The Unmet Clinical Needs in Thrombosis Oral Fibrinolytic
R W M Kaligis, MD, SpJP (K), FIHA, FASCC, FICA
Terapi Komprehensif Trombosis
Fokus terapi:
1.
Hyper Coagulability : anti platelet, 2.
Hypofibrinolysis ?
anti koagulan
Hypofibrinolysis, a Risk Factor for Penurunan sistem fibrinolisis tubuh
1. Atherosclerosis (The ARIC Study Circulation 1995,91 .284-290)
2. Trombosis Arteri (Myocard infarct, Ischemic Stroke, PAD) dan Trombosis Vena (DVT) (2009 British Journal of Haematology, 145, 115–120, Ton Lisman et al. BLOOD, 1 FEBRUARY 2005)
Hypofibrinolysis berperan sejak awal proses atherosclerosis sampai dengan saat terjadinya serangan
Alternatip terapi hypofibrinolysis :
PARENTERAL Fibrinolytic • •
Streptokinase Recombinant Tissue Plasminogen Activator (alteplase, reteplase, tenecteplase)
atau
ORAL Fibrinolytic
Unmet Clinical Needs in Thrombosis 1
Parenteral anticoagulants to replace heparin as ajunct to a) Thrombolytic therapy b) Glycoprotein IIb/IIIa antagonists in acute coronary syndrome
2
Oral anticoagulants to replace coumarin
3
Oral antiplatelets drugs for combined use with aspirin
4
Oral compounds to enhance fibrinolysis ( oral fibrinolytic )
5
Agents that modulate angiogenesis
6
Drugs to modulate restenosis after angioplasty Seminars in HEMATOLOGY Vol 38, No 2, Suppl 5, April 2001.
fibrinolitik/thrombolytic parenteral (streptokinase, urokinase, rtpA): efek samping: alergi & perdarahan, tidak dipakai jangka panjang mengatasi Hypofibrinolysis untuk pencegahan
unmet clinical need in thrombosis Oral Compound To Enhance Fibrinolysis (Seminar in Haematology April 2001)
Oral Fibrinolytic atasi hypofibrinolysis untuk pencegahan
sejak 2003 sudah tersedia di Indonesia, penelitian dan keberhasilan Tromboles pada penggunaan klinik di Indonesia, sudah dilaporkan didalam berbagai forum ilmiah sejak 2005
Thrombosis adalah terbentuknya bekuan darah patologik (thrombus) didalam pembuluh darah, yang menutup aliran darah melalui sistem sirkulasi.
THROMBOSIS akibat retak/pecah nya atherosclerotic plaque rapuh
Gambar Mikroskopik: Trombus atau Emboli Bagian tampak seperti serabut jala disebut Cross-Linked Fibrin, didalamnya terdapat keping darah merah (platelet, trombosit) dan sel darah merah (eritrosit). Cross-Linked Fibrin ini merupakan serabut alamiah yang paling elastik, lebih elastik dari sarang laba-laba, dapat ditarik hingga 2,8 kali panjangnya tidak putus, hanya akan diputus bila ditarik hingga 4,3 kali panjangnya (Wake Forest University) Sistem tubuh yang menghancurkan Cross-Linked Fibrin, trombus atau emboli disebut sistem fibrinolisis, tetapi menurut British Journal of Haematology 2009, bahwa kondisi sistem fibrinolisis penderita berada dalam keadaan Hypofibrinolysis.
Trombus/Emboli , pencetus serangan
Berbagai manifestasi klinik, tergantung lokasi pembuluh darah yang tersumbat
Dalam kondisi patologik tertentu walaupun pembuluh darah tidak terluka, bekuan darah patologik (thrombus) dapat terbentuk di lumen pembuluh darah → penyumbatan → dapat berakibat fatal.
Thromboembolism adalah kombinasi thrombosis dan komplikasi utamanya embolism (terlepasnya thrombus menjadi embolus) yang mengikuti aliran darah dan dapat mengakibatkan penyumbatan di tempat lain. Contoh Kasus: ● Thrombosis arteri koroner di jantung → Serangan Jantung (miokard infark). ● Thrombosis arteri karotis di leher yang terlepas menjadi embolus → penyumbatan arteri otak → Stroke ● Thrombosis Vena Dalam (Deep Venous Thrombosis, DVT) di betis yang terlepas menjadi embolus → Emboli Paru (Pulmonary Embolism, PE)
THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE Volume 15, Number 5, 2009, pp. 539-544 © Mary Ann Liebert, Inc. DOI: 10.1089/acm.2008.0506
Improved Myocardial Perfusion in Stable Angina Pectoris by Oral Lumbrokinase (TROMBOLES): A Pilot Study
Manoefris Kasim, M.D.,1 Andrew Alexander Kiat, 2 Mohammad Saifur Rohman, M.D., Ph.D.,1 Yasmina Hanifah, M.D.,1 and Hosen Kiat, M.B.B.S., F.A.C.C., F.A.C.P., F.C.C.P., F.R.A.C.P.3
Methods
10 stable angina pectoris patients were randomly selected from proved CAD population in national cardiovascular center Harapan Kita. Diagnosis of CAD determined by typical chest pain symptom and confirmed by MSCT or coronary angiography examination.
Methods
They were given additional 2 capsules of Tromboles (containing 250 mg lumbrokinase for each capsul) three times daily for 30 days to a standard therapy including nitrate, ß blocker, statin and aspirin. Perfusion imaging 99mTc-Sestimibi was used to evaluate the perfusion and viability of myocardium before and after treatment using DSX rectangular gamma Sophy camera.
Methods The improvement was assessed by semi quantitative myocardial perfusion SPECT 20 segment scoring system.
Figure 2. A case example of a patient's stress myocardial perfusion before and at the end of 30 day treatment with Lumbrokinase. Corresponding representative apical (a), mid (b) and basal (c) short axis, and mid vertical long axis (d) tomographic perfusion images demonstrating significant reduction ion the extent and degree of inducible ischemia in the anterior (arrows) and lateral (arrow heads) left ventricular wall.
Penderita angina pektoris diberikan tambahan Tromboles sehari 3 kali 2 kapsul, setelah penggunaan selama 30 hari, dievaluasi dengan Tc-Sestamibi didapati bahwa 70% dari penderita yang mengkonsumsi Tromboles perfusi myocard membaik bermakna vs kelompok tanpa Tromboles, dan rasa nyeri dada menghilang (p<0.001), tanpa efek samping.
One month treatment of oral Tromboles (lumbrokinase) resulted in an improvement myocardial perfusion in stable angina pectoris with metabolic syndrome without bleeding complication
Tromboles pada kasus Stroke Iskemik (Ischmic Stroke with Right ICA Occlusion) Dr.RWM Kaligis SpJP. KKV
diberikan tambahan: Tromboles sehari 3 kali 2 kapsul selama 2(dua) bulan, trombus berhasil dilarutkan, Internal Carotid Artery terbuka kembali (rekanalisasi)
sebelum pemakaian Tromboles
sesudah pemakaian Tromboles
nges in Detection of Pulmonary Embolism Challenges in Detection of Pulmonary Emboli uccessful Treatment with Lumbrokinase and Successful Treatment with Lumbrokinas an Oral Thrombolytic Agent an Oral Thrombolytic Agent Manoefris Kasim, Hartono B, Ariwibowo D, Harimurti Manoefris GM Kasim, Hartono B, Ariwibowo D, Harimurti GM
Department of Cardiology and Vascular Medicine Department of Cardiology and Vascular Medicine ersity of Indonesia, National Cardiovascular Centre, Harapan Kita Hospital University of Indonesia, National Cardiovascular Centre, Harapan Kita Hospital
Medical Management of Acute Limb Ischemia The Role of Lumbrokinase (Tromboles)
Manoefris Kasim, I Made Junior Rina Artha, Syarief Hidayat, Beny Hartono, Ganesja M. Harimurti Department of Cardiology and Vascular Medicine Faculty of Medicine, University of Indonesia/National Cardiovascular Center Harapan Kita Jakarta
Diagnosis • 60 yrs man
• Stage IIB Acute Limb Ischemia • • • •
Atrial fibrilation with normoventricular response Moderate mitral stenosis Type-2 DM Stage-1 hypertension
Treatment • Surgical Procedures (Surgical Thrombectomy) Refused
• Tromboles (Lumbrokinase), 3 x 3 kalsul • • • • •
Cilostazol, 2 x 100mg Digoxin, 1 x 0,25mg ISDN, 3 x 10mg Metformin, 2 x 500mg Irbesartan, 1 x 100mg
Day-4
Pain and numbness of both legs disappear Patient only felt stiffness on dorsum pedis and toes Physical examination: weak pulsation of tibialis anterior and dorsalis pedis arteries
Day-15
CT angiography: better contrast flow on bothn legs After 2 weeks of treatment with Lumbrokinase discharged with good conditions
Day-50
CT angiography: normal contrast flow on both legs trombus dihancurkan, semua bagian pembuluh darah arteri yang tersumbat terbuka kembali (rekanalisasi total)
Resolusi Trombosis Vena Dalam dengan Lumbrokinase (Tromboles) Manoefris Kasim MD, Syarief Hidayat MD, Ismoyo Sunu, Departemen Kardiologi dan Kedokteran Vaskuler, Fakultas Kedokteran, Universitas Indonesia, Pusat Jantung Nasional Harapan Kita Jakarta.
Penderita dengan keluhan bengkak pada tungkai disertai nyeri, kemerahan, teraba hangat disertai gambaran dilatasi vena (Homans sign positif), pemeriksaan duplex sonografi tungkai dipastikan menderita Deep Vein Thrombosis (DVT) partial vena femoralis kiri, Deep Vein Thrombosis (DVT) total pada vena Poplitea, vena Tibialis posterior kiri dan terlihat trombus menempel pada pangkal katup vena Poplitea kanan.
Trombosis Vena Dalam (DVT)
Trombosis Vena Dalam (DVT)
Penderita diberikan tambahan Tromboles sehari 3 kali 2 kapsul, setelah satu minggu penggunaan keluhan bengkak dan nyeri sudah jauh berkurang, evaluasi duplex sonografi tungkai dilakukan setelah satu bulan penggunaan Tromboles, sebagian trombus di vena-vena sudah terlarut.
Conclusion • Tromboles (lumbrokinase) could be considered as an alternative medical treatment for acute limb ischemia, especially in patient who refused surgical treatment. • The role of Tromboles (lumbrokinase) as a treatment option of acute limb ischemia need further evaluation on large, well design, study.
nges in Detection of Pulmonary Embolism Challenges in Detection of Pulmonary Emboli uccessful Treatment with Lumbrokinase and Successful Treatment with Lumbrokinas an Oral Thrombolytic Agent an Oral Thrombolytic Agent Manoefris Kasim, Hartono B, Ariwibowo D, Harimurti Manoefris GM Kasim, Hartono B, Ariwibowo D, Harimurti GM
Department of Cardiology and Vascular Medicine Department of Cardiology and Vascular Medicine ersity of Indonesia, National Cardiovascular Centre, Harapan Kita Hospital University of Indonesia, National Cardiovascular Centre, Harapan Kita Hospital
Challenges in Detection of Pulmonary Embolism and Successful Treatment with Lumbrokinase an Oral Thrombolytic Agent Manoefris Kasim, Hartono B, Ariwibowo D, Harimurti GM Department of Cardiology and Vascular Medicine University of Indonesia, National Cardiovascular Centre, Harapan Kita Hospital
Case-1 • • • • • • • •
69 yrs old man Escalating shortness of breath since 10 days ago Clinical Prediction Probability (Well’s Score): low ECG: tachycardia, S1Q3T3, incomplete RBBB with T inverted from V1-4 Chest X-ray : within normal Echocardiography: RVdilatation with hypokinetic of apical free wall (Mc Connel Sign) predicted sign for PE D-dimer assay test: High (2100) Lung Perfusion Scanning: Consistent with the Dx of PE
Treatment •
TROMBOLES (Lumbrokinase), 3 X 3 kapsul
•
Aspilet, 1 X 80mg
After 10 days of Treatment Improvement • • •
Clinically (short of breath) Laboratory (D-dimer decrease) Lung Perfusion Scan
day 30
day 10
day 0
Conclusion • Diagnosis of pulmonary embolism is somewhat challenging. • Treatment with TROMBOLES (Lumbrokinase) showed a satisfaction result.
Kesimpulan 1)
PENYAKIT TROMBOSIS (MI, IS, PAD, DVT, PE, dll) penyebab morbiditas dan mortalitas utama
2) HYPOFIBRINOLYSIS berperan penting dalam patogenesis peny trombosis, bahkan sejak awal proses atherogenesis 3) Oral Fibrinolytic mengatasi Hypofibrinolysis
1) TROMBOLES , Natural Oral Fibrinolytis, Plus (+) AntiPlatelet, Anti-Koagulan.
