Since the invention of low molecular heparin (LMWH) in the 1970s, it has been widely used in clinical anticoagulation therapy with good results due to its good antithrombotic effect and lower anticoagulant effect than ordinary heparin. However, little is known about the role of heparin in non-anticoagulation. In this paper, we only review some of the progress of LMWH in non-anticoagulant effect for readers’ reference. 1.Role in obstetrics and pregnancy Patients with normal menstrual cycle, in good health, without adenomyosis and endometriosis benign uterine prolapse or fibroids were selected for hysterectomy to take endometrial tissue samples, and endometrial mesenchymal cells were cultured with progesterone and 17β estradiol, while human thrombin, human FXa, common heparin (UFH), dextran sulfate and four different commercial LMWH were incubated, and insulin-like growth factor (IGF-I) was measured by ELISA on day 3, and recombinant human insulin-like growth factor binding protein 1 (IGFBP-1) and prolactin (PRL) concentrations were measured on day 12, and the results showed that thrombin and FXa significantly increased IGF-I secretion compared with hormone stimulation alone, and dextran sulfate Dextran and heparin similarly stimulated IGF-I and PRL while inhibiting IGFBP-1, suggesting that the effect of heparin on endometrial interstitial cells is independent of its anticoagulant effect, and that UFH has the same effect compared with different commercial LMWH, except that LMWH has a slightly lower effect than UFH, and that IGF-I secretion is dose-dependent benefit with heparin, and interestingly, this Dose-dependent secretion of IGF-I was a constant even at supraphysiological doses of heparin, suggesting that the effect of heparin on human endometrium is a direct benefit rather than a physiological effect through the formation of complexes by interacting molecules. Noble et al. separately controlled 25 women treated with LMWH and 25 women treated with UFH and with low-dose aspirin for anticardiolipin antibody syndrome (ASP) with pregnancy found a 14% miscarriage rate in the LMWH group and 20% in the UFH group, suggesting that LMWH and UFH have the same role in preventing miscarriage in patients with ASP pregnancy; classical complement channels and hormone Immune system related, it was found that there is a mediating effect between LMWH and C1 subunit C1q, which is 4-fold higher than the initial anti-factor X activity, showing that the mediating effect between LMWH and C1q has not only an independent effect but also an independent anti-inflammatory and miscarriage preventing effect. However, Berker et al. divided patients who failed two consecutive intracytoplasmic sperm injection and embryo transfer (ICSI-ET) into two groups, one treated with LMWH, with 104 cases available for analysis, and the other control group, with 103 cases available for analysis. LMWH treatment was administered 12 to 14 days after embryo implantation and continued until the 12th week of gestation in case of a positive pregnancy test, and was discontinued in case of a negative test. The clinical pregnancy rate (CPR), live birth rate (LBR), implantation rate and multiple birth rate were 34.6%, 30.7%, 22.6% and 41.6%, respectively, in the LMWH group, compared to 33.9%, 29.1%, 21.1% and 42.8%, respectively, in the control group, with no significant difference between the two groups. In contrast, for patients with 3 or more implantation failures (RIF) the CPR, LBR, rate of placement and multiple births were 35.4%, 31.2%, 21.1%, 23.5% and 27.9%, 23.2%, 15.8%, 25.0% in the LMWH group (n=48) control group (n=43), respectively, although the ratios were higher, but still not statistically significant. This study denies the therapeutic benefit of LMWH in patients with multiple RIF. A retrospective controlled study of 72 patients who all had severe pregnancy complications and placental vasculopathy, 32 in the experimental group, i.e., LMWH, and 40 in the control non-LMWH group, showed that the incidence of severe pre-eclampsia, fetal growth restriction (FGR), fetal death at >20 weeks, placental abruption, and overall adverse outcomes in the LMWH group were 3.13%, 6.25%, 0%, 0%, and 9.4%, respectively, compared with 20%, 22.5%, 2.5%, 15%, and 60% in the control group, with significant differences in all outcomes except FGR and fetal death at >20 weeks. These results suggest that pregnant women treated with LMWH are effective in reducing the risk of severe placental abruption and preeclampsia. Preeclampsia is correlated with placental protein 13 (PP13), a member of the β-galactoside-binding S-type galactose lectin family, which is expressed only in placental tissues of higher primates and is present only in multinucleated syncytial trophoblasts in the trophoblastic layer of the chorionic villi, where PP13 is expressed and released into the intervillous space and into the maternal circulation. The serum concentration of PP13 is increased in normal pregnancy from the beginning to the second trimester, while when a pregnant woman develops pre-eclampsia starts with a lower than normal PP13 in the first trimester and then, when the clinical symptoms progress, PP13 is higher than normal, which alternates in the middle trimester. However, the results of Grimpel et al. showed no correlation between LMWH and PP13. 2. Effects on tumors and tumor metastasis A meta-analysis of 38 experiments conducted by 29 authors on the effects of heparin/low molecular heparin on lung metastasis of cancer cells. 38 experiments included injecting tumor cells of human, rabbit or mouse with breast cancer, melanoma, colon cancer, lung cancer, squamous cell carcinoma and osteosarcoma into mice, and then injecting different doses of UFH/LMWH into the tumor cells for 24 hours before The results showed that among 38 experiments with 55 groups, only 6 experiments with 8 groups had no effect, and the remaining 32 experiments with 42 groups showed that heparin reduced the lung metastasis of cancer cells, and the effect was time- and dose-dependent. Further studies confirmed that the biological mechanism of heparin’s anti-cancer metastasis is related to inhibition of heparinase, blockade of P- and L-selectin-mediated cell adhesion, and inhibition of vascular proliferation. p-selectin binds mainly to heparan sulfate and heparin fragments on a large scale, whereas L-selectin may require recognition with more specific sequences, although the sialyl-Lewis X motif bound on mucin-like molecules (Sialyl Lewis X motif) bound on the mucin-like molecule is thought to be a shared ligand between selectins, the interaction is weak, a result that suggests that the mechanism of heparin-selectin interaction involves a clustered anionic patch rather than a linear- defined oligosaccharide). In addition, LMWH interferes with and inhibits the interaction of integrin α4β1 (VLA-4) with VCAM-1, inhibits melanoma cell-platelet interaction mediated by platelet integrin αIIbβ3, inhibits thrombin-dependent protease-activated receptor 1 (PAR1) activity, and thus further inhibits platelet and endothelial cell activity and L- and P-selectin-mediated cell-cell adhesion. CD24, a ligand for P-selectin, is also involved in tumor metastasis, and LMWH inhibits the P-selectin/CD24 interaction to prevent platelet adhesion to tumor cells. Similarly, in the study of the effect of LMWH on tumor metastasis, lung cancer cells were injected into mice through the tail vein to make an animal model of tumor metastasis, and they were divided into control group, multiligand glycan group, LMWH group and LMWH+multiligand glycan group. 14 days after the experiment, the mice were executed, their lung tissues were dissected and the formation of lung tumor foci was observed. The formation of lung tumor foci was significantly higher in the control and multiligand polysaccharide groups than in the LMWH and LMWH+polysaccharide groups, indicating that LMWH has an inhibitory effect on lung cancer cell metastasis, and the mechanism may be related to the endothelial cell polysaccharide, as the acetyl heparan sulfate chain of the heparin polysaccharide led to a decrease in experimental tumor metastasis, and in addition, LMWH protects these enzymes from damage to the vascular endothelium by competitively binding to heparanase or hyaluronidase and its barrier function, thus inhibiting tumor metastasis. In addition, a mixture of melanoma and pancreatic cancer tumor cells were cultured and injected into hamsters for growth, and then implanted subcutaneously into rats to make an animal model. 46 rats were used, of which 23 were injected subcutaneously with LMWH 200 IU and another group of 23 were used as controls, and the number (N) and length (L) of microvessels, vascular area fraction (AF), erythrocyte velocity (V), microvascular density (MVD), vascular fractal dimension and perivascular cell coverage index (PCI), and the results showed that N, L and AF were significantly increased in the control group, while N and L were not significantly changed and AF was significantly decreased in the LMWH group; V was increased in the initial stage in both groups, but an early decrease was observed over time in the LMWH group; MVD and vascular fractal dimension were significantly decreased while PCI was significantly increased. It is suggested that LMWH can inhibit tumor vascular proliferation leading to normalization of microvasculature. However, Vivarelli et al. performed small lobectomy in 229 patients with cirrhosis complicated by hepatocellular carcinoma; 157 patients in one group were treated with LMWH for thrombosis prevention and 72 patients in the other group were not treated with LMWH; the results showed that in the group without LMWH, the model for end-stage The multifactorial analysis of venous thrombosis and bleeding complications revealed that only esophageal varices had a high risk of bleeding, while thrombotic risk factors such as body mass index (BMI), diabetes mellitus and cardiovascular disease, and bleeding disorders were significantly lower in both groups. disease, and the occurrence of bleeding disorders were not significantly different between the two groups. Therefore, the authors concluded that, unless there are clinical guideline criteria derived from large case studies, caution is needed as to whether prophylactic use of LMWH at the time of surgery is necessary in patients with such high bleeding risk. 3. Effects on vascular proliferation and vascular endothelium Vascular endothelial growth factor (VEGF) has an extremely critical role in embryonic angiogenesis and neonatogenesis and in adult neovascularization. natural VEGF inhibitors such as soluble VEGF-trapping receptor Flt1 (soluble VEGF-trapping receptor Flt1, sFlt1) sFlt1 is involved in the regulatory role of VEGF, and either decreased VEGF or elevated sFlt1 is involved in the pathophysiology of certain clinical disorders such as pre-eclampsia. Acetyl heparan sulfate (HS) proteoglycans bind sFlt1-secreting cells. sFlt1 isoforms are excellent heparin-binding agents, and this potent ability to bind heparin may affect their biological activity. sFlt1’s main sites of secretion are the aortic arch and placental chorionic cells. yagel et al. used LMWH to prevent the risk of coagulation dysfunction in pregnant women and found that application of LMWH to pregnant women Serum sFlt1 levels were significantly higher in pregnant women with LMWH than in those without LMWH, but interestingly, pregnant women with LMWH also had a 2-4 fold increase in VEGF levels compared to sFlt1, suggesting that the body has a physiological response to safeguard the VEGF/sFlt1 ratio. Further studies revealed that HS binds to sFlt1 to form the sFlt1-HS complex, which is deposited in placental tissue, and when heparinase is added, the release of sFlt1 from the placenta is increased due to shearing of the HS chain by heparinase. Comparing non-pregnant wild-type mice with overexpressing heparinase transgenic mice (HTG), serum sFlt1 levels were found to be more than 2-fold higher in HTG mice than in wild-type mice; the difference was even more pronounced in pregnant wild-type HTG mice, and increased exponentially with late gestation. When heparinase was neutralized in placental villous cells, sFlt1 secretion was reduced by 35% compared to controls. These findings suggest that LMWH has the effect of increasing sFtl1 and thus inhibiting VEGF. Norrby et al. treated rats with LMWH alone, epoetin and the combination of both drugs and measured their mean microvascular expansion space (VA), microvascular length (MVL) and total microvascular length (TMVL, VA X MVL) to observe the effect of the drugs on tumor vascular proliferation, respectively. It was found that the stimulatory effect of LMWH alone on vascular proliferation was inversely correlated with the dose, epi-adriamycin had no meaningful effect on vascular proliferation, while LMWH plus epi-adriamycin had a significant inhibitory effect on vascular proliferation. This result suggests that LMWH has the utility to promote angiogenesis under in vivo conditions, whereas LMWH combined with epi-adriamycin significantly inhibits vascular proliferation, suggesting that vascular inhibition under in vivo conditions is a compound benefit of the drug.Park et al. conjugated LMWH with deoxycholic acid (DOCA) to form the LMWH derivative LHD, and according to the ratio of LMWH to DOCA LHD1, LHD1.5, LHD2 and LHD4 were synthesized in increasing order according to different ratios of LMWH to DOCA, and the above drugs were applied to murine squamous cell carcinoma (SCC7) inoculated mice and SCC7 and A549 (human lung cancer cells) cell lines, respectively, and it was found that there was no significant effect on cellular activity LMWH and LHD in all groups, indicating that DOCA did not significantly increase the cytotoxic effect; regardless of tumor volume, tumor weight and microvascular proliferation, LHD4 had a significant inhibitory effect compared with all other groups, and was positively correlated with the dose while the anticoagulant effect was almost zero. After 275 patients with more than 50% lesions of femoral N vessels by angiography or ultrasound were treated with percutaneous transluminal angioplasty (PTA), they were randomly divided into two groups and treated with aspirin and aspirin plus LMWH for prevention of restenosis and observation of regenerative revascularization and clinical peripheral vascular lesions (such as claudication, rest pain, gangrenous ulcers, etc.), and the incidence of stenosis in the LMWH group was 44% and 50% in the control group, with no significant difference, and the incidence of severe peripheral vascular lesions was 43% and 41%, respectively, while in patients with severe limb ischemia vascular regeneration was significantly lower in the LMWH group compared to the control group , 45% and 72%, respectively [15]. Rectenwald et al. investigated the effect of LMWH on pulmonary artery injury by making a silicone model of pulmonary embolism in experimental rats and treating them with subcutaneous LMWH injections, and obtaining rat lung tissue after 21 days to detect total collagen, monocyte chemoattractant protein-1 (MCP-1), interleukin-13 (IL-13) and transforming growth factor-β (TGF-β). It was found that all pulmonary emboli could cause a significant decrease in PaO2, and the silicone emboli group (the silicone emboli group) had significantly higher IL-13, MCP-1 and all inflammatory mediators (all inflammatory Mediators) on day 1, day 4 and day 14, respectively, compared to the control group; along with these In addition, compared to the control group, the silicone embolus group showed a significant increase in pulmonary artery intima on days 4 and 21, while IL-13 levels were lower in the heparin-treated group at all times and TGF-β was significantly lower in the LMWH-treated group on days 4 and 14, in addition to the control group and other treatment groups (tPA, gIIB/IIIA antagonist abciximab abciximab)-treated rats), only the heparin-treated group showed a reduction in intimal hyperplasia on day 14. These results demonstrate that sustained pulmonary artery dilation caused by inert substances can produce significant inflammatory responses and intimal hyperplasia unrelated to thrombosis. Compared to the untreated PE group, LMWH was the only agent with a therapeutic effect associated with a significant reduction in advanced intimal hyperplasia, TGF-β, and low fibrogenic growth factor production. Therefore, clinically, LMWH should be used as early as possible for pulmonary embolism in order to minimize the injury response and the associated persistent pulmonary artery obstruction. 4. Effects on lipid metabolism In 20 chronic hemodialysis (HD) patients, UFH and LMWH were used to observe the changes of lipoprotein lipase (LPL), and it was found that the LPL activity was increased at 40 and 180 minutes in HD patients with LMWH, and after 6 months of treatment study, it was observed that at the beginning and end of HD, LPL activity and heparin activity always existed significant correlation, indicating that tissue LPL was not depleted; triglycerides were higher at LMWH than UFH during HD, concluding that heparin use in HD patients does not deplete the LPL system. Näsström et al. treated hemodialysis patients with LMWH to prevent in vitro coagulation and found that LMWH had a greater effect on lipoprotein esterase (LPL) than plain heparin. nine patients were given plain heparin (UFH) first and then LMWH two weeks later, and samples were collected at different times after dosing to determine plasma LPL, HL (hepatic lipase), and triglyceride (TG), cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL), and it was found that TG, cholesterol, HDL and LDL did not differ significantly in the two groups of cases. However, the effect of both UFH and LMWH on LPL was not significant in the early phase of dialysis (before 180 min), while the activity of plasma LPL decreased significantly in the late phase of dialysis (after 180 min), while LMWH was more significant than UFH, 6 mU/ml vs 22 mU/ml (180 min) and 5 mU/ml vs 11 mU/ml. The mean LPL activity area under the curve (AUC) was not significantly different between them at the early stage of dialysis, while the AUC of LMWH was significantly lower than that of UFH from 180 to 240 min. In addition, 60 hemodialysis patients with a mean dialysis duration of 4.15 ± 0.52 years were divided into 2 groups, 27 in one group with normal heparin prophylaxis and 33 in the other group with LMWH prophylaxis, with a mean age of 58.54 ± 2.24 The mean age was 58.54±2.24 years, and the study was observed for 12 months. The results showed that LMWH significantly reduced HDL cholesterol compared with standard normal heparin, while there was no significant difference for LDL cholesterol, and also LMWH had better effect than UFH in systemic perfusion and dialysis fluid, and LMWH resulted in improved lipids in female dialysis patients, while male patients with UFH in the first 6 The anticoagulant effect of UFH was better than that of female patients in the first 6 months, and there was a significant decrease in the mean blood clot rate in the second half of the year compared to the first half of the year for both UFH and LMWH, and the decrease was more significant for UFH than for LMWH. However, Katopodis et al. divided 6 hemodialysis, peritoneal dialysis and healthy control patients into 2 phases, treated with UFH and LMWH, and measured their total cholesterol, triglycerides, high and low density lipoproteins at 1, 2, 3 and 4 hours after drug administration, respectively, and found that only triglycerides were reduced while other lipoproteins were not affected during the 2 treatment periods in all test groups. 5. Effects on bone metabolism When UFH and LMWH were used to treat murine osteoclasts, it was found that standard doses of UFH (0.1-10U/ml) and LMWH (1-100 anti-Xa IU/ml) could change in both directions, leading to increased osteoclast formation in rats at low doses, and at high doses (UFH10U/ml,LMWH100 anti-Xa IU/ml) leading to increased osteoclast formation in rats. XaIU/ml) led to a decrease in osteoclast formation; whereas in mouse bone marrow culture, heparin inhibited osteoclast formation. This mechanism may be related to the ability of heparin protein binding to protect the properties of certain growth factors through a high affinity for heparin, which binds to the bone matrix and mediates changes in cell types in the bone microenvironment, including interactions with osteoblast lineage cells to release growth factors and cytokines that induce osteoclast formation from individual nuclear precursor pluripotent stem cells in the bone microenvironment. In addition, heparin increased IL-11-induced RANKL expression in mouse cranial osteoblasts, and RANKL-expressing osteoblasts formed mature osteoclasts under M-CSF conditions. In contrast to data showing that danalaparin inhibits osteoblast proliferation, protein synthesis, and decreases osteocalcin and alkaline phosphatase levels, sulforaphane (fondaparinux) does not have its effects. Exposure of osteoblasts to fondaparinux showed a significant increase in mitochondrial activity and protein synthesis compared to unexposed fondaparinux. In contrast, therapeutically relevant concentrations of heparin, danalaparin or enoxaparin decreased osteoblast matrix collagen type II content and calcification, while sulforaphane lacked a corresponding effect. However, a systematic review by Lefkou et al. regarding the effects of LMWH on bone found that the incidence of osteoporotic fractures due to common heparin was approximately 2.5-5%, whereas LMWH was relatively rare and lacked a corresponding risk level analysis. A literature review of patients with long-term LMWH use (longer than 3 months) showed that the conclusions were difficult to standardize, and in the literature review, essentially all cases were reported on an individual basis, with the authors’ most recognized cases of LMWH-induced osteoporotic fractures or systemic osteoporosis totaling only 11 cases, eight of which were in patients during pregnancy. (Two cases reported severe osteoporosis due to long-term LMWH use.) In addition, a systematic review of the largest group of data on LMWH use in pregnant patients showed that only 1 osteoporotic fracture, or 0.04%, was reported in 2,777 pregnant patients, including 64 study groups, and 2 osteoporotic vertebral fractures were reported in 728 pregnant patients in another systematic review group. Comparison of the effects of long-term UFH and LMWH use by measuring bone mineral density (BMD) revealed that 1 of 49 patients (2.3%) on LMWH experienced a meaningful reduction in BMD, whereas none of the 40 in the UFH group experienced osteoporosis. In a randomized open trial, 44 pregnant patients, randomized into two groups, 21 with LMWH and 23 with UFH, along with a control group of 19 normal subjects, were treated with heparin to prevent thrombotic events during pregnancy and the puerperium, and BMD was measured at weeks 1, 6, 16, and 52 (after 3 years if possible), showing that the UFH group had a significantly lower BMD in the lumbar spine than the LMWH group. BMD reduction was significantly lower in the UFH group than in the LMWH and normal control groups, with no significant difference between the LMWH and normal control groups. Another study comparing BMD changes in patients on long-term LMWH versus coumarin for secondary thrombosis prevention found that, over the course of 3 to 24 months of observation, 15 patients on natriuretic heparin and 42 patients on enoxaparin had a mean reduction in femoral BMD of 3.1% versus 1.8% and 4.8% versus 2.6% at year 1 and 2 follow-up, respectively, compared with 29 patients on coumarin. 4.8% versus 2.6%. Therefore, from the reports of these studies, it is difficult to conclude that LMWH does induce osteoporosis in pregnant patients. 6.Action on apoptosis When glutamate was co-cultured with rat brain cortical cells to observe its apoptosis-inducing effect, it was found that the apoptosis rate of rat cortical cells treated with glutamate increased by 33.21%, and the [Ca2+] concentration increased, Bcl-2 expression was down-regulated, Bax expression was up-regulated, and cysteine aspartate protein kinase 3 activity increased after 24 hours of glutamate treatment of cortical cells. The addition of ULMWH slowed down the rate of increase of both bound and free calcium, upregulated Bcl-2 expression, and downregulated Bax expression and cysteine aspartate protein kinase 3 activity. This suggests that ULMWH has a protective effect on neuronal cells by modifying the apoptotic process through the release of Ca2+. Similarly, Deepa et al. studied the pharmacological effects of adriamycin and LMWH on the heart and kidney of rats and came to the same conclusion. One group of experimental rats was given adriamycin alone and one group was given LMWH one week after adriamycin injection, and it was found that the reactive nitrogen species (RNS) in heart and kidney tissues were increased by 1 in the adriamycin alone group compared with the control group. RNS) increased 1.51-fold and 2.36-fold, TNF-α increased 2.4-fold and 7-fold, respectively, and standard apoptotic ladder bands appeared in DNA electrophoresis; while RNS and TNF-α in the group with LMWH were basically restored to the level of control group, and apoptotic electrophoretic bands disappeared. These results demonstrated that LMWH has good antiapoptotic effect on myocardial and renal tissue cells induced by adriamycin. In addition, Kukner et al. investigated the protective effect of LMWH on liver cells by dividing 30 mice into 5 groups, namely, control group, olive oil plus CCL4 group, CCL4 plus LMWH group, LMWH group and olive oil group, and liver tissues were taken after 4 weeks of the test to observe the value-added and apoptotic activities of hepatocytes by histochemical staining and cellular immunity, and the results showed that CCL4 could cause liver The results showed that CCL4 could cause significant necrosis of hepatocytes around the central vein, as well as the value-added of inflammatory cells and mast cells; hepatocyte lipid droplet deposition, hepatic glycogen reduction, apoptosis and nuclear swelling, while LMWH could significantly reduce necrosis, apoptosis and the number of mast cells in hepatocytes damaged by CCL4, but did not affect the deposition of hepatocyte lipid droplets. Therefore, LMWH can effectively reduce the early damage to hepatocytes by CCL4. 7.Anti-inflammatory effect By studying the effect of heparin on horseshoe plate inflammation, it was found that heparin could significantly inhibit the activity of equine neutrophil myeloperoxidase (MPO) in a dose-dependent manner, and the highest LMWH concentration could produce the highest MPO inhibition. the capture of MPO was higher in arterial cells, but the inhibition of heparin was more significant in venous cells, these results suggest that heparin has inhibitory effect on the inflammatory response, and there was no significant difference between UHF and LMWH. Luo et al. prepared LMWH as an oral colonic sustained-release dosage form to observe the effect of LMWH on ulcerative colitis in mice. The investigators divided six experimental groups of 20 mice each into model control, excipient control, dalteparin sodium treatment, enoxaparin treatment, normal heparin treatment and 5-aminosalicylic acid treatment groups. In vivo and in vitro observations of colonic histological changes, serum TNF-α, IL-6, FXa, and colonic Musashi-1 expression (an enterohepatocyte marker) revealed that oral administration of colon-specific extended-release capsules containing LMWH significantly reduced the features of colitis under visual and histological observations, significantly reduced TNF-α, IL-6, and FXa serological levels and significantly increased the expression of Musashi-1 in the colon. These results suggest that orally administered LMWH has a potential therapeutic role in inflammatory bowel disease. The results of 84 patients with progressive hepatitis cirrhosis who were treated with LMWH and studied its related indicators showed that 7 of the 84 patients had bleeding complications due to esophageal varices and hypertensive gastropathy, but there were no deaths due to bleeding and no thrombotic events. Antithrombin III (AT) was positively correlated with anti-Xa activity, AT was negatively correlated with childhood liver function classification (CTD classification), while precoagulation factors such as prothrombin time and platelet count were not correlated with anti-Xa. Anti-Xa was negatively correlated with patients’ body mass index (BMI) and ascites status, and AST/ALT, bilirubin, glucose and lipids were not correlated with anti-Xa. These study data show that treatment of cirrhotic patients with standard doses of LMWH does not achieve the recommended prophylactic or therapeutic doses of anti-Xa levels, as assessed by CTD or MELD scores, which are negatively correlated with the severity of cirrhotic disease, and that AT levels are positively correlated with anti-Xa values, suggesting a direct role of hepatic synthetic function, especially in the presence of LMWH, and AT as a monitoring tool that can accurately detect standard anti-Xa activity. In conclusion, LMWH is safe for use in cirrhosis, but the standard dose appears to be too low to produce a sufficient effect of anti-Xa activity, most likely due to increased lysis and impaired AT synthesis. However, further studies are needed to balance the risk of bleeding with the benefits of anticoagulation. 8. Other Haim et al. reported a case of premature neonate with concomitant respiratory disease who was treated with LMWH and developed increased FT4, which returned to normal after discontinuation of LMWH. Since heparin causes the release of lipoprotein lipase, it causes an increase in plasma free fatty acids, which leads to the dissociation of thyroxine from its bound protein, resulting in an increase in free thyroxine, which does not cause symptoms of hyperthyroidism and does not require treatment. Previously, Stevenson et al. conducted a controlled study of 9 healthy male volunteers (aged 33-54 years) and 19 cardiac patients (13 males and 6 females, aged 42-87 years), focusing on the biological effects of subcutaneous LMWH injections, with blood drawn before, 3 hours, 24 hours, and 48 hours after heparin injection for FT4, lipids, etc. and comparing the changes The results showed that in 9 healthy volunteers, there was no significant change in either free fatty acids, FT4 or TSH itself before and after heparin injection, but there was a significant correlation between the changes in free fatty acids, triglycerides and FT4 concentrations; however, for hospitalized cardiac patients, 2-6 hours after LMWH injection, 4 out of 10 patients had a significant increased, and further observation, 18 patients had a mild increase in FT4 and a significant increase in free fatty acids 10 hours after heparin injection, and all were higher than the level in healthy volunteers. These results suggest that LMWH has the effect of increasing FT4, and this biological effect may be related to the release of free fatty acids. To investigate the effect of LMWH on the renal-angiotensin-aldosterone system, 30 study subjects were divided into three groups of 10 each: a group of diabetic nephropathy patients, a group of non-diabetic nephropathy patients, and a healthy control group. LMWH was given 4000 IU per day, subcutaneously, respectively, and the study observation period was 11 weeks. The results showed that LMWH did not affect angiotensin II-induced changes in renal hemodynamics, nor did it reduce aldosterone levels in either the salt intake group or the salt restriction group, and glomerular filtration rate was unchanged in all study groups; however, LMWH significantly reduced proteinuria in the diabetic nephropathy group. significantly reduce proteinuria. thomas et al. observed a case of elderly diabetic patients on LMWH, resulting in hyperkalemia. thought to be related to aldosterone suppression. In conclusion, both regular heparin and LMWH have many non-anticoagulant benefits in addition to their well-known anticoagulant effects, and these non-anticoagulant effects, as well as other pharmacological effects that may still exist that we do not yet know about, are something that requires our active attention and exploration.