Comparison Pharmacokinetic Dosing Tools in Hemophilia A Children.

Prophylaxis is the gold standard for the management of hemophilia A patients. It has been shown that prophylaxis regulated with pharmacokinetic (PK) data reduces frequency of bleeding and cost of treatment. To determine the best prophylaxis regimen, PK dosing tools using the Bayesian method have been developed. We aimed to compare two PK dosing tools. Blood samples were drawn before, 4, 24, and 48 h after FVIII infusions from patients with severe hemophilia A and inhibitor negative. FVIII levels were measured by PTT-based one-stage assay method. PK parameters obtained using WAPPS and myPKFiT, which are web-accessible PK dosing tools using Bayesian algorithm, and daily prophylaxis dose estimated by the programs were compared. Forty-two hemophilia A patients [median age 13 years (IQR 8.9-16.4)] included in the study. There was no difference between the daily dose of FVIII given for prophylaxis and the dose recommended by the myPKFiT for the 1% trough level; whereas, a significant difference was found with the WAPPS. The half-lives of FVIII did not differ between the two dosing tools; however, significant differences were found in the estimated dose, clearances, and times to 1% trough level. There was no significant difference between PK data of patients who received Advate® and those who received non-Advate® factor concentrates. Choice of PK dosing tool can affect recommended FVIII dose. However, target trough levels should be individualized according to bleeding phenotype and daily activity of patient. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01671-0.

The Effects of Coronavirus Disease 2019 Pandemic on Patients with Hemophilia and Inherited Bleeding Disorders: Results from 2 Centers in Turkey.

OBJECTIVE: Patients with inherited bleeding disorders faced problems in accessing healthcare during coronavirus disease 2019 pandemic. This study aimed to investigate the health problems of patients with inherited bleeding disorders during the coronavirus disease 2019 pandemic. MATERIAL AND METHODS: Children and adult patients with inherited bleeding disorders who had a coronavirus disease 2019 infection between March 2020 and November 2021 were retrospec- tively evaluated. RESULTS: Seven hundred seventy-two patients were reviewed, and 65 patients who had a coro- navirus disease 2019 infection (Male/Female: 58/7, mean age 28.2 ±14.1 years) were analyzed. Sixty patients (92%) had hemophilia A or B or von Willebrand's disease and 5 (8%) had rare bleeding disorders. Sixteen (24.6%) patients had a comorbid disease and 6 (9.2%) needed hospitalization due to severe coronavirus disease 2019 infection. Seven patients (10.7%) expe- rienced a bleeding episode and were treated with factor concentrates. Totally, 64 (98.46%) patients recovered from the coronavirus disease 2019 infection and 1 died. CONCLUSION: Patients with inherited bleeding disorders and coronavirus disease 2019 infection mostly had a mild/moderate course of the disease.

Clinical Evaluation of Balance in Children With Hemophilic Arthropathy.

Purpose: Hemophilia is a hereditary coagulation disorder characterized by acute hemorrhages into the musculoskeletal system, leading eventually to arthropathy and disability. Chronic inflammation of the synovial membrane arises as a result of frequent joint hemorrhage. Proteolytic enzymes in the blood and cartilage cause deterioration after that, and joint space narrows. Chronic hemophilic arthropathy develops as a result of these unfavorable developments, which occur more quickly, especially in the target joints. Balance is a process that allows us to maintain our orientation in three-dimensional space while also regulating our body posture to avoid falling. After the central nervous system evaluates deep stimuli from sensory, visual, and auditory receptors, movement of the corresponding muscle groups is delivered. Methods: The goal of this study was to investigate how impairment to deep sensory receptors (proprioception) in the arthropathic joint structure affected hemophiliacs' balance. The study comprised 34 patients with hemophilic arthropathy, and 34 age and weight matched healthy volunteers. Results: When balance tests of patients with hemophilic arthropathy were compared to healthy controls, hemophiliacs had a greater risk of falling. As the degree of arthropathy increased, so did the risk of falling and balance test values in individuals with hemophilic arthropathy. Conclusions: Treatment and coagulation factor prophylaxis to prevent the onset of arthropathy will improve patients' quality of life and reduce morbidity associated with frequent falls and bleeding. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01526-0.

Retrospective evaluation of children with immune thrombocytopenic purpura and factors contributing to chronicity.

OBJECTIVE: Immune thrombocytopenic purpura (ITP) is the most common cause of acquired thrombocytopenia children. The aim of this retrospective study is to describe presenting features and clinical characteristics of ITP and evaluate clinical course, treatment modalities, and complications and determine the effects of preceding infection history, age, gender, treatment modality, and admission platelet count on chronicity. METHOD: Two hundred and eleven patients who were diagnosed ITP and followed-up in Department of Pediatric Hematology, Ankara Children Hematology Oncology Education and Research Hospital between January 2008 and September 2012 were included. Age of the patients, gender, date of admission, date of diagnosis, complaint in the application, previous infection and laboratory tests were recorded. RESULTS: Mean age of the patients on diagnosis was 5.4 ± 4.1 years. The female/male ratio was 1.03. The clinical courses were determined as acute or chronic in 72% and 28% of patients respectively. Mean age at diagnosis was significantly higher in chronic ITP (p < 0.01). Chronic course was significantly higher in female patients (p < 0.05). The most frequent complaint was bruises on the skin (68%). The most common physical examination findings were petechiae, purpura and ecchymosis (89%). Patients with a history of past infection (53.6%) and who had serologically positive infection (15.6%) frequently had acute course (p < 0.01). The most common serologically positive infection was Rubella. The mean platelet count was significantly higher in chronic ITP (p < 0.01). In the initial treatment of patients admitted in the acute phase, megadose methylprednisolone (MDMP) was used in 31% of patients, intravenous immune globulin (IVIG) in 55% of patients and anti-D in 2% of patients while 12% did not receive any treatment. There were no significant differences between the recurrence rate and treatment modality (p > 0.05). CONCLUSION: In our study, in females and in patients without any history of past infection, platelet count >20 × 109/L and initial diagnosis age > 10 years were found to increase the probability of chronic disease, which is compatible with the literature.

Experience and Prognosis of Systemic Neonatal Thrombosis at a Level III NICU.

OBJECTIVE: The objective of this article was to evaluate neonates diagnosed systemic thrombosis and their outcomes. METHODS: We retrospectively evaluated data of neonatal systemic thrombosis between January 2011 and December 2016. RESULTS: Among 4376 hospitalized, 30 neonates (0.69%) were diagnosed systemic thrombosis. Their mean birth weight was 2422±1152 g (680 to 4750 g), gestational age was 35±5.4 weeks (25 to 41 wk). There were 25 neonates (83.3%) with venous, 5 patients (16.7%) with arterial thrombosis. The most common sites that thrombi localized were major vessels (n=11) and central nervous system (n=8). Central catheter insertion (76.7%) and prematurity (46.7%) were the most common risk factors. Congenital prothrombotic risk factors included G1691A mutation in factor V Leiden (n=1), mutation in factor XIII (n=1), C677T mutation in methylenetetrahydrofolate reductase (n=6). More than 1 congenital risk factor was identified in 5 patients. The patients were treated with low-molecular weight heparin. The mortality rate was 13.3% (n=4). Two patients required amputation (left foot, left upper extremity). Unilateral renal atrophy (n=1), cerebral palsy (n=2), hemiparesis (n=1) were identified among followed 24 patients. CONCLUSIONS: Critically ill neonates are at risk for thrombosis, and devastating consequences can result. As indwelling catheters and prematurity are important, careful monitorization, early diagnosis and therapy, cautious care of central catheter might reduce the incidence and adverse outcome.

Reactive thrombocytosis in children.

The aim of this study was to evaluate the causes of thrombocytosis, which was defined as a platelet count greater than 500 x 10(9)/L, and to compare the groups with mild and severe thrombocytosis. A total of 484 patients were evaluated for the etiology of thrombocytosis. Patients with a platelet count between 500-800 x 10(9)/L were considered to have mild thrombocytosis, while those with a count of ≥800 x 10(9)/L were considered as having severe thrombocytosis. Of 484 patients included, 63% had thrombocytosis due to an infectious disease, 11.4% had a chronic inflammatory condition, 8.5% had anemia, and 5.2% had tissue injury. The frequency of chronic inflammation was higher in the severe thrombocytosis group compared to the mild thrombocytosis group (p=0.006). In conclusion, severe infections and chronic inflammatory conditions should be considered in the differential diagnosis of a patient with severe thrombocytosis.

The role of tumor necrosis factor-alpha -308 G/A and transforming growth factor-beta 1 -915 G/C polymorphisms in childhood idiopathic thrombocytopenic purpura.

OBJECTIVE: To increase our understanding of the etiology of idiopathic thrombocytopenic purpura (ITP) some cytokine gene polymorphisms were analyzed for susceptibility to the disease. The aim of this study was to investigate the role of tumor necrosis factor-alpha (TNF-α) -308 G/A and transforming growth factor-beta 1 (TGF-ß1) -915 G/C polymorphisms in the development and clinical progression of childhood ITP. METHODS: In all, 50 pediatric patients with ITP (25 with acute ITP and 25 with chronic ITP) and 48 healthy controls were investigated via LightCycler® PCR analysis for TNF-α -308 G/A and TGF-ß1 -915 G/C polymorphisms. RESULTS: The frequency of TNF-α -308 G/A polymorphism was 20%, 16%, and 22.9% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05). The frequency of TGF-ß1 -915 G/C polymorphism was 16%, 8%, and 8.3% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05). The risk of developing ITP and clinical progression were not associated with TNF-α -308 G/A (OR: 0.738, 95% CI: 0.275-1.981, and OR: 0.762, 95% CI: 0.179-3.249) or TGF-ß1 -915 G/C (OR: 1.5, 95% CI: 0.396-5.685, and OR: 0.457, 95% CI: 0.076-2.755) polymorphisms. CONCLUSION: The frequency of TNF-α -308 G/A and TGF-ß1 -915 G/C polymorphisms did not differ between pediatric ITP patients and healthy controls, and these polymorphisms were not associated with susceptibility to the development and clinical progression of the disease.

The Importance of Serum Transferrin Receptor and TfR-F Index in the Diagnosis of Iron Deficiency Accompanied by Acute and Chronic Infections.

This study evaluated the diagnostic superiority of serum transferrin receptor (sTfR) measurement to other laboratory tests performed for the determination of iron deficiency caused by chronic disease (CD). Study group consisted of 114 anemic patients allocated into 3 groups at the pediatrics clinic of Ankara University, Faculty of Medicine and 32 healthy pediatric subjects as the control group. sTfR value ranged between 11.00 nmol/L and 26.20 nmol/L for the control group. However, it was 61.29 ± 39.33 nmol/L in iron deficiency anemia (IDEA) group, consisting of 51 patients. While there was a significant positive correlation between sTfR and Hb, MCV, serum iron, ferritin levels, there was a significantly inverse correlation between sTfR with RDW in the IDEA group. Mean sTfR value was found 47.05 ± 28.07 nmol/L in the acute infection (AI) group consisting of 22 patients, 39.31 ± 26.16 nmol/L in the CD group with 41 patients. Statistically significant difference was found between sTfR of IDEA group and sTfR of the AI group, though accompanied by iron deficiency. These findings showed that sTfR levels were suppressed. That all hematologic parameters including ferritin and sTfR of all patients in the CD group were heterogenous and revealed both normal and abnormal values was noteworthy. To determine the existence of accompanying iron deficiency, sTfR values above 28.10 nmol/L were chosen. It was concluded that the diagnosis of these patients was not possible without sTfR measurement. TfR-F index (sTfR/log ferritin) was found 97.72 ± 108.81 in the IDEA group, 52.16 ± 66.25 in the AI group, and 24.36 ± 43.00 in the CD group (p< 0.001). TfR-F index values of the chronic disease anemia group (ACD) and the iron deficiency anemia group accompanied by chronic disease (COMBI) were compared. The difference between these two groups was statistically significant (p< 0.001). Thus, TfR-F index proved useful in evaluating the changes of iron metabolism and reducing iron necessities in patients.