OBJECTIVES: To investigate the application value of thromboelastography (TEG) in assessing coagulation function in children with severe hemophilia A (HA) after emicizumab (EMI) therapy. METHODS: A retrospective analysis was performed on the activated partial thromboplastin time (APTT) and TEG testing results of 17 children with severe HA before and after EMI treatment at Shenzhen Children's Hospital from January 2023 to July 2024. Correlation analysis was conducted between coagulation factor VIII (FVIII) equivalent activity and reaction time (R value) measured by TEG. RESULTS: After EMI treatment, the mean bleeding rate for children with severe HA was 1.6 events per year, with 15 children (88%) without spontaneous bleeding or joint bleeding. The children with severe HA showed a significant reduction in APTT after EMI treatment (P<0.05), with a significantly shorter APTT than the normal control group (P<0.05). There was no correlation between APTT and FVIII equivalent activity after treatment (P>0.05). After EMI treatment, TEG parameters, including R value, kinetic time, alpha angle (α), maximum amplitude, clot strength, and coagulation index, shifted from a hypocoagulable state before treatment to a nearly normal state after treatment (P<0.05). The R value demonstrated a strong negative correlation with FVIII equivalent activity (r=-0.758, P<0.05). CONCLUSIONS The bleeding condition of children with severe HA can be effectively controlled after EMI treatment. Routine APTT testing cannot reflect true coagulation function, whereas TEG testing is clinically valuable in assessing the coagulation function of children with severe HA undergoing EMI treatment.
Humans ; Thrombelastography ; Hemophilia A/physiopathology* ; Male ; Child ; Antibodies, Bispecific/therapeutic use* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Blood Coagulation/drug effects* ; Child, Preschool ; Retrospective Studies ; Female ; Partial Thromboplastin Time ; Adolescent ; Infant

OBJECTIVETo observe the phenotypic heterogeneity of severe hemophilia A in China and investigate the clinical factors for defining the severity of the clinical presentations.

METHODSThe data including the age of first bleeding and first joint bleeding, bleeding frequency, the number of joint deformities and body mass index (BMI) were collected from 223 patients with severe hemophilia A (FVIII:C≤2%).

RESULTSThe median age at first bleeding was 1 year (range: 0-35 years). The percentages of patients with first bleeding age<1 year, ≥2 years and ≥6 years were 44.3% (94/212), 34.4% (73/212), and 10.8% (23/212), respectively. The median age at first joint bleeding was 2.25 years. The percentages of patients with first joint bleeding age ≤1 year, ≥2 years and ≥6 years were 25.5% (24/94), 57.4% (54/94), and 18.1% (17/94), respectively. The percentage of patients who did not have joint bleeding was 7.4% (7/94). The median annual bleeding frequency was 24 per year (range: 1-120), and the proportion of patients with annual bleeding episodes of less than 6 times was 12.9%. Only 24.7% of the patients were free of any joint deformities. Analysis showed that milder cases had older ages of first bleeding and first joint bleeding than the severe cases, and the milder cases had also significantly lower BMI.

CONCLUSIONThe age of first bleeding and first joint bleeding and BMI may predict the clinical severity of hemophilia A in China in the early stage.

Adolescent ; Adult ; Age of Onset ; Aged ; Body Mass Index ; Child ; Child, Preschool ; China ; epidemiology ; Hemophilia A ; diagnosis ; epidemiology ; Hemorrhage ; Humans ; Infant ; Joints ; abnormalities ; physiopathology ; Male ; Middle Aged ; Phenotype ; Young Adult

OBJECTIVETo analyze the clinical characteristics and effects of rehabilitation treatment on hemophiliacs with iliopsoas hemorrage.

METHODSThe hemophilia patients with iliopsoas bleeding treated in Peking Union Medical College Hospital between January 2006 to December 2010 were enrolled. The clinical characteristics including symptoms, signs, complications, and rehabilitation treatment were analyzed retrospectively.

RESULTSAll of the forty-one hemophiliacs with iliopsoas bleeding were male, 20 cases wee the left bleeding, 18 the right, and 3 the bilateral. The median median age was 18 (6 - 61) years old(y). The median age of the iliopsoas bleeding for the first time was 17 (6 - 20) y. 34 patients accompanied with femoral nerve injury, 19 of them had secondary knee bleeding on the same side. 20 patents had quadriceps atrophy. Pelvic pseudotumor developed in 2 patients and permanent abnormal posture in 2 patients. The main finding of the ultrasound image was low-echo mass in iliopsoas muscles or inguinal region. 34 patients received rehabilitation therapy for 8 - 12 weeks under the support of factor replacement, complete hematomas absorption in 33 of them, with hip range of motion recovering back to baseline. 27 of 32 (84.4%) cases with femoral nerve injury got quadriceps strength above 4/5 grade, 20 cases of femoral nerve injury (62.5%) still had numbness on front of their thigh after treatment.

CONCLUSIONSIn this cohort of iliopsoas bleeding, most of the patients are adolescent. High prevalence of the femoral nerve injury and the secondary knee bleeding are found. Rehabilitation treatment under the support of factor replacement is safe and effective on hematoma absorption and neurological function recovery.

Adolescent ; Adult ; Child ; Hematoma ; etiology ; rehabilitation ; Hemophilia A ; complications ; rehabilitation ; Hemorrhage ; etiology ; rehabilitation ; Humans ; Male ; Middle Aged ; Muscular Diseases ; diagnosis ; etiology ; rehabilitation ; Psoas Muscles ; physiopathology ; Retrospective Studies ; Young Adult

BACKGROUND: Hemophiliacs have extrinsic tightness from quadriceps and flexion contractures. We sought to examine the effect of a focused physical therapy regimen geared to hemophilic total knee arthroplasty. METHODS: Twenty-four knees undergoing intensive hemophiliac-specific physical therapy after total knee arthroplasty, at an average age of 46 years, were followed to an average 50 months. RESULTS: For all patients, flexion contracture improved from -10.5 degrees preoperatively to -5.1 degrees at final follow-up (p = 0.02). Knees with preoperative flexion less than 90 degrees were compared to knees with preoperative flexion greater than 90 degrees. Patients with preoperative flexion less than 90 degrees experienced improved flexion (p = 0.02), along with improved arc range of motion (ROM) and decreased flexion contracture. For those patients with specific twelve-month and final follow-up data points, there was a significant gain in flexion between twelve months and final follow-up (p = 0.02). CONCLUSIONS: Hemophiliacs with the poorest flexion benefited most from focused quadriceps stretching to a more functional length, with gains not usually seen in the osteoarthritic population. This data may challenge traditional views that ROM gains are not expected beyond 12-18 months.
Adult ; Aged ; Arthroplasty, Replacement, Knee/*methods ; Female ; Follow-Up Studies ; Hemophilia A/complications/*physiopathology/*therapy ; Humans ; Joint Diseases/*blood/complications/surgery ; Knee Joint/*physiopathology/surgery ; Male ; Middle Aged ; *Physical Therapy Modalities ; Range of Motion, Articular/physiology ; Retrospective Studies ; Treatment Outcome

OBJECTIVEFactor VIII( FVIII) gene knockout mouse model was established for further study on the treatment of hemophilia A.

METHODSExons 16-19 of the mouse FVIII gene were knocked out by ET clone, ES homologous recombination and tetraploid embryo compensation technology. PCR, reverse transcriptase-PCR(RT-PCR) and immunohistochemistry were used to detect the transcription and translation pattern of FVIII. The phenotype of the knockout mice was analyzed by examining the activated partial thromboplastin time (APTT) and FVIII activity (FVIII:C).

RESULTSPCR, RT-PCR and immunohistochemistry confirmed that FVIII was deficient in the FVIII gene knockout mouse. The APTT results showed that FVIII-deficient mouse plasma had a prolonged clotting time compared to normal mouse plasma. The FVIII:C in heterozygous, hemizygous and homozygous mice was 80%, 8% and 10% of that in normal mice, respectively.

CONCLUSIONThe phenotype of the FVIII gene knockout mouse appears grossly similar to that of human with hemophilia A. Establishment of this model may promote the development of new technologies of treatment to hemophilia A.

Animals ; Disease Models, Animal ; Embryo, Mammalian ; Factor VIII ; genetics ; metabolism ; Female ; Hemophilia A ; genetics ; metabolism ; physiopathology ; Humans ; Male ; Mice ; Mice, Inbred ICR ; Mice, Knockout ; Partial Thromboplastin Time

OBJECTIVETo evaluate the short-term effects of ankle joint replacement for the patients with hemophilic arthritis. To find out the main points for improving the joint function and the patients' life quality. To accumulate more experience for clinical treatment.

METHODSThe Kofoed evaluation system and the AOFAS evaluation system were used to follow-up 6 hemophilic patients with ankle arthritis (6 males, ranging in age from 23 to 57 years, with an average of 41.2 years), who were treated with ankle joint replacement from 2004.7 to 2007.7. The scores before operation, and the 6th,12th months after operation were compared.

RESULTSThe Kofoed evaluation system showed the joint replacement significantly improved the scores for relieving pain, joint function, range of motion and the total score (P<0.05). Except the score for relieving pain, the other three also had significant differences between the 6th month and the 12th month after the operation (P<0.05). Compared with each details of the joint function, there was significant improvement before and after the operation (P<0.05). The ankle got more extended range of motion in the 12th month after operation than the 6th month (P<0.05). The AOFAS evaluation system showed the joint replacement significantly improved the scores for relieving pain, joint function, X-ray measurement and the total score (P<0.05). There was no differences between the 6th month after operation and the 12th month in the results for relieving pain and the X-ray measurement (P>0.05). However, the joint function and the total score had significant differences (P<0.05). Compared with each details of the joint function, there was also significant improvement before and after the operation (P< 0.05), and the walk distance, as well as the joint flexion and extension activities, had differences between the 6th month and the 12th month after the operation. Both of the two evaluation system showed the operation could get good curative effects (P< 0.05), and the artificial joint could constantly be in good condition from the 6th month to the 12th month after operation (P> 0.05).

CONCLUSIONIn this short-term observation, the joint replacement can significantly improve the life quality for the hemophilic patients with ankle arthritis.

Adult ; Ankle Joint ; physiopathology ; surgery ; Arthritis ; etiology ; physiopathology ; surgery ; Arthroplasty, Replacement ; methods ; Hemophilia A ; complications ; Humans ; Male ; Middle Aged

Factor VIIa ; Genetic Therapy ; Hemophilia A ; drug therapy ; epidemiology ; genetics ; physiopathology ; History, 21st Century ; Humans ; Recombinant Proteins ; Singapore ; epidemiology