RESUMO
Acquired factor V deficiency (AFVD) is a rare autoimmune bleeding disorder. Unlike acquired hemophilia, bypass therapies with recombinant activated factor VII and activated prothrombin complex concentrates are ineffective for severe bleeding due to AFVD. Although several treatment strategies have been attempted, a standard of care for severe hemorrhage induced by AFVD is lacking. Herein, we report a case of AFVD with severe bleeding that responded to plasma exchange (PE) combined with immunosuppression. We also reviewed previously reported AFVD cases with severe hemorrhage and suggest that PE may be an effective initial treatment for AFVD-induced severe hemorrhage.
Assuntos
Deficiência do Fator V/complicações , Hemorragia/etiologia , Hemorragia/terapia , Troca Plasmática , Autoimunidade , Biomarcadores , Testes de Coagulação Sanguínea , Deficiência do Fator V/diagnóstico , Deficiência do Fator V/etiologia , Hemorragia/sangue , Hemorragia/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Troca Plasmática/efeitos adversos , Troca Plasmática/métodos , Índice de Gravidade de Doença , Avaliação de Sintomas , Tomografia Computadorizada por Raios X , Resultado do TratamentoAssuntos
Códon sem Sentido , Deficiência do Fator V/complicações , Hemofilia A/complicações , Lectina de Ligação a Manose/genética , Adulto , Povo Asiático , Deficiência do Fator V/etiologia , Família , Feminino , Hemofilia A/etiologia , Hemorragia/etiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , LinhagemAssuntos
Anemia Refratária com Excesso de Blastos/complicações , Doenças Autoimunes/etiologia , Azacitidina/uso terapêutico , Deficiência do Fator V/etiologia , Fator V/imunologia , Idoso de 80 Anos ou mais , Anemia Refratária com Excesso de Blastos/tratamento farmacológico , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Azacitidina/efeitos adversos , Diagnóstico Precoce , Deficiência do Fator V/tratamento farmacológico , Deficiência do Fator V/imunologia , Hemorragia Gengival/etiologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Tempo de Tromboplastina Parcial , Prednisona/uso terapêutico , Tempo de ProtrombinaRESUMO
Acquired coagulation factor inhibitors are rare. Among them, coagulation factor V (FV) inhibitor is particularly uncommon and presents with variable clinical manifestations. Certain acquired FV inhibitor patients have only mild bleeding or, in select cases, no symptoms at all, leading to spontaneous recovery. Others have life-threatening bleeding that requires medical attention. Thus, a prompt decision regarding diagnosis and clinical intervention is crucial for such patients. In five acquired FV inhibitor cases treated in our facility, each patient had a malignancy as an underlying disease and all unexpectedly showed prolongation of both prothrombin time (PT) and activated partial thromboplastin time (APTT). They all also displayed a discrepancy between PT and Normotest (Hepaplastintest, HPT) results. All but one patient experienced no bleeding at the time of diagnosis and achieved spontaneous recovery in 1-3 weeks. The patient with bleeding symptoms received plasma exchanges and a platelet transfusion. Useful markers in diagnosing the presence of an acquired FV inhibitor were a sudden prolongation of PT and APTT, and a discrepancy between the PT/APTT and HPT assays. Spontaneous recovery can be expected for patients with only minor bleeding.
Assuntos
Inibidores dos Fatores de Coagulação Sanguínea/sangue , Testes de Coagulação Sanguínea/métodos , Deficiência do Fator V/diagnóstico , Deficiência do Fator V/etiologia , Fator V/antagonistas & inibidores , Tempo de Protrombina , Idoso , Deficiência do Fator V/sangue , Feminino , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina ParcialRESUMO
INTRODUCTION: We describe our experience with managing an unusual case of acquired Factor V deficiency (aFVd) in a myeloma patient with demonstrated amyloidosis. METHODS: Following diagnosis, records of previous investigations were sought. Specific clotting factors and inhibitors were tested. The clinical progress and treatment response measured by serial factor V levels and coagulation parameters was then prospectively tracked. RESULTS: A 57â¯year-old woman presented with spontaneous right knee haemarthrosis in association with bilateral symmetrical polyneuropathy and proteinuria. Coagulation screen showed prolongation of both PT (18.6â¯s, normal range [9.9-11.4â¯s]) and aPTT (41.4â¯s, normal range [25.7-32.9â¯s]), which were both fully correctable following a mixing study. Liver function, fibrinogen, clotting factor II/VIII/X assays and disseminated intravascular coagulopathy screen was normal. FV level was reduced (19%, normal range [70-170%]). Inhibitor titer was undetectable. Congenital FVd was excluded as her previous coagulation screen was normal. Bone marrow investigation performed for suspected underlying plasma cell dyscrasia showed 60% neoplastic plasma cells. Congo red staining was positive for amyloid within vascular walls of the marrow trephine. She was diagnosed with light chain myeloma and aFVd. She received Bortezomib/Cyclophosphamide/Dexamethasone (VCD) chemotherapy. After one cycle of VCD, serum kappa free light chain (SFLC) was reduced from 6951â¯mg/L to 3354â¯mg/L with serial measurements of FV levels showing increment to 76% and normalization of PT/aPTT. CONCLUSION: Plasma cell dyscrasia with amyloidosis should be sought as a cause for aFVD, in particular one where bleeding manifestation is profound even with the absence of demonstrable inhibitors.
Assuntos
Amiloidose/complicações , Deficiência do Fator V/etiologia , Mieloma Múltiplo/complicações , Amiloidose/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/patologiaRESUMO
: Acquired factor V deficiency (AFVD) is a rare haemostatic disorder that is primarily because of the development of factor V inhibitors. Approximately, 200 cases have been reported and the greatest portion of these cases was because of bovine thrombin exposure. We report a case of a man who presented with haematuria followed by multiple haemorrhages associated with an elevated prothrombin time and an activated partial thromboplastin time. A workup revealed reduced factor V activity and a factor V inhibitor level of 1.9âBU, which were likely secondary to a urinary tract infection. Using corticosteroids, we successfully eliminated the inhibitor and controlled the bleeding. We review the published literature to identify the conditions that are associated with nonbovine thrombin AFVD. We assume that AFVD should be kept in mind for patients who present with multiple haemorrhages.
Assuntos
Deficiência do Fator V/diagnóstico , Fator V/imunologia , Hematúria , Hemorragia , Infecções Urinárias/patologia , Corticosteroides/uso terapêutico , Animais , Autoanticorpos/sangue , Testes de Coagulação Sanguínea , Bovinos , Diagnóstico Diferencial , Fator V/antagonistas & inibidores , Deficiência do Fator V/tratamento farmacológico , Deficiência do Fator V/etiologia , Hemorragia/tratamento farmacológico , Transtornos Hemorrágicos , Humanos , Masculino , Pessoa de Meia-Idade , Trombina , Infecções Urinárias/complicaçõesRESUMO
Inhibitors directed against factor V rarely occur, and the clinical symptoms vary. We herein report the case of a patient who presented with a decreased factor V activity that had decreased to <3 %. We administered vitamin K and 6 units of fresh frozen plasma, but she thereafter developed an intracerebral hemorrhage. It is unclear whether surgery >10 years earlier might have caused the development of a factor V inhibitor. The treatment of acquired factor V inhibitors is mainly the transfusion of platelet concentrates and corticosteroids. Both early detection and the early initiation of the treatment of factor V inhibitor are thus considered to be important.
Assuntos
Hemorragia Cerebral/etiologia , Deficiência do Fator V/etiologia , Deficiência do Fator V/terapia , Fator V/antagonistas & inibidores , Idoso , Feminino , Humanos , Plasma , Transfusão de PlaquetasRESUMO
BACKGROUND: Factor V (FV) deficiency may be inherited as an autosomal recessive disease or acquired as a result of autoantibody formation, either spontaneously or secondary to exposure to bovine thrombin or medications. Congenital FV deficiency has traditionally been treated with plasma transfusions. However, recent evidence has suggested that platelet (PLT) transfusions may be a better alternative as FV stored within PLT alpha granules has greater procoagulant potential and is released locally at sites of vascular injury. We report three cases of FV deficiency, one congenital and two acquired, and emphasize the different management approaches. CASE REPORTS: Patient 1 was a 30-year-old man with congenital FV deficiency who presented with a trauma-induced hematoma of his lower extremity. He was treated with 5 PLT units over 48 hours. Patient 2 was a 64-year-old woman who presented with an upper-extremity thrombus and was discovered to have a FV inhibitor, likely secondary to antibiotics. Patient 3 was a 75-year-old woman with hepatitis C virus (HCV) who presented with minor ecchymosis and was found to have a FV inhibitor secondary to either HCV or antibiotic exposure. Corticosteroids alone were able to eradicate the inhibitors in both patients with acquired inhibitors. CONCLUSIONS: FV deficiency can present with a diverse range of symptoms. For bleeding patients, PLT transfusions should be the initial therapy. In patients with thrombosis, the risks and benefits of anticoagulation must be carefully assessed before treatment. For patients with minor bleeds, transfusions may be withheld, and elimination of the inhibitor should be the primary objective.
Assuntos
Deficiência do Fator V/terapia , Corticosteroides/uso terapêutico , Adulto , Idoso , Autoanticorpos/sangue , Gerenciamento Clínico , Fator V/antagonistas & inibidores , Fator V/uso terapêutico , Deficiência do Fator V/complicações , Deficiência do Fator V/etiologia , Feminino , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Transfusão de Plaquetas , Trombose/tratamento farmacológico , Trombose/etiologiaRESUMO
Acquired coagulation factor deficiency is a rare disorder that occurs in patients with drug reactions, malignancy and collagen diseases as well as during pregnancy. Most cases are caused by factor VIII inhibitors. We herein describe the case of a 61-year-old Japanese man with acquired factor V inhibitor who developed symptoms 11 days after lung surgery for empyema. The patient required mechanical ventilation to treat acute respiratory failure due to severe pulmonary hemorrhage. He responded poorly to steroid pulse therapy; however, treatment with rituximab was successful.
Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Deficiência do Fator V/complicações , Hemorragia/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Pneumopatias/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Empiema/cirurgia , Deficiência do Fator V/etiologia , Hemorragia/etiologia , Humanos , Pneumopatias/etiologia , Pneumopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , RituximabRESUMO
An 82-year-old man referred to our medical ward because of epistaxis and melena was found to have 12 Bethesda units of factor V inhibitor. He was managed for bleeding with supportive care, followed by corticosteroid therapy. The bleeding completely stopped 1 week after corticosteroid therapy. Medical history revealed dysphagia during the past 6 months and further evaluation brought to light a squamous cell carcinoma (SCC) in the esophagus. This is the first case of an acquired factor V inhibitor developing in a patient with esophageal SCC without any other risk factors such as surgery.
Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Carcinoma de Células Escamosas/imunologia , Neoplasias Esofágicas/imunologia , Deficiência do Fator V/imunologia , Fator V/imunologia , Síndromes Paraneoplásicas/imunologia , Corticosteroides/uso terapêutico , Idoso de 80 Anos ou mais , Autoanticorpos/biossíntese , Doenças Autoimunes/etiologia , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/radioterapia , Transtornos de Deglutição/etiologia , Diagnóstico Tardio , Epistaxe/etiologia , Transfusão de Eritrócitos , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/radioterapia , Fator V/antagonistas & inibidores , Deficiência do Fator V/etiologia , Evolução Fatal , Gastroscopia , Hematúria/etiologia , Humanos , Imunossupressores/uso terapêutico , Inibidor de Coagulação do Lúpus/sangue , Masculino , Melena/etiologia , Síndromes Paraneoplásicas/etiologia , Prednisolona/uso terapêutico , RadiografiaAssuntos
Deficiência do Fator V/diagnóstico , Fator V/antagonistas & inibidores , Febre de Causa Desconhecida/diagnóstico , Poliangiite Microscópica/diagnóstico , Vasculite Sistêmica/diagnóstico , Idoso , Autoanticorpos/imunologia , Azatioprina/uso terapêutico , Diagnóstico Diferencial , Deficiência do Fator V/etiologia , Evolução Fatal , Febre de Causa Desconhecida/etiologia , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Coeficiente Internacional Normatizado , Masculino , Poliangiite Microscópica/complicações , Poliangiite Microscópica/tratamento farmacológico , Tempo de Tromboplastina Parcial , Vasculite Sistêmica/complicaçõesRESUMO
Acquired inhibitors to factor V are considered rare events and the cause is often unknown. Diagnostic haemostasis assays to correctly assess this phenomenon are not always perfect and reproducible. Various treatments have been attempted but a standardised management of patients is still lacking. We report the case of a patient who developed a factor V inhibitor and we take the opportunity to make an inventory of the latest data.
Assuntos
Inibidores dos Fatores de Coagulação Sanguínea , Deficiência do Fator V , Idoso de 80 Anos ou mais , Deficiência do Fator V/diagnóstico , Deficiência do Fator V/tratamento farmacológico , Deficiência do Fator V/etiologia , Feminino , HumanosRESUMO
Combined deficiency of factor V and VIII (F5F8D) is a rare, autosomal recessive disorder caused by mutations of either lman1 or mcfd2. To identify mutations of these two genes in a Chinese F5F8D family, the samples of peripheral blood were collected from the proband and her parents. Coagulation tests were carried out, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fg) and coagulate activity of FV, FVIII (FV:C, FVIII:C). The genomic DNA was extracted, then all the exons and intron/exon boundaries of these two genes were amplified by polymerase chain reaction (PCR). The products were finally analyzed by direct sequencing. The results showed that the proband's APTT, PT, TT, Fg, FV:C and FVIII:C were 82.2 sec, 19.6 sec, 18.6 sec, 2.9 g/L, 7.1% and 18.7% respectively, while those parameters of the parents were all within the normal range. Two pathogenic mutations were identified in lman1 gene of the proband: one was the heterozygous c.912_913insA in exon 8 resulting in a frameshift of p.Glu305fsX20; the other was the heterozygous c.1366C > T in exon 11 resulting in p.Arg456X. The proband's father and mother were heterozygous for c.1366C > T and c.912_913insA respectively. It is concluded that F5F8D of the proband is caused by a novel compound heterozygous mutation of the lman1 gene, which has never been reported.
Assuntos
Deficiência do Fator V/genética , Hemofilia A/genética , Lectinas de Ligação a Manose/genética , Proteínas de Membrana/genética , Mutação , Criança , Éxons , Fator V/genética , Deficiência do Fator V/etiologia , Fator VIII/genética , Feminino , Hemofilia A/etiologia , Heterozigoto , Humanos , LinhagemAssuntos
Autoanticorpos/imunologia , Doenças Autoimunes/etiologia , Proteínas Sanguíneas/metabolismo , Deficiência do Fator V/etiologia , Fator V/antagonistas & inibidores , Imunoglobulina G/imunologia , Idoso de 80 Anos ou mais , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Terapia Combinada , Endocitose , Fator V/imunologia , Fator V/metabolismo , Deficiência do Fator V/imunologia , Deficiência do Fator V/terapia , Fator Va/metabolismo , Evolução Fatal , Hemorragia/etiologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/imunologia , Ligação Proteica , Trombina/biossínteseRESUMO
Rituximab has already been successfully used to treat immune-mediated bleeding disorders such as acquired factor VIII inhibitor. We report here a case of severe acquired factor V (FV) inhibitor deficiency due to FV inhibitor which has been dramatically improved after rituximab.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Deficiência do Fator V/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Idoso , Anticorpos Monoclonais Murinos , Fator V/efeitos dos fármacos , Fator V/metabolismo , Deficiência do Fator V/etiologia , Feminino , Humanos , Tempo de Protrombina , RituximabRESUMO
Combined factor V and factor VIII deficiency (F5F8D) is an extremely rare worldwide congenital hemorrhagic disorder that is more prevalent in the Mediterranean area. We report the clinical presentations and the identification of a LMAN1 mutation in a 3-year-old Italian boy who was diagnosed with F5F8D. The mutation identified (M1T) has already been found in several Italian patients. Since the LMAN1 M1T mutation has been identified in most patients with F5F8D, we suggest that the search for this mutation should be the first step in the molecular characterization of patients from an Italian ethnic background.
Assuntos
Deficiência do Fator V/genética , Deficiência do Fator VII/genética , Lectinas de Ligação a Manose/genética , Proteínas de Membrana/genética , Mutação , Pré-Escolar , Deficiência do Fator V/etiologia , Deficiência do Fator VII/etiologia , Humanos , Itália , MasculinoRESUMO
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.