Beta-2 Glycoprotein Antibodies Research Articles

A CASE OF BORDETELLA BRONCHISEPTICA AND PNEUMOCYSTIS JIROVECI PNEUMONIA IN A YOUNG PATIENT

A CASE OF BORDETELLA BRONCHISEPTICA AND PNEUMOCYSTIS JIROVECI PNEUMONIA IN A YOUNG PATIENT

A CASE REPORT ON EXTENSIVE ARTERIAL THROMBOSIS AS A COMPLICATION OF COVID-19 INFECTION

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Coronavirus disease (COVID-19) is a global health crisis. It is associated with increased activation of the clotting system leading to thrombotic complications in 5 to 23% of cases[1]. It is known to cause significant venous thromboembolism and few cases with arterial thrombosis with increased risk of life-threatening complications like myocardial infarction, ischemic stroke, splenic infarct, and left ventricular clot have been reported[2]. CASE PRESENTATION: A 70-year-old female with a past medical history of coronary artery disease, Hypertension, COPD, recent COVID-19 (3 weeks ago) not requiring admission to hospital presented to the hospital with bilateral leg and forearm pain. Leg pain was worse with activity. She had feeble peripheral pulses on palpation.She underwent Computed Tomography angiography which showed extensive arterial thrombosis involving the distal abdominal aorta, left common iliac artery, superior mesenteric artery, and also showed an area of wedge-shaped infarction in the spleen. She had a thrombus at the apex of the left ventricle, with incidental 1.3 cm spiculated mass in the left lung. There was no evidence of venous thromboembolism in imaging.She was started on therapeutic anticoagulation with heparin. After multidisciplinary discussion with Hematology, Vascular surgery, and Cardiology, her anticoagulation was changed to Enoxaparin. She was managed medically. Workup including JAK2, beta-2 glycoprotein antibodies, lupus anticoagulant, and anticardiolipin antibodies was negative. DISCUSSION: The exact mechanisms that activate coagulation cascade in SARS-CoV-2 infection are still unknown, but they are found to be associated with increased thrombogenesis. SARS-CoV-2 viral infection can activate the plasmatic clotting system by activating multiple procoagulant pathways. Angiotensin-converting enzymes 2 are normally found on various cells such as lymphocytes, alveolar cells, monocytes/macrophages, and platelets. In SARS-CoV-2 infection, Surface S protein of SARS-CoV-2 binds to its target transmembrane receptor( ACE2 protein) and down-regulates the expression of ACE2 protein. It leads to the accumulation of angiotensin II in the body which interacts with platelets and endothelial cells leading to further promotion of clot formation[3]. This was the likely cause of hypercoagulable state in our patient leading to thrombosis. CONCLUSIONS: An extensive arterial clot can be the initial presentation in COVID-19 patients and can be treated promptly with anticoagulation. Early introduction of prophylactic anticoagulation is necessary to prevent clot formation. REFERENCE #1:.Thromboinflammation and the hypercoagulability of COVID-19. Connors JM, Levy JH J Thromb Haemost.2020 Jul;18(7):1559-1561. REFERENCE #2: Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV, and lessonsfrom the past.Giannis D, Ziogas IA, Gianni P J Clin Virol. 2020 Jun;127():104362. REFERENCE #3: Smith S A, Mutch N J, Baskar D, Rohloff P, Docampo R, Morrissey J H. Polyphosphate modulates bloodcoagulation and fibrinolysis. Proc Natl Acad Sci U S A. 2006;103(04):903–908. DISCLOSURES: No relevant relationships by Sumit Gami, source=Web Response No relevant relationships by Subash Ghimire, source=Web Response No relevant relationships by Sushmita Khadka, source=Web Response No relevant relationships by Shobha Mandal, source=Web Response

HEAVILY CALCIFIED CLOTS IN A PATIENT WITH CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION PRESENTING WITH BACTEREMIA

SESSION TITLE: Medical Student/Resident Pulmonary Vascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Antiphospholipid syndrome (APLS) is an autoimmune disorder that can lead to thrombotic disease. Here, we present a challenging case of catastrophic antiphospholipid syndrome with calcified clots, and chronic thromboembolic pulmonary hypertension (CTEPH) presenting with persistent bacteremia. CASE PRESENTATION: A 23-year-old female patient with a history of diabetes mellitus, methamphetamine and intravenous drug use disorder presented to an outside hospital with dry cough, shortness of breath, pleuritic chest pain, chills, and fatigue for 2 weeks. Blood cultures upon admission grew methicillin sensitive staphylococcus aureus (MSSA). Other labs were notable for thrombocytopenia and acute kidney injury. CT scan of chest and abdomen without contrast showed a large clot in her left pulmonary artery, inferior vena cava (IVC) extending into the right atrium (RA) with impressive calcifications (Figure 1). Transesophageal echocardiography showed no vegetations but revealed a large atrial thrombus extending from IVC into a dilated RA, dilated right ventricle, moderate tricuspid regurgitation with calculated right ventricular systolic pressure 55mmHg. Ventilation perfusion (VQ) scan showed a diffuse left lung perfusion defect without matched ventilation defect. She was transferred to our hospital for further care, her work-up revealed positive dilute Russell's viper venom time (dRVVT), cardiolipin antibodies and beta2-glycoprotein antibodies suggesting triple positive antiphospholipid syndrome. She was treated with intravenous heparin, however, developed hemoptysis requiring multiple blood transfusions and intubation, thus bronchial artery embolization was performed. Furthermore, she developed ST elevation myocardial infarction and splenic infarcts which were managed medically with resumption of heparin and antiplatelet therapy. She was eventually discharged on coumadin after completing six weeks of cefazolin and rifampin. DISCUSSION: This case illustrates an unusual presentation and calcification pattern of chronic clot, possibly due to the underlying infection, in a patient with CTEPH secondary to APLS. Mainstay of treatment for CTEPH remains anticoagulation followed by evaluation for pulmonary thromboendarterectomy (PTE) which is the only definite treatment (1). However, patients must tolerate anticoagulation, be clear of any infection and demonstrate adherence to therapy to undergo surgery. Furthermore, coumadin with an INR goal of 2.5 to 3.5 is recommended over direct oral anticoagulants in APLS with thromboembolism (2). CONCLUSIONS: In conclusion, CTEPH is associated with high morbidity and mortality, mainly from right heart failure (3). High level of suspicion is required to diagnose and promptly treat this rare disease with atypical presentation. Reference #1: Fedullo P, Kerr KM, Kim NH, Auger WR. Chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med 2011; 183:1605. Reference #2: Pengo V, Denas G, Zoppellaro G, et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. 2018;132:1365–71. Reference #3: Hoeper MM, Mayer E, Simonneau G, Rubin LJ. Chronic thromboembolic pulmonary hypertension. Circulation 2006; 113:2011. DISCLOSURES: No relevant relationships by Timothy Fernandes, source=Web Response No relevant relationships by Abdurrahman Husain, source=Web Response No relevant relationships by Alexandra Rose, source=Web Response No relevant relationships by Qais Zawaydeh, source=Web Response

A Case Series of Antiphospholipid Syndrome Patients

Introduction: Antiphospholipid syndrome (APS) is a pro-thrombotic, autoimmune mediated clinical syndrome associated with increased propensity for venous and arterial thrombosis and recurrent fetal loss. A significant clinical heterogeneity exists in the condition ranging from minor easily managed venous thromboses and TIAs to unusual, catastrophic, or refractory thromboses. It is generally unknown what factors are useful in predicting the clinical course. Our goal was to characterize our cohort and to look for any other factors that may be associated with thrombosis.Methods: We analyzed the records of 979 patients seen in a single physician cohort over a 4-year period at an academic institution. 81 had some mention of APS. Out of 81 patients, 23 patients were included. Seven of these patients did not meet our criteria precisely, but were considered as having APS due to high clinical suspicion by the treating physician. We defined APS by the presence of a thrombotic event or recurrent fetal loss in association with one of the following laboratory criteria repeatedly positive at least 12 weeks apart: Lupus anticoagulant (LAC), Beta-2 Glycoprotein antibodies (aB2GP), Cardiolipin antibodies (aCL). Cardiolipin and Beta-2-Glycoprotein antibodies were defined as abnormal if levels were above 40 mpl/gpl; IgA antibodies for Beta-2-Glycoprotein were also allowed. The tests for LAC were as follows: dilute Russell Viper Venom time (dRVVT), hexagonal lipid neutralization, partial thromboplastin time (PTT) mixing study, and tissue thromboplastin inhibition (TTI) 1:50/1:500. The TTI could not be the only abnormal test and TTIs were excluded if the Prothrombin time (PT) was prolonged for any reason. LAC tests done with patients on dabigatran, apixiban, or rivaroxaban were considered uninterruptable.Results: Table 1 and Table 2 outline our findings. As we had so few double or triple positive patients we were unable to detect a difference in clinical severity related to the number of laboratory criteria met. 6/14 women were on hormonal therapy at time of diagnosis. 5/18 patients who were tested for thrombophilias were found to have one; three with prothrombin gene variant (PGM) and two with factor V Leiden (FVL). In carefully assessing for concurrent risk factors, 18/23 (78%) of our patients had at least one risk factor for thrombosis, 9 (39%) had at least two risk factors, and four (17%) had at least three risk factors. Notably all five (22%) of the patients with no preexisting risk factors had no recurrence of thrombosis. We also found that two (9%) of our patients normalized the APS laboratory abnormalities over time.Discussion: Thrombophilia testing in patients with thromboses has grown dramatically over the last several decades and there are questions as to the utility in managing patients. The presence of antiphospholipid antibodies that are associated with APS, can be seen in asymptomatic patients, but are also seen in patients with catastrophic thromboses, thromboses refractory to anticoagulation, and in thromboses in unusual locations. In our case series, most patients were single positive and most had concurrent risk factors for thrombosis. We did not see evidence that double or triple positive APS patients had a more severe clinical course as compared to single positive patients, but we had so few multiple positive APS patients to allow us to conclude this with any certainty. An interesting observation was how many of the patients in our cohort had other known risk factors for thromboses specifically FVL, PGM, and hormonal therapy. We noted that patients with no other known risk factor other than APS seemed to have a better clinical course, while those with multiple risk factors had a more severe clinical course. Lastly, we noted some patients, who had met the diagnostic criteria for LAC, had their laboratory testing normalize over time. We plan to extend this case series in a larger patient cohort at our institution. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Report of Rare Urachal Carcinoma Presenting with Thrombocytopenia and Microangiopathic Hemolytic Anemia

Introduction:Thrombotic microangiopathy (TMA) is clinical syndrome characterized by microvascular thrombosis, consumptive thrombocytopenia and microangiopathic hemolytic anemia (MAHA). It is a feature of a number of clinical conditions, most prominently thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) and rarely an initial manifestation of systemic malignancy.Case:A previously healthy 31-year-old black woman presented to the emergency department with a 2 week history of lower back pain and hematuria and 1 week history of dyspnea on exertion and dizziness. She denied diarrhea, hematochezia, fever, or abdominal pain. Physical findings were unremarkable with normal blood pressure. Initial laboratory results revealed a white blood cell count of 4.4 x103/µL, hemoglobin of 4.4 g/dL, hematocrit 12.9%, platelets 43 x103/µL, absolute reticulocyte count 259.8 x103/µL, reticulocyte percentage 23.1%, haptoglobin <10 L mg/dL, LDH 1424 units/L, creatinine 0.7 mg/dL, total bilirubin 1.6 mg/dL, negative pregnancy test, and 10-15 white blood cells and >50 red blood cells per high powered field on microscopic urinalysis. Coombs test results were negative, the coagulation profile was normal, and peripheral blood smear revealed evidence of thrombocytopenia and MAHA (figure 1a). Diagnosis of TTP was made and treatment with daily therapeutic plasma exchange (TPE) was initiated. On hospital day 4, ADAMTS13 level drawn at diagnosis before initiation of plasma exchange returned at 94%, prompting further investigation as to the cause of her TMA. Serologic tests for hepatitis B & C virus, human immunodeficiency virus, antinuclear antibody (ANA), cardiolipin and beta-2 glycoprotein antibodies and computerized tomography (CT) scan of the abdomen and pelvis were all negative. Despite daily TPE for 6 days, she remained thrombocytopenic and continued to have ongoing hemolysis. Therefore, on hospital day 6, bone marrow aspiration and biopsy (figure 1b) was performed which showed a normocellular bone marrow for age (cellularity 70%) with full-spectrum trinlineage hematopoiesis, involved by metastatic signet-cell ring carcinoma. Immunostains were positive for CK7, CK20, CK 8/18, CDX2, pancytokeratin, and negative for PAX-8 and mammoglobin. TPE was discontinued and she was supported with packed red blood cell and platelet transfusions.Positron emission tomography–computed tomography (PET-CT) revealed a heterogeneously enhancing mass in the midline superior anterior wall of the bladder measuring 2.7 x 5.1 cm, but without abnormal uptake on PET. She underwent cystourethroscopy and a transurethral resection of bladder tumor which revealed a 6 cm solid sessile mass. Final pathology confirmed the diagnosis of moderate to poorly differentiated invasive urachal adenocarcinoma with mucinous and signet-ring cell features.Given the presence of metastatic disease, she was treated with a chemotherapy regimen consisting of cisplatin, fluorouracil, and leucovorin on days 1 through 5. Gemcitabine was held due to elevated liver transaminases. On day 1 of treatment, platelet count was 24 x103/µL and hemoglobin 8.1 g/dL. By treatment day 7, platelets had risen to 79 x103/µL. She last required a PRBC transfusion on treatment day 4.Discussion:TMA can occur in a variety of disorders, including TTP, HUS, malignant hypertension, scleroderma, antiphospholipid antibody syndrome, systemic lupus erythematosus, preeclampsia, HIV infection, and disseminated malignancy. Patients presenting with evidence of TMA and thrombocytopenia should elicit a high clinical suspicion for TTP and be urgently treated with plasma exchange. Deficiency of the von Willebrand factor-cleaving metalloproteinase ADAMTS13, or the presence of antibodies to ADAMTS13 plays a key role in the pathogenesis of primary TTP, although these findings are not necessary to make the diagnosis. However, patients with a high or normal ADAMTS13 level and without antibodies to ADAMTS13, especially those who do not improve with plasma exchange, should prompt an investigation for other causes of TMA. To our knowledge, we report the first case of metastatic urachal carcinoma presenting with features of MAHA and thrombocytopenia.Conclusion:TMA associated with malignancy is a rare, but potentially fatal condition. Recognition of this rare entity is critical to the initiation of appropriate treatment of underlying malignancy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Catastrophic Multi-Organ Failure with Bone Marrow Necrosis in a Sickle Cell Beta Plus Thalassemia Patient

The variant sickle cell hemoglobinopathies have a variety of phenotypic presentations. Sickle cell beta plus thalassemia is an uncommon variant with an incidence that is 1/10th of sickle cell trait. This phenotype usually is associated with a milder clinical course, however often the first clinical presentation of such patients can be fatal vaso-occlusive crisis. Our case involves a 47 year old African American male with a reported history of sickle cell trait presenting with acute on chronic lower back pain for which an organic cause could not be identified with plain Xrays. He was treated with benzodiazepines and narcotics and later admitted to the ICU after being found unresponsive at home. He required intubation for airway protection. He was started on a Narcan drip for presumed narcotic overdose, without improvement. Noncontrast CT imaging of the head was negative. Laboratory findings were significant for anemia, thrombocytopenia, leukocytosis, acute kidney injury and elevated liver enzymes. Hemolysis was suspected with a markedly elevated LDH. Peripheral smear showed mild microangiopathic changes with 0-1 schisctocytes per hpf without evidence of sickle cells. Hematology was consulted and the patient was started on plasma exchange for a presumed diagnosis of TTP, however it was discontinued when his ADAMTS13 returned at a low-normal 67%, and TTP was felt less likely. MRI of the brain showed multiple focal and patchy areas infarcts throughout white matter of both cerebral hemispheres. MRI of the lumbar and thoracic spine showed a heterogeneous appearance of the bone marrow, concerning for a marrow infiltrative process. Work up for infectious or vasculitic causes were unremarkable. Hemoglobin electrophoresis showed Hb A1 20.2 (L), A2 5.8 (H), Hb F 2.2 (H), Hb S 71.8 (H), identifying doubly heterozygous sickle cell beta plus thalassemia. Bone marrow biopsy was hyperplastic with areas of geographic necrosis with sickle cells causing sludging and congested sinusoidal spaces suggesting ischemic necrosis due to vaso-occlusion. He was treated with exchange transfusion, with repeat hemoglobin electrophoresis showing A1 73.2 (L), A2 3.5 (H), HbS 23.3 (H). His lupus anticoagulant was positive raising concern for APLAS contributing to his catastrophic clinical course and severe neurologic disease,so he was started on anticoagulation with Lovenox and high dose steroids at a dose of 1 mg/kg daily. When the anticardiolipin and beta2 glycoprotein antibodies returned negative, the steroids were tapered and eventually discontinued. The clinical significance of the lupus inhibitor remains unclear. Shortly after initiation of plasma exchange and simple transfusion, the patient did stabilize hematologically. Platelets returned to the normal range and there was no evidence to suggest ongoing hemolysis. Renal and liver function improved. However he made no neurological recovery. He continued to require ventilator support and underwent a tracheostomy. A repeat MRI head showed progressive infarcts of both cerebral hemispheres, with new cerebellar infarcts. He was declared brain dead after 23 days and care was withdrawn. This case demonstrates that sickle cell beta plus thalassemia can present with acute hemolysis and bone marrow necrosis in otherwise healthy adults. The literature supports bone marrow necrosis and subsequent fat emboli as the likely pathophysiologic nidus responsible for multiorgan system failure including the catastrophic neurologic insult in this patient. Prompt recognition of this uncommon and challenging disease presentation and timely treatment with exchange transfusion may lead to improved clinical outcomes. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Antiphospholipid syndrome: pathogenesis and a window of treatment opportunities in the future

Antiphospholipid syndrome (APS) is a systemic autoimmune vascular disease characterized by recurrent thrombotic episodes and/or obstetric complications. Management of this disease has been restricted mainly to anticoagulation; however, in recent years, significant advancement has been made in elucidating the pathophysiology of the disease including antiphospholipid antibody (aPL)-induced activation of the platelets, endothelial cells, monocytes, complement and coagulation cascade. Stemming from these advances, potential targeted therapeutic approaches have been proposed. We utilized a computer-assisted search of the literature (MEDLINE, National Library of Medicine, Bethesda, MD, USA) up until September 2009 using the keywords: antiphospholipid syndrome, antiphospholipid antibodies, anticardiolipin antibodies, lupus anticoagulant, anti beta-2 glycoprotein antibodies, complement system, tissue factor, p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor kappa B, toll-like receptors, annexin, Rituximab, statins and tumour necrosis factor. Several study groups have separately demonstrated the importance of inflammatory mediators in the pathogenesis of APS. It was also established that tissue factor, MAPK, nuclear factors kappa B, and the complement system are integral to the disease process. Toll-like receptors and annexin have as well been associated with the disease pathophysiology. Some study groups proposed new targeted therapeutic strategies some of which have shown promising results in preclinical studies. These include Rituximab, complement inhibition, anti-cytokine therapy, p38 MAPK inhibitors, nuclear factor inhibitors and tissue factor inhibitors. As more insight is being gained into the pathophysiology of APS, newer therapeutic strategies are being proposed that might lead to safer and more efficacious treatment modalities in the future.

Clinical Reasoning: A 62-year-old woman with deafness, unilateral visual loss, and episodes of numbness

In May 2007, a 62-year-old woman presented with two episodes of right-hand numbness. The episodes were accompanied by profound fatigue. Each event lasted 5 minutes, and both occurred within a 2-week period. She also recalled an episode of right-sided numbness 30 years previously. She had a past medical history of hypothyroidism, hypertension, hypercholesterolemia, and multiple miscarriages. About 15 years ago, she began losing hearing in her left and then right ear, and she had been completely deaf for the last 8 years. Prior testing had revealed that the patient had sensorineural hearing loss, but the etiology could not be determined. Family and social history were unremarkable. ### Questions for consideration: 1. What is the differential diagnosis for episodic neurologic abnormalities? 2. What diagnostic testing would you perform? The differential diagnosis of transient sensory dysfunction is broad and includes TIA, complicated migraine, seizure, metabolic derangement, peripheral nerve compression, compressive myelopathy, multiple sclerosis (MS), and conversion disorder.1 Particularly in patients over the age 55, transient neurologic attacks that are focal, nonfocal, or a mixture of both are associated with an increased risk of stroke. Therefore, an evaluation of our patient should include carotid ultrasound, transthoracic echocardiogram, and head CT or MRI of the brain.2 The history of multiple miscarriages raises the suspicion for antiphospholipid syndrome, which may cause a hypercoagulable state. Anticardiolipin antibodies, anti beta-2 glycoprotein antibodies, and lupus anticoagulant assays could be performed to investigate this possibility. An EEG may be considered to identify epileptiform discharges, especially given the patient’s post-event fatigue. A diagnostic evaluation for the cause of her two episodes of numbness was unrevealing. Then, in January 2008, the patient noted blurred vision in her left eye that progressed over 3 days. She denied pain on eye movements, photopsia, metamorphopsia, or other neurologic deficit. Initial eye examination showed a left relative afferent defect …

Antiphosphatidylserine antibodies in patients with autoimmune diseases and HIV-infected patients: Effects of Tween 20 and relationship with antibodies to ?2-glycoprotein I

Antiphospholipid antibodies (aPL) react with negatively charged phospholipids, which may often be complexed with a protein cofactor such as beta2 glycoprotein (beta2GPI) and prothrombin. Cofactor requirements may be assessed by measuring antibodies to beta2GPI or by adding Tween 20 to some reagents in the assays for aPL (anticardiolipin and antiphosphatidyIserine). We have measured anticardiolipin antibodies (aCL), antiphosphatidylserine antibodies (aPS), and anti beta2 glycoprotein antibodies (abeta2GPI) in the serum of 10 normal subjects, 20 patients with systemic autoimmune diseases (SAD) diagnosed as having systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS), and 12 patients with HIV infection. Adding Tween 20 to aPS, the assay couldn't differentiate protein cofactor dependent from independent antibodies, but this can be done by measuring abeta2GPI (P= 0.0008). There was a significant correlation between aCL and a(beta)2GPI in the control group and in the patients with SAD, but not in the HIV-positive (HIV+) patients. After excluding the HIV+ patients, the best Spearman correlation was obtained between a(beta)2GPI and aCL (0.64, P< 0.0005). In 3 out of 7 patients with positive a(beta)2GPI and in 5 out of 6 patients with moderate or high positive aCL of the group of SAD, there was a history of venous thrombosis. The presence of moderate or high values of aCL either alone or together with a(beta)2GPI was significantly associated with a history of venous thrombosis (P < 0.05). Moderate or high aCL concentrations and their association with a(beta)2GPI seems to be useful for the assessment of the risk of venous thrombosis in unselected patients with SLE or APS.

Correlation between beta 2-glycoprotein antibodies and antiphospholipid antibodies in patients with reproductive failure.

Antiphospholipid antibodies (APAs) are important in the etiology of reproductive failure. Studies have shown that binding proteins are necessary for the detection of APAs. One of these, beta 2-glycoprotein, has been shown to be necessary for detection of anticardiolipin antibodies. It is felt that some APAs may be directed to the binding protein itself, or to a combination of the binding protein and phospholipid. In this study, a comparison of APAs vs. anti beta 2-glycoprotein antibodies was performed on the sera of 123 women younger than 40 years of age with a history of reproductive failure. Antibodies to six phospholipid epitopes, cardiolipin, phosphatidyle-thanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, phosphatidylglycerol, and phosphatidylserine, were measured. Of the 123 women tested, 33 had one or more positive immunoglobulin (Ig)G antibodies to phospholipids, of which 9 were to cardiolipin. However, only 1 of 123 women had IgG antibodies to beta 2-glycoprotein and she was APA negative. Thirty-eight of 123 women had one or more IgM antibodies to phospholipids, with none directed to cardiolipin IgM. In contrast, only 8 of the 123 women had IgM antibodies to beta 2-glycoprotein. Five of the eight patients had IgM APA; 4 of 5 had IgM antibodies to PE, 1 to PI. There is no correlation between beta 2-glycoprotein antibodies and APA status in this population. To date, our most sensitive test for detecting phospholipid autoimmune-mediated in vitro fertilization failure still appears to be the ELISA assay for APA.