Netraumatski obostrani subduralni hematom uzrokovan antiagregacijskom terapijom: Prikaz slučaja i pregled literature

A 64-year-old female receiving clopidogrel and aspirin antiaggregation therapy after percutaneous coronary intervention for non-STEMI myocardial infarction developed nontraumatic bilateral subdural hematoma with dizziness, vertigo and headache. Craniotomy had to be postponed because of reduced ADP platelet aggregability. Four days after clopidogrel withdrawal and transfusion of 12 platelet concentrate units, ADP aggregation transiently normalized and bilateral trepanation with hematoma evacuation was performed. The procedure was followed by excellent neurologic and clinical recovery; however, decreased platelet aggregability was recorded by postoperative day 12 despite strict clopidogrel and other platelet inhibitor withdrawal. Suspicion of Glanzmann thrombastenia was excluded by flow cytometry. Two weeks after neurosurgery, the right femoral vein thrombosis was detected by color doppler ultrasonography and therapy with fractionated heparin was initiated, followed by warfarin. The risk and incidence of hemorrhagic complications of antiaggregation and anticoagulation therapy are discussed. Caution is warranted on prescribing this potentially harmful therapy to older patients, generally burdened with other chronic comorbidities.U 64-godišnje bolesnice koja je zbog ne-STEMI srčanog infarkta dobivala aspirin i klopidogrel razvio se netraumatski obostrani subduralni hematom praćen smušenošću, vrtoglavicom i glavoboljom. Kod prijma je utvrđena smanjena agregacija trombocita u ADP testu pa je kraniotomija i dekompresija odgođena za 4 dana. Četiri dana nakon prestanka uzimanja klopidogrela i aspirina te uz transfuziju od 12 doza trombocita prolazno se normalizirala agregabilnost trombocita pa je učinjena obostrana trepanacija i uklonjeni su hematomi. Slijedio je odličan neurološki oporavak. Smanjena agregabilnost trombocita bila je prisutna do 12. poslijeoperacijskog dana. Sumnja na Glanzmannovu trombasteniju isključena je protočnom citometrijom. Četrnaestoga poslijeoperacijskog dana nastala je tromboza desne femoralne vene koja je liječena smanjenim dozama heparina i varfarina. Uz prikaz bolesnice analizira se rizik od krvarenja i tromboze u bolesnika koji uzimaju antitrombocitne lijekove. Preporuča se oprez u starijih bolesnika kod kojih su prisutne i druge teške bolesti, što povećava rizik od krvarenja

Recidivi venske tromboze unatoč “optimalne antikoagulantne terapije” antifosfolipidnog sindroma. Mogu li novi peroralni antikoagulansi riješiti problem ?

The aim was to determine the validity of the international normalized ratio (IN R) and prothrombin time (PT ) as a monitor for warfarin therapy in patients with lupus anticoagulants and recurrent thrombosis, and to investigate alternative approaches to monitoring warfarin therapy and new treatment options in these patients. A case is described of a 63-year-old female with antiphospholipid syndrome and recurrent venous thrombosis despite optimal adjusted warfarin therapy. In patients with lupus anticoagulants, the IN Rs obtained while receiving warfarin vary and often overestimate the extent of anticoagulation, while PT without receiving warfarin is often prolonged. In conclusion, lupus anticoagulants can influence PT and lead to IN R that does not accurately reflect the true level of anticoagulation. Optimizing of (warfarin) oral anticoagulation therapy could be achieved by individual monitoring of anticoagulation effect with a test that is insensitive to lupus anticoagulants (chromogenic factor X assay). Emerging oral anticoagulants, direct thrombin inhibitors and direct factor Xa inhibitors, such as dabigatran and rivaroxaban, with a predictable anticoagulant response and little potential for food or drug interactions, have been designed to be administered in fixed doses without coagulation monitoring and could be the treatment choice for these patients.Cilj je bio analizirati uzroke neuspjeha “optimalno doziranog” varfarina kod prevencije recidiva duboke venske tromboze u bolesnika s antifosfolipidnim sindromom. Opisuje se slučaj 63-godišnje bolesnice s antifosfolipidnim sindromom i recidivima venske tromboze tijekom uzimanja varfarina. Vrijednosti IN R bile su u terapijskim granicama. Analizirali su se patofiziološki mehanizmi nastanka tromboze i literaturni podaci. Rezultati su pokazali kako u bolesnika s pozitivnim lupus antikoagulans (LA) testom vrijednost PV -IN R ne daje pravu sliku protuzgrušavajućeg učinka varfarina. Aktivnost PV je zbog interferencije često lažno smanjena, iako u času mjerenja bolesnik ne uzima varfarin ili drugi antagonist vitamina K. Zaključak je kako prisutnost LA može interferencijom lažno smanjiti aktivnost u PV testu i rezultirati nalazom IN R koji ne odražava pravo stanje protuzgrušavajuće aktivnosti izazvane varfarinom. U tom bi slučaju umjesto PV testa trebalo mjeriti aktivnost faktora Xa kromogenom metodom koja je neosjetljiva na LA. Drugo moguće rješenje bi u bolesnika s antifosfolipidnim sindromom bila zamjena varfarina novim lijekovima, oralnim inhibitorima trombina i faktora X. Ovi lijekovi u fiksnoj dozi s predvidivim te o hrani i lijekovima uglavnom neovisnim protuzgrušavajućim učinkom imaju djelotvornost i nuspojave uglavnom slične varfarinu, ali ne trebaju kontrole IN R

Pedesetpet godina (1955.-2010.) Odsjeka za koagulaciju pri hematološkom laboratoriju Kliničke bolnice Sestara milosrdnica i njegova osnivača, hematologa Ljubomira Popovića

The Coagulation Section at Laboratory of Hematology, Sestre milosrdnice University Hospital, Zagreb, was founded in 1955 by Ljubomir Popović, hematologist and assistant at School of Medicine, University of Zagreb, in cooperation with hard-working laboratory technicians. Apart from papers on hematologic neoplasms, plasmacytoma and lymphoma, Ljubomir Popović published a number of papers in the field of anticoagulant therapy with heparin and oral anticoagulants, some of which are also in use today. After Ljubomir Popović left the Hospital in 1964, the Laboratory was run by Professor Nedjeljko Milić, head of the newly founded Division of Hematology. In 1968, the management of the Laboratory of Hematology was taken over by Biserka Raić, MS , medical biochemist, until her retirement in 2007. Great development in morphological and cytometric studies of blood and blood cells has been paralleled by continuous progress and almost dominating activities in the diagnosis of hemostasis disorders. In the 1970s, Marko Koprčina, hematologist, and Biserka Raić introduced the then latest tests in practice at all Hospital departments. In that golden age of the Coagulation Section, M. Koprčina, B. Raić and their associates transferred their knowledge to all colleagues in the Hospital. Through that collaboration, high standards in the diagnosis of hemostasis disorders were achieved, from which the currently high level of clinical knowledge about coagulation disorders and their treatment has derived, making Sestre milosrdnice University Hospital one of the leading hospitals in this field in the country. By describing development of the Coagulation Section and the life of its founder Ljubomir Popović, the authors tried to provide an answer to the following question: can today’s clinicians still have a deciding role in laboratory development, considering that assessments of different phenomena are always initiated by an interested clinician who is trying to interpret and understand the nature of the disorder? This means that the clinician’s place may still be in the laboratory, or else, it will become clear that the laboratory, as well as knowledge in general, has undergone such an expansion that the clinician is no longer able to run it by himself. It is our belief that the answer will assert itself through the survey of the history of the Coagulation Section at Laboratory of Hematology, Division of Hematology, and the lives of its founders and beneficiaries.Koagulacijski odsjek Hematološkog laboratorija u Kliničkoj bolnici “Sestre milosrdnice” osnovao je davne 1955. godine hematolog Ljubomir Popović, uza svesrdno zalaganje suradnika laboratorijskih tehničara. Doktor Popović je tada bio asistent na Medicinskom fakultetu i voditelj Odsjeka hematologije na internom odjelu. U novoosnovanom laboratoriju doktor Popović traži rješenja i odgovore na pitanja koja se javljaju u kliničkoj praksi uz bolesnički krevet. Stručni napredak praćen je objavljivanjem niza članaka o hemoblastozama i protuzgrušavajućoj terapiji, koje postavke vrijede i danas. Ujesen 1964. godine Popović u naponu snage napušta Bolnicu, a Koagulacijski laboratorij dalje vodi profesor Nedjeljko Milić, pročelnik novostvorenoga Zavoda za hematologiju. Godine 1968. dolazi inženjerka medicinske biokemije magistra Biserka Raić i vodi Hematološki laboratorij do svog umirovljenja 2007. godine. Golem napredak bilježi dijagnostika poremećaja hemostaze, ali i citometrijske i morfološke analize krvnih stanica. Sedamdesetih i osamdesetih godina prošloga stoljeća, u zlatno doba razvoja i rada Koagulacijskog laboratorija, hematolog Marko Koprčina sa suradnicima te inženjeri biokemije Biserka Raić i Biserka Getaldić uvode niz novih koagulacijskih i viskozimetrijskih testova u kliničku praksu Bolnice. Ovaj hematološko-koagulacijski klinički rad čini Zavod za hematologiju naše bolnice, s liječnicima i inženjerima, jedinstvenim i prepoznatljivim. Uz opis razvoja Koagulacijskog laboratorija te života njegova osnivača Ljubomira Popovića autori pokušavaju odgovoriti na pitanje može li i mora li danas, kao prije pedeset godina, kliničar imati odlučujuću ulogu u razvoju i radu laboratorija. Autori smatraju da je kliničaru internistu i dalje mjesto u laboratoriju, ali uz gotovo neispunjiv uvjet sinteze bazičnih znanja iz biologije, tehnologije s kliničkom praksom. Razvoj Koagulacijskog laboratorija te životni put njegova osnivača doktora Ljubomira Popovića pokazuju kako bi njemu ova sinteza, isto kao i prije 55 godina, možda uspjela i danas

Kombinirana megaloblastična i imunohemolitička anemija - Prikaz slučaja

A 55-year-old female with a history of psychosis and rheumatoid arthritis was admitted to the hospital for fatigue and dizziness. At admission, macrocytic anemia, high serum lactic acid dehydrogenase (LDH) and gastrin concentrations, decreased serum vitamin B concentration, with macroovalocytes and poikilocytes in peripheral blood smear suggested the diagnosis of pernicious anemia. Indirect antiglobulin test (IAT) was negative. Surprisingly, treatment by vitamin B and folic acid administered for two weeks was ineffective and followed by transitory worsening of hemoglobin concentration on day 8. Repeat direct antiglobulin test (DAT) and IAT were positive. This immunotransfusion conversion, suggesting the presence of autoimmune hemolytic anemia, could be explained by change in the macroblastic erythrocyte population, i.e. emerging red cells with completely exposed membrane antigens due to vitamin B treatment and/or higher degree of dysregulation of the lymphocyte clone secreting erythrocyte autoantibodies. We proposed the coexistence of pernicious and autoimmune hemolytic anemia; therefore, methylprednisolone was added to vitamin B treatment. This therapy successfully improved hemoglobin and erythrocyte concentration. Although megaloblastic-pernicious anemia is a common disease, association of pernicious and autoimmune hemolytic anemia with two mechanisms of hemolysis (ineffective erythropoiesis and immune mechanism) is a rare condition, with only several dozens of cases described so far.Opisuje se 55-godišnja bolesnica koja je primljena u bolnicu zbog slabosti i vrtoglavica. Ranije je bila liječena od reumatoidnog artritisa i psihoze. Pri dolasku su nalazi makrocitne anemije s makroovalocitima i hipersegmentiranim neutrofilima u perifernom razmazu, u serumu visoka koncentracija laktat dehidrogenaze (LDH) i gastrina, te snižena koncentracija vitamina B upućivali na dijagnozu perniciozne anemije. Indirektni antiglobulinski test (IAT) bio je negativan. Dvotjedno liječenje vitaminom B i folnom kiselinom ne samo da nije imalo učinka, nego se osmog dana liječenja pogoršao stupanj anemije. Razmatralo se liječenje transfuzijom eritrocita, ali su kontrolni IAT i direktni antiglobulinski test (DAT) sada bili pozitivni, što je ukazivalo na autoimunu hemolitičku anemiju (AIHA). Ova imunotransfuziološka konverzija, uz ostale razloge možda vezana i uz dvotjedno liječenje vitaminom B , mogla je biti uzrokovana pojačanom reaktivnošću i "gubitkom nadzora" klona limfocita koji luče anteritrocitna antitijela i/ili promjenama u sazrijevanju i konformaciji eritrocitne membrane makroblasta s jačim izražajem antigena na koje su reagirali "nekontrolirani" limfociti. Anemija je tada shvaćena kao združena pojava perniciozne anemije i AIHA. Dodatkom metilprednisolona vitaminu B postignut je porast hemoglobina i eritrocita, a stanje bolesnice se popravilo. Iako je perniciozna anemija česta bolest, udružena perniciozna i autoimuna hemolitička anemija su opisane samo u nekoliko desetaka slučajeva, uglavnom u sastavu drugih autoimunih bolesti

Combined megaloblastic and immunohemolytic anemia associated - case report

A 55-year-old female with a history of psychosis and rheumatoid arthritis was admitted to the hospital for fatigue and dizziness. At admission, macrocytic anemia, high serum lactic acid dehydrogenase (LDH) and gastrin concentrations, decreased serum vitamin B concentration, with macroovalocytes and poikilocytes in peripheral blood smear suggested the diagnosis of pernicious anemia. Indirect antiglobulin test (IAT) was negative. Surprisingly, treatment by vitamin B and folic acid administered for two weeks was ineffective and followed by transitory worsening of hemoglobin concentration on day 8. Repeat direct antiglobulin test (DAT) and IAT were positive. This immunotransfusion conversion, suggesting the presence of autoimmune hemolytic anemia, could be explained by change in the macroblastic erythrocyte population, i.e. emerging red cells with completely exposed membrane antigens due to vitamin B treatment and/or higher degree of dysregulation of the lymphocyte clone secreting erythrocyte autoantibodies. We proposed the coexistence of pernicious and autoimmune hemolytic anemia; therefore, methylprednisolone was added to vitamin B treatment. This therapy successfully improved hemoglobin and erythrocyte concentration. Although megaloblastic-pernicious anemia is a common disease, association of pernicious and autoimmune hemolytic anemia with two mechanisms of hemolysis (ineffective erythropoiesis and immune mechanism) is a rare condition, with only several dozens of cases described so far