Safety and efficacy of damoctocog alfa pegol prophylaxis in patients with severe haemophilia A: Results of an interventional, post-marketing study.

INTRODUCTION: Damoctocog alfa pegol (BAY 94-9027, Jivi® ) is an approved extended half-life factor VIII (FVIII) for treatment of previously treated patients with haemophilia A aged ≥12 years. We report the final results of an interventional, post-marketing study of damoctocog alfa pegol prophylaxis in patients with severe haemophilia A. METHODS: In this open-label, interventional, post-marketing, phase 4 trial (NCT04085458), previously FVIII-treated patients with severe haemophilia A aged ≥18 years received damoctocog alfa pegol for ≥100 exposure days (EDs). Patients initially received 45 IU/kg every 5 days (recommended) or 40 IU/kg twice-weekly. At Visit 3, patients' doses could be increased, or treatment frequency adapted. The primary endpoint was FVIII inhibitor development (titre ≥.6 Bethesda units). Secondary endpoints included anti-polyethylene glycol (PEG) antibody development, treatment-emergent adverse events (AEs) and annualized bleeding rate (ABR). RESULTS: Overall, 36 patients were enrolled; 32 patients received treatment, of whom, 27 completed the study. No patients developed FVIII inhibitors; three tested transiently positive for low-titre anti-PEG antibodies without clinical relevance. Three patients reported study-drug-related AEs of mild or moderate intensity. Two patients discontinued the study due to AEs. No deaths occurred. Most patients (70%) were treated with E5D/E7D regimens. The median (Q1;Q3) total ABR (N = 30) was 3.0 (.0;9.0) pre-study and 1.8 (.7;5.9) during the study. CONCLUSION: Damoctocog alfa pegol individualized prophylaxis regimens were well-tolerated with no immunogenicity concerns. ABRs improved following the switch from pre-study prophylaxis to damoctocog alfa pegol prophylaxis. These results support the favourable safety and efficacy profile of damoctocog alfa pegol prophylaxis.

A post hoc analysis of PROTECT VIII kids assessing long-term efficacy and safety of damoctocog alfa pegol in adolescents with severe haemophilia A.

INTRODUCTION: The safety and efficacy of the extended half-life factor VIII (FVIII) product damoctocog alfa pegol (BAY 94-9027, Jivi®) has been demonstrated in the PROTECT VIII Kids study (NCT01775618), where male previously-treated patients (PTPs) aged <12 years old with severe haemophilia A and ≥ 50 exposure days (EDs) were treated prophylactically. The PROTECT VIII Kids extension study assessed the long-term safety and efficacy of damoctocog alfa pegol in the same population. AIM: To evaluate the long-term impact of damoctocog alfa pegol in a post hoc subgroup analysis of adolescent patients in the PROTECT VIII Kids study and its extension from 12th birthday onwards. METHODS: The current analysis included PTPs aged ≥12 years old, who remained in the extension for ≥6 months following their 12th birthday. The observation period was defined as the time from 12th birthday to the end of the extension period; all data from this birthday were included whether in the main study or extension phase. The main efficacy variable was annualised bleeding rate (ABR) and the main safety variable was the frequency of inhibitor development. RESULTS: This subgroup analysis comprised 25 patients. Median observation time after 12th birthday was 3.2 years. Median total/joint/spontaneous ABRs in the observation period were 1.7/0.7/0.3, respectively. Safety findings were consistent with those reported for the overall study population; no confirmed FVIII inhibitors or anti-drug antibodies were reported. CONCLUSIONS: Damoctocog alfa pegol is efficacious with a favourable safety profile in adolescents with haemophilia A, supporting its long-term use in children and adolescents.

Long-Term Efficacy and Safety of Damoctocog Alfa Pegol Prophylaxis in Patients with Haemophilia A Aged 12-<18 Years at Enrolment into PROTECT VIII.

INTRODUCTION: The phase 2/3 PROTECT VIII study demonstrated long-term efficacy and safety of damoctocog alfa pegol (BAY 94-9027; Jivi®), a B-domain-deleted recombinant factor VIII (FVIII), site-specifically PEGylated to improve its pharmacokinetic profile. We report a post hoc assessment of bleeding and safety outcomes in the subgroup of patients, aged 12-<18 years at enrolment. METHOD: PROTECT VIII was a multicentre, open-label study of previously treated males aged 12-65 years with severe haemophilia A (FVIII <1%). Twelve patients were included in this analysis. All received damoctocog alfa pegol prophylaxis for the total time in study (median [range] time in study 4.0 [1.3-6.2] years). RESULTS: Overall median (Q1; Q3) total and joint annualised bleeding rates were 1.8 (0.4; 5.1) and 0.7 (0.2; 1.8), respectively, for the entire study. During the last 6 months of treatment, eight (66.7%) and ten (83.3%) out of 12 patients experienced zero total and joint bleeds, respectively. No patient developed FVIII inhibitors. No deaths or thrombotic events were reported. CONCLUSION: Efficacy and safety of damoctocog alfa pegol were confirmed in adolescent patients with haemophilia A, with data for up to 6 years supporting its use as a long-term treatment option in this group as they transition into adulthood.

PROTECT VIII kids extension study: Long-term safety and efficacy of BAY 94-9027 (damoctocog alfa pegol) in children with severe haemophilia A.

INTRODUCTION: BAY 94-9027 (damoctocog alfa pegol; an extended half-life PEGylated recombinant factor VIII [FVIII]) demonstrated efficacy and safety in previously treated paediatric patients (PTPs) aged <12 years with severe haemophilia A in the PROTECT VIII Kids study (NCT01775618). AIM: To evaluate the long-term safety of BAY 94-9027 in PTPs aged <12 years at enrolment. METHODS: In the PROTECT VIII Kids study, boys <12 years with severe haemophilia A were enrolled in two age cohorts (6-<12 years and <6 years) and treated prophylactically twice weekly, every 5 days or every 7 days, with BAY 94-9027 for ≥50 exposure days (EDs). Patients who had completed ≥50 EDs and ≥6 months in the main study or 12-week safety expansion study were eligible to participate in the extension. Primary safety variable was frequency of inhibitor development; main efficacy variable was annualised bleeding rate (ABR). RESULTS: Of 73 PTPs from the main/expansion studies, 59 (81%) entered the extension phase for a median (range) duration of 5.0 (0.4-5.9) years. Overall, 39 patients completed ≥5 years of treatment. No patients developed FVIII inhibitors/anti-PEG antibodies, and two patients aged <6 years discontinued. Median ABR for total bleeds was 1.5 (<6 years) and 1.9 (6-<12 years). Total ABR improved in the extension vs. the main study. In the last 12 months of treatment, median spontaneous ABR was 0.0 in both age groups. CONCLUSIONS: BAY 94-9027 showed long-term safety and efficacy for the prevention and treatment of bleeds in younger and older paediatric patients with severe haemophilia A.

Confirmed long-term safety and efficacy of prophylactic treatment with BAY 94-9027 in severe haemophilia A: final results of the PROTECT VIII extension study.

INTRODUCTION: The phase 2/3 PROTECT VIII main study demonstrated efficacy and safety of BAY 94-9027 (damoctocog alfa pegol; Jivi® ), a B-domain-deleted recombinant factor VIII (FVIII), site-specifically PEGylated to extend its half-life. AIM: To report the final efficacy and safety data for BAY 94-9027 from the PROTECT VIII extension. METHODS: Previously treated males aged 12-65 years with severe haemophilia A (FVIII <1%) who completed the multicentre, open-label PROTECT VIII main study were eligible for the extension. Patients received either on demand or prophylaxis treatments (30-40 IU/kg twice weekly [2 × W], 45-60 IU/kg every 5 days [E5D], or 60 IU/kg every 7 days [E7D]) and could switch to any prophylaxis regimen (variable frequency) as needed. Annualised bleeding rates (ABR), zero bleeds and safety outcomes were included in this final analysis. RESULTS: At extension completion, patients (n = 121) received BAY 94-9027 for a median (range) total time of 3.9 (0.8-7.0) years. Median (Q1; Q3) total ABR was 1.49 (0.36; 4.80) for prophylaxis patients (n = 107), compared with 34.09 (20.3; 36.6) for on-demand patients (n = 14). Median total ABRs for 2 × W (n = 23), E5D (n = 33), E7D (n = 23) and variable frequency (n = 28) groups were 1.57, 1.17, 0.65 and 3.10, respectively. Of prophylaxis patients, 20.6% were bleed-free during the entire extension (median time, 3.2 years) and 50.0% were bleed-free during the last 6 months. No patient developed FVIII inhibitors. No deaths or thrombotic events were reported. CONCLUSIONS: Efficacy and safety of BAY 94-9027 was confirmed, with extension data supporting its use as a long-term treatment option for patients with haemophilia A.

BAY 94-9027 prophylaxis is efficacious and well tolerated for up to >5 years with extended dosing intervals: PROTECT VIII extension interim results.

INTRODUCTION: BAY 94-9027 is an extended-half-life, site-specifically PEGylated, B-domain-deleted recombinant factor VIII (FVIII). The PROTECT VIII main study demonstrated efficacy of bleed control using extended-interval prophylaxis with BAY 94-9027 for 36 weeks. AIM: To report long-term efficacy and safety of prophylaxis with BAY 94-9027 in a descriptive analysis of the ongoing PROTECT VIII extension with a total treatment time of up to >5 years. METHODS: Previously treated males aged 12-65 years with severe haemophilia A who completed the PROTECT VIII main study were eligible for the open-label extension. Patients received on-demand treatment or prophylaxis (30-40 IU/kg twice weekly, 45-60 IU/kg every 5 days, or 60 IU/kg every 7 days) and could switch regimens as needed. RESULTS: Patients (N = 121; on demand, n = 14; prophylaxis, n = 107) accumulated a median (range) of 3.9 years (297-1965 days) and 223 (23-563) total exposure days by 31 January 2018. During the extension, median (quartile [Q]1; Q3) annualized bleeding rates (ABRs) for total bleeds were 1.6 (0.3; 4.6) for patients receiving prophylaxis and 34.1 (20.3; 36.6) for patients receiving on-demand treatment. ABRs for twice-weekly (n = 23), every-5-days (n = 33), every-7-days (n = 23) and variable frequency (n = 28) treatments were 1.7, 1.2, 0.7 and 3.1, respectively. Of prophylaxis patients, 20.6% were bleed-free throughout the extension (median time, 3.2 years), and 44.5% were bleed-free during the last 6 months. No patients developed FVIII inhibitors. CONCLUSIONS: BAY 94-9027 prophylaxis was efficacious and well tolerated with dosing intervals up to every 7 days for a median (range) of 3.9 years (0.8-5.4 years).

BAY 81-8973, a full-length recombinant factor VIII: Human heat shock protein 70 improves the manufacturing process without affecting clinical safety.

BAY 81-8973 is a full-length, unmodified recombinant human factor VIII (FVIII) approved for the treatment of hemophilia A. BAY 81-8973 has the same amino acid sequence as the currently marketed sucrose-formulated recombinant FVIII (rFVIII-FS) product and is produced using additional advanced manufacturing technologies. One of the key manufacturing advances for BAY 81-8973 is introduction of the gene for human heat shock protein 70 (HSP70) into the rFVIII-FS cell line. HSP70 facilitates proper folding of proteins, enhances cell survival by inhibiting apoptosis, and potentially impacts rFVIII glycosylation. HSP70 expression in the BAY 81-8973 cell line along with other manufacturing advances resulted in a higher-producing cell line and improvements in the pharmacokinetics of the final product as determined in clinical studies. HSP70 protein is not detected in the harvest or in the final BAY 81-8973 product. However, because this is a new process, clinical trial safety assessments included monitoring for anti-HSP70 antibodies. Most patients, across all age groups, had low levels of anti-HSP70 antibodies before exposure to the investigational product. During BAY 81-8973 treatment, 5% of patients had sporadic increases in anti-HSP70 antibody levels above a predefined threshold (cutoff value, 239 ng/mL). No clinical symptoms related to anti-HSP70 antibody development occurred. In conclusion, addition of HSP70 to the BAY 81-8973 cell line is an innovative technology for manufacturing rFVIII aimed at improving protein folding and expression. Improved pharmacokinetics and no effect on safety of BAY 81-8973 were observed in clinical trials in patients with hemophilia A.

Efficacy and safety of damoctocog alfa pegol prophylaxis in patients ⩾40 years with severe haemophilia A and comorbidities: post hoc analysis from the PROTECT VIII study.

Background: Advances in treatment have enabled patients with haemophilia A to live longer and therefore may be subjected to comorbidities associated with ageing, in addition to disease-associated morbidities. There have been few reports to date on efficacy and safety of treatment specifically in patients with severe haemophilia A and comorbidities. Objective: To explore the efficacy and safety of damoctocog alfa pegol prophylaxis in patients with severe haemophilia A aged ⩾40 years with comorbidities of interest. Design: A post hoc analysis of data from the phase 2/3 PROTECT VIII study and its extension. Methods: Bleeding and safety outcomes were analysed in a subgroup of patients aged ⩾40 years with ⩾1 comorbidity receiving damoctocog alfa pegol (BAY 94-9027; Jivi®) prophylaxis. Results: Thirty-four patients with severe haemophilia A were included in this analysis, with a mean age of 49.4 years at time of enrolment. The most prevalent comorbidities were hepatitis C (n = 33; chronic, n = 23), hepatitis B (n = 8) and hypertension (n = 11). Four patients had human immunodeficiency virus. All received damoctocog alfa pegol prophylaxis for the entire study [median (range) time in study = 3.9 (1.0-6.9) years]. During the main study and extension, median total annualised bleeding rates (ABRs) (Q1; Q3) were 2.1 (0.0; 5.8) and 2.2 (0.6; 6.0), respectively; median joint ABRs were 1.9 (0.0; 4.4) and 1.6 (0.0; 4.0), respectively. Mean adherence with prophylaxis schedule was greater than 95% throughout the study. No deaths or thrombotic events were reported. Conclusion: Efficacy, safety and adherence of damoctocog alfa pegol were confirmed in patients aged ⩾40 years with haemophilia A and one or more comorbidities, with data for up to 7 years supporting its use as a long-term treatment option in this group. Plain language summary: Advances in treatment mean that people with haemophilia A are now living longer and, as a result, may have additional medical conditions that occur with ageing. We aimed to investigate the efficacy and safety of the long-acting replacement factor VIII damoctocog alfa pegol in people with severe haemophilia A who had additional medical conditions. To do this, we investigated the recorded information about patients aged 40 years of age or older who had been treated with damoctocog alfa pegol in a previously completed clinical trial. We found that the treatment was well-tolerated; no deaths or thrombotic events (undesirable clotting events) were reported. Treatment was efficacious in reducing bleeding in this group of patients. The findings support the use of damoctocog alfa pegol as a long-term treatment for older patients with haemophilia A and coexisting conditions.

Immunoglobulin G treatment of postcardiac surgery patients with score-identified severe systemic inflammatory response syndrome--the ESSICS study.

OBJECTIVE: A minority of patients develop severe systemic inflammatory response syndrome (SIRS) with high mortality following cardiopulmonary bypass-assisted cardiac surgery. We assessed whether intravenous immunoglobulin G (ivIgG) improves postoperative short-term (5-day) morbidity and reduces 28-day mortality in these patients. DESIGN: Randomized, double-blind, placebo-controlled, multicenter trial. SETTING: Intensive care units of 11 cardiothoracic centers. PATIENTS AND INTERVENTIONS: Of 6,984 patients screened, we identified 244 with severe SIRS (Acute Physiology and Chronic Health Evaluation II score > or = 28 on the first postoperative day). INTERVENTIONS: The 244 patients with severe SIRS were randomly assigned to receive an intravenous infusion of either albumin 0.1% (placebo group, 6 mL [6 mg]/kg of body weight on day 1 and 3 mL [3 mg]/kg of body weight on day 2) or immunoglobulin G 10% (ivIgG group, 6 mL [600 mg]/kg of body weight on day 1 and 3 mL [300 mg]/kg of body weight on day 2). MEASUREMENTS AND MAIN RESULTS: The prospectively defined primary end points were improvement in morbidity on day 5 and death from any cause assessed on day 28. A total of 218 patients received both doses of the study drug (placebo n = 108, ivIgG n = 110). Acute Physiology and Chronic Health Evaluation II scores in the placebo group decreased from 31.8 +/- 4.0 (day 1) to 25.8 +/- 9.3 (day 5) and in the ivIgG group from 31.8 +/- 3.4 (day 1) to 25.9 +/- 10.3 (day 5), with no significant difference between the groups (p = .56). The 28-day mortality rate was not significantly different between the groups (per protocol population, placebo group 31.5%, ivIgG group 39.1%; intent-to-treat population, placebo group 37.2%, ivIgG group: 44.7%). No effect of ivIgG on plasma levels of interleukin-6, tumor necrosis factor, and tumor necrosis factor receptor I/II was observed. Drug-related adverse events were rare in both groups. CONCLUSIONS: Patients undergoing cardiac surgery (involving cardiopulmonary bypass) who develop severe SIRS derive no improvement in short-term morbidity or 28-day mortality from ivIgG.

Safety and efficacy of sucrose-formulated full-length recombinant factor VIII: experience in the standard clinical setting.

The safety of full-length sucrose-formulated recombinant factor VIII (rFVIII-FS; Kogenate FS) for up to 24 months of use was evaluated in a postmarketing observational study in Europe. Long-term safety and efficacy data were available for 212 patients with severe haemophilia A, including 13 previously untreated patients (PUPs) and 12 patients with 1-19 exposure days (EDs). Patients accumulated a mean (+/- SD) of 187 (121) EDs to rFVIII-FS and received a total of 39,627 infusions, mainly for prophylaxis and for the treatment of 4,283 spontaneous or trauma-related bleeds during an average observation time of 710 (136) days. Of these bleeding episodes, 85.4% were successfully treated with one or two infusions of rFVIII-FS. Haemostasis was also evaluated during 46 minor to major surgical procedures, and the response to infusion was "excellent" or "good" in all cases. FVIII inhibitor formation was observed in six patients (two de novo; four persistent or recurrent). The de novo cases represent 8.0% (2 of 25) of patients who reported 0-19 previous EDs at study entry. Four of the five patients who reported possible drug-related adverse effects developed inhibitors. The results of this observational study demonstrate the efficacy and safety of rFVIII-FS during normal clinical use in the treatment of patients with severe haemophilia A. Furthermore, these findings are consistent with those of previous phase III clinical studies with rFVIII-FS, particularly with regard to its efficacy and low incidence of inhibitor formation.

Matching-adjusted indirect comparisons of efficacy of BAY 81-8973 vs two recombinant factor VIII for the prophylactic treatment of severe hemophilia A.

BACKGROUND: No head-to-head trials comparing recombinant factor VIII (rFVIII) products currently exist. This was a matching-adjusted indirect comparison (MAIC) study of efficacy of BAY 81-8973 with antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM) and turoctocog alfa for the prophylaxis of severe hemophilia A. METHODS: A systematic literature review was conducted to identify trials of rAHF-PFM and turoctocog alfa. Comparisons were conducted using BAY 81-8973 individual patient data (IPD) from LEOPOLD trials and published data from rAHF-PFM and turoctocog alfa trials. Differences in outcome reporting were reconciled using transformation of BAY 81-8973 IPD. Patients in pooled LEOPOLD trials were weighted to match baseline characteristics for rAHF-PFM or turoctocog alfa trials using MAICs. After matching, annualized bleed rates (ABRs) were compared using weighted t-tests. RESULTS: Two rAHF-PFM trials and one turoctocog alfa trial were identified. In these trials, rFVIIIs were dosed thrice weekly or every other day; in LEOPOLD trials, BAY 81-8973 was dosed twice- or thrice weekly. Three MAICs were conducted because the two rAHF-PFM trials calculated ABRs differently, matching for age, race, and weight (turoctocog alfa only). BAY 81-8973 had similar ABR of all bleeds vs rAHF-PFM (two trials: 4.8 vs 6.3, 1.9 vs 1.8 [square root transform]) and lower ABR of spontaneous bleeds and trauma bleeds (2.6 vs 4.1, 2.1 vs 4.7; both P<0.05). BAY 81-8973 showed lower ABR of all bleeds and spontaneous bleeds vs turoctocog alfa (4.3 vs 6.5, 2.8 vs 4.3; both P<0.05) and similar ABR of trauma bleeds (1.5 vs 1.6). In subgroup analysis, twice-weekly BAY 81-8973 had similar ABRs of all bleeds, spontaneous bleeds, and trauma bleeds compared to rAHF-PFM and turoctocog alfa. CONCLUSION: This indirect comparison found that prophylaxis with BAY 81-8973, even including the lower frequency of two times a week and lower factor VIII consumption, has efficacy comparable to rAHF-PFM and turoctocog alfa, which were dosed thrice weekly or every other day. The use of IPD enabled adjustments for differences in calculation of ABRs and population characteristics between trials.

Sucrose-Formulated Recombinant Factor VIII Dosing Flexibility in Prophylaxis Regimens: Experience from Postmarketing Surveillance Studies.

Objectives. Prophylaxis regimens for severe hemophilia A allowing more flexible dosing while maintaining efficacy may improve adherence and decrease the cost of prophylaxis. Here, we compared the clinical effectiveness of once- or twice-weekly versus ≥3-times-weekly prophylaxis with sucrose-formulated recombinant factor VIII (rFVIII-FS) in a "real-world" practice setting. Methods. Data from 3 postmarketing studies were pooled. Patients with severe hemophilia A receiving ≥1 prophylaxis infusion/wk of rFVIII-FS for ≥80% of a prophylaxis observation period (≥5 months) were included. Patients were categorized based on physician-assigned treatment regimens of 1-2 prophylaxis injections/wk (n = 63) or ≥3 prophylaxis injections/wk (n = 76). Descriptive statistics were determined for annualized bleeding rates (ABRs). Results. Median (quartile 1; quartile 3) ABR for all bleeds was 2.0 (0; 4.0) in the 1-2 prophylaxis injections/wk group and 3.9 (1.5; 9.3) in the ≥3 prophylaxis injections/wk group. Median ABRs for joint, spontaneous, and trauma-related bleeds were numerically lower with 1-2 prophylaxis injections/wk. As an estimate of prophylaxis success, 63% (≥3 prophylaxis injections/wk) to 84% of patients (1-2 prophylaxis injections/wk) had ≤4 annualized joint bleeds. Conclusions. Dosing flexibility and successful prophylaxis with rFVIII-FS were demonstrated. Very good bleeding control was achieved with both once-twice-weekly and ≥3-times-weekly prophylaxis dosing regimens.

Efficacy and safety of prophylaxis with once-weekly BAY 79-4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients. A randomised, active-controlled, double-blind study.

The benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79-4980 is an investigational drug consisting of rFVIII-FS (sucrose-formulated recombinant FVIII) reconstituted with liposome solvent. Previous clinical studies showed extended protection from bleeding after a single injection of BAY 79-4980 (13.3 ± 6.2 days) compared with rFVIII-FS (7.2 ± 1.7 days). The effect of once-a-week prophylaxis with BAY 79-4980 (35 IU/kg) compared with three times-per-week rFVIII-FS (25 IU/kg) in previously treated, severe haemophilia A patients was evaluated in a 52-week, double-blind, two-arm, randomised, controlled study. The primary and secondary endpoints were protection from total bleeds and joint bleeds, respectively. Short- and long-term safety and tolerability of BAY 79-4980 including effects on lipid levels were assessed. A total of 139 and 131 subjects were evaluable for safety and efficacy analyses, respectively. A large difference in efficacy between treatment groups was observed with 72.1% (49/68) in the rFVIII-FS control group demonstrating <9 bleeds/year compared with 38.1% (24/63) of BAY 79-4980-treated subjects. A similar difference was seen in annualised joint bleeds, with 43 subjects (63.2%) in the control group demonstrating <5 joint bleeds/year compared with 24 subjects (38.1%) treated with BAY 79-4980. The distribution of bleeds seven days post-prophylactic treatment with BAY 79-4980 showed that 61% of bleeds occurred after day 4 post dosing. There were no safety concerns identified. The investigational treatment arm was prematurely discontinued due to failure to achieve the primary endpoint.

Estudio inmunologicos en fiebre reumatica activa y endocarditis infecciosa. / Immunologic studies in active rheumatic fever and infective endocarditis

Se comparan las caracteristicas clinicas e inmunologicas de la fiebre reumatica activa (19 casos) y la endocarditis infecciosa (7 casos), condiciones clinicas que en ocasiones representan problemas de diagnostico diferencial. En esta pequena serie hubo casos de fiebre reumatica con esplenomegalia y/o purpura vascular, y de endocarditis infecciosa con nodulos subcutaneos. Las pruebas de laboratorio que establecen diferencias con significado estadisticos son: determinacion de factor reumatoide usando particulas de latex sensibilizadas con IgG humana (X2 4.27 p <.05); las que reflejan la presencia de complejos inmunitarios circulantes, como la actividad hemolitica de antigammaglobulina (X2 3.79 p < 0.05) y la presencia de productos de degradacion de C3 en la circulacion (X2 5.92 p < 0.01), que ocurren preferente o exclusivamente en endocarditis. Aunque en el caso promedio la clinica es suficiente para diferenciar entre la fiebre reumatica y la endocarditis, el laboratorio especializado ofrece recursos de utilidad diagnostica

Anticuerpos IgM e IgC antirubeola en cardiopatía congénita / Anti-rubella antibodies IgM and IgC in congenital heart disease

Una causa conocida de cardiopatía congénita es la infección in útero con virus de rubeola. Se estudió la presencia de anticuerpos clase IgM (respuesta primaria) o IgG (respuesta anamnésica) en el suero de 32 niños con cardiopatía congénita, y se comparó con un grupo de 12 niños sanos de la misma extracción socioeconómica. Excepto en un caso con síndrome de rubeola congénita que tenía títulos muy altos de anticuerpo IgG antirubeola, no hubo diferencias en la prevalencia de anticuerpos IgM o IgG entre ambos grupos. Concluimos que la búsqueda de anticuerpos a rubeola no tiene valor en el estudio de la etiopatogenia de la cardiopatía congénita aislada

Actividad procoagulante asociada a células mononucleares en fiebre reumática activa / Procoagulant activity associated with mononuclear cells in active rheumatic fever

La fiebre reumática activa (FRA) se caracteriza por inflamación diseminada, con lesiones en donde predomina el depósito de proteínas de la coagulación, particularmente en válvulas cardíacas y en miocardio. La participación inmune en la patogenia de la enfermedad ha sido sospechada desde hace mucho, aunque no hay un mecanismo satisfactoriamente demostrado. La activación de la respuesta inmune celular genera factores activadores celulares (linfocinas) a partir de linfocitos T y entre ellos un factor que confiere capacidad procogulante a mononucleares. Se estudió la actividad procoagulante (APC) de las células mononucleares de la sangre periférica en la fiebre reumática, así como en otras condiciones. Se encontro que en la FRA existe APC 1-5 a 15 veces mayor que la que tiene células obtenidas de controles sanos comparables. La APC se asocia con la presencia de proteína C reactiva y otros indicadores de fase aguda. Es posible que la APC de mononucleares de enfermos con FRA sea uno de los mecanismos que expliquen el depósito de fibrina en las lesiones tisulares

Anomalía de Ebstein en el lactante / Ebstein's anomalies in infant

La anomalía de Ebstein es una malformación congénita de la válvula tricúspide que causa alteraciones hemodinámicas variables dependiendo de los cambios anatómicos de la válvula, presencia o ausencia de defecto septal atrial y del deterioro de la función ventricular. Se estudiaron 19 lactantes con el diagnóstico de anomalía de Ebstein. El tiempo de seguimiento fue de 1 semana a 16 años con un promedio de 40 meses. Se perdieron 6 pacientes; 8 pacientes fallecieron y cinco sobreviven. Se compararon las características del grupo de sobrevivientes con las del grupo que falleció. El período crítico para la sobrevida en los recién nacidos con anomalía de Ebstein es el primer año de vida. Concluimos que el grupo con cianosis precoz y con lesiones asociadas tiene mal pronóstico. Si el niño logra sobrevivir el primer año, tolera mejor la evolución de la cardiopatía

Doble camara ventricular derecha aislada. Informe de dos casos. / Isolated double chamber right ventricle. Report of two cases

Se presentan dos casos de doble camara ventricular derecha, sin comunicacion interventricular, diagnosticados por medio del estudio hemodinamico y corregidos quirurgicamente con exito. Asi mismo se discuten las teorias embriologicas y los metodos de diagnostico de la malformacion