Ivo V Elezovic | University of Belgrade (original) (raw)
Papers by Ivo V Elezovic
Blood Coagulation & Fibrinolysis, Dec 1, 2015
Owing to the heterogeneity in the clinical phenotype of haemophilia A and B, it is now recognized... more Owing to the heterogeneity in the clinical phenotype of haemophilia A and B, it is now recognized that disease severity (based on factor VIII/IX activity) may no longer be the most appropriate guide for treatment and that a 'onesize-fits-all' approach is unlikely to achieve optimal therapy. Based on the present literature and consensus views of a group of experts in the field, this article highlights key gaps in the understanding of the diverse relationships between bleeding phenotype and factors such as joint health, genetic susceptibility, laboratory parameters, quality of life and management of pain. Early prophylaxis is a potential 'gold standard' therapy and issues surrounding inhibitor development, variations in its clinical use and long-term outcomes are discussed. Comprehensive treatment should be individualized for all patients (including those with mild or moderate haemophilia and carriers). Wherever possible all patients should be given prophylaxis. However, adult patients with a milder haemophilia phenotype may be candidates for ceasing prophylaxis and switching to ondemand treatment. Regardless, all treatment (on-demand and prophylaxis) should be tailored towards both the patient's personal needs and their clinical profile. In addition, as the associations between risk factors (psychosocial, condition-related and treatment-related) and clinical features are unique to each patient, an individualized approach is required to enable patients to alter their behaviour in response to them. The practical methodologies needed to reach this goal of individualized haemophilia care, and the health economic implications of this strategy, are ongoing topics for discussion. Blood Coagul Fibrinolysis 26:849-857
Srpski Arhiv Za Celokupno Lekarstvo, 2012
Journal of Clinical Pharmacy and Therapeutics, Feb 6, 2016
Although thrombopoietin receptor agonists are a second‐line treatment for refractory immune throm... more Although thrombopoietin receptor agonists are a second‐line treatment for refractory immune thrombocytopenia (ITP), we lack guidelines recommending maintenance modality in patients who achieve complete remission (CR).
Hematology, 2012
Historically in hemophilia, outcome measures have not been collected systematically. Hence, there... more Historically in hemophilia, outcome measures have not been collected systematically. Hence, there are insufficient clearly defined, evidence-based measures that can be applied consistently across hemophilia trials. This review focuses on some key challenges to evaluating patient outcomes and performing trials identified by experts at the Fourth and Fifth Zurich Haemophilia Forums. As procedures appear inconsistent across Europe, guidelines require modification to be more appropriate and/or realistically achievable. The outcome measures utilized, and the timing of their collection, should also be standardized, and more objective measures used where feasible. Implementation of outcome measures could be refined through greater understanding of patient heterogeneity, and tailored to differentiate between hemophiliaand aging-related disease effects. Furthermore, robust outcome measures that can also inform healtheconomic decisions are increasingly needed. Lastly, as patient recruitment poses a challenge, the panel proposed a call for action to motivate physicians and patients to participate in clinical trials.
European Journal of Haematology, Feb 7, 2012
Patients with congenital hemophilia require lifelong replacement therapy with a clotting factor c... more Patients with congenital hemophilia require lifelong replacement therapy with a clotting factor concentrate: factor (F) VIII in hemophilia A and FIX in hemophilia B (1). However, patients can develop inhibitors to these exogenous factors, resulting in the most serious treatment-related complication in hemophilia (2, 3). Once inhibitors have developed, it is more challenging to achieve hemostasis than in non-inhibitor patients. Furthermore , the presence of inhibitors has a major impact on patients' physical functioning, quality of life, morbidity, and mortality (4-6). In patients with high-titer inhibitors [ ‡5 Bethesda units (BU)], immune tolerance induction (ITI) aims to eradicate anamnestic inhibitors and restore normal responses to replacement therapy. The process of ITI involves regular infusion of FVIII or FIX concentrate with the goal
Journal of Thrombosis and Haemostasis, 2015
Background: Vatreptacog alfa, a recombinant human factor VIIa (rFVIIa) analog developed to improv... more Background: Vatreptacog alfa, a recombinant human factor VIIa (rFVIIa) analog developed to improve the treatment of bleeds in hemophilia patients with inhibitors, differs from native FVIIa by three amino acid substitutions. In a randomized, double-blind, crossover, confirmatory phase III trial (adept TM 2), 8/72 (11%) hemophilia A or B patients with inhibitors treated for acute bleeds developed anti-drug antibodies (ADAs) to vatreptacog alfa. Objectives: To characterize the formation of anti-vatreptacog alfa ADAs in hemophilia patients with inhibitors. Methods/patients: This was a post hoc analysis of adept TM 2. Immunoglobulin isotype determination, specificity analysis of rFVIIa cross-reactive antibodies, epitope mapping of rFVIIa single mutant analogs and pharmacokinetic (PK) profiling were performed to characterize the ADAs. Results: Immunoglobulin isotyping indicated that the ADAs were of the immunoglobulin G subtype. In epitope mapping, none of the rFVIIa single mutant analogs (V158D, E296V or M298Q) contained the complete antibody epitope, confirming that the antibodies were specific for vatreptacog alfa. In two patients, for whom PK profiling was performed both before and after the development of ADAs, vatreptacog alfa showed a prolonged elimination phase following ADA development. During the follow-up evaluation, the rFVIIa cross-reactivity disappeared after the last vatreptacog alfa exposure, despite continued exposure to rFVIIa as part of standard care. Conclusions: Results from the vatreptacog alfa phase III trial demonstrate that the specific changes made, albeit relatively small, to the FVIIa molecule alter its clinical immunogenicity.
PubMed, 1979
This report presents the case of a 36 year old woman with an inborn haemorrhagic syndrome, who ex... more This report presents the case of a 36 year old woman with an inborn haemorrhagic syndrome, who exhibited a lifelong history of spontaneous bruising, nose bleeding, prolonged bleeding after tooth extraction, and menometrorrhagia. The routine tests of haemostasis were consistent with impaired platelet functions. The diagnosis of the "Aspirin-like defect" was made on the basis of the following findings: the bleeding time was prolonged, whereas the platelet count and morphology were normal; platelet retention in glass bead filters was unmeasurable. ADP-induced platelet aggregation was normal, while it was markedly reduced with collagen and epinephrine. The platelet ADP and ATP content, as well as the ATP/ADP ratio were within normal limits. Aggregation of platelets pre-incubated with aspirin was only slightly reduced when induced by ADP, collagen, or epinephrine. These findings suggest that the thrombocytopathy in our patient is due to an impaired ADP release from the platelet granules containing normal quantities of adenine nucleotides. A similar disorder is observed in normal subjects after aspirin ingestion, and therefore the defect described in this paper is referred to as the "Aspirin-like" defect.
PubMed, 1993
We present a case of an unusual multi-systematic disorder whose cardinal signs were severe progre... more We present a case of an unusual multi-systematic disorder whose cardinal signs were severe progressive sensorimotor polyneuropathy, hepatomegaly, endocrinopathy, plasma cell dyscrasia with osteosclerotic bone lesions and M-protein production as well as skin lesions (termed POEMS Syndrome) whose pathophysiology is still unknown, as well as its relationship with myeloma multiplex. The patient, 67 years old, had a history of progressive weakness and numbness of the lower legs, clinically revealed as sensomotor polyneuropathy, hepatomegaly, IgG lambda monoclonal protein in the serum, endocrine abnormalities and skin lesions. The final and definite diagnosis was established by open, surgical biopsy of the second lumbal vertebra.
PubMed, May 1, 1995
HELLP-syndrome comprises microangiophatic hemolytic anemia, elevated liver enzymes and low platel... more HELLP-syndrome comprises microangiophatic hemolytic anemia, elevated liver enzymes and low plateled count in patients with severe preeclampsia/eclampsia. It carries high risk of maternal and perinatal mortality and It's necessary to be recognized and treated on time. The authors present a woman, 22 years old, with pospartum eclampsia and HELLP syndrome. The patient was treated successfully and was cured in short time.
PubMed, May 1, 1994
A 36-year old woman with recurrent thrombosis manifested in the form of venous thrombosis of the ... more A 36-year old woman with recurrent thrombosis manifested in the form of venous thrombosis of the leg, thrombus in the right atrium and ventricle of the heart, pulmonary embolism and recurrent foetal loss, is described. Laboratory results showed prolonged APTT and normal coagulation factors. All this suggested to lupus anticoagulant (LA), which was confirmed by prolonged KCT, DRVVT, false positive VDRL test, and high level of anticardiolipin antibodies (ELISA). The diagnosis of primary antiphospholipid syndrome was established by clinical findings of recurrent thrombosis, foetal loss, presence of LA and anticardiolipin antibodies.
PubMed, Jul 1, 1989
Immune thrombocytopenic purpura may be the sole clinical manifestation of HIV infection. Results ... more Immune thrombocytopenic purpura may be the sole clinical manifestation of HIV infection. Results of the treatment of 6 patients with spontaneous bleeding due to severe thrombocytopenia, are presented. In all patients immune thrombocytopenic purpura was the only clinical manifestation of HIV infection. Four of them were intravenous narcotic addicts, and the other two patients did not belong to high risk groups. Prednisone treatment of 1 mg/kg daily was sufficient to resolve bleeding and achieve platelet count elevation above 50 X 10(9)/l in five of six patients. Lowering the dose of prednisone of therapy withdrawal were associated with a fall in the platelet count. In three patients the complete remission was not achieved and danazol was administered, 600-800 mg orally daily, with variable efficacy. One of these patients achieved platelet count elevation above 50 X 10(9)/l, while the two others did not respond.
Srpski Arhiv Za Celokupno Lekarstvo, Nov 1, 1991
The article deals with a successfull extirpation of femoral pseudotumour in a 53-year-old patient... more The article deals with a successfull extirpation of femoral pseudotumour in a 53-year-old patient with severe haemophilia A (F VIII: C less than 1%) and an inhibitor to factor VIII. Such case is the first one reported in Yugoslavia. A combination of ultrasonography, computed axial tomography, angiography and Tc-99m labelled red blood cell scintigraphy was used for precise diagnosis of the pseudotumour. Preoperative preparation consisted of 50 units/kg of concentrate of F VIII (Hemate P) and 50 units/kg of activated prothrombine complex concentrate (FEIBA). A pseudotumour, 15 cm in diameter, was extirpated, as well as a few dauther cysts. F VIII concentrate was used for postoperative supportive therapy. On the 5-th postoperative day the patient prematurely rose from his bed and the "secondary bleeding" had to be treated with F VIII concentrate. The success of complex operations in haemophiliacs is possible only in big centres which can provide the best diagnostic procedures, trained surgeon teams, and modern and various supportive therapy.
![Research paper thumbnail of [Hereditary deficiency of antithrombin III, protein C, protein S and factor XII in 121 patients with venous or arterial thrombosis]](https://attachments.academia-assets.com/111273637/thumbnails/1.jpg)
](PubMed, Jun 23, 1999
Introduction: Hereditary thrombophilia is caused by various inherited disorders which lead to fam... more Introduction: Hereditary thrombophilia is caused by various inherited disorders which lead to familial tendency to recurrent venous thrombosis usually at an early age and with spontaneous onset. In the studies reported so far, the different prevalence of hereditary thrombophilia among patients with venous thrombosis was found, greatly depending on criteria for selection of patients. Arterial thrombosis is most often the consequence of arteriosclerosis but the prevalence of hereditary thrombophilia among young patients with arterial thrombosis and without recognized risk factors for arteriosclerosis is not known . In this study, the frequency of hereditary deficiencies of antithrombin III (AT III), protein C (PC), protein S (PS), plasminogen (PLMG), factor XII (F XII) and dysfibrinogenaemia was investigated over a 2-year period in 121 patients with venous or arterial thrombosis selected according to the recommendations of the British Committee for Standards in Haematology. Patients and methods: The study included total a of 121 patients (58 males and 63 females) with documented venous or arterial thrombosis. Table 1 shows patient's characteristics regarding gender, age and clinical manifestation of thrombosis. Each patient fulfilled at least one of the following criteria: a) venous thrombosis prior to the age of 45; b) arterial thrombosis prior to the age of 30, without risk factors for arteriosclerosis; c) recurrent thrombosis; d) familial tendency to thrombosis; e) thrombosis of unusual localization. A detailed history was taken from each patient on earlier personal or familial occurrence of thrombosis. For the purpose of this study, thrombophilia was characterized as congenital when the deficient protein was constantly below normal value and when the same deficiency was confirmed in a close family member; acquired when the acquired disorder predisposing to thrombosis was present in absence of constant protein deficiency; and idiopathic when the cause of thrombosis was unknown. All tests were performed in plasma obtained after centrifugation of venous blood anticoagulated with 0.129 mol/1 sodium citrate. Concentrations of fibrinogen, PT, PTT and F XII were measured by standard clotting methods. At III, PC and plasminogen activity were determined by chromogenic methods using commercial reagents (Boehring, Marburg, Germany). AT III, PC and total PS antigen were assayed by Laurell immunoelectrophoresis. The presence of lupus anticoagulant was investigated by recommended tests. Results: A total of 15 patients (12.4%) fulfilled criteria for hereditary thrombophilia. Seven of them (5.8%) had AT III deficiency, five (4.1%) PC deficiency, two (1.6%) PS deficiency, and one patient had F XII deficiency. Secondary thrombophilia was found in 21.5% of patients and the cause of thrombosis in 66.1% of patients was not elucidated. A high frequency of hereditary thrombophilia has been found in patients with arterial thrombosis (40%). Among patients with hereditary thrombophilia thrombosis occurred at significantly younger age (29.9 vs. 42.2 and 40.9 yr.) compared to the patients with secondary and idiopathic thrombophilia, respectively. Patients with hereditary thrombophilia had also a higher occurrence of positive family history related to thrombosis (66.7% vs. 7.7% and 27.5%). Discussion: The prevalence of hereditary thrombophilia in nonselected patients with venous thrombosis is relatively low, and for that reason the selection of patients, according recommended criteria, in whom the screening tests for congenital thrombophilia should be performed, is strongly suggested by many authors. In our study we used the generally accepted recommendations for investigation of patients with venous and arterial thrombosis. The presence of congenital thrombophilia was found in 15 (12.4%) of 121 studied patients, what is in accordance with results of other similarly designed studies. (ABSTRACT TRUNCATED)
Srpski Arhiv Za Celokupno Lekarstvo, Jul 1, 1994
ABSTRACT
Srpski Arhiv Za Celokupno Lekarstvo, Jul 1, 1988
We describe a 51-year old-woman with haemorrhagic syndrome manifested as spontaneous bruising, an... more We describe a 51-year old-woman with haemorrhagic syndrome manifested as spontaneous bruising, and prolonged and abundant menstrual bleeding. She had hed these symptomes for six months prior to admission, but denied lifelong bleeding tendency. Gynaecological examination revealed a myomatouse uterus. Occasionally, the patient had crops of erythemo-exudative skin lesion which were shown on biopsy to represent urticarial (leukocytoclastic) vasculitis. No evidence of systemic connective tissue disease was found. Haemostasis testing revealed: prolonged bleeding time, decreased platelet adhesiveness to glass beads, lowered FVIII : C, absence of ristocetin-induced platelet aggregation and unmeasurable FVIII : Af and vWf. There was no evidence for an inhibitor to FVIII : C. However, patient's plasma, when mixed ana partes equales with normal plasma, reduced the FVIII : Ag and vWf level to 48% and 46% respectively, as compared to the mixture of normal plasma and buffer. When incubated at room temperature, patient's washed platelets spontaneously released vWf and aggregated in the presence ristocetin. However, when patient's plasma was added aggregation was inhibited. On the basis of these findings and the lack of anamnestic data suggestive of congenital haemorrhagic disorder, we concluded that the patient had acquired von Willebrand disease due to an inhibitor to vWf and FVIII : Ag, associated with urticarial vasculitis and myomatouse uterus. To our knowledge, this association has not yet been reported.
Blood Coagulation & Fibrinolysis, Dec 1, 2015
Owing to the heterogeneity in the clinical phenotype of haemophilia A and B, it is now recognized... more Owing to the heterogeneity in the clinical phenotype of haemophilia A and B, it is now recognized that disease severity (based on factor VIII/IX activity) may no longer be the most appropriate guide for treatment and that a 'onesize-fits-all' approach is unlikely to achieve optimal therapy. Based on the present literature and consensus views of a group of experts in the field, this article highlights key gaps in the understanding of the diverse relationships between bleeding phenotype and factors such as joint health, genetic susceptibility, laboratory parameters, quality of life and management of pain. Early prophylaxis is a potential 'gold standard' therapy and issues surrounding inhibitor development, variations in its clinical use and long-term outcomes are discussed. Comprehensive treatment should be individualized for all patients (including those with mild or moderate haemophilia and carriers). Wherever possible all patients should be given prophylaxis. However, adult patients with a milder haemophilia phenotype may be candidates for ceasing prophylaxis and switching to ondemand treatment. Regardless, all treatment (on-demand and prophylaxis) should be tailored towards both the patient's personal needs and their clinical profile. In addition, as the associations between risk factors (psychosocial, condition-related and treatment-related) and clinical features are unique to each patient, an individualized approach is required to enable patients to alter their behaviour in response to them. The practical methodologies needed to reach this goal of individualized haemophilia care, and the health economic implications of this strategy, are ongoing topics for discussion. Blood Coagul Fibrinolysis 26:849-857
Srpski Arhiv Za Celokupno Lekarstvo, 2012
Journal of Clinical Pharmacy and Therapeutics, Feb 6, 2016
Although thrombopoietin receptor agonists are a second‐line treatment for refractory immune throm... more Although thrombopoietin receptor agonists are a second‐line treatment for refractory immune thrombocytopenia (ITP), we lack guidelines recommending maintenance modality in patients who achieve complete remission (CR).
Hematology, 2012
Historically in hemophilia, outcome measures have not been collected systematically. Hence, there... more Historically in hemophilia, outcome measures have not been collected systematically. Hence, there are insufficient clearly defined, evidence-based measures that can be applied consistently across hemophilia trials. This review focuses on some key challenges to evaluating patient outcomes and performing trials identified by experts at the Fourth and Fifth Zurich Haemophilia Forums. As procedures appear inconsistent across Europe, guidelines require modification to be more appropriate and/or realistically achievable. The outcome measures utilized, and the timing of their collection, should also be standardized, and more objective measures used where feasible. Implementation of outcome measures could be refined through greater understanding of patient heterogeneity, and tailored to differentiate between hemophiliaand aging-related disease effects. Furthermore, robust outcome measures that can also inform healtheconomic decisions are increasingly needed. Lastly, as patient recruitment poses a challenge, the panel proposed a call for action to motivate physicians and patients to participate in clinical trials.
European Journal of Haematology, Feb 7, 2012
Patients with congenital hemophilia require lifelong replacement therapy with a clotting factor c... more Patients with congenital hemophilia require lifelong replacement therapy with a clotting factor concentrate: factor (F) VIII in hemophilia A and FIX in hemophilia B (1). However, patients can develop inhibitors to these exogenous factors, resulting in the most serious treatment-related complication in hemophilia (2, 3). Once inhibitors have developed, it is more challenging to achieve hemostasis than in non-inhibitor patients. Furthermore , the presence of inhibitors has a major impact on patients' physical functioning, quality of life, morbidity, and mortality (4-6). In patients with high-titer inhibitors [ ‡5 Bethesda units (BU)], immune tolerance induction (ITI) aims to eradicate anamnestic inhibitors and restore normal responses to replacement therapy. The process of ITI involves regular infusion of FVIII or FIX concentrate with the goal
Journal of Thrombosis and Haemostasis, 2015
Background: Vatreptacog alfa, a recombinant human factor VIIa (rFVIIa) analog developed to improv... more Background: Vatreptacog alfa, a recombinant human factor VIIa (rFVIIa) analog developed to improve the treatment of bleeds in hemophilia patients with inhibitors, differs from native FVIIa by three amino acid substitutions. In a randomized, double-blind, crossover, confirmatory phase III trial (adept TM 2), 8/72 (11%) hemophilia A or B patients with inhibitors treated for acute bleeds developed anti-drug antibodies (ADAs) to vatreptacog alfa. Objectives: To characterize the formation of anti-vatreptacog alfa ADAs in hemophilia patients with inhibitors. Methods/patients: This was a post hoc analysis of adept TM 2. Immunoglobulin isotype determination, specificity analysis of rFVIIa cross-reactive antibodies, epitope mapping of rFVIIa single mutant analogs and pharmacokinetic (PK) profiling were performed to characterize the ADAs. Results: Immunoglobulin isotyping indicated that the ADAs were of the immunoglobulin G subtype. In epitope mapping, none of the rFVIIa single mutant analogs (V158D, E296V or M298Q) contained the complete antibody epitope, confirming that the antibodies were specific for vatreptacog alfa. In two patients, for whom PK profiling was performed both before and after the development of ADAs, vatreptacog alfa showed a prolonged elimination phase following ADA development. During the follow-up evaluation, the rFVIIa cross-reactivity disappeared after the last vatreptacog alfa exposure, despite continued exposure to rFVIIa as part of standard care. Conclusions: Results from the vatreptacog alfa phase III trial demonstrate that the specific changes made, albeit relatively small, to the FVIIa molecule alter its clinical immunogenicity.
PubMed, 1979
This report presents the case of a 36 year old woman with an inborn haemorrhagic syndrome, who ex... more This report presents the case of a 36 year old woman with an inborn haemorrhagic syndrome, who exhibited a lifelong history of spontaneous bruising, nose bleeding, prolonged bleeding after tooth extraction, and menometrorrhagia. The routine tests of haemostasis were consistent with impaired platelet functions. The diagnosis of the "Aspirin-like defect" was made on the basis of the following findings: the bleeding time was prolonged, whereas the platelet count and morphology were normal; platelet retention in glass bead filters was unmeasurable. ADP-induced platelet aggregation was normal, while it was markedly reduced with collagen and epinephrine. The platelet ADP and ATP content, as well as the ATP/ADP ratio were within normal limits. Aggregation of platelets pre-incubated with aspirin was only slightly reduced when induced by ADP, collagen, or epinephrine. These findings suggest that the thrombocytopathy in our patient is due to an impaired ADP release from the platelet granules containing normal quantities of adenine nucleotides. A similar disorder is observed in normal subjects after aspirin ingestion, and therefore the defect described in this paper is referred to as the "Aspirin-like" defect.
PubMed, 1993
We present a case of an unusual multi-systematic disorder whose cardinal signs were severe progre... more We present a case of an unusual multi-systematic disorder whose cardinal signs were severe progressive sensorimotor polyneuropathy, hepatomegaly, endocrinopathy, plasma cell dyscrasia with osteosclerotic bone lesions and M-protein production as well as skin lesions (termed POEMS Syndrome) whose pathophysiology is still unknown, as well as its relationship with myeloma multiplex. The patient, 67 years old, had a history of progressive weakness and numbness of the lower legs, clinically revealed as sensomotor polyneuropathy, hepatomegaly, IgG lambda monoclonal protein in the serum, endocrine abnormalities and skin lesions. The final and definite diagnosis was established by open, surgical biopsy of the second lumbal vertebra.
PubMed, May 1, 1995
HELLP-syndrome comprises microangiophatic hemolytic anemia, elevated liver enzymes and low platel... more HELLP-syndrome comprises microangiophatic hemolytic anemia, elevated liver enzymes and low plateled count in patients with severe preeclampsia/eclampsia. It carries high risk of maternal and perinatal mortality and It's necessary to be recognized and treated on time. The authors present a woman, 22 years old, with pospartum eclampsia and HELLP syndrome. The patient was treated successfully and was cured in short time.
PubMed, May 1, 1994
A 36-year old woman with recurrent thrombosis manifested in the form of venous thrombosis of the ... more A 36-year old woman with recurrent thrombosis manifested in the form of venous thrombosis of the leg, thrombus in the right atrium and ventricle of the heart, pulmonary embolism and recurrent foetal loss, is described. Laboratory results showed prolonged APTT and normal coagulation factors. All this suggested to lupus anticoagulant (LA), which was confirmed by prolonged KCT, DRVVT, false positive VDRL test, and high level of anticardiolipin antibodies (ELISA). The diagnosis of primary antiphospholipid syndrome was established by clinical findings of recurrent thrombosis, foetal loss, presence of LA and anticardiolipin antibodies.
PubMed, Jul 1, 1989
Immune thrombocytopenic purpura may be the sole clinical manifestation of HIV infection. Results ... more Immune thrombocytopenic purpura may be the sole clinical manifestation of HIV infection. Results of the treatment of 6 patients with spontaneous bleeding due to severe thrombocytopenia, are presented. In all patients immune thrombocytopenic purpura was the only clinical manifestation of HIV infection. Four of them were intravenous narcotic addicts, and the other two patients did not belong to high risk groups. Prednisone treatment of 1 mg/kg daily was sufficient to resolve bleeding and achieve platelet count elevation above 50 X 10(9)/l in five of six patients. Lowering the dose of prednisone of therapy withdrawal were associated with a fall in the platelet count. In three patients the complete remission was not achieved and danazol was administered, 600-800 mg orally daily, with variable efficacy. One of these patients achieved platelet count elevation above 50 X 10(9)/l, while the two others did not respond.
Srpski Arhiv Za Celokupno Lekarstvo, Nov 1, 1991
The article deals with a successfull extirpation of femoral pseudotumour in a 53-year-old patient... more The article deals with a successfull extirpation of femoral pseudotumour in a 53-year-old patient with severe haemophilia A (F VIII: C less than 1%) and an inhibitor to factor VIII. Such case is the first one reported in Yugoslavia. A combination of ultrasonography, computed axial tomography, angiography and Tc-99m labelled red blood cell scintigraphy was used for precise diagnosis of the pseudotumour. Preoperative preparation consisted of 50 units/kg of concentrate of F VIII (Hemate P) and 50 units/kg of activated prothrombine complex concentrate (FEIBA). A pseudotumour, 15 cm in diameter, was extirpated, as well as a few dauther cysts. F VIII concentrate was used for postoperative supportive therapy. On the 5-th postoperative day the patient prematurely rose from his bed and the "secondary bleeding" had to be treated with F VIII concentrate. The success of complex operations in haemophiliacs is possible only in big centres which can provide the best diagnostic procedures, trained surgeon teams, and modern and various supportive therapy.
PubMed, Jun 23, 1999
Introduction: Hereditary thrombophilia is caused by various inherited disorders which lead to fam... more Introduction: Hereditary thrombophilia is caused by various inherited disorders which lead to familial tendency to recurrent venous thrombosis usually at an early age and with spontaneous onset. In the studies reported so far, the different prevalence of hereditary thrombophilia among patients with venous thrombosis was found, greatly depending on criteria for selection of patients. Arterial thrombosis is most often the consequence of arteriosclerosis but the prevalence of hereditary thrombophilia among young patients with arterial thrombosis and without recognized risk factors for arteriosclerosis is not known . In this study, the frequency of hereditary deficiencies of antithrombin III (AT III), protein C (PC), protein S (PS), plasminogen (PLMG), factor XII (F XII) and dysfibrinogenaemia was investigated over a 2-year period in 121 patients with venous or arterial thrombosis selected according to the recommendations of the British Committee for Standards in Haematology. Patients and methods: The study included total a of 121 patients (58 males and 63 females) with documented venous or arterial thrombosis. Table 1 shows patient's characteristics regarding gender, age and clinical manifestation of thrombosis. Each patient fulfilled at least one of the following criteria: a) venous thrombosis prior to the age of 45; b) arterial thrombosis prior to the age of 30, without risk factors for arteriosclerosis; c) recurrent thrombosis; d) familial tendency to thrombosis; e) thrombosis of unusual localization. A detailed history was taken from each patient on earlier personal or familial occurrence of thrombosis. For the purpose of this study, thrombophilia was characterized as congenital when the deficient protein was constantly below normal value and when the same deficiency was confirmed in a close family member; acquired when the acquired disorder predisposing to thrombosis was present in absence of constant protein deficiency; and idiopathic when the cause of thrombosis was unknown. All tests were performed in plasma obtained after centrifugation of venous blood anticoagulated with 0.129 mol/1 sodium citrate. Concentrations of fibrinogen, PT, PTT and F XII were measured by standard clotting methods. At III, PC and plasminogen activity were determined by chromogenic methods using commercial reagents (Boehring, Marburg, Germany). AT III, PC and total PS antigen were assayed by Laurell immunoelectrophoresis. The presence of lupus anticoagulant was investigated by recommended tests. Results: A total of 15 patients (12.4%) fulfilled criteria for hereditary thrombophilia. Seven of them (5.8%) had AT III deficiency, five (4.1%) PC deficiency, two (1.6%) PS deficiency, and one patient had F XII deficiency. Secondary thrombophilia was found in 21.5% of patients and the cause of thrombosis in 66.1% of patients was not elucidated. A high frequency of hereditary thrombophilia has been found in patients with arterial thrombosis (40%). Among patients with hereditary thrombophilia thrombosis occurred at significantly younger age (29.9 vs. 42.2 and 40.9 yr.) compared to the patients with secondary and idiopathic thrombophilia, respectively. Patients with hereditary thrombophilia had also a higher occurrence of positive family history related to thrombosis (66.7% vs. 7.7% and 27.5%). Discussion: The prevalence of hereditary thrombophilia in nonselected patients with venous thrombosis is relatively low, and for that reason the selection of patients, according recommended criteria, in whom the screening tests for congenital thrombophilia should be performed, is strongly suggested by many authors. In our study we used the generally accepted recommendations for investigation of patients with venous and arterial thrombosis. The presence of congenital thrombophilia was found in 15 (12.4%) of 121 studied patients, what is in accordance with results of other similarly designed studies. (ABSTRACT TRUNCATED)
Srpski Arhiv Za Celokupno Lekarstvo, Jul 1, 1994
ABSTRACT
Srpski Arhiv Za Celokupno Lekarstvo, Jul 1, 1988
We describe a 51-year old-woman with haemorrhagic syndrome manifested as spontaneous bruising, an... more We describe a 51-year old-woman with haemorrhagic syndrome manifested as spontaneous bruising, and prolonged and abundant menstrual bleeding. She had hed these symptomes for six months prior to admission, but denied lifelong bleeding tendency. Gynaecological examination revealed a myomatouse uterus. Occasionally, the patient had crops of erythemo-exudative skin lesion which were shown on biopsy to represent urticarial (leukocytoclastic) vasculitis. No evidence of systemic connective tissue disease was found. Haemostasis testing revealed: prolonged bleeding time, decreased platelet adhesiveness to glass beads, lowered FVIII : C, absence of ristocetin-induced platelet aggregation and unmeasurable FVIII : Af and vWf. There was no evidence for an inhibitor to FVIII : C. However, patient's plasma, when mixed ana partes equales with normal plasma, reduced the FVIII : Ag and vWf level to 48% and 46% respectively, as compared to the mixture of normal plasma and buffer. When incubated at room temperature, patient's washed platelets spontaneously released vWf and aggregated in the presence ristocetin. However, when patient's plasma was added aggregation was inhibited. On the basis of these findings and the lack of anamnestic data suggestive of congenital haemorrhagic disorder, we concluded that the patient had acquired von Willebrand disease due to an inhibitor to vWf and FVIII : Ag, associated with urticarial vasculitis and myomatouse uterus. To our knowledge, this association has not yet been reported.