Retrospective analysis of 1,226 Chinese patients with haemophilia in a single medical centre.

Haemophilia A (HA) and B (HB) are X-linked congenital disorders caused by deficiencies of Factor VIII and FIX. Being the world's most populous country, China potentially has a large population of haemophilia patients. During the last decade, no studies have been published regarding the clinical information of haemophilia in China. A retrospective study was conducted in patients with HA and HB referred to Tianjin Haemophilia Centre between 2002 and 2012. We identified 1,226 males with haemophilia (1,019 HA and 207 HB). The results revealed that activate partial thromboplastin time was negatively correlated plasma factor level of person with haemophilia. Our data did not offer sufficient evidence of any relationship existed between disease severity and risk or site of haemorrhage. There was a trend toward a higher inhibitor incidence induced by plasma-derived factor VIII products, than by recombinant FVIII (rFVIII) alone. It seemed that second generation of rFVIII more likely developed inhibitor, and first generation of rFVIII was nevertheless more closely connected to high-titer inhibitor. We found that delay in diagnosis and blood-borne infections were significantly reduced, while the joint deformity rate did not decrease despite the wide variety of products to choose from in this decade. The development of inhibitor still remains a major challenge in replacement therapy in haemophilia.

Acquired factor V inhibitor after liver transplantation.

Acquired inhibitors against coagulation factor V (FV) occur rarely, the clinical symptoms vary to a great extent, from asymptomatic laboratory abnormalities to life-threatening bleeding. Coagulation factor V (FV) is a plasma-cofactor mostly existing in the plasma, and approximately 20-25% (Tracy et al. (1982), Kane (2006)) of FV exist in platelet granules. Patients' reaction is the prolonging of prothrombin time (PT) and activated partial thromboplastin time (APTT), but there is no exact reason, and that can not be corrected after normal plasma transfusion (Morris and Curris (2009), Lucia and Aguilar (2005)). We report here a case of the occurrence of FV inhibitors after orthotopic liver transplantation (OLT). With gastrointestinal bleeding, patient's haemostatic response was not achieved after using fresh frozenplasma (FFP), platelet concentrates (PC), prothrombin complex concentrates (PCC) or recombinant activated FVII (rFVIIa). After using high-dose intravenous immunoglobulin (IVIg) and change of immunosuppressant from tacrolimus (FK506) to cyclosporine, the bleeding stopped and better laboratory examination results was achieved thereafter.

[Study on activated protein C resistance and disordered coagulation in patients with myeloproliferative neoplasms].

OBJECTIVE: To study the correlation of activated protein C (APC) resistance, coagulation factors and inhibitors abnormality and JAK2V617F mutation burden in patients with myeloproliferative neoplasms (MPN). METHODS: The APC resistance was defined as the ratio of activated partial thromboplastin time (APTT) in the presence and absence of APC, i.e. APC sensitivity ratio (APCsr). Plasma protein C (PC), protein S (PS), prothrombin (FII), factor V (FV), factor VIII levels and CD11b expression on neutrophils were measured. The percentage of mutated JAK2V617F allele (V617F%) was evaluated by real time polymerase chain reaction (qRT-PCR). RESULTS: Expression of CD11b on neutrophils was significantly elevated in MPN patients compared with that of the control group. APCsr, PS and FV levels were reduced in patients with MPN. The APCsr level was decreased mainly in patients with thrombosis and JAK2V617F mutant burden higher than 75%. APCsr was not only positively correlated with PS levels but also inversely correlated with JAK2V617F allele burden in JAK2V617F mutant gene carriers. CONCLUSION: The neutrophil was activated and PS, FV level were reduced in MPN patients. The APCsr level was decreased and the occurrence of relatively acquired APC resistance was found in MPN patients with thrombosis. The APCsr is correlated with the PS level and JAK2V617F mutational furden.

[Immune tolerance induction in a severe hemophilia A patient with inhibitor].

OBJECTIVE: To explore the immune tolerance induction (ITI) in a severe hemophilia A patient with inhibitor, and to improve the therapeutic efficacy for patient. METHODS: The FVIII:C was assayed by one-stage method and FVIII antibody by Bethesda method. Mutation screening of FVIII gene intron 22 inversion was performed using LD-PCR. RESULTS: FVIII gene intron 22 inversion was detected in this patient. Clinical tolerance to FVIII was successfully induced after administration of the ITI regimen combined with immunosuppression. A fall of inhibitor titer from 8 BU to 0 BU after treatment for 3 months, and in vivo FVIII recovery (> 66%) was normalized. The patient had no bleeding episode in the following 6 months. CONCLUSION: This is the first case report on successful immune tolerance induction therapy in Chinese hemophilia A patient. ITI is the most effective therapy for hemophilia A with inhibitor.