Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019087 (hemorrhagic diathesis)
 678 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By virtue of a severely prolonged aPTT with a normal thromboplastin time (prothrombin time) and a normal thrombin time, severe FXII deficiency has been diagnosed in a woman without a bleeding diathesis or a history of thromboembolic complications. A deficiency of a factor of the contact activation system (FXII, prekallikrein, high molecular weight kininogen) is usually diagnosed during routine coagulation tests demonstrating a prolonged aPTT. The severe and partial deficiency of FXII, of prekallikrein or high molecular weight kininogen is not associated with a bleeding tendency. In contrast, severely factor XI deficient subjects may suffer from a mild hemorrhagic diathesis, whereas FVIII deficiency (hemophilia A, autoimmune "hemophilia", von Willebrand disease) and FIX deficiency (hemophilia B) are associated with a bleeding tendency of varying severity, depending on the clotting activity of FVIII or FIX, respectively. An isolated prolongation of the aPTT due to a lupus anticoagulant, however, is frequently associated with arterial and/or venous thrombosis. Therefore, in case of a prolongation of the aPTT, its cause has to be determined.
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PMID:[A patient with isolated prolongation of aPTT without hemorrhagic diathesis anamnesis: severe, hereditary factor XII deficiency]. 1051 21

Fibrinogen plays a complex role in hemostasis, thrombosis, and vascular disease. Hyperfibrinogenemia is an independent vascular risk factor and dysfibrinogenemia can provoke thrombosis. Afibrinogenemia is usually responsible for hemorrhagic diathesis, and unexpected ischemic lesions are intriguing. We report the case of an afibrinogenemic patient, who at the age of 30 developed ischemic lesions of the feet related to severe stenosis of the iliac and hypogastric arteries. The biopsy of the iliac artery lesion showed an intense myointimal hyperplasia. We performed standard hemostatic analysis and analyzed the activation markers of platelets and coagulation factors and the kinetics of thrombin generation in the patient and in normal control plasmas treated or not with reptilase. Occlusive arterial lesions were attributed to a disruptive hematoma penetrating the vascular lumen. Thrombin concentration after calcium addition increase markedly in the afibrinogenemic patient and in defibrinated normal plasma, as compared to untreated normal plasma. Thrombin-antithrombin complexes (T-AT) were markedly enhanced while F1+2 prothrombin fragments stayed in the normal range. These results suggested activation of coagulation and in vivo circulating thrombin. Thrombin activates the platelets that secrete growth factors for smooth muscle cells and generate the intimal hyperplasia. Recurrent hemorrhage within the vessel wall might induce injury and local thrombin generation. Thrombin not trapped by the clot is available for platelet activation and smooth muscle cell migration and proliferation. The absence of a protective fibrin cap on the intima might account for intima vulnerability and embolization. Afibrinogenemia appears in this paradoxical situation as a vascular risk factor.
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PMID:Embolized ischemic lesions of toes in an afibrinogenemic patient: possible relevance to in vivo circulating thrombin. 1136 14

We report the result of a randomized, controlled, open trial of anti-thrombin therapy for herpes zoster-associated pain. Fifty-five herpes zoster patients within 8 days after the onset of skin lesion were enrolled in the trial. Patients were treated with an optimal dose of oral acyclovir (4000 mg/day for 7 days) with or without intravenous administration of a specific anti-thrombin agent, argatroban (10 mg/day, three times a week). Administration of argatroban reduced pain intensity at the 4th through 21st day after the initiation of treatment as determined by visual analogue scale (Mann-Whitney U test, p < 0.05). It also shortened the median time to cessation of analgesic use (14 days vs. 24 days, p = 0.02, logrank test), although it did not significantly reduce the median time to cessation of pain (21 days vs. 43 days, p = 0.07, logrank test). None of the enrolled patients showed evidence of adverse effects including hemorrhagic diathesis. The results suggested that relatively low doses of argatroban are effective in reducing herpes zoster-associated pain. Up-regulation of prothrombin expression by the vascular endothelial and sweat gland epithelial cells in the active skin lesion and transient elevation of plasma thrombin-antithrombin III complex levels in a proportion of patients suggest a lesional generation of thrombin in herpes zoster. This may be relevant to the beneficial effects of the anti-thrombin treatment on the resolution of herpes zoster-associated pain.
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PMID:A specific thrombin inhibitor, argatroban, alleviates herpes zoster-associated pain. 1144 71

Congenital afibrinogenaemia is a rare hemorrhagic disorder characterized by the absence of fibrinogen. We report a case of congenital afibrinogenaemia presented with leg ulcer. A 30-year-old man presented with a history of prolonged bleeding from birth. His parents are cousins. He repeatedly showed haematoma after traumas on his leg. He was diagnosed as having congenital afibrinogenaemia because of plasma fibrinogen deficiency. Because his leg ulcer gradually increased in size, he was admitted to our department for treatment. Laboratory examinations revealed prolonged bleeding time, prolonged coagulation time, prolonged prothrombin time, prolonged activated partial thromboplastin time and plasma fibrinogen was not measurable. Histological examination revealed hyperkeratosis, acanthosis and severe fibrotic change in the whole dermis. Severe hemosiderin deposit was found in the middle dermis. His leg ulcer cured 2 months after the beginning of fresh frozen plasma administration (FFP), but recurrence of the leg ulcer after FFP treatment was found. This is the second reported case of congenital afibrinogenaemia presented with leg ulcer.
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PMID:Leg ulcer presenting in a patient with congenital afibrinogenaemia. 1180

In a patient who presented with a severe coagulation deficiency in plasma contrasting with a very mild hemorrhagic diathesis a homozygous Arg67His mutation was identified in the prothrombin gene. Wild-type (factor IIa [FIIa]-WT) and mutant Arg67His thrombin (FIIa-MT67) had similar amidolytic activity. By contrast, the k(cat)/K(m) value of fibrinopeptide A hydrolysis by FIIa-WT and FIIa-MT67 was equal to 2.1 x 10(7) M(-1)s(-1) and 9 x 10(5) M(-1)s(-1). Decreased activation of protein C (PC) correlated with the 33-fold decreased binding affinity for thrombomodulin (TM; K(d) = 65.3 nM vs 2.1 nM, in FIIa-MT67 and in FIIa-WT, respectively). In contrast, hydrolysis of PC in the absence of TM was normal. The Arg67His mutation had a dramatic effect on the cleavage of protease-activated G protein-coupled receptor 1 (PAR-1) 38-60 peptide (k(cat/)K(m) = 4 x 10(7) M(-1)s(-1) to 1.2 x 10(6) M(-1)s(-1)). FIIa-MT67 showed a weaker platelet activating capacity, attributed to a defective PAR-1 interaction, whereas the interaction with glycoprotein Ib was normal. A drastic decrease (up to 500-fold) of the second-order rate constant pertaining to heparin cofactor II (HCII) interaction, especially in the presence of dermatan sulfate, was found for the FIIa-MT67 compared with FIIa-WT, suggesting a severe impairment of thrombin inhibition by HCII in vivo. Finally, the Arg67His mutation was associated with a 5-fold decrease of prothrombin activation by the factor Xa-factor Va complex, perhaps through impairment of the prothrombin-factor Va interaction. These experiments show that the Arg67His substitution affects drastically both the procoagulant and the anticoagulant functions of thrombin as well as its inhibition by HCII. The mild hemorrhagic phenotype might be explained by abnormalities that ultimately counterbalance each other.
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PMID:Molecular and functional characterization of a natural homozygous Arg67His mutation in the prothrombin gene of a patient with a severe procoagulant defect contrasting with a mild hemorrhagic phenotype. 1214 17

Acquired factor X deficiency has been described in patients with amyloidosis but acquired factor V deficiency is quite rare. We report here a case of life-threatening bleeding and acquired factor V deficiency associated with primary amyloidosis. A 50-year-old man who had no previous hemorrhagic diathesis was referred to our hospital because of recurrent epistaxis, gingival bleeding and hemospermia. The laboratory examination revealed that both the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) were significantly prolonged, and factor V activities were markedly decreased to 14-39% of the normal value. Other coagulation factors such as fibrinogen, prothrombin, factor VII, factor VIII, factor IX and factor X were subnormal and normal. Transaminases were slightly elevated but serological tests of hepatitis B and hepatitis C were negative. Mild hepatosplenomegaly was noted without sign of liver cirrhosis. The PT and aPTT obtained 8 years ago when he received a cholecystectomy due to cholecystitis were both normal. Specific assays for the detection of factor V inhibitor were repeatedly performed but no factor V inhibitor was found. Furthermore, a significant recovery of the infused factor V was noted shortly after an intravenous administration of 5-10 U fresh frozen plasma, but it did not last more than 6 h. Melena, bleedings into the left shoulder and buttock, and finally mortal retroperitoneal hemorrhage developed despite repeated infusions of large amounts of fresh frozen plasma. Acquired factor V deficiency associated with primary amyloidosis was suspected but histological diagnosis was not obtained because of the severe bleeding tendency. Autopsy revealed hepatosplenomegaly and massive deposits of AL amyloid in the liver, spleen, heart and other parenchymal organs. Perivascular amyloid deposition and factor V deficiency are both thought to be the cause of the severe hemorrhagic tendency seen in this patient.
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PMID:Life-threatening bleeding and acquired factor V deficiency associated with primary systemic amyloidosis. 1219 8

We report a severe hemorrhagic disorder in two pediatric patients with lupus anticoagulant (LA) associated to acquired factor II (prothrombin) deficiency. In both patients, hemorrhagic symptoms resolved after corticosteroid therapy. Serial coagulation studies showed that Staclot LA assay was more sensitive than DVVconfirm and Staclot PNP tests to confirm the presence of LA when associated with severe factor II deficiency. Both patients had non-neutralizing anti-prothrombin antibodies and their titers inversely correlated with factor II activity (r = -1.0, P < 0.0001). Associated findings in these patients included positive immunologic tests for systemic lupus erythematosus, a positive anti-cardiolipin antibody, and anti-beta(2) GPI antibodies in one case. Our findings point out the difficulty in diagnosing LA associated with acquired factor II deficiency and suggest that, in confirmation of its phospholipid dependency, the inclusion of a source of normal human plasma in the test sequence to correct for any factor deficiency and a confirmatory step utilizing hexagonal (II) phase phospholipids may be crucial to the diagnosis of LA in some patients with LA-hypoprothrombinemia syndrome.
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PMID:Diagnosis of lupus anticoagulant in the lupus anticoagulant-hypoprothrombinemia syndrome: report of two cases and review of the literature. 1241 May 76

Glanzmann's thrombasthenia is an inherited hemorrhagic disorder characterized by a severe reduction in, or absence of, platelet aggregation in response to multiple physiologic agonists due to qualitative or quantitative abnormalities of platelet glycoprotein IIb-IIIa. Glanzmann's thrombasthenia is characterized by potentially major mucocutaneous bleeding and prolonged bleeding time. Platelet counts, platelet morphology, prothrombin, and activated thromboplastin times are all within normal ranges in patients with Glanzmann's thrombasthenia. Pregnancy and delivery are rare in Glanzmann thrombasthenia patients and have been associated with immediate postpartum hemorrhage. We describe the peripartum management of a 31-year-old primipara with Glanzmann's thrombasthenia who underwent spontaneous vaginal delivery. Four units of single-donor platelets, two units of packed red blood cells, 36 microg/kg recombinant human coagulation Factor VIIa (rFVIIa) were given during peripartum management.
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PMID:The use of recombinant factor VIla in a primigravida with Glanzmann's thrombasthenia during delivery. 1549 26

Severe hemorrhagic diathesis due to lupus anticoagulant complicated by hypoprothrombinaemia resulting from prothrombin autoantibodies is a rare disorder and is often associated with systemic lupus erythematosus (SLE). We report a case in which a 15-year-old girl with SLE developed marked haemorrhagic manifestations due to menorrhagia and nosebleeds. The acute bleeding episode was treated with SAGM, tranexamic acid and recombinant factor VIIa. Lupus anticoagulant, cardiolipin antibodies and antiprothrombin antibodies were successfully depressed within weeks after corticosteroid therapy was begun.
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PMID:[Serious bleeding in systemic lupus erythematosus complicated by lupus anticoagulant-hypoprothrombinaemia syndrome]. 1647 41

A patient with a severe prothrombin deficiency and a hemorrhagic diathesis was found to have positive cross-reactive material in plasma and a homozygous F299V mutation (F7V in the A chain). This mutation reinforces the previous conclusion that the A chain affects the geometry of the catalytic triad. Marked prolongation of the Taipan venom and Russell venom clotting times also demonstrated a defective activation mechanism and a defective interaction with factor Xa.
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PMID:Prothrombin Suresnes: a case of homozygous F299V mutation responsible for hypodysprothrombinemia. 1650 55


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