Anticardiolipin Antibody Test Research Articles

A RARE CASE OF POST TUBERCULAR PLEURAL EFFUSION WITH SEROPOSITIVE SYSTEMIC LUPUS ERYTHEMATOSUS WITH NSIP PATTERN INTERSTITIAL LUNG DISEASE

Connective tissue disorders like systemic lupus erythematosus can have serious pulmonary complications like ILD. In this case report we had studied 25year male patient who came to OPD of Department of Respiratory Medicine NKPSIMS AND RC Nagpur Maharashtra, with complaint of breathlessness on exertion since 3-4 years and was on medication. Patient was case of post tubercular pleural effusion with Systemic Lupus Erythematosus(seropositive) with ILD. X ray chest showed prominent broncho-vascular markings in bilateral lung lobes. Pulmonary Function test showed Moderate Restriction with moderate obstruction with small airway disease. ANA & Anti-cardiolipin antibody tests were positive. Patient got symptomatically relief after starting tab Deazacort (oral steroids) and inhaled corticosteroids formoterol and beclomethasone (Inhaler) with hydroxychloroquine tablet. Thus, concluding that early treatment of SLE leads to better remission of ILD.

Compound Homozygous Factor V Leiden and Heterozygous Prothrombin Gene Mutation: The First Report in a Pregnant African with Extensive Thrombosis

Background: Factor V Leiden (FVL) mutation and Protein gene G20210A mutation (PGM) are the most common inherited thrombophilias in the world. (Limdi NA et.al, Blood Cells Mol Dis. 2006 Sep-Oct;37(2):100-6) Both are inherited in an autosomal recessive fashion with individuals who are homozygous having higher risk of thrombosis compared to those who are heterozygous.(Rodger MA et.al, PLoS Med. 2010 Jun 15;7(6):e1000292.) The global prevalence of FVL and PGM is variable with Caucasians carrying the highest prevalence and Africans living in Africa, Asians and Native Americans having the lowest rate of these mutations; it is zero in West and Southern African countries, 2.4%-3.9% in North African countries including Morocco, Tunisia, and Algeria. (Limdi NA et.al, Blood Cells Mol Dis. 2006 Sep-Oct;37(2):100-6, Dziadosz M et. al, Blood Coagul Fibrinolysis. 2016 Jul;27(5):481-9)Pregnancy increases the risk of developing venous thromboembolism (VTE) by 0.05-1.8 %, (Eldor A, Thromb Haemost. 2001 12.12.2017;86(07):104-11) which is 4 to 5 fold greater than in non-pregnant female.(Croles FN et.al, BMJ. 2017;359, Greer IA, N Engl J Med. 2015 Aug 6;373(6):540-7) Inheritance of FVL and PGM increases the risk for development of VTE in pregnancy, the risk is higher with homozygous than heterozygous mutations.(Rodger MA et.al, PLoS Med. 2010 Jun 15;7(6):e1000292.) Concurrent presentation of FVL and PGM in pregnancy presenting as thrombosis is not common.Aim: The aim of this case report is to present a patient of African descent with concurrent FVL and PGM mutation who had thrombosis during pregnancy.The Case: A 32-year-old Nigerian female who was 28 weeks pregnant presented to the gynecologist with a swollen left leg. Physical examination and the Wells score were very suggestive of a deep vein thrombosis (DVT). The Duplex Doppler performed confirmed a diagnosis of bilateral lower limb DVT. The patient was referred to a physician, who together with the haematologist performed a thrombophilia screen including FVL, PGM, Protein C, Protein S and Anticardiolipin antibody tests. The D-DIMERS were raised and the viral markers including HIV, HBV, and HCV were negative. The PT, APTT and full blood counts were normal. The thrombophilia tests revealed that the patient was homozygous for FVL and also heterozygous for the PGM mutations. The rest of the thrombophilia screen including Protein C, Protein S and Antithrombin tests were all negative. She has no family history of thrombosis; no past history of hormone based contraceptives. She was counselled on the need for using anticoagulation, low molecular weight heparin (LMWH) during the rest of her pregnancy period, and therapeutic anticoagulation with a LMWH at a dose of 1mg/kg twice a day until onset of labour was started. During labour LMWH was discontinued, delivery was per vaginal and was uncomplicated. Postpartum LMWH was continued at therapeutic doses for six weeks with no bleeding or thrombotic events. After six weeks, the patient was started on lifelong warfarin.Results (See Table)Discussion: To our knowledge this is a first case of a patient born and living in Africa presenting with thrombosis and found to have homozygous FVL and heterozygous PGM during pregnancy, the one report that is similar was in a second generation South African woman of German, Dutch and French ancestry. (Wilson J et. al, Medical Technology SA. [Case Report]. December 2011;25(2):4) Most reports have shown ethnic and regional affectation. (Limdi NA et.al, Blood Cells Mol Dis. 2006 Sep-Oct;37(2):100-6, Bavikatty NR, et.al, Am J Clin Pathol. 2000 Aug;114(2):272-5)There is no single agreed reason as to why the mutation is rare in Africa though founder effect is being studied to define how the mutation came about, it could have taken place before divergence of race. (Jadaon MM. [Thrombosis, Familiar Thrombophilia]. 2011 2011-11-28;3(1)We could not do family studies to help define the origin of this mutation whether it is denovo for Nigeria; this has to do with sentiments about genetic inheritance in Africa.Conclusion: Concurrent inheritance of both FVL and PGM is possible in Africa. This rare case has open opportunities to revisit the prevalence of thrombophilia in Nigeria and other African countries. DisclosuresMahlangu:Alnylam: Consultancy, Research Funding, Speakers Bureau; Biomarin: Research Funding, Speakers Bureau; Catalyst Biosciences: Consultancy, Research Funding; Chugai: Consultancy; Amgen: Consultancy; Bayer: Research Funding; Biogen: Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; NovoNordisk: Consultancy, Research Funding, Speakers Bureau; LFB: Consultancy; Roche: Consultancy, Research Funding, Speakers Bureau; Sanofi: Research Funding, Speakers Bureau; Shire: Consultancy, Research Funding, Speakers Bureau; Sobi: Research Funding, Speakers Bureau; Spark: Consultancy, Research Funding.

A brief history of antiphospholipid antibodies and antiphospholipid syndrome

AIMS: To review the historical reports on antiphospholipid antibodies (aPL) from the early years of the 20th century; to outline the cardinal features of the antiphospholipid syndrome (APS) from 1983 on, including clinical criteria, etiopathogenesis and current therapy.METHODS: Literature review using PubMed. Articles on the history of aPL and APS were selected.RESULTS: The original aPL were described in patients with syphilis yet in 1906 by Wassermann. A first definition of lupus anticoagulant was proposed in 1963,while the anticardiolipin antibody (aCL) test was depicted twenty years later. The APS, initially reported by Hughes in 1985as the “aCL syndrome”, is one of the most prevalent acquired thrombophilia. Venous and arterial thrombosis, associated or not to pregnancy morbidity, comprise the main features. It is a novel disorder firstly associated to systemic lupus erythematosus. A primary form of APS was put forward in 1989, and many APS variants are currently known. Lifelong, full-dose anticoagulation is the mainstream for treatment of thrombotic APS. In obstetric APS, the combination of acetil-salicilic acid and enoxoparin has been a mostly effective therapy.CONCLUSIONS: The sequential characterization of aPL since Wassermann in 1906, and later of the APS in the 1980-thies, is a rather interesting example of how a new entity is sketched step by step. APS is an intriguing novel cause of autoimmune thrombophilia, with a complex pathogenesis and a plethora of clinical and laboratory abnormalities. Treatment is based on life-long anticoagulation.

Recurrent pregnancy loss evaluation combined with 24-chromosome microarray of miscarriage tissue provides a probable or definite cause of pregnancy loss in over 90% of patients.

Will the addition of 24-chromosome microarray analysis on miscarriage tissue combined with the standard American Society for Reproductive Medicine (ASRM) evaluation for recurrent miscarriage explain most losses? Over 90% of patients with recurrent pregnancy loss (RPL) will have a probable or definitive cause identified when combining genetic testing on miscarriage tissue with the standard ASRM evaluation for recurrent miscarriage. RPL is estimated to occur in 2-4% of reproductive age couples. A probable cause can be identified in approximately 50% of patients after an ASRM recommended workup including an evaluation for parental chromosomal abnormalities, congenital and acquired uterine anomalies, endocrine imbalances and autoimmune factors including antiphospholipid syndrome. Single-center, prospective cohort study that included 100 patients seen in a private RPL clinic from 2014 to 2017. All 100 women had two or more pregnancy losses, a complete evaluation for RPL as defined by the ASRM, and miscarriage tissue evaluated by 24-chromosome microarray analysis after their second or subsequent miscarriage. Frequencies of abnormal results for evidence-based diagnostic tests considered definite or probable causes of RPL (karyotyping for parental chromosomal abnormalities, and 24-chromosome microarray evaluation for products of conception (POC); pelvic sonohysterography, hysterosalpingogram, or hysteroscopy for uterine anomalies; immunological tests for lupus anticoagulant and anticardiolipin antibodies; and blood tests for thyroid stimulating hormone (TSH), prolactin and hemoglobin A1c) were evaluated. We excluded cases where there was maternal cell contamination of the miscarriage tissue or if the ASRM evaluation was incomplete. A cost analysis for the evaluation of RPL was conducted to determine whether a proposed procedure of 24-chromome microarray evaluation followed by an ASRM RPL workup (for those RPL patients who had a normal 24-chromosome microarray evaluation) was more cost-efficient than conducting ASRM RPL workups on RPL patients followed by 24-chromosome microarray analysis (for those RPL patients who had a normal RPL workup). A definite or probable cause of pregnancy loss was identified in the vast majority (95/100; 95%) of RPL patients when a 24-chromosome pair microarray evaluation of POC testing is combined with the standard ASRM RPL workup evaluation at the time of the second or subsequent loss. The ASRM RPL workup identified an abnormality and a probable explanation for pregnancy loss in only 45/100 or 45% of all patients. A definite abnormality was identified in 67/100 patients or 67% when initial testing was performed using 24-chromosome microarray analyses on the miscarriage tissue. Only 5/100 (5%) patients, who had a euploid loss and a normal ASRM RPL workup, had a pregnancy loss without a probable or definitive cause identified. All other losses were explained by an abnormal 24-chromosome microarray analysis of the miscarriage tissue, an abnormal finding of the RPL workup, or a combination of both. Results from the cost analysis indicated that an initial approach of using a 24-chromosome microarray analysis on miscarriage tissue resulted in a 50% savings in cost to the health care system and to the patient. This is a single-center study on a small group of well-characterized women with RPL. There was an incomplete follow-up on subsequent pregnancy outcomes after evaluation, however this should not affect our principal results. The maternal age of patients varied from 26 to 45 years old. More aneuploid pregnancy losses would be expected in older women, particularly over the age of 35 years old. Evaluation of POC using 24-chromosome microarray analysis adds significantly to the ASRM recommended evaluation of RPL. Genetic evaluation on miscarriage tissue obtained at the time of the second and subsequent pregnancy losses should be offered to all couples with two or more consecutive pregnancy losses. The combination of a genetic evaluation on miscarriage tissue with an evidence-based evaluation for RPL will identify a probable or definitive cause in over 90% of miscarriages. No funding was received for this study and there are no conflicts of interest to declare. Not applicable.

Bilateral pulmonary embolism and ilio-femoral DVT associated with recent amputation of lower limb, long distance air travel and suspected thrombophilia.

We present a 36 years old Bangladeshi male, known smoker, while working in Bahrain, suffered from arterial thromboembolism on left lower extremity resulting in gangrene of left leg. He underwent above knee amputation of the affected limb. After 16 days stay in the hospital with an open amputated stump wound, he was sent back to Bangladesh by air. While in the airplane, he complained of chest discomfort about two hours before landing at Dhaka airport of Bangladesh. Following disembarkation he was admitted into local cardiac hospital where a diagnosis of left ventricular failure with unstable angina was made. Five days later he was transferred to ICU of Ibn Sina Hospital for better management. Patient had high serum D-dimer level and fibrin degradation products (FDP) level. negative antinuclear antibody (ANA) test, negative anti-cardiolipin antibody test, normal troponin I, Homocysteine, antithrombin III, protein S, & protein C levels. Initial X-ray chest showed left lower zone wedge shaped density. ECG showed sinus tachycardia. CT angiogram of chest showed bilateral pulmonary embolism (PE) and large left pleural effusion. Contrast CT abdomen showed bilateral iliac vein thrombus extending to lower inferior vena cava. Left pleural effusion was found to be grossly hemorrhagic. Patient was treated with low molecular weight heparin and warfarin. As thrombolysis was not feasible, he was advised to have thrombo-embolectomy. He refused surgical option and left hospital against medical advice. This case illustrates that multiple risk factors can be responsible for PE, and appropriate & timely interventions are always needed to prevent morbidity and or mortalityBangladesh Crit Care J March 2016; 4 (1): 46-50

Clinical Application of Revised Laboratory Classification Criteria for Antiphospholipid Antibody Syndrome: Is the Follow-Up Interval of 12 Weeks Instead of 6 Weeks Significantly Useful?

Background. According to revised classification criteria of true antiphospholipid antibody syndrome, at least one of three antiphospholipid antibodies should be present on two or more occasions at least 12 weeks apart. However, it can be inconvenient to perform follow-up tests with interval of 12 weeks. We investigated clinical application of follow-up tests with interval of 12 weeks. Method. Totals of 67, 199, and 332 patients tested positive initially for the lupus anticoagulants confirm, the anti-β 2 glycoprotein-I antibody, and the anti-cardiolipin antibody test, respectively, from Jan 2007 to Jul 2009. We investigated clinical symptoms of patients, follow-up interval, and results of each test. Results. Among patients with initial test positive, 1.5%–8.5% were subjected to follow-up tests at interval of more than 12 weeks. Among 25 patients with negative conversion in tests, patients with interval of more than 12 weeks showed clinical symptom positivity of 33.3%, which was higher than that of 12.5% with 6–12 weeks. Among 34 patients with persistent test positive, clinical symptoms positivity trended to be more evident in patients at interval of 6–12 weeks (47.4% versus 26.7%, P = 0.191) than more than 12 weeks. Conclusion. Less than 10% of patients with initial test positive had follow-up tests at interval of more than 12 weeks and the patients with persistent test positive at interval of more than 12 weeks showed trends toward having lower clinical symptoms than 6–12 weeks. More research is needed focused on the evidence that follow-up test at interval of more than 12 weeks should be performed instead of 6 weeks.

A Case of Acute-Onset, Painful Acral Granuloma Annulare.

Dear Editor: Acute-onset, painful acral granuloma annulare (GA), a rare variant first described by Brey et al.1 in 2006, is characterized by sudden onset of painful lesions on the hands and feet, and scattered lesions at other sites. Patients may have associated arthralgia, diarrhea, and fever. The erythrocyte sedimentation rate (ESR) may be elevated1. A 57-year-old woman presented with painful lesions on the hands and legs 4 months ago. The lesions abruptly began as small erythematous plaques and slightly enlarged after beginning. The patient experienced febrile sensations, myalgia, and back pain a month before developing the lesions. Intermittent treatment of oral prednisolone from a local clinic alleviated her back pain, but new cutaneous lesions persistently develop. Physical examination revealed tender, erythematous, annular plaques on the palms, lateral sides of the fingers, and the legs (Fig. 1). Initial laboratory examination by a rheumatologist revealed an elevated ESR of 52 with otherwise unremarkable findings for rheumatoid factor, anti-neutrophilic cytoplasmic antibody, anti-cardiolipin antibody and thyroid function test. Biopsy specimen from the left second finger revealed a palisade of histiocytes surrounding degenerated collagen and mucin in the dermis (Fig. 2A, B). Alcian blue (pH 2.5) staining highlighted mucin in the center of the granuloma (Fig. 2C). Based on the clinical and histological findings, acute-onset, painful acral GA was diagnosed. Fig. 1 Tender erythematous annular plaques on the lateral side of second and third finger. Fig. 2 (A) Palisade of histiocytes surrounding degenerated collagen and mucin in the dermis. A broad zone of mucinous degenerated collagen fibers with infiltrating lymphohistiocytic granuloma (H&E, ×100). (B) (H&E, ×400). (C) ... Although the occurrence of GA on the dorsum of the hands is frequent, the involvement of the palms appears to be very rare2,3,4,5. Generally, GA is characterized by asymptomatic or mildly pruritic lesions, but GA on the palms manifests variable clinical presentations, including painful or pruritic papules and plaques2,3,4. Acute-onset, painful acral GA also manifests unusual painful lesions similar to GA lesions on the palms. However, the former shows constitutional symptoms in addition to skin lesions, which may raise suspicion about an autoimmune disease. Therefore, unnecessary examinations and treatments may be performed and final diagnosis may be delayed. Brey et al.1 reported 2 of 4 patients presenting with arthralgia, which increased authors' concern that the disease might represent an early manifestation of an autoimmune disease. However, extensive serologic and radiologic examinations for autoimmune diseases were negative. Our patient was initially also evaluated by a rheumatologist, but all serologic findings for autoimmune diseases were unremarkable except for an elevated ESR. From this clinical viewpoint, we assume that acute-onset, painful acral GA could be classified as a distinct variant of GA distinguishing it from GA on the palms. Acute-onset painful acral GA should be differentiated from conditions including Sweet's syndrome, interstitial granulomatous dermatitis with arthritis, palisaded neutrophilic and granulomatous dermatitis, and rheumatoid nodule, which may present similar clinical presentations like painful papules or plaques and constitutional symptoms1. Herein, we report a very rare and interesting case of acute-onset, painful acral GA. Clinicians should be aware of the atypical clinical presentation of GA such as painful and/or tender acral eruptions with constitutional symptoms. To classify acute-onset, painful acral GA as a variant of GA, more reports of cases are needed.

Mixing studies in lupus anticoagulant testing are required at least in some type of samples

According to the ISTH guidelines for lupus anticoagulant (LAC) testing, the second step in the three-step procedure (screening, mixing, and confirmation) is the mixing test, which improves the discrimination between the presence of an inhibitor and coagulation factor deficiencies such as those occurring in patients receiving vitamin K antagonists (VKAs). From a retrospective analysis of dilute Russell viper venom (dRVVT) results, we evaluated the impact of the mixing test result on the interpretation of LAC positivity. We interpreted the dRVVT clotting times with and without taking into account the results of the mixing test in a patient population with prolonged screening test (n=267) with special attention to the patients receiving VKAs. The number of samples classified as 'LAC positive' differed substantially depending on the method of interpretation; 170 and 235 of 267 samples were classified as LAC positive with the three- and two-step procedure, respectively. Discrepancy between the two-step (without mixing step) and the three-step procedure was due to not including a mixing test and was more pronounced in the VKA patient population. Screen/confirm ratios carried out on a 1:1 mix of patient and normal pooled plasma (NPP) gave a lower incidence of 59 of 267. We advise continuing to perform mixing test to avoid false-positives. In patients with discrepant results between the two- and three-step dRVVT interpretation, mainly observed in VKA-treated patients, we advise retesting of the patients preferable beyond the period of anticoagulant therapy and additional testing for anti-beta2GPI and/or anti-cardiolipin antibodies.

Seroprevalence of syphilis in patients attending a tertiary care hospital in Southern India

ABSTRACT Objective To report our experience with two tests, anti-cardiolipin antibody test [venereal disease reasearch laboratory (VDRL) test] and specific treponemal test ( Treponema pallidum hemagglutination assay), used for screening antenatal, high risk cases and cases from sexually transmitted infection in a tertiary care hospital from January 2006 till December 2008. Methods A total of 14 639 samples received from various patient groups including antenatal cases, patients attending sexually transmitted disease (STD) clinic, blood donors and HIV positive patients were screened. Results Among the 14 639 samples collected, 103 were positive by VDRL test. Of these 89 cases were confirmed by quantitative VDRL test and Treponema pallidum hemagglutination assay. The cumulative seroprevalence over two years was found to be 0.61% in this study. The syphilis seroprevalence reduced from 0.88% in 2006 to 0.40% in 2008. Among the various sub-populations studied, patients attending the sexually transmitted infection clinic showed a seroprevalence of 2.62%. The seroprevalence decreased significantly from 4.00% in 2006 to 1.39% in 2008. Conclusions Our study showed a statistically significant declining rate of syphilis in STD clinics as well as the overall seroprevalence. These findings could be interpreted as indicators of improved programmes for prevention and management of STDs.

A New Eu3+-Labeled Method for Anticardiolipin Antibody IgM

The anticardiolipin antibodies (aCL) test has become a laboratory standard for the clinical diagnosis of antiphospholipid syndrome (APS). To better the quantitative detection of aCL-IgM so as to classify patients correctly and timely as APS positive, we established herein a new immunoassay based on a time-resolved fluoroimmunoassay (TRFIA). The complex of cardiolipin plus bovine anti-β2 glycoprotein-I was used as antigen fixed on microtiter plates to detect serum aCL-IgM, and Eu(3+) -labeled rabbit antihuman IgM was used as conjugate. The precision, sensitivity, specificity, coefficient of recovery, and stability of the assay were evaluated, and comparison with the traditional, classical enzyme-linked immunosorbent assay (ELISA) was also made. The detection limit of the aCL-IgM TRFIA kit we established was 0.1 MPL U/ml, with a wider detectable range than commercial ELISA ones when a strong-positive specimen was diluted from 2,630.9 to 0.08 MPL U/ml. There was a good liner range within 0.16 to 2,630.9 MPL U/ml, whereas it was within 5.14 to 328.86 MPL U/ml when using three commercial ELISA ones. The average intra- and interassay variability was 3.19 and 3.70%, respectively. The mean recovery rate was 101.95%. The clinical diagnostic specificity was 98%. Additionally, the established assay kit presented good characteristics of stability and correlated well with the ELISA, and the correlation coefficient was 0.955. The aCL-IgM TRFIA provides an approach to a more sensitive and reliable diagnosis of APS. Further validation of its use is required.

Antiphopholipid Antibodies and Functional Activated Protein C Resistance in Patients With Breast Cancer During Anthracycline-Based Chemotherapy Administered Through an Intravenous Port-Catheter Device

Venous thromboembolic events (VTEs) are life-threatening complications in patients with cancer and remain the second most common cause of death in hospitalized patients with cancer, after death from cancer itself. Patients with breast cancer, however, are considered to be at relatively low risk of developing VTE. In a cohort of 108 255 patients with breast cancer, the 1and 2-year cumulative incidence of VTE was estimated to be 0.9% and 1.2%, respectively. Both chemotherapy in general and the agent used in particular were found to increase the risk of developing VTE. A systematic screening for thrombosis during anthracycline-based regimens in adjuvant settings revealed a higher VTE (10%) rate when compared to the conventional cyclophosphamide methotrexate fluorouracil therapy (5.4%). The route of application of chemotherapeutic agents represents another high risk factor for the development of VTE. Catheter-related thrombosis (CRT) involves 70% to 80% of all upper extremity thrombotic events and represents about 10% of all cases of VTE in patients with cancer receiving chemotherapy. The role of acquired thrombophilia such as the induction of antiphospholipid antibodies (aPL-abs) and lupus anticoagulant (LAC) in the pathogenesis of VTE in patients with breast cancer has been reported but is still a matter of debate. In a prospective, case-controlled study, we assessed the rate of symptomatic VTE in primary nonmetastatic, patients with breast cancer who received adjuvant anthracycline-based chemotherapy regimens postoperatively via an intravenous port-catheter device (Hickman port, Celsite Access Port venous low-profile composite access ports with titanium chamber, Braun Melsungen AG, Germany). The standard combination administered every 3 weeks and for 6-treatment cycles was as follows: cyclophosphamide 500 mg/m, doxorubicin/epirubicin 15 mg/m, and flurouracil 1000 mg/m. Prior to primary surgery and each of the 6 cycles of chemotherapy, laboratory tests for anticardiolipin antibodies (aCL-ab; immunoglobulin [Ig] G-, IgM-enzyme-linked immunosorbent assay [ELISA] >15 U/mL), LAC (partial thromboplastin time ratio > 1.2), resistance to activated protein C (APC, Coatest; Chromogenix, Molndal, Sweden; APC ratio 500 mg/L) were performed. None of the patients received anticoagulants unless thrombosis was confirmed. Concomitantly, clinical signs for thrombosis were assessed, namely, increasing girth, marked edema, vague pain, and redness in the corresponding upper limb. The collected data were tabulated and analyzed using PSPP-project version 0.7.9, released February 2012. Over a period of 1.5 years, 42 patients with breast cancer (age: 60.6 + 7.5 years) were recruited; 49 age-matched healthy women served as controls (age: 59.0 + 11.2 years; P 1⁄4 .41). In the study period, 7.2% of the patients with breast cancer (n 1⁄4 3) developed symptomatic VTE, which were all localized in the subclavian vein at the side of the port-catheter. All of them occurred after the first chemotherapy cycle and were proven by contrast phlebography. Low-molecular-weight heparin at therapeutic dose was initiated and continued until removal of the device after the sixth cycle of chemotherapy. Symptomatic thrombosis of the pelvic veins, lower extremities, or in other regions was not detected in any of the patients during the

Tomography and blood vessels in Hughes syndrome

Antiphospholipid antibody syndrome (APS) or Hughes syndrome is a multisystem autoimmune disorder that is characterized by venous and arterial thrombosis and/or pregnancy complications (miscarriage and fetal death, preeclampsia, placental insufficiency, and fetal growth restriction), and positive serologic tests for anticardiolipin antibodies (aCL), lupus anticoagulant (LA), or antibodies against beta2-glycoprotein I (anti-ß₂GPI) either of IgG or IgM isotype. APS is characterized by accelerated atherosclerosis that, together with an increased tendency toward thrombosis, leads to the occurrence of various vascular events. Timely diagnosis of vascular changes, preferably in the subclinical phase, is required both because of their severity and the high mortality rate. Detection of arterial and venous changes is performed by various invasive and noninvasive diagnostic methods. Computed tomographic angiography (CTA) seems to be the most precise method with low exposure time, giving clinicians an opportunity for early diagnosis and timely treatment of APS patients.

Antiphospholipid syndrome

The antiphospholipid syndrome (APS) is defined by venous or arterial thrombosis and/or pregnancy morbidity in patients with persistent presence of antiphospholipid antibodies (aPLs). Catastrophic APS is the most severe form of APS, which is associated with rapid development of microvascular thrombosis resulting in multiorgan failure in patients with aPLs. Patients with APS and catastrophic APS are recognized to have a high risk of recurrent thrombosis that can occur despite anticoagulant therapy. Although antithrombotic therapy remains the mainstay of treatment, bleeding manifestations can complicate management and contribute to increased morbidity. Patients with persistently elevated aPL levels, particularly those who exhibit positive testing for lupus anticoagulant, anticardiolipin antibodies, and anti-β2GPI antibodies (triple positivity), appear to be at increased risk for thrombosis and pregnancy complications, whereas isolated positivity for aPLs appears to be associated with low risk. Recognizing that patients with APS have different thrombotic risk profiles may assist clinicians in assessing the risks and benefits of anticoagulation. The optimal type, intensity, and duration of anticoagulation in the treatment of APS remain controversial, particularly for arterial thrombosis and recurrent thrombosis. Future studies that delineate thrombotic risk in APS and evaluate current and novel anticoagulants as well as nonanticoagulant therapies are required.

Síndrome antifosfolípido

Antiphospholipid syndrome is described as a form of autoantibody induced thrombophilia The cardinal symptoms are thrombosis, both venous and arterial, and recurrent obstetric complications, mainly the recurrent abortions or premature deliveries. These autoantibodies are antiphospholipid antibodies that are detected by three diagnostic tests: test for anticardiolipin antibodies (ACL), test of anti β2-glycoprotein I (β2GPI) and lupus anticoagulant (LA). In addition to thrombosis and obstetric complications, these patients may have other clinical manifestations such as renal thrombotic microangiopathy, valvulopathy, cognitive impairment or livedo reticularis. Used for diagnosis classification criteria Sydney (2006), which require at least one clinical and analytical criteria. Your treatment is twofold, that of primary prophylaxis in patients who have not submitted prior thrombosis phenomena, and the treatment or secondary prophylaxis in patients with previous thrombosis

Definition and significance of high positivity aCL ELISA

We conducted a prospective study of anticardiolipin antibody (aCL) testing, performed in our university hospital. Among 6321 consecutive patients tested for both IgG and IgM aCL, 91 patients with medium or high positivity (>99th percentile) had a subsequent confirmatory test. Among them, 53 had a persistent positivity at 12 weeks. In this real world setting, patients with transient positivity had lower values than patients with persistent positivity.

Anti-cardiolipin and anti-β2-glycoprotein I antibodies: normal reference ranges in northwestern Italy

Laboratory tests for anticardiolipin antibodies (aCL) and anti-β2glycoprotein I antibodies (a-β2GPI) face problems common to many autoantibody assays: the lack of a reference standard and the need for each laboratory to assess assay-specific cut-off values. The aims of the study were to evaluate the reference range upper limits (99th percentile) used for aCL and a-β2GPI in the northwest of Italy and to investigate the analytical performances of these assays with the newly obtained reference ranges. We assayed aCL and a-β2GPI in 104 serum samples from patients without a history of thrombosis, pregnancy morbidity, tumours, infections and/or autoimmune diseases (30 males and 74 non-pregnant females). We tested all the commercial assays available in our regions (i.e. Orgentec Diagnostika, Aesku Diagnostics and Inova Diagnostics ELISA; CliA Zenit-RA and EliA Phadia Laboratory Systems). A further 30 serum samples, including 10 from healthy subjects, 10 from antiphospholipid syndrome (APS) patients and 10 from septic patients were assessed to investigate the analytical performance of the obtained cut-off limits. Reference range upper limits obtained with the commercial kits differ among assays and from the values reported by the manufacturer. Moreover, normal reference ranges calculated for IgG and IgM aCL differed from the arbitrary selected laboratory classification values suggested in the guidelines of 40 GPL and MPL.

Delayed ischemic stroke associated with bromocriptine-induced reversible cerebral vasoconstriction syndrome

Reversible cerebral vasoconstriction syndromes (RCVS) are a group of disorders characterized by prolonged but reversible vasoconstriction of the cerebral arteries, usually associated with acute-onset, severe, recurrent headaches, with or without additional neurologic signs and symptoms [1]. These syndromes are known to occur secondarily to the use of drugs such as cannabis, cocaine, ecstasy, amphetamine, selective serotonin-reuptake inhibitors (SSRIs) and nasal decongestants, or during pregnancy or the puerperal period itself [2]. RCVS which presents at puerperium is known as postpartum cerebral angiopathy (PCA) and is associated with the concomitant use of vasospastic drugs such as bromocriptine [3]. However, RCVS induced by bromocriptine beyond the puerperal period has not so far been reported. We describe here a case of bromocriptineinduced RCVS with ischemic stroke arising 1 year after the birth of second baby. A 32-year-old woman presented with an episode of transient left-sided weakness and dysarthria that lasted approximately 15 min, and a progressively worsening headache over several days. She had given birth to a second healthy baby 1 year before the present admission and it was uncomplicated as was her first pregnancy. Sixteen days before admission she had started on a course of 2.5 mg oral bromocriptine mesylate twice a day for 7 days to suppress lactation. After 7 days use of the bromocriptine, she was admitted to an outside hospital because of severe headache, transient left-sided weakness and dysarthria. At that time her vital signs were stable, including blood pressure of 130/85 mmHg and neurologic examination was unremarkable. Diffusion and fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) revealed focal high-signal areas in the right frontal lobe (Fig. 1a, b) and magnetic resonance angiography (MRA) showed up severe stenosis in both middle cerebral arteries (Fig. 2a). A transcranial Doppler (TCD) disclosed abnormally high flow velocities in both middle cerebral arteries, and a CSF examination was normal. Low-dose acetylsalicylic acid (100 mg once a day) was initiated on a suspicion of transient ischemic attack with right middle cerebral artery stenosis. The patient was referred to our hospital 9 days after the onset of her symptoms due to recurrent severe headache. Upon arrival, vital signs were stable including a blood pressure of 125/80 mmHg. The patient had severe headache without any abnormalities of neurologic examination. Laboratory examinations including renal function, urinalysis, international normalized ratio, partial thromboplastin time, thrombin time, antithrombin III, protein C, protein S, D-dimer, and fibrin monomers were unremarkable. In addition, tests for antinuclear and anticardiolipin antibodies, and complement indices were normal. On the second day in our hospital, her headache worsened with newly developed left-sided weakness and dysarthria. At that time, diffusion and FLAIR images demonstrated extended highsignal areas in the bilateral fronto-parietal area (Fig. 1c, d). Y. S. Kim W. Baek J. Kim H. Y. Kim Department of Neurology, College of Medicine, Hanyang University, Seoul, Republic of Korea

Anticardiolipin antibodies do not mediate macrovascular complications of type 2 diabetes

The relationship of anticardiolipin antibodies (ACA), markers of the antiphospholipid syndrome, with vascular complications of diabetes mellitus is polemic. This cross-sectional study assessed the frequency of IgG, IgM, and IgA ACA in type 2 diabetics with and without history of vascular events for the last 5 years, and in healthy controls. ACA were detected by enzyme immunoassay. A total of 73 type 2 diabetics (33 with history of vascular events) and 54 healthy controls were tested. Most diabetics were female (p = 0.003), and older than controls (p 0.09). ACA positivity rates were also similar when diabetics with and without history of vasculopathy were compared (p > 0.47). After adjusting for gender, age, hypertension, and smoking status, a weak but statistically insignificant association between IgM ACA and diabetics with vasculopathy was found (adjusted OR 2.7; 95% CI 0.2 - 34.2; p = 0.441). Overall, levels of IgG (r = 0.25; p = 0.005) and IgM (r = 0.23; p = 0.010) ACA were associated with increasing age. In short, the frequency of a positive ACA test in type 2 diabetics (with or without previous macrovasculopathy) was not significant as compared to healthy controls. There was no association of ACA with vascular events in patients with type 2 diabetes.

Strategies for Managing Heparin Therapy in Patients with Antiphospholipid Antibody Syndrome

Antiphospholipid antibody syndrome (APS) is a common acquired thrombophilia. The diagnosis of APS is based on both clinical and laboratory criteria. The clinical criteria include vascular thrombosis or pregnancy morbidity. The laboratory criteria include a positive test for lupus anticoagulant, anticardiolipin antibodies, or anti-β(2)-glycoprotein I (anti-β(2)GPI) antibodies on two or more occasions at least 12 weeks apart. Antiphospholipid antibodies with lupus anticoagulant activity may prolong phospholipid-dependent coagulation tests such as the activated partial thromboplastin time (aPTT) and the activated clotting time (ACT). This prolongation adds a level of complexity to monitoring heparin therapy in patients with APS who have thrombosis. A literature search of the PubMed database was conducted for relevant articles published from 1995-April 2011. The usual management approach in nonsurgical patients with APS is to switch to low-molecular-weight heparin. In patients in whom heparin remains the agent of choice, management options include monitoring heparin antifactor Xa levels, determining an individualized therapeutic aPTT range, targeting an aPTT goal of 2 times the baseline aPTT, or using an aPTT reagent insensitive to lupus anticoagulant. An algorithm for anticoagulation management in nonsurgical patients with APS who require heparin is provided. The strategies to monitor intraoperative heparin in patients undergoing cardiac surgery include measuring heparin concentrations by an automated protamine titration device, targeting twice the baseline ACT, using preoperative in vitro heparin-ACT titration curves, and measuring heparin antifactor Xa levels. The available published case reports on the use of these strategies are reviewed. Each institution should determine an approach to managing heparin in patients with APS that best meets its needs and resources.

Symmetrical peripheral gangrene: a rare presentation of antiphospholipid syndrome

A 25-year-old woman presented with complaints of dark discolouration of the hands, feet and the tip of the nose 1 week after normal delivery of a preterm baby (28 weeks) in April 2009. The onset was subacute and the discolouration progressed to the wrists and just above the ankles in a bilaterally symmetrical fashion. There was a history of fever from the onset of symptoms. There was no prior history of diabetes or cardiovascular illness. The baby had to be kept in the neonatal intensive care unit for 2 weeks hospitalization, as he was premature, and suffering from acute respiratory distress. On examination, the vital signs were: pulse 94 beats per minute and blood pressure of 118/72 mm/Hg, respirations 18 breaths/min. She had superficial pregangrene of the tip of the nose (Fig. 1), hands and feet extending to the distal leg. Superficial ulcerations were absent (Fig. 2). The skin of pregangrenous area was dry. The patient could move her hands and feet, but there was partial loss of sensation in the area of superficial pregangrene. She had moderate pallor, but no cyanosis. Examinations of the chest and abdomen were normal. The hemoglobin was 9.5 gm%, blood urea 22 mg% and serum creatinine 1 mg%. Her platelet count, prothrombin time and activated partial thromboplastin time were normal. A blood culture was negative. The anticardiolipin antibody (aCL) test was positive however a Lupus anticoagulant (LCA) test was not done. Protein C, protein S and antithrombin III levels were normal. Antinuclear antibody test and antibodies to double stranded DNA (ds-DNA) for systemic lupus erythematosus were negative. The chest X-ray study as well as a urinalysis was normal. The ultrasonography of the pelvis showed a mildly enlarged uterus without any fluid collection in the pelvis. The aCL test was still positive after 6 weeks.