Fifty-five years (1955-2010) of the Coagulation Section at Laboratory of Hematology, Sestre milosrdnice University Hospital, and its founder, hematologist Ljubomir Popovic.

The Coagulation Section at Laboratory of Hematology, Sestre milosrdnice University Hospital, Zagreb, was founded in 1955 by Ljubomir Popovic, 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 Popovic 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 Popovic left the Hospital in 1964, the Laboratory was run by Professor Nedjeljko Milic, head of the newly founded Division of Hematology. In 1968, the management of the Laboratory of Hematology was taken over by Biserka Raic, 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 Koprcina, hematologist, and Biserka Raic introduced the then latest tests in practice at all Hospital departments. In that golden age of the Coagulation Section, M. Koprcina, B. Raic 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 Popovic, 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.

Nontraumatic bilateral subdural hematoma caused by antiaggregation therapy: case report and review of the 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.

Recurrent venous thrombosis despite 'optimal anticoagulation therapy' for antiphospholipid syndrome--could new oral anticoagulants solve the problem?

The aim was to determine the validity of the international normalized ratio (INR) 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 INRs 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 INR 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 thatis 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.

Combined megaloblastic and immunohemolytic anemia associated--a 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 B12 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 B12 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 B12 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 B12 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.