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"Telah dilakukan penelitian unruk menetapkan nilai rujukan masa trombin di Bagian Patologi Klinik FKUI-RSUPNCM, dengan menggunakan reagen Bovine thrombin. dengan kadar 10 NIB unit/ml. Penelitian ini berhasil mendapatkan nilai rujukan untuk laki-laki sebesar 8,49 - 15.61 detik dan wanita sebesar 9.13 - 12.89 detik. Pada penyimpangan larutan kerja trombin pada suhu -20°C ternyata reagen Bovine Thrombin stabil sampai minggu ke 4. Pada uji sensitivitas terhadap fibrinogen kadar rendah, reagen Bovine Thrombin 10 NIH unit/ml lebih sensitif daripada reagen Fibrindex 3 NIH unit/mi. Pada uji sensitivitas terhadap heparin, larutan kerja Bovine Thrombin 10 Ni-I unit/ml lebih sensitif sedikit dari pada larutan kerja Fibrindex 3 NIH unit/ml."

"Latar Belakang: Deep Vein Thrombosis (DVT) merupakan salah satu masalah dengan angka mortalitas jangka pendek dan morbiditas jangka panjang. Sebanyak 60% kasus DVT tidak memiliki gejala. Seiring bertambahnya usia, insiden DVT akan terus meningkat. Sekitar 1 dari 100.000 orang tiap tahunnya akan menderita DVT dibawah usia 50 tahun dan meningkat menjadi 1000 dari 100.000 per tahun di usia 85 tahun. Pada satu pertiga kasus bermanifestasi sebagai emboli paru, sedangkan dua pertiga lainnya hanya sebatas DVT. Terdapat kenaikan kadar fibrinogen maupun d-dimer pada pasien dengan keganasan.Penelitian ini bertujuan menganalisa dan membandingkan kadar fibrinogen, d-dimer dan dosis heparin terapeutik pada pasien DVT dengan keganasan dan non keganasan. Metode: Penelitian ini merupakan kohort retrospektif menggunakan rekam medis di RS Cipto Mangunkusumo. Variabel bebas adalah terapi pada pasien DVT sedangan variabel terikatnya adalah kadar D-dimer, fibrinogen dan aPTT terapeutik. Analisa statistic menggunakan SPSS versi 20, nilai p<0.05 menunjukkan terdapat hubungan bermakna secara statistik. Hasil: 63 pasien masuk dalam penelitian, didapatkan pasien DVT dengan keganasan sebanyak 33 pasien (52,4%) dan pasien DVT non keganasan sebanyak 30 pasien (47,6%). Kadar fibrinogen, D-dimer awal dan akhir pada pasien DVT dengan keganasan memiliki kadar yang lebih tinggi secara bermakna dibandingkan dengan DVT non keganasan (p<0,001). Terdapat perbedaan signifikan pada penurunan D-dimer pasien DVT dengan keganasan dibandingakan dengan pasien DVT non kegananasan. Dosis heparin awal pasien DVT dengan keganasan memiliki nilai tidak bermakna dibandingkan dengan DVT non keganasan (p>0,001). Dosis heparin terapeutik pada pasien DVT dengan keganasan bermakna signifikan lebih tinggi dibandingkan DVT non keganasan (p<0,001). Simpulan: Terdapat perbedaan yang bermakna pada kadar fibrinogen, d-dimer awal dan akhir yang bermakna antara pasien DVT keganasan dengan pasien DVT non keganasan. Terdapat perbedaan yang bermakna pada penurunan D-dimer pasien DVT dengan keganasan dan DVT non keganasan. Ditemukan perbedaan bermakna pada dosis heparin terapeutik pasien DVT dengan keganasan dan DVT non keganasan.

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Background: Deep Vein Thrombosis (DVT) is a problem with short-term mortality and long-term morbidity. As many as 60% of DVT cases have no symptoms. With age, the incidence of DVT will continue to increase. About 1 in 100,000 people each year will suffer from DVT under the age of 50 years and this increases to 1000 from 100,000 per year at the age of 85 years. In one third of cases it manifests as a pulmonary embolism, while in the other two thirds only a DVT is present. There is an increase in the levels of fibrinogen and d-dimer in patients with malignancy. This study aims to analyze and compare the levels of fibrinogen, d-dimer and therapeutic doses of heparin in malignant and non-malignant DVT patients.

Method: This study is a retrospective cohort using medical records at Cipto Mangunkusumo Hospital. The independent variable is therapy in DVT patients while the dependent variable is the level of D-dimer, fibrinogen and therapeutic aPTT. Statistical analysis using SPSS version 20, p value <0.05 indicates that there is a statistically significant relationship.

Results: 63 patients were included in the study, 33 patients with malignant DVT were found (52.4%) and 30 patients with non-malignant DVT (47.6%). The initial levels of fibrinogen in patient with malignant DVT were significantly higher than those of non malignant DVT (p<0.05). The final levels of fibrinogen in patient with malignant DVT were significant higher than those of non malignant DVT (p<0,05).There was significant higher of D-dimer initial levels beetween patient with malignant DVT and patient with non malignant DVT (p<0,05). There was significant higher of D-dimer final levels beetween patient with malignant DVT and patient with non malignant DVT (p<0,05). There was a significant difference in the decrease of d-dimer levels between DVT patients with malignancy compared to non-malignant DVT patients who were given heparin therapy. The initial heparin dose in patients with malignant DVT had no significant value compared to non malignant DVT (p>0.001). The therapeutic dose of heparin in patients with malignant DVT was significantly higher than that of non malignant DVT (p<0.001).

Conclusion: There was a significant difference in the levels of fibrinogen and D- dimer initial and final which was significant between malignant DVT patients and non-malignant DVT patients. There is a significant difference in the decrease in D-dimer in patients with malignant DVT and non-malignant DVT. A significant difference was found in the therapeutic dose of heparin in patients with malignant DVT and non-malignant DVT."

"Latar Belakang: Proses inflamasi dengan respons maladaptif merupakan mekanisme terjadinya disfungsi multiorgan dan kematian pada sepsis. Heparin merupakan sediaan yang digunakan secara luas untuk terapi gangguan koagulasi, secara in-vitro heparin juga memiliki pengaruh sebagai antiinflamasi melalui penurunan aktivitas nuclear factor kappa B (NFkB) dan tumor necrosis factor alpha (TNF-. Penggunan heparin pada sepsis, khususnya sebagai antiinflamasi, masih merupakan kontroversi dan memerlukan penelitian lebih lanjut.Tujuan Penelitian: Tujuan primer penelitian ini adalah mengetahui pengaruh terapi heparin terhadap konsentrasi NFkB, inhibitor kappa B kinase beta (IKK dan TNF-pada pasien sepsis berat Tujuan sekunder adalah menilai pengaruh terapi heparin terhadap mortalitas dan perbaikan disfungsi organ.Metode: Uji klinis acak tersamar ganda membandingkan terapi heparin tidak terfraksinasi, dosis 10 unit/kg berat badan/24 jam, infus kontinu selama 72 jam, dengan plasebo. Kriteria inklusi adalah: subjek usia 18 tahun atau lebih dengan sepsis berat awitan maksimal 48 jam dan bersedia berpartisipasi dalam penelitian. Seleksi subjek dilakukan secara konsekutif dengan alokasi subjek secara acak. Pemantauan terhadap respons klinis dilakukan dengan menilai mortalitas 14 hari serta perbaikan skor APACHE II. Analisis intention to treat (ITT) dilakukan terhadap subjek yang telah mendapat terapi heparin minimal selama 24 jam, pada subjek yang melengkapi seluruh protokol penelitian dilakukan analisis per-protocol (PP).Hasil: Sebanyak 115 subjek telah diinklusi dan dirandomisasi, 58 subjek mendapat heparin dan 57 subjek plasebo. Rentang usia 21 hingga 82 tahun dengan rerata 51 tahun. Analisis ITT dan PP dilakukan terhadap masing-masing 46 dan 22 subjek kelompok heparin dan 50 dan 28 subjek kelompok kontrol. Tidak didapatkan perbedaan yang bermakna konsentrasi NFkBterfosforilasi dan IKK terfosforilasi kelompok heparin dibandingkan kontrol. Didapatkan penurunan konsentrasi TNF-pada kelompok heparin dibandingkan kontrol walaupun secara statistik belum bermakna. Didapatkan penurunan mortalitas pada analisis PP (RR 0,212 [IK 95% 0,053 - 0,815], p = 0,008), dengan ARR 33,8 % dan NNT 3. Terdapat kecenderungan perbaikan disfungsi organ pada kelompok heparin, walaupan secara statistik belum menunjukkan kemaknaan.Simpulan: Terapi heparin memberikan pengaruh terhadap proses inflamasi pada pasien sepsis berat, terlihat dari penurunan konsentrasi TNF-, walaupun pada pengujian statistik tidak didapatkan perbedaan bermakna. Tidak didapatkan pengaruh terapi heparin terhadap penurunan konsentrasi IKKdanNFkB. Heparin memberikan manfaat terhadap penurunan mortalitas, terutama pada subjek yang mendapat heparin selama 72 jam. Pada pengamatan selama 72 jam, heparin belum telihat memberikan pengaruh terhadap perbaikan disfungsi organ.

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Background. Multiple organ dysfunction and mortality in sepsis are developed as the consequence of the inflammation with maladaptive host response. Heparin has been widely used as an anticoagulant treatment. Based on in vitro evaluation, heparin has an antiinflammatory property by reducing the activity of nuclear factor kappa B (NFkB) and tumor necrosis factor alpha (TNF-. However, the effect of heparin as the anti-inflammatory agent is still controversial. To ascertain the anti-inflammatory effects of heparin in sepsis, further study is needed.Objectives. The primary aim of this study was to determine the effect of heparin in severe sepsis based on the concentration of NFkB, Inhibitor kappa B kinase beta (IKK), and TNF-. Secondary objective was to determine the effect of heparin on mortality rate and improvement of organ dysfunction.Methods. A randomized, double-blind, clinical trial was conducted to compare the unfractionated heparin (UFH) treatment, in dosage of 10 units/ kg BW for 24 hours, continuous infusion for 72 hours, in comparison to placebo. The inclusion criteria were subject 18 years old or above, with severe sepsis in maximum 48 hours after onset and agreed to participate in this study. Furthermore, subjects were consecutively selected and randomly allocated. Clinical responses were monitored by evaluating the 14-days mortality rate and improvement of APACHE II score. Subjects who had received heparin treatment for at least 24 hours were analyzed by intention to treat (ITT), while others who had completed all the protocol, were analyzed by per protocol (PP).Results. There were 115 subjects included and randomly assigned to heparin (n = 58) and placebo (n = 57) groups. The range of age was 21 to 82 years, mean of age was 51 years. ITT and PP analysis were conducted to 46 and 22 subjects in heparin group; 50 and 28 subjects in control group respectively. There were no significant differences in concentration of Phosphorylated-NFkB and Phosphorylated-IKK in both groups. The concentration of TNF-decreased in heparin groups, although statistically was not significant. The 14 days mortality rate reduced in PP analysis (RR 0.212 [95% CI 0.053 – 0.815], p = 0.008), with ARR 33.8 % and NNT 3. Moreover, there are trend of organ dysfunction improvement in heparin group, yet not statistically significant.Conclusion. Heparin treatment has an impact on inflammatory process in severe septic patients; as shown in the reduction of the TNF- concentration, although was not significant statistically. There was no clear impact of heparin treatment on IKK and NFkB concentration. Moreover, heparin shows benefit in reducing the mortality, especially in subjects who has received heparin for 72 hours. No benefit on improvement of organ dysfunction was shown in 72-hour monitoring of heparin treatment."

"The aim of this volume is to summarise the developments that have led to the current status of both heparins as drugs and the field of heparin research, with a focus on the particularly rapid progress that has been made over the past three decades. Individual sections are dedicated to the nature of heparin as a biological molecule, the current approaches and techniques that are used to ensure the safety and reliability of heparin as a medicine, the clinical pharmacology of heparin as an anticoagulant drug, effects and potential applications of heparin aside of those involving haemostasis and, finally, the nature and potential uses of heparin-like materials from both natural and synthetic sources."

"Amlodipine besilat dan valsartan adalah obat kombinasi tetap untuk terapi anti-hipertensi. Obat ini memiliki konsentrasi yang rendah dalam plasma, sehingga diperlukan metode analisis yang selektif dan sensitif. Antikoagulan diperlukan untuk mendapatkan plasma saat analisis analit dilakukan dalam plasma. Plasma yang diperoleh dari Palang Merah Indonesia digunakan untuk memvalidasi metode analisis in vitro menggunakan antikoagulan sitrat. Sedangkan pada studi in vivo, biasanya digunakan EDTA dan heparin. Adanya antikoagulan yang berbeda dapat mempengaruhi analisis sehingga perlu dilakukan evaluasi yaitu validasi parsial. Penelitian ini bertujuan untuk mengevaluasi pengaruh jenis antikoagulan terhadap analisis amlodipine besylate dan valsartan dalam plasma menggunakan spektrometri massa tandem kromatografi cair kinerja ultra tinggi. Kondisi analisis optimal diperoleh dengan menggunakan kolom Acquity BEH C18 Waters (2.1 × 100 mm; 1.7 μm); fase gerak asam format 0,1% dalam air - asetonitril; metode elusi gradien; laju aliran 0,2 mL / menit; dan irbesartan sebagai standar internal. Aliquot diperoleh dengan ekstraksi cair - cair menggunakan amonium asetat pH 4,83 sebagai buffer dan etil asetat sebagai pelarut ekstraksi. Akurasi dan presisi dalam plasma sitrat, heparin dan analisis EDTA memenuhi persyaratan dan kurva kalibrasi linier dalam kisaran konsentrasi 0,2-10 ng / mL untuk amlodipine besylate dan 5-6000 ng / ml untuk valsartan. Hasil stabilitas dan recovery tidak menunjukkan perbedaan yang signifikan (p> 0,05), sedangkan rasio luas puncak menunjukkan perbedaan yang signifikan (p <0,05) pada ketiga plasma. Secara keseluruhan, analisis dengan plasma heparin memberikan hasil yang lebih baik daripada plasma sitrat dan EDTA.Amlodipine besylate and valsartan are fixed combination drugs for anti-hypertensive therapy. This drug has a low concentration in plasma, so a selective and sensitive method of analysis is required. Anticoagulants are required to obtain plasma when analyte analysis is performed in plasma. The plasma obtained from the Indonesian Red Cross was used to validate the in vitro analysis method using citrate anticoagulants. Whereas in vivo studies, EDTA and heparin are usually used. The existence of different anticoagulants can affect the analysis so it is necessary to evaluate, namely partial validation. This study aims to evaluate the effect of the type of anticoagulant on the analysis of amlodipine besylate and valsartan in plasma using ultra high performance liquid chromatography tandem mass spectrometry. The optimal analysis conditions were obtained using the Acquity BEH C18 Waters column (2.1 × 100 mm; 1.7 μm); mobile phase of formic acid 0.1% in water - acetonitrile; gradient elution method; flow rate 0.2 mL / min; and irbesartan as internal standards. Aliquots were obtained by liquid - liquid extraction using ammonium acetate pH 4.83 as a buffer and ethyl acetate as the extraction solvent. Accuracy and precision in plasma citrate, heparin and EDTA analysis meet the requirements and linear calibration curves in the concentration range of 0.2-10 ng / mL for amlodipine besylate and 5-6000 ng / ml for valsartan. The stability and recovery results did not show a significant difference (p> 0.05), while the peak area ratio showed a significant difference (p <0.05) in the three plasmas. Overall, analysis with heparin plasma gave better results than plasma citrate and EDTA."

"Pendahuluan: Heparin dapat digunakan sebagai terapi bagi pasien COVID-19. Namun, indikasi dan efeknya masih berbeda di berbagai penelitian. Oleh karena itu, penelitian ini bertujuan untuk menilai efektivitas pemberian heparin dalam menurunkan keparahan gejala klinis. Metode :Studi retrospektif dilakukan dari rekam medis pasien COVID-19 kondisi sedang-berat yang dirawat di Rumah Sakit Universitas Indonesia (RSUI). Parameter yang diperiksa adalah kondisi klinis pasien (tingkat mortalitas dan total lama perawatan), kadar D-dimer, dan trombosit pada dua kelompok, kelompok yang diberikan heparin dan yang tidak. Hasil:Penelitian ini menyertakan 110 subjek penelitian. Terdapat tingkat mortalitas yang lebih tinggi pada kelompok heparin dibandingkan kontrol (45,3% vs 5 10,9%; p<0,01). Hal ini dapat disebabkan perbedaan derajat sedang dan berat. Mayoritas kelompok heparin berkondisi berat (58,1% vs 28,2%) jika dibandingkan kontrol. Pada pengecekan laboratorium, heparin menurunkan kadar D-dimer (790 ke 500 vs 725 ke 4.475 µg/L) dan trombosit (366 ke 208x103 vs 217 ke 318x103/µL)secara signifikan (p<0,01). Kesimpulan: Kelompok heparin memiliki tingkat mortalitas yang tinggi akibat tingkat kondisi yang lebih berat, tetapi kadar D-dimer dan trombosit menurun dibandingkan kelompok kontrol.

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Introduction: Heparin can be used as therapy for COVID-19 patients. However, the indications and effects still differ in various studies. Therefore, this study aims to assess the effectiveness of heparin administration in reducing the severity of clinical symptoms. Methods: A retrospective study was conducted from medical records of moderate-severe COVID-19 patients treated at the University of Indonesia Hospital (RSUI). The parameters examined were the patient's clinical condition (mortality rate and total length of treatment), D-dimer levels, and platelets in two groups, those given heparin and those not. Results: This study included 110 research subjects. There was a higher mortality rate in the heparin group compared to controls (45.3% vs 5 10.9%; p<0.01). This is due to the difference in moderate and severe degrees. The majority of the heparin group had severe conditions (58.1% 28.2%) when compared to controls. In laboratory tests, heparin reduced the levels of D-dimer (790 to 500 vs 725 to 4,475 µg/L) and platelets (366 to 208x103 vs 217 to 318x103/µL) significantly (p<0.01). Conclusion: The heparin group had a high mortality rate due to more severe conditions, but D-dimer and platelet levels decreased compared to the control group"