RESUMO
BACKGROUND: Acquired factor V deficiency (AFVD) caused by Factor V (FV) inhibition is a rare event, characterized by prolonged prothrombin time and activated partial thromboplastin time. To date, various factors were reported as triggers for developing FV inhibitor. Clinical symptoms range from asymptomatic to life-threatening bleeding. Case Report and Conclusions: Here, we report an 84-year-old Japanese male on hemodialysis due to renal failure who developed subcutaneous hemorrhage after administration of cefepime (CFPM) to treat bacteremia. Deficient FV activity (< 1.0%) was identified and AFVD with FV inhibitor titer of 9 BU/mL was diagnosed. Although the patient had multiple risks for developing FV inhibitor, CFPM was thought to be the major culprit in this case. After the diagnosis, oral prednisolone (30 mg/day) was initiated, but the patient died of respiratory/cardiac failure, unrelated to AFVD.
Assuntos
Cefepima/efeitos adversos , Deficiência do Fator V/diagnóstico , Fator V/antagonistas & inibidores , Hemorragia/diagnóstico , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Bacteriemia/tratamento farmacológico , Testes de Coagulação Sanguínea , Deficiência do Fator V/sangue , Deficiência do Fator V/induzido quimicamente , Evolução Fatal , Hemorragia/sangue , Hemorragia/induzido quimicamente , Humanos , Masculino , Diálise RenalRESUMO
Acquired factor V (FV) inhibitor is a rare disorder. Herein we report a case of an 82-year-old Japanese woman with FV inhibitor exhibiting a pseudo decline in the activities of the multiple coagulation factors. After rectal cancer surgery, she received antibiotic therapy for wound infection. As prothrombin and activated partial thromboplastin time was prolonged, heparin for atrial fibrillation was discontinued without improvement. Coagulation factor activity assays revealed deficiencies in II, V, VII, VIII, IX, X, XI, and XII factor activities; in particular, the FV activity was markedly decreased to <1%. The cross-mixing test findings revealed an inhibitor pattern, and multiple coagulation factor inhibitors were positive. The FV inhibitor level was high at 62 Bethesda U/ml. The patient exhibited no bleeding tendency with the prolonged wound infection without immunosuppressive therapy. The inhibitor disappeared four months after the onset.
Assuntos
Antibacterianos/efeitos adversos , Deficiência do Fator V/induzido quimicamente , Infecção da Ferida Cirúrgica/tratamento farmacológico , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Testes de Coagulação Sanguínea , Feminino , Humanos , Tempo de Tromboplastina ParcialAssuntos
Antibacterianos/efeitos adversos , Antifúngicos/efeitos adversos , Autoanticorpos/imunologia , Doenças Autoimunes/induzido quimicamente , Deficiência do Fator V/induzido quimicamente , Fator V/imunologia , Pneumonia/tratamento farmacológico , Idoso , Antibacterianos/administração & dosagem , Especificidade de Anticorpos , Antifúngicos/administração & dosagem , Ceftriaxona/efeitos adversos , Cefalosporinas/efeitos adversos , Ciprofloxacina/efeitos adversos , Substituição de Medicamentos , Quimioterapia Combinada , Fluoroquinolonas/efeitos adversos , Humanos , Levofloxacino/efeitos adversos , Masculino , Meropeném/efeitos adversos , Micafungina/efeitos adversos , Tempo de Tromboplastina Parcial , Tempo de ProtrombinaRESUMO
Acquired factor V (FV) inhibitor is a rare coagulation disorder, the causes and clinical symptoms of which are known to vary widely. Acquired FV inhibitor mostly occurs with exposure to fibrin glues during surgical procedures. We experienced a case with asymptomatic acquired FV inhibitor caused by antibiotic therapy for aspiration pneumonia.A man in his eighties had been treated for chronic atrial fibrillation, cerebral infarction and spinal canal stenosis. He was admitted after antibiotic therapy for aspiration pneumonia in a previous hospital. On admission, the screening test for blood coagulation revealed extreme prolongation of both prothrombin time (PT) and activated partial thromboplastin time (APTT). Vitamin K was administered intravenously after cessation of warfarin, but neither PT nor APTT showed any improvement. Subsequently, a cross mixing test was performed and showed an inhibitor pattern. Furthermore, a high titer of FV inhibitor was detected by the Bethesda method and an acquired FV inhibitor was thus diagnosed. Despite the presence of FV inhibitor, the patient showed no bleeding symptoms. Eight months later, both PT and APTT had diminished to normal clotting time values without immunosuppressive therapies.
Assuntos
Antibacterianos/efeitos adversos , Inibidores dos Fatores de Coagulação Sanguínea/sangue , Deficiência do Fator V/induzido quimicamente , Deficiência do Fator V/diagnóstico , Pneumonia Aspirativa/tratamento farmacológico , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Fator V , Deficiência do Fator V/sangue , Humanos , Masculino , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Remissão EspontâneaRESUMO
Autoimmune factor V deficiency (AiFVD) is a rare bleeding disorder caused by factor V inhibitors. In this report, we present the case of an 89-year-old man who developed bleeding tendency during surgery to create arteriovenous fistula for hemodialysis. The bleeding tendency developed with prolongation of activated partial thromboplastin and prothrombin time, following drug-induced eruption and eosinophilia. Significant reduction in coagulation factor activity and inhibitory pattern in cross-mixing tests suggested the presence of inhibitors to coagulation factors. Subsequently, we detected a factor V inhibitor and anti-factor V autoantibodies was confirmed using enzyme-linked immunosorbent assay with purified human plasma factor V. Thus, the patient was 'definitely diagnosed' with AiFVD in accordance with the diagnostic criteria enacted by the Japanese Ministry of Health, Labor, and Welfare. The bleeding tendency improved after initiating oral prednisolone 50 mg (1 mg/kg) followed by normalization of activated partial thromboplastin time and prothrombin time at the 34th day. After improving the coagulation system prolongation, the inhibitor and autoantibodies has been eradicated. Since it is suggested that drug-induced immune response can cause AiFVD, AiFVD should be considered in patients who undergo hemodialysis and develop failure of hemostasis and drug-induced eruption.
Assuntos
Eosinofilia , Exantema , Deficiência do Fator V , Falência Renal Crônica , Masculino , Humanos , Idoso de 80 Anos ou mais , Testes de Coagulação Sanguínea , Deficiência do Fator V/induzido quimicamente , Deficiência do Fator V/diagnóstico , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Eritema , AutoanticorposRESUMO
OBJECTIVE: To report a case of cephalosporin-induced factor V inhibitor development, an uncommon but potentially fatal condition characterized by severe hemorrhage. CASE SUMMARY: A 71-year-old Chinese man presented with factor V inhibitors after a 7-day cephradine course for a urinary tract infection, characterized by abnormal prothrombin time (PT) and activated partial thromboplastin time (aPTT), gross hematuria, upper gastrointestinal bleeding, and left groin hematoma. Systemic corticosteroid administration restored his factor V activity levels, PT, and aPTT to within normal limits, and hemorrhagic symptoms resolved. Three weeks after successful treatment of bleeding diathesis, he received another 8-day cephradine course for cellulitis. After another 4 weeks, he suffered from recurrent factor V inhibitors presented with abnormal PT, aPTT, and upper gastrointestinal bleeding. The patient eventually died due to hemorrhagic shock despite a second course of corticosteroids. DISCUSSION: Cephalosporins are known to cause coagulopathy via hypoprothrombinemia. Another pathway seldom mentioned in the literature is factor V inhibitor induction, which may result in factor V deficiency. In our patient, factor V deficiency due to inhibitors developed each time that the patient received repeated cephradine treatment. According to the Naranjo probability scale, the relation between the formation of factor V inhibitors and cephradine treatment was probable. CONCLUSIONS: Because cephalosporins are commonly used for their wide therapeutic index and few adverse effects, iatrogenic complications associated with these drugs may be neglected or underdiagnosed. On the basis of our patient's report, careful review of medical records to avoid reexposure to the offending drug cannot be overemphasized.
Assuntos
Antibacterianos/efeitos adversos , Autoanticorpos/sangue , Cefradina/efeitos adversos , Deficiência do Fator V/induzido quimicamente , Fator V/imunologia , Idoso , Antibacterianos/uso terapêutico , Cefradina/uso terapêutico , Fator V/antagonistas & inibidores , Deficiência do Fator V/imunologia , Evolução Fatal , Hemorragia/induzido quimicamente , Hemorragia/imunologia , Humanos , Masculino , Infecções Urinárias/tratamento farmacológicoRESUMO
Acquired factor V (FV) inhibitors occur rarely and classically develop after exposure to bovine thrombin. The clinical presentation is variable, ranging from asymptomatic with incidental laboratory abnormalities to significant bleeding. With the development of human-derived thrombin agents, bovine thrombin is less frequently used. We report a case of an acquired FV inhibitor that developed in a patient after exposure to human thrombin used as a hemostatic agent during an otorhinolaryngology surgical procedure. Our review of the literature revealed only one prior reported case of FV inhibitor after exposure to human thrombin. Hematologists and surgeons should be aware of this rare, but potentially life-threatening, complication in the postprocedural setting.
Assuntos
Autoanticorpos/sangue , Perda Sanguínea Cirúrgica/prevenção & controle , Deficiência do Fator V/induzido quimicamente , Fator V/imunologia , Hemostáticos/efeitos adversos , Procedimentos Cirúrgicos Otorrinolaringológicos , Hemorragia Pós-Operatória/prevenção & controle , Trombina/efeitos adversos , Administração Tópica , Idoso , Biomarcadores/sangue , Fator V/metabolismo , Deficiência do Fator V/sangue , Deficiência do Fator V/diagnóstico , Deficiência do Fator V/imunologia , Feminino , Hemostáticos/administração & dosagem , Humanos , Procedimentos Cirúrgicos Otorrinolaringológicos/efeitos adversos , Trombina/administração & dosagem , Fatores de TempoRESUMO
We report the case of a 59-year-old Chinese man who showed an asymptomatic coagulation factor V deficiency pattern after second intravenous treatment with ceftazidime. Normal pooled plasma failed to correct the abnormalities in a mixing test, and the presence of factor V inhibitor was confirmed by the Bethesda method. The coagulopathy was not corrected by transfusion of fresh frozen plasma and prothrombin complex concentrate, but rather by treatment with prednisone and withdrawal of dubious drugs. The findings reported here should prompt clinicians to watch for drug-induced coagulation factor deficiency.
Assuntos
Antibacterianos/efeitos adversos , Ceftazidima/efeitos adversos , Deficiência do Fator V/induzido quimicamente , Deficiência do Fator V/tratamento farmacológico , Fator V/antagonistas & inibidores , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Testes de Coagulação Sanguínea , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/patologia , Ceftazidima/uso terapêutico , Humanos , Hemorragias Intracranianas/complicações , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/patologia , Masculino , Pessoa de Meia-Idade , Plasma , Prednisona/uso terapêutico , Protrombina/uso terapêutico , Tomografia Computadorizada por Raios XRESUMO
Bovine thrombin-induced factor V deficiency was though to be a very rare acquired coagulopathy, with only three documented cases. We report a series of nine patients seen during a period of 32 months; these patients had normal preoperative coagulation profiles, and this unique coagulopathy developed 1 to 2 weeks after cardiovascular operations. The coagulopathy was characterized by a markedly elevated prothrombin time (40.9 +/- 5.8 seconds), an elevated activated partial thromboplastin time (96.3 +/- 12.2 seconds), a study positive for lupus anticoagulation (9/9), and markedly decreased levels of factor V (0.09 +/- 0.03 U/ml) and factor XI (0.04 +/- 0.02 U/ml), respectively. All patients had been exposed to commercially available bovine thrombin during prior cardiovascular or vascular operations and received a second bovine thrombin challenge during the latest procedure. Coagulopathic bleeding developed in four of the nine patients. Bleeding was unrelated to absolute fall in factor V level, but cessation of hemorrhage appeared to correlate with improvement in factor V level. Treatment with vitamin K, fresh frozen plasma, and platelet infusion were all unsuccessful in altering prothrombin time or factor V levels. Intravenous gamma globulin was used in three patients, two of whom were bleeding. All three patients showed a transient increase in factor V levels. Bleeding stopped in one of the two patients; the other continued to bleed and subsequently died. The third patient was treated prophylactically to increase factor V levels in preparation for flap reconstruction of his sternum. His factor V level increased from 0.26 to 0.49 U/ml, and he underwent the procedure without incident. Bovine thrombin-induced factor V deficiency may have been previously unrecognized. This deficiency should be suspected in patients who have undergone redo cardiovascular operations and in whom marked elevations in their prothrombin time occur 7 to 10 days after exposure to bovine thrombin. The resulting coagulopathy, although usually self-limited, has the potential to produce devastating bleeding complications. Intravenous gamma globulin (1 gm/kg during each of 2 days) has been used to increase factor V levels transiently but its role in therapy of this coagulopathy requires further investigation.
Assuntos
Deficiência do Fator V/induzido quimicamente , Cardiopatias/cirurgia , Complicações Pós-Operatórias/sangue , Trombina/efeitos adversos , Administração Tópica , Coagulação Sanguínea/fisiologia , Feminino , Cardiopatias/sangue , Hemorragia/etiologia , Humanos , Masculino , Complicações Pós-Operatórias/fisiopatologia , Tempo de Protrombina , Reoperação , Trombina/administração & dosagemAssuntos
Hemorragia Cerebral/induzido quimicamente , Deficiência do Fator V/induzido quimicamente , Fator V/efeitos dos fármacos , Penicilinas/efeitos adversos , Idoso , Antiulcerosos/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hemorragia Cerebral/patologia , Fator V/antagonistas & inibidores , Evolução Fatal , Humanos , Hipertensão/complicações , Pneumopatias/tratamento farmacológico , Pneumopatias/microbiologia , Masculino , Nicardipino/uso terapêutico , Omeprazol/uso terapêuticoRESUMO
Topical hemostatic products containing thrombin are commonly used in burn surgery to facilitate focal hemostasis and graft adherence. Until recently, thrombin was available only from a bovine source, which has been documented to produce antibodies to endogenous clotting factors and to induce coagulation defects and severe bleeding complications. This report documents the first case of factor V deficiency and profound coagulopathy in a burn patient after intraoperative exposure to bovine thrombin. A 38-year-old woman was admitted after a 75% total body surface area burn. The patient underwent repeated excision and grafting during which an epinephrine solution that contained bovine thrombin was used to facilitate hemostasis. During the fourth and subsequent operative procedures, the patient developed profound coagulopathy as evidenced by excessive bleeding and abnormal laboratory coagulation parameters, requiring the administration of supplemental clotting factors through fresh frozen plasma and cryoprecipitate. Hematology work-up revealed a factor V deficiency. Subsequent procedures in which bovine thrombin was avoided were uneventful. The use of topical bovine thrombin in patients who have been previously exposed results in an increased risk of perioperative coagulopathy and clinically significant bleeding complications. Thus, the use of bovine-thrombin-containing products should be avoided in burn patients with prior exposure to bovine thrombin.
Assuntos
Queimaduras/cirurgia , Deficiência do Fator V/induzido quimicamente , Trombina/efeitos adversos , Adulto , Animais , Bandagens , Bovinos , Feminino , Hemostasia Cirúrgica/métodos , HumanosAssuntos
Transtornos da Coagulação Sanguínea/induzido quimicamente , Coagulação Sanguínea/efeitos dos fármacos , Fenobarbital/farmacologia , Alanina Transaminase/sangue , Animais , Animais Recém-Nascidos , Gatos , Depressão Química , Relação Dose-Resposta a Droga , Interações Medicamentosas , Deficiência do Fator V/induzido quimicamente , Fator VII/biossíntese , Deficiência do Fator VII/induzido quimicamente , Feminino , Ácido Fólico/sangue , Hemofilia A/induzido quimicamente , Hipoprotrombinemias/induzido quimicamente , Fígado/metabolismo , Troca Materno-Fetal , Fenobarbital/administração & dosagem , Fenitoína/farmacologia , Gravidez , Primidona/administração & dosagem , Primidona/farmacologia , Ratos , Vitamina K/farmacologiaAssuntos
Transtornos da Coagulação Sanguínea/induzido quimicamente , Fatores de Coagulação Sanguínea/análise , Soluções Hipertônicas/efeitos adversos , Cloreto de Sódio/efeitos adversos , Adolescente , Adulto , Afibrinogenemia/induzido quimicamente , Âmnio , Contagem de Células Sanguíneas , Testes de Coagulação Sanguínea , Plaquetas , Isótopos de Carbono , Coagulação Intravascular Disseminada/induzido quimicamente , Deficiência do Fator V/induzido quimicamente , Feminino , Hemofilia A/induzido quimicamente , Hemofilia B/induzido quimicamente , Humanos , Injeções , Masculino , Métodos , GravidezRESUMO
STUDY DESIGN: A report of two cases is presented. OBJECTIVE: To raise awareness of bovine thrombin-induced factor V deficiency. SUMMARY OF BACKGROUND DATA: Bovine thrombin is a frequently used hemostatic agent in spinal surgery. Current preparations contain clotting factors in addition to thrombin, particularly factor V, which are immunogenic. Re-exposure of sensitized patients to bovine thrombin products during subsequent surgery may lead to the formation of antibodies that cross-react with human clotting factors, most commonly against factor V. Hemorrhagic complications have been reported in nonspinal patients due to a bovine thrombin-induced factor V deficiency. METHODS: Two spinal cases are reported, and the literature is reviewed. RESULTS: In the cases outlined, both patients underwent revision spinal surgery, with re-exposure to bovine thrombin. Both patients developed abnormal coagulation profiles, with an acquired factor V deficiency. No hemorrhagic complications occurred; however, second-stage surgery was delayed in one patient and not undertaken in the other. In both patients, the coagulopathy resolved spontaneously. CONCLUSIONS: Bovine thrombin-induced coagulopathy is well recognized in cardiac surgery but has not been reported in spinal surgical patients. Data available from cardiac surgical patients suggests that those who are sensitized to two or more bovine clotting factors are at greatest risk of hemorrhagic complications. The cases we present demonstrate that this phenomenon occurs in spinal surgical patients and serve to raise awareness of the potential danger of bovine thrombin in sensitized patients.
Assuntos
Deficiência do Fator V/induzido quimicamente , Fator V/antagonistas & inibidores , Cifose/imunologia , Estenose Espinal/imunologia , Trombina/efeitos adversos , Fator V/imunologia , Deficiência do Fator V/imunologia , Feminino , Humanos , Cifose/cirurgia , Masculino , Pessoa de Meia-Idade , Dispositivos de Fixação Ortopédica , Tempo de Protrombina , Reoperação , Fusão Vertebral , Estenose Espinal/cirurgia , Trombina/administração & dosagemRESUMO
PURPOSE: We report that treatment of an immune mediated postoperative Factor V (FV) deficiency with intravenous immune globulin (IVIg) resulted in serological and clinical disappearance of the inhibitor. PATIENTS AND METHODS: A 9-year-old girl was exposed to bovine thrombin during cardiovascular surgery and subsequently developed severe, refractory hemorrhage caused by acquired FV deficiency (FV activity < 5%). Despite blood product transfusions, hemorrhage continued, and the patient was given IVIg, 400 mg/kg daily, for 9 day. RESULTS: Prolonged clotting times immediately trended toward normal, and the hemorrhage ceased by the fifth IVIg treatment day, concomitant with increasing plasma FV activity and disappearance of human FV inhibitor activity. The patient's plasma initially had a much higher inhibitor titer against bovine FV (122-215 Bethesda units) than against human FV (3-4 Bethesda units). Circulating antibodies (IgM and IgG) to bovine and human thrombin and FV were detected by enzyme-linked immunosorbent assay (ELISA). After completion of IVIg treatment, IgG antibodies to bovine FV and thrombin persisted, as did high-titer inhibition of bovine FV, whereas the subpopulation of IgG and IgM antibodies reactive with human FV were undetectable. CONCLUSIONS: The inhibitor likely developed from a heterogenetic immune response to bovine FV contaminating the topical thrombin preparation used during surgery. To our knowledge, this is the first demonstration of immunological clearance of an acquired FV antibody associated with the use of IVIg. The data suggest an antiidiotypic mechanism of IVIg in modulating clearance of antihuman FV antibodies.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Deficiência do Fator V/induzido quimicamente , Deficiência do Fator V/terapia , Fator V/antagonistas & inibidores , Imunoglobulinas Intravenosas/uso terapêutico , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/terapia , Trombina/efeitos adversos , Anticorpos/análise , Criança , Reações Cruzadas , Feminino , Hemorragia/etiologia , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Tempo de Tromboplastina Parcial , Complicações Pós-Operatórias/sangue , Trombina/imunologiaRESUMO
A few neonates born to mothers receiving anticonvulsant drugs during pregnancy have shown defects in vitamin K dependent clotting factors with or without clinical bleeding. Experimentally, phenytoin (diphenyl hydantoin, DPH) has induced clotting defects in cats and inhibited production of clotting factors in rat liver slices. Phenobarbital has produced similar but milder defects. Anticonvulsants have been observed to produce clotting defects in 9 children, 2 weeks to 8 years in age. Elevated levels of phenytoin or other anticonvulsants, or a combination of anticonvulsants were measured in the children. Six patients were on drug combination including two or more of the following: phenytoin, phenobarbital, primidone, carbamazepine, diazepam, ethosuximide. Clotting defects included: elevated prothrombin time, elevated partial thromboplastin time, diminished factors V, VII or X. All children had neurologic symptoms of anticonvulsant toxicity, but the only hematologic problems were oozing from venipuncture sites and increased bruising in 3. All patients were on normal diets and had normal liver function tests. By lowering the level of anticonvulsants, clotting factors returned toward normal. Elevated levels of anticonvulsants can potentially produce clotting defects in neonates and young children.
Assuntos
Anticonvulsivantes/farmacologia , Transtornos da Coagulação Sanguínea/induzido quimicamente , Coagulação Sanguínea/efeitos dos fármacos , Anticonvulsivantes/efeitos adversos , Testes de Coagulação Sanguínea , Criança , Pré-Escolar , Deficiência do Fator V/induzido quimicamente , Deficiência do Fator VII/induzido quimicamente , Deficiência do Fator X/induzido quimicamente , Feminino , Hemofilia A/induzido quimicamente , Humanos , Lactente , Recém-Nascido , Masculino , Troca Materno-Fetal , Gravidez , Tempo de Protrombina , TromboplastinaRESUMO
BACKGROUND: FV inhibitors are a largely preventable iatrogenic coagulopathy in which the frequency is increasing in clinical practice. STUDY DESIGN AND METHODS: Three cases associated with our institution are reported. A systematic review of the MEDLINE database was performed, and reference lists were reviewed to identify relevant publications. RESULTS: One hundred twenty-six cases of FV inhibitors have been reported in the world's literature. Eighty-seven have been reported in the last decade, of which two thirds are due to exposure to bovine thrombin. Bovine thrombin-associated FV antibodies develop in 40 to 66 percent of cardiac surgery patients and in 20 percent of neurosurgery patients. Thirty-three percent of reported patients developed bleeding complications. Inhibitors persisted on average 2.3 months. Standard coagulation assays do not reliably predict clinical manifestations. Multimodality therapy, including immunosuppression, is useful for treatment of symptomatic patients. CONCLUSIONS: FV inhibitors are a common complication of bovine thrombin exposure that can have devastating clinical consequences. Transfusion medicine specialists and hematologists can play a critical role in reducing the incidence of FV inhibitors by educating the medical community about safer alternative fibrin sealants.