Hemophilia

Haemophilia is a common hereditary bleeding disorder and is caused either by a lack of coagulation factor VIII or IX. The extent of the factor deficiency determines the probability and severity of bleeding. Bleeding in deeper tissue or joints mostly develop within hours after trauma. the diagnosis by a specific factor analysis is confirmed. The suspected hemophilia, patients with prolonged PTT and normal PT with normal platelet counts. If acute bleeding is suspected, they have already been confirmed or if it is likely that acute bleeding develop (eg. As before surgery), treatment consists primarily in the replacement of the missing clotting factor.

Haemophilia is a common hereditary bleeding disorder and is caused either by a lack of coagulation factor VIII or IX. The extent of the factor deficiency determines the probability and severity of bleeding. Bleeding in deeper tissue or joints mostly develop within hours after trauma. the diagnosis by a specific factor analysis is confirmed. The suspected hemophilia, patients with prolonged PTT and normal PT with normal platelet counts. If acute bleeding is suspected, they have already been confirmed or if it is likely that acute bleeding develop (eg. As before surgery), treatment consists primarily in the replacement of the missing clotting factor.

(See also coagulation disorders at a glance.) Hemophilia is a common hereditary bleeding disorder and is caused by a deficiency either coagulation factor VIII or IX. The extent of the factor deficiency determines the probability and severity of bleeding. Bleeding in deeper tissue or joints mostly develop within hours after trauma. the diagnosis by a specific factor analysis is confirmed. The suspected hemophilia, patients with prolonged PTT and normal PT with normal platelet counts. If acute bleeding is suspected, they have already been confirmed or if it is likely that acute bleeding develop (eg. As before surgery), treatment consists primarily in the replacement of the missing clotting factor. Hemophilia A (factor VIII deficiency), which affects about 80% of patients with hemophilia, and hemophilia B (factor IX deficiency) show at the appropriate screening tests, the same clinical images and changes. Both disorders are inherited X-linked. specific factors analyzes are necessary to distinguish between the two types. Etiology In hemophilia is a hereditary disease that is the result of mutations, deletions, or inversions of the genes for factor VIII or factor IX. Because these genes are located on the X chromosome, hemophilia usually affects only men. Daughters of men with haemophilia are always Genträgerinnen (Konduktorin), sons, however, are healthy. At every son of a wearer there is a 50% probability to develop a hemophilia, and each daughter is a 50% probability of a wearer. Pathophysiology for normal hemostasis (see Figure paths of blood clotting) are required> 30% of normal factor VIII or-IX levels. Most patients with hemophilia have mirror <5%; some have extremely low levels (<1%). The functional level (activity) of Factor VIII or IX in hemophilia A and B (and therefore the severity of blood flow) varies depending on the specific mutation of the factor VIII or IX gene. Scheme of blood clotting. The female carriers usually have levels of about 50%. Rarely can cause a random inactivation of a normal X chromosome in the early embryonic phase, which gene carriers also have factor VIII or-IX levels of <30%. Most patients with hemophilia who received treatment in the early 1980s were infected by contaminated factor concentrates with HIV. Occasionally, patients have developed an immune thrombocytopenia due to HIV infection, causing bleeding were reinforced. Symptoms and discomfort patients with hemophilia suffer bleeding in tissue (eg. As haemarthrosis, muscle hematomas, retroperitoneal bleeding). The bleeding can use immediately or with a delay, depending on the extent of the trauma and the plasma levels of factor VIII or factor IX. Often occur with the onset of bleeding in pain, sometimes even before the development of signs of bleeding. Chronic or recurrent haemarthrosis can cause synovitis and arthropathy. Even a slight blow to the head can cause intracranial hemorrhage. Bleeding at the base of the tongue can lead to life-threatening compression of the airways. A severe hemophilia (factor VIII or-IX levels <1% of normal) can live long cause severe bleeding. These often begin shortly after birth (eg. As scalp hematoma after birth or excessive bleeding after circumcision). At a moderate hemophilia (factor levels of 1-5% of normal) Minimal trauma usually lead already bleeding. With a slight hemophilia (factor level of 5-25% of normal), excessive bleeding may occur after surgery or tooth extractions. Diagnosis platelet count, PT, PTT, factor VIII and factor IX analyzes Occasionally Von Willebrand Factor activity and antigen -Multimer analysis The suspected hemophilia, patients with recurrent bleeding, unexplained hemarthroses or an extension the PTT. If a hemophilia suspected, PTT, PT, platelet count and factor VIII-IX and analyzes should be performed. In hemophilia there is a prolonged PTT, however, platelet count and PT are normal. By factor VIII-IX and assays of the type and severity of hemophilia are detected. Since the factor VIII levels may be reduced even when von Willebrand disease (vWD), are for patients newly diagnosed with hemophilia A and Von Willebrand factor (vWF) activity, vWF antigen amount and vWF -Multimer composition determined, especially when the disease is weak and history of both men and women are affected in the family. To determine whether a woman is Konduktorin hemophilia A, sometimes the measurement of factor VIII levels may be sufficient. Similarly, the Konduktorin hemophilia B can be often identified by the measurement of factor IX levels. A PCR analysis which is carried out in special laboratories of the factor VIII gene, it can be determined whether a patient is hemophilia gene carriers. The corresponding prenatal diagnosis via a chorionic villus sampling at the 12th week of pregnancy (SSW) or amniocentesis in the 16th week of pregnancy. However, these methods are associated with a risk of miscarriage of 0.5-1%. After repeated exposure to factor VIII replacement therapy 15-35% of Hemophilia A patients develop a Factor VIII allo-antibody (alloantibodies) that inhibits the clotting activity of each further added factor VIII. In particular, before elective surgery which make factors replacement therapy required, patients should be tested in this isoantibodies by screening (eg., By measuring the degree of the PTT shortening immediately after the mixture of patient's plasma with an equal volume of normal plasma and a subsequent re-test after one hour of incubation). If isoantibodies are present, their titre can be measured by the extent of factor VIII inhibition is determined by serial dilutions of patient plasma. Tips and risks Since the factor VIII levels may also be reduced in von Willebrand's disease, are in patients with newly diagnosed hemophilia A and Von Willebrand factor (vWF) activity, vWF antigen amount and vWF -Multimer composition determined. Prevention Patients should avoid aspirin and NSAIDs (both inhibit platelet function). Regular dental care is important to avoid tooth extractions or other dental surgeries. Drugs should be administered orally or i.v. are administered. Intramuscular injections can cause bruising. In addition, patients should be vaccinated against hepatitis B with hemophilia. Treatment replacement of the factor for which there is a lack Occasionally Antifibrinolytics If symptoms suggestive of bleeding should begin treatment immediately, even if the diagnostic tests have not been completed. For example, should the treatment of headaches, suggestive of intracranial hemorrhage, done before the CT imaging. The primary therapy consists in the replacement of the missing clotting factor. In hemophilia A, the values ??for factor VIII should be temporarily increased to about 30% of normal to prevent bleeding after tooth extractions or joint bleeding 50% if greater joint bleeding or intramuscular bleeding were detected 100% if major surgery is to be performed or intracranial , intracardiac or other life-threatening bleeding should Thereafter maintenance doses of 50% of the initial dose every 8-12 h are administered to stabilize the values ??of> 50%. This should be done after major surgery or life-threatening bleeding about 7-10 days time. Each unit / kg of factor VIII raises the factor VIII value by about 2%. Therefore z. B. about 25 units / kg required to raise the values ??of 0 to 50%. Factor VIII can be obtained from different donors are given as purified concentrate. This factor VIII concentrate is virus inactivated, thereby parvovirus or Hepatitis A Virus are not necessarily killed. Recombinant factor VIII is free of viruses and is usually preferred when patients have not been seropositive for HIV or hepatitis B or C. In hemophilia B Factor IX can h be administered as purified or recombinant virus-inactivated product every 24th The target values ??for the factors raising are the same as in hemophilia A. However, the doses must be increased in order to achieve these values ??because factor IX is less than factor VIII and unlike factor VIII has a large extravascular distribution. Fresh frozen plasma contains factors VIII and IX. However, if no plasma exchange is performed, the administration of fresh frozen plasma in patients with severe hemophilia usually not sufficient in order to raise the plasma levels of factor VIII or IX to the point that bleeding can be prevented or controlled. Therefore, fresh frozen plasma should only be used when a quick replacement is necessary and not a factor concentrate available. In addition, fresh frozen plasma can be used when the patient’s coagulopathy is not clearly diagnosed. Recently, it was from a recombinant Factor VIII Fc fusion protein (1) and a recombinant factor IX Fc fusion protein (2) and a pegylated recombinant factor IX (3) reports with longer in vivo survival times that successfully bleeding in hemophilia A and B control. developing the treatment of choice in patients with hemophilia Factor VIII inhibitors, the repeated administration of activated factor VII (VIIa) in high doses (for. example, 90 ug / kg). Both VWF and Factor VIII are stored in the Weibel-Palade bodies of endothelial cells and are secreted in response to cell stimulation of endothelial cells (4). The adjunctive therapy for hemophilia A thus contains in vivo stimulation of endothelial cells of patients with the synthetic vasopressin analogue DDAVP (deamino-U-arginine vasopressin, also known as desmopressin known). As with VWD desmopressin may temporarily increase the factor VIII levels. However, the response of the patient should be checked prior to therapeutic administration of desmopressin. The use of desmopressin for small traumas or before elective maxillofacial surgery can help avoid the factor replacement therapy. However, only in patients with mild hemophilia A (factor VIII basal values ??? 5%) should be used desmopressin in which a response was detected on desmopressin. An antifibrinolytic agent (aminocaproic acid 2.5-4 g po four times a day for 1 week or tranexamic acid 1.0-1.5 g po three or four times daily for one week) may also be administered as adjunctive therapy in hemophilia A or B to avoid delayed bleeding after tooth extractions or other oropharyngeal mucous membrane trauma (z. B. Zungenbiss). Treatment References 1. Mahlangu J, Powell JS, Ragni MV, et al. Phase 3 trial of recombinant Factor VIII Fc fusion protein with severe hemophilia A. Blood 123: 317-325, 2014. 2. Powell JS, Pasi KJ, Ragni MV, et al. Phase 3 trial of recombinant Factor IX Fc fusion protein in hemophilia B. N Engl J Med 369: 2313-2323, 2013. 3. Collins PW, Young G, Knobe K, et al. Recombinant long-acting glycoPEGylierter factor IX in hemophilia B: A multinational, randomized Phase 3 study. Blood 124: 3880-3886, 2014. 4. Turner NA and Moake JL. Factor VIII is synthesized in human endothelial cells, packed in Weibel-Palade bodies and secreted to UL-vWF bound threads. PLoS ONE 10 (10): e0140740, 2015. Key points hemophilia are X-linked recessive Koagulationskrankheiten. Hemophilia A (about 80% of patients) is a factor VIII deficiency and hemophilia B associated with a factor IX deficiency. The patients have bleeding into the tissue (eg haemarthrosis, muscle hematomas, retroperitoneal bleeding.) Following minimal injury; it can lead to fatal intracranial bleeding. PTT is lengthened, but PT and platelet counts are normal; by factor VIII-IX and assays of the type and severity of hemophilia are detected. In patients with bleeding, or those in which bleeding is expected (. Eg, prior to surgery or tooth extraction), a compensation factor is administered, preferably using a recombinant product; The dosage depends on the circumstances. About 15 to 35% of patients with hemophilia A, necessary for the repeated factor VIII infusions develop factor VIII antibodies.

Health Life Media Team

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