1/36. Lupus anticoagulant-hypoprothrombinemia syndrome associated with systemic lupus erythematosus: report of 2 cases and review of literature.We describe two patients whose initial presentation of systemic lupus erythematosus (SLE) was accompanied by haemorrhagic episodes and significant coagulopathy. Further investigation demonstrated positive lupus anticoagulant and decreased Factor II (prothrombin) activity. Both patients were diagnosed with lupus anticoagulant-hypoprothrombinemia syndrome (LAC-HPS) as a result of non-neutralizing antibodies directed against Factor II. LAC-HPS is a rare clinical entity that can occur in association with SLE, transient viral infections, drug reactions or even in healthy individuals. Mixing studies, which can be affected by other coagulation factor inhibitors, play an important role in the diagnosis of LAC-HPS. Factor VII level was decreased in the second patient, a finding that has not previously been reported in association with SLE. In both patients, bleeding stopped promptly and coagulation studies improved significantly with high dose corticosteroids. We discuss the pathogenesis, diagnosis and management of LAC-HPS in patients with SLE.- - - - - - - - - - ranking = 1keywords = coagulation (Clic here for more details about this article) |
2/36. Gingival bleeding, epistaxis and haematoma three days after gastroenteritis: the haemorrhagic lupus anticoagulant syndrome.A 3 year and 9 month-old girl presented with gingival bleeding, epistaxis, and multiple haematomas 3 days after an acute episode of gastroenteritis. prothrombin time and activated partial thromboplastin time were prolonged with reduced clotting activity of factor II (< 10%), VIII (<1%), IX (3%), XII (10%) and evidence of a high titre inhibitor. Prothrombin (factor II) level was below the detection limit, both in a functional and immunological assay. It did not increase after administration of vitamin k or fresh frozen plasma. Further studies revealed presence of a strong lupus anticoagulant and a specific IgG antibody against prothrombin. factor viii antigen levels also were reduced (31%), but to a lesser extent than functionally determined factor viii (<1%). blood coagulation normalised following clinical recovery 6 weeks after admission. The pathophysiology of this acquired inhibitor phenomenon (accelerated clearance of complexes of clotting factors and phospholipids) is discussed. CONCLUSION: The haemorrhagic lupus anticoagulant syndrome (acquired hypoprothrombinaemia lupus anticoagulant syndrome) is a rare presentation of acquired bleeding diathesis in childhood. Since most cases in post-infectious children are asymptomatic, it might be underdiagnosed. In children with newly appearing bleeding symptoms or unclear prolonged prothrombin time or activated partial thromboplastin time, one has to consider this syndrome which could lead to relevant bleeding.- - - - - - - - - - ranking = 0.5keywords = coagulation (Clic here for more details about this article) |
3/36. Acquired bleeding disorder in a patient with malignant lymphoma: antibody-mediated prothrombin deficiency.BACKGROUND: Bleeding manifestations secondary to acquired hemostatic abnormalities in cancer patients have been well described. Bleeding due to the development of hemostatic inhibitors is observed less frequently. In this report, the authors describe a patient with a low grade lymphoma who presented with an acquired bleeding disorder and abnormal hemostatic screening tests. methods: Patient plasma samples were collected initially and during the course of treatment. Mixing studies and specific coagulation factor assays were performed to detect and confirm any deficiencies. Patient immunoglobulin g was isolated from plasma, and binding to prothrombin was demonstrated by immunoblot method and enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: Initial prolongations in the prothombin time and the activated partial thromboplastin time suggested a factor deficiency in the common pathway of coagulation. Factor assays confirmed that the coagulation abnormality in this patient was the result of an acquired prothrombin (factor II) deficiency. This was confirmed by an immunoassay for prothrombin antigen. Further studies demonstrated the presence of a noninhibitory antibody to prothrombin that interacted with a calcium dependent epitope. CONCLUSIONS: Successful treatment of the lymphoma resulted in clearance of the antibody and complete correction of all hemostatic abnormalities and manifestations. An acquired prothrombin deficiency has not been reported previously in association with a malignancy, and this patient represents the first such documented case.- - - - - - - - - - ranking = 1.5keywords = coagulation (Clic here for more details about this article) |
4/36. Combined deficiency of factors II, VII, IX, and X (Borgschulte-Grigsby deficiency) in pregnancy.BACKGROUND: Combined deficiency of vitamin k-dependent coagulation factors (II, VII, IX, X) is an uncommon challenge for the expectant gravida. CASE: A 34-year-old primigravida had congenital combined deficiency of factors II, VII, IX, and X that were incompletely sensitive to vitamin k. She had an altered form of vitamin k-dependent factors that retained immunologic activity but lacked coagulant activity and the normal complement of gamma-carboxyglutamic acid residues. She required vitamin k supplementation throughout her life. After an uneventful pregnancy she had postpartum hemorrhage resulting from an episiotomy. Fresh frozen plasma was administered to achieve hemostasis. The remainder of her postpartum course was normal. CONCLUSION: Combined congenital deficiency of factors II, VII, IX, and X can be managed in pregnancy with the use of vitamin k and fresh frozen plasma.- - - - - - - - - - ranking = 0.5keywords = coagulation (Clic here for more details about this article) |
5/36. diagnosis of lupus anticoagulant in the lupus anticoagulant-hypoprothrombinemia syndrome: report of two cases and review of the literature.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.- - - - - - - - - - ranking = 0.5keywords = coagulation (Clic here for more details about this article) |
6/36. A common mutation, Arg457-->Gln, links prothrombin deficiencies in the Puerto Rican population.Five unrelated families with Puerto Rican ancestry were identified as having at least one member with bleeding due to a prothrombin deficiency. Genetic prothrombin deficiencies are extremely rare, but at the University of puerto rico Hemophilia Center, prothrombin deficiency is the third most common congenital coagulation factor deficiency. Because puerto rico is relatively isolated, there was a reasonable expectation of a founder effect. Prothrombin genes from probands and their parents were directly sequenced from PCR amplified exons using forward and reverse primers. Four novel prothrombin mutations were identified. The first, a G-->A substitution at dna position 10150 predicting an Arg457-->Gln (R457Q) replacement, is common to all five families. In two of the families, the proband children are homozygous for R457Q. In the other three families, the probands are compound heterozygotes for R457Q and one of the other three mutations, which include another point mutation (gamma16Q), a deletion and a splice junction mutation. The two point mutations have been designated puerto rico I and puerto rico II. The crystal structure of alpha-thrombin predicts that the R457Q mutation removes a salt bridge that links the A- and B-chains of thrombin. The primary effect of this defect appears to be destabilization of the circulating prothrombin, creating a moderate hypoprothrombinemia. However, prothrombin antigen/activity ratios indicate a dysprothrombinemia as well, most likely due to the inability of R457Q prothrombin to activate fully to thrombin.- - - - - - - - - - ranking = 0.5keywords = coagulation (Clic here for more details about this article) |
7/36. Prothrombin Shanghai: hypoprothrombinaemia caused by substitution of Gla29 by Gly.Prothrombin deficiency is a rare bleeding disorder inherited as an autosomal recessive trait. In this study, we reported a Chinese family with hereditary prothrombin deficiency. The proposita had a prolonged activated partial thromboplastin time (APTT, 71.6 s) and prothrombin time (PT, 28.0 s). The coagulation factors activities were normal except that prothrombin coagulation activity was markedly reduced, and the prothrombin antigen level was moderately decreased. Nucleotide sequencing of amplified dna revealed a novel mutation, Glu (GAG) to Gly (GGG) at residue 29, which normally undergoes gamma-carboxylation within the Gla domain of prothrombin. The proposita was identified as homozygous, while her father, mother and maternal grandmother were heterozygous for the mutation. Gla29 has been demonstrated as one of the key residue for Ca2 -binding, membrane interaction and biological activity of prothrombin.- - - - - - - - - - ranking = 1keywords = coagulation (Clic here for more details about this article) |
8/36. anterior spinal artery syndrome in two children with genetic thrombotic disorders.BACKGROUND: Spinal cord infarction is a well-described, but rare, etiology of myelopathy, especially in children. The most common syndrome, anterior spinal artery syndrome (ASAS), is caused by interruption of blood flow to the anterior spinal artery, producing ischemia in the anterior two-thirds of the cord, with resulting neurologic deficits. Causes of ASAS include aortic disease, thoracolumbar surgery, sepsis, hypotension, and thromboembolic disorders. methods: case reports of 2 patients. RESULTS: Two children developed spinal cord infarctions consistent with ASAS, mostly likely caused by previously undiagnosed thrombotic disorders. A child with prothrombin variant experienced acute bilateral lower limb weakness without any preceding event. magnetic resonance imaging (MRI) revealed increased T2 signal in the anterior cord from midthoracic level to the conus medullaris. A child with protein s deficiency developed lower limb weakness 1 day after a posterior thoracolumbar fusion for idiopathic scoliosis. Computed tomography (CT) myelogram revealed no spinal cord compression. The prothrombin variant mutation is associated with a 2-fold risk of thrombotic events. Individuals with protein s deficiency have an 8-fold increased risk of thrombosis. CONCLUSION: As knowledge of the coagulation pathways grows, it is likely that more patients with spinal cord infarctions will be diagnosed with genetic thrombotic disorders as the etiology of their injury. We review these two disorders, prothrombin variant and protein s deficiency, and the considerations for long-term anticoagulation.- - - - - - - - - - ranking = 1keywords = coagulation (Clic here for more details about this article) |
9/36. Severe prothrombin deficiency caused by prothrombin-Edmonton (R-4Q) combined with a previously undetected deletion.BACKGROUND: During infancy, a male patient experienced several life-threatening bleeding episodes. Standard coagulation tests revealed that the patient's plasma prothrombin activity was 8%, while his father's and mother's levels were 74% and 62%, respectively. OBJECTIVES: A molecular genetic approach was used to determine the molecular basis of prothrombin deficiency within the family. PATIENT/methods: Prothrombin genomic dna fragments were amplified by using the polymerase chain reaction (PCR). In addition, liver cDNA fragments were amplified from the patient by using reverse transcription (RT) and PCR. The nucleotide sequences of the dna fragments were determined. RESULTS: A novel, heterozygous point mutation (g.1755 G > A, named prothrombin-Edmonton) was detected in the patient and his mother, resulting in the mutation of Arg-4 in the prothrombin propeptide to Gln (R-4Q). RT-PCR analysis of the patient's liver sample demonstrated the presence of two mRNA transcripts that differed by the presence or absence of exon 11. Real-time PCR analysis on genomic dna and cDNA confirmed a deletion (g.10435_10809del) in the paternal allele. CONCLUSIONS: The patient has a maternally-inherited point mutation (R-4Q) and a paternally-inherited deletion. By analogy with the previously reported factor ix San Dimas, the R-4Q mutation probably causes under-carboxylation of prothrombin and poor cleavage of the propeptide in the hepatocyte. The deletion probably results in a polypeptide that lacks 50 amino acids from the protease domain; this is likely to impair folding, secretion, stability and/or activity of the truncated prothrombin. The two mutations combine to give the prothrombin deficiency observed in the patient.- - - - - - - - - - ranking = 0.5keywords = coagulation (Clic here for more details about this article) |
10/36. Decreased hypoprothrombinemic response to warfarin secondary to the warfarin-nafcillin interaction.patients who are receiving multiple medications must be screened for significant drug interactions. The specific mechanism of a drug interaction determines whether the patient may experience a subtherapeutic effect or a potentially toxic reaction. Three cases of relative warfarin resistance, possibly related to high-dose nafcillin, are described in this report. Several reports have suggested that penicillinase-resistant penicillins, such as nafcillin and dicloxacillin, exert an important enzyme-inducing effect in patients receiving warfarin. This potential interaction must be appropriately recognized and managed in order to maintain adequate anticoagulation in this patient population.- - - - - - - - - - ranking = 0.5keywords = coagulation (Clic here for more details about this article) |
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