Liječenje venske tromboembolije argatrobanom u bolesnice s heparinskom trombocitopenijom tipa ii ( HIT II ) - prikaz slučaja

Representing this patient our intention was to stress the importance of monitoring platelet number in patient on heparin therapy. We have, for the first time, in our hospital used reversibile thrombine inhibitor, that showed efficacy in treatening HIT II complications. HIT II immunologicaly caused side-effect of heparin therapy, characterized by decrease in thrombocyte number for more than 50 %, with increased inclination to thromboembolic incidents. The disease most commonly appears 5-10 days after initiation of mainly unfractionated heparin therapy. Application of ’4 T score’ in clinical judgement for HIT probability, and laboratory investigation for presence of anti-heparin antibodies markedly contribute to in time detection and treatment of this illness. If anti-heparin antibodies are detected, heparin application must be stopped immidiately, and must be replaced by some anti-heparin anticoagulant preparation ( Fxa inhibitor, heparinoide, or direct inhibitor of thrombine). In time application of substitutional preparation for heparin markedly diminishes the occurence of thromboembolic complications. We presented the case of patient hospitalized in our institution by reason of complete thrombosis of left illiac vein, joint femoral vein, deep veins of femoral region, popliteal vein and initial part of great saphenous vein. Treatment started by non-fractionated heparin and continued by warfarin, but the patient developed clinical feature of HIT II, so, current anticoagulant therapy was stopped , and fondaparinux was introduced. Although thrombocyte number increased, D-dimers were in additional rise, and patient developed pulmonary embolism. Reversible thrombin inhibitor argatroban was introduced in therapy in daily dose of 2 μg/kg/min in continual infusion lasting 15 days, followed by continual APTT monitoring,in therapeutic range 1.5-2 times of basic value. Rise in platelet number was monitored, decrease of D-dimer, and local clinical improvement. Marginal recanalization of veins in left femoral region and complete passage of popliteal vein were documented by color doppler. Further, clinical estimation of HIT II probability using „4T“ graduating system, and laboratory investigation to antiheparin antibodies, had significant role in diagnosis confirmation, and in selecting suitable substitutional preparation for heparin.Prikazom smo željeli naglasiti važnost praćenja broja trombocita kod liječenja heparinom. Uporabili smo po prvi puta reverzibilni inhibitor trombina; koji je pokazao učinkovitost u liječenju komplikacija HIT-a II. HIT II je imunološka nuspojava heparinske terapije praćena trombocitopenijom > 50% i povećanom sklonošću tromboemboliji. Najčešće se javlja 5. do 10. dana terapije nefrakcioniranim heparinom. Otkrivanju i liječenju ove nuspojave značajno pridonosi primjena „ 4T zbira“ i otkirvanje prisutnosti protutijela na heparin. Ukoliko se protutijela dokažu; heparin se isključuje i nastavlja se ne-heparinskim antikoagulansom (inhibitorom FX a; heparinoidom ili direktnim inhibitorom trombina); čime se smanjuje rizik tromboembolije. Prikazali smo slučaj bolesnice s kompletnom trombozom lijeve ilijačne vene; zajedničke femoralne vene; dubokih vena natkoljenice; poplitealne vene i početnog dijela velike vene safene. Liječenje je započelo nefrakcioniranim heparinom i nastavljeno varfarinom. Bolesnica je razvila kliničku sliku HIT-a II. Prekinuta se dosadašnja antikoagulantna terapija i uvoden je fondaparinux. Broj trombocita je počeo rasti; D-dimeri tako|er. Razvila se plućna embolija. Liječenje je nastavljeno reverzibilnim inhibitorom trombina argatrobanom u dnevnoj dozi od 2 μg/kg/min kontinuiranom infuzijom u trajanju od 15 dana. Pratili smo APTV; čije su vrijednosti bile 1.5-2 puta duže od bazične vrijednosti. Broj trombocita je rastao; koncentracija D-dimera se snizila; nastupilo je lokalno kliničko poboljšanje. Obojeni doppler je pokazao rubnu rekanalizaciju vena lijeve natkoljenice i potpunu prohodnost poplitealne vene. Klinička procjena vjerojatnosti HIT II s „4T“ bodovnim sustava otkrivanja heparinskih protutijela imala je značajnu ulogu u potvrdi dijagnoze i odluci o odabiru odgovarajućeg zamjenskog lijeka za heparin

Liječenje venske tromboembolije argatrobanom u bolesnice s heparinskom trombocitopenijom tipa ii ( HIT II ) - prikaz slučaja

Representing this patient our intention was to stress the importance of monitoring platelet number in patient on heparin therapy. We have, for the first time, in our hospital used reversibile thrombine inhibitor, that showed efficacy in treatening HIT II complications. HIT II immunologicaly caused side-effect of heparin therapy, characterized by decrease in thrombocyte number for more than 50 %, with increased inclination to thromboembolic incidents. The disease most commonly appears 5-10 days after initiation of mainly unfractionated heparin therapy. Application of ’4 T score’ in clinical judgement for HIT probability, and laboratory investigation for presence of anti-heparin antibodies markedly contribute to in time detection and treatment of this illness. If anti-heparin antibodies are detected, heparin application must be stopped immidiately, and must be replaced by some anti-heparin anticoagulant preparation ( Fxa inhibitor, heparinoide, or direct inhibitor of thrombine). In time application of substitutional preparation for heparin markedly diminishes the occurence of thromboembolic complications. We presented the case of patient hospitalized in our institution by reason of complete thrombosis of left illiac vein, joint femoral vein, deep veins of femoral region, popliteal vein and initial part of great saphenous vein. Treatment started by non-fractionated heparin and continued by warfarin, but the patient developed clinical feature of HIT II, so, current anticoagulant therapy was stopped , and fondaparinux was introduced. Although thrombocyte number increased, D-dimers were in additional rise, and patient developed pulmonary embolism. Reversible thrombin inhibitor argatroban was introduced in therapy in daily dose of 2 μg/kg/min in continual infusion lasting 15 days, followed by continual APTT monitoring,in therapeutic range 1.5-2 times of basic value. Rise in platelet number was monitored, decrease of D-dimer, and local clinical improvement. Marginal recanalization of veins in left femoral region and complete passage of popliteal vein were documented by color doppler. Further, clinical estimation of HIT II probability using „4T“ graduating system, and laboratory investigation to antiheparin antibodies, had significant role in diagnosis confirmation, and in selecting suitable substitutional preparation for heparin.Prikazom smo željeli naglasiti važnost praćenja broja trombocita kod liječenja heparinom. Uporabili smo po prvi puta reverzibilni inhibitor trombina; koji je pokazao učinkovitost u liječenju komplikacija HIT-a II. HIT II je imunološka nuspojava heparinske terapije praćena trombocitopenijom > 50% i povećanom sklonošću tromboemboliji. Najčešće se javlja 5. do 10. dana terapije nefrakcioniranim heparinom. Otkrivanju i liječenju ove nuspojave značajno pridonosi primjena „ 4T zbira“ i otkirvanje prisutnosti protutijela na heparin. Ukoliko se protutijela dokažu; heparin se isključuje i nastavlja se ne-heparinskim antikoagulansom (inhibitorom FX a; heparinoidom ili direktnim inhibitorom trombina); čime se smanjuje rizik tromboembolije. Prikazali smo slučaj bolesnice s kompletnom trombozom lijeve ilijačne vene; zajedničke femoralne vene; dubokih vena natkoljenice; poplitealne vene i početnog dijela velike vene safene. Liječenje je započelo nefrakcioniranim heparinom i nastavljeno varfarinom. Bolesnica je razvila kliničku sliku HIT-a II. Prekinuta se dosadašnja antikoagulantna terapija i uvoden je fondaparinux. Broj trombocita je počeo rasti; D-dimeri tako|er. Razvila se plućna embolija. Liječenje je nastavljeno reverzibilnim inhibitorom trombina argatrobanom u dnevnoj dozi od 2 μg/kg/min kontinuiranom infuzijom u trajanju od 15 dana. Pratili smo APTV; čije su vrijednosti bile 1.5-2 puta duže od bazične vrijednosti. Broj trombocita je rastao; koncentracija D-dimera se snizila; nastupilo je lokalno kliničko poboljšanje. Obojeni doppler je pokazao rubnu rekanalizaciju vena lijeve natkoljenice i potpunu prohodnost poplitealne vene. Klinička procjena vjerojatnosti HIT II s „4T“ bodovnim sustava otkrivanja heparinskih protutijela imala je značajnu ulogu u potvrdi dijagnoze i odluci o odabiru odgovarajućeg zamjenskog lijeka za heparin

Smjernice Hrvatskog društva za hematologiju i transfuzijsku medicinu u dijagnostičko-terapijskom postupku za trombocitopeniju izazvanu heparinom (HIT) [Croatian Society for Haematology and Transfusion Medicine Guidelines on the diagnosis and management of heparin induced thrombocytopenia (HIT)]

Heparin induced thrombocytopenia (HIT) is a serious complication of heparin administration. In the last decade, this clinical syndrome has come into the focus of interest, primarily because of the severe thromboembolic complications that may lead to lethal outcome. In addition, great improvements have been made in the treatment with direct thrombin inhibitors and in laboratory diagnosis of HIT. As guidelines for diagnostic and management of HIT upgrade the quality of patient treatment, activities for their development have been launched in the Republic of Croatia. Based on British Committee for Standards in Haematology (BCSH) recommendations on diagnostic and treatment of HIT from 2006, activities for the introduction of new assays for anti-heparin antibodies were launched in 2008 and 2009, including algorithm of laboratory testing for HIT, sheet for clinical assessment of HIT (4T score), and education oftransfusiologists and clinicians. Upon evaluation of the results collected during one-year period, the Croatian Society of Haematology and Transfusion Medicine nominated a task force for the development of guidelines for HIT in January 2010. Following wide-ranging discussion, the guidelines were adopted in May 2011

Croatian Society for Haematology and Transfusion Medicine Guidelines on the Diagnosis and Management of Heparin Induced Thrombocytopenia (HIT)

Trombocitopenija izazvana heparinom (HIT) teška je nuspojava heparinske terapije. U posljednjih desetak godina ovaj kliničkopatološki sindrom u središtu je interesa primarno zbog teških tromboembolijskih komplikacija, koje mogu imati i smrtni ishod. Znatno poboljšanje u liječenju HIT-a, postignuto je primjenom direktnih inhibitora trombina u zamjenu za heparin, a laboratorijsko ispitivanje antiheparinskih protutijela znatno je unaprijedilo dijagnostiku HIT-a. Uvođenje smjernica za dijagnostičko-terapijski postupak za HIT ima znatan učinak na kvalitetu liječenja bolesnika. Godine 2008. u Republici Hrvatskoj (RH) pokrenut je niz aktivnosti u cilju uspostavljanja smjernica za HIT, temeljenih na britanskim preporukama za dijagnostiku i liječenje trombocitopenije izazvane heparinom iz 2006. godine. Tijekom 2008/09. godine uvedeni su novi testovi za antiheparinska protutijela, algoritam laboratorijskog ispitivanja i obrazac za kliničku procjenu HIT-a te izobrazba transfuziologa i kliničara. U siječnju 2010. godine na stručnom sastanku Hrvatskog društva za hematologiju i transfuzijsku medicinu (HDHTM), nakon evaluacije rezultata jednogodišnje primjene preporuka osnovana je radna skupina za donošenje smjernica HDHTM-a za HIT. Nakon usuglašavanja i javne rasprave smjernice su prihvaćene u svibnju 2011. godine.Heparin induced thrombocytopenia (HIT) is a serious complication of heparin administration. In the last decade, this clinical syndrome has come into the focus of interest, primarily because of the severe thromboembolic complications that may lead to lethal outcome. In addition, great improvements have been made in the treatment with direct thrombin inhibitors and in laboratory diagnosis of HIT. As guidelines for diagnostic and management of HIT upgrade the quality of patient treatment, activities for their development have been launched in the Republic of Croatia. Based on British Committee for Standards in Haematology (BCSH) recommendations on diagnostic and treatment of HIT from 2006, activities for the introduction of new assays for anti-heparin antibodies were launched in 2008 and 2009, including algorithm of laboratory testing for HIT, sheet for clinical assessment of HIT (4T score), and education of transfusiologists and clinicians. Upon evaluation of the results collected during one-year period, the Croatian Society of Haematology and Transfusion Medicine nominated a task force for the development of guidelines for HIT in January 2010. Following wide-ranging discussion, the guidelines were adopted in May 2011