -6 bp/1494 deletion also had a higher rate of message degradation compared to the +6 bp/1494 construct. Individuals homozygous for the insertion (+6 bp/+6 bp) had significantly higher TS mRNA levels compared to individuals that were homozygous for the deletion (-6 bp/-6 bp) (P < 0.007). We determined the frequency of the -6 bp/1494 deletion polymorphism to be 41% in non-Hispanic whites, 26% in Hispanic whites, 52% in African-Americans and 76% in Singapore Chinese. CONCLUSIONS: These results suggest that the -6 bp/1494 deletion polymorphism in the 3'UTR of TS is associated with decreased mRNA stability in vitro and lower intratumoral TS expression in vivo. Further, the 6 bp/1494 polymorphism varies greatly within different ethnic populations and is in linkage disequilibrium with the TS 5' tandem repeat enhancer polymorphism. Taken together, these data suggest that the 6 bp/1494 polymorphism may be a useful screening tool in predicting TS mRNA expression.

3' Untranslated Regions↗

PubMed2004

Capecitabine: the new generation of fluoropyrimidines in colorectal cancer.

Colorectal cancer is the second leading cause of cancer death in the USA and fluoropyrimidines have been the mainstay of treatment for over 40 years. Currently, capecitabine is the only orally available fluoropyrimidine approved for treatment in the USA. As a single agent it has demonstrated activity and equivalence to 5-fluorouracil (5-FU) intravenous administration via the Mayo Clinic regimen, in both the metastatic and adjuvant settings. Ongoing clinical trials are evaluating the efficacy of capecitabine in combination with oxaliplatin and irinotecan as more convenient substitutes for infusional 5-FU in the 5-FU/leucovorin/oxaliplatin and 5-FU/irinotecan regimens.

Antimetabolites, Antineoplastic↗

PubMed2003

Targeted therapy and pharmacogenomic programs.

The goal in administering chemotherapeutics is to develop the ability to predict the outcome of therapy in terms of response and toxicity. Technology has been developed to allow tumor profiling with measurement of protein expression, gene expression levels of markers, and even genetic polymorphisms, which may predict response to particular chemotherapeutics. The chemotherapeutics for which particular markers have been shown to predict outcome include the fluoropyrimidines and platinums. The next step is to develop clinical trials that will assess prospectively the benefits of profiling a patient's particular tumor, which should translate into an improvement in response and toxicity.

Antineoplastic Agents↗

PubMed2003

Molecular predictors of treatment and outcome in colorectal cancer.

Understanding of the metabolism and mechanisms of resistance of tumors to chemotherapeutic agents is essential so that we can administer therapy to maximize response and minimize toxicity. In this review we describe molecular markers associated with fluoropyrimidine and platinum-based chemotherapy that may predict the outcome of therapy when patients are treated with these agents. We discuss the ways in which determination of gene expression levels can enhance the treatment of colorectal cancer through prediction of patient response and tailoring of chemotherapy to the characteristics of an individual tumor.

Antineoplastic Agents↗

PubMed2002

Detection of lupus anticoagulant identifies patients with autoimmune haemolytic anaemia at increased risk for venous thromboembolism.

Venous thromboembolism (VTE) is a well-recognized complication of autoimmune haemolytic anaemia (AIHA), and is a major cause of morbidity and mortality in this disorder. However, the incidence, pathogenesis and risk-factors for VTE in AIHA remain poorly defined. Lupus anticoagulants (LA) and anticardiolipin (ACA) antibodies are autoantibodies directed against epitopes on prothrombin or beta2 glycoprotein I (beta2-GPI). Both LA and ACA (together called antiphospholipid antibodies, APLA) are associated with VTE. We have prospectively studied the occurrence of VTE and APLA in 30 patients with AIHA. VTE was objectively documented in eight (27%) patients. APLA were detected in 19 (63%) patients with AIHA, of whom nine (30%) had a LA and 17 (57%) ACA. Seven patients had both LA and ACA. Among the eight patients with VTE, LA was detected in five (63%) and ACA in four (50%). There was a statistically significant association between presence of LA and occurrence of VTE (RR: 7.50, 95% CI: 1.25-45.2, P = 0.03). VTE is a frequent and life-threatening complication of AIHA. Detection of the lupus anticoagulant in patients with AIHA identifies individuals at significantly increased risk for VTE. Future studies should address the role of prophylactic anticoagulation in patients with AIHA.

Adult↗