Risk of recurrent venous thromboembolism and bleeding in patients with acute isolated subsegmental pulmonary embolism.

INTRODUCTION: Approximately 10 % of all diagnosed pulmonary embolism are isolated to the subsegmental vessels. The risk of recurrent venous thromboembolism (VTE) in patients with an acute subsegmental pulmonary embolism (SSPE) managed with or without anticoagulant therapy remains poorly understood. METHODS: This is an observational cohort study including consecutive adult patients diagnosed with acute isolated SSPE between June 01, 2019, and August 31, 2022. We excluded patients with a concomitant diagnosis of deep vein thrombosis and those who had an indication for long-term anticoagulation. The primary outcome was objectively confirmed recurrent VTE. RESULTS: Overall, 118 patients with acute SSPE were included in the analysis. The mean (± standard deviation [SD]) age of the participants was 59 ± 17 years and 44 % of them had active cancer. Mean (±SD) duration of follow-up was 438 ± 426 days. Seventy-seven patients (65 %) were initially treated with anticoagulation, whereas 41 patients (35 %) were not. Of the 77 patients receiving anticoagulant therapy, 23 (30 %) received extended-duration anticoagulation (beyond 3 months) for secondary prevention. Overall, recurrent VTE events occurred in 6/118 (5 %, 95 % CI 2.4 to 10.7) patients. Four events (4/77 = 5.2 %, 95 % CI 2.0 to 12.6) occurred in initially treated patients. Two recurrent VTE occurred in patients initially left untreated (2/41 = 4.9 %, 95 % CI 1.4 to 16.1). Half of the recurrent VTE occurred in patients with active cancer. CONCLUSIONS: Most patients diagnosed with an acute SSPE received anticoagulation. The incidence of recurrent VTE detected over time was relatively high, especially in patients with cancer.

A retrospective multicenter cohort study of the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19.

BACKGROUND: Patients with critical COVID-19 have a high risk of thromboembolism, but intensified thromboprophylaxis has not been proven beneficial. The activity of low-molecular-weight heparins can be monitored by measuring anti-Factor Xa. We aimed to study the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19. METHOD: This retrospective cohort study included adult patients with critical COVID-19 admitted to an intensive care unit at three Swedish hospitals between March 2020 and May 2021 with at least one valid peak and/or trough anti-Factor Xa value. Within the peak and trough categories, patients' minimum, median, and maximum values were determined. Logistic regressions with splines were used to assess associations. RESULTS: In total, 408 patients had at least one valid peak and/or trough anti-Factor Xa measurement, resulting in 153 patients with peak values and 300 patients with trough values. Lower peak values were associated with thromboembolism for patients' minimum (p = 0.01), median (p = 0.005) and maximum (p = 0.001) values. No association was seen between peak values and death or bleeding. Higher trough values were associated with death for median (p = 0.03) and maximum (p = 0.002) values and with both bleeding (p = 0.01) and major bleeding (p = 0.02) for maximum values, but there were no associations with thromboembolism. CONCLUSIONS: Measuring anti-Factor Xa activity may be relevant for administrating low-molecular-weight heparin to patients with critical COVID-19. Lower peak values were associated with an increased risk of thromboembolism, and higher trough values were associated with an increased risk of death and bleeding. Prospective studies are needed to confirm the results. TRIAL REGISTRATION: The study was retrospectively registered at Clinicaltrials.gov, NCT05256524, February 24, 2022.

Anti-Xa level monitoring of low-molecular-weight heparin during intermittent venovenous hemofiltration.

Low-molecular-weight heparin (LMWH) is an anticoagulant used to prevent clotting during blood purification treatments. This study aimed to evaluate the clinical use of the anti-factor Xa level (anti-Xa) for monitoring LMWH anticoagulant levels during intermittent venovenous hemofiltration (IVVHF). This prospective observational study enrolled patients who required IVVHF for renal failure in Beijing Hospital between May 2019 and February 2021. The LMWH anticoagulation was assessed by the coagulation grade of the filter and line. One hundred and ten participants were included. There were 90 patients with a filter and line coagulation grade of ≤ 1 and 20 patients with grade > 1. The anti-Xa level of 0.2 IU/mL was a critical value. The multivariable logistic regression analysis showed that anti-Xa level > 0.2 IU/mL (odd ratio [OR] = 2.263; 95% CI: 1.290-4.871, P = 0.034) and cardiovascular disease (OR = 10.028; 95% CI: 1.204-83.488; P = 0.033) were independently associated with the coagulation grade of the filter and line. Anti-Xa level could monitor LMWH anticoagulation during IVVHF.

Hereditary thrombophilia and low -molecular -weight heparin in women: useful determinants, including thyroid dysfunction, incorporating the management of treatment and outcomes of the entity

SUMMARY OBJECTIVE: Our study purposed to examine the complex relationship between low-molecular-weight heparin therapy, multiple pregnancy determinants, and adverse pregnancy outcomes during the third trimester in women with inherited thrombophilia. METHODS: Patients were selected from a prospective cohort of 358 pregnant patients recruited between 2016 and 2018 at the Clinic for Obstetrics and Gynecology, University Clinical Centre of Serbia, Belgrade. RESULTS: Gestational age at delivery (β=-0.081, p=0.014), resistance index of the umbilical artery (β=0.601, p=0.039), and D-dimer (β=0.245, p<0.001) between 36th and 38th weeks of gestation presented the direct predictors for adverse pregnancy outcomes. The model fit was examined using the root mean square error of approximation 0.00 (95%CI 0.00-0.18), the goodness-of-fit index was 0.998, and the adjusted goodness-of-fit index was 0.966. CONCLUSION: There is a need for the introduction of more precise protocols for the assessment of hereditary thrombophilias and the need for the introduction of low-molecular-weight heparin.

Priapism Secondary to Low-Molecular-Weight Heparins: A Case Report.

Priapism may be a side effect of low-molecular-weight heparins, and its mechanism remains unknown. The authors present a clinical case of a 51-year-old male patient with oligodendroglioma. The patient presented ischemic priapism on the third month after starting tinzaparin, without other recent changes to his medication and he denied the use of other new medicines. The patient went through surgery and the erection was resolved but presented fibrosis of the cavernous body which left him with erectile dysfunction. Since this event, the patient is no longer receiving Heparin and has had no other episodes of priapism. The prompt recognition of this side effect may decrease its morbidity and consequent impact on the quality of life. More studies are needed to better understand its pathophysiology.

O priapismo pode ser um efeito adverso das heparinas de baixo peso molecular, cuja fisiopatologia não é totalmente compreendida. Os autores apresentam o caso de um doente, do sexo masculino, 51 anos, com diagnóstico de oligodendroglioma. O doente apresentou um episódio de priapismo, no terceiro mês sob tinzaparina, sem nenhuma outra alteração recente da sua medicação habitual e com consumo de outros medicamentos negado. Foi submetido a cirurgia, com resolução do priapismo, mas apresentou fibrose sequelar dos corpos cavernosos, com consequente disfunção eréctil. Desde então o doente não retomou heparina e não apresentou novos episódios de priapismo. Um célere reconhecimento do quadro pode contribuir para menores sequelas, com consequente diminuição da morbilidade e impacto na qualidade de vida. Mais investigação é necessária para aumentar o conhecimento sobre a fisiopatologia desta situação.

Prevention and risk factors analysis of lower extremity deep vein thrombosis after high tibial osteotomy / 中华骨科杂志

Objective:To investigate the prevention and risk factors of deep vein thrombosis (DVT) in the lower extremity after medial open wedge high tibial osteotomy (HTO).Methods:A total of 128 patients who underwent medial open wedge HTO in the Third Hospital of Hebei Medical University from January 2020 to October 2022 were retrospectively analyzed, including 45 males and 83 females, aged 59.3±6.8 years (range, 44-87 years). Postoperative anticoagulation with enoxaparin sodium was applied at a randomized dose of 4,000 AXaIU/d or 6,000 AXaIU/d. Gender, age, history of chronic diseases (hypertension, diabetes), smoking history, body mass index, and body fat percentage were collected. On admission, the risk of DVT was assessed using the Caprini scale and calf circumference was measured. Hemoglobin, D-dimer, antithrombin III, activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), fibrinogen degradation products (FDP), glutathione, glutathione, urea, creatinine, uric acid were recorded. Patients were divided into DVT group and non-DVT group according to whether DVT occurred after operation. Binary logistic regression was used to analyze the independent risk factors of DVT after HTO. The receiver operating characteristic (ROC) curve was plotted, and the area under curve (AUC) was calculated to analyze the predictive value of the postoperative Caprini scale in the occurrence of DVT after HTO.Results:A total of 128 patients were enrolled, 83 patients were treated with enoxaparin sodium 4 000 AXaIU/d and 45 patients were treated with enoxaparin sodium 6 000 AXaIU/d. According to the results of color Doppler examination of bilateral lower extremity veins on the third day after operation, DVT occurred in 39% (50/128) of patients, including 39 cases of calf intermuscular thrombosis, 6 cases of peroneal vein thrombosis, 4 cases of posterior tibial vein thrombosis, and 1 case of popliteal vein thrombosis. DVT occurred in 36% (30/83) of patients receiving 4 000 AXaIU/d enoxaparin sodium and 44% (20/45) of patients receiving 6 000 AXaIU/d enoxaparin sodium, with no statistically significant difference (χ 2=0.84, P=0.358). Univariate analysis showed that smoking history, postoperative Caprini scale≥8, and female may be associated with the development of DVT after HTO ( P<0.05). They were included in the binary logistic regression, and the results showed that postoperative Caprini scale≥8 was an independent risk factor for DVT after HTO. The ROC curve of postoperative Caprini scale for predicting DVT after HTO was drawn, and the AUC was 0.847 (95% CI: 0.73, 0.96), the optimal cut-off value was 8, and the sensitivity and specificity were 84.2% and 77.6%, respectively. Conclusion:Caprini scale≥8 is an independent risk factor for DVT after medial open wedge HTO. Caprini scale has a good value in predicting the occurrence of DVT after HTO. The recommended dose of enoxaparin sodium is 4 000 AXaIU/d for the prevention of postoperative DVT, and increasing the dose is not associated with a decreased risk of DVT.

The efficacy of Yunkang oral liquid combined with dexamethasone and low-molecular-weight heparin in the treatment of recurrent miscarriage complicated with prethrombotic state in pregnant women / 中国医师杂志

Objective:To investigate the clinical efficacy of Yunkang oral liquid combined with dexamethasone and low-molecular-weight heparin in the treatment of recurrent spontaneous abortion (RSA) complicated with pre thrombotic state (PTS), and its effects on thromboelastogram and serum progesterone, β-human chorionic gonadotropin (β- hCG), and helper T cell (Th) 1/Th2 cytokine levels in patients with recurrent spontaneous abortion (RSA).Methods:A prospective selection of 94 RSA patients with PTS admitted to the Baoding Second Central Hospital from January 2015 to December 2020 was conducted. They were randomly divided into two groups using a random number table method, with 47 patients in each group. The control group was treated with dexamethasone combined with low molecular weight heparin, while the observation group was treated with Yunkang oral liquid in addition to the control group. Continuously treat until 12 weeks of pregnancy to evaluate the efficacy of both groups and observe the adverse reactions in both groups. Two sets of thromboelastogram parameters were compared before and after treatment, including clot formation time (K value), clot reaction time (R value), and clot formation rate (α angle), maximum clot strength (MA value), and coagulation comprehensive index (CI), as well as serum progesterone β- hCG, Th1/Th2 cytokine levels. The pregnancy outcomes of the two groups were followed up.Results:The total effective rate of the observation group [95.7%(45/47)] was significantly higher than that of the control group [83.0%(39/47), P<0.05]. After treatment, the K and R values of both groups were significantly prolonged compared to before treatment (all P<0.05), the angle α, MA value, and CI value were significantly reduced compared to those before treatment (all P<0.05); After treatment, the K and R values in the observation group were significantly longer than those in the control group (al P<0.05), The angleα, MA value, and CI value were significantly lower than those of the control group (all P<0.05). After treatment, the levels of β- hCG serum progesterone of the two groups were significantly higher than those before treatment (all P<0.05), and The β-hCG levels of the serum progesterone were all higher than those in the control group (all P<0.05). After treatment, The levels serum Th1 cytokines [interferon-γ (INF- γ), tumor necrosis factor- α (TNF- α)] of both groups were significantly decreased compared to those before treatment (all P<0.05), and the levels of serum Th2 cytokines [interleukin-4, IL-10] were significantly increased compared to those before treatment (all P<0.05); After treatment, the observation group's serum IFN- γ, TNF- α were significantly lower than those of the control group (all P<0.05), and The levels of serum IL-4 and IL-10 were significantly higher than those of the control group all P<0.05). The live birth rate of the observation group was 87.2%(41/47), which was higher than that of the control group [70.2%(33/47)] ( P<0.05). There was no statistically significant difference in the adverse reaction rate between the observation group [6.4%(3/47)] and the control group [4.3%(2/47)] ( P>0.05). Conclusions:The treatment of RSA combined with PTS with Yunkang oral liquid, dexmedroxyprogesterone, and low molecular weight heparin can significantly alleviate blood hypercoagulability, increase reproductive endocrine hormone levels, regulate Th1/Th2 cytokine balance, improve live birth rate and clinical efficacy, and is safe and reliable.

Step down to 6 months of prophylactic-dose low molecular weight heparin after initial full-dose anticoagulation for the treatment of cancer-associated thrombosis (STEP-CAT): A pilot study.

BACKGROUND: Patients with cancer-associated thrombosis (CAT) are treated with full-dose anticoagulation for at least 3 months, but optimal dosing thereafter is unknown. AIM: We explored the feasibility of extended prophylactic-dose low molecular weight heparin (LMWH) treatment following a minimum of 3 months of full-dose LMWH. METHODS: We conducted a multicenter prospective pilot study of patients with CAT who completed at least 3 months of therapeutic-dose LMWH. Patients received 6 months of prophylactic-dose subcutaneous enoxaparin (40 mg once daily). The primary outcome was recurrence of deep vein thrombosis (DVT) or pulmonary embolism (PE), and secondary outcomes included major, clinically relevant non-major (CRNM), and minor bleeding. RESULTS: From August 2016 to May 2019, 52 patients with a mean age of 64.1 years were included. The study was stopped early because of poor recruitment. Breast (23.1%) and colorectal (19.2%) were the most common cancers, and 61.0% had stage IV malignancy. Index CAT consisted of DVT alone in 57.7% of patients and pulmonary embolism (PE) with or without DVT in 42.3%. Patients received a mean of 7.6 months of weight-adjusted LMWH before enrollment. During a mean follow-up of 5.6 months, one patient was diagnosed with recurrent incidental PE (0.0035 events/subject-month). There were no major bleeding events, one CRNM, and one minor bleeding event. Eight (15.4%) patients died; six from cancer and two from respiratory disease unrelated to PE. CONCLUSIONS: These results, in part, provide support for trials of extended reduced-dose anticoagulation for the secondary prevention of CAT. (ClinicalTrials.gov: NCT02752607).

Trombocitopenia inducida por heparina de bajo peso molecular en un paciente con COVID-19

RESUMEN Aunque el sistema respiratorio resulta el más afectado por la COVID-19, hoy conocemos que también predispone a la enfermedad tromboembólica, debido a la excesiva inflamación, activación plaquetaria, disfunción endotelial y estasis que suele ocasionar. La aplicación profiláctica de heparinas de bajo peso molecular ha sido una de las principales recomendaciones en pacientes hospitalizados por esta emergencia sanitaria, práctica no exenta de eventos secundarios, y que tiene entre sus complicaciones más graves la trombocitopenia. Con el propósito de alertar sobre la aparición de esta entidad y evitar mayores complicaciones, se expone un caso en el cual se constató trombocitopenia luego de recibir siete dosis de enoxaparina, y que luego de 48 horas de suspenderse esta, comenzó el ascenso progresivo del número de plaquetas, hasta alcanzar sus niveles de normalidad.

ABSTRACT Although the respiratory system is the most affected by COVID-19, today we know that it also predisposes to thromboembolic disease, due to the excessive inflammation, platelet activation, endothelial dysfunction and stasis that it usually causes. The prophylactic application of low molecular weight heparins has been one of the main recommendations in patients hospitalized for this health emergency, a practice that is not exempt from secondary events, and which has thrombocytopenia among its most serious complications. In order to alert about the appearance of this entity and avoid further complications, a case is presented in which thrombocytopenia was found after receiving seven doses of enoxaparin, and after 48 hours of suspending this, the progressive rise of platelets in number began, until they reach their normal levels.

Efficacy of intermittent pneumatic compression combined with drugs in the prevention of lower extremity deep venous thrombosis after joint replacement and its risk factors / 中国基层医药

Objective:To investigate the efficacy of intermittent pneumatic compression (IPC) combined with drugs in the prevention of lower extremity deep venous thrombosis (DVT) after joint replacement and its risk factors.Methods:A total of 80 patients receiving joint replacement surgery in Jinhua People's Hospital from January 2019 to December 2020 were included in this study. They were randomly divided into observation and control groups, with 40 patients in each group. To prevent lower extremity deep venous thrombosis, the control group was given low molecular weight heparin, and the observation group was given IPC in addition to DVT. The incidence of DVT post-surgery and coagulation function pre- and post-surgery were compared between the two groups. The incidence of adverse reactions was recorded in each group. In addition, 40 patients who developed DVT after joint replacement surgery from January 2019 to December 2020 (DVT group) and 40 patients who did not develop DVT (no DVT group) were included. The factors influencing the occurrence of DVT were analyzed by binary logistic regression.Results:The incidence of DVT in the observation group was significantly lower than that in the control group (5.00% vs. 20.00%, χ2 = 4.11, P < 0.05). At 7 days after surgery, prothrombin time, activated partial thromboplastin time, fibrinogen in the observation group were (11.73 ± 0.51) seconds, (27.05 ± 1.17) seconds, (3.89 ± 0.52) g/L, respectively, which were significantly lower than (12.03 ± 0.43) seconds, (27.65 ± 1.30) seconds, and (4.18 ± 0.59) g/L in the control group ( t = 2.84, 2.33, 2.17, all P < 0.05). There was no significant difference in the incidence of adverse reactions between observation and control groups (5.00% vs. 2.50%, χ2 = 0.00, P > 0.05). There were significant differences in age, body mass index, history of hypertension, and operative time between patients with DVT and those without DVT ( χ2 = 4.11, 5.16, 4.71, 8.65, all P < 0.05). Logistic regression analysis showed that age ( OR = 1.57, 95% CI = 1.239 - 2.014), body mass index ( OR = 6.71, 95% CI = 1.298 - 34.794), history of hypertension ( OR = 3.23, 95% CI = 1.980 - 5.296), operative time ( OR = 6.29, 95% CI = 2.058 - 19.225) were independent risk factors for DVT after joint replacement surgery (all P < 0.05). Conclusion:There are many factors that influence the occurrence of DVT after joint replacement surgery. Intermittent pneumatic compression combined with drugs for prevention of lower extremity DVT is safe and effective.

Blood circulation activating effect of Sanqi (Radix Notoginseng) on venous thromboembolism rat.

OBJECTIVE: To explore the blood circulation activating effect and mechanism of Sanqi (Radix Notoginseng) in vivo, using a venous thromboembolism (VTE) rat model. METHODS: We established the VTE rat model, and then intervened with low molecular weight heparin (LMWH), as well as low, medium and high doses of Sanqi (Radix Notoginseng), to observe the blood circulation activating effect of Sanqi (Radix Notoginseng) on VTE rats. RESULTS: After the treatment with high concentrations of Sanqi (Radix Notoginseng), the pulmonary thromboembolism was alleviated, and the lower limb thrombosis was markedly improved. Moreover, the expression quantities of plasma activated partial thromboplastin time, prothrombin time and D-dimer, as well as endothelin, von Willebrand factor, and plasminogen activator inhibitor-1 in thrombosis segment tissues were markedly down-regulated; while those of nitric oxide and tissue-type plasminogen activator were up-regulated. After low and medium concentration Sanqi (Radix Notoginseng) treatment, no obvious improvement was observed in each index. Moreover, the high concentration Sanqi (Radix Notoginseng) showed comparable efficacy to the positive drug LMWH. CONCLUSION: This data suggests that high concentration of Sanqi (Radix Notoginseng) is effective in preventing and treating VTE.

Hiponatremia e hiperpotasemia persistente inducida por enoxaparina y revertida con hidrocortisona en paciente con metástasis lumbares / Low molecular weight heparin-induced hyperkalemia and hyponatremia: report of one case

Low molecular weight heparin-induced hyperkalemia is not an uncommon side effect. The development of hyponatremia is well described although it is less common. We report a 72-year-old woman with lumbar metastases who developed hyponatremia and hyperkalemia on the tenth day of hospitalization. Hyponatremia, with limited criteria for syndrome of inappropriate secretion of antidiuretic hormone, did not resolve with vigorous volume restriction. Hyperkalemia without an acid-base disorder or baseline renal failure, did not resolve after losartan was stopped. Enoxaparin-induced hypoaldosteronism was proposed and the drug was discontinued. After four days' persistence of the electrolyte disturbance, dexamethasone was changed to Hydrocortisone, and parameters normalized in 24 hours. The patient remained well until discharge and during outpatient control.

Systemic thrombosis in a large cohort of COVID-19 patients despite thromboprophylaxis: A retrospective study.

BACKGROUND: Incidence of thrombotic events associated to Coronavirus disease-2019 (COVID-19) is difficult to assess and reported rates differ significantly. Optimal thromboprophylaxis is unclear. OBJECTIVES: We aimed to analyze the characteristics of patients with a confirmed thrombotic complication including inflammatory and hemostatic parameters, compare patients affected by arterial vs venous events and examine differences between survivors and non-survivors. We reviewed compliance with thromboprophylaxis and explored how the implementation of a severity-adjusted protocol could have influenced outcome. METHODS: Single-cohort retrospective study of COVID-19 patients admitted, from March 3 to May 3 2020, to the Infanta Leonor University Hospital in Madrid, epicenter of the Spanish outbreak. RESULTS: Among 1127 patients, 80 thrombotic events were diagnosed in 69 patients (6.1% of the entire cohort). Forty-three patients (62%) suffered venous thromboembolism, 18 (26%) arterial episodes and 6 (9%) concurrent venous and arterial thrombosis. Most patients (90%) with a confirmed thrombotic complication where under low-molecular-weight heparin treatment. Overt disseminated intravascular coagulation (DIC) was rare. Initial ISTH DIC score and pre-event CRP were significantly higher among non-survivors. In multivariate analysis, arterial localization was an independent predictor of mortality (OR = 18, 95% CI: 2.4-142, p < .05). CONCLUSIONS: Despite quasi-universal thromboprophylaxis, COVID-19 lead to a myriad of arterial and venous thrombotic events. Considering the subgroup of patients with thrombotic episodes, arterial events appeared earlier in the course of disease and conferred very poor prognosis, and an ISTH DIC score ≥ 3 at presentation was identified as a potential predictor of mortality. Severity-adjusted thromboprophylaxis seemed to decrease the number of events and could have influenced mortality. Randomized controlled trials are eagerly awaited.

Research progress in application of low molecular weight heparin assisted by anti-X activity monitoring in the prevention of thrombosis after traumatic brain injury / 中华创伤杂志

The incidence of venous thromboembolism（VTE）in patients with traumatic brain injury（TBI）, especially in patients with severe TBI, is significantly increased due to disturbance of consciousness and limb movement. In the acute phase of VTE, low molecular weight heparin（LMWH）is the most commonly used safe and effective measure to prevent thrombosis. Due to the changes of injury condition of trauma patients, the deviation of clinicians' understanding of VTE and the medication habits of various medical institutions, there are significant differences in the initial time and dose of LMWH prevention. Insufficient or excessive dose of LMWH will lead to thrombus or bleeding complications. In recent years, administration of LMWH with anti-X activity monitoring has been paid more and more attention in patients with TBI, playing an important role in reducing the incidence of thrombosis. The authors review the research progress in the application of LMWH with anti-X activity monitoring in thrombus prevention in patients with TBI from the aspects of mechanism in LMWH use with anti-X activity monitoring, LWMH medication time window and anti-X activity monitoring, LWMH dose adjustment and anti-X activity monitoring, in order to provide references for clinical treatment.

Low molecular weight heparin through TLR4/MyD88/NF-κB pathway protects PC12 cells against oxygen glucose deprivation induced inflammation / 中国医师杂志

Objective:To investigate the effect of low molecular weight heparin (LMWH) on the inflammatory response of PC12 cells induced by oxygen glucose deprivation (OGD) and its related mechanism.Methods:The PC12 cells were cultured in vitro were randomly divided into sham(control) group, OGD group, LMWH group and blocking agent group. The latter group was divided into six groups: Eritoran+ OGD group, LMWH+ Eritoran+ OGD group, ST2825+ OGD group, LMWH+ ST2825+ OGD group, pyrrolidinedithiocarbamate (PDTC)+ OGD group and LMWH+ PDTC+ OGD group. OGD cell model was established. Cell counting kit-8 (CCK-8) assay was used to detect cell activity. The expressions of toll-like receptor 4 (TLR4), MyD88 and nuclear factor κB (NF-κB) mRNA and protein were detected by real time polymerase chain reaction (qRT-PCR) and Western blot. The concentration of interleukin (IL)-1β, IL-6, tumor necrosis factor-α(TNF-α) and S100β were determined by enzyme linked immunosorbent assay (ELISA). Results:The cell activity of OGD group was significantly lower than that of control group on the first, second, third day ( P<0.05). Compared with OGD group, the activity of LMWH group was increased on the second, third day ( P<0.05), but lower than that of control group ( P<0.01). The mRNA expression of TLR4, MyD88 and NF-κB was significantly increased in OGD group compared with the control group ( F=144.9, F=710.5, 79.51, P<0.01). Compared with OGD group, the mRNA expression of TLR4, MyD88 and NF-κB were significantly decreased after treatment with LMWH ( P<0.01), and the specific inhibitor of TLR4, MyD88 and NF-κB enhanced the anti-inflammatory effect of LMWH. The protein expression of this pathway was consistent with that of the gene. The concentration of IL-1β, IL-6, TNF-α and S100β in OGD group was significantly higher than control group ( P<0.05). After treatment with LMWH, the concentrations of inflammatory factors and S100β were significantly decreased compared with OGD group ( P<0.01). When hinder TLR4, MyD88 and NF-κB respectively by Eritoran, ST2825 and PDTC, the concentrations of inflammatory factors and S100β were significantly decreased, but it was still higher than control group ( P<0.05). Conclusions:OGD can cause pathological damage of PC12 cells, including high expression level of S100β and aggravation of inflammatory reaction. LMWH can improve cell activity, down-regulate inflammatory reaction degree and protect the cells. Using inhibitors of TLR4/MyD88/NF-κB pathway to inhibit the corresponding target, the up-regulation of inflammatory factors by OGD can be inhibited in varying degrees. These suggested that LMWH may regulate inflammatory reaction of PC12 cells induced by OGD through TLR4/MyD88/NF-κB pathway.

Effects of adjuvant therapy with low molecular weight heparin on nephrotic syndrome in 32 cases / 中国基层医药

Objective:To investigate the clinical efficacy of adjuvant therapy with low molecular weight heparin on nephrotic syndrome.Methods:Sixty-four patients with nephrotic syndrome who received treatment in Linyi People's Hospital between January 2018 and January 2020 were included in this study. They were randomly assigned to receive either conventional treatment combined with low molecular weight heparin treatment (observation group, n = 32) or conventional treatment (control group, n = 32) for 28 successive days. Before and after treatment, renal function indexes, blood lipid, coagulation function indexes, clinical efficacy, and adverse reactions were compared between the two groups. Results:After treatment, serum creatinine, urea nitrogen, 24-hour urinary protein, total cholesterol and triacylglycerol levels in the observation group were (109.21 ± 9.81) μmol/L, (5.35 ± 1.01) mmol/L, (1.12 ± 0.25) g/L, (5.12 ± 1.09) mmol/L, (1.52 ± 0.18) mmol/L, respectively, which were significantly lower than those in the control group [(120.54 ± 9.72) μmol/L, (6.05 ± 0.95) mmol/L, (1.42 ± 0.28) g/L, (6.92 ± 1.15) mmol/L, (1.96 ± 0.22) mmol/L, t = 4.641, 2.855, 4.521, 6.426, 8.756, all P < 0.05]. The activated partial thromboplastin time and prothrombin time in the observation group were (1.52 ± 0.18) seconds and (14.57 ± 1.70) seconds, respectively, which were significantly longer than those in the control group [(31.02 ± 4.59) seconds, (12.62 ± 1.67) seconds, t = -4.388, -4.628, both P < 0.05]. Total effective rate in the observation group was significantly higher than that in the control group [96.88% (31/32) vs. 75.00% (24/32), χ2 = 6.335, P < 0.05]. The time to relief of symptom in the observation group was significantly shorter than that in the control group [(3.12 ± 1.42) weeks vs. (5.04 ± 1.24) weeks, t = -5.761, P < 0.05). The incidence of adverse reactions in the observation group was significantly lower than that in the control group [3.13% (1/32) vs. 21.88% (7/32), χ2 = 5.143, P < 0.05]. Conclusion:Based on conventional treatment, adjuvant therapy with low molecular weight heparin for nephrotic syndrome can greatly improve clinical symptoms, increase clinical efficacy, and decrease the incidence of adverse reactions.

Effect of anticoagulation combined with average volumeassuredpressuresupporton acute exacerbation of chronic obstructive pulmonary disease patients with type Ⅱrespiratory failure / 中国医师进修杂志

Objective:to investigate the therapeutic effect of low molecular weight heparin combined with average volumeassuredpressuresupport (AVAPS) on patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with type Ⅱ respiratory failure.Methods:A total of 82 patients with AECOPD combined with type Ⅱ respiratory failure in the Second People′s Hospital of Xindu District of Chengdu from February 2018 to April 2020 were selected as the research objects, and they were randomly divided into two groups with 41 cases in each group. The control group was given AVAPS mode, and the observation group was given low molecular weight heparin combined with AVAPS mode. The arterial partial pressure of oxygen (PaO 2), arterial carbon dioxide (PaCO 2), and forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1), maximum peak expiratory flow rate (PEF), interleukin (IL)-6, IL-8, tumor necrosis factor-(TNF-α), 16 kDa Clara cell protein (CC16), surfactant protein D(SP-D), adiponectin (APN), superoxide dismutase (SOD), D-dimer, fibrinogen before and after treatment were compared between the two groups and the incidence of adverse reactions were observed. Results:After treatment, the levels of FEV 1, FVC, PEF, PaO 2 in the observation group were higher than those in the control group: (1.78 ± 0.29) L vs. (1.47 ± 0.25) L, (2.47 ± 0.29) L vs.(2.20 ± 0.25) L, (5.14 ± 0.37) ml/s vs. (4.69 ± 0.35) ml/s, (88.37 ± 10.52) mmHg (1 mmHg = 0.133 kPa) vs. (80.16 ± 9.87) mmHg; and the level of PaCO 2 was lower than that in the control group: (65.07 ± 6.71) mmHg vs. (70.84 ± 6.50) mmHg; and the differences were statistically significant ( P<0.05). After treatment, the levels of IL-6, IL-8 and TNF-α in the observation group were lower than those in the control group: (0.47 ± 0.09) ng/L vs. (0.58 ± 0.10) ng/L, (64.37 ± 7.25) ng/L vs. (88.24 ± 8.34) ng/L, (45.37 ± 4.63) ng/L vs. (66.31 ± 4.92) ng/L; and the levels of SOD and APN were higher than those in the control group: (92.37 ± 10.85) U/mg vs. (76.13 ± 9.84) U/mg, (13.94 ± 0.76) mg/L vs. (11.58 ± 1.21) mg/L; and the differences were statistically significant ( P<0.05). After treatment, the level of CC16 in the observation group was higher than that in the control group: (114.78 ± 12.15) μg/L vs. (107.41 ± 11.06) μg/L; while the levels of SP-D, D-dimer and FIB were lower than those in the control group: (93.24 ± 9.85) μg/L vs. (103.25 ± 10.78) μg/L, (0.58 ± 0.07) mg/L vs. (0.79 ± 0.11) mg/L, (1.98 ± 0.29) g/L vs. (2.56 ± 0.34) g/L; and the differences were statistically significant ( P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Low-molecular-weight heparin combined with AVAPS mode in the treatment of AECOPD complicated with type Ⅱ respiratory failure can significantly improve the lung inflammation and coagulation function in patients, adjust blood gas analysis and CC16, SP-D levels, and promote the recovery of patients′ lung function.

Does Enoxaparin treatment have any effects on the placenta in women with unexplained histories of habitual abortion? A case control study

ABSTRACT BACKGROUND: It is very common to offer low molecular weight heparin (LMWH) medications to women with unexplained habitual abortion, to increase the livebirth rate. Although no benefit from LMWH has been clearly demonstrated, examination of the effects of enoxaparin on placental structure is lacking. OBJECTIVE: To assess placental structural changes in pregnancies treated with enoxaparin, compared with controls. DESIGN AND SETTING: Case-control study in an obstetrics and gynecology unit of a tertiary-level university hospital in Turkey. METHODS: Forty patients who had had term pregnancies and live births but also histories of habitual abortion were recruited for this study. Placentas were sampled using a systematic random sampling method. Tissue samples were obtained, embedded and sectioned for routine histological analyses. Hematoxylin and eosin staining was used. Surface area and length estimates from placental components were evaluated by using Image J. Cell proliferation and apoptosis were also assessed via immunohistochemistry. RESULTS: There were no significant differences between the groups regarding maternal age, abortion rate, birth weight or gestational age. Comparison of the enoxaparin and control groups showed that there were no significant differences in terms of surface area and ratios of placental components. We found that Bcl-2 was generally expressed at high levels in the enoxaparin group, while there was no difference in terms of Ki-67 between the groups. CONCLUSIONS: This study demonstrates that enoxaparin did not show any significant effect on the placental structure of cases that had histories of habitual abortion.

Osteoporotic fracture rates in chronic hemodialysis and effect of heparin exposure: a retrospective cohort study.

BACKGROUND: Patients receiving chronic hemodialysis treatments are at a higher risk of fracture compared to the general population. While the use of heparin during dialysis is crucial to avoid thrombosis of the extracorporeal circuit, the association of unfractionated heparin (UFH) and the risk of osteoporotic fracture has been shown for many years. However, this association was not as clear for low-molecular-weight heparin (LMWH) and the few collected data originated from studies among pregnant women. Our aim was to measure osteoporotic fracture rate among hemodialysis patients and to evaluate the association of LMWH compared to UFH in hemodialysis. METHODS: A retrospective cohort study was conducted on data extracted from the RAMQ and Med-Echo databases from January 2007 to March 2013 with patients chronically hemodialyzed in 21 participating centers. Incidence rates for each fracture sites were measured per 1000 patient-year (p-y) and their 95% confidence intervals (CI). Osteoporotic fracture risk for a first event with LMWH compared to UFH was estimated using a cox proportional hazard model using demographics, comorbidities and drug use as covariates. RESULTS: 4796 patients undergoing chronic hemodialysis were identified. The incidence rate for all fracture sites was 22.7 /1000 p-y (95% CI: 19.6-26.1) and 12.8 /1000 p-y (95% CI: 10.5-15.4) for hip and femur fractures. We found a similar risk of osteoporotic fracture for LMWH compared to UFH (adjusted HR = 1.01; 95%CI: 0.72-1.42). Age and malignancy increased the risk of fracture while cerebrovascular disease decreased the risk of fracture. CONCLUSIONS: Compared to UFH, LMWH did not change the risk of osteoporotic fracture when used for the extracorporeal circuit anticoagulation in chronic hemodialysis.