1/11. Spontaneous inhibitors to coagulation factors.Spontaneous inhibitors to coagulation factors are autoantibodies that usually appear in the elderly, but may also occur in patients with immunological disorders such as lupus, lymphoma, asthma or drug reactions. Most antibodies are directed against factor viii, but any coagulation protein may be affected. They should be suspected in individuals who previously had normal haemostasis, but who now begin to experience bleeding into the skin and muscles, or suffer haemorrhages after routine procedures such as insertion of vascular catheters, intramuscular injections, or minor surgery. The haemostasis laboratory is critical in identifying the particular inhibitor and quantitating its potency. factor viii inhibitors prolong the partial thromboplastin time (PTT) but not the prothrombin time (PT), and incubating mixtures of patient plasma and normal plasma enhances the prolongation of the clotting time. The Bethesda assay provides a rough assessment of inhibitor potency. Inhibitors of von willebrand factor prolong the bleeding time and impair ristocetin-induced platelet aggregation. Factor V inhibitors are associated with a prolonged PTT and PT, not correctable with normal plasma. patients will often have a history of exposure to bovine thrombin in fibrin glue. The antibodies most difficult to recognize are those that alter fibrin polymerization or stabilization. Abnormal clot retraction or clot solubility in urea solutions are an important clue. The management of these disorders depends on characterization of the inhibitor, and using appropriate clotting factor concentrates to control acute bleeding. For example, recombinant human factor viii or desmopressin may be effective for patients with low titre factor viii inhibitors, whereas porcine factor viii, recombinant factor Vlla, or prothrombin complex concentrates stem bleeding in those with high titres. Inhibitors of von willebrand factor may be amenable to desmopressin, cryoprecipitate, or von willebrand factor concentrates. Some patients with factor V inhibitors have responded to platelet transfusions, as the platelet factor V may be shielded from the autoantibody. Bleeding due to factor xiii inhibitors may be managed with fibrogammin, a factor xiii concentrate. All patients should be treated for underlying disorders and given drugs such as corticosteroids and cytotoxic agents to suppress inhibitor formation. Major advances in new immunosuppressive technologies, such as monoclonal B-cell antibodies, offer hope of more effective therapies for spontaneous inhibitors to coagulation factors.- - - - - - - - - - ranking = 1keywords = bovine (Clic here for more details about this article) |
2/11. Homozygous factor V splice site mutation associated with severe factor v deficiency.We investigated a family whose proband has a severe bleeding disorder and factor V antigenic and functional levels of 8% and less than 1% of control values, respectively. Molecular analysis of the factor V gene revealed a novel homozygous mutation in the last nucleotide of exon 10. 1701G>T causes activation of a cryptic exonic splice site in exon 10, which encodes part of the factor V heavy chain (A2 domain). This leads to the deletion of 35 nucleotides and results in a frameshift with a premature stop codon at amino acid position 498. The G1701 and corresponding Gln509 are conserved in murine, bovine, and porcine factor V and in human factor viii. Few factor v deficiency mutations have been identified as yet. Several are present in the heterozygous form in combination with factor V Leiden (Arg506Gln). This is the first reported homozygous splice site mutation in a patient with factor v deficiency.- - - - - - - - - - ranking = 1keywords = bovine (Clic here for more details about this article) |
3/11. Autoantibody to plasma fibrinopeptide a in a patient with a severe acquired haemorrhagic syndrome.We describe a 50-year-old man with a severe acquired haemorrhagic syndrome. He had slightly prolonged clotting times using bovine thrombin, human thrombin and reptilase. His plasma contained a polyclonal IgG which interfered with the generation of fibrin monomers without inhibiting the aggregation of preformed monomers. The inhibitor delayed thrombin-induced fibrinopeptide a release. The IgG bound to insolubilized synthetic fibrinopeptide a (one binding site per molecule) and, with higher affinity, to fibrinogen (two binding sites per molecule). It did not bind to insolubilized fibrin monomers. The IgG did not impair the catalytic activity of thrombin toward a small synthetic substrate but inhibited the binding of thrombin to fibrinogen without binding to thrombin. The binding of the anti-fibrinopeptide a autoantibody to fibrinogen might have impaired thrombin-induced fibrinogen to fibrin conversion in vivo. This may have favoured the reported haemorrhagic syndrome which was associated with severe chronic renal insufficiency.- - - - - - - - - - ranking = 55590.596001042keywords = haemorrhagic syndrome, bovine (Clic here for more details about this article) |
4/11. High-dose intravenous immunoglobulin treatment in two patients with acquired factor V inhibitors.We report two patients who developed acquired factor V (FV) inhibitors not related to exposure to bovine thrombin. Associated conditions were found in one patient (surgery, antibiotic administration) but none in the other one. Bleeding complications occurred only in the patient with idiopathic FV inhibitor, leading to packed red cell infusion. Laboratory findings showed the presence of specific FV inhibitors with titers of 5.5 and 5 Bethesda units, respectively. These two patients received high-dose intravenous immunoglobulin and FV levels normalized within a few days with a concomitant disappearance of FV inhibitors.- - - - - - - - - - ranking = 1keywords = bovine (Clic here for more details about this article) |
5/11. Factor V inhibitors: rare or not so uncommon? A multi-laboratory investigation.Acquired deficiencies of, or inhibitors to, factor V are considered rare events. We report a series of 14 acquired factor V deficiencies, 10 of which were confirmed to have inhibitors to factor V, as identified within australia in the past 5 years following a multi-laboratory investigation. The initial index case seen by one laboratory was followed within 4 months by a separate similar case. This prompted local contact with colleagues (n = 20) working in other haemostasis referral laboratories to identify the current case series. In total, nearly one-half of all haemostasis referral laboratories contacted had seen a case within the past 5 years. Clinical features and the apparent associated risk of bleeding complications generally varied, as did laboratory findings and the likely causal event. There were three females and 11 males. Age ranged from 44 to 95 years (median, 81 years). The level of inhibitor ranged from undetectable to over 250 Bethesda units. The probable cause leading to development of the inhibitors ranged from exposure to bovine thrombin, exposure to antibiotics, surgery and malignancy. Of additional interest was the apparent association of anti-phospholipid antibodies in many of the cases. For example, in the two similar index cases, with factor V inhibitor titres > 200 Bethesda units, high levels of anti-cardiolipin antibodies (> 70 GPL units) were also detected. Although less clear because of inhibitor interference, many of the cases also showed evident co-associated lupus anticoagulant activity. In conclusion, we report a series of factor V inhibitors recently identified within our geographic region that would represent an annual incidence of around 0.29 cases per million Australians. Although considered a rare finding, there is a high likelihood that most haemostasis referral laboratories will see a case every five or so years.- - - - - - - - - - ranking = 1keywords = bovine (Clic here for more details about this article) |
6/11. Development of antibodies to thrombin and factor V with recurrent bleeding in a patient exposed to topical bovine thrombin.A 65 year old patient who was exposed to topical bovine thrombin during cardiac surgery developed markedly prolonged clotting times and a severe bleeding diathesis. Mixing studies with normal plasma failed to correct the clotting times. Platelet transfusions, immunosuppressive and immunomodulatory therapies were ineffective, but plasmapheresis was effective in decreasing clotting times and in the resolution of clinical bleeding events. The patient's purified IgG reacted with bovine thrombin by immunoblotting and enzyme-linked immunosorbent assay (ELISA). However, the IgG reacted minimally with human thrombin. In view of the severe bleeding, a coexisting inhibitor was sought. The patient's factor V activity was 1% of normal and was not corrected by mixing with normal plasma, demonstrating the presence of an inhibitor against factor V. The patient's IgG reacted with both bovine and human factor V. immunoblotting localized the site of antibody binding to the light chain of activated bovine factor V. Detectable amounts of bovine factor V were found in commercial bovine thrombin preparations by ELISA. The data suggest that patients exposed to topical bovine thrombin may develop antibodies to thrombin and factor V. Anti-thrombin antibodies may mask coexisting factor V inhibitors responsible for clinical bleeding.- - - - - - - - - - ranking = 11keywords = bovine (Clic here for more details about this article) |
7/11. Modified Cabrol shunt for control of hemorrhage in repair of type A dissection of the aorta.A technique of modifying the Cabrol shunt using preserved bovine pericardium and a patch of autologous pericardium to deal with postoperative hemorrhage from an ascending aortic operation is described. A fistula to the right atrium was created for autotransfusion. This simple technique is very useful for dealing with the catastrophic complication of such postoperative hemorrhage.- - - - - - - - - - ranking = 1keywords = bovine (Clic here for more details about this article) |
8/11. An unclassified platelet function disorder associated with bleeding tendency.A 7-year-old boy with a history of bleeding tendency showed a prolongation of bleeding time and a decrease in platelet adhesiveness. The platelets of the patient, however, had a normal reaction to ADP, collagen, epinephrine, arachidonic acid, bovine fibrinogen, ristocetin, A-23187 and thrombin-induced aggregation, and their shape was determined by electron microscopy to be normal. Therefore, this disorder could not be thought to belong to any known platelet dysfunction. On the other hand, an increase in clot retraction, a reversal of ATP/ADP, a decrease in beta-thromboglobulin and platelet factor 4 in the platelets, and an elevation of plasma levels of released beta-thromboglobulin from the platelets were observed in the patient. We don't know any cases with such an association of hypo- and hyperfunction of platelets.- - - - - - - - - - ranking = 1keywords = bovine (Clic here for more details about this article) |
9/11. aortic rupture caused by fungal aortitis: successful management after heart transplantation.A 26-year-old man with end-stage idiopathic cardiomyopathy was supported with a Pierce-Donachy left ventricular assist device for 31 days before orthotopic heart transplantation. Fungal endocarditis was discovered at the time of recipient cardiectomy, and antifungal therapy was begun. Fungal mediastinitis developed 4 days after transplantation and was treated with mediastinal irrigation. Massive mediastinal hemorrhage caused by fungal aortitis occurred on two occasions and was successfully treated with a bovine pericardial patch. The patient is well 9 months after transplantation.- - - - - - - - - - ranking = 1keywords = bovine (Clic here for more details about this article) |
10/11. life salvage with fibrin glue in three cases of exsanguinating hemorrhage.Fibrin glue, although widely used in europe for a decade, has not been commercially available in north america because its fibrinogen component is obtained from multiple, pooled, human blood donors with the subsequent increased risk of blood transmissible diseases. Techniques developed recently to isolate fibrinogen from single-donor plasma will circumvent these potential hazards. In canada the use of fibrin glue has not been widespread even though biologic fibrin glue can be made from components readily available within most hospitals. Equal amounts of cryoprecipitate from fresh frozen plasma and bovine thrombin will combine within 2 minutes to form the fibrin glue. Simultaneous injections of each component at bleeding sites form a film of the glue that will effectively control even small arterial bleeding. The authors present three case reports to illustrate how use of the glue can save lives in cases of exsanguinating hemorrhage. They discuss the multiple applications of the fibrin glue which they believe will soon be part of the armamentarium of all Canadian surgeons.- - - - - - - - - - ranking = 1keywords = bovine (Clic here for more details about this article) |
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