Thawing of fresh frozen plasma (FFP) in South Africa is not standardized and thawing at high temperatures may cause clotting factor activation and disseminated intravascular coagulation (DIC). This research project studies the in-vitro effects of thawing FFP at various temperatures on coagulation. Twenty units of FFP were each divided into 4 satellite bags which were respectively thawed at 22ºC, 37ºC, 45ºC and 60ºC and tested for Fibrinogen, DDimers, PT, PTT, r value, Alpha Angle and Maximum Amplitude (MA). FFP thawed at 60ºC showed significant differences suggesting clotting factor inactivation. FFP thawed at 45ºC showed significantly elevated D-Dimers. Clotting factors thawed at 22ºC may be partially inactivated. High thawing temperatures may activate and then denature the factors therein. Twenty two degrees may partially inactivate FFP until it is warmed to body temperature. The clinical implications and recommendations of this study are to thaw FFP at 37ºC.

Made available in DSpace on 2014-06-11T19:24:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2005Bitstream added on 2014-06-13T20:51:08Z : No. of bitstreams: 1 kitamura_ea_me_botfmvz.pdf: 643374 bytes, checksum: acf4c3d1531bf42eaabaf871100eca42 (MD5) / Na clínica de pequenos animais, rotineiramente, observam-se casos de intoxicações de cães por rodenticidas anticoagulantes. Isto é conseqüência da grande utilização deste pesticida, que é de fácil aquisição para o uso doméstico no controle de roedores. Estes animais comumente apresentam distúrbios de hemostasia secundária com quadro hemorrágico. O presente trabalho teve por objetivo avaliar as alterações hematológicas, hemostáticas e a resposta terapêutica de cães intoxicados experimentalmente por varfarina. Foram utilizados 28 cães, adultos, machos e fêmeas, que foram divididos em 2 grupos de 14 animais, sendo: Grupo I (varfarina + vitamina K1) e Grupo II (varfarina + vitamina K1 e plasma fresco congelado). Os cães foram intoxicados com a varfarina sódica (30mg/kg) por via oral e foram tratados com vitamina K1 (1mg/kg) por via subcutânea e a transfusão do plasma fresco congelado (PFC) na dose de 10mL/kg por via intravenosa. Os exames laboratoriais como hemograma, plaquetas, fibrinogênio, tempo de sangramento em mucosa oral (TSMO), tempo de coagulação (TC), tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPA) e tempo de trombina (TT) foram realizados em sete momentos: M0 (controle), M1 (48 horas), M2 (72 horas), M3 (78 horas), M4 (96 horas), M5 (120 horas) e M6 (168 horas) após a intoxicação. O tratamento com a vitamina K1 foi iniciado após o M2, continuando a cada 24 horas até o último momento, e a transfusão de PFC foi realizada somente uma vez imediatamente após o M2. Os resultados laboratoriais demonstraram que o TP é o mais sensível para o monitoramento da intoxicação por varfarina. TTPA e o TC também se apresentam prolongados pelo efeito anticoagulante do veneno, sendo que estes três testes devem ser utilizados conjuntamente no diagnóstico diferencial da intoxicação por varfarina. O tratamento com o PFC associado... / Anticoagulant rodenticide intoxication is very common in the small animal practice. This is due to the high prevalence of its use as a domestic pesticide and its purchase availability. These animals usually present secondary hemostatic defects, with a hemorrhage. The aim of this work was to evaluate the hematological and hemostatic changes and the therapeutic response of dogs experimentally intoxicated by warfarin. Twenty eight adult dogs, males and females, were divided in two groups of 14 dogs: Group I (warfarin + vitamin K1) and Group II (warfarin + vitamin K1 and fresh frozen plasma). Dogs were intoxicated with sodium warfarin (30mg/kg) by the oral route and treated with vitamin K1 (1mg/kg) by the subcutaneous route. Fresh frozen plasma (FFP) was administrated intravenously (10mL/kg). The CBC, platelet count, fibrinogen, bucal mucosa bleeding time (BMBT), clotting time (CT), prothrombin time (PT), activated partial prothrombin time (APPT) and thrombin time (TT) were evaluated at seven moments: M0 (control), M1 (48h), M2 (72h), M3 (78h), M4 (96h), M5 (120h) and M6 (168h) pos-intoxication. Vitamina K1 administration was initiated immediately after M2 and repeated each 24 hours until the end of the experiment and the fresh frozen plasma was given only after M2. The results demonstrated that PT is the most sensible test for the follow up of warfarin toxicosis. APPT and CT also had been presented prolonged by the anticoagulation effect of the venom; therefore these three tests should be used together in the differential diagnosis of warfarin intoxication. Treatment with FFP associated to vitamin K1 promoted a considerable shortening on the time of coagulation tests, earlier than the treatment with the vitamin K1 alone.

Resumo: Na clínica de pequenos animais, rotineiramente, observam-se casos de intoxicações de cães por rodenticidas anticoagulantes. Isto é conseqüência da grande utilização deste pesticida, que é de fácil aquisição para o uso doméstico no controle de roedores. Estes animais comumente apresentam distúrbios de hemostasia secundária com quadro hemorrágico. O presente trabalho teve por objetivo avaliar as alterações hematológicas, hemostáticas e a resposta terapêutica de cães intoxicados experimentalmente por varfarina. Foram utilizados 28 cães, adultos, machos e fêmeas, que foram divididos em 2 grupos de 14 animais, sendo: Grupo I (varfarina + vitamina K1) e Grupo II (varfarina + vitamina K1 e plasma fresco congelado). Os cães foram intoxicados com a varfarina sódica (30mg/kg) por via oral e foram tratados com vitamina K1 (1mg/kg) por via subcutânea e a transfusão do plasma fresco congelado (PFC) na dose de 10mL/kg por via intravenosa. Os exames laboratoriais como hemograma, plaquetas, fibrinogênio, tempo de sangramento em mucosa oral (TSMO), tempo de coagulação (TC), tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPA) e tempo de trombina (TT) foram realizados em sete momentos: M0 (controle), M1 (48 horas), M2 (72 horas), M3 (78 horas), M4 (96 horas), M5 (120 horas) e M6 (168 horas) após a intoxicação. O tratamento com a vitamina K1 foi iniciado após o M2, continuando a cada 24 horas até o último momento, e a transfusão de PFC foi realizada somente uma vez imediatamente após o M2. Os resultados laboratoriais demonstraram que o TP é o mais sensível para o monitoramento da intoxicação por varfarina. TTPA e o TC também se apresentam prolongados pelo efeito anticoagulante do veneno, sendo que estes três testes devem ser utilizados conjuntamente no diagnóstico diferencial da intoxicação por varfarina. O tratamento com o PFC associado... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Anticoagulant rodenticide intoxication is very common in the small animal practice. This is due to the high prevalence of its use as a domestic pesticide and its purchase availability. These animals usually present secondary hemostatic defects, with a hemorrhage. The aim of this work was to evaluate the hematological and hemostatic changes and the therapeutic response of dogs experimentally intoxicated by warfarin. Twenty eight adult dogs, males and females, were divided in two groups of 14 dogs: Group I (warfarin + vitamin K1) and Group II (warfarin + vitamin K1 and fresh frozen plasma). Dogs were intoxicated with sodium warfarin (30mg/kg) by the oral route and treated with vitamin K1 (1mg/kg) by the subcutaneous route. Fresh frozen plasma (FFP) was administrated intravenously (10mL/kg). The CBC, platelet count, fibrinogen, bucal mucosa bleeding time (BMBT), clotting time (CT), prothrombin time (PT), activated partial prothrombin time (APPT) and thrombin time (TT) were evaluated at seven moments: M0 (control), M1 (48h), M2 (72h), M3 (78h), M4 (96h), M5 (120h) and M6 (168h) pos-intoxication. Vitamina K1 administration was initiated immediately after M2 and repeated each 24 hours until the end of the experiment and the fresh frozen plasma was given only after M2. The results demonstrated that PT is the most sensible test for the follow up of warfarin toxicosis. APPT and CT also had been presented prolonged by the anticoagulation effect of the venom; therefore these three tests should be used together in the differential diagnosis of warfarin intoxication. Treatment with FFP associated to vitamin K1 promoted a considerable shortening on the time of coagulation tests, earlier than the treatment with the vitamin K1 alone. / Orientador: Regina Kiomi Takahira / Coorientador: Michiko Sakate / Banca: Raimundo Souza Lopes / Banca: Nayro Xavier de Alencar / Mestre

Severe congenital heart disease (CHD) is diagnosed in the United States 147.4 times per 100,000 live births, excluding still births and abortions^1. With the advancement of diagnostic methods, prenatal care, and screening modalities, the total CHD birth prevalence has increased substantially^2. In turn, this increases the number of cardiac surgery cases. With the advancement of technology and cardiac surgery, smaller and younger patients are undergoing more complex cardiac procedures that involve cardiopulmonary bypass (CPB). Neonates and infants undergoing CPB are susceptible to adverse effects of CPB on the coagulation cascade due to their smaller weight and hematologic immaturity^3,4. In addition to these physiological issues in neonates and infants, CPB decreases circulating coagulation factors and anti- thrombin III levels to 50% and platelet counts to 70%^5, which can contribute to the post-operative bleeding.During CPB, neonates' and infants' coagulation factors become extremely diluted causing multiple coagulation defects^6. Optimizing the CPB circuit volume and the use of anti-fibrinolytic, packed red blood cells (pRBCs), platelets, cryoprecipitate, and ultrafiltration are among the most widely used methods in preserving and aiding coagulation factors^3,7-9. Another method of improving hemodilution-related coagulation dysfunction bleeding is by transfusing Fresh Frozen Plasma (FFP)^10. However, there are only a small number of articles focusing on the effect of FFP in post-operative bleeding in neonates and infants following complex cardiac surgery with CPB. I postulate that adding FFP during CPB will lower the possibility of patients to experience post-operational bleeding, thus, shortening their length of stay (LOS).

Introdução: O efeito da transfusão de plasma fresco congelado (PFC) para corrigir coagulopatia na cirrose ainda não foi devidamente esclarecido. As diretrizes internacionais permanecem sem uma indicação clara neste cenário e pacientes com cirrose chegam a consumir 30% do estoque de plasma dos bancos de sangue. Nosso objetivo foi avaliar o efeito do PFC na geração de trombina (GT) corrigida por trombomodulina (TM) em pacientes com cirrose e testes convencionais de coagulação alterados. Métodos: neste estudo observacional foram incluídos pacientes adultos, o i o om i g ó i o i o , RNI/TP >= 1,5 i i ç o PFC o médico assistente com intuitos profiláticos e/ou terapêuticos. Amostras de sangue foram coletadas antes e em até 6 horas após transfusão. O desfecho principal foi a melhora do parâmetro de GT, ETP adicionado de TM (ETP TM). Todas as amostras foram testadas para RNI/TP, TTPa e todos parâmetros de GT com e sem TM. Resultados: 53 pacientes receberam dose média de plasma de 11,26 ± 1,3 mL/kg. Após transfusão RNI, TP e TTPa diminuíram significantemente (p < 0,00001), correspondendo a melhora de 33,7%, 23, 5% e 16,6% respectivamente. Entretanto, foram atingidos valores <1,5 para RNI e TP em apenas 8 (15%) e 21 (40%) dos pacientes. O PFC aumentou a ETP TM em apenas 8% (1008 ± 345 a 1090 ± 341 nMol / L*min; p = 0,019). Antes da transfusão, evidência de GT normal ou alta foi encontrada em 96% por ETP TM e em 98% dos pacientes pelo parâmetro ETPr. Apenas 2 (3,8%) pacientes apresentaram valores de ETP TM abaixo da faixa normal e a transfusão de PFC corrigiu a geração de trombina em um deles. Nenhum destes sangrou. O ETP TM diminuiu em uma média de 12,8% em 18 (34%) pacientes após a transfusão (1270 ± 256 a 1107 ± 278 nMol / L* min ; p = <0,0001). O ETPrazão (com/sem TM) permaneceu praticamente inalterado (de 0,81 ± 0,13 para 0,80 ± 0,12, p = 0,75). Conclusão: Pacientes com cirrose e testes convencionais da coagulação alterados parecem ter GT preservada em seus estados basais. A transfusão de PFC aumenta a GT e melhora os testes convencionais de coagulação em um número limitado destes pacientes, e piorou a ETP TM em um terço dos casos / Background and aims: the efficacy of fresh frozen plasma (FFP) transfusion in correcting coagulopathy in cirrhosis has not been fully clarified. International manuals remain without a clear indication in this scenario and patients with cirrhosis consume up to 30% of the blood bank stock of plasma. Our aim was to assess the effect of FFP transfusion on thrombomodulin(TM)-corrected thrombin generation (TG) in patients with cirrhosis and impaired conventional coagulation tests. Methods: consecutive adult patients with INR/PT ratio >= 1.5 and receiving standard FFP dose for bleeding treatment and/or before invasive procedures were enrolled in this observational study. Primary endpoint was the amelioration of the GT parameter ETP with TM (ETPTM) after FFP transfusion (TM was added to mimic in vivo conditions). PT/INR, aPTT and all TG parameters (with and without TM) were examined in patients with cirrhosis before and after FFP transfusion. Results: 53 patients received FFP at a mean dose of 11,26 ± 1,3 mL/kg. FFP enhanced ETP TM by only 8% (1008±345 to 1090±341 nMol/L*min; p= 0.019). Before transfusion, evidence of normal or high TG was found in 96% by ETP TM and 98% of patients by the ETP ratio parameter. Only 2 (3.8%) had ETP TM values below normal range and FFP transfusion corrected thrombin generation in one of them. None of them bled. ETP TM had a 12.8% mean decrease in 18 (34%) after FFP transfusion (1270±256 to 1107±278 nMol/L*min; p= <0.0001). ETP ratio (with/without TM) remained practically unchanged (from 0.81 ± 0.13 to 0.80 ± 0.12, p = 0.75). FFP significantly ameliorated INR/PT values (p < 0.0001), but correction of INR and PT ratio for values <1.5 was observed in only 8 (15%) and 21 (40%) of the patients. Conclusions: Patients with cirrhosis and coagulopathy seem to have normal results of GT at baseline. FFP transfusion enhances TG and ameliorates conventional coagulations tests in a limited number of those patients, and might worsen ETP TM in in a third of cases

Abstract Coronary artery bypass grafting (CABG) is the treatment of choice for patients with three-vessel disease or left main stenosis. However, it is associated with considerable risk of perioperative complications such as myocardial infarction, stroke, infections, and mortality to which excessive bleeding is a contributing factor. This thesis aims to determine the factors involved in and clinical implications of bleeding after CABG. The 1st study evaluated the effects of preoperative ASA discontinuation on the patient’s outcome after CABG. The results showed that late or no discontinuation of low-dose ASA before CABG may decrease the risk of postoperative stroke without increasing the risk of postoperative bleeding. In the 2nd study the use of warfarin was found to be a safe during CABG with no excess bleeding nor other major complications. The 3rd study estimated the impact of surgeons´ performances on blood loss and need for re-exploration after CABG. With 2001 study patients, this study clearly demonstrated that an individual surgeon is a powerful determinant of postoperative bleeding and need for re-exploration after CABG. Using systematic review and meta-analysis, we estimated the risk of complications related to re-exploration for bleeding after CABG. In literature search in 2011, 8 articles with 557 923 patients fulfilled the inclusion criteria. Re-exploration for bleeding after cardiac surgery carries a significantly increased risk of postoperative mortality and morbidity, and thus has a major impact on the patient’s immediate postoperative outcome. We also studied the impact of blood transfusion on the development of post-operative stroke after CABG. Of the study population of 2 226 CABG patients, stroke occurred postoperatively in 53 patients (2.4%). The statistical analysis showed that transfusion of blood products after CABG has a strong, dose-dependent association with the risk of stroke. The use of Octaplas® and platelet transfusions seem to have an even larger impact on the development of stroke than red blood cell transfusions. The 6th study investigated the impact of transfusion of blood products on intermediate outcome after CABG in 2001 patients. The findings indicated that transfusion of any blood product is associated with a significant risk of all-cause and cardiac mortality after CABG. / Tiivistelmä Sepelvaltimotauti on yleisin kuolinsyy ja sepelvaltimoiden ohitusleikkaus hyvine pitkäaikaistuloksineen on todettu parhaaksi hoidoksi potilailla, joilla on monen suonen tai vasemman päärungon tauti. Ohitusleikkaukseen liittyy kuitenkin verenvuodon sekä näihin kytkeytyvien komplikaatioiden riski. Tämän väitöskirjan tavoitteena oli määrittää verenvuodon riskitekijöitä sekä verituotteiden siirtojen vaikutusta ohitusleikkauspotilaiden ennusteeseen. Verenhyytymistä estävien lääkkeiden tiedetään lisäävän verenvuotoja. Ensimmäinen tutkimus osoitti, että ASA:n jatkaminen keskeytyksettä ohitusleikkauksissa vähentää aivoinfarktien riskiä lisäämättä silti verenvuodon riskiä. Toisessa tutkimuksessa pitkäaikainen warfariinihoito osoittautui turvalliseksi ohitusleikkauksen aikana eikä sen käyttö lisännyt verenvuotoja eikä muita komplikaatioita. Kolmas tutkimus osoitti kirurgin taidon merkityksen verenvuotojen ja uusintaleikkausten määrään 2001 potilaalla. Verenvuotojen vuoksi tehtävien uusintaleikkausten negatiivinen vaikutus postoperatiiviseen mortaliteettiin sekä morbiditeettiin on todettu yksiselitteisesti useissa tutkimuksissa. Vuonna 2011 tehdyllä systemaattisella kirjallisuuskatsauksella ja meta-analyysillä selvitimme yhteensä 557 923 ohitusleikkauspotilaan aineistosta, että verenvuodon jälkeisiin uusintaleikkauksiin liittyy huomattava kuoleman ja komplikaatioiden riski. Verenvuotoja hoidetaan yleisesti verensiirroilla, vaikkakin useat tutkimukset ovat osoittaneet verituotteiden annon lisäävän mortaliteettia sekä komplikaatioriskiä. Viides tutkimus selvitteli sepelvaltimoleikkauksissa potilaalle annettujen verituotteiden ja leikkauksen yhteydessä sairastettujen aivoinfarktien välistä yhteyttä. Osoittautui, että verituotteiden käyttöön liittyy annosriippuvaisesti lisääntynyt riski saada aivoinfarkti leikkauksen yhteydessä. Varsinkin verihiutale- ja jääplasmasiirtoihin on todettu liittyvän vielä suurempi aivoinfarktin riski kuin punasolusiirtoihin. Kuudes tutkimus selvitteli sepelvaltimoleikkauksien yhteydessä annettujen verituotteiden vaikutusta 2001 potilaan keskipitkään ennusteeseen. Tutkimus osoitti, että minkä tahansa verituotteen antoon sepelvaltimoleikkauksissa liittyy lisääntynyt kuoleman ja sydänkuoleman riski.