Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684275 (haemophilia)
 10,958 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disappearance of an inhibitor to factor IX in an 11-year-old boy with haemophilia B is described. He had been given a total of 14,200 units of a prothrombin complex concentrate (PCC) before an inhibitor to factor IX developed. He subsequently received four separate infusions of PCC and his inhibitor titre rose in response to the treatment for the following 4 years. No inhibitor is presently detected despite repeated administration of PCC. Immunological characterization of the inhibitor by inhibitor neutralization assays, modified crossed-immunoelectrophoresis and enzyme-linked immunosorbent assay demonstrated that it contained IgG2 and IgG4 heavy chains and kappa and lambda light chains. No large deletion of the factor IX gene in the patient was observed using cDNA (cVII).
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PMID:Disappearance of inhibitor to factor IX in a patient with severe haemophilia B and immunological characterization of the inhibitor. 284 18

Twelve boys with haemophilia and factor VIII inhibitors have received initial treatment for each episode of bleeding with prothrombin-complex concentrate. The follow-up period for these boys has ranged from two months to 14 years, and a total of 732 bleeding episodes were reviewed. Each boy underwent a full clinical and radiological assessment of knee-joint function, and this was compared with knee-joint function in 29 patients with severe haemophilia but without factor VIII antibodies. A change of treatment from prothrombin-complex concentrate to some other form of therapy was considered to be required in only 4% of the bleeding episodes. Of 10 severe bleeding episodes, five episodes clearly were controlled with prothrombin-complex concentrate, but five episodes necessitated alternative treatment. Four of the 12 families considered prothrombin-complex concentrate as relatively ineffective. All boys who were older than 10 years of age showed grade-1 or grade-2 impairment of knee-joint mobility, as well as radiological evidence of moderate-to-severe knee-joint changes. In the group of haemophiliac patients who were older than 10 years of age and did not have factor VIII antibodies, only 10 of the 58 knee-joints that were examined showed grade-1 or grade-2 functional impairment. Although prothrombin-complex concentrates were effective in the control of the majority of minor bleeding episodes, they were effective in only 50% of severe episodes of bleeding and did not prevent the early development of haemophilic arthropathy.
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PMID:Long-term results of the treatment of children with factor VIII inhibitors with prothrombin-complex concentrates. 311 53

A novel factor IX gene mutation (factor IX London 2) has been characterized. This causes severe crm+ haemophilia B as the patient's plasma shows normal factor IX antigen level and less than 1% clotting activity. Sequence analysis of the entire cloned coding and promoter regions revealed a single point mutation: a G----A transition at position 31,119. This region of the patient's DNA was amplified in vitro by the polymerase chain reaction and the nucleotide change was confirmed by direct sequencing of the amplified products. The mutation results in the substitution of the arginine at position 333 by glutamine. This arginine residue is absolutely conserved in the catalytic domain of normal human and bovine factor IX, X and prothrombin. The substitution by glutamine causes the loss of a positive charge from the surface of the factor IX London 2 protein. This mutation pinpoints a previously unknown, functionally critical feature of factor IX which may be involved in substrate or co-factor binding.
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PMID:A factor IX mutation, verified by direct genomic sequencing, causes haemophilia B by a novel mechanism. 318 Nov 27

A case of ruptured cerebral aneurysm with hemophilia B is reported, and discussion is made concerning the management of mild type hemophilia in surgical operations. A 41-year-old male came to our hospital with complaints of severe headache, vomiting, and transient consciousness disturbance. His dentist said the patient had a mild bleeding tendency when he was 30 years old, however no postoperative hemorrhage was repeated in appendectomy in his childhood. He also had had no episodes of spontaneous bleeding. CT scan on admission showed subarachnoid hemorrhage, and angiography revealed a ruptured aneurysm at the trifurcation of the left middle cerebral artery. His coagulation screening tests (bleeding time, clotting time, prothrombin time, and activated partial thromboplastin time) were normal. An aneurysmal neck clipping was carried out, and operators did not detect any bleeding tendency during the surgery. CT scan on the next day showed no remarkable finding. On the third postoperative day, right hemiparesis occurred. Left putaminal hemorrhage took place. His coagulation tests and FDP were also normal. The hematoma was partially evacuated. After the second operation his condition was good, and rehabilitation program started. On the 15th hospital day his consciousness deteriorated suddenly, and CT scan showed a massive epidural hematoma on the left. His prothrombin time elongated mildly, but other tests were normal. Coagulation factors VIII and IX were examined and the factor IX was 22.5% of control. He was thought to be a patient with mild type hemophilia B. Despite a third operation for hematoma removal he died on the 20th hospital day. Mild type hemophilia B does not bleed spontaneously.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Unusual postoperative hemorrhage in a patient with ruptured aneurysm and hemophilia B]. 321 Dec 77

Ageing does not bring with it any major changes in the coagulation or fibrinolytic proteins or platelets. It does bring a greater burden of disease, with less reserves, and so when haemorrhage occurs in the elderly it has more serious consequences. The cause of a bleeding diathesis can usually be determined after a careful history, and examination of the patient followed by simple tests--the platelet count, blood film, bleeding time, prothrombin time, partial thromboplastin time, thrombin time, fibrin degradation products and the euglobulin clot lysis time. Other confirmatory tests, assays and inhibitor titres, will seal the diagnosis. Treatment is mainly directed at removing the underlying cause, if possible, and remedying the defect, with platelet transfusion, fresh frozen plasma or factor concentrates. These treatments will not be effective where there is an inhibitor or antibody present; steroids, splenectomy (for ITP), plasma exchange or immunosuppression are needed. Two major advances have occurred in the early 1980s. One has been the introduction of high-dose intravenous immunoglobulin in the management of ITP, although worries remain about thrombotic events in elderly patients. The other is the spreading use of DDAVP, originally introduced for von Willebrand's disease and mild haemophilia, and now finding a role in uraemia and with cardiopulmonary bypass. Drugs are a significant and potentially preventable cause of bleeding in the elderly. The most frequent problems arise with anticoagulants. The risk of interactions increase with the number of other medications which are prescribed.
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PMID:Bleeding and coagulation disorders in the elderly. 332 49

In this paper, a five generation Greek family is described with haemophilia B. The disease is characterized by a normal ox-brain prothrombin time, normal levels of the vitamin-K dependent clotting factors VII and X and a proportional reduction of factor IX activity and antigen levels all of which is consistent with the cross-reacting material negative form of haemophilia B. However, in this family the factor IX levels in the three patients of generation V are around 1 U/dl while the three older patients in generation III have factor IX levels ranging from 28 to 44 U/dl. In the oldest patient of generation V we observed a rise of the factor IX level from 1 U/dl up to the age of 13 to 10 U/dl at age 14. In addition, the older patients have very mild bleeding symptoms or none at all, while the young ones have occasional spontaneous haemorrhages in muscles and joints, compatible with severe or moderately severe haemophilia. The disease appears to be similar to haemophilia B Leyden which has been described in a Dutch family.
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PMID:Haemophilia B Leyden in Greece. 356 65

Factor IX is the precursor of a serine protease that functions in the intrinsic blood clotting pathway. Deficiencies in this plasma glycoprotein result in haemophilia B (or Christmas disease) and occur in about 1 in 30,000 males. Patients are currently treated with fresh frozen plasma or prothrombin complex concentrates prepared from pooled plasma from normal individuals. There are several problems with this method of treatment, including the probable exposure of the patients to contaminants such as the viral agents responsible for hepatitis and AIDS (acquired immune deficiency syndrome). As a first step towards an alternative source of pure human factor IX, we report here on the use of recombinant DNA techniques to produce biologically active factor IX in cultured mammalian cells. Stable cell lines were produced by cotransfecting a baby hamster kidney (BHK) cell line with a plasmid containing a gene for factor IX and a plasmid containing a selectable marker. Protein secreted by these cell lines reduces the clotting time of plasma from factor IX-deficient patients. We present additional evidence that this protein is authentic human factor IX.
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PMID:Expression of active human factor IX in transfected cells. 389 76

Appropriate long-term oral anticoagulation prevents cardiogenic thromboembolism to a large extent in patients with artificial heart valves, rheumatic heart disease, myocardiopathy, atrial fibrillation of non-rheumatic origin, sick sinus syndrome, cardiac aneurysm, and in the exceptional cases of mitral valve prolapse with thromboembolic complications. In arterial thrombosis, oral anticoagulation remains a controverted, probably because a much higher intensity would be needed to achieve the same degree of effectiveness. With target prothrombin times between 3.5 and 4 International Normalized Ratios (INRs) and a compliance of the INRs with the range of 2.5-5 INRs for greater than or equal to 80%, cardiogenic thromboemboli can be prevented in approximately 95% whereas only about two thirds of the cases of recurrent coronary thrombosis can be avoided. The intensity and stability of treatment needed in cardiovascular thrombosis involve a considerable risk of bleeding, but--as shown by the results of the Dutch Sixty Plus Reinfarction Study--intracranial haemorrhages are more than compensated for by the prevention of cerebrovascular thromboembolic events. Appropriate administration of oral anticoagulation requires painstaking laboratory and therapeutic control, the former being based on continuous quality assessment and strict standardization of the prothrombin time. Therapeutic control consists of continuous patient education and adequate dosage regulation. Similar to the situation prevailing for hemophilia patients, an organization must be available to which long-term anticoagulated patients can apply for expert advice. In The Netherlands, an organization has been built up on a voluntary basis, called Federation of Thrombosis Centres, meeting this requirement and covering more than 90% of the country.
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PMID:[What can be expected today from long-term anticoagulation for cardiac and arterial thrombosis?]. 390 83

An abnormal life-threatening haemorrhagic diathesis occurred 6 weeks after delivery in a 25-year-old female. The reason was a spontaneously acquired factor VIIIC inhibitor haemophilia. The clinical presentation was characterised by extensive deep-seated soft-tissue haemorrhages of the extremities, a retroperitoneal haemorrhage, haematuria and recurrent joint bleedings. The activity of factor VIIIC decreased to below 1% of normal. The factor VIII inhibitor reached a maximum of 122 Bethesda units. The recurrent knee joint haemorrhages responded well to treatment with an activated prothrombin complex concentrate (Feiba). Repeated Feiba administration did not lead to an increase of the factor VIII inhibitor. It disappeared completely within 16 months and did not recur during a second pregnancy. The pregnancy was without complications and delivery on time resulted in a healthy child. Six months after the second pregnancy both mother and child showed no evidence of a disorder of haemostasis.
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PMID:[Postpartum hemophilia A with factor VIII inhibitor]. 392 27

Type and quantity of replacement treatment, together with haematological and immunological parameters were determined in 37 boys with severe haemophilia A and 41 children with other bleeding disorders. The quantity of factor VIII concentrate given to boys with severe haemophilia A (mean U/year) showed a significant inverse correlation with total white cell counts, lymphocyte counts, platelet counts, and the ratio of monoclonal antibody defined T lymphocyte subsets, T4 and T8 (T4:T8). Of the boys with severe haemophilia A, 49% had inversed T4:T8 ratios and 24% had thrombocytopenia. Treatment with high dose factor VIII concentrate (more than 25 000 U/year) was associated with low platelet counts, low lymphocyte counts, low T4:T8 ratios, and hypergammaglobulinaemia. In addition, six patients with severe haemophilia A and factor VIII inhibitors had inversed T4:T8 ratios. Patients treated exclusively with cryoprecipitate or prothrombin complex concentrates had normal T4:T8 ratios and platelet counts. The severity of the haematological and immunological abnormalities observed seems to be associated with high usage of factor VIII concentrates. Similar abnormalities have been described in patients with the acquired immune deficiency syndrome (AIDS). Prospective study of haemophiliacs is required to assess long term sequelae of factor concentrate usage, including the possible development of AIDS.
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PMID:Lymphocyte subset ratios and factor VIII usage in haemophilia. 392 94


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