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"Latar Belakang: Risiko perdarahan tidak berkorelasi linear dengan jumlah trombosit pada kondisi trombositopenia. Terdapat perbedaan fungsi trombosit pada trombositopenia gangguan produksi dengan destruksi perifer. Pada trombositopenia, hasil fungsi agregasi trombosit dengan light transmission aggregometry tidak valid. Diperlukan pemeriksaan fungsi trombosit yang dapat dikerjakan pada kondisi trombositopenia.Tujuan: Mengkaji fungsi agregasi trombosit pada pasien trombositopeniaMetode: Studi potong lintang terhadap 60 pasien trombositopenia gangguan produksi dan destruksi perifer di Rumah Sakit Cipto Mangunkusumo selama Desember 2023 sampai April 2024. Dilakukan pemeriksaan jumlah trombosit, IPF, dan fungsi agregasi trombosit.Hasil: Terdapat perbedaan fungsi agregasi antara trombositopenia gangguan produksi dengan destruksi perifer (40% vs 77,7%). Didapatkan perbedaan nilai IPF antara trombositopenia gangguan produksi dengan destruksi perifer (5,65% vs 21%). Tidak didapatkan korelasi antara jumlah trombosit dengan fungsi agregasi trombosit pada trombositopenia gangguan produksi maupun destruksi perifer (r=0,214, p=0,231; r=0,364 p=0,062). Tidak didapatkan korelasi antara jumlah trombosit dengan fungsi agregasi trombosit pada trombositopenia gangguan produksi maupun destruksi perifer. Didapatkan titik potong IPF 10,25% untuk membedakan trombositopenia gangguan produksi dan destruksi perifer dengan sensitivitas 80,8% dan spesifisitas 68%.Kesimpulan: Fungsi agregasi trombosit pada trombositopenia destruksi perifer lebih baik daripada trombositopenia gangguan produksi. Fungsi agregasi trombosit tidak berkorelasi dengan jumlah trombosit maupun dengan IPF.

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Background: The risk of bleeding does not linearly correlate with platelet count in thrombocytopenia.There is difference between platelet function in central and peripheral thrombocytopenia. Platelet aggregation function assay performed by light transmission aggregometry is not valid in thrombocytopenia. Platelet aggregation assay that can be performed in thrombocytopenia is needed.

Objective: To assess platelet function in thrombocytopenia patients.

Methods: A cross-sectional study was conducted on 60 thrombocytopenic patients at Cipto Mangunkusumo Hospital from December 2023 to April 2024. Platelet count and immature platelet fraction (IPF) were done by automatic blood cell counter while platelet aggregation by Plateletworks ADP Kit

Results: There was a difference in platelet aggregation function between central thrombocytopenia and peripheral thrombocytopenia (40% vs 77.7%). A difference in IPF values was found between central thrombocytopenia and peripheral thrombocytopenia (5.65% vs. 21%). No correlation between platelet count and platelet aggregation function in thrombocytopenia (r=0.214, p=0.231 vs. r=0.364, p=0.062). No correlation was found between IPF and platelet aggregation function (r=-0.139, p=0.498 vs. r=-0.282, p=0.171). The cut-off value of IPF was 10.25% to distinguish central and peripheral thrombocytopenia.

Conclusion: Platelet aggregation function in peripheral thrombocytopenia was better than central thrombocytopenia. Platelet aggregation function did not correlate neither platelet count nor IPF."

"Latar belakang: Immune thrombocytopenia (ITP) didiagnosis dengan mengekslusi penyebab lain trombositopenia. Mekanisme trombositopenia terjadi melalui 2 mekanisme, yaitu destruksi trombosit seperti pada pasien ITP dan penurunan produksi trombosit pada pasien leukemia. Aspirasi sumsum tulang merupakan metode yang dapat membedakan mekanisme trombositopenia yang terjadi, tetapi karena invasif tidak rutin dilakukan untuk diagnosis. Seiring dengan perkembangan zaman, dapat dilakukan pemeriksaan trombosit muda dengan teknik flouresensi untuk menilai kadar immature platelet fraction (IPF). Penelitian ini dilakukan untuk membandingkan kadar IPF pada pasien ITP dibandingkan dengan leukemia. Metode: Studi potong-lintang kadar IPF pasien anak dengan ITP dan leukemia, yang dilaksanakan dari 2017-2020 di RSUPN Cipto Mangunkusumo, Jakarta. Sampel penelitian adalah pasien anak umur kurang dari 18 tahun, yang menderita ITP dan leukemia, yang belum mendapatkan kemoterapi ataupun imunosupresan. Data penelitian diambil dari rekam medis atau pemeriksaan darah rutin. Hasil: Dari 42 pasien, didapatkan 21 pasien ITP dan 21 pasien leukemia. Terdapat perbedaan bermakna (16,6 poin) dari rerata kadar IPF pasien ITP dibandingkan pasien leukemia (P<0,001). Pasien ITP memiliki kadar rerata IPF sebesar 18,6%(SB 12,1%). Pasien leukemia memiliki kadar IPF 2%(SB 1,31%). Kesimpulan: Terdapat perbedaan bermakna kadar IPF pada pasien ITP dibandingkan pasien leukemia akut.

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.Background and aim: Immune thrombocytopenia (ITP) is diagnosed by excluding other causes of thrombocytopenia. The thrombocytopenia itself could occur through 2 mechanisms, which were platelet destruction as in ITP, and decrease platelet production as in leukemia. Bone marrow aspiration used to be done to distinguish the mechanism of thrombocytopenia, but it has not been routinely done due to its invasiveness. Examination of young platelets with fluorescence technique are currently done to assess the level of Immature Platelet Fraction (IPF). This study was conducted to evaluate the differences in IPF levels in ITP patients compared with leukemia patients.

Methods: A cross-sectional study was carried out on the IPF levels on patients with ITP and leukemia, from 2017-2020 at Cipto Mangunkusumo General Hospital, Jakarta. The study sample was pediatric patients, less than 18 years old, diagnosed with ITP and acute leukemia, whom had not received any chemotherapy or immunosuppressants. Research data were taken from medical records and/or routine blood tests.

Results: Total of 42 patients, 21 ITP patients and 21 leukemia patients were found. There was a significant difference (16,6 poin) in the mean of IPF levels of ITP patients compared with leukemia patients (P <0.001). ITP patients had an average IPF level of 18,6% (SB 12,1). Leukemia patients have 2% IPF levels (SB 1,31).

Conclusions: There is a subtantial different in IPF in ITP patient compared to acute leukemia patients. "

"ABSTRAKLatar belakang : Etiologi trombositopenia sangat beragam sehingga sulit untukdiidentifikasi. Sangat penting mengetahui penyebab terjadinya trombositopeniakarena berhubungan erat dengan rencana penatalaksanaan yang diberikan. Belumtersedia tes diagnostik sederhana, cepat dan mudah untuk mengetahui aktivitastrombopoiesis. Immature platelet merupakan trombosit muda yang berhubunganerat dengan aktivitas trombopoiesis. Diharapkan pengukuran persentase immatureplatelet dapat membedakan etiologi trombositopenia yang terjadi karenagangguan produksi megakariosit di sumsum tulang atau karena meningkatnyadestruksi di perifer sehingga dapat menghindari tindakan pemeriksaan aspirasisumsum tulang.Tujuan : Penelitian ini bertujuan menilai pemeriksaan IPF sebagai penandaaktivitas trombopoiesis pada pasien trombositopenia. Mendapatkan nilai rujukanparameter IPF pada orang dewasa normal di Jakarta menggunakan alat sel hitungotomatik Sysmex XE-5000. Mendapatkan nilai cutt-off IPF untuk membedakantrombositopenia yang disebabkan oleh gangguan produksi atau gangguandestruksi.Metode : Desain penelitian adalah potong lintang. Menggunakan 256 orangpeserta medical check up di RS MMC dan 203 pasien trombositopenia yangberasal dari RSCM dan RS MMC.Hasil : Nilai rujukan IPF orang dewasa di Jakarta menggunakan Sysmex XE-5000 sebesar 0.64-3.20%. Nilai cutt-off IPF untuk membedakan trombositopeniadengan aktifitas trombopoiesis meningkat atau trombositopenia dengan aktifitastrombopoiesis normal atau rendah sebesar 7.65% dengan sensitivitas 91% danspesifisitas 92%.Kesimpulan : Kami menyimpulkan bahwa IPF dapat dijadikan salah satupenanda aktivitas trombopoiesis pada pasien trombositopenia sehingga dapatmembedakan penyebab trombositopenia karena gangguan produksi trombosit disumsum tulang atau gangguan destruksi perifer.

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ABSTRACTBackground: It is difficult to identify the etiology of thrombocytopenia due to itsvarious types. A simple, fast and easy diagnostic test is not available yet toidentify thrombopoiesis activity. Immature Platelet Fraction is anevaluation/assessment of immature platelet, which represents the state ofthrombopoiesis. It is expected that the immature platelet measurement will be ableto distinguish the etiology of current thrombocytopenic caused by defectmegakaryocytic production in the bone marrow or by the increased peripheralplatelet destruction, thereby avoiding the need for bone marrow aspirationexamination.Aims: The IPF examination is a marker of thrombopoiesis activity on patientswith thrombocytopenia. This study was performed to establish reference rangeof IPF on healthy adults in Jakarta and its cut-off values to distinguishthrombocytopenia caused by production disturbance or destruction by usingSysmex XE-5000 automated hematology analyzer.Method: Cross-sectional study in thrombocytopenic patients. We have analyzedIPF in 256 people who undergo medical check-up at MMC Hospital and 203thrombocytopenia patients from RSCM and MMC Hospital.Results: The reference range of adult IPF was 0.64-3.20%. The IPF cut-off todistinguish thrombocytopenia caused by increasing thrombopoiesis activity orthrombocytopenia with normal or low thrombopoiesis activity was 7.65% and itssensitivity and specificity were 91% and 92% respectively.Conclusions: We conclude that IPF can be used as thrombopoiesis activitymarker in thrombocytopenic patients; hence, it can distinguish the cause ofthrombocytopenia caused by platelet production disorder in the bone marrow orperipheral destruction."

"PendahuluanKarsinoma nasofaring (KNF) merupakan jenis keganasan yang unik dengan distribusi geografis dan etnis tertentu. Daerah Cina Selatan dan Asia Tenggara memiliki insidens kejadian yang tinggi. Indonesia memiliki insidens 5,66 kasus per 100.000 penduduk per tahun. Salah satu penyebab kematian pasien dengan keganasan adalah trombosis. Kadar soluble Platelet-selectin (sP-selectin) yang tinggi dalam plasma, hasil dari aktivasi sel-sel endotel dan trombosit, adalah prediktor kejadian trombosis.TujuanMengetahui kadar sP-selectin pada berbagai stadium karsinoma nasofaring dan korelasinya dengan hitung trombosit.MetodeDilakukan studi potong lintang pada 60 kasus karsinoma nasofaring yang baru terdiagnosis di Rumah Sakit Cipto Mangunkusumo pada periode Maret hingga November 2012. Kadar sP-selectin diukur dengan teknik Enzyme Linked Immunosorbent Assay.HasilRerata usia adalah 43,9 tahun dengan rasio laki-laki terhadap perempuan 3:1. Jenis patologi terbanyak adalah karsinoma tidak berdiferensiasi (83,3%). Sepuluh persen pasien mengalami trombositosis. Median kadar sP-selectin adalah 45,73 ng/mL dengan rentang interkuartil: 42,02-57,66 ng/mL. Secara statistik terdapat perbedaan kadar sP-selectin diantara stadium IVC dengan stadium lainnya (stadium IVB, p = 0,001 dan kelompok stadium I-IVA, p < 0,001). Hitung trombosit tidak berkorelasi dengan sP-selectin (r: 0,185; p = 0,158).SimpulanTerdapat perbedaan kadar sP-selectin pada berbagai stadium karsinoma nasofaring. Hitung trombosit tidak berkorelasi dengan kadar sP-selectin.

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Background

Nasopharyngeal carcinoma (NPC) is an unique malignancy because of its geographical and ethnic patterns. South China and South East Asia have the highest incidence, while in Indonesia is about 5.66 cases per 100,000 populations per year. Thrombosis is one of the complications of malignancy. High plasma levels of soluble Platelet-Selectin (sP-selectin) produced by activated endothelial cells and platelets, are predictive of thrombosis.

Objective

To measure sP-selectin levels in various stages of nasopharyngeal carcinoma and its correlation with platelet count.

Methods

This was a cross sectional study including 60 patients with newly diagnosed nasopharyngeal carcinoma at Cipto Mangunkusumo Hospital, Jakarta, Indonesia in period of April to November 2012. Soluble P-selectin levels in various stages of NPC measured with Enzyme Linked Immunosorbent Assay was compared and correlated with platelets count.

Results

From 60 patients of NPC, the mean age was 43.9 years with ratio of men to women was 3:1. The most prevalence histopathology was undifferentiated carcinoma (83.3%). Ten percent of the patients had thrombocytosis. The median level of sP-selectin was 45.73 ng/mL (inter quartile range: 42.02-57.66). Soluble P-selectin levels were statistically significantly higher among patients with stage IVC than other stages (with stage IVB, p = 0.001 and with group of stage I-IVA, p < 0.001). There was no correlation between platelet count and sP-selectin levels (r = 0.185; p = 0.158).

Conclusion

There were different levels of sP-selectin between various stages of nasopharyngeal carcinoma. There was no correlation between platelets count and sP-selectin levels."

"Latar belakang. Transfusi trombosit ditujukan untuk mencegah dan mengatasi perdarahan pada pasien trombositopenia. Trombosit dapat mengalami aktivasi walaupun tidak terjadi perdarahan sehingga dapat menimbulkan suatu keadaan yang disebut hiperagregasi seperti pada trombosit dari seseorang dengan hiperlipidemia. AABB menganjurkan untuk membuang semua produk darah yang berasal dari donor dengan plasma yang lipemia. Penelitian ini bertujuan untuk mengetahui pengaruh status lipid donor trombosit aferesis terhadap fungsi trombosit dan kadar malondialdehid selama penyimpanan. Metodologi. Penelitian ini menggunakan desain deskriptif analitik pada 31 sediaan trombosit aferesis yang berasal dari donor trombosit aferesis yang memenuhi kriteria inklusi dan eksklusi. Sediaan trombosit aferesis dibagi menjadi dua grup, yaitu grup hiperlipidemia dan normolipidemia. Dilakukan pengujian terhadap kandungan trombosit, fungsi agregasi dan kadar MDA pada hari pertama, kedua dan keempat penyimpanan. Hasil. Terjadi peningkatan kandungan trombosit selama penyimpanan pada kedua grup, yang berhubungan dengan proses apoptosis. Pada hari keempat terjadi kenaikan kandungan trombosit yang lebih banyak pada grup hiperlipidemia. Pada hari kedua didapatkan perbedaan yang bermakna pada agregasi trombosit dengan agonis ADP 2 μM. Pada hari keempat didapatkan perbedaan kadar MDA yang bermakna. Didapatkan korelasi yang positif dan bermakna antara kolesterol total, LDL dan trigliserida terhadap kadar MDA. Tidak didapatkan korelasi yang bermakna antara kolesterol total, trigliserida dan kadar MDA terhadap agregasi trombosit. Simpulan. Status lipid donor meningkatkan terjadinya apoptosis trombosit aferesis, lebih sensitif terhadap agonis ADP dan peningkatan kadar MDA. Perlunya mengingatkan donor trombosit aferesis untuk diet rendah lemak sebelum proses aferesis dilaksanakan. Perlunya penelitian lebih lanjut untuk menentukan kadar lipid yang masih dapat ditoleransi.

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Background. Platelet transfusions is intended to prevent and resolve bleeding in patients with thrombocytopenia. Platelet activation may have occured although there were no bleeding that can lead to a condition called hyperaggregation as in someone with hyperlipidemia. AABB recommends to dispose of all products from donors with plasma lipemia. This study aimed to determine the effect of lipid status of the donor platelet apheresis to platelet function and levels of malondialdehyde with in storage.

Methodology. This study used descriptive analytic design in 31 platelet apheresis concentrates. Samples were divided into two groups, hyperlipidemia and normolipidemia. The assay for the content of platelets, aggregation functions and levels of MDA was tested on the first day, second and fourth of platelet storage.

Results. An increase in the content of platelets during storage in both groups, which are associated with the process of apoptosis. On the fourth day there was higher of contents platelets in hyperlipidemic grup than normolipidemic grup. There were significant difference in platelet aggregation with ADP 2 μM at second day and levels of MDA at fourth day. There were positive and significant correlations between total cholesterol, LDL and triglyceride to the levels of MDA. There were no significant correlation between total cholesterol, triglycerides and MDA levels to platelet aggregation.

Conclusion. Improved of the lipid status of the donor platelet apheresis will increase platelet apoptosis, more sensitive to agonist ADP and increase MDA levels. The need to remind donors platelet apheresis to a low fat dietary before apheresis process implemented. Need for further research to determine the lipid levels that can still be tolerated."

"Latar belakang: Morbiditas akibat duktus arteriosus paten (DAP) pada neonatus cukup bulan (NCB) cukup tinggi. Peran prostaglandin E2 (PGE2), trombosit (immature platelet fraction, IPF), dan vascular endothelial growth factor (VEGF) pada penutupan DA secara fungsional dan anatomis pada NCB belum banyak diteliti. Patofisiologi terjadinya DAP dapat memengaruhi tata laksana farmakologi dini yang belum terstandardisasi pada NCB. Penggunaan obat antiinflamasi nonsteroid seperti ibuprofen dimungkinkan dapat menghambat jalur sintesis prostaglandin dengan efek samping minimal.Tujuan: Mengkaji peran prostaglandin E2, VEGF, IPF, dan efek pemberian ibuprofen oral dalam proses penutupan DA pada NCB.Metode: Penelitian dilakukan di rumah sakit (RS) Sanglah Denpasar, RS Prima Medika Denpasar, dan RS Umum Daerah Wangaya Denpasar, dalam periode Maret sampai Agustus 2015. Penelitian terdiri dari 2 desain, pertama desain potong lintang pada pasien dengan DAP dan tanpa DAP secara consecutive sampling dan desain kedua uji klinis acak terkontrol ganda pada pasien DAP usia ≥ 48 jam. Pasien dengan DAP kemudian dimasukkan dalam uji klinis, dilakukan randomisasi untuk diberikan perlakuan ibuprofen oral dosis hari pertama 10 mg/kg, hari kedua dan ketiga 5 mg/kg atau plasebo. Pemantauan hemodinamik dan efek samping obat dilakukan selama pemberian perlakuan. Pemeriksaan ekokardiografi, PGE2, VEGF, IPF, dan kreatinin dilakukan pada hari pertama dan keempat pascapemberian perlakuan.Hasil: Terdapat 64 subjek yang diteliti pada desain pertama dan 32 subjek pada desain kedua. Rerata kadar PGE2 lebih tinggi pada kelompok dengan DAP dibanding tanpa DAP, sedangkan rerata kadar VEGF dan IPF tidak berbeda. Ibuprofen oral tidak terbukti menurunkan diameter DA pascaperlakuan, tidak terdapat perbedaan rerata diameter pada kedua kelompok. Terdapat hubungan positif sedang terhadap perubahan kadar PGE2 dengan perubahan diameter DAP pascaperlakuan. Tidak terdapat perubahan hemodinamik atau efek samping akibat pemberian ibuprofen oral atau plasebo pada NCB dengan DAP.Simpulan: Tingginya kadar PGE2 terbukti berperan dalam patensi DA pada NCB. Ibuprofen oral dosis 10 - 5 - 5 mg/kgBB tidak mengecilkan diameter DAP.

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Background: Serious morbidity impact due to patent ductus arteriosus (PDA) in full-term neonates remains high. The functional role of prostaglandin E2 (PGE2), platelet (immature platelet fraction, IPF), and vascular endothelial growth factor (VEGF) has not been studied in the closure mechanism of ductus arteriosus (DA). Understanding of pathophysiology of PDA may influence early pharmacological treatments, which have not been standardized in full-term neonates. The use of non-steroidal anti-inflammatory drugs such as ibuprofen can be beneficial as a pharmacological agent in enhancing the closure of PDA with minimal adverse effects.

Objectives: To evaluate the role of prostaglandin E2, VEGF, IPF, and the effect of oral ibuprofen in the process of DA closure in full-term neonates.

Methods: This study was conducted in Sanglah General Hospital, Prima Medika Hospital, and Wangaya Hospital Denpasar. The study consisted of two designs, the first was cross-sectional design in subjects with and without PDA using consecutive sampling and the second was double blind randomized controlled trial in full-term infant aged ≥ 48 hours. Subjects with PDA were randomized to oral ibuprofen and placebo administration, in which ibuprofen was given consecutively 10 - 5 - 5 mg/kg. All subjects underwent echocardiography, PGE2, VEGF, and IPF assays. Hemodynamics monitoring was evaluated during trial and adverse effect due to ibuprofen was recorded by measuring urine volume and plasma creatinine level.

Results: From March to August 2015, there were 64 subjects recruited for the first design and 32 subjects in the second design. The mean level of PGE2 was higher significantly in the group with PDA than non PDA group, while the mean levels of VEGF and IPF showed no difference. In the second design, oral ibuprofen showed no effect in reducing DA diameter after treatment. There were no differences in mean diameter of DA in both groups before and after treatments. There was moderate positive relationship between levels of PGE2 and the change of PDA diameter. There were neither hemodynamic changes nor adverse effect due to the administration of oral ibuprofen or placebo.

Conclusions: A high level of PGE2 appears to play a pivotal role in DA patency of full-term neonates. Administration of oral ibuprofen in 10 - 5 - 5 mg/kg schedule could not induce PDA closure in full-term neonates."

"Trombositopenia merupakan manifestasi hematologis pada pasien lupus eritematosus sistemik (LES) yang berhubungan dengan prognosis buruk. Kadar C3, C4, dan anti-dsDNA berhubungan dengan aktivitas penyakit pada pasien LES. Peningkatan aktivitas penyakit berhubungan dengan penurunan kadar trombosit pada pasien LES melalui aktivasi komplemen dan interaksi autoantibodi dengan trombosit. Tujuan dari penelitian ini adalah mengetahui korelasi kadar serum C3, C4, dan anti-dsDNA terhadap hitung trombosit pada pasien LES dengan trombositopenia. Penelitian ini merupakan penelitian analitik observasional dengan menggunakan desain studi potong lintang. Penelitian ini merekrut subjek LES dengan hitung trombosit <150.000/µL. Kadar C3, C4, dan anti-dsDNA serta hitung trombosit diukur pada awal kunjungan pasien. Didapatkan 41 subjek LES dengan trombositopenia. Hitung trombosit memiliki korelasi yang bermakna terhadap kadar C3 (p=0.004; r=0.445) dan anti-dsDNA (p=0.001; r=-0.481). Namun, tidak ditemukan korelasi yang signifikan antara hitung trombosit dengan kadar C4 (p=0.052; r=0.306). Terdapat korelasi yang bermakna antara hitung trombosit dengan aktivitas penyakit dan kadar C3 serta anti-dsDNA pada subjek LES dengan trombositopenia. Namun, tidak terdapat korelasi yang bermakna antara hitung trombosit dengan kadar C4.

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Thrombocytopenia is a hematological manifestation in systemic lupus erythematosus (SLE) patients that is associated with a poor prognosis. C3, C4, and anti-dsDNA levels have been associated with disease activity in SLE patients. Increased disease activity is associated with decreased platelet levels in SLE patients through complement activation and autoantibody interactions with platelets. The aim of this study was to determine the correlation of serum levels of C3, C4, and anti-dsDNA with platelet counts in SLE patients with thrombocytopenia. This research is an observational analytical study using a cross-sectional study design. This study recruited subjects of SLE patients with platelet counts <150,000/µL. C3, C4, and anti-dsDNA levels and platelet counts were measured at the initial patient visit. This study recruit 41 samples of SLE patients with thrombocytopenia. Platelet count had a significant correlation with C3 levels (p=0.004; r=0.445) and anti-dsDNA (p=0.001; r=-0.481). However, no significant correlation was found between platelet count and C4 levels (p=0.052; r=0.306). There is  a significant correlation between platelet count and disease activity and C3 and anti-dsDNA levels in SLE patients with thrombocytopenia. However, there was no significant correlation between platelet count and C4 levels."

"ABSTRAKRuang Lingkup dan Cara Penelitian: Kemampuan asam asetilsalisilat (ASA) dalam menghambat agregasi trombosit, sering dikaitkan dengan pencegahan infark jantung. Dewasa ini, dalam upaya menurunkan resiko terjadinya infark jantung, ada kecenderungan menggunakan ASA dengan dosis makin kecil. Sehubungan dengan itu, dilakukan penelitian yang bertujuan untuk mengetahui berapa lama, dan apakah ada perbedaan yang bermakna antara intensitas antitrombotik beberapa tingkat dosis ASA (50 mg, 100 mg, 200 mg, dan 300 mg). Kemampuan agregasi trombosit diukur dengan metode baru yang berdasarkan intensitas transmisi cahaya. Hasil pemeriksaan tercermin sebagai suatu kurva agregasi trombosit. Disain yang dipakai adalah rancangan pola silang, dengan 11 orang sukarelawan sehat yang setelah diacak, masing-masing mendapat 4 tingkat dosis ASA dengan selang waktu 2 minggu. Bahan pemeriksaan terdiri dari 'platelet rich plasma', 'platelet poor plasma' dan adenosin difosfat yang berkadar akhir 10 uM, sebagai agregator. Parameter hambatan agregasi trombosit adalah berkurangnya nilai agregasi maksimal dan atau meningkatnya reversibilitas kurva agregasi trombosit, disbanding nilai sebelum mendapat ASA. Data dianalisis dengan ANOVA dua arah dan 'Planned comparison'. Untuk data dengan distribusi tidak normal, dipakai tes non parametrik (tes Friedman).Hasil dan Kesimpulan: Bila berdasarkan adanya salah satu parameter hambatan agregasi trombosit, maka ASA 50 mg, 100 mg, dan 200 mg per oral dapat menghambat agregasi trombosit selama 4 hari, sedangkan ASA 300 mg selama 5 hari (p > 0,01). Namun bila berdasarkan adanya kedua parameter hambatan agregasi trombosit, maka ASA 50 mg dapat menghambat agregasi trombosit pada 3 jam sesudah pemberian obat, sedangkan ASA 100 mg dan 200 mg, sampai 4 hari sesudah pemberian ASA. Intensitas antitrombotik ke empat dosis ASA, pada hari yang sama setelah makan obat, tidak menunjukkan perbedaan yang bermakna (p}0,07). Untuk menyatakan hambatan agregasi trombosit, kriteria peningkatan reversibilitas kurva agregasi lebih peka di-banding kriteria pengurangan nilai agregasi maksimal.

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ABSTRACT

Scope and Method of Study: The ability of acetylsalicylic acid (ASA) to inhibit the platelet aggregation is related with its use to the prevention myocardial infarction. Currently there is a trend to use small doses of ASA for this purpose. In this context, the present trial was conducted to find out how long the antithrombotic effect persist after small oral doses of ASA, and also to observe whether in the same days different small doses of ASA exert significant difference in their anti-thrombotic intensity. The antithrombotic effect of ASA was measured according to the method described by Born which was based on light transmission. The results were recorded as platelet aggregation curve. Eleven healthy volunteers participated in this trial after giving their' informed consents. Each subject received single doses (i.e. 50, 100, 200 and 300 mg) of ASA in a randomized and cross-over design. Wash out period between doses was 2 weeks. Materials being tested included platelet rich plasma, platelet poor plasma and adenosine diphosphate (aggregating agent) with final concentration of 10 uM. Inhibition of platelet aggregation by ASA was evaluated using two parameters, i.e. decrease of maximal aggregation and/or increase of aggregation curve's reversibility (compared to their pre-ASA values). Data was analysed with two way ANOVA and planned comparison test. Friedman test was used for non-Gaussian data.

Results and conclusions: If criterion of platelet aggregation inhibition is based on one of the two criteria mention above, ASA 50, 100, and 200 mg inhibited platelet aggregation for four days; meanwhile the 300 mg dose did it for five days (p < 0,01). If criterion of platelet aggregation inhibition is based on both of the above mentioned criteria, however, ASA 50 mg inhibited plate-let aggregation at 3 hours after dosing; meanwhile the 100 and 200 mg doses did it for four days. There is no significant difference in antithrombotic intensity between the four doses in the same days after drug administrations (p > 0,01). In addition, reversibility of platelet aggregation curve is a more sensitive parameter than maximal aggregation for measuring platelet aggregation."

"Latar Belakang COVID-19 ditetapkan sebagai pandemi sejak tahun 2020. Berbagai terapi telah dikembangkan akan tetapi terdapat laporan kejadian trombosis pasca COVID-19. Diduga salah satu mekanisme yang berperan adalah aktivasi trombosit oleh antibodi.Hal tersebut dikemukakan akibat adanya temuan manifestasi mirip Heparin-Inducued Thrombocytopenia (HIT) pada COVID-19. HIT terjadi akibat adanya antibodi antiPF4/heparin yang berikatan dengan reseptor FcIIR di trombosit. Terdapat banyak penanda aktivasi trombosit, salah satunya P-selektin.Tujuan. Mengetahui perbedaan rerata kadar antiPF4, P-selektin serum, serta agregasi trombosit antar derajat COVID-19.Metode. Penelitian ini menggunakan sampel penelitian sebelumnya Hubungan Kadar 25-Hydroxy Vitamin D dengan Luaran Pasien Terkonfirmasi COVID-19 di Rumah Sakit Cipto Mangunkusumo (RSCM) dan Rumah Sakit Wisma Atlit pada Oktober 2021 sampai Januari 2022. Sampel serum tersebut disimpan di lab RSCM Kencana dan dilakukan simple random sampling. Pemeriksaan kadar P-selektin dan antiPF4 dilakukan dengan metode ELISA di Lab Diagnos, sedangkan agregasi trombosit pasca paparan serum di Lab RSCM.Hasil. Dilakukan analisis pada 160 sampel. Berdasarkan severitas terdapat 21 orang termasuk COVID-19 berat/kritis dan sisanya ringan/sedang. Komorbiditas, penyakit jantung, ginjal kronik, DM tipe 2, dan serebrovaskular secara bermakna lebih banyak pada kelompok berat kritis. Kadar P-selektin secara bermakna lebih tinggi pada kelompok berat kritis (median 43791,79 vs. 39112,3 pg/ml). Selain itu juga didapatkan agregasi yang lebih tinggi pada kelompok berat-kritis dengan agonis ADP 10 dan 5 uM (median masing-masing 32,8 vs 13,8 dan 28,5 vs 11,1 persen). Tidak terdapat perbedaan bermakna antiPF4 antar derajat COVID-19.Kesimpulan. Terdapat perbedaan bermakna kadar P-selektin dan agregasi trombosit antar derajat COVID-19.

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Background. COVID-19 became pandemic since 2020. While its treatment was being developed there were reports of thromboses event after COVID-19. One mechanism suggested was platelet activation due to antibody because of observation similar manifestation with heparin-induced thrombocytopenia in COVID-19. Main culprit of HIT is antibody to PF4/heparin. Which bind FcIIR receptor in thrombocyte, leading to its activation. There are many markers of thrombocyte activation, one of them is P-selectin.

Objectives. Determine the mean difference of P selectin and antiPF4 levels in serum and thrombocyte aggregation between COVID-19 severity.

Methods. This study uses samples already taken before, in Association of 25-Hydroxy-Vitamin D Levels with Outcome of COVID-19 Patients research from October 2021 to January 2022. Serum was stored in -20 C degrees in RSCM Laboratory. We planned to

do a simple random sampling. P-selectin and antiPF4 measured with ELISA in Diagnos Laboratory. Thrombocyte aggregation was measured by Light Transmission Aggregometry in RSCM.

Results. A total of 160 subjects analyzed 21 of them had severe/critical COVID-19. Comorbidities, heart disease, diabetes type 2, cerebrovascular disease were significantly higher in severe/critical disease. The median of P-selectin is significantly higher in severe covid (43791,79 vs. 39112,3 pg/ml). As aggregometry we find significantly higher

aggregation in severe disease with 10 and 5 uM ADP agonist. There is no difference of antiPF4 levels between groups.

Conclusion. There is a significant difference in P-selectin level and maximal aggregation between severe and non-severe COVID-19."

"Latar Belakang: Respon antar-individu yang bervariasi terhadap obat antiplatelet (clopidogrel) telah dilaporkan. Perbedaan tingkat metabolisme clopidogrel untuk metabolit aktif tiol menggambarkan variabilitas antar-individu dalam penghambatan trombosit. Sitokrom P4502C19 (CYP2C19) memetabolisme zat metabolit aktif tiol. Carier polimorfisme yang menyebabkan hilangnya fungsi CYP2C19 * 2 dan * 3 alel pada terapi antiplatelet mengakibatkan berkurangnya penghambatan agregasi trombosit. Informasi mengenai hubungan antara CYP2C19 * 2 dan * 3 dengan inhibisi agregasi trombosit pada pasien Sindroma koroner akut di Indonesia masih terbatas. Tujuan dari penelitian ini adalah untuk mengetahui hubungan antara dua varian, CYP2C19 * 2 (6816>A) dan CYP2C19 * 3 (636G>A) terhadap penurunan fungsi inhibisi agregasi trombosit. Bahan dan Metode: Desain penelitian cross sectional. Jumlah responden adalah 114 orang (dipilih berdasarkan kriteria inklusi dan kriteria ekslusi). Pemeriksaan polimorfisme CYP2C19 dilakukan dengan menggunakan teknik Real Time-Polymerase Chain Reaction (RT-PCR) TaqMan SNP Genotyping Assays dengan alat dari applied Biosystems 7500 Fast/7900HT Fast Real Time PCR Systems (in standart or 9600 emulation mode). Inhibisi agregasi trombosit diperiksa dengan menggunakan metode Light Transmisi Aggregometry (LTA) dengan alat Helena AggGRAM Analyzer pada penambahan 5umol/L ADP sebagai agregator. Hasil: Distribusi inhibisi agregasi trombosit menunjukkan perbedaan rerata antara responden non carier polimorfisme dengan responden carier polimorfisme (16,9 CI95%: 12,1-21,6 vs 9,4 CI95%: 2,9 - 15,0). Analisis regresi linier menunjukkan bahwa responden carier polimorfisme memiliki inhibisi agregasi trombosit lebih rendah dibandingkan dengan responden non carier polimorfisme. Analisis regresi logistik menunjukkan bahwa responden carier polimorfisme mempunyai odds untuk merespon kurang baik terhadap clopidogrel sebesar 1,9 kali jika dibandingkan dengan responden yang non carier setelah dikontrol oleh variabel umur dan jenis kelamin, hal tersebut mengindikasikan bahwa carier polimorfisme mempunyai inhibisi yang rendah terhadap agregasi trombosit. Kesimpulan: Temuan kami membuktikan adanya hubungan antara CYP2C19 * 2 dan * 3 polimorfisme dengan inhibisi agregasi trombosit.

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Background: Inter-individual variability in response to antiplatelet drugs (clopidogrel) has been reported. The difference in the extent of metabolism of clopidogrel to its active metabolite tiol is the most plausible mechanism for the observed inter-individual variability in platelet inhibition. The cytochrome P4502C19 (CYP2C19) metabolizes the active metabolite tiol. The carrier polymorphisms of reduced - functions of CYP2C19*2 and *3 allele on antiplatelet therapy showed diminished platelet aggregation inhibition. There is limited information on the association between CYP2C19 *2 and *3 with platelet aggregation inhibition in ACS patients generally in Indonesia Population. The aim of this study was to determine the association between two variants, CYP2C19*2 (6816>A) and CYP2C19*3 (636G>A) reduced function with platelet aggregation inhibition.

Material & Method: a cross sectional study was done with 114 subjects (selected by inclusions and exclusions criteria). The CYP2C19 polymorphisms were genotype using the PCR method with TaqMan SNP Genotyping Assays from applied Bio systems 7500 Fast/7900HT Fast Real Time PCR Systems (in standard or 9600 emulation mode). The platelet aggregation inhibition was tested using Light Transmission Aggregometry (LTA) by Helena AggGRAM Analyzer with 5umol/L ADP as aggregator.

Results: The distribution of platelet inhibition aggregation showed difference between respondents with non-carrier polymorphisms and carrier polymorphisms (16,9 CI95%: 12,1 -21,6 vs 9,4 CI95%: 2,9 - 15,0). The linier regression analysist indicated that the carrier polymorphisms have lowest platelet aggregation inhibition compared with non-carrier polymorphisms. The logistic regression analysis indicated that carrier polymorphisms respondents has 1,9 odds to be low response to clopidogrel if compared with non-carrier polymorphisms respondents after adjusted with age and sex and it is indicated that it has low platelet aggregation inhibition.

Conclusion: Our present findings the evidence of an association between CYP2C19 *2 and *3 polymorphisms and platelet aggregation inhibition."