BACKGROUND Acquired haemophilia(AH)is a serious autoimmune haematological disease caused by the production of auto-antibodies against coagulation factor VIII.In some patients,AH is associated with a concomitant malign...BACKGROUND Acquired haemophilia(AH)is a serious autoimmune haematological disease caused by the production of auto-antibodies against coagulation factor VIII.In some patients,AH is associated with a concomitant malignancy.In case of surgical intervention,AH poses a high risk of life-threatening bleeding.CASE SUMMARY A 60-year-old female patient with multiple recurrences of non-muscle invasive bladder cancer underwent transurethral tumour resection.A severe haematuria developed postoperatively warranting two endoscopic revisions;however,no clear source of bleeding was identified in the bladder.Subsequent haematological examination established a diagnosis of AH.Treatment with factor VIII inhibitor bypass activity and immunosuppressive therapy was initiated immediately.The patient responded well to the therapy and was discharged from the hospital 21 d after the primary surgery.At the 38-mo follow-up,both AH and bladder cancer remained in complete remission.CONCLUSION AH is a rare,life-threatening haematological disease.AH should be considered in patients with persistent severe haematuria or other bleeding symptoms,especially if combined with isolated activated partial thromboplastin time prolongation.展开更多
The case of a forty-five year old woman is presented who consulted for spontaneous haematomas of the thighs. The diagnosis of acquired haemophilia A associated to renal cancer was retained. She received anti CD20 mono...The case of a forty-five year old woman is presented who consulted for spontaneous haematomas of the thighs. The diagnosis of acquired haemophilia A associated to renal cancer was retained. She received anti CD20 monoclonal antibody treatment allowing her to undergo partial nephrectomy 4 months later without major complication. One year after surgery there is no sign of tumour recurrence.展开更多
AIM To collect data from joint replacement in inhibitor patients, evaluate haemostatic and patient outcomes, and analyse the costs.METHODS We report our 21-year, single-centre cumulative experience of 15 joint arthrop...AIM To collect data from joint replacement in inhibitor patients, evaluate haemostatic and patient outcomes, and analyse the costs.METHODS We report our 21-year, single-centre cumulative experience of 15 joint arthroplasties in six inhibitor patients.RESULTS Two low responder inhibitor patients were in the early days treated with FVIII, whereas bypassing agents were used in the rest of the high responder patients. The primary haemostatic outcome was good in 8/15, fair in 4/15 and poor in 3/15 operations. The overall patient outcome, including joint health and patient satisfaction, was good in 10/15, fair 4/15 and poor in 1/15. No deep infections were observed. Cost analysis was most beneficial in low responders and in two immune-tolerized, high responder patients. In all cases, factor replacement comprised the main treatment costs.CONCLUSION Our experience supports the initial use of bypassing agents as well as preoperative immune-tolerance induction when possible. Despite the challenges of haemostasis and severe joint disease, total joint arthroplasty can reach a good outcome, even in inhibitor patients. The risk for deep infection might be smaller than previously reported. Individual planning, intense multidisciplinary teamworkand execution of operations should be centralised in a professional unit.展开更多
Objective: To assess the role of early prophylaxis with recombinant activated factor VII (rFVIIa) in young haemophiliacs with inhibitors and to determine whether it can reduce bleeding episodes and prevent joint damag...Objective: To assess the role of early prophylaxis with recombinant activated factor VII (rFVIIa) in young haemophiliacs with inhibitors and to determine whether it can reduce bleeding episodes and prevent joint damage. Patients and Methods: Ten severe haemophiliacs, less of three years old, with up to four joint bleeds and inhibitors to FVIII who started early prophylaxis with rFVIIa, were included. A number of haemorrhages/year/patient and haemarthroses/ year/patient were compared before the start of prophylaxis, which include both the time before (initial period) and after inhibitor diagnosis (inhibitor period), with those during prophylaxis (prophylaxis period). Results: The mean time of inhibitor diagnosis was 15.6 months (range: 2.3-34.1). The mean time between inhibitor diagnosis and the start of prophylaxis was 7.1 months (range: 0-23.2), shorter than the time of rFVIIa prophylaxis (mean: 10.3 months;range: 4.1-32.0). Bleeding episodes for the three time periods were 45, 36 and 17, respectively, or 0.29 and 0.51 haemorrhages/year/patient in the two periods prior to prophylaxis compared to 0.17 during prophylaxis. Total haemarthroses for the three-time periods were 7, 5 and 5, respectively. The haemarthroses/year/patient in the pre-prophylaxis period were 0.032 and 0.070, compared to0.049 inthe prophylaxis period. rFVIIa schedules were either 90 μg/kg three times weekly or 90 μg/kg daily. Conclusions: Early prophylaxis with rFVIIa may be efficacious in young haemophiliacs with inhibitors, reducing joint bleeds. After the risky period of inhibitor presence, they are able to continue rFVIII prophylaxis with success assured to prevent arthropathy.展开更多
Background: Hemophilic arthropathy is a debilitating morbidity of hemophilia caused by recurrent joint bleeds. We investigated if the joint bleed volume, before initiation of treatment, was linked to the subsequent de...Background: Hemophilic arthropathy is a debilitating morbidity of hemophilia caused by recurrent joint bleeds. We investigated if the joint bleed volume, before initiation of treatment, was linked to the subsequent degree of histopathological changes and the development of bone pathology in a mouse model of hemophilic arthropathy.Methods: FVIII knock-out(F8-KO) mice were dosed with a micro-CT blood pool agent prior to induction of hemarthrosis. Eight hours after induction, the bleed volume was quantified with micro computed tomography(micro-CT) and recombinant FVIII treatment initiated. On Day 8, inflammation in the knees was characterized by fluorescence molecular tomography. On Day 14, knee pathology was characterized by micro-CT and histopathology. In a second study, contrast agent was injected into the knee of wild-type(WT) mice, followed by histopathological evaluation on Day 14.Results: The average joint bleed volume before treatment was 3.9 mm3. The inflammation-related fluorescent intensities in the injured knees were significantly increased on Day 8. The injured knees had significantly increased synovitis scores, vessel counts, and areas of hemosiderin compared to un-injured knees. However, no cartilage-or bone pathology was observed. The bleed volume before initiation of treatment correlated with the degree of synovitis and was associated with high fluorescent intensity on Day 8. In F8-KO and WT mice, persistence of contrast agent in the joint elicited morphological changes.Conclusion: When applying a delayed on-demand treatment regimen to hemophilic mice subjected to an induced knee hemarthrosis, the degree of histopathological changes on Day 14 reflected the bleed volume prior to initiation of treatment.展开更多
Numerous studies are being carried out on polymorphisms within the genes coding for factors VIII and IX due to their clinical relevance in the context of hereditary disorders. The quests for polymorphism can be used t...Numerous studies are being carried out on polymorphisms within the genes coding for factors VIII and IX due to their clinical relevance in the context of hereditary disorders. The quests for polymorphism can be used to screen for haemophilia through an affected family. In Cameroon, very few studies on factors VIII and IX gene polymorphisms have been conducted. Thus, this study was aimed at detecting HindIII SNP of the F8 gene and MseI SNP of the F9 gene by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RLFP) method and determining their involvement in the severity and complications of haemophilia. Fifty-five consented haemophilia patients from the Centre Hospitalier et Universitaire de Yaoundé (CHUY) were recruited for this study on a convenience sampling basis. Finger-prick blood was collected and spotted on filter papers from which DNA was extracted and then subjected to the PCR-RFLP. We were able to recruit 55 (37.16%) patients out of the 148 haemophilia patients registered at the CHUY until December 2018. The average age was 15 years. Of the 55 haemophilia patients, 42 (76.36%) had type A haemophilia and 13 (23.64%) had type B haemophilia, 41 patients (74.55%) had a severe form, 10 (18.18%) had a moderate form and 4 (7.27%) a mild form). Of the 55 patients recruited, 38 (69.09%) already had an osteoarticular complication and the remaining 17 (30.91%) had no complication. Fifty-three (96.36%) participants had HindIII SNP and a significant association was found with the severity of hemophilia (P = 0.00). No association (P = 0.56) was found with osteoarticular complications of haemophilia. On the other hand, 15 (27.27%) participants were diagnosed with MseI SNPs and no association was found with the severity (P = 0.89) or complications (P = 0.68) of haemophilia.展开更多
基金Supported by conceptual development of research organization,Ministry of Health,Czech Republic,No.FNOs/2023.
文摘BACKGROUND Acquired haemophilia(AH)is a serious autoimmune haematological disease caused by the production of auto-antibodies against coagulation factor VIII.In some patients,AH is associated with a concomitant malignancy.In case of surgical intervention,AH poses a high risk of life-threatening bleeding.CASE SUMMARY A 60-year-old female patient with multiple recurrences of non-muscle invasive bladder cancer underwent transurethral tumour resection.A severe haematuria developed postoperatively warranting two endoscopic revisions;however,no clear source of bleeding was identified in the bladder.Subsequent haematological examination established a diagnosis of AH.Treatment with factor VIII inhibitor bypass activity and immunosuppressive therapy was initiated immediately.The patient responded well to the therapy and was discharged from the hospital 21 d after the primary surgery.At the 38-mo follow-up,both AH and bladder cancer remained in complete remission.CONCLUSION AH is a rare,life-threatening haematological disease.AH should be considered in patients with persistent severe haematuria or other bleeding symptoms,especially if combined with isolated activated partial thromboplastin time prolongation.
文摘The case of a forty-five year old woman is presented who consulted for spontaneous haematomas of the thighs. The diagnosis of acquired haemophilia A associated to renal cancer was retained. She received anti CD20 monoclonal antibody treatment allowing her to undergo partial nephrectomy 4 months later without major complication. One year after surgery there is no sign of tumour recurrence.
文摘AIM To collect data from joint replacement in inhibitor patients, evaluate haemostatic and patient outcomes, and analyse the costs.METHODS We report our 21-year, single-centre cumulative experience of 15 joint arthroplasties in six inhibitor patients.RESULTS Two low responder inhibitor patients were in the early days treated with FVIII, whereas bypassing agents were used in the rest of the high responder patients. The primary haemostatic outcome was good in 8/15, fair in 4/15 and poor in 3/15 operations. The overall patient outcome, including joint health and patient satisfaction, was good in 10/15, fair 4/15 and poor in 1/15. No deep infections were observed. Cost analysis was most beneficial in low responders and in two immune-tolerized, high responder patients. In all cases, factor replacement comprised the main treatment costs.CONCLUSION Our experience supports the initial use of bypassing agents as well as preoperative immune-tolerance induction when possible. Despite the challenges of haemostasis and severe joint disease, total joint arthroplasty can reach a good outcome, even in inhibitor patients. The risk for deep infection might be smaller than previously reported. Individual planning, intense multidisciplinary teamworkand execution of operations should be centralised in a professional unit.
文摘Objective: To assess the role of early prophylaxis with recombinant activated factor VII (rFVIIa) in young haemophiliacs with inhibitors and to determine whether it can reduce bleeding episodes and prevent joint damage. Patients and Methods: Ten severe haemophiliacs, less of three years old, with up to four joint bleeds and inhibitors to FVIII who started early prophylaxis with rFVIIa, were included. A number of haemorrhages/year/patient and haemarthroses/ year/patient were compared before the start of prophylaxis, which include both the time before (initial period) and after inhibitor diagnosis (inhibitor period), with those during prophylaxis (prophylaxis period). Results: The mean time of inhibitor diagnosis was 15.6 months (range: 2.3-34.1). The mean time between inhibitor diagnosis and the start of prophylaxis was 7.1 months (range: 0-23.2), shorter than the time of rFVIIa prophylaxis (mean: 10.3 months;range: 4.1-32.0). Bleeding episodes for the three time periods were 45, 36 and 17, respectively, or 0.29 and 0.51 haemorrhages/year/patient in the two periods prior to prophylaxis compared to 0.17 during prophylaxis. Total haemarthroses for the three-time periods were 7, 5 and 5, respectively. The haemarthroses/year/patient in the pre-prophylaxis period were 0.032 and 0.070, compared to0.049 inthe prophylaxis period. rFVIIa schedules were either 90 μg/kg three times weekly or 90 μg/kg daily. Conclusions: Early prophylaxis with rFVIIa may be efficacious in young haemophiliacs with inhibitors, reducing joint bleeds. After the risky period of inhibitor presence, they are able to continue rFVIII prophylaxis with success assured to prevent arthropathy.
文摘Background: Hemophilic arthropathy is a debilitating morbidity of hemophilia caused by recurrent joint bleeds. We investigated if the joint bleed volume, before initiation of treatment, was linked to the subsequent degree of histopathological changes and the development of bone pathology in a mouse model of hemophilic arthropathy.Methods: FVIII knock-out(F8-KO) mice were dosed with a micro-CT blood pool agent prior to induction of hemarthrosis. Eight hours after induction, the bleed volume was quantified with micro computed tomography(micro-CT) and recombinant FVIII treatment initiated. On Day 8, inflammation in the knees was characterized by fluorescence molecular tomography. On Day 14, knee pathology was characterized by micro-CT and histopathology. In a second study, contrast agent was injected into the knee of wild-type(WT) mice, followed by histopathological evaluation on Day 14.Results: The average joint bleed volume before treatment was 3.9 mm3. The inflammation-related fluorescent intensities in the injured knees were significantly increased on Day 8. The injured knees had significantly increased synovitis scores, vessel counts, and areas of hemosiderin compared to un-injured knees. However, no cartilage-or bone pathology was observed. The bleed volume before initiation of treatment correlated with the degree of synovitis and was associated with high fluorescent intensity on Day 8. In F8-KO and WT mice, persistence of contrast agent in the joint elicited morphological changes.Conclusion: When applying a delayed on-demand treatment regimen to hemophilic mice subjected to an induced knee hemarthrosis, the degree of histopathological changes on Day 14 reflected the bleed volume prior to initiation of treatment.
文摘Numerous studies are being carried out on polymorphisms within the genes coding for factors VIII and IX due to their clinical relevance in the context of hereditary disorders. The quests for polymorphism can be used to screen for haemophilia through an affected family. In Cameroon, very few studies on factors VIII and IX gene polymorphisms have been conducted. Thus, this study was aimed at detecting HindIII SNP of the F8 gene and MseI SNP of the F9 gene by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RLFP) method and determining their involvement in the severity and complications of haemophilia. Fifty-five consented haemophilia patients from the Centre Hospitalier et Universitaire de Yaoundé (CHUY) were recruited for this study on a convenience sampling basis. Finger-prick blood was collected and spotted on filter papers from which DNA was extracted and then subjected to the PCR-RFLP. We were able to recruit 55 (37.16%) patients out of the 148 haemophilia patients registered at the CHUY until December 2018. The average age was 15 years. Of the 55 haemophilia patients, 42 (76.36%) had type A haemophilia and 13 (23.64%) had type B haemophilia, 41 patients (74.55%) had a severe form, 10 (18.18%) had a moderate form and 4 (7.27%) a mild form). Of the 55 patients recruited, 38 (69.09%) already had an osteoarticular complication and the remaining 17 (30.91%) had no complication. Fifty-three (96.36%) participants had HindIII SNP and a significant association was found with the severity of hemophilia (P = 0.00). No association (P = 0.56) was found with osteoarticular complications of haemophilia. On the other hand, 15 (27.27%) participants were diagnosed with MseI SNPs and no association was found with the severity (P = 0.89) or complications (P = 0.68) of haemophilia.
