Thrombin Generation Measured Ex Vivo Following Microvasculor Injury Is Increased in SLE Patients with Antiphospholipid-protein Antibodies

1997 ◽  
Vol 78 (04) ◽  
pp. 1173-1177 ◽  
Author(s):  
Jacek Musiał ◽  
Jakub Swadźba ◽  
Miłosz Jankowski ◽  
Marek Grzywacz ◽  
Stanisława Bazan-Socha ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Thrombin Generation ◽  
Ex Vivo ◽  
Skin Incision ◽  
Anticardiolipin Antibodies ◽  
Small Blood Vessel ◽  
Anionic Phospholipids ◽  
Increased Risk ◽  
High Concentrations

SummaryAntiphospholipid-protein antibodies (APA) include lupus-type anticoagulant (LA) and antibodies recognizing complexes of anionic phospholipids (e.g. cardiolipin) and proteins (e.g. prothrombin and (β2-glycoprotein I). The presence of APA is associated with an increased risk of both arterial and venous thrombosis. However, the pathogenic mechanism leading to thrombosis in patients with APA remains unclear. We studied 32 patients with systemic lupus erythematosus (SLE) who were divided into two groups depending on the presence (n = 19) or absence (n = 13) of APA. Healthy volunteers (n = 12) matched by age and sex served as controls. In all subjects LA and IgG class anticardiolipin antibodies (ACA) were determined. Thrombin generation was monitored ex vivo measuring fibrinopeptide A (FPA) and prothrombin fragment F1 + 2 (F1 + 2) in blood emerging from a skin microvasculature injury, collected at 30 second intervals. In subjects with antiphospholipid antibodies mean FPA and F1 + 2 concentrations were signiF1cantly higher at most blood sampling times than in controls. In some SLE patients with APA the process of thrombin generation was clearly disturbed and very high concentrations of F1brinopeptide A were detected already in the F1rst samples collected. Two minutes after skin incision SLE patients without APA produced slightly more FPA, but not F1 + 2, as compared to healthy subjects. Mathematical model applied to analyze the thrombin generation kinetics revealed that APA patients generated signiF1cantly greater amounts of thrombin than healthy controls (p = 0.02 for either marker). In contrast, in the same patients generation of thrombin in recalciF1ed plasma in vitro was delayed pointing to the role of endothelium in the phenomenon studied. In summary, these data show for the F1rst time that in SLE patients with antiphospholipid-protein antibodies thrombin generation after small blood vessel injury is markedly increased. Enhanced thrombin generation might explain thrombotic tendency observed in these patients.

scholarly journals Ex vivo Retrieval of Mature Oocytes for Fertility Preservation in a Patient with Bilateral Borderline Ovarian Tumor

2021 ◽  
Author(s):  
Bruno Ramalho de Carvalho ◽  
Geórgia Fontes Cintra ◽  
Taise Moura Franceschi ◽  
Íris de Oliveira Cabral ◽  
Leandro Santos de Araújo Resende ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
Ovarian Stimulation ◽  
Ovarian Tumor ◽  
Ex Vivo ◽  
Oocyte Retrieval ◽  
Ovarian Response ◽  
Malignant Cell ◽  
Borderline Ovarian Tumor ◽  
Increased Risk

AbstractWe report a case of ultrasound-guided ex vivo oocyte retrieval for fertility preservation in a woman with bilateral borderline ovarian tumor, for whom conventional transvaginal oocyte retrieval was deemed unsafe because of the increased risk of malignant cell spillage. Ovarian stimulation with gonadotropins was performed. Surgery was scheduled according to the ovarian response to exogenous gonadotropic stimulation; oophorectomized specimens were obtained by laparoscopy, and oocyte retrieval was performed ∼ 37 hours after the ovulatory trigger. The sum of 20 ovarian follicles were aspirated, and 16 oocytes were obtained. We performed vitrification of 12 metaphase II oocytes and 3 oocytes matured in vitro. Our result emphasizes the viability of ex vivo mature oocyte retrieval after controlled ovarian stimulation for those with high risk of malignant dissemination by conventional approach.

Biochemical and Pharmacological Properties of SANORG 34006, a Potent and Long-Acting Synthetic Pentasaccharide

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4197-4205 ◽  
Author(s):  
J.M. Herbert ◽  
J.P. Hérault ◽  
A. Bernat ◽  
R.G.M. van Amsterdam ◽  
J.C. Lormeau ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Factor Xa ◽  
Therapeutic Index ◽  
Inhibitory Effect ◽  
Experimental Models ◽  
Treatment And Prevention ◽  
Long Acting

Abstract SANORG 34006 is a new sulfated pentasaccharide obtained by chemical synthesis. It is an analog of the “synthetic pentasaccharide” (SR 90107/ ORG 31540) which represents the antithrombin (AT) binding site of heparin. SANORG 34006 showed a higher affinity to human AT than SR 90107/ORG 31540 (kd = 1.4 ± 0.3 v 48 ± 11 nmol/L), and it is a potent and selective catalyst of the inhibitory effect of AT on factor Xa (1,240 ± 15 anti–factor Xa U/mg v850 ± 27 anti-factor Xa U/mg for SR 90107/ORG 31540). In vitro, SANORG 34006 inhibited thrombin generation occurring via both the extrinsic and intrinsic pathway. After intravenous (IV) or subcutaneous (SC) administration to rabbits, SANORG 34006 displayed a long-lasting anti–factor Xa activity and inhibition of thrombin generation (TG) ex vivo. SANORG 34006 was slowly eliminated after IV or SC administration to rats, rabbits, and baboons, showed exceptionally long half-lives (between 9.2 hours in rats and 61.9 hours in baboons), and revealed an SC bioavailability near 100%. SANORG 34006 displayed antithrombotic activity by virtue of its potentiation of the anti–factor Xa activity of AT. It strongly inhibited thrombus formation in experimental models of thromboplastin/stasis-induced venous thrombosis in rats (IV) and rabbits (SC) (ED50values = 40.0 ± 3.4 and 105.0 ± 9.4 nmol/kg, respectively). The duration of its antithrombotic effects closely paralleled the ex vivo anti–factor Xa activity. SANORG 34006 enhanced rt-PA–induced thrombolysis and inhibited accretion of125I-fibrinogen onto a preformed thrombus in the rabbit jugular vein suggesting that concomitant use of SANORG 34006 during rt-PA therapy might be helpful in facilitating thrombolysis and preventing fibrin accretion onto the thrombus under lysis. Contrary to standard heparin, SANORG 34006 did not enhance bleeding in a rabbit ear incision model at a dose that equals 10 times the antithrombotic ED50 in this species and, therefore, exhibited a favorable therapeutic index. We suggest that SANORG 34006 is a promising compound in the treatment and prevention of various thrombotic diseases.

scholarly journals Sulfated agaran with 4,6-pyruvated form from red seaweed Acanthophora muscoides attenuates thrombin formation: in vitro and ex vivo studies

2021 ◽  
Vol 43 ◽  
pp. e55043
Author(s):  
José Ariévilo Gurgel Rodrigues ◽  
Johnny Peter Macedo Feitosa ◽  
Sandra de Aguiar Soares ◽  
Norma Maria Barros Benevides
Keyword(s):  
Thrombin Generation ◽  
Ex Vivo ◽  
Polyacrylamide Gel Electrophoresis ◽  
Deae Cellulose ◽  
Continuous Model ◽  
Sulfated Polysaccharides ◽  
Extrinsic Pathway ◽  
Plasma Fraction ◽  
Thrombin Formation

In vitro studies have described the sulfated agaran from Acanthophora muscoides as an intrinsic inhibitor of thrombin generation (TG), but not in ex vivo assay. This investigation partially characterized a pyruvate fraction with in vitro and ex vivo effects on an intrinsic/extrinsic pathway-induced thrombin generation (TG) continuous model using 36 or 60-fold diluted mice or defibrinated, normal human plasma. Fraction separated by DEAE-cellulose chromatography exhibited charge homogeneity and non-sulfated polysaccharides (<100 kDa) by agarose and polyacrylamide gel electrophoresis, respectively, using Stains-all alone. Fourier Transform Infrared and Nuclear Magnetic Resonance studies indicated a 4,6-pyruvated agaran-structure. The fraction and heparin had no effect on prothrombin time, but there was a preponderant intrinsic rather than extrinsic pathway inhibition in TG assay; themselves, acting on both free and fibrin bound thrombin activity without chromogenic substrate interaction. Both fractions, desulfated and native, anticipated and induced thrombin formation in activators-devoid or normal plasma. In addition, mice pretreated with fraction (20 mg kg-1, intraperitoneally) reduced intrinsically plasma TG ex vivo after 2h. Heparin suppressed TG in vitro, but induced it ex vivo. Therefore, agaran from A. muscoides blocks TG on in vitro and ex vivo studies, suggesting to evaluate the blood coagulability status.

scholarly journals Hemoperfusion leads to impairment in hemostasis and coagulation process in patients with acute pesticide intoxication

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Samel Park ◽  
Md-Imtiazul Islam ◽  
Ji-Hun Jeong ◽  
Nam-Jun Cho ◽  
Ho-yeon Song ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Thrombin Generation ◽  
Degradation Products ◽  
Treatment Modalities ◽  
Platelet Surface ◽  
Distribution Width ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Significant Change

Abstract Hemoperfusion (HP) is one of the important treatment modalities in extracorporeal therapy for patients with acute intoxication. Its use has declined during the past 20 years despite its efficacy, because of its side effects, especially an increased risk of bleeding. Mechanisms of hemostasis impairment have not been clearly elucidated and studies demonstrating the mechanism are lacking. It is not clear which step of the hemostatic process is impaired during HP, and whether it leads to an increased risk of bleeding. We performed both in vivo and in vitro studies to elucidate the mechanism of impairment in the hemostatic process. In patients with acute pesticide intoxication who underwent HP, the platelet count decreased rapidly during the first 30 minutes from 242.4 ± 57.7 × 103/μL to 184.8 ± 49.6 × 103/μL, then gradually decreased even lower to 145.4 ± 61.2 × 103/μL over time (p < 0.001). As markers of platelet activation, platelet distribution width increased continuously during HP from 41.98 ± 9.28% to 47.69 ± 11.18% (p < 0.05), however, mean platelet volume did not show significant change. In scanning electron microscopy, activated platelets adhered to modified charcoal were observed, and delayed closure time after HP in PFA-100 test suggested platelet dysfunction occurred during HP. To confirm these conflicting results, changes of glycoprotein expression on the platelet surface were evaluated when platelets were exposed to modified charcoal in vitro. Platelet expression of CD61, fibrinogen receptor, significantly decreased from 95.2 ± 0.9% to 73.9 ± 1.6%, while those expressing CD42b, von Willebrand factor receptor, did not show significant change. However, platelet expression of CD49b, collagen receptor, significantly increased from 24.6 ± 0.7% to 51.9 ± 2.3%. Thrombin-antithrombin complex, a marker for thrombin generation, appeared to decrease, however, it was not statistically significant. Fibrin degradation products and d-dimers, markers for fibrinolysis, increased significantly during HP. Taken together, our data suggests that hemoperfusion leads to impairment of platelet aggregation with incomplete platelet activation, which was associated with reduced thrombin generation, accompanied by increased fibrinolysis.

scholarly journals Activity Pattern Analysis Indicates Increased but Balanced Systemic Coagulation Activity in Response to Surgical Trauma

TH Open ◽  
2018 ◽  
Vol 02 (04) ◽  
pp. e350-e356
Author(s):  
Max Friedrich ◽  
Jan Schmolders ◽  
Yorck Rommelspacher ◽  
Andreas Strauss ◽  
Heiko Rühl ◽  
...  
Keyword(s):  
Activity Pattern ◽  
Plasma Levels ◽  
Thrombin Generation ◽  
Pattern Analysis ◽  
Activity Level ◽  
Surgical Trauma ◽  
Coagulation Activity ◽  
Increased Risk ◽  
D Dimer

AbstractIn the nonbleeding patient, constant low-level activation of coagulation enables a quick procoagulant response upon an injury. Conversely, local activation of coagulation might influence the systemic activity level of coagulation. To characterize this interaction in more detail, activity pattern analysis was performed in patients undergoing elective surgeries. Blood samples were taken before, during, and 24 hours after surgery from 35 patients undergoing elective minor (n = 18) and major (n = 17) orthopaedic surgeries. Plasma levels of thrombin and activated protein C (APC) were measured using oligonucleotide-based enzyme capture assays, while those of prothrombin fragment 1.2, thrombin–antithrombin-complexes, and D-dimer were measured using commercially available enzyme-linked immunosorbent assays. In vitro thrombin generation kinetics were recorded using calibrated automated thrombography. Results showed that median plasma levels of up to 20 pM thrombin and of up to 12 pM APC were reached during surgery. D-dimer levels started to increase at the end of surgery and remained increased 24 hours after surgery, while all other parameters returned to baseline. Peak levels showed no significant differences between minor and major surgeries and were not influenced by the activity state at baseline. In vitro thrombin generation kinetics remained unchanged during surgery. In summary, simultaneous monitoring of the procoagulant and anticoagulant pathways of coagulation demonstrates that surgical trauma is associated with increased systemic activities of both pathways. Activity pattern analysis might be helpful to identify patients at an increased risk for thrombosis due to an imbalance between surgery-related thrombin formation and the subsequent anticoagulant response.

Trace FVIII Augments Rfviia Induced Thrombin Generation and Improves Hemostasis in Hemophilia A Patients with Inhibitors: A clinical Cohort Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 40-40
Author(s):  
Tami Livnat ◽  
Uri Martinowitz ◽  
Shirley Azar-Avivi ◽  
Ariela Zivelin ◽  
Gili Kenet
Keyword(s):  
Thrombin Generation ◽  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Therapy Response ◽  
Response To Therapy ◽  
Individual Therapy ◽  
Severe Bleeding ◽  
Inhibitor Level

Abstract Abstract 40 Treatment of Hemophilia A patients with inhibitors is challenging, as correlation between inhibitor level and hemostatic response to therapy may be limited. Thrombin generation (TG) assays may be used to monitor hemostasis and/or predict patients' response to various bypass agents. Since combination of excess FVIII and bypassing agents may potentiate improved TG in inhibitor plasma tested in-vitro, we aimed to define the therapeutic feasibility of co-administration of rFVIIa and FVIII in hemophilia A patients with inhibitors. Patients and Methods: Following consent, blood was sampled from 15 hemophilia patients (age: 0.5–46y) with inhibitor (0.5–668 BU). Platelet poor plasma (PPP) was prepared, spiked and incubated with excess FVIII. Ex-vivo kinetics of FVIII neutralization over time was evaluated by sequential measurements of residual FVIII activity. We then used recalcification induced-TG (performed in PPP supplemented with 4μM phospholipids), to measure the ex-vivo response to increasing concentrations of FVIII (0–200%) and rFVIIa (0–6.8μg/ml), alone or in combination. Based upon these ex-vivo studies, an individually tailored therapeutic regimen of concomitant bolus doses of rFVIIa and FVIII was applied to nine hemophilia patients with inhibitors. Results: FVIII ex- vivo measurements post incubation detected either rapid or slow neutralization- not correlating with inhibitor level. Flat baseline TG curves were recorded for all inhibitor patients, with variable responses to FVIII and/or rFVIIa. Combined spiking with FVIII and rFVIIa dramatically increased rFVIIa induced ETP (762.7 ±305.7 as compared to 339.3±179.9 nM/min with rFVIIa only) and peak height (48.7±23.6 vs 23.7±16.6) in all patients' plasma samples. Based upon individual ex vivo assays, concomitant bolus doses of rFVIIa (120–200 mcg/kg) and FVIII (50–100 U/Kg), were applied to 9 patients, for a total of 333 episodes during study period (February 2010-Septemeber 2012). Patients during immune tolerance received rFVIIa prophylaxis with combined rFVIIa/FVIII dosing applied 3 times weekly. For most mild- moderate joint bleeds hemostasis was defined as satisfactory following a single combined dose. Severe bleeding episodes or target joint bleeds responded to 2–8 (median:3) combined doses, applied every 12 hours. During study period the median number of spontaneous joint bleeds decreased from 4 to 1 per month. Neither thrombosis nor any other complications evolved. Conclusions: Prediction of individual therapy response may be achieved by pre-analytical studies, assessing FVIII neutralization kinetics as well as ex-vivo TG responses to combined bypass/FVIII therapy. Such studies enabled treatment of inhibitor patients according to individually tailored regimens. We confirmed for the first time that the in- vitro advantage of combining FVIII and rFVIIa, indeed accounts for improved hemostasis and may safely be applied to inhibitor patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Ex Vivo Evaluation of the Effect of Plasma-Derived Factor VIII/Von Willebrand Factor in Patients with Severe Hemophilia_A on Prophylaxis with Emicizumab By Thrombin Generation Assay

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4233-4233
Author(s):  
Maria-Isabel Bravo ◽  
Aida Raventós ◽  
Alba Pérez ◽  
Elena G Arias-Salgado ◽  
María Teresa Alvarez Román ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Research Funding ◽  
Thrombin Generation ◽  
Ex Vivo ◽  
Concomitant Treatment ◽  
Healthy Controls ◽  
Normal Range ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Introduction: Hemophilia A (HA) patients under emicizumab prophylaxis treatment may require the concomitant use of procoagulant factors for breakthrough bleedings or immune tolerance induction. Thromboembolic events have been described with the concomitant use of emicizumab and activated prothrombin complex concentrate (aPCC), but not with recombinant activated factor VII (rFVIIa). Previous studies showed that the in vitro combination of emicizumab and plasma-derived Factor VIII/Von Willebrand Factor (pdFVIII/VWF) had a non-additive effect on thrombin generation (TG)(Bravo M-I, et al J Thromb Haemost. 2020;18:1934-39). The aim of this study was to evaluate the TG resulting from ex vivo combination of plasma samples from HA patients treated with emicizumab, with a pdFVIII/VWF concentrate (Fanhdi ®, Grifols). Methods: Twelve adult patients with severe HA without inhibitors on prophylaxis with emicizumab and nine healthy controls were included in the study. Blood samples were drawn in citrate plus corn trypsin inhibitor tubes. Then, platelet poor plasma (PPP) was collected for the TG assay, which measures the whole kinetics of TG. Thrombin peak (TP) and endogenous thrombin potential (ETP) were calculated using calibrated automated thrombogram (Thrombinoscope ™ software, Stago) after in vitro activation of coagulation by trigger solution, PPP Reagent LOW TM (4 μM phospholipids/1 pM tissue factor), fluorogenic substrate and CaCl 2 (FLUKAkit TM) reagents (Diagnostica Stago). Fluorescence was read in a Fluoroskan Ascent reader (Thermo) equipped with a 390/460 filter set. Samples were spiked with increasing concentrations of pdFVIII/VWF (10 to 400 IU/dL), rFVIIa (0.9 µg/mL) or aPCC (0.5 U/mL). Results: TG from healthy control samples was measured to establish TP and ETP normal ranges. TP and ETP results obtained from HA plasma with emicizumab were lower than in healthy controls. The addition of pdFVIII/VWF as of 25 IU/kg (prophylaxis dose in HA w/o inhibitors) to samples from HA patients concomitantly treated with emicizumab restored TP and ETP levels within healthy controls normal range (Table 1). Increasing ex vivo concentrations of pdFVIII/VWF maintained TP and ETP similar to healthy controls. The highest concentration of concomitant treatment with pdFVIII/VWF (200 IU/kg) and emicizumab did not result in excessive TP and, importantly, ETP levels were always within the normal range. The combination with the bypassing agent rFVIIa moderately increased TP and ETP values up to normal range. However, when HA plasma was spiked with aPCC in the presence of emicizumab, TP and ETP dramatically increased above normal range resulting in a synergistic procoagulant profile. Conclusions: The concomitant use of pdFVIII/VWF in patients with prophylaxis with emicizumab did not trigger a multiplying effect on TG. These results were aligned with previous in vitro data and suggested the low risk of overdose and thrombotic events of concomitant treatment emicizumab with the pdFVIII/VWF concentrate in HA patients. Figure 1 Figure 1. Disclosures Bravo: Grifols: Current Employment, Other: Grifols is a manufacturer of the pdFVIII/VWF concentrate, Fanhdi®. Raventós: Grifols: Current Employment, Other: Grifols is a manufacturer of the pdFVIII/VWF concentrate, Fanhdi®. Pérez: Grifols: Current Employment, Other: Grifols is a manufacturer of the pdFVIII/VWF concentrate, Fanhdi®. Alvarez Román: Grifols: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novo-Nordisk: Consultancy, Honoraria, Research Funding; Sobi: Consultancy, Honoraria, Research Funding; Octapharma: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; CSL-Behring: Consultancy, Honoraria, Research Funding; Biomarin: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Butta: CSL-Behring: Research Funding; Roche: Speakers Bureau; Takeda: Research Funding, Speakers Bureau; Novo-Nordisk: Speakers Bureau. Jiménez-Yuste: Bayer: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; BioMarin: Consultancy; Sobi: Consultancy, Honoraria, Research Funding; Octapharma: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; NovoNordisk: Consultancy, Honoraria, Research Funding; Grifols: Consultancy, Honoraria, Research Funding. Costa: Grifols: Current Employment, Other: Grifols is a manufacturer of the pdFVIII/VWF concentrate, Fanhdi®. Willis: Grifols: Current Employment, Other: Grifols is a manufacturer of the pdFVIII/VWF concentrate, Fanhdi®.

scholarly journals Increased thrombin generation and activity in patients with systemic lupus erythematosus and anticardiolipin antibodies: evidence for a prothrombotic state [see comments]

Blood ◽  
1993 ◽  
Vol 81 (11) ◽  
pp. 2958-2963
Author(s):  
JS Ginsberg ◽  
C Demers ◽  
P Brill-Edwards ◽  
M Johnston ◽  
R Bona ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Thrombin Generation ◽  
Anticardiolipin Antibodies ◽  
Laboratory Evaluation ◽  
Prothrombotic State ◽  
Systemic Lupus ◽  
Cross Sectional ◽  
Significant Difference ◽  
The Mean

The objective of this study is to determine whether patients with systemic lupus erythematosus (SLE) and anticardiolipin antibodies (ACA) have biochemical evidence of an ongoing prothrombotic state. Using a cross-sectional analysis of a cohort design in an outpatient SLE clinic setting, 43 consecutive patients with SLE participated. Patients underwent clinical and laboratory evaluations on two separate occasions at least 3 months apart. As part of the clinical evaluation, the following were ascertained: (1) the ongoing use of warfarin therapy; (2) the presence of prior venous and arterial thromboembolic disease by history, critical review of objective tests, and examination for reflux in the deep veins of the legs as an indicator of venous thrombosis; and (3) disease-related activity by performing a lupus activity criteria count (LACC). As part of the laboratory evaluation, blood was taken on both occasions and assayed for prothrombin fragments (F1 + 2) and fibrinopeptide A (FPA), as indices of thrombin generation and activity, respectively, and ACA. For the analyses, patients were classified as ACA+ if the assay was abnormal on both occasions and ACA- if the assay was negative on both occasions or negative on one occasion and positive on the other. ACA+ patients had: (1) a significantly higher mean level of F1 + 2 (1.07 nmol/L) than ACA- patients (0.79 nmol/L; P = .02) and patients receiving warfarin (0.47 nmol/L; P = .009) and (2) a significantly higher mean level of FPA (1.01 nmol/L) than ACA- patients (0.45 nmol/L; P = .02). When patients with prior thromboembolism were excluded from the analysis, significant differences in the mean levels of F1 + 2 and FPA between ACA+ and ACA- patients were still seen, whereas when patients with prior thromboembolism and/or active disease were excluded from the analysis, a significant difference in the mean level of FPA and a nonsignificant trend in the mean level of F1 + 2 were seen. The results of this study support the hypothesis that the presence of ACA in SLE patients is associated with an ongoing prothrombotic state.

scholarly journals An Unusual Presentation of Partial Hemolysis, Elevated Liver Enzyme Levels, and Low Platelet Levels Syndrome in a Case of in vitro Fertilization-DEM Pregnancy

2016 ◽  
Vol 7 (2) ◽  
pp. 73-75
Author(s):  
Nupur Garg ◽  
Revathi Govind ◽  
Smitha Avula
Keyword(s):  
Liver Enzyme ◽  
Lupus Erythematosus ◽  
Hellp Syndrome ◽  
Elevated Liver Enzyme ◽  
Unusual Presentation ◽  
Retroperitoneal Hemorrhage ◽  
Increased Risk ◽  
Autoimmune Conditions ◽  
Donor Embryo

ABSTRACT Pregnancy in women with systemic lupus erythematosus (SLE) or autoimmune conditions is complicated by complementmediated injury and is associated with increased risk of preeclampsia. Immunological intolerance between the mother and the fetus may play an important role in the pathogenesis of preeclampsia. The present case highlights the influence of susceptibility to preeclampsia/hemolysis, elevated liver enzyme levels, and low platelet levels (HELLP) syndrome due to preexisting autoimmune conditions. In vitro fertilization (IVF)- Donor embryo pregnancy (DEM) pregnancy is one such unique scenario where there exists partial immunological disparity between the native intrauterine environment and the implanted donor embryo that could predispose to autoimmune problems in pregnancy. This case illustrates a similar scenario in which a pregnant woman with IVF-DEM conception and antinuclear antibody (ANA) positive status manifested with a normotensive partial HELLP syndrome which was reiterated by the fact that there was clinical evidence of retroperitoneal hemorrhage intraoperatively during cesarean along with the neonate who was diagnosed to have L-carnitine deficiency, which is unique to fetuses with mothers of HELLP syndrome. How to cite this article Garg N, Govind R, Avula S, Rao KA. An Unusual Presentation of Partial Hemolysis, Elevated Liver Enzyme Levels, and Low Platelet Levels Syndrome in a Case of in vitro Fertilization-DEM Pregnancy. Int J Infertil Fetal Med 2016;7(2):73-75.

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