Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recessive type 3 von Willebrand disease (VWD) is caused by homozygosity or double heterozygosity for two non-sense mutations (null alleles). Type 3 VWD is easy to diagnose by the combination of a strongly prolonged bleeding time (BT), absence of ristocetine-induced platelet aggregation (RIPA), absence of von Willebrand factor (VWF) protein, and prolonged activated partial thromboplastin time (aPTT) due to factor VIII:coagulant (FVIII:C) deficiency. VWD type 3 is associated with a pronounced tendency to mucocutaneous and musculoskeletal bleedings since early childhood. Carriers of one null allele are usually asymptomatic at VWF levels of 50% of normal. Recessive severe type 1 VWD is caused by homozygosity or double heterozygosity for a missense mutation. Recessive type 1 VWD differs from type 3 VWD by the presence of detectable von Willebrand factor: antigen VWF:Ag and FVIII:C levels between 0.09 and 0.40 U/mL. Patients with recessive type 1 VWD show an abnormal VWF multimeric pattern in plasma and/or platelets consistent with severe type 2 VWD. Carriers of a missense mutation may have mild bleeding and mild VWF deficiency and can be diagnosed by a double VWF peak on cross immunoelectrophoresis (CIE). There will be cases of mild and moderate recessive type 1 VWD due to double heterozygosity of two missense mutations, or with the combination of one missense mutation with a non-sense or bloodgroup O. Mild deficiency of VWF in the range of 0.20 to 0.60 U/mL, with normal ratios of von Willebrand factor: ristocetine cofactor/antigen VWF:RCo/Ag and VWF:collagen binding/antigen (VWF:CB/Ag), normal VWF multimers, and a completely normal response to desmopressin acetate (DDAVP) with VWF level rising from below to above 1.00 U/mL are very likely cases of so-called pseudo-VWF deficiency in individuals with normal VWF protein and gene. Autosomal dominant type 1 VWD variants are in fact type 2 variants caused by a heterozygous missense mutation in the VWF gene that produces a mutant VWF protein that has a dominant effect on normal VWF protein produced by the normal VWF allele with regard to the synthesis, processing, storage, secretion, and/or proteolysis of VWF in endothelial cells. A DDAVP challenge test clearly differentiates between dominant type 1 VWD phenotype and dominant type 2 M VWD.
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PMID:Characterization of recessive severe type 1 and 3 von Willebrand Disease (VWD), asymptomatic heterozygous carriers versus bloodgroup O-related von Willebrand factor deficiency, and dominant type 1 VWD. 1695 81

In recent years a new understanding of trauma-associated hemorrhaging and trauma-induced coagulopathy has been achieved. This coagulopathy is multifactorial with the predominant mechanisms being tissue trauma, shock and hypoperfusion which can lead to hyperfibrinolysis by activation of the endothelium. Routinely tested coagulation parameters, such as prothrombin time and partial thromboplastin time, are frequently employed for decision making but remain problematic as they do not give any information on clot stability, lysis or platelet function. Thrombelastometry seems to be a useful alternative. A pro-active anticipatory approach is required for a successful outcome to be achieved as rescue correction is more difficult than prevention. While the pathophysiological conception of causal relationship of the mentioned therapeutic options is conclusive, an evidence-based validation by randomized controlled studies is mostly lacking. The emergency and anesthesiological concept of damage control resuscitation consists of limiting volume therapy with crystalloids and colloids to reach a mean arterial pressure > or =65 mmHg (higher for head injuries), active (re-)warming management, the prevention of a pH< or =7.2 and a base excess (BE) < or =-6 mmol/l. The early and sufficient application of hemostatic drugs is essential. Because erythrocytes play a substantial role in the coagulation process, hemoglobin (Hb) values of around 6. 2 mmol/l (10 g/dl) and/or a hematocrit of 30% should be strived for when massive non-arrested hemorrhaging occurs. After severe multiple trauma a fibrinogen deficit develops and must be adequately compensated. If coagulation therapy is carried out using fresh frozen plasma sufficient quantities (20-30 ml/kgBW) must be administered to correspondingly raise the coagulation factors. Prothrombin complex concentrates can be helpful to optimize thrombin generation during severe hemorrhaging. Because hyperfibrinolysis occurs more often than previously assumed during severe trauma, an anti-fibrinolytic therapy should be used especially for patients with an instable circulation. The platelet count should not go below 100,000/microl when hemorrhaging occurs after multiple trauma. For thrombocytopathic patients with diffuse bleeding desmopressin (DDAVP) is a therapeutic option and the "off label" use of recombinant activated factor VIIa (rFVIIa) remains an option for individual situations with stringent indications and when the above named measures to optimize the coagulation situation have been taken.
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PMID:[Coagulation management in the treatment of multiple trauma]. 1981 62

Acquired inhibitors against coagulation factor VIII (FVIII), also termed acquired haemophilia A, neutralize its procoagulant function and result in severe or often life-threatening bleeding. The antibodies arise in individuals with no prior history of clinical bleeding. Acquired haemophilia occurs rarely with the incidence of approximately 1 to 4 per million/year, with severe bleeds in up to 90% of affected patients, and high mortality between 8-22%. About 50% of diagnosed patients were previously healthy, while the remaining cases may be associated with postpartum period, autoimmune diseases, malignancy, infections, or medications. Most patients have spontaneous haemorrhages into the skin, muscles or soft tissues, and mucous membranes, or after trauma and surgery, whereas haemarthroses are uncommon. The diagnosis of acquired haemophilia A based on the prolongation of activated partial thromboplastin time which does not normalize after the addition of normal plasma, reduced FVIII, with evidence of FVIII inhibitor measured by the Bethesda assay (Nijmegen modification). The treatment of acute bleeding episodes and the long-term eradication of the autoantibodies in acquired haemophilia are the main therapeutic strategy. Two options are currently available for acute bleeding control: the use rFVIIa or FEIBA in patients with higher inhibitor titer (> 5 BU), or to raise the level of FVIII by administration of DDAVP or concentrates of FVIII in patients with low level of inhibitors (< 5 BU). Treatment with FEIBA (50-100 IU/ kg every 8-12 hours) has shown good haemostatic response in 76-89% of the bleeding episodes. Patients treated with rFVIIa (90 microg/kg every 2-6 hours) have achieved good response in 95-100% as a first-line, and 75-80% as a salvage therapy. Patients with low inhibitor titer and lower response can be treated with concentrate of FVIII in the recommended dose of 40 IU/kg plus 20 IU/kg for each BU of inhibitor. The treatment of non-life-threatening haemorrhages with desmopressin (DDAVP 0.3 microg/kg) may increase both FVIII and vWF. Sometimes inhibitors disappear spontaneously, but long-term management is necessary for eradication of inhibitors by immunosuppression (prednisone 1 mg/kg 3 weeks alone or in combination cyclophosphamide 2 mg/kg), immunomodulation, intravenous immunoglobulin (HD IgG 2 g/kg 2 or 5 d), physical removal of antibodies (plasmapheresis or immunoadsorption), or various combinations. Recently, a therapy with rituximab, an anti-CD20 monoclonal antibody, has shown to be effective in acquired haemophilia.
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PMID:Acquired haemophilia syndrome: pathophysiology and therapy. 2022 86

As new anticoagulants become available, and the number of anticoagulated patients continues to rise, it is necessary to know how to deal with associated bleeding complications. In this review, reversal strategies for traditional anticoagulants (warfarin and heparin) as well as newer anticoagulants are described. Prothrombin complex concentrates (PPCs) can be used to reverse vitamin K antagonists (VKA), and plasma may be used where they are not available. Recombinant activated factor VII (rFVIIa) may be useful to reverse pentasaccharide anticoagulants. 1-Desamino-8-D-arginine vasopressin (DDAVP), cryoprecipitate, PCCs, and dialysis may help to reverse direct thrombin inhibitors, while rFVIIa seems to be ineffective. The effect of direct factor Xa inhibitors may be reversed by PCCs, FVIIa, or factor Xa concentrates.
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PMID:Management of bleeding complications in the anticoagulated patient. 2200 94

A 61-year-old female with no history of bleeding was admitted to our hospital owing to persistent bleeding after the left knee joint injection and activated partial thromboplastin time prolongation. Subsequent coagulation tests revealed a critically declined level of the von Willebrand factor (VWF) antigen (<10%) and activity (<10%) measurement besides a significantly declined factor VIII activity (4%). Despite diagnosing her with acquired von Willebrand syndrome (AvWS) and managing her bleeding with desmopressin acetate hydrate (DDAVP), we could not precisely make a definitive diagnosis the underlying disorder. More than 15 months after the onset of AvWS, CD20-positive atypical lymphocytes appeared in the peripheral blood and bone marrow without systemic lymphadenopathy. We initiated rituximab monotherapy eight times a week for CD20-positive lymphoproliferative disorders. The treatment not only caused the disappearance of the clonal expansion of CD20-positive atypical lymphocytes in both peripheral blood and bone marrow but also exhibited the clinical remission of AvWS. In addition, the maintenance therapy with rituximab every 3 months resulted in the durable remission of over 5 years. AvWS is a rare bleeding disorder, similar to von Willebrand disease, which arises from various underlying diseases. Our experience with this case highlights that rituximab proved to be one of the effective and well-tolerated treatment options for AvWS associated with CD20-positive B-cell lymphoproliferative disorders.
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PMID:[Durable remission attained with rituximab therapy in a patient with acquired von Willebrand syndrome associated with CD20-positive lymphoproliferative disorder]. 2974 2

Oral anticoagulants are commonly prescribed in patients with kidney diseases having atrial fibrillation and thromboembolic risk. It is very important to understand their clinical pharmacology and changes that may occur as GFR declines. Risks and benefits of newer oral anticoagulants are different in patients with CKD and patients with ESRD. Patients with GFR < 30 ml/min per 1.73 m2, including those on dialysis, were systematically excluded from landmark trials. All of the NOACs are dependent on renal clearance to some degree and so the risk of NOAC associated bleeding may be expected to be greater in patients with renal failure. Apixaban may be at least as safe as (or possibly safer than) warfarin in individuals with ESRD. Until more data become available, use of dabigatran, rivaroxaban, and edoxaban in patients with CKD stage 5 and ESRD is not indicated. Available strategies for reversing the anticoagulant effect of NOAC are - specific reversal agents available for dabigatran (idarucizumab) and for the oral direct factor Xa inhibitors - andexanet alfa, antifibrinolytic agents, DDAVP and prothrombin complex concentrates (PCCs). In this review clinical and pharmacological aspects of newer oral anticoagulants in the setting of chronic kidney disease will be discussed.
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PMID:Newer Oral Anticoagulant in Chronic Kidney Disease: What we Should Know. 3179 71


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