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  1. Aiyede M, Lim XY, Russell AAM, Patel RP, Gueven N, Howells DW, et al.
    J Neurotrauma, 2023 Jan;40(1-2):4-21.
    PMID: 35880422 DOI: 10.1089/neu.2022.0020
    The identification of effective pharmacotherapies for traumatic brain injury (TBI) remains a major challenge. Treatment with heparin and its derivatives is associated with neuroprotective effects after experimental TBI; however, the optimal dosage and method of administration, modes of action, and effects on hemorrhage remain unclear. Therefore, this review aimed to systematically evaluate, analyze, and summarize the available literature on the use of heparin and low molecular weight heparins (LMWHs) as treatment options for experimental TBI. We searched two online databases (PubMed and ISI Web of Science) to identify relevant studies. Data pertaining to TBI paradigm, animal subjects, drug administration, and all pathological and behavior outcomes were extracted. Eleven studies met our pre-specified inclusion criteria, and for outcomes with sufficient numbers, data from seven publications were analyzed in a weighted mean difference meta-analysis using a random-effects model. Study quality and risk of bias were also determined. Meta-analysis revealed that heparin and its derivatives decreased brain edema, leukocyte rolling, and vascular permeability, and improved neurological function. Further, treatment did not aggravate hemorrhage. These findings must be interpreted with caution, however, because they were determined from a limited number of studies with substantial heterogeneity. Also, overall study quality was low based on absences of data reporting, and potential publication bias was identified. Importantly, we found that there are insufficient data to evaluate the variables we had hoped to investigate. The beneficial effects of heparin and LMWHs, however, suggest that further pre-clinical studies are warranted.
    Matched MeSH terms: Heparin, Low-Molecular-Weight/pharmacology; Heparin, Low-Molecular-Weight/therapeutic use
  2. Kow CS, Hasan SS
    J Vasc Surg Venous Lymphat Disord, 2020 09;8(5):900-901.
    PMID: 32561464 DOI: 10.1016/j.jvsv.2020.06.006
    Matched MeSH terms: Heparin, Low-Molecular-Weight*
  3. Jawad AK, Alalaf SK, Ali MS, Bawadikji AA
    Clin Appl Thromb Hemost, 2019;25:1076029619896629.
    PMID: 31880168 DOI: 10.1177/1076029619896629
    Stillbirth is a devastating event to the parents, relatives, friends, and families. The role of anticoagulants in the prevention of unexplained stillbirths is uncertain. An open-label interventional prospective cohort study was conducted on 144 women with a history of unexplained stillbirths. The intervention group had a high umbilical artery resistance index (RI) and received bemiparin. The nonintervention group had a normal RI and did not receive any intervention. We measured the adjusted odds ratio (OR) and 95% confidence interval (CI) of the main outcome for these variables using logistic regression analysis. Fresh stillbirth and early neonatal death rates were lower (P = .005, OR = 11.949 and 95% CI = 2.099-68.014) and newborn weight was higher (P = .015, OR = 0.048, 95% CI = 0.004-0.549) in the group that received bemiparin. Bemiparin is effective in decreasing the rate of stillbirth in women with a history of previous unexplained stillbirths.
    Matched MeSH terms: Heparin, Low-Molecular-Weight/pharmacology; Heparin, Low-Molecular-Weight/therapeutic use*
  4. Hassan, S., Sutton, P.A., Smith, D.C., Kosai, N.R., Reynu, R., Shuhaili, M.A.
    Medicine & Health, 2018;13(1):291-295.
    MyJurnal
    Rectus sheath hematoma (RSH) is a rare clinical entity that has been associated with the use of injectable anticoagulant therapy. Although low molecular weight heparin (LMWH) was proven to have a better safety profile than its predecessor, it is not without its own risk of bleeding. The increase in use of self-injectable LMWH in both in-patient as well as out-patient basis warrants greater awareness among health care providers, patients and caregivers regarding the potential risks and identification of possible complications. We present a fatal case of rectus sheath hematoma in an elderly man that occurred following erroneous technique of Dalteparin injection.
    Matched MeSH terms: Heparin, Low-Molecular-Weight
  5. Kasim S, Amir Rudin PNF, Malek S, Aziz F, Wan Ahmad WA, Ibrahim KS, et al.
    PLoS One, 2024;19(2):e0298036.
    PMID: 38358964 DOI: 10.1371/journal.pone.0298036
    BACKGROUND: Traditional risk assessment tools often lack accuracy when predicting the short- and long-term mortality following a non-ST-segment elevation myocardial infarction (NSTEMI) or Unstable Angina (UA) in specific population.

    OBJECTIVE: To employ machine learning (ML) and stacked ensemble learning (EL) methods in predicting short- and long-term mortality in Asian patients diagnosed with NSTEMI/UA and to identify the associated features, subsequently evaluating these findings against established risk scores.

    METHODS: We analyzed data from the National Cardiovascular Disease Database for Malaysia (2006-2019), representing a diverse NSTEMI/UA Asian cohort. Algorithm development utilized in-hospital records of 9,518 patients, 30-day data from 7,133 patients, and 1-year data from 7,031 patients. This study utilized 39 features, including demographic, cardiovascular risk, medication, and clinical features. In the development of the stacked EL model, four base learner algorithms were employed: eXtreme Gradient Boosting (XGB), Support Vector Machine (SVM), Naive Bayes (NB), and Random Forest (RF), with the Generalized Linear Model (GLM) serving as the meta learner. Significant features were chosen and ranked using ML feature importance with backward elimination. The predictive performance of the algorithms was assessed using the area under the curve (AUC) as a metric. Validation of the algorithms was conducted against the TIMI for NSTEMI/UA using a separate validation dataset, and the net reclassification index (NRI) was subsequently determined.

    RESULTS: Using both complete and reduced features, the algorithm performance achieved an AUC ranging from 0.73 to 0.89. The top-performing ML algorithm consistently surpassed the TIMI risk score for in-hospital, 30-day, and 1-year predictions (with AUC values of 0.88, 0.88, and 0.81, respectively, all p < 0.001), while the TIMI scores registered significantly lower at 0.55, 0.54, and 0.61. This suggests the TIMI score tends to underestimate patient mortality risk. The net reclassification index (NRI) of the best ML algorithm for NSTEMI/UA patients across these periods yielded an NRI between 40-60% (p < 0.001) relative to the TIMI NSTEMI/UA risk score. Key features identified for both short- and long-term mortality included age, Killip class, heart rate, and Low-Molecular-Weight Heparin (LMWH) administration.

    CONCLUSIONS: In a broad multi-ethnic population, ML approaches outperformed conventional TIMI scoring in classifying patients with NSTEMI and UA. ML allows for the precise identification of unique characteristics within individual Asian populations, improving the accuracy of mortality predictions. Continuous development, testing, and validation of these ML algorithms holds the promise of enhanced risk stratification, thereby revolutionizing future management strategies and patient outcomes.

    Matched MeSH terms: Heparin, Low-Molecular-Weight
  6. Liew NC, Lee L
    World J Surg, 2016 07;40(7):1788-9.
    PMID: 26464151 DOI: 10.1007/s00268-015-3273-4
    Matched MeSH terms: Heparin, Low-Molecular-Weight/therapeutic use
  7. Che Yaakob CA, Dzarr AA, Ismail AA, Zuky Nik Lah NA, Ho JJ
    PMID: 20556784 DOI: 10.1002/14651858.CD007801.pub2
    BACKGROUND: Thromboembolic complications are much higher in pregnancy due to procoagulant changes. Heparin does not cross the placenta and the use of unfractionated heparin (UFH) is the current established practice in prophylaxis and treatment for thromboembolism in pregnancy.

    OBJECTIVES: To compare the effectiveness of anticoagulant therapies for the treatment of deep vein thrombosis in pregnancy. The anticoagulant drugs included are UFH, low molecular weight heparin (LMWH) and warfarin.

    SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2010) and reference lists of retrieved studies.

    SELECTION CRITERIA: Randomised controlled trials comparing any combination of warfarin, UFH, LMWH and placebo in pregnant women.

    DATA COLLECTION AND ANALYSIS: We used methods described in the Cochrane Handbooks for Systemic Reviews of Interventions for assessing the eligibility of studies identified by the search strategy. A minimum of two review authors independently assessed each study.

    MAIN RESULTS: We did not identify any eligible studies for inclusion in the review.We identified three potential studies; after assessing eligibility, we excluded all three as they did not meet the prespecified inclusion criteria. One study compared LMWH and UFH in pregnant women with previous thromboembolic events and, for most of these women, anticoagulants were used as thromboprophylaxis. There were only three women who had a thromboembolic event during the current pregnancy and it was unclear whether the anticoagulant was used as therapy or prophylaxis. We excluded one study because it included only women undergoing caesarean birth. The third study was not a randomised trial.

    AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials on the effectiveness of anticoagulation for deep vein thrombosis in pregnancy. Further studies are required.

    Matched MeSH terms: Heparin, Low-Molecular-Weight/therapeutic use
  8. Tan W, Abd Ghani F, Seong Lim CT
    Indian J Nephrol, 2019 8 20;29(4):288-290.
    PMID: 31423065 DOI: 10.4103/ijn.IJN_153_18
    Acute renal cortical necrosis (ACN) is a potentially fatal renal condition. Our objective is to report a case of ACN in a young man who had developed premature atherosclerotic vascular disease and required intermittent hemodialysis support. His renal biopsy showed diffuse cortical necrosis. Subsequently, 2 weeks after the renal insult, he developed a cardioembolic stroke and was anticoagulated with low-molecular-weight heparin. Thrombophilia screen revealed elevated serum homocystein and he was treated with folate supplement and vitamin B12 injection. With these treatments, he had partial renal recovery and became dialysis independent. In conclusion, this is a rare case of ACN, which may have occurred as a complication of hyperhomocysteinemia.
    Matched MeSH terms: Heparin, Low-Molecular-Weight
  9. Singh V, Haque S, Kumari V, El-Enshasy HA, Mishra BN, Somvanshi P, et al.
    Sci Rep, 2019 04 24;9(1):6482.
    PMID: 31019210 DOI: 10.1038/s41598-019-42740-7
    Arterial/venous thrombosis is the major cardiovascular disorder accountable for substantial mortality; and the current demand for antithrombotic agents is extensive. Heparinases depolymerize unfractionated heparin (UFH) for the production of low molecular-weight heparins (LMWHs; used as anticoagulants against thrombosis). A microbial strain of Streptomyces sp. showing antithrombotic activity was isolated from the soil sample collected from north India. The strain was characterized by using 16S rRNA homology technique and identified as Streptomyces variabilis MTCC 12266 capable of producing heparinase enzyme. This is the very first communication reporting Streptomyces genus as the producer of heparinase. It was observed that the production of intracellular heparinase was [63.8 U/mg protein (specific activity)] 1.58 folds higher compared to extracellular heparinase [40.28 U/mg protein]. DEAE-Sephadex A-50 column followed by Sepharose-6B column purification of the crude protein resulted 19.18 folds purified heparinase. SDS-PAGE analysis of heparinase resulted an estimated molecular-weight of 42 kDa. It was also found that intracellular heparinase has the ability to depolymerize heparin to generate LMWHs. Further studies related to the mechanistic action, structural details, and genomics involved in heparinase production from Streptomyces variabilis are warranted for large scale production/purification optimization of heparinase for antithrombotic applications.
    Matched MeSH terms: Heparin, Low-Molecular-Weight
  10. Voon HY, Chai MC, Hii LY, Amin R, Suharjono HN
    J Obstet Gynaecol, 2018 May;38(4):493-497.
    PMID: 29433369 DOI: 10.1080/01443615.2017.1389867
    Strategies to prevent mortality from obstetric venous thromboembolism begin with identification, risk stratification and subsequently, implementation of prophylactic measures. We sought to identify the burden of pharmacologic thromboprophylaxis in postpartum women, including the main clinical indications and its uptake in a multireligious population, with Islam as the official religion. A total of 2514 deliveries between 1st January to 31st December 2016, across three centres in Malaysia were reviewed retrospectively from hospital-based registries. 770 (30.62%) patients fulfilled the criteria for thromboprophylaxis based on the revised 2015 criteria proposed by the Royal College of Obstetricians and Gynaecologists. A combination of age, parity, BMI, caesarean section and preterm births were the main indications. One out of the five patients who delivered vaginally required thromboprophylaxis. In our setting with a sizable Muslim population, low molecular weight heparin was the thromboprophylaxis of choice in more than two-third of the patients. The information obtained from this study allows better local resource planning. Impact statement What is already known on this subject: Risk factors for venous thromboembolism in pregnancy and puerperium are largely drawn from registries due to the rarity of the index event. Up to 7% of women require antenatal thromboprophylaxis based on the criteria proposed by the Royal College of Obstetrician and Gynaecologists in 2009. What do the results of this study add: Using the RCOG guideline revised in 2015, a significant proportion of women delivering vaginally would require postnatal thromboprophylaxis based on age, parity and BMI. When either age or parity, both with relatively low odds ratio for thrombosis were omitted, a substantial proportion of women would not achieve the threshold for prophylaxis. Despite a sizable Muslim population in the country, the uptake of low molecular weight heparin was relatively high. What are the implications of these findings for clinical practice and/or future research: Cost-benefit studies should consider the adjusted odds ratio of individual indications on a VTE event. While uptake and acceptability is high, prospective studies on medication adherence is equally pertinent.
    Matched MeSH terms: Heparin, Low-Molecular-Weight/therapeutic use*
  11. Saheb Sharif-Askari F, Syed Sulaiman SA, Saheb Sharif-Askari N
    Adv Exp Med Biol, 2017;906:101-114.
    PMID: 27628006
    Patients with chronic kidney disease (CKD) are at increased risk for both thrombotic events and bleeding. The early stages of CKD are mainly associated with prothrombotic tendency, whereas in its more advanced stages, beside the prothrombotic state, platelets can become dysfunctional due to uremic-related toxin exposure leading to an increased bleeding tendency. Patients with CKD usually require anticoagulation therapy for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of anticoagulant-induced bleeding. Treatment of patients with CKD should be based on evidence from randomized clinical trials, but usually CKD patients are excluded from these trials. In the past, unfractionated heparins were the anticoagulant of choice for patients with CKD because of its independence of kidney elimination. However, currently low-molecular-weight heparins have largely replaced the use of unfractionated heparins owing to fewer incidences of heparin-induced thrombocytopenia and bleeding. We undertook this review in order to explain the practical considerations for the management of anticoagulation in these high risk population.
    Matched MeSH terms: Heparin, Low-Molecular-Weight/administration & dosage; Heparin, Low-Molecular-Weight/pharmacokinetics*
  12. Suria, A.A., Hafizah, H., Nurasyikin, Y., Azlin, I., Yousuf, R., Azma, R Z., et al.
    Medicine & Health, 2018;13(2):208-216.
    MyJurnal
    Idiopathic hypereosinophilic syndrome (HES) is an uncommon disorder which usually presents with prolonged and significant primary eosinophilia with end-organ dysfunction. Damaging proteins released by the eosinophilic granules are responsible for the tissues and organ system damage. Here we report two cases of idiopathic HES. Both the patients were young lady presented with high grade fever and concomitant symptoms. Laboratory findings showed leucocytosis with predominant neutrophilia and marked eosinophilia. A diagnosis of idiopathic HES was made after excluding secondary causes of eosinophilia. However, the first patient was complicated with multiple venous thrombosis and intravenous heparin was started which was later changed to subcutaneous low molecular weight heparin (LMWH). The patient developed pleural effusion and consolidation. Intravenous Tazoscin, tablet Prednisolone and tablet Hydroxyurea was started and the patient responded well. Despite treatment, two weeks later, suddenly the patient collapsed and unfortunately succumbed. On the other hand, the second patient was complicated with fever, thrombocytopenia, haemolytic anaemia, acute renal failure and neurological deficit which were part and parcel of thrombotic thrombocytopenic purpura (TTP). Plasma exchange was commenced and patient’s condition had slowly improved. Nevertheless, the hypoxia which she sustained during the multiple episodes of fits had resulted in permanent brain injury and thus requiring a tracheostomy for prolonged ventilatory support. Currently, there is no cure for HES. The main aim of treatment is to minimise the tissue damage caused by the hypereosinophilia. Early diagnosis and intervention are therefore crucial in preventing the spread of the disease and the end-organ damage.

    Matched MeSH terms: Heparin, Low-Molecular-Weight
  13. Noraida Mohamed Shah, Azmi Sarriff, Rosnani Hashim
    MyJurnal
    Low-molecular-weight heparins (LMWHs) are antithrombotic agents utilised in the treatment of acute coronary syndromes. They have been shown to be more effective than unfractionated heparins (UFHs) in reducing ischeamic events, which include death, myocardial infarction (MI) and urgent revascularisation. Enoxaparin is one of the products of LMWHs. Its safety and efficacy has been proven in the ESSENCE and TIMI IIB studies. This study was carried out to identify risk factors that may affect bleeding complications associated with the use of enoxaparin for non-ST-elevation MI (NSTEMI) or unstable angina (UA) in Universiti Kebangsaan Malaysia Hospital (HUKM). This observational, longitudinal study was conducted on patients who were admitted to the Coronary Care Unit (CCU), Coronary Rehabilitation Ward (CRW), Medical 1 and Medical 2 wards at HUKM and initiated on enoxaparin for NSTEMI/UA from 22nd of March until 22nd of April 2004. A total of 40 patients were included in the study with median age of 65 years, male to female ratio of 3:1, diagnosed with NSTEMI (55%) and UA (45%). 45% of patients developed an episode of bleeding and among them 83.3% (15 patients) characterised by haematuria. Higher percentages of women (80%) and those with creatinine clearance of < 30ml/min (100%) had incidence of bleeding as compared to men (50%) and those with creatinine clearance = 30 ml/min, respectively (p < 0.05 for both parameters). Age, enoxaparin dose and duration of therapy, smoking and concomitant aspirin/ticlopidine therapy did not significantly affect the incidence of bleeding. In conclusion, renal impairment and gender were associated with bleeding in relation with the use of enoxaparin that may require dose adjustments.
    Matched MeSH terms: Heparin, Low-Molecular-Weight
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