Hemophilia: An Updated Review

1995 ◽  
Vol 16 (8) ◽  
pp. 290-298
Author(s):  
Beverly Bell ◽  
David Canty ◽  
Michelle Audet
Keyword(s):  
Soft Tissues ◽  
Hemophilia A ◽  
Genetic Disorder ◽  
Von Willebrand Disease ◽  
Clotting Factors ◽  
Genetic Transmission ◽  
Viii And Ix ◽  
Recessive Disorders ◽  
Recessive Defect ◽  
Von Willebrand

Introduction Hemophilia is a genetic disorder that results in either an inactive or inadequate supply of a plasma protein needed for normal blood clotting. The two most common forms are hemophilia A and B, caused by a defect or deficiency in clotting factors VIII and IX, respectively. Both types are X-linked recessive disorders characterized by prolonged bleeding and hemorrhages, typically into joints and soft tissues. Hemophilia C is an autosomal recessive defect that results in a deficiency of factor XI. Marked by bleeding in mucous membranes, hemophilia C exhibits a somewhat different clinical pattern of hemorrhaging than hemophilia A or B but similar to that in von Willebrand disease. This review will focus on hemophilia A and B. Hemophilia has served as a model for the treatment of chronic illness through the comprehensive approach to care. If a child who has hemophilia is managed appropriately with early factor replacement therapy and attempts to avoid the long-term consequences of bleeding, the prospects for a long, full, and healthy life are very good. Epidemiology/Genetic Transmission The incidence of hemophilia A and B is about 15 to 20 per 100 000 males born worldwide and occurs in all races and socioeconomic groups. Hemophilia A, also known as "classical hemophilia," accounts for about 80% of cases of hemophilia, occurs in one of 10 000 male births, and affects about 17 500 individuals in North America.

Bleeding Diseases

2019 ◽  
pp. 50-54
Author(s):  
Kevin B. Hoover
Keyword(s):  
Disease Management ◽  
Musculoskeletal System ◽  
Major Bleeding ◽  
Soft Tissues ◽  
Genetic Diseases ◽  
Von Willebrand Disease ◽  
Factor Ix ◽  
Clotting Factors ◽  
Intramuscular Hemorrhage ◽  
Von Willebrand

Chapter 79 discusses bleeding diseases, which result from disruption of the normal blood clotting process. Genetic diseases that cause reduction or dysfunction of clotting factors (hemophilia A and B) and less commonly platelets (von Willebrand disease) are the major bleeding diseases of the musculoskeletal system. The most common bleeding disease of the musculoskeletal system, hemophilia, is caused by deficiency of either factor VIII or factor IX. Hemophilia commonly results in intraarticular hemorrhage resulting in hemophiliac arthropathy and less commonly intramuscular hemorrhage. Imaging of the joints and soft tissues, especially by MRI, is important in disease management.

scholarly journals PATIENTS REFERRED FOR BLEEDING SYMPTOMS OF UNKNOWN CAUSE: DOES EVALUATION OF THROMBIN GENERATION CONTRIBUTE TO DIAGNOSIS?

2016 ◽  
Vol 8 ◽  
pp. 2016014 ◽  
Author(s):  
Elena Holm ◽  
Eva Zetterberg ◽  
Susanna Lövdahl ◽  
Erik Berntorp
Keyword(s):  
Thrombin Generation ◽  
Assessment Tool ◽  
Correlation Coefficients ◽  
Von Willebrand Disease ◽  
Assessment Tools ◽  
Clotting Factors ◽  
Viii And Ix ◽  
Bleeding Score ◽  
Von Willebrand ◽  
Willebrand Factor

IntroductionPatients with mild to moderate bleeding symptoms referred for coagulation investigation sometimes never receive a definitive diagnosis. Bleed assessment tools have been developed and validated to assess the severity of symptoms. Global coagulation assays, e.g., the thrombin generation test (thrombogram) have a potential to identify hemostatic defects that are not detected in specific assays.Material and MethodsOne hundred and eighty-five patients referred to our centre because of bleeding symptoms were evaluated using  the bleeding assessment tool (BAT) described by Tosetto and colleagues in 2006.  Blood samples were investigated for thrombin generation (TG) capacity (Technoclone) , in platelet poor (PPP)  plasma , and specific clotting factors, i.e, von Willebrand factor, factor VIII and IX, as well as INR, APTT, platelet count, and platelet adhesion.ResultsOf the 185 patients, five women were diagnosed with mild von Willebrand disease and one male with mild hemophilia A. The remaining 179 subjects (76% females and 24% males with average ages of 33 and 28 years, respectively) were evaluated further. In the total cohort and among women, peak TG, and lag time   correlated with bleeding score (p=0.01 and p=0.04, respectively with correlation coefficients).  No such correlations were found among males. Discussion and conclusion Although our study showed some correlation between TG and bleeding score, results are generally consistent with a previous report which failed to demonstrate the value of TG measurement in a similar setting. In conclusion, the complexity of the mechanisms underlying clinical bleeding complicates the ability to use TG tests as reliable predictors of bleeding. Mild congenital bleeding disorders, especially VWD, should be specifically screened for in patients with mild/moderate symtoms.

The Most Prominent Hemophilia Clotting Factors in the Province of Nineveh

2021 ◽  
pp. 85-91
Author(s):  
Salih khudhair Abdullah ◽  
Asmaa Mohammed Khaleel ◽  
Khalid Satam Sultan
Keyword(s):  
Von Willebrand Disease ◽  
Clotting Factor ◽  
Recessive Mutation ◽  
Clotting Factors ◽  
Ibn Sina ◽  
Genetic History ◽  
Study Results ◽  
Different Types ◽  
Von Willebrand

Background: Hemophilia is a recessive mutation in X-linked chromosome. Hemophilia A is characterized by a deficiency of clotting factor F-VIII. Hemophilia B is characterized by a deficiency of clotting factor F-IX. Fibrin Stabilizer is a deficiency of F-XIII. Alexander's disease is a deficiency of clotting factor F-VII. Von Willebrand disease is a deficiency of clotting factor VWF. Afibrinogenemia is a deficiency of clotting factor F-I. Aim: This study amid to find out prevalence of deficiency clotting factors in Nineveh province. Methods: This research was conducted at Ibn-Sina Teaching Hospital. Staco special kits were used to determine factors under the study. Results: 365 out of 829 total patients have been detected deficiency in one or more of different types of factors. The most prevalence of deficiency factors in Nineveh are F-VIII, FIX and VWF. Infected males are more than females. The ages between 1-20 years and blood groups (A⁺, B⁺, and O⁺) are most prevalent. Conclusions: It is necessary to monitor patients during the initial disease, follow it up, and use effective treatment methods to limit the increased number of cases. Moreover, it is necessary to follow up on the family's genetic history to avoid new infections.

scholarly journals The roles of von Willebrand factor and factor VIII in arterial thrombosis: studies in canine von Willebrand disease and hemophilia A

Blood ◽  
1993 ◽  
Vol 81 (10) ◽  
pp. 2644-2651 ◽  
Author(s):  
TC Nichols ◽  
DA Bellinger ◽  
RL Reddick ◽  
SV Smith ◽  
GG Koch ◽  
...  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Arterial Thrombosis ◽  
Hemophilia A ◽  
Full Range ◽  
Von Willebrand Disease ◽  
Arterial Stenosis ◽  
Canine Plasma ◽  
Von Willebrand ◽  
Willebrand Factor

We have studied the roles of von Willebrand factor (vWF) and factor VIII in arterial thrombosis in four canine phenotypes: normal (n = 6), hemophilia A (n = 11), von Willebrand disease (vWD) (n = 9), and hemophilia A/vWD (n = 1). vWF activity was determined by botrocetin- induced agglutination of fixed human platelets and vWF antigen (vWF:Ag) by Laurell electroimmunoassay and crossed immunoelectrophoresis. Plasma from normal dogs and those with hemophilia A had vWF activity, vWF:Ag, and a full range of vWF:Ag multimers on gel electrophoresis equivalent to normal canine plasma pool. Platelet cytosol contents were isolated by freezing and thawing, triton X-100 solubilization, or sonication of washed platelets with and without protease inhibitors and inhibitors of platelet activation. Washed platelets were also stimulated with calcium ionophore and MgCl2. There was no measurable vWF activity or vWF:Ag in platelet lysates or releasates in any dog regardless of phenotype. All dogs were studied using a standard arterial stenosis and injury procedure to induce arterial thrombosis. Thromboses were detected by cyclic reductions in Doppler blood flow velocity. Vessels were examined by light and scanning electron microscopy. Thrombosis developed in the arteries of normal (9 of 10) and hemophilia A dogs (16 of 16) but in none of the vWD dogs (0 of 10). Infusion of canine vWF cryoprecipitate into vWD dogs markedly shortened bleeding time but did not support thrombosis as seen in dogs with vWF in the plasma and subendothelium. Thrombosis, then, fails to occur when vWF is absent from the plasma and subendothelial compartments or present only in the plasma compartment. These data are consistent with the hypothesis that vWF in the plasma and subendothelium supports thrombosis. Neither plasma FVIII nor platelet vWF is essential for thrombosis in this model.

scholarly journals Autoimmune- and complement-mediated hematologic condition recrudescence following SARS-CoV-2 vaccination

2021 ◽  
Vol 5 (13) ◽  
pp. 2794-2798
Author(s):  
Andrew Jay Portuguese ◽  
Cassandra Sunga ◽  
Rebecca Kruse-Jarres ◽  
Terry Gernsheimer ◽  
Janis Abkowitz
Keyword(s):  
Hemophilia A ◽  
De Novo ◽  
Medical Center ◽  
Vaccine Dose ◽  
Von Willebrand Disease ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Acquired Von Willebrand Disease ◽  
Autoimmune Conditions ◽  
Von Willebrand

Abstract A variety of autoimmune disorders have been reported after viral illnesses and specific vaccinations. Cases of de novo immune thrombocytopenia (ITP) have been reported after SARS-CoV-2 vaccination, although its effect on preexisting ITP has not been well characterized. In addition, although COVID-19 has been associated with complement dysregulation, the effect of SARS-CoV-2 vaccination on preexisting complementopathies is poorly understood. We sought to better understand SARS-CoV-2 vaccine-induced recurrence of autoimmune- and complement-mediated hematologic conditions. Three illustrative cases were identified at the University of Washington Medical Center and the Seattle Cancer Care Alliance from January through March 2021. We describe the recrudescence of 2 autoimmune conditions (ITP and acquired von Willebrand Disease [AvWD]/acquired hemophilia A) and 1 complementopathy (paroxysmal nocturnal hemoglobinuria [PNH]). We report the first known case of AvWD/acquired hemophilia A, and describe the first PNH exacerbation in the absence of complement inhibition after SARS-CoV-2 vaccination. Although SARS-CoV-2 vaccine-induced ITP is a known concern, our case clearly depicts how thrombocytopenia in the setting of preexisting ITP can sequentially worsen with each vaccine dose. Based on our experiences and these examples, we provide considerations for how to monitor and assess risk in patients with underlying autoimmune- and complement-mediated hematologic conditions.

DDAVP at a Maximal Dose of 15 ug Administered Subcutaneously Is a Safe and Effective Alternative to 20 ug IV for Patients > 50 kg with von Willebrand Disease or Mild Hemophilia A.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1793-1793
Author(s):  
Joy Mangel ◽  
Lori Laudenbach ◽  
Sheila Schembri ◽  
Lawrence Jardine ◽  
Reinhard Lohmann
Keyword(s):  
Hemophilia A ◽  
Maximum Dose ◽  
Standard Dose ◽  
Subcutaneous Administration ◽  
Von Willebrand Disease ◽  
The Body ◽  
Effective Alternative ◽  
Median Baseline ◽  
Median Increase ◽  
Von Willebrand

Abstract Background: DDAVP (desmopressin) is commonly used for the prophylaxis and treatment of bleeding in patients with mild forms of von Willebrand disease (VWD) and Hemophilia A (HemA). The standard dose is 0.3 ug/kg IV, to a maximum of 20 ug. In 1995, our Bleeding Disorders Program began to use a maximum dose of 15 ug both for DDAVP challenges and for therapeutic purposes. This dosing change was triggered by the new availability of 15 ug (1 ml) vials of DDAVP. We also switched to subcutaneous administration rather than intravenous, given the smaller volume (1 ml), and the body of evidence supporting this route of administration (De Sio et al, Thrombosis and Hemostasis1985; 54:387–9). With this strategy, patients weighing <50 kg continue to receive a weight-based dose, but those weighing ≥ 50 kg receive 15ug. Method: In order to evaluate this new dosing regimen, a retrospective review was performed of 62 patients with VWD (n=36) or mild hemophilia (n=26) weighing ≥ 50kg who underwent DDAVP challenges using a 15 ug s/c dose of DDAVP. Data was also collected on the 9 patients (5 VWD, 4 HemA) tested prior to 1995 who received 20 ug IV of DDAVP. Results: Levels of von Willebrand factor antigen (vWFag), ristocetin cofactor activity (RCof) and factor VIII (FVIII) were measured immediately prior to and 1 hour after administration of DDAVP. In the VWD patients (14M, 22F), median baseline levels of vWFag, RCof and FVIII were 31, 27 and 45 U/ml respectively, and rose to a median of 93, 90 and 177 U/ml following a 15 ug dose of DDAVP. This resulted in a median increase of 64 for vWFag (range 0–180), 55 for RCof (24–191) and 121 for FVIII (21–237). Results were comparable in the 5 pts who received 20 ug doses of DDAVP, achieving median increases of 77 (range 17–125), 53 (40–91) and 98 (79–184) respectively. In the HemA patients (19M, 7F), median baseline level of FVIII was 23 U/ml, and rose to a median of 57 U/ml following 15 ug DDAVP. Median increase in FVIII levels was 33 U/ml (range 2–108). These results compare favorably to the 4 patients who received 20 ug DDAVP and achieved a median FVIII increase of 19 U/ml (range 9–60). Chart review identified 26 patients (14 VWD, 12 HemA) who successfully received 15 ug doses of DDAVP in 44 clinical settings, either for the treatment of an acute bleeding episode or as prophylaxis prior to a planned surgical or dental procedure. Conclusions: DDAVP given subcutaneously to a maximum dose of 15 ug appears to be a safe and effective alternative to 20 ug IV for pts > 50 kg with VWD or mild hemophilia A.

Analytical Characterization of Infusion Volume Reduced Humate-P®/Haemate® P.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4167-4167
Author(s):  
Hubert J. Metzner ◽  
Ernst-Jürgen Kanzy ◽  
Antje Kalbass ◽  
Holger Lind ◽  
Heinz-Georg Mueller ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Von Willebrand Disease ◽  
Active Ingredients ◽  
Current Product ◽  
Factor Viii Concentrates ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Application Volume

Abstract Commercially available von Willebrand factor (VWF)/factor VIII concentrates are therapy of choice in severe von Willebrand disease (VWD), clinically characterized by serious bleedings, as well as in some cases of hemophilia A. Humate-P®/Haemate® P is one of the few products approved for therapy and prophylaxis in both indications, VWD and hemophilia A. As it was desirable to further improve the convenience of application for the patients by reducing the application volume, an infusion volume reduced (i.v.r.) Humate-P®/Haemate® P was developed increasing the product concentration while keeping the well-known positive product characteristics. Eight i.v.r. Humate-P®/Haemate® P batches were produced and vials of each batch were reconstituted using the reduced volume of water for injection, i.e. 5 mL (250 IU F VIII), 10 mL (500 IU F VIII), for 15 mL (1.000 IU F VIII). These lots were compared analytically with 18 lots of current Humate-P®/Haemate® P. The analytical comparison demonstrated that the i.v.r. product contains twofold increased concentrations of the active ingredients VWF and F VIII (see table). As the purification and virus inactivation processes have not been changed, the quality of the active ingredients is maintained. This e.g. could be shown by a high VWF:RCo/F VIII:C ratio of about 2.4 for the volume reduced as well as the current product. Additionally, the VWF:RCo/VWF:Ag ratio and the high molecular weight (HMW) multimer structure of i.v.r. Humate-P®/Haemate® P are equivalent to current Humate-P®/Haemate® P (see table) and close to that of NHP indicating a comparably good efficacy of i.v.r. and current products. Based on the analytical investigations described here, it can be concluded that the development of i.v.r. Humate-P®/Haemate® P resulted in a product of unchanged quality of the active ingredients but very high VWF concentration. This allows the application of VWF in small volumes and, consequently, will furthermore improve the convenience of VWD and hemophilia A treatment. Table Humate-P®/Haemate® P i.v.r. Humate-P®/Haemate® P Parameter 250/500 IU (n=12) 1000 IU (n=6) 250/500 IU (n=5) 1000 IU (n=3) F VIII:C (1-stage), IU/mL 24.5±1.3 31.2±2.0 51.2±0.8 66.3±4.2 VWF:RCo, IU/mL 58.3±4.1 78.3±4.0 119.8±10.9 159.3±14.2 VWF:RCo/VWF:Ag 0.78 ± 0.08 0.81 ± 0.06 VWF:RCo/F VIII:C (1-stage) 2.43 ± 0.12 2.36 ± 0.15 VWF HMW Multimers (>10) 75 ± 5.5% of NHP 77 ± 3.5% of NHP

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