Low-dose Low Molecular Weight Heparin Research Articles

The incidence of venous thromboembolism after curative colon cancer surgery within an enhanced recovery after surgery programme

AimBased on three randomised controlled trials performed more than a decade ago, several national guidelines recommend prolonged venous thromboprophylaxis for 28 days following elective surgery for colon cancer. None of these studies were conducted within enhanced recovery after surgery setting. Newer studies indicate that prolonged prophylaxis might not be necessary with enhanced recovery after surgery. We aimed to provide further evidence to this unresolved discussion. MethodRetrospective study of patients undergoing elective surgery for colon cancer stage I-III with enhanced recovery after surgery in the Capital Region of Denmark from 2014 to 2017. Patients were excluded if discharged on postoperative day 28 or later, dying before discharge, undergoing concomitant rectum resection, or discharged with vitamin K antagonists, direct-oral anticoagulants, or low molecular weight heparin treatment. All patients received only low-dose low molecular weight heparin as prophylaxis during their admission.The primary endpoint was symptomatic lower limb deep venous thrombosis or pulmonary embolism diagnosed within 60 days postoperatively. ResultsOut of the included population of 1806 patients, only three experienced a symptomatic venous thromboembolic event; none was fatal. Two had pulmonary embolism associated with pneumonia, while one patient was diagnosed with lower limb deep venous thrombosis at postoperative day 15 after an uncomplicated course with first discharge at postoperative day 2. ConclusionThe risk of symptomatic venous thromboembolism after elective surgery for colon cancer with enhanced recovery after surgery seems negligible even without prolonged prophylaxis. The current guidelines need to be reconsidered.

Intermediate-dose Versus Low-dose Low–molecular-weight Heparin in Pregnant and Postpartum Women With a History of Venous Thromboembolism (Highleow study): An Open-label, Multicenter, Randomized, Controlled Trial

(Lancet. 2022;400:1777–1787) Venous thromboembolism (VTE) and subsequent major bleeding are leading causes of maternal morbidity and mortality worldwide, and the risk for recurrence increases for women with a history of VTE. Despite this, evidence-based research on thromboprophylaxis strategies is lacking and the optimal dose of low–molecular-weight heparin (LMWH) thromboprophylaxis during the peripartum and postpartum periods is uncertain. This study aimed to assess the safety and efficacy of low-dose compared to intermediate-dose LMWH for pregnant women with past occurrences of VTE.

Heparin for women with recurrent miscarriage and inherited thrombophilia (ALIFE2): an international open-label, randomised controlled trial

Anticoagulant therapy might reduce the number of miscarriages and adverse pregnancy outcomes in women with recurrent pregnancy loss and inherited thrombophilia. We aimed to assess use of low-molecular-weight heparin (LMWH) versus standard care in this population. The ALIFE2 trial was an international open-label, randomised controlled trial undertaken in hospitals in the UK (n=26), the Netherlands (n=10), the USA (n=2), Belgium (n=1), and Slovenia (n=1). Women aged 18-42 years who had two or more pregnancy losses and confirmed inherited thrombophilia, and who were trying to conceive or were already pregnant (≤7 weeks' gestation), were eligible for inclusion. Women were randomly assigned (1:1) to use low-dose LMWH or not (alongside standard care in both groups) once they had a positive urine pregnancy test. LMWH was started at or before 7 weeks' gestation and continued until the end of pregnancy. The primary outcome measure was livebirth rate, assessed in all women with available data. Safety outcomes included bleeding episodes, thrombocytopenia, and skin reactions, and were assessed in all randomly assigned women who reported a safety event. The trial was registered within the Dutch Trial Register (NTR3361) and EudraCT (UK: 2015-002357-35). Between Aug 1, 2012, and Jan 30, 2021, 10 625 women were assessed for eligibility, 428 were registered, and 326 conceived and were randomly assigned (164 to LMWH and 162 to standard care). 116 (72%) of 162 women with primary outcome data in the LMWH group and 112 (71%) of 158 in the standard care group had livebirths (adjusted odds ratio 1·08, 95% CI 0·65 to 1·78; absolute risk difference, 0·7%, 95% CI -9·2% to 10·6%). 39 (24%) of 164 women in the LMWH group and 37 (23%) of 162 women in the standard care group reported adverse events. LMWH did not result in higher livebirth rates in women who had two or more pregnancy losses and confirmed inherited thrombophilia. We do not advise use of LMWH in women with recurrent pregnancy loss and inherited thrombophilia, and we advise against screening for inherited thrombophilia in women with recurrent pregnancy loss. National Institute for Health and Care Research and the Netherlands Organization for Health Research and Development.

Association of lupus anticoagulants with risk factors for obstetric complications and adverse gestational outcome.

Lupus anticoagulant (LA) may be a cause of poor obstetric outcome. To search the association of LA with risk factors for obstetric complications and adverse gestational outcome. This retrospective cohort was consisted of 2 groups of pregnancies with poor obstetric history; 1) LA (+) gestations (Study Group, n= 20) and 2) LA (-) gestations (Control Group, 78). All patients were admitted to a special antenatal care program and were examined in terms of risk factors for thrombotic events, placenta-related obstetric complications, and poor gestational outcomes. Patients were administered low-dose low-molecular-weight heparin (LMWH), low-dose salicylic acid and low-dose corticosteroid (if necessary) within the framework of a prophylaxis protocol in addition to their already existing medications. We have shown that adverse gestational outcome was 1.7-fold more frequent in LA (+) pregnancies with poor obstetric history (p= 0.039, 70% vs. 41%). Higher rates of autoimmune diseases and hereditary thrombophilia were observed among LA (+) patients compared to LA (-) gestations (35% vs. 10.3%, p< 0.012 and 55% vs. 19.2%, p< 0.003, respectively). To identify the effectiveness of low-dose LMWH prophylaxis protocol, we compared gestational outcomes and demonstrated that the miscarriage rate was significantly decreased to half in current pregnancies compared to the previous gestations (73.6% vs. 35%, p= 0.003). Autoimmune diseases and hereditary thrombophilia are more frequent in LA (+) pregnancies, and these women are prone to obstetric problems. Low-dose LMWH and salicylic acid prophylaxis are critical in the management of LA (+) pregnant women.

Intermediate-Dose Versus Low-Dose Low-Molecular-Weight Heparin in Pregnant and Post-Partum Women with a History of Venous Thromboembolism (Highlow Study): An Open-Label, Multicentre, Randomised, Controlled Trial

ABSTRACT Venous thromboembolism (VTE) in pregnancy is a major cause of maternal morbidity and mortality, but its prevention, medical thromboprophylaxis, can cause bleeding complications. Without thromboprophylaxis, up to 10% of women with a history of VTE are at risk of pregnancy-related recurrence. For those women with a history of VTE who are not on long-term anticoagulation medication, guidelines recommend subcutaneous low-molecular-weight heparin (LMWH) in all women in the postpartum stage. For those with moderate or high risk of recurrent VTE, antepartum thromboprophylaxis is recommended. In both cases, the optimal dose of heparin is unknown, and professional societies do not provide clear specific guidance often recommending multiple different dosing approaches without clear evidence to guide recommendations. The aim of this study was to assess the efficacy and safety of low- versus intermediate-dose LMWH in pregnant women with a history of VTE. This was an open-label, randomized controlled study conducted at 70 hospitals in the Netherlands, France, Belgium, Norway, Demark, Canada, the United States, and Russia. Included were adult pregnant women with a history of objectively confirmed VTE, either unprovoked or provoked by hormonal or minor risk factors, and a gestational age ≤14 weeks. Excluded were women with previous VTE related to a major risk factor, indication for therapeutic-dose anticoagulants, or contraindication to LMWH. Eligible women were randomly assigned to receive either weight-adjusted intermediate-dose heparin or fixed, low-dose heparin. Participants self-administered their allocated dose of heparin once daily and participated in in-person or telephone contacts 2 weeks after randomization; at 20 and 30 weeks of gestation; and 1 week, 6 weeks, and 3 months postpartum. The primary efficacy outcome was symptomatic VTE, and the primary safety outcome was major bleeding. A total of 1110 women were included in the analysis—555 were randomized to the intermediate-dose group and 555 to the low-dose group. Approximately 81% of women had a history of VTE related to hormone use, pregnancy, or the postpartum period. From randomization to 6 weeks postpartum, VTE occurred in 2% of women in the intermediate-dose group and 3% in the low-dose group (relative risk, 0.69; 95% confidence interval, 0.32–1.47; P = 0.33). Antepartum VTE occurred in 1% of women in each treatment group; postpartum VTE occurred in 1% in the intermediate-dose group and 2% in the low-dose group. These findings remained consistent up to 3 months postpartum. From randomization to 6 weeks postpartum, major bleeding occurred in 4% of women in the intermediate-dose group and 4% in the low-dose group (relative risk, 1.16; 95% confidence interval, 0.65–2.09; p = 0.63). Antepartum major bleeding occurred in &lt;1% of women in each treatment group. Early postpartum bleeding occurred in 4% in the intermediate-dose group and 3% in the low-dose group. Last postpartum bleeding occurred in &lt;1% in the intermediate-dose group and none in the low-dose group. In comparing weight-adjusted, intermediate-dose LMWH with fixed, low-dose LMWH, the risk of VTE was similar in pregnant women with a history of VTE in the antepartum and postpartum periods. Moreover, no differences were observed in the occurrence of major bleeding between the 2 treatment groups. These findings provide evidence-based guidance that low-dose heparin is appropriate for preventing pregnancy-related recurrent VTE.

Onset of labor and use of analgesia in women using thromboprophylaxis with 2 doses of low-molecular-weight heparin: insights from the Highlow study

BackgroundPeripartum management of women using low-molecular-weight heparin (LMWH) varies widely. Minimum time intervals are required between LMWH injection and neuraxial procedure, and they differ by dose. ObjectivesThe objective of this study was to describe the onset of labor and use of analgesia in women using LMWH and to compare practices between intermediate-dose and low-dose LMWH. MethodsIn the Highlow study (NCT 01828697), 1110 women were randomized to intermediate-dose or low-dose LMWH and were instructed to discontinue LMWH when labor commenced unplanned or 24 hours prior to planned delivery. The required time interval since last injection to receive a neuraxial procedure was ≥24 hours for intermediate-dose LMWH or ≥12 hours for low-dose LMWH. ResultsIn total, 1018 women had an ongoing pregnancy for ≥24 weeks. Onset of labor was spontaneous in 198 of 509 (39%) women on intermediate-dose LMWH and in 246 of 509 (49%) on low-dose LMWH. With unplanned onset, a neuraxial procedure was performed in 37% on intermediate-dose and in 48% on low-dose LMWH (risk difference −11%, 95% CI −20% to −2%). Based on time interval, 61% on intermediate-dose and 82% on low-dose LMWH were eligible for a neuraxial procedure. With planned onset, 68% on intermediate-dose and 66% on low-dose LMWH received a neuraxial procedure, whereas 81% and 93%, respectively, were eligible for a neuraxial procedure (risk difference −13%, 95% CI −18% to −8%). ConclusionWith spontaneous onset of labor, neuraxial procedures were performed less often in women using intermediate-dose LMWH. Irrespective of onset, fewer women on intermediate-dose LMWH than those on low-dose LMWH were eligible for neuraxial procedures based on required time intervals since the last LMWH injection.

Anticoagulation and Antiplatelet Strategies in Non-Critically Ill Patients with Covid-19

Background Optimal thromboprophylaxis for hospitalized patients with Covid-19 is uncertain. Most published clinical trials comparing different anticoagulation protocols in hospitalized patients with Covid-19 have recruited patients in high-income countries (HIC) and results may not be generalizable to patients in low and middle-income countries (LMIC). Furthermore, the incidence of VTE varies by ethnic background with higher rates reported amongst Caucasian compared to diverse Asian populations. We report the results of an international (incorporating both HIC and LMIC regions) adaptive platform randomized trial in hospitalized non-critically ill patients with Covid-19 comparing the effectiveness of low-dose, intermediate-dose, therapeutic-dose anticoagulation, and low-dose plus aspirin on survival and need for organ support. Methods The Australasian COVID-19 Trial (ASCOT) is an investigator-initiated, open-label, pragmatic adaptive platform randomized clinical trial of therapeutics (anticoagulation, antiviral, and therapeutic antibody domains) for non-critically ill patients hospitalized with Covid-19. In our anticoagulation trial, we initially randomly assigned patients to low-dose low-molecular-weight heparin (LMWH) thromboprophylaxis, intermediate-dose or low-dose plus aspirin. In response to external evidence, the aspirin intervention was discontinued and a therapeutic-dose arm added. The primary endpoint was death or the requirement for new organ support by day-28, analyzed with a Bayesian logistic model. Enrolment was closed due to operational constraints. Results Between February 2021 and April 2022, we screened 2,203 patients in 32 hospitals (15 in Australia, 4 in New Zealand, 11 in India, and 2 in Nepal) and enrolled 1574 into the anticoagulation domain (619 assigned to low-dose, 620 to intermediate-dose, 285 to low dose plus aspirin, and 50 to therapeutic-dose). Eighteen participants withdrew consent and 30 were lost to follow-up leaving 1526 included in the primary analysis population (1273 from India, 138 from Australia and New Zealand, 115 from Nepal). The median age of participants was 49 years, 633 (41%) were female, 1291 (83%) were Indian, 480 (31%) were vaccinated against SARS-CoV-2, and 629 (40%) had one or more comorbidities. Adherence to the trial protocol was 98% in the low-dose, 98% in the intermediate-dose, 97% in the low-dose plus aspirin and 92% in the therapeutic-dose anticoagulation arms. All participants received enoxaparin except for one participant in the intermediate group who received tinzaparin. At 28 days after randomization, 35/596 (5.9%) participants assigned to low-dose, 25/601 (4.2%) intermediate-dose, 20/279 (7.2%) low-dose plus aspirin, and 7/50 (14%) therapeutic-dose anticoagulation had died or required organ support. Compared to low-dose thromboprophylaxis, the median adjusted odds ratio (aOR) for the primary outcome for intermediate-dose was 0.74 (95% credible interval [CrI] 0.43 to 1.27, posterior probability of effectiveness [aOR < 1] [Pr] 86%), for low-dose plus aspirin 0.88 (95% CrI 0.47 to 1.64, Pr 65%) and for therapeutic-dose 2.22 (95% CrI 0.77 to 6.20, Pr 7%). The results were consistent in a number of sensitivity analyses including when restricting the analysis populations to concurrent randomizations. The results were also broadly consistent across the predefined subgroups, with the posterior probability of effectiveness for intermediate-dose compared to low-dose ranging from 56% (corticosteroid exposure) to 94% (>7 days of symptom onset to hospitalization). Overall thrombotic and bleeding rates were 0.8% and 0.4%, respectively. Conclusions In hospitalized adults with Covid-19, compared to low-dose, there was an 86% posterior probability that intermediate-dose, and 7% posterior probability that therapeutic-dose, reduced the odds of death or requirement for organ support by day 28. No treatment strategy met pre-specified statistical stopping criteria prior to trial closure. Trial registration number: NCT04483960

Hydroxychloroquine therapy in women with autoimmune recurrent pregnancy loss, refractory to low dose aspirin and heparin: a randomized controlled trial

Hydroxychloroquine (HCQ) is a novel medication for women suffering from autoimmune-related recurrent pregnancy loss. Many autoimmune disorders have been related to poor obstetric outcomes; anti-phospholipid syndrome (APS) is the only autoimmune disorder in which pregnancy loss is a diagnostic requirement. The goal of this study is to see how beneficial it is to provide hydroxychloroquine (HCQ) in addition to low-molecular-weight heparin (LMWH) and low-dose aspirin (LDA) to females having a record of autoimmune-related recurrent pregnancy loss and refractoriness to low-dose aspirin and LMWH in previous pregnancies, both during preconception and gestation. Patients and methods. Between January 2019 and January 2021, 120 females with a history of autoimmune recurrent pregnancy loss at Ain Shams University Maternity Hospital were examined. Participants were divided into two classes using computer-based randomization procedures. During preconception and gestation, class A (60 cases) received hydroxychloroquine (HCQ), while class B (60 cases) received a placebo. Also, they received LDA and LMWH. The primary outcome measure in this study was the rate of live births. Secondary outcomes included gestational age at delivery, birth weight, mode of delivery, Apgar score at 5 minutes, neonatal morbidity, rate of neonatal intensive care unit (NICU) admission, and postneonatal mortality rate. Results. The live birth rate was 66% in class A and 42.3 % in class B. So, it was significantly higher in class A than in class B (p-value = 0.016). Additionally, gestational age at delivery was substantially greater in class A than in class B. In terms of live births, C-section was slightly less common in class A than in class B (p-value = 0.015). Notably, the mean birth weight was 2.509 kg in class A and 1.972 kg in class B, indicating that neonatal birth weight was substantially greater in class A than in class B (p-value = 0.003). Finally, NICU admission was significantly less common in class A than in class B (p-value = 0.044). Conclusion. HCQ is a potent, safe, and cost-effective medication used to prevent adverse obstetric outcomes in females with a history of autoimmune-related recurrent pregnancy loss with refractoriness to LDA and LMWH in previous pregnancies. This randomized controlled trial (RCT) provided additional evidence to support previous studies (non-criteria or seronegative APS), in which the diagnosis of APS is made solely based on the medical history, regardless of laboratory findings for antiphospholipid antibodies (aPL). Trial registration: Pan African Clinical Trial registration number is: PACTR2021104858485905. Key words: hydroxychloroquine; anti-phospholipid syndrome; heparin; low dose aspirin; autoimmune recurrent pregnancy loss

Management and Outcomes of Women with Antiphospholipid Antibodies or Antiphospholipid Syndrome during Pregnancy

BackgroundPregnant women with antiphospholipid antibodies (aPLs) or antiphospholipid syndrome have an increased risk for thrombosis. Although a combination of low-dose aspirin and unfractionated heparin (UFH) or low molecular weight heparin (LMWH) are usually prescribed in pregnancy, there is no consensus on optimal dosing of these agents. Despite the use of low-dose aspirin and LMWH, approximately 30% of women with a positive lupus anticoagulant (LA), underlying autoimmune disease, or a previous history of thrombosis have unfavorable outcomes.AimTo describe the management and outcomes of women with either aPLs or APS during pregnancy at a university medical center.MethodsWe conducted a retrospective cohort study of pregnant women with either aPLs or APS seen in our hematology clinic in consultation between January 2006 and August 2021. Data collected included demographics, reason for aPLs testing, personal or family history of thrombosis or autoimmune disease, and presence of other thrombophilias. Antiphospholipid antibodies included the LA, anti-cardiolipin (aCL) and anti-beta-2 glycoprotein 1 (ß2GP1) confirmed on two occasions at least 12 weeks apart. Data was collected on antithrombotic agents used during pregnancy, including aspirin, dose of LMWH, UFH and certolizumab. We recorded the following obstetric outcomes: live births, early delivery, fetal loss, early pregnancy loss <10 weeks gestational age (GA), pre-eclampsia, venous thromboembolic events (VTE), arterial thromboembolism (ATE), and post-partum hemorrhage (PPH). We compared management and outcomes in the presence or absence of LA. Statistical comparisons between groups were conducted with the Fisher's exact test.ResultsThere was a total of 202 pregnancies in 62 women with 11% of pregnancies achieved with assisted reproductive techniques. The most common reasons for aPLs testing were pregnancy loss (35%), VTE (23%), and ATE (8%). Antiphospholipid antibody profiles consisted of 56% triple positive, 8% positive LA plus either aCL or anti- ß2GP1, 13% positive LA alone and 22% with either double positive aCL and anti- ß2GP1 or single aCL or anti- ß2GP1. Twenty-tree percent of women had an additional inherited thrombophilia (Table 1). Of the 202 pregnancies, 52% resulted in live births, 20% in pregnancy loss <10 weeks, 12% in pregnancy loss >10 weeks, and 28% were either electively terminated, resulted on an ectopic pregnancy, or the outcome was unknown due to lost to follow up. Antithrombotic therapy was used in 47% of pregnancies: 26% used aspirin and LMWH, 10% used LMWH alone, and 7% used aspirin alone (Table 2). In 10% of pregnancies, patients were transitioned to UFH prior to delivery. Pre-eclampsia with or without HELLP syndrome occurred in 10% of pregnancies and maternal thromboembolic complications occurred in 6%. On analysis of outcomes stratified by LA status, there was a trend toward a higher rate of preterm births in the presence of a positive LA (Table 3). The rate of live births was increased with the use of antithrombotic therapy (Table 4).ConclusionPatients with antiphospholipid antibodies (aPLs) and antiphospholipid syndrome had elevated rates of complications and adverse outcomes during pregnancy. LA positive status was associated with a trend toward a higher rate of preterm births. Further studies are needed to clarify the factors associated with adverse outcomes and optimal anticoagulation management. [Display omitted] DisclosuresDesancho: Sanofi-Genzyme: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure:Certolizumab with the hypothesis of improving clinical outocomes

Standard Dose Prophylaxis Application and Venous Thromboembolism Findings in Patients Who Had Bariatric Surgery

Aim: Venous thromboembolism (VTE) events covering deep vein thrombosis (DVT) and pulmonary embolism (PE) constitute the most important morbidity-mortality cause in obesity surgery. The objective of this study was to assessment of thromboembolism results in patients who underwent bariatric surgery with standard dose prophylaxis. Patients and Methods: The patients who were operated for morbid obesity in our clinic between 2015 and 2019 were retrospectively examined. Cases that had laparoscopic sleeve gastrectomy and were applied standard dose Enoxaparin prophylaxis were included in the study. Demographic data, preoperative preparation and postoperative antiembolic treatment conditions of the patients were registered. Results: Eighty-seven patients who had laparoscopic sleeve gastrectomy were included in the study. 66 (%75,8) of the patients were female and 21 (%24,1) were male. The mean age was 38.7 (18-55). Mean hospitalization duration was 6.6 (3-69) days. Four patients (% 4,5) had postoperative complication. PE developed in two patients while leak-related mediastinitis and incisional hernia (%1,1) developed in one case each. Conclusion: Despite available prophylaxis methods, VTE constitutes an important morbidity and mortality cause in patients who had bariatric surgery. While high-dose low-molecular weight heparin (LMWH) use may cause bleeding, the possibility of VTE increases with using low-dose LMWH. This situation appears as a limitation of LMWHs. New studies are needed for increased dose at early period and standard dose application after discharge.

Efficacy and safety of low-dose aspirin combined with low-molecular-weight heparin in treatment of preeclampsia: a meta-analysis and systematic review.

The role of low-dose aspirin combined with low-molecular-weight heparin (LMWH) in the treatment of preeclampsia (PE) remains unclear. We aimed to assess the efficacy and safety of low-dose aspirin combined with LMWH in PE treatment, to provide evidence for clinical PE management. We searched PubMed and other databases for randomized controlled trials (RCTs) on the effects and safety of low-dose aspirin and LMWH in the treatment of PE up to January 31, 2021. Two researchers strictly followed the inclusion and exclusion criteria to independently conduct the literature screening, data extraction and quality evaluation. We used RevMan 5.3 statistical software for synthesized analysis. A total of 8 RCTs involving 861 patients were included. The synthesized outcome indicated that the differences in systolic blood pressure (MD = -10.61, 95% CI: -13.19 - -8.02), diastolic blood pressure (MD = -9.24, 95% CI: -14.49- -4.00), 24-hour urinary protein (MD = -2.24, 95% CI: -3.97- -0.50), prothrombin time (MD = 1.42, 95% CI: 0.53-2.32), activated partial thromboplastin time (MD = 2.91, 95% CI: 2.06-3.75), FIB (MD = -1.24, 95% CI: -1.32- -1.15), and adverse perinatal outcomes (MD = 0.41, 95% CI: 0.20-0.85) between the two groups were statistically significant (all p < 0.05), while the difference in the adverse reactions of pregnant women (MD = 0.44, 95% CI: 0.18-1.10) between the two groups was not statistically significant (p = 0.08). No publication bias was detected in all the synthesized outcomes (all p > 0.05). Low-dose aspirin combined with LMWH treatment of PE may be advantageous to improve blood pressure, 24-hour proteinuria and coagulation function, and it may reduce the adverse reactions in pregnant women without increasing adverse perinatal outcomes.

Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization.

Simple SummaryRadioembolization has failed to prove survival benefit in randomized trials, and, depending on various factors including tumor biology, response rates may vary considerably. Studies showed positive correlations between survival and absorbed tumor dose. Therefore, increasing currently prescribed tumor doses may be favorable for improving patient outcomes. The dominant limiting factor for increasing RE dose prescriptions is the relatively low tolerance of liver parenchyma to radiation with the possible consequence of a radiation-induced liver disease. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. Our study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients. The results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis to increase dose prescriptions in radioembolization.Background: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8–86.8) vs. 40.2 Gy (12.5–83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

ROTEM Analyses of Low Molecular heparin effects with Vitro Induced Thrombocytopenia

Background: Thrombocytopenia is correlated to hemorrhagic complications in patients with low molecular weight heparin (LMWH) thromboprophylaxis. Aims: The aims of our study were to investigate an experimentally induced in vitro thrombocytopenia and then adding 2 types of LMWHs in vitro. Our hypothesis was that a platelet depleted whole blood sample could reflect a stronger synergistic anticoagulative effect of in vitro added LMWH than in the non-manipulated blood. Method: Two venous citrated blood samples were consecutively drawn from 8 patient’s gynaecologic cancer and normal routine coagulation laboratory analyses immediately preopewratively. One of the two samples had its buffy coat pipetted away into a separate tube. Half of the buffy coat was returned to the same sample (treated sample). 3x500 μl of blood from the non-treated sample was added to 3 separate microtubes and corresponding for the treated sample. Thromboprophylactic doses corresponding to an in vivo peak effect 0.5 anti-Xa international units/ml of tinzaparin and enoxaparin were added both to untreated and treated samples – 2 microtubes were unheparinized (treated/untreatedsample). All samples were analysed with rotational thromboelastometry (ROTEM). Results: Wilcoxon matched-pairs signed rank tests of the in-group differences between non-non-treated and treated samples showed no significant differences (p≤0.05) for any of the parameters analysed with the ROTEM-INTEM reagent regardless of heparinization or not. Calculation of non-parametric spearman correlation for clotting time (CT) vs. platelet count (PLC) were not significant for any group. Tinzaparin was clearly observed to prolong CT in the buffy-coat lowered blood from two patients. Conclusions: Our results corroborate previous research that ROTEM cannot detect anticoagulative effects of low dose LMWH in patients with normal PLC. In two patients there was a clear prolongation of clot initiation after tinzaparin that warrants further studies on a more developed in vitro induced thrombocytopenia model.

Use of plasmapheresis in treatment of patients with unfavorable anamnestic pregnancy outcomes coupled to antiphospholipid antibodies

Aim: to evaluate efficacy of plasmapheresis combined with low molecular weight heparins (LMWH) and acetylsalicylic acid (ASA).Materials and Methods. 327 plasmapheresis sessions were performed for 75 patients: 17 (22.6 %) patients during preparation for pregnancy, 11 (19.0 %) pregnant women in the first trimester, 33 (56.9 %) pregnant women in the second trimester, and 34 (58.6 %) pregnant women in the third trimester. Study inclusion criteria were as follows: high titers of antiphospholipid antibodies (APA) as well as included non-inclusion criteria in pregnant women with miscarriages and unfavorable anamnestic pregnancy outcome. 36 (62.1 %) women had pregnancy loss in anamnesis. All patients received low-dose ASA and LMWH therapy; 15 (25.86 %) pregnant women also received courses of intravenous immunoglobulins in the first and second trimesters.Results. 47 pregnant women had delivery, whereas 10 of women had pregnancy in progress. Term delivery was in 40 (85.1 %) patients, so that 23 (48.9 %) pregnant women had delivery per vias naturales. The average weight of the fetus was 3364.00 ± 393.76 g, height - 52.13 ± 1.82 cm. In 100 % cases, Apgar score was 8 points. 24 (51.1%) pregnant women had delivery via cesarean section. The average blood loss comprised 528.64 ± 166.10 ml. The average fetal weight in group after surgical delivery was 2982.14 ± 582.88 g, average height - 49.14 ± 4.09 cm, the Apgar score - 7.69 ± 0.47 points. Preterm births were observed in 7 (14.9%) cases, all via cesarean section. In 1 case, early fetal death was at gestational age of 8/9 weeks; according to the karyotyping data, a fetal chromosomal abnormality was detected. No severe obstetric complications were observed.Conclusions. Combining plasmapheresis with low dose LMWH and ASA therapy demonstrated high efficacy in treating obstetric APS manifested as high percentage of favorable pregnancy outcomes and low number of obstetric complications.

Effective treatment option for lichen planus: Steroids or low molecular weight heparins?

Background: Data on safety and efficacy of low molecular weight heparin (LMWH) in lichen planus (LP) and comparison with oral corticosteroids (OCs) in Indian patients is limited. Aims: The aim of this article is to compare the clinical efficacy of LMWH and systemic corticosteroids in LP. Materials and Methods: This study was a single-center prospective comparative study. The patients received either LMWH subcutaneously (3 mg weekly for 6 weeks) or OC (20 mg/day for 6 weeks, tapered gradually). Results: Fifty patients were enrolled in the study, and 35 (70.0%) were females. Mean age of the study population was 35.46 years with age ranging between 21 and 40 years. Itching (92.0%) was a common symptom; generalized cutaneous lesions (90.0%) and involvement of mucous membrane were seen in 40%. Classical LP was common (56.0%). Early results were seen with OC (week 4) compared to LMWH (week 5); higher cure rate was seen with OC (89.47% vs. 76.0%) at week 6. There was no significant statistical difference (P > 0.05) in the therapeutic response between the study groups. No new lesions were noted in 23 and 13 patients treated with OC and LMWH, respectively. Relapse rate (33.33%) was higher in patients treated with LMWH (P < 0.05). Treatment with low-dose LMWH was associated with no side effects, whereas gastric irritation (42.1%) was the most common side effect followed by facial puffiness (31.57%) and acneiform eruptions (26.31%) with OC. The cost of treatment was more for LMWH compared with OC. Conclusion: Both treatment modalities were comparable in efficacy and tolerated well. LMWH had no adverse effect but had a high relapse rate. Therapy with OC is cost-effective.

Evaluation and Management of Women who Have Experienced Stillbirth in Their Previous Pregnancies

Objective: To evaluate the subsequent pregnancy outcomes of women who have experienced unexplained stillbirth in their previous gestations.Study Design: This retrospective cohort consisted of 14 pregnancies who had stillbirth (without known risk factors) in their previous pregnancies. These patients had been included in a special preconceptional care program to be evaluated in terms of etiological risk factors for stillbirth. At least one of the risk factors, such as methylenetetrahydrofolate reductase (MTHFR) polymorphisms, hereditary thrombophilias and autoimmune problems, were defined in this study population. After detection of pregnancy, the patients were administered low-dose low-molecular-weight heparin (LMWH) (enoxaparin, 1×2000 Anti-XA IU/0.2 mL/day), low-dose salicylic acid (100 mg/day) and low-dose corticosteroid (methylprednisolone, 1×4 mg/day orally) in necessary cases.Results: Out of 14 pregnancies, 4 (28.5%) ended up with miscarriages at 9, 11, 11 and 15 gestational weeks, respectively. The remaining 10 pregnancies ended up with alive deliveries. The mean gestational week at birth was 36.4±0.51, while the mean birthweight was 2882±381.01 g. Out of 10 pregnancies, only one was diagnosed as IUGR. Only two newborn necessitated hospitalization in the neonatal intensive care unit (NICU) due to respiratory problems. Both newborns were discharged from the NICU without any further complication at the post-partum 5th day. Conclusion: Patients with a prior stillbirth should be screened for MTHFR polymorphisms, autoimmune problems and hereditary thrombophilias, especially in case of absence of any etiological factor. Management of these patients with low-dose aspirin, low-dose low molecular weight heparin and corticosteroids seemed to be beneficial for increasing live birth rates and avoiding obstetric complications.

The prognostic impact of therapeutic anticoagulation after biological aortic valve replacement

Abstract Background Recent guidelines state that in patients with surgical biological aortic valve replacement (AVR), the use of anti-platelet therapy is as a valid alternative to postoperative anticoagulation (AC) in the absence of a further indication for AC. However, the prognostic impact of different anti-thrombotic strategies after biological AVR has not clearly been investigated so far and outcome data remain scare and inconclusive. Moreover, the AC strategy of patients presenting with post-operative atrial fibrillation (POAF), has not been investigated so far. Therefore, we aim to picture the therapeutic AC approach after biological AVR and whether the presence of POAF effects decision making with regard to anti-thrombotic management. Methods Within this prospective observational study 515 patients undergoing elective cardiac valve and or coronary artery bypass graft (CABG) surgery were enrolled. All patients were continuously screened for the development of POAF and followed until the primary endpoint (mortality) was reached. Logistic regression analysis was performed to elucidate the effect of AC on outcome. Results A total of 200 individuals underwent biological AVR (including 81 [40.3%] combined AVR+CABG surgeries, median age: 77 years [IQR: 71–80 years]; 133 [66.3%] male gender). 97 (48.3%) patients received therapeutic AC at the time of discharge, including 42 (43.4%) on vitamin K antagonists (VKA), 53 (54.6%) on low-dose low-molecular weight heparin (LMWH) and 2 (2.0%) non-vitamin K antagonist oral anticoagulants (NOACs). 103 (51.2%) patients received another anti-thrombotic approach including 23 (22.3%) on dual anti-platelet therapy (DAPT) and 72 (69.9%) with prophylactic LMWH. Interestingly, the fraction of patients that received AC were comparable between POAF (CHA2DS2-Vasc score 4, IQR: 3–5) and non-POAF individuals (51.9% vs. 44.6%; p=0.304). After a median follow-up time of 1069 days (IQR: 673–1475 days) 21 patients (10.4%) died, referring to 9 (8.3%) non-POAF and 12 (13.0%) POAF individuals. We found that a therapeutic AC after surgery showed a strong and inverse association with 3-year mortality with a crude odds ratio (OR) of 0.31 (95% CI 0.12–0.79; p=0.015). The prognostic potential remained stable after adjustment for potential confounders (p=0.029). Conclusion Therapeutic AC showed a strong and independent inverse association with 3-year mortality, mirroring a potential benefit on outcome compared to anti-platelet therapy or low-dose LMWH. However, the fraction of patients receiving therapeutic AC was considerably low – especially NOACs were not commonly used. Despite its association with fatal cardiac adverse events, the presence of POAF was not a relevant value for decision making for the initiation of AC. Further prognostic data on both thromboembolic and bleeding events are needed to elucidate a net-benefit of therapeutic AC in patients with surgical biological AVR who have an indication for AC or present with POAF. Kaplan-Meier Survival plot Funding Acknowledgement Type of funding source: None

Effect of low or high doses of low‐molecular‐weight heparin on thrombin generation and other haemostasis parameters in critically ill patients with COVID‐19

The clinical picture of the coronavirus 2 (SARS-CoV-2)/COVID-19-related acute respiratory syndrome is often associated with a coagulopathy. An elevated D-dimer has been linked with an unfavorable prognosis in COVID-19 patients.

Low-dose low-molecular-weight heparin prophylaxis against obstetrical complications in pregnancies with metabolic and immunological disorder-associated placental inflammation

Objective We investigated the importance of prophylactic administration of low-dose low-molecular-weight heparin (LMWH) in women with risk factors associated with placental inflammation. Materials and methods This retrospective cohort study included 300 pregnant women with a singleton pregnancy (30 primigravidas and 270 multigravidas) who received prophylactic low-dose LMWH to prevent placental inflammation. Based on maternal risk factors, patients were categorized into 3 groups as follows: Group 1: Patients with metabolic risk factors for placental inflammation (n = 205), Group 2: Patients with immunological risk factors for placental inflammation (n = 42), Group 3: Patients with metabolic and immunological risk factors for placental inflammation (n = 53). Obstetric histories, demographic features, clinical characteristics, and present pregnancy outcomes were compared between groups. Live birth rates, composite adverse obstetric outcomes, and the Beksac obstetric index were compared between present and previous pregnancies in multigravidas. Results Pregnancy outcomes were significantly better in the present pregnancy than in previous pregnancies. A significant increase was observed in live birth rates (33.4% vs. 69.9%, 27.5% vs. 60.5%, and 30.1% vs. 69.4% in groups 1, 2, and 3, respectively) and in the Beksac obstetric index (0.32 vs. 0.43, 0.33 vs. 0.47, and 0.38 vs. 0.57 in groups 1, 2, and 3 respectively) (p < .001 for all). A significant decrease in composite adverse pregnancy outcome rates was observed during the present pregnancy (23.5% vs. 100%, 28.9% vs. 100%, and 24.5% vs. 100% in groups 1, 2, and 3, respectively) (p < .001 for all). Live birth and composite adverse obstetric outcome rates were 70% and 33.3%, respectively in primigravidas. Conclusion Low-dose low-molecular-weight heparin prophylaxis is useful to prevent metabolic and immunological disorders causing placental inflammation, which is the most likely pathophysiological mechanism contributing to various obstetrical complications.

PD09-03 EFFICACY AND SAFETY OF PHARMACOLOGICAL THROMBOPROPHYLAXIS IN PATIENTS UNDERGOING NONCARDIAC SURGERY: A NETWORK META-ANALYSIS

INTRODUCTION AND OBJECTIVE:Urological surgery is a known risk factor for venous thromboembolism (VTE). Low-dose low molecular weight heparin (LMWH) and direct oral anticoagulants (DOAC) may be reas...