<p>Uvod Napredak hirur&scaron;kih i anesteziolo&scaron;kih tehnika učinio je hirur&scaron;ku intervenciju ugradnje totalne proteze kolena uspe&scaron;nom i bezbednom. Međutim, po&scaron;to spada u opsežne ortopedske intervencije, praćena je značajnim gubicima krvnog volumena, kao i značajnom potro&scaron;njom krvi i krvnih derivata. Trendovi u savremenoj medicini idu u pravcu restrikcije upotrebe krvi i krvnih derivata i čine se veliki napori u istraživanju i razvijanju metoda i tehnika koje mogu biti alternative alogenoj transfuziji krvi. Traneksamična kiselina koja ima antifibrinolitičko dejstvo, može dovesti do značajnog smanjenja perioperativnog krvarenja. Ciljevi istraživanja su bili utvrđivanje uticaja traneksamične kiseline na perioperativno krvarenje kod operacija ugradnje totalne proteze kolena, kao i utvrđivanje postojanja uticaja traneksamične kiseline na perioperativnu upotrebu alogene krvi kod operaacija ugradnje totalne proteze kolena. Matrijal i metode u studiju je bilo uključeno 96 bolesnika oba pola, starijih od 18 godina, kojima je bila ugrađivana primarna elektivna totalna proteza kolena. Oni su bili podeljeni u dve grupe, 48 u ispitivanoj grupi kod kojih je primenjivana traneksamična kiselina i 48 bolesnika koji su bili kontrolna grupa. Svi bolesnici su bili u spinalnoj anesteziji i primenjivana je pneumatska poveska na ekstremitetu koji se operisao. Ispitivana grupa je dobijala traneksamičnu kiselinu u dva navrata u dozi od 15 mg /kg i 10 mg/kg u vidu kontinuirane i.v. infuzije u trajanju od 15 minuta. Prvo davanje leka je bilo neposredno nakon uvoda u anesteziju. Drugo davanje leka je bilo 15 minuta pre otpu&scaron;tanja pneumatske poveske. Kontrolna grupa je dobijala istu količinu 0.9% fiziolo&scaron;kog rastvora koji je primenjivan na isti način. Intraoperativni gubitak krvi je beležen i meren kao gubitak u aspiratoru i gubitak na gazama. Postoperativn gubitak krvi se merio nakon 6, 12 sati i nakon 24 sata, kao gubitak na drenove Beležio se i broj primenjenih jedinica krvi i broj ukupno dobijenih mililitara krvi i ostalih krvnih produkata, kao i vreme njihove primene. Rezultati Postoji statistički značajna razlika u prosečnom intraoperativnom krvarenju između grupa (Z = -7,281; p = 000). Prosečno intraoperativno krvarenje u ispitivanoj grupi je bilo 100 &plusmn; 92,690 ml, a u kontrolnoj 447 &plusmn; 299,282 ml. U kontrolnoj grupi bolesnici imaju statistički značajno veće ukupno postoperativno krvarenje od bolesnika iz ispitivane grupe (T test, t=4,024, p&lt;0,01) ( ispitivana grupa 309,78&plusmn; 143,612 ml, kontrolna grupa 455,42 &plusmn; 201,177 ml). Razlika je bila statistički značajna nakon 6 sati (p &lt; 001) i nakon 12 sati u korist ispitivane grupe (p&lt;0,05). Postji statistički značajna razlika u ukupnom perioperativnom krvarenju među grupama i traneksamična kiselina je statistički značajno (p&lt;0,000) smanjila ukupno krvarenje од 919,36 ml (95%IP 822,083-1016,640) na 405, 32 ml (95% IP 353, 407-457, 231). Ukupno perioperativno krvarenje je u proseku iznosilo 662, 34 ml i kretalo se u intervalu od 100 do 1700 ml. U ispitivanoj grupi je samo 5 (10,4%) ispitanika primilo transfuziju, dok je u kontrolnoj grupi 39 (81,3%), &scaron;to je statistički značajna razlika (2=45,692; p=0,000). Prosečna količina date alogene krvi u ispitivanoj grupi je 33,33 &plusmn; 99,2 ml, dok je prosečna količina date alogene krvi u kontrolnoj grupi bila skoro deset puta veća i iznosila je 319,2 &plusmn; 230 ml, &scaron;to je statistički značajno veće (Z = -6,625; p = 000). Postoperativne vrednosti hemoglobina, hematokrita i trombocita bile su statistički značajno veće u isptivanoj grupi. Bolesnici iz ispitivane grupe su statistički značajno ranije postoperativno uzimali prvi obrok, sedeli i ustajali od bolesnika u kontrolnoj grupi. Zaključci Iz dobijenih rezultata o intraoperativnom, postoperativnom i ukupnom perioperativnom krvarenju može se zaključiti da je traneksamična kiselina veoma efikasan lek i da statistički značajno smanjuje krvarenje vezano za ugradnju totalne proteze kolena i da smanjuje upotrebu transfuzije alogene krvi za 66,7%. Traneksamična kiselina je uticajem na smanjenje perioperativnog krvarenja dovela do očuvanja vrednosti hemoglobina, hematokrita i trombocita. Bolesnici koji su dobijali traneksamičnu kiselinu su takođe imali brži i kvalitetniji neposredni postoperativni oporavak.</p> / <p>Uvod Napredak hirur&scaron;kih i anesteziolo&scaron;kih tehnika učinio je hirur&scaron;ku intervenciju ugradnje totalne proteze kolena uspe&scaron;nom i bezbednom. Međutim, po&scaron;to spada u opsežne ortopedske intervencije, praćena je značajnim gubicima krvnog volumena, kao i značajnom potro&scaron;njom krvi i krvnih derivata. Trendovi u savremenoj medicini idu u pravcu restrikcije upotrebe krvi i krvnih derivata i čine se veliki napori u istraživanju i razvijanju metoda i tehnika koje mogu biti alternative alogenoj transfuziji krvi. Traneksamična kiselina koja ima antifibrinolitičko dejstvo, može dovesti do značajnog smanjenja perioperativnog krvarenja. Ciljevi istraživanja su bili utvrđivanje uticaja traneksamične kiseline na perioperativno krvarenje kod operacija ugradnje totalne proteze kolena, kao i utvrđivanje postojanja uticaja traneksamične kiseline na perioperativnu upotrebu alogene krvi kod operaacija ugradnje totalne proteze kolena. Matrijal i metode u studiju je bilo uključeno 96 bolesnika oba pola, starijih od 18 godina, kojima je bila ugrađivana primarna elektivna totalna proteza kolena. Oni su bili podeljeni u dve grupe, 48 u ispitivanoj grupi kod kojih je primenjivana traneksamična kiselina i 48 bolesnika koji su bili kontrolna grupa. Svi bolesnici su bili u spinalnoj anesteziji i primenjivana je pneumatska poveska na ekstremitetu koji se operisao. Ispitivana grupa je dobijala traneksamičnu kiselinu u dva navrata u dozi od 15 mg /kg i 10 mg/kg u vidu kontinuirane i.v. infuzije u trajanju od 15 minuta. Prvo davanje leka je bilo neposredno nakon uvoda u anesteziju. Drugo davanje leka je bilo 15 minuta pre otpu&scaron;tanja pneumatske poveske. Kontrolna grupa je dobijala istu količinu 0.9% fiziolo&scaron;kog rastvora koji je primenjivan na isti način. Intraoperativni gubitak krvi je beležen i meren kao gubitak u aspiratoru i gubitak na gazama. Postoperativn gubitak krvi se merio nakon 6, 12 sati i nakon 24 sata, kao gubitak na drenove Beležio se i broj primenjenih jedinica krvi i broj ukupno dobijenih mililitara krvi i ostalih krvnih produkata, kao i vreme njihove primene. Rezultati Postoji statistički značajna razlika u prosečnom intraoperativnom krvarenju između grupa (Z = -7,281; p = 000). Prosečno intraoperativno krvarenje u ispitivanoj grupi je bilo 100 &plusmn; 92,690 ml, a u kontrolnoj 447 &plusmn; 299,282 ml. U kontrolnoj grupi bolesnici imaju statistički značajno veće ukupno postoperativno krvarenje od bolesnika iz ispitivane grupe (T test, t=4,024, p&lt;0,01) ( ispitivana grupa 309,78&plusmn; 143,612 ml, kontrolna grupa 455,42 &plusmn; 201,177 ml). Razlika je bila statistički značajna nakon 6 sati (p &lt; 001) i nakon 12 sati u korist ispitivane grupe (p&lt;0,05). Postji statistički značajna razlika u ukupnom perioperativnom krvarenju među grupama i traneksamična kiselina je statistički značajno (p&lt;0,000) smanjila ukupno krvarenje od 919,36 ml (95%IP 822,083-1016,640) na 405, 32 ml (95% IP 353, 407-457, 231). Ukupno perioperativno krvarenje je u proseku iznosilo 662, 34 ml i kretalo se u intervalu od 100 do 1700 ml. U ispitivanoj grupi je samo 5 (10,4%) ispitanika primilo transfuziju, dok je u kontrolnoj grupi 39 (81,3%), &scaron;to je statistički značajna razlika (2=45,692; p=0,000). Prosečna količina date alogene krvi u ispitivanoj grupi je 33,33 &plusmn; 99,2 ml, dok je prosečna količina date alogene krvi u kontrolnoj grupi bila skoro deset puta veća i iznosila je 319,2 &plusmn; 230 ml, &scaron;to je statistički značajno veće (Z = -6,625; p = 000). Postoperativne vrednosti hemoglobina, hematokrita i trombocita bile su statistički značajno veće u isptivanoj grupi. Bolesnici iz ispitivane grupe su statistički značajno ranije postoperativno uzimali prvi obrok, sedeli i ustajali od bolesnika u kontrolnoj grupi. Zaključci Iz dobijenih rezultata o intraoperativnom, postoperativnom i ukupnom perioperativnom krvarenju može se zaključiti da je traneksamična kiselina veoma efikasan lek i da statistički značajno smanjuje krvarenje vezano za ugradnju totalne proteze kolena i da smanjuje upotrebu transfuzije alogene krvi za 66,7%. Traneksamična kiselina je uticajem na smanjenje perioperativnog krvarenja dovela do očuvanja vrednosti hemoglobina, hematokrita i trombocita. Bolesnici koji su dobijali traneksamičnu kiselinu su takođe imali brži i kvalitetniji neposredni postoperativni oporavak.</p> / <p>Introduction: Total knee arthroplasty today is efficient and safe surgical procedure. Being extensive orthopaedic surgical procedure poses a risk from substantial perioperative bleeding and consecutive usage of blood products.&nbsp; Trends in modern medicine and surgery are in favor of restrictive usage of blood products and there are paramount efforts in researching and developing new techniques and methods of allogenic blood transfusion alternatives. Tranexamic acid as fibrinolytic agent is good example of substance that can be used to reduce preoperative bleeding in orthopaedic surgery. Aims of the study: We wanted to explore effects of tranexamic acid on perioperative bleeding reduction in total knee arthroplasty, and it&rsquo;s effect on reduction of blood product usage in this surgical population. Маterial and methods: We conducted double blind, randomized controlled trial with 96 adult patient (older than 18 years) in the study, 48 in two groups. All patients had elective, unilateral total knee arthroplasty. First group got tranexamic acid(TA), and second (control) group got normal saline. Surgery was performed in spinal anaesthesia with usage of pneumatic tourniquet in all patients. First group got tranexamic acid 15mg /kg/ bw и 10 mg/kg/bw as continuous intravenous infusion in duration of 15 min. Control group got same amount of normal saline. First dose of TA was given at the beginning of the operation and second dose 15 min before release of the tourniquet. Control group got normal saline at the same way. Intraoperative blood loss was measured as blood loss in suction bottle and blood loss on the surgical sponges. Postoperative blood loss was measured as blood loss in surgical wound drains after 6, 12, and 24 hours. Number of blood units and total amount of blood and blood products in milliliters were also recorded. Results There are statistically significant difference in average intraoperative bleeding between groups in favor tranexamic acid group (Z = -7,281; p = 000).Average intraoperative bleeding in TA group is 100 &plusmn; 92,690 mil, vs 447 &plusmn; 299,282 mil in control group. Patient in TA group has statistically significant less total postoperative bleeding (T test, t=4,024, p&lt;0,01)( TA group 309,78&plusmn; 143,612 mil vs,420 &plusmn; 201,177 mil). Blood loss was statistically significant less after 6 (p &lt; 001) and 12 hrs (p &lt;0,05). in TA group. Total perioperative bleeding was statistically significant less (p&lt; 0,000) in TA group and TA decreased total blood loss from 919,36 ml (95%IP 822,083-1016,640) to 405,32 ml (95%IP 353,407-457,231).Average total blood loss was 662,34 ml with interval from 100 to 1700 ml. In TA group only 5 (10,4%) patients received vs control group where 39 (81,3%) patients received allogenic blood transfusion and that is statistically significant (2=45,692; p=0,000).Average blood usage in TA group was 33,33 &plusmn; 99,2 ml vs 319,2 &plusmn; 230 ml in the control group (Z = -6,625; p = 000). Postoperative hemoglobin, haematocrit and platelets count values were statistically significant less in control group. Patient in TA group had earlier first postoperative meal, sitting and standing earlier than patient in the control group. Concliusions Data from this study clearly shows that intraoperative, postoperative and total perioperative blood loss in total knee arthroplasty are reduced with usage of tranexamic acid. Tranexamic acid is effective in reducing perioperative blood loss and usage of allogenic blood transfusion, which dropped for 66,7%.This reduced blood loss led to higher postoperative hemoglobin levels. Patients from TA group showed faster postoperative functional recover.</p>

Trauma-induced coagulopathy (TIC) is a recently described condition which traditionally has been diagnosed by the common coagulation tests (CCTs) such as prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), platelet count, and fibrinogen levels. The varying sensitivity and specificity of these CCTs have led trauma coagulation researchers and clinicians to use Viscoelastic Tests (VET) such as Thromboelastography (TEG) to provide Targeted Thromboelastographic Hemostatic and Adjunctive Therapy (TTHAT) in a goal directed fashion to those trauma patients in need of hemostatic resuscitation. This review describes the utility of VETs, in particular, TEG, to provide TTHAT in trauma and acquired non-trauma-induced coagulopathy.

<p>Deep vein thrombosis (DVT) and Pulmonary embolism (PE) are responsible for over 900,000 cases and 100,000 deaths each year in the US. Direct fibrinolytic agents such as plasmin are being investigated for their treatment. However, plasmin administration is not widely studied as low plasmin concentrations are rapidly inactivated by antiplasmin in vivo, whereas high plasmin doses would deplete endogenous antiplasmin and impose bleeding risks. Thus, a plasmin delivery system that can achieve efficient clot lysis while minimizing inactivation by antiplasmin and has reduced bleeding risks is needed. To address this, we propose using reversible inhibitors of plasmin that can sequester plasmin from antiplasmin and release it on the surface of a fibrin clot to achieve clot lysis. The inhibition must be tuned such that it is strong enough to protect plasmin from antiplasmin and weak enough to release plasmin at the clot for lysis. To achieve this, we utilize principles of multivalency to synthesize three classes of inhibitors with varying potencies and mechanisms of inhibition: (i) Multivalent benzamidines (ii) Multivalent tranexamic acids (TXA), and (iii) Hetero-multivalent inhibitors having both benzamidine and TXA. Benzamidine is a competitive inhibitor of plasmin’s active site. TXA, on the other hand, is an FDA-approved weak active site inhibitor that is primarily used to disrupt plasmin(ogen) from binding to fibrin on the clot by inhibiting plasmin’s kringle domains. Multivalent inhibitors were synthesized using amine-reactive chemistry, purified using RP-HPLC and confirmed with Mass Spectrometry. Inhibition assays were performed to assess inhibition potency by determining Ki values (inhibition constants). Lower Ki values indicate stronger inhibition. With multivalent benzamidine derivatives, it was observed that changing valency and linker length substantially impacted inhibition and resulted in Ki values ranging from 2.1 to 1,395 μM. Inhibitors of higher valencies and shorter linker lengths exhibited stronger inhibition. Multivalent TXAs of valencies 1 to 16 were also tested and they exhibited Ki values varying from 2.5 to 21,370 μM indicating up to 8,548-fold improvement in inhibition due to valency. It was found that monovalent TXA, primarily a kringle inhibitor, can be converted into a stronger active site inhibitor by multivalency. With hetero-bivalent TXA-dPEG36-AMB, simultaneous binding of benzamidine to the active site and TXA to the kringle domains was achieved to attain improved inhibition. These results indicate that multivalency can significantly alter the potency of inhibitors and can modulate plasmin inhibition for drug delivery.</p>

<p>U savremenoj hirurgiji imperativ je da hirur&scaron;ka procedura bude efikasna, ali i da obezbedi kvalitetan i brz oporavak. Najbitniji segment operativnog lečenja je obezbediti maksimalan učinak kako bi se osobi omogućio brz i potpun povratak aktivnostima dnevnog života. Posebno je pojačano&nbsp;&nbsp; interesovanje za rekonstrukciju prednjeg ukr&scaron;tenog ligamenta kod mlađe i sporsko aktivne populacije. Trendovi u medicini kao i u ortopedskoj hirurgiji idu u pravcu smanjenja postoperativnog krvarenja, bola i skraćenja postoperativnog oporavka. Supstancija sa antifibrinolitičkim delovanjem, kao &scaron;to je traneksamična kiselina, svakako je na&scaron;la svoje mesto u smanjenju postoperativnog krvarenja. Ciljevi istraživanja su se odnosili na utvrđivanje uticaja lokalno aplikovane traneksamične kiseline tokom rekonstrukcije prednjeg ukr&scaron;tenog ligamenta kolena na postoperativno krvarenje, posmatrane laboratorijske parametre, mere obima kolena, učestalosti postoperativnih komplikacija i kvaliteta postoperativnog oporavka između dve grupe ispitanika (ispitivana i kontrolna grupa). Studija je bila eksprimentalnog karaktera i sprovedena je u Kliničkom centru Vojvodine u Novom Sadu uz odobrenje etičke komisije. U istraživanje, metodom slučajnog izbora, bila su uključena 124 ispitanika oba pola raspoređena u dve grupe (ispitivana i kontrolna), a kod kojih je indikovana operativno zbrinjavanje prekida prednjeg ukr&scaron;tenog ligamenta kolena i koji su dali pristanak da budu uključeni u studiju. Svi prikupljeni podaci su beleženi u protokol, koji je za ovo istraživanje posebno dizajniran. Ispitanici su bili podvrgnuti operativnom zahvatu, uz primenu op&scaron;te ili spinalne anestezije, sa postavljenom pneumatskom poveskom na operisanom ekstremitetu. Ispitivanoj grupi bilo je lokalno aplikovano 20 ml traneksamične kiseline, dok je u kontolnoj grupi na isti način aplikovano 20 ml NaCl 0,9 % rastvora. Postoperativni gubici krvi su praćeni i beleženi tokom 24 h od operacije, dok su laboratorijki nalazi uzorkovani preoperativno i sedmog postoperativnog dana. U posmatranom periodu (preoperativno, sedmog postoperativnog dana, treće i &scaron;este postoperativne nedelje) kod ispitanika je praćen obim kolena i pojava komplikacija (hematom, hemartroza). Nakon sprovedenog istraživanje, prikupljeni podaci su dokumentovani i statistički obrađeni. Rezultati istraživanja jasno ukazuju da postoji statistički značajna razlika (t=7.181, p&lt;0.001) u količni postoperativnog krvarenja između grupa. Prosečno postoperativno krvarenje u ispitivanoj grupi je bilo 71.29&plusmn;40.76 ml, u odnosu na kontrolnu grupu gde je postoperativno krvarenje iznosilo 154.35&plusmn;81.45 ml. U kontrolnoj grupi, postoperativno se beleže niže vrednosti hemoglobina (t=9.608, p&lt;0.001) i hematokrita (t=8.325, p&lt;0.001), i vi&scaron;e vrednosti trombocita (t=2.201, p=0.032) nego u ispitivanoj grupi. Podaci o postoperativnom bolu ispitanika govore u prilog statistički značajnoj razlici u jačini bola prve nedelje nakon operacije između ispitivane i kontrolne grupe (t=2.405, p=0.018) i treće nedelje nakon operacije (t=3.700, p&lt;0.001). U ispitivanoj grupi zabeležena je ređa pojava hematoma 6.45% (n=4), dok je u kontrolnoj grupi 19.35% (n=12). Svi pacijenti u uzorku su popunili upitnik o postoperativnom kvalitetu oporavka. Nije zabeležena statistički značajna razlika u kvalitetu postoperativnog oporavka nakon operacije između dve analizirane grupe ispitanika. Dobijeni rezultati o postoperativnom krvarenju, nakon aplikovane traneksamične kiseline, ukazuju na efikasnost leka i pri lokalnoj primeni tokom rekonstrukcije prednjeg ukr&scaron;tenog ligamenta kolena. S obzirom na insuficijentnost podataka, ovo ispitivanje stvara &scaron;iru osnovu za dalja istraživanja.</p> / <p>In modern surgery, we need an effective surgical procedure, which provides quality and rapid recovery. The most important segment of surgical treatment is to provide maximum impact to allow a person to return quickly and fully to the activities of daily living. There has been particular interest in the reconstruction of the anterior cruciate ligament in the younger and sport active population. Trends in medicine, as well as in orthopedic surgery, are heading towards reducing postoperative bleeding, pain, and postoperative recovery. A substance with antifibrinolytic activity, such as tranexamic acid, has certainly found its place in reducing postoperative bleeding. The objectives of the study were to determine the effect of locally applied tranexamic acid during the reconstruction of the anterior cruciate knee ligament on postoperative bleeding, observed laboratory parameters, measures of knee circumference, frequency of postoperative complications, and quality of postoperative recovery between the two groups of subjects (study and control group). The study was prospective, conducted at the Clinical Center of Vojvodina in Novi Sad with the approval of the ethics committee. The study, by random selection method, included 124 subjects of both sexes, divided into two groups (tested and control), which indicated operative management of the anterior cruciate ligament rupture and gave informed consent for inclusion in the study. All data collected were recorded in a protocol, which was specifically designed for this research. Subjects underwent surgery, with general or spinal anesthesia, with pneumatic attachment placed on the extremity undergoing surgery. The test group was given topically 20 ml of tranexamic acid, while the control group was administered 20 ml in the same way. NaCl 0.9% solution. Postoperative blood losses were monitored and recorded within 24 h of surgery, while laboratory findings were sampled preoperatively and on the seventh postoperative day. During the observed period (preoperatively, on the seventh postoperative day, on the third and sixth postoperative weeks), the knee volume and the occurrence of complications (hematoma, hemarthrosis) were monitored in the subjects. Following the survey, the data collected were documented and statistically processed. The study results indicate that there was a statistically significant difference (t = 7.181, p &lt;0.001) in the amount of postoperative bleeding between groups. The mean postoperative bleeding in the study group was 71.29 &plusmn; 40.76 ml, compared to the control group where postoperative bleeding was 154.35 &plusmn; 81.45ml. In the control group, lower hemoglobin values (t = 9.608, p &lt;0.001) and hematocrit (t = 8.325, p &lt;0.001) were observed postoperatively, and higher platelet counts (t = 2.201, p = 0.032) than in the study group. The data on the postoperative pain of the respondents support a statistically significant difference in the severity of pain on the first week after surgery between the study and the control group (t = 2.405, p = 0.018) and the third week after surgery (t = 3.700, p &lt;0.001). In the study group, the incidence of hematoma was less than 6.45% (n = 4), while in the control group it was 19.35% (n = 12). All patients in the sample completed a questionnaire on postoperative quality of recovery. There was no statistically significant difference in the quality of postoperative recovery after surgery between the two analyzed groups of subjects. The results of post-operative bleeding, after administrated tranexamic acid, indicate the efficacy of the drug and at a local application during the reconstruction of the anterior cruciate ligament. Due to the insufficiency of data, this study creates a broad basis for further research.</p>

No description available.