Assuntos
Síndrome Antifosfolipídica , Hipoprotrombinemias , Lúpus Eritematoso Sistêmico , Humanos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Inibidor de Coagulação do Lúpus , Hipoprotrombinemias/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnósticoRESUMO
We describe the case of a 50-year-old woman with a history of SLE and APS that presented with a spontaneous subdural haematoma, prolonged aPTT, PT and INR and positive LA. The activity of the coagulation factors II, VIII, IX and XI was extremely low, and anti-prothrombin antibody IgG was positive. LAHS was established, with inhibition of the intrinsic pathway, as an acquired haemophilia. The patient received corticosteroids and cyclophosphamide as treatment. To the best of our knowledge, this is one of the few reports of spontaneous intracranial bleeding, an unusual and initial manifestation of LAHS in an adult patient.HighlightsLAHS is characterised by the presence of LA and hypoprothrombinaemia caused by anti-prothrombin antibodies.Prolonged aPTT and INR, and positive LA are important laboratory findings that help the suspicion of LAHS.Intracranial bleeding is an unusual manifestation of LAHS associated with low factor II activity.Corticosteroids are the first-line treatment of LAHS.The prognosis of LAHS is good with adequate treatment, with a reported mortality of 5%.
Assuntos
Síndrome Antifosfolipídica , Hipoprotrombinemias , Síndrome Antifosfolipídica/diagnóstico , Feminino , Hematoma Subdural/etiologia , Humanos , Hipoprotrombinemias/diagnóstico , Inibidor de Coagulação do Lúpus , Pessoa de Meia-IdadeRESUMO
Antiphospholipid syndrome (APS) is an autoimmune disease characterized clinically by the occurrence of venous or arterial thrombosis, and/or pregnancy morbidity. The detection of persistently elevated levels of antiphospholipid antibodies (aPL) is a requisite laboratory feature for the diagnosis of APS. The positivity for at least one aPL test: lupus anticoagulant and/or IgG/IgM anticardiolipin and/ or IgG/IgM anti-ß2 glycoprotein I antibodies must be detected. Sometimes aPL coagulopathy may start with a hemorrhagic syndrome when a severe thrombocytopenia, or an acquired thrombocytopathy, or an acquired factor VIII inhibitor, or an acquired prothrombin deficiency is present. aPL-associated thrombocytopenia is usually moderate without clinical manifestations. Except in the occasional situations in which thrombocytopenia is associated with thrombotic microangiopathy, such as catastrophic APS, bleeding is uncommon in APS patients. When platelet counts are less than 30 × 109/L and there are symptoms of bleeding, the treatments used are the same for idiopathic thrombocytopenic purpura. In rare occasions a hemorrhagic diathesis due to the occurrence of non-neutralizing anti-prothrombin antibodies causing severe hypoprothrombinemia (HPT) can be observed. Levels of prothrombin in plasma are less than 10-20% in cases with HPT-related bleeding requiring transfusion and/or corticosteroid treatment. The APS mainly causes thrombosis, and pregnancy losses. However, other clinical manifestations are also associated with the presence of persistent autoimmune aPL. Bleeding is uncommon but can be the first clinical manifestation in patients having severe thrombocytopenia or prothrombin deficiency.
Assuntos
Síndrome Antifosfolipídica/complicações , Hemorragia/complicações , Hipoprotrombinemias/complicações , Trombocitopenia/complicações , Síndrome Antifosfolipídica/diagnóstico , Feminino , Humanos , GravidezRESUMO
OBJECTIVE: To identify if anemia, hypoalbuminemia, hypocalcemia, elevated values of creatinephosphokinase and hypoprothrombinemia are risk for mortality in necrotizing fasciitis according to the anatomical site and affected surface. METHODS: A case and controls study was done in one prospective cohort. We documented age, associated factors, infection location, affected corporal surface, laboratory data, germs, treatment and evolution. We defined two groups of patients: deceased and survivors and we stratified in 6 subgroups according to the anatomical site. RESULTS: 394 patients were included; 252 men and 142 women, age average 52.8 years. We stratified in subgroups: extremities (n = 113), masculine genital (n = 103), trunk and abdomen (n = 64), neck and thorax (n = 44), feminine genital, perineum, groin (n = 42), sacrum and buttocks (n = 28). Hypoalbuminemia (OR = 3.8, CI = 1.5-9.5, p < 0.000), hypocalcemia (OR = 5.7, CI = 3.2-9.9, p= 0.030), elevated creatinephosphokinase (OR = 1.5, CI 1.0-2.4, p < 0.000) and anemia (OR = 4.4, CI 2.8-6.9, p < 0.000), were associated to mortality. Logistic regression analysis found that albumin (OR = 3.8, CI = 1.5-8.9), prothrombin (OR = 6.6, CI = 3.6-19.5) and evolution time (OR 5.2, IC = 1.2-8.3) showed statistically significant relationship with mortality (p < 0.05). CONCLUSIONS: Hypocalcemia, hypoprothrombinemia, anemia, elevated creatinephosphokinase and evolution time could be risk markers for mortality.
Assuntos
Fasciite Necrosante/sangue , Fasciite Necrosante/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/complicações , Biomarcadores/sangue , Estudos de Casos e Controles , Creatina Quinase/sangue , Fasciite Necrosante/complicações , Fasciite Necrosante/patologia , Feminino , Humanos , Hipoalbuminemia/sangue , Hipoalbuminemia/complicações , Hipocalcemia/sangue , Hipocalcemia/complicações , Hipoprotrombinemias/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
Prothrombin deficiency is a very rare autosomal recessive bleeding disorder associated with mild to severe bleeding symptoms. We identified this bleeding disorder in a US-born patient as due to prothrombin Puerto Rico I. Unlike other prothrombin deficiencies, prothrombin Puerto Rico I is a series of concordant polymorphisms found in people of Puerto Rican descent with a much higher frequency than those prothrombin deficiencies found in the general population. This case underscores the importance of family history in identifying rare bleeding disorders.
Assuntos
Hipoprotrombinemias/enzimologia , Hipoprotrombinemias/patologia , Protrombina/genética , Protrombina/metabolismo , Feminino , Humanos , Hipoprotrombinemias/genética , Pessoa de Meia-Idade , Mutação/genética , Protrombina/classificação , Estados UnidosRESUMO
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.
Assuntos
Hipoprotrombinemias/genética , Mutação de Sentido Incorreto , Adolescente , Adulto , Análise Mutacional de DNA , Saúde da Família , Feminino , Heterozigoto , Homozigoto , Humanos , Masculino , Mutação Puntual , Polimorfismo de Nucleotídeo Único , Conformação Proteica , Protrombina/química , Protrombina/genética , Porto RicoRESUMO
La paciente motivo del presente informe no cumplía los criterios para diagnóstico de LES. La presencia de ACL, serología falsamente positiva, aCL elevadas e hipocomplementemia asociada a diátesis hemorrágica, además de las respuestas clínicas y de las pruebas de la coagulación con esteroides en dosis altas, nos hace pensar que se trata de un síndrome ACL-HP. Sería además el primer caso informado con henmorragia uterina anormal.
Assuntos
Transtornos Hemorrágicos , HipoprotrombinemiasRESUMO
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.
Assuntos
Hemorragia/diagnóstico , Hemorragia/etiologia , Hipoprotrombinemias/sangue , Hipoprotrombinemias/complicações , Inibidor de Coagulação do Lúpus/sangue , Adolescente , Anticorpos/análise , Anticorpos Anticardiolipina/análise , Criança , Feminino , Glicoproteínas/imunologia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Síndrome , beta 2-Glicoproteína IRESUMO
Fulminant hepatic failure (FHF) is an acute and eventually fatal illness, caused by a severe hepatocyte damage with massive necrosis. Its hallmarks are hepatic encephalopathy and a prolonged prothrombin time (<40 percent). FHF is currently defined as hyperacute (encephalopathy appearing within 7 days of the onset of jaundice), acute (encephalopathy appearing between 8 and 28 days) or subacute (encephalopathy appearing between 5 and 12 weeks). FHF can be caused by viruses, drugs, toxins, and miscellaneous conditions such as Wilson's disease, Budd-Chiari syndrome, ischemia and others. However, a single most common etiology is still not defined. Factors that are valuable in assessing the likelihood of spontaneous recovery are age, etiology, degree of encephalopathy, prothrombin time and serum bilirubin. The management is based in the early treatment of infections, hemodynamic abnormalities, cerebral edema, and other associated conditions. Liver transplant has emerged as the most important advance in the therapy of FHF, with a survival rate that ranges between 60 and 80 percent. The use of hepatic support systems, extracorporeal liver support and auxiliary liver transplantation are innovative therapies