scholarly journals Targeted DNA Sequencing for Hemophilia A, B, and von Willebrand Disease: Analytical Precision in Clinical Laboratories and Improved Disease Characterization

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5042-5042
Author(s):  
Patricia Severino ◽  
Liliane Santana Oliveira ◽  
Natalia Torres ◽  
Joao Carlos Guerra ◽  
Nelson Hamerschlak ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Sanger Sequencing ◽  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Coagulation Factor ◽  
Von Willebrand Disease ◽  
Targeted Sequencing ◽  
Probe Design ◽  
Clinical Laboratories ◽  
Von Willebrand

Abstract Hemophilia A, B, and von Willebrand disease correspond to more than 90% of all inherited bleeding disorders associated with coagulation factor deficiencies. Symptoms between these deficiencies may vary greatly and yet are often phenotypically similar. Bleeding episodes can range from mild to severe, at times with life threatening hemorrhages. Currently, biochemical assays are performed to assess the function of each coagulation factor, but diagnosis remains cumbersome and prone to multiple sources of variability between laboratories. Genetic evaluation allows for the examination of multiple coagulation factor genes simultaneously and may quickly identify possible causes to the disease. Additionally, genetic testing should be more reproducible and readily comparable between clinical laboratories. In this work we evaluate the potential use of targeted sequencing of three coagulation factors genes – F8, F9 and VWF – for the concurrent diagnosis and characterization of hemophilia A, B, and von Willebrand disease samples. For targeted DNA sequencing we selected specific DNA probes using genomic coordinates spanning the complete intronic and exonic regions of the three genes, as well as flanking gene sequences. Eleven hemophilia A samples and four hemophilia B samples, clinically characterized and submitted to Sanger sequencing for F8 and F9 genes coding regions, respectively, were included in this study. Our results indicate that even though DNA quality may be ideal for traditional DNA sequencing, enrichment techniques require more intact fragments, as reflected by variations in sequencing coverage between samples: quadruplicate results per sample showed 100X coverage varying from 80% of sequenced regions to less then 20%. Point substitutions found in F9 genes by Sanger sequencing were confirmed by targeted sequencing, but results for F8 gene were less satisfactory, in agreement with probe design limitations at this point. Of interest for hemophilia A patients, four samples possessed, in addition to the alterations in F8, point mutations in VWF. Probe design and sequencing parameters did not allow for the identification of F8 intron 1 and intron 22 inversions, frequent alterations in hemophilia A, but optimization procedures are currently underway. We conclude that targeted sequencing approach may be a viable and more complete solution for the diagnosis and management of hemophilia A, B and von Willebrand disease. Disclosures No relevant conflicts of interest to declare.

Hemophilia in the Peruvian Social Security System: Report of Five Centers.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4446-4446
Author(s):  
Gloria Chumpitaz ◽  
Fernando Cauvi ◽  
Juan Ramon Navarro ◽  
Karina Pedraza
Keyword(s):  
Conflicts Of Interest ◽  
Age Groups ◽  
Coagulation Factor ◽  
Von Willebrand Disease ◽  
Severe Illness ◽  
Factor Deficiency ◽  
Coagulation Factor Deficiency ◽  
Receive Treatment ◽  
New Diagnosis ◽  
Von Willebrand

Abstract Abstract 4446 The Hemophilia Unit of the Hematology Department of the National Hospital Edgardo Rebagliatti Martins- ESSALUD, is one of the most important Hemophilia Centers through the country, that assists patients not only in its jurisdiction but also a great amount referred from other institutions due the complexity of their treatment, like acquired inhibitor disorders as well as orthopedic and mayor cardiovascular surgeries and severe hemorrhages. The Hemophilia ESSALUD system is compounded of centers in Lima (02), Callao (01) and provinces (05) (Arequipa, Chiclayo, Trujillo, Piura and Cuzco). The range of patients with new diagnosis is about 5 to 20 patients per year. The prevalence of Hemophilia in the last 5 years, accounts 83.38% patients of the global amount with coagulation disorders. Of the 331 patients in treatment, 228 (68.8%) have Hemophilia A. Considering the classification of status severity, 12.5% patients of this group belong to mild status hemophilia, 39.47% patients to moderate status, and 41.43% to severe status. In relation to Hemophilia B, we account 48 (14.5%) patients; 5.2% corresponds to mild status, 23.68% moderate status and 52.63% severe status. The rest of the patients have other disorders of coagulation such as Von Willebrand disease and rare coagulation factor deficiency (V, VII, XI and XII). According to the age group distribution for this series, a mayor proportion of 44.68%of patients belong to the group between 16 to 35 years old. The group above 35 years accounts 30%.The age groups of 6 to 15 years old and the group of 1 to 5 year old account 16.48% and 8.51%, respectively. Finally, it is important to point out that 37.76% of our hemophiliac patients are in the group of moderate illness status and 44.14% in the group of severe illness status. All the patients receive treatment with plasma-derived coagulation factor concentrates and in some cases recombinant therapy. Children receive prophylactic treatment. Disclosures: No relevant conflicts of interest to declare.

Phase II Biologic Effects Trial of Recombinant Interleukin-11 (rhIL-11, Neumega) in Moderate or Mild Hemophilia A or Von Willebrand Disease Unable to Use DDAVP,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3308-3308
Author(s):  
Margaret V. Ragni ◽  
Enrico M. Novelli ◽  
Anila Murshed ◽  
Elizabeth P. Merricks ◽  
Mark T. Kloos ◽  
...  
Keyword(s):  
Phase Ii ◽  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Postoperative Bleeding ◽  
Fold Increase ◽  
Von Willebrand Disease ◽  
Fluid Restriction ◽  
Biologic Effects ◽  
Von Willebrand

Abstract Abstract 3308 Background: DDAVP is the treatment of choice for individuals with type 1 von Willebrand disease (VWD), although 20% are unresponsive, and of the 80% who do respond, the VWF increase is transient, as endothelial stores are depleted after 3 days. Further, administration requires a 30- minute intravenous infusion in a medical facility. Plasma-derived concentrates may be used in these settings, but are more costly and have potential risk of transmissible infection. We recently demonstrated that recombinant human IL-11 (rhIL-11, Neumega®), a gp-130 signaling cytokine with hematopoietic and anti-inflammatory activity, increases VWF activity up to 2-fold when given daily by subcutaneous injection, with levels persisting each day it is given, and reduces menstrual and postoperative bleeding. The effects of rhIL-11 in individuals with VWD unresponsive or allergic to DDAVP, or hemophilia A, however, have not been evaluated. Methods: We conducted a phase II trial to evaluate the safety and biologic effects of rhIL-11 in VWD patients unresponsive or allergic to DDAVP (VWD-Un) or mild hemophilia A (HemA). rhIL-11 was given subcutaneously at 25 μg/kg daily for 4 days in the non-bleeding state, followed on day 4, 30 minutes after rhIL-11, by one dose of DDAVP intravenously, 0.3 μg/kg, if not contraindicated (pt. 2). Fluid restriction was recommended. Fluid status was assessed by height, weight, and exam. Pre- and post-dosing laboratory assays included the VWD profile, VWF multimers by SDS gel electrophoresis, and platelet VWF mRNA by qPCR. Results: The results of the first six subjects, including three with VWD (one type IIB and two type 1 VWD), VWF:RCo 0.10–0.20 U/ml, and three with mild hemophilia A, F.VIII 0.08–0.12 U/ml, are presented. All subjects were healthy, with no hypertension or cardiac disease, and all had normal physical exams and normal EKGs. By day 4, among VWD-Un subjects, there was a 1.2-fold increase in VWF:RCo (15±3% vs. 12±0%); a 1.6-fold increase in VWF:Ag (22±8% vs.14±6%); and a 1.3-fold increase in VIII:C (34±36% vs. 27±10%), as compared with pre-rhIL-11 levels (Figure). Following DDAVP (except pt. 2), there was an additional 2.0-fold, 1.7-fold, and 2.6-fold increase in VWF:RCo, VWF:Ag, and VIII:C, respectively. Among HemA subjects, by day 4, there was a 1.8-fold increase in VWF:RCo (160±25% vs. 88±12%); a 1.8-fold increase in VWF:Ag (182±28% vs.99±18%), p<0.01; and a 1.5-fold increase in VIII:C (21±8% vs. 14±5%), as compared with pre-rhIL-11 levels. Following DDAVP, there was an additional 1.5-fold (p<0.01), 1.7-fold, and 2.8-fold (p<0.05) increase in VWF:RCo, VWF:Ag, and VIII:C, respectively. The drug was well tolerated well with less than grade 1 mild conjunctival erythema, local erythema and tenderness at the injection site; in one subject transient hyponatremia, Na 129 meq/L, occurred after excess oral fluid intake for diabetic hyperglycemia, which resolved with fluid restriction. Discussion: These data suggest that rhIL-11 increases VWF and VIII levels modestly in VWD patients unresponsive/allergic to DDAVP, and in mild hemophilia A, suggesting the potential use in treatment of clinical bleeding in these disorders. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Novel therapeutics for hemophilia and other bleeding disorders

Blood ◽  
2018 ◽  
Vol 132 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Michael U. Callaghan ◽  
Robert Sidonio ◽  
Steven W. Pipe
Keyword(s):  
Factor Viii ◽  
New Technologies ◽  
Hemophilia A ◽  
Coagulation Factor ◽  
Von Willebrand Disease ◽  
Bleeding Disorders ◽  
Routes Of Administration ◽  
New Approaches ◽  
Dosing Regimens ◽  
Von Willebrand

Abstract Hemophilia and von Willebrand disease are the most common congenital bleeding disorders. Treatment of these disorders has focused on replacement of the missing coagulation factor to prevent or treat bleeding. New technologies and insights into hemostasis have driven the development of many promising new therapies for hemophilia and von Willebrand disease. Emerging bypass agents including zymogen-like factor IXa and Xa molecules are in development and a bispecific antibody, emicizumab, demonstrated efficacy in a phase 3 trial in people with hemophilia A and inhibitors. Tissue factor pathway inhibitor, the protein C/S system, and antithrombin are targets of novel compounds in development to alter the hemostatic balance and new approaches using modified factor VIII molecules are being tested for prevention and eradication of inhibitor antibodies in hemophilia A. The first recombinant von Willebrand factor (VWF) product has been approved and has unique VWF multimer content and does not contain factor VIII. These new approaches may offer better routes of administration, improved dosing regimens, and better efficacy for prevention and treatment of bleeding in congenital bleeding disorders.

Risk and Management of Intracerebral Hemorrhage in Patients with Bleeding Disorders

2022 ◽  
Author(s):  
Akbar Dorgalaleh ◽  
Yadolah Farshi ◽  
Kamand Haeri ◽  
Omid Baradarian Ghanbari ◽  
Abbas Ahmadi
Keyword(s):  
Risk Factors ◽  
Intracerebral Hemorrhage ◽  
Platelet Function ◽  
Hemophilia A ◽  
Coagulation Factor ◽  
Von Willebrand Disease ◽  
Vacuum Extraction ◽  
Bleeding Disorders ◽  
Platelet Function Disorders ◽  
Von Willebrand

AbstractIntracerebral hemorrhage (ICH) is the most dreaded complication, and the main cause of death, in patients with congenital bleeding disorders. ICH can occur in all congenital bleeding disorders, ranging from mild, like some platelet function disorders, to severe disorders such as hemophilia A, which can cause catastrophic hemorrhage. While extremely rare in mild bleeding disorders, ICH is common in severe coagulation factor (F) XIII deficiency. ICH can be spontaneous or trauma-related. Spontaneous ICH occurs more often in adults, while trauma-related ICH is more prevalent in children. Risk factors that can affect the occurrence of ICH include the type of bleeding disorder and its severity, genotype and genetic polymorphisms, type of delivery, and sports and other activities. Patients with hemophilia A; afibrinogenemia; FXIII, FX, and FVII deficiencies; and type 3 von Willebrand disease are more susceptible than those with mild platelet function disorders, FV, FXI, combined FV–FVIII deficiencies, and type 1 von Willebrand disease. Generally, the more severe the disorder, the more likely the occurrence of ICH. Contact sports and activities can provoke ICH, while safe and noncontact sports present more benefit than danger. An important risk factor is stressful delivery, whether it is prolonged or by vacuum extraction. These should be avoided in patients with congenital bleeding disorders. Familiarity with all risk factors of ICH can help prevent occurrence of this diathesis and reduce related morbidity and mortality.

Overuse of Cryoprecipitate: A Chronic Condition,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4212-4212
Author(s):  
Manpreet K. Sandhu ◽  
Trishala Agrawal ◽  
Maya Shah ◽  
Alice J. Cohen
Keyword(s):  
Hemophilia A ◽  
Tertiary Care Hospital ◽  
Conflicts Of Interest ◽  
Medical Center ◽  
Tertiary Care ◽  
Laboratory Data ◽  
Von Willebrand Disease ◽  
Care Hospital ◽  
Blood Products ◽  
Von Willebrand

Abstract Abstract 4212 Background: Literature has revealed that there is considerable inappropriate use of blood products including cryoprecipitate (cryo). Appropriate indications for cryo use according to American Association of Blood Banks (AABB) guidelines include bleeding due to hypofibrinogenemia (fibrinogen level < 100mg/dl) or dysfibrinogenemia, factor XIII deficiency, bleeding associated with Hemophilia A or von Willebrand disease (when appropriate factor concentrates are not available) and uremic bleeding (DDAVP preferred). To determine appropriateness of use of cryo at Newark Beth Israel Medical Center, a review of cryo utilization was conducted at this tertiary care hospital. Methods: A retrospective audit of cryo utilization was performed from January to May 2011. Medical records of all patients (pts) who received cryo during this time were reviewed for demographic information (age, sex, clinical diagnosis) and relevant laboratory data (PT, PTT, fibrinogen levels, serum creatinine). The number of units transfused per pt as well as the hospital service requesting the transfusion in each case was noted. The indication of cryo in each case was evaluated as appropriate or inappropriate, depending on AABB transfusion guidelines. Results: A total of 62 pts received 71 pooled cryo transfusions (total of 691 units). Out of the 71 transfusions, 61 in 52 pts (585 units) were evaluable with complete data. Mean age of these pts was 53 years (yrs) (range 0–83), with 42% being females. Mean number of units given per transfusion was 9.7(range 1–20). The majority of cryo use was by cardiothoracic (CT) surgery (360/585, 62%) followed by hematology/oncology (hem/onc) (177/585, 30%). The remainder was used by Pediatrics (Peds) (23/585, 4%) and Obstetrics/Gynecology (Ob/Gyn) (25/585, 4%). All the transfusions were given in the setting of bleeding. The most common reason for transfusion (201/585, 34%) was post-operative bleeding, without any clear indication based on guidelines, and predominantly ordered by CT surgery (165/201, 82%). 180/585 (31%) of the units were transfused intraoperatively with 160/180 (89%) of those transfusions occurring during cardio-thoracic procedure. In 8 pts, 81 cryo units (81/585, 14%) were transfused to correct uremic bleeding, and were all ordered by hem/onc. 12 pts received 93 units (93/585, 16%) for bleeding related to hypofibrinogenemia. 11/12 of these pts had disseminated intravascular coagulation (DIC), with 1/11 cases of DIC due to underlying malignancy, 9/11 due to sepsis and 1/11 due to acute fatty liver of pregnancy. Overall, 174/585 (30%) of cryo units were transfused appropriately as per AABB guidelines: 93/174(53%) for hypofibrinogenemia and 81/174 (47%) for uremic bleeding. The highest incidence of cryo transfusions for appropriate indications was in the hem/onc department (131/174, 75%). The total cost of inappropriate transfusions was $23,838 (411/585 units, calculated using $58 per unit). Of note, none of the cryo transfusions were used for bleeding Hemophilia A or von Willebrand disease pts since our medical center uses recombinant factor for those indications. Conclusions: Cryo utilization varied by departments. CT surgery followed by hem/onc services are the principal users of cryo in our tertiary care hospital. As only 30% of cryo was used in accordance with established guidelines, the opportunities may exist for lower cryo usage. Further education of the medical community is warranted regarding the appropriate clinical indications for the use of cryo, in order to decrease the risks with transfusion (such as transmission of infectious agents) as well as to save the cost of unnecessarily transfused blood products. Disclosures: No relevant conflicts of interest to declare.

Development of Platforms to Phenotype Variants of Uncertain Significance in VWF

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1386-1386
Author(s):  
Andrew Yee ◽  
Manhong Dai ◽  
Colin Kretz ◽  
Fan Meng ◽  
David Ginsburg
Keyword(s):  
Dna Sequencing ◽  
Mammalian Cells ◽  
Conflicts Of Interest ◽  
Von Willebrand Disease ◽  
Variants Of Uncertain Significance ◽  
Platelet Receptor ◽  
Platelet Binding ◽  
Uncertain Significance ◽  
A1 Domain ◽  
Von Willebrand

Abstract Platelet sequestration at sites of vascular injuries and factor VIII (FVIII) stabilization critically relies on von Willebrand factor (VWF). Specific domains within VWF coordinate these functions and may harbor mutations that result in von Willebrand disease (VWD). To survey all possible mutations that may lead to type 2 VWD, we developed prokaryotic and eukaryotic systems to display VWF fragments that are screened for a specific function and identified by DNA sequencing. We constructed an M13 filamentous phage display library consisting of ~2.8x106 independent clones that express random VWF fragments. Following a single round of selection for platelet binding, bound phage were eluted and analyzed by next generation DNA sequencing, revealing an optimal fragment spanning the A1 domain and a second region of weaker enrichment over the D4 domain. All A1 fragments encompassed C1272-C1458, indicating that intramolecular disulfide bridging of these cysteines optimizes platelet binding. Competitive binding assays between phage displaying a fragment of the D4 domain vs. a control phage resulted in enrichment of the former, suggesting a potential, novel role for the VWF D4 domain. Analogous to our previously reported method for analyzing VWF proteolysis (Kretz CA et al. Proc Natl Acad Sci USA. 2015), we mutagenized and displayed the VWF A1 domain to determine the spectrum of mutations that may alter the interaction between VWF and its platelet receptor, GPIbα. The mutant A1 library comprised ~5x106 independent clones, sufficient to represent all 3,933 single substitutions. Screening this library against platelets in the presence of excess control phage resulted in an enrichment of phage displaying an A1 fragment. DNA sequencing identified mutations located outside the VWF A1/platelet GPIbα interface, indicating allosteric control of this interaction. Screening phage displayed VWF fragments for FVIII binding, however, failed to identify critical residues; thus, we adapted our approach for eukaryotes. When displayed on mammalian cells, the VWF D'D3 domains retained their capacity to bind FVIII. Introduction of the VWD subtype 2N mutation, R816W, into the displayed VWF D'D3 domains abolished FVIII binding, demonstrating feasibility for mutational analyses. Together, these results demonstrate the utility of phage and mammalian display for structure-function analyses and that these platforms provide an efficient method for phenotyping variants of uncertain significance. Disclosures No relevant conflicts of interest to declare.

Von Willebrand disease and Weibel-Palade bodies

2010 ◽  
Vol 30 (03) ◽  
pp. 150-155 ◽  
Author(s):  
J. W. Wang ◽  
J. Eikenboom
Keyword(s):  
Platelet Adhesion ◽  
Coagulation Factor ◽  
Von Willebrand Disease ◽  
Inflammatory Factors ◽  
Limited Data ◽  
Storage Organelle ◽  
And Function ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryVon Willebrand factor (VWF) is a pivotal haemostatic protein mediating platelet adhesion to injured endothelium and carrying coagulation factor VIII (FVIII) in the circulation to protect it from premature clearance. Apart from the roles in haemostasis, VWF drives the formation of the endothelial cell specific Weibel-Palade bodies (WPBs), which serve as a regulated storage of VWF and other thrombotic and inflammatory factors. Defects in VWF could lead to the bleeding disorder von Willebrand disease (VWD).Extensive studies have shown that several mutations identified in VWD patients cause an intracellular retention of VWF. However, the effects of such mutations on the formation and function of its storage organelle are largely unknown. This review gives an overview on the role of VWF in WPB biogenesis and summarizes the limited data on the WPBs formed by VWD-causing mutant VWF.

A randomised pilot trial of the anti-von Willebrand factor aptamer ARC1779 in patients with type 2b von Willebrand disease

2010 ◽  
Vol 104 (09) ◽  
pp. 563-570 ◽  
Author(s):  
Petra Paulinska ◽  
Petra Jilma-Stohlawetz ◽  
James Gilbert ◽  
Renta Hutabarat ◽  
Paul Knöbl ◽  
...  
Keyword(s):  
Pilot Trial ◽  
Coagulation Factor ◽  
Von Willebrand Disease ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Maximal Increase ◽  
Double Blind Design ◽  
Von Willebrand

SummaryDesmopressin aggravates thrombocytopenia in type 2B von Willebrand disease (VWF type 2B) by release of large and hyper-adhesive von Wille-brand Factor (VWF) multimers. This pilot study investigated whether the anti-VWF aptamer ARC1779 can prevent desmopressin-induced thrombocytopenia and interferes with the excessive VWF turnover in patients with VWF type 2B. Concentration effect curves of ARC1779 were established for five patients in vitro and two patients with VWF type 2B were treated by infusion of ARC1779, desmopressin, or their combination in a randomised, controlled, double-blind design. ARC1779 concentrations in the range of 1–3 μg/ml blocked free A1 domain binding sites by 90% in vitro. In vivo, desmopressin alone induced a profound (-90%) drop in platelet counts in one of the patients. ARC1779 (4–5 μg/ml) completely inhibited VWF A1 domains and prevented this desmopress-in-induced platelet drop. Desmopressin alone increased VWF antigen two- to three-fold, accompanied by concordant changes in VWF Ristocetin cofactor activity (RCo) and coagulation factor VIII activity. ARC1779 substantially enhanced the desmopressin-induced maximal increase in these parameters, and improved multimer patterns. No treatment related adverse events were observed and no bleeding occurred despite marked thrombocytopenia. These data provide first proof of concept in humans and evidence that ARC1779 is a potent inhibitor of VWF. ARC1779 prevented the rapid consumption of VWF multimers together with agglutinated platelets that occurred in response to desmopressin challenge in patients with VWD type 2B.Clinical Trial registration number: NCT00632242.

scholarly journals Diagnosis and Treatment of Acquired Hemophilia: One Single-Center Experience from PR. China

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4250-4250
Author(s):  
Rong-Fu Zhou ◽  
Yueyi Xu ◽  
Wenjin Gao
Keyword(s):  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Clinical Manifestations ◽  
Coagulation Factor ◽  
Factor Vii ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Coagulation Factor Vii ◽  
Prolonged Aptt ◽  
Inhibitor Titer

Abstract Objective: To deepen the understanding of the clinical manifestations of acquired hemophilia A for timely and correctly treatment. Methods: The clinical data of the acquired hemophilia A patients diagnosed in the hospital from Jan 2006 to Mar 2021 were retrospectively analyzed, and the relevant literature was reviewed. Results: 17 patients with acquired hemophilia A, male: female =10: 7, median age 61 years (19 to 78 years), were diagnosed and treated in the hospital with the median time from the onset to diagnosis 21 days (2 days to 6 months). Six patients had comorbidity, including hepatitis B carrying, chronic myelomonocytic leukemia, diabetes, hypertension and positive autoantibodies, pemphigoid and gastric cancer, respectively. Other 11 patients were healthy before the onset. All patients had large large ecchymosis of skin, and one case was combined with hematuria, and one case with retroperitoneal hematoma. All patients had APTT extension (45s-144.7s) and the prolonged APTT could not be corrected with normal mixed plasma with and without incubation at 37℃ for 2 hours. FVIII activity was 1% - 8.9% and inhibitor titer 2 - 128 Bu/ml. All patients with bleeding were with prothrombin complex/recombinant activated coagulation factor VII, some of them with pd-coagulation factor FVIII preparations. Inhibitors were removed with prednisone acetate (1 case) + chemotherapy (1 case), prednisone acetate / + CTX (11 cases) + chemotherapy (1 case), prednisone acetate/prednisolone + mabthera (2 cases) + CTX (1 case), respectively. The removal time of inhibitor was from 8 days to 4 years. During the treatment process, two patients developed lower extremity venous thrombosis, and one patient was complicated with lung infection. Conclusion: Patients with unexplained bleeding and prolonged APTT should be conducted normal mixed plasma correction test, coagulation factor activity and inhibitor titer examination. After correctly diagnosis, bypass agents /coagulation factor VIII preparations should be given timely for hemostasis, protocol based on glucocorticoid + CTX/mabthera to remove the inhibitor and symptomatic treatment for patients with primary comorbidity disease at the same time. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document