Browsing by Author "Elezovic, I. (12782840600)"

Repeated thromboses are the most frequent clinical manifestation of antiphospholipid syndrome (APS) in the presence of antiphospholipid antibodies (aPL). The objective of this study was to observe the prevalence and localization of thrombosis, and to investigate the importance of aPL type and level for thrombosis-related events in patients diagnosed with APS. These are the first results of patients enrolled in Serbian National Cohort Study which comprises 256 patients: 162 with primary antiphospholipid syndrome (PAPS) and 94 with APS associated with systemic lupus erythematosus (SLE). aPL analysis included detection of aCL (IgG/IgM), β2GPI, and lupus anticoagulant. Thrombosis was diagnosed in 119 (46.5%) patients, with higher prevalence in PAPS compared with SLE patients (51.2% and 38.3%, respectively, p = 0.045). There was similar prevalence of arterial thrombosis in PAPS and SLE groups (34.6% and 34%, respectively, p = 0.932) although venous thrombosis was more frequent in PAPS (25.9% and 8.5%, respectively, p = 0.001). Thrombosis was observed in 92 (55.8%) patients who had more than one type of antibody (category I), in 13 (41.9%) patients with category IIa, in 19 (46.3%) patients with category IIb, and in 73 (44.2%) patients with category IIc (p = 0.10). The patients with thrombosis were older than those without thrombosis (49.8 and 39.8 years, respectively, p = 0.001). Overall, older age was a risk factor for thrombosis. The prevalence of venous thrombosis was higher in the PAPS group, but with lower frequency than in literature data. Any aPL type and level is a risk factor for thrombosis. © The Author(s), 2012.

Five instances of inhibitor to factor XII-XI have been reported so far. These have arisen in two women suffering from systemic lupus erythematosus and in three patients with Waldenstrom macroglobulinaemia. None of these patients had a bleeding tendency. The authors believe that it is of interest to report a 45-year-old female with an 18 years history of a bleeding tendency, who developed life-threatening vaginal bleeding following total hysterectomy for rupture of an ovarian cyst. Coagulation studies revealed a prolonged whole blood clotting time of 19 min and an activated partial thromboplastin time of 199 s (control 40 s). Further experiments showed that the patient's plasma at the dilution of 1:32 inhibited a contact product preparation thus indicating an inhibitor to factor XII-XI. The patient was treated with a variety of blood products without success but the administration of FEIBA 60 units/kg/d for 4 d was followed by the arrest of bleeding. The patient recovered completely. She had no evidence of an associated systemic disease but the inhibitor is still present in the plasma.

Few randomized studies have reported on the use of factor IX (FIX) for secondary prophylaxis in haemophilia B patients. This study aimed to evaluate the efficacy and safety of two secondary prophylaxis regimens of recombinant coagulation FIX, nonacog alfa, compared with on-demand therapy. Male subjects aged 6-65 years with severe or moderately severe haemophilia B (FIX:C ≤ 2, n = 50) and ≥12 bleeding episodes (including ≥6 haemarthroses episodes) within 12 months of study participation were enrolled in this multicentre, randomized, open-label, four-period crossover trial. The primary measure was the annualized bleeding rate (ABR) of two prophylactic regimens vs. on-demand therapy. In the intent-to-treat group, mean ABR values were 35.1, 2.6 and 4.6 for the first on-demand period, the 50 IU kg-1 twice-weekly period, and the 100 IU kg-1 once-weekly period respectively. Differences in ABR between the first on-demand period and both prophylaxis regimens were significant (P < 0.0001); no significant differences were observed between prophylaxis regimens (P = 0.22). Seven serious adverse events occurred in five subjects, none related to study drug. Results demonstrated that secondary prophylaxis therapy with nonacog alfa 50 IU kg-1 twice weekly or 100 IU kg-1 once weekly reduced ABR by 89.4% relative to on-demand treatment. Both prophylaxis regimens demonstrated favourable safety profiles in subjects with haemophilia B. © 2014 John Wiley & Sons Ltd.

Introduction: Thrombin activatable fibrinolysis inhibitor (TAFI) down-regulates fibrinolysis after activation by thrombin/thrombomodulin. We investigated the effect of treatment with FVIII concentrate on plasma levels of pro-TAFI and activated TAFI in haemophilia A patients. Methods: Samples were collected pre and posttreatment from patients treated prophylactically or on-demand. Pro-TAFI, TAFI/TAFIi and FVIII levels were measured in all samples. Results: Treatment had no effect on pro-TAFI levels. Pro-TAFI was similar in both patient groups but higher than in controls. Patients from the prophylactic treatment group had measurable FVIII levels pretreatment while in the treatment-on-demand group FVIII levels were ≤0.01IU/mL. In the prophylactic treatment group, the levels of TAFI/TAFIi were significantly lower pre- and posttreatment (4.31±3.14 and 3.48±2.65ng/mL respectively) than in the on-demand group (13.02±3.47 and 14.87±3.47ng/mL respectively). This difference may be due to release of tissue factor at the injury site in the on-demand group. This could induce thrombin and TAFI activation within the clot counterbalancing fibrinolysis in these patients. In the prophylactic group, no injury existed, thus there was insufficient thrombin generation within the clot to activate TAFI. Conclusion: These findings suggest that in patients to whom FVIII is administered on demand the fibrinolysis activity is more down regulated than in patients following a prophylactic treatment regime. © 2011 Blackwell Publishing Ltd.

Introduction: Thrombin activatable fibrinolysis inhibitor (TAFI) down-regulates fibrinolysis after activation by thrombin/thrombomodulin. We investigated the effect of treatment with FVIII concentrate on plasma levels of pro-TAFI and activated TAFI in haemophilia A patients. Methods: Samples were collected pre and posttreatment from patients treated prophylactically or on-demand. Pro-TAFI, TAFI/TAFIi and FVIII levels were measured in all samples. Results: Treatment had no effect on pro-TAFI levels. Pro-TAFI was similar in both patient groups but higher than in controls. Patients from the prophylactic treatment group had measurable FVIII levels pretreatment while in the treatment-on-demand group FVIII levels were ≤0.01IU/mL. In the prophylactic treatment group, the levels of TAFI/TAFIi were significantly lower pre- and posttreatment (4.31±3.14 and 3.48±2.65ng/mL respectively) than in the on-demand group (13.02±3.47 and 14.87±3.47ng/mL respectively). This difference may be due to release of tissue factor at the injury site in the on-demand group. This could induce thrombin and TAFI activation within the clot counterbalancing fibrinolysis in these patients. In the prophylactic group, no injury existed, thus there was insufficient thrombin generation within the clot to activate TAFI. Conclusion: These findings suggest that in patients to whom FVIII is administered on demand the fibrinolysis activity is more down regulated than in patients following a prophylactic treatment regime. © 2011 Blackwell Publishing Ltd.

What is known and objective 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). Case summary We report a patient with refractory ITP who achieved CR on romiplostim. Obtaining romiplostim for 6 months of therapy, we decided to try extending this by modifying the standard treatment regimen. Romiplostim was successfully administered 'on-demand', only if the patient's platelet count dropped below 150 × 109/L, over a period of 12 months. What is new and conclusion The strategy of 'on-demand' therapy is a promising procedure for the maintenance of response, lowering costs and improving treatment safety. © 2016 John Wiley & Sons Ltd.

What is known and objective 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). Case summary We report a patient with refractory ITP who achieved CR on romiplostim. Obtaining romiplostim for 6 months of therapy, we decided to try extending this by modifying the standard treatment regimen. Romiplostim was successfully administered 'on-demand', only if the patient's platelet count dropped below 150 × 109/L, over a period of 12 months. What is new and conclusion The strategy of 'on-demand' therapy is a promising procedure for the maintenance of response, lowering costs and improving treatment safety. © 2016 John Wiley & Sons Ltd.

[No abstract available]

The study included 48 untreated patients with monoclonal gammopathies (MG). Paraprotein was isolated from the serum of 10 patients with decreased platelet aggregation. Platelet aggregation was measured before and after the addition of the isolated paraprotein to platelet-rich plasma (PRP) from 10 healthy donors, in vitro. Expression of platelet von Willebrand factor (vWF) receptor glycoprotein (GP)Ib and platelet collagen receptor GPVI was determined by flow cytometry in the PRP of healthy donors before and after the addition of isolated paraprotein using the monoclonal antibodies, CD42b (for GPIb) and CD36 (for GPVI). Flowcytometry showed that expression of CD42b and CD36 positive cells was reduced after the addition of isolated paraprotein to PRP from healthy donors (p < 0.001). These investigations demonstrated that paraprotein causes platelet dysfunction in patients with MG due to specific binding to the platelet vWF receptor GPIb and platelet collagen receptor GPVI. Copyright © 2013 S. Karger AG, Basel.