Rhinoplasty in a patient with Von Willebrand disease: case report

Abstracts

JUSTIFICATIVA E OBJETIVOS: Os pacientes portadores da doença de von Willebrand apresentam sangramento anormal após ferimentos e procedimentos cirúrgicos, já que esta afeta a hemostasia primária e secundária devido à alteração do fator VIII. O objetivo deste relato é elucidar o manuseio pré-, peri- e pós-operatório de pacientes com tal doença. RELATO DO CASO: Paciente do sexo feminino, 42 anos, branca, 165 cm, 61 kg, ASA II, foi submetida à avaliação pré-anestésica para realização de rinoplastia, com diagnóstico prévio de doença de von Willebrand do tipo 1, sendo liberada para a intervenção cirúrgica após avaliação hematológica, com teste de DDAVP IN26 responsivo. No dia da operação, após medicação pré-anestésica e monitoração adequada, foi ofertado oxigênio por cateter nasal e infundida a solução de desmopressina (0,4 µg.kg-1 em 100 mL de NaCl a 0,9% por via venosa) 30 minutos antes da operação. Em seguida, iniciou-se a indução anestésica com sufentanil (1 µg.kg-1), propofol (4 mg.kg-1) e rocurônio (0,6 mg.kg-1) por via venosa. Em seqüência, realizou-se intubação traqueal seguida de ventilação controlada mecânica em sistema com absorção de CO2, mantida com O2, N2O e sevoflurano. O ato cirúrgico durou 90 minutos. No intra-operatório a paciente manteve-se hemodinamicamente estável, apresentando sangramento desprezível. Ao final da operação foi extubada e encaminhada à sala de recuperação pós-anestésica, onde permaneceu por 120 minutos. No pós-operatório foi prescrito ácido aminocapróico (500 mg por via oral a cada oito horas, por 48 horas), com alta hospitalar após 24 horas, sem apresentar nenhuma complicação pós-operatória. CONCLUSÕES: A infusão de crioprecipitado ou plasma, utilizado na profilaxia e no tratamento das complicações hemorrágicas, produz um pico de concentração máxima de fator VIII após 48 horas, e é sustentado por 72 horas; entretanto, mesmo aprovado pelo FDA, tem sido uma prática utilizada somente em circunstâncias emergenciais, devido ao risco relativo de contaminação viral. A 1-desamino, 8-D-arginina vasopressina (DDAVP-desmopressina) estimula o aumento da concentração do fator VIII, tendo a vantagem de eliminar a exposição aos patógenos transmitidos pelo sangue, além da possibilidade de administração por vias nasal, subcutânea e venosa.

CIRURGIA, Plástica; DOENÇAS, Hematológica

CLINICAL REPORT

Rhinoplasty in a patient with Von Willebrand disease. Case report ^*

Rinoplastia en paciente con enfermedad de Von Willebrand. Relato de caso

Roberto Martins Matos Junior^I; Rogério da Costa Godoy^I; Mônica da Cunha Gobbo, TSA^II; João Lian Junior, TSA^III; Gilson Luis Duz^IV

^IME₂ do CET HMCP/PUC

^IIAnestesiologista e Responsável pelo CET HMCP/PUC

^IIIProfessor da Faculdade de Medicina da PUC de Campinas; Coordenador do Serviço de Anestesiologia do HMCP/PUC

^IVMembro da Sociedade Brasileira de Cirurgia Plástica; Médico Assistente do HMCP/PUC

^{Correspondence to}

SUMMARY

BACKGROUND AND OBJECTIVES: Patients with von Willebrand disease present abnormal bleeding after being wounded or during surgeries since it affects primary and secondary hemostasia due to changes in factor VIII. The objective of this report was to elucidate the pre-, peri-, and postoperative management of patients with this disorder.

CASE REPORT: A 42-year old white female, with 165 cm, 61 kg, ASA II, with a diagnosis of type 1 von Willebrand disease, underwent pre-anesthetic evaluation for rhinoplasty. She was cleared for surgery after hematological evaluation with a positive DDAVP IN26 test. On the day of the surgery, the patient received pre-anesthetic medication, was adequately monitored, oxygen was administered through a nasal cannula and intravenous desmopressin (0.4 µg.kg^-1 in 100 mL of normal saline) was administered 30 minutes before the surgery. Induction was accomplished with intravenous sufentanil (1 µg.kg^-1), propofol (4 mg.kg^-1), and rocuronium (0.6 mg.kg^-1). The patient was intubated and installed on mechanical ventilation with a CO₂ absorber system and maintenance consisted of O₂, N₂O and sevoflurane. The surgery lasted 90 minutes. During the surgery the patient remained hemodynamically stable with negligible blood loss.

CONCLUSIONS: Infusion of cryoprecipitate or plasma, used in the prophylaxis and treatment of bleeding complications, produces peak concentrations of factor VIII after 48 hours and it is sustained for 72 hours; however, even though it has been approved by the FDA this has been used only in emergencies due to the relative risk of viral contamination. 1-Deamino-8-D-arginine vasopressin (DDAVP-desmopressin) increases the concentration of factor VIII besides eliminating exposure to blood borne pathogens and it has the possibility of being administered by the nose, subcutaneous, and intravenous.

Key Words: DISEASES, Hematologic: von Willebrand's disease; SURGERY, Plastic: rhinoplasty.

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: Los pacientes portadores de la enfermedad de von Willebrand presentan sangramiento anormal después de heridas y procedimientos quirúrgicos, ya que esta afecta la hemostasia primaria y secundaria debido a la alteración del factor VIII. El objetivo de este relato es elucidar el manoseo pre, peri y postoperatorio de pacientes con tal enfermedad.

RELATO DEL CASO: Paciente del sexo femenino, 42 años, blanca, 165 cm, 61kg, ASA II, fue sometida a la evaluación preanestésica para la realización de rinoplastia, con diagnóstico previo de enfermedad de von Willebrand del tipo 1, siendo liberada para la intervención quirúrgica después de la evaluación hematológica, con test de DDAVP IN26 responsivo. El día de la operación, y después de la medicación preanestésica y del monitoreo adecuado, se le dio oxígeno por catéter nasal e infundida la solución de desmopresina (0,4 µg.kg^-1 en 100 mL de NaCl a 0,9% por vía venosa) 30 minutos antes de la operación. Enseguida se inició la inducción anestésica con sufentanil (1 µg.kg^-1), propofol (4 mg.kg^-1) y rocuronio (0,6 mg.kg^-1) por vía venosa. A continuación se realizó la intubación traqueal seguida de ventilación controlada mecánica en sistema con absorción de CO₂, mantenida con O₂, N₂O y sevoflurano. El acto quirúrgico duró noventa minutos. En el intraoperatorio la paciente se mantuvo hemodinámicamente estable, presentando sangramiento sin importancia. Al final de la operación fue extubada y llevada a la sala de recuperación post anestésica, donde permaneció por 120 minutos. En el postoperatorio fue prescrito ácido amino caproico (500 mg por vía oral a cada 8 horas, por 48 horas), con alta hospitalaria después de 24 horas, sin presentar ninguna complicación postoperatoria.

CONCLUSIONES: La infusión de crioprecipitado o plasma, utilizado en la profilaxis y tratamiento de las complicaciones hemorrágicas, produce un pico de concentración máxima de factor VIII después 48 horas, y se sustenta por 72 horas; sin embargo, incluso aprobado por el FDA, ha sido una práctica utilizada solamente en circunstancias de emergencia, debido al riesgo relativo de contaminación viral. A 1-desamino, 8-D-arginina vasopresina (DDAVP-desmopresina) estimula el aumento de la concentración del factor VIII, con la ventaja de eliminar la exposición a patógenos transmitidos por la sangre, además de la posibilidad de administración por vía nasal, subcutánea y venosa.

INTRODUCTION

Von Willebrand disease is a hereditary disorder that affects up to 3% of the population and it is caused by a deficiency of von Willebrand factor. The von Willebrand factor is a glycoprotein responsible for one phase of platelet aggregation and for the transportation of factor VIII (antihemophiliac), avoiding its degradation.

The clinical presentation of this disorder varies and it can manifest after trauma or surgery ¹.

The objective of this report was to present the case of a patient with von Willebrand disease undergoing rhinoplasty, treated preoperatively with DDAVP, and to describe the anesthetic management.

CASE REPORT

A 42-year old white female, weighing 61 kg, height of 165 cm, physical status ASA II due to type I von Willebrand disease diagnosed after tonsillectomy as a teenager, when she developed important postoperative bleeding.

She underwent pre-anesthetic evaluation for a rhinoplasty, with the following laboratory results: hemoglobin 12.3 g.dL^-1, hematocrit 37.2%, platelets 278,000.mm^-3, normal aPTT, normal PT, AP 55%, and INR 1.2. After complete and detailed anamnesis followed by the physical examination, the patient was referred for hematologic evaluation and she was cleared for surgery after a positive DDAVP IN26 test. The administration of an intravenous infusion of 0.4 µg.kg^-1 of desmopressin in normal saline 30 minutes before surgery was recommended.

Intramuscular midazolam 5 mg was administered 60 minutes before surgery. In the operating room, with the patient in dorsal horizontal decubitus, an 18G catheter was introduced intravenously in the left arm and the patient was monitored with continuous electrocardiogram (ECG), automatic non-invasive blood pressure, and pulse oximetry; 100% O₂ was administered via a nasal cannula at 2 L.min^-1 and the intravenous infusion of desmopressin (24 µg in 100 ml of normal saline) was initiated to run over a 30-minute period. At the end of the infusion, 2 L.min^-1 of 100% O₂ was administered with a face mask. Induction was initiated with intravenous sufentanil 1 µg.kg^-1, propofol 4 mg.kg^1-1 and rocuronium 0.6 mg.kg^-1. The patient was then intubated with a 7.5 ETT with cuff and installed on mechanical ventilation, controlled, with intermittent positive pressure, with a CO₂ absorber system; maintenance of anesthesia was accomplished with O₂, N₂O and 2% sevoflurane.

Intraoperatively, the patient remained hemodynamically stable with minimal bleeding. The surgery lasted 90 minutes. After waking from anesthesia, the patient was extubated and taken to the postanesthetic care unit, where she remained for 120 minutes until her condition allowed her to be transferred to the regular ward.

Aminocaproic acid, 500 mg by mouth every 8 hours for 48 hours, was prescribed postoperatively, and the patient was discharged from the hospital 24 hours after the surgery without sings of bleeding or any other complication.

DISCUSSION

This disorder was described in 1926 by Erik von Willebrand as an autosomal dominant hemorrhagic disease that affects primary and secondary hemostasis, affecting both genders without ethnic predominance, being the most common bleeding disorder with an incidence of 1% to 3% in the general population. It is characterized by a platelet dysfunction and deficiency in coagulant factor VIII (VIII:C). Homozygous individuals are rare and result from a recessive mutant gene ^1-3.

Von Willebrand factor is a multimeric glycoprotein responsible for facilitating platelet aggregation and it also works as a serum transporter of factor VIII (antihemophiliac) and changes in vWF can manifest by different signs and symptoms, determining the disease subtypes classification, which helps guiding therapy ².

Type 1 is inherited as an autosomal dominant disorder and is seen in 75% to 80% of the cases. It is caused by a quantitative deficiency in factor VIII:vWF and can be accompanied by a reduction in factor VIII:C.

Type 2 is inherited as a dominant or recessive disorder, affecting 20% of the patients. It is due to a qualitative abnormality of factor VIII:vWF and factor VIII:C can be normal. It is further divided in subtypes 2A, 2B, 2M, and 2N, of which 2A is the most common with a reduction in platelet aggregation associated with the absence of high molecular weight multimers. Subtype 2B has greater affinity for glycoprotein 1b. Subtype 2M also shows a reduction in platelet aggregation, which is not associated with the absence of high molecular weight multimers; and 2N is more rare, with a reduction in the affinity by factor VIII coagulant, resembling hemophilia A.

Type 3, inherited as a recessive disorder, is extremely rare, being characterized by an almost total absence of circulating vWF, presenting as a more severe condition ¹.

Most patients present mild disease that might not be diagnosed until the patient needs a surgery or suffers any trauma. Asymptomatic patients might bruise easily and present frequent mucosal bleeding (epistaxis and gastrointestinal bleeding), besides menorrhagia in 50% to 70% of the women as the presenting symptom. Pregnant women have increased incidence of bleeding after delivery, especially if it is associate with surgical delivery and episiotomy. All symptoms can be exacerbated by the use of drugs that inhibit platelet aggregation (ASA, NSAIDs) ^1,4,5.

The physical exam might reveal non-specific signs of bleeding and ecchymosis. Laboratorial exams show prolonged bleeding time, which might be influenced by the thrombocytopenia present in type 2B; activated partial thromboplastin time (aPTT) shows variable increase due to a deficiency in factor VIII; however, a normal exam does not exclude the diagnosis. In most cases, platelet count is normal, but in subtype 2B it can be reduced ^1,2,6.

Diagnosis can be confirmed by the following exams:

– determination of factor VIII:C, which is extremely low in type 3 and can be normal in other types;

– quantification of vWF antigen, which measures the immunological expression of vWF;

– activity of the ristocetin co-factor (vWF:CoFR) (an antibiotic that promotes the interaction of vWF for platelet aggregation). This test is the most specific for the evaluation of platelet aggregation ^1,2.

The quantification of vWF and activity of vWF:CoFR are acute phase reagents and are increased in stress situations, liver diseases, pregnancy, and oral contraceptive use, but are decreased in hypothyroidism and in patients with O blood type. Genetic studies are the most specific tests to establish the diagnosis of vWF variants. When evaluating a patient, hematocrit, hemoglobin, thromboplastin time, bleeding time, and protrombina time are recommended, along with specific levels of factor VIII, activity of vWF, and vWF:Ag are recommended ¹.

In anesthetic procedures the epidural catheter can be used especially if the patient has normal coagulation studies, with bleeding time below 10 minutes and platelets above 100,000; however, it should only be removed after repeating the exams, which should be normal. Subarachnoid block is an option for elective surgeries ^5,7.

The objectives of the treatment of von Willebrand disease include correction of the deficiency in activity of vWF to values above 50% of normal, and the activity of factor VIII to appropriate levels. Two main agents are used to achieve those goals: DDAVP and blood products, such as concentrates of factor FVIII and vWF.

Infusion of cryoprecipitate and fresh frozen plasma (FFP), used in the prophylaxis or treatment of bleeding complications, produce a maximal concentration of factor VIII:C 48 hours after the infusion that is maintained for 72 hours. Therefore, it should be administered the night before the surgery; however, correction of the bleeding time (primary hemostatic defect) lasts only 2 to 6 hours and for this reason it should also be administered immediately before surgery. When preoperative fibrinogen levels are lower than 0.8 g.L^-1 and the bleeding time is altered or levels of factor VIII:C are lower than 50% of normal, cryoprecipitate, which contains 5 to 10 times more factor VIII and vWF than FFP, should be infused. However, even though it is approved by the FDA, due to the risk of viral contamination this treatment has been used only in emergencies with bleeding or when bleeding should be avoided in cases when desmopressin is not effective. Since concentrates of factor VIII and vWF do not present the same risk, they are the preferred choice at a dose of 60 IU.kg^-1 once a day. On the day of the surgery, the levels of factor VIII:C should be determined every 12 hours and every 24 hours in the postoperative period ^1,5,7.

Treatment with 1-deamino-8-D-arginine vasopressin (DDAVPdesmopressin) increases the levels of factor VIII:C and vWF, besides improving subendotelial platelet aggregation. Although its mechanism of action is not known, it is believed that it promotes the release of vWF and factor VIII from plasma storage sites, in the endothelium and in hepatic sinusoids. This method eliminates transmission of blood carried pathogens and is the preferred treatment for the preoperative prophylaxis of type 1; but prior therapeutic test should be done to establish the response pattern of each patient. The recommended dose is 0.3 to 0.4 µg.kg^-1 in 50 mL of normal saline, subcutaneous or intravenously, infused over 20 minutes. The intranasal route can also be used: 150 µg in each nostril, in adults, every 12 or 24 hours ^2,5-7.

The acquired disease is very rare, and appears as a complication of other disorders. In these cases, the treatment is similar to the congenital disorder although with an unpredictable response.

In the case presented here, desmopressin was used in the preoperative management, proving to be effective in preventing intra- and postoperative bleeding. A complete pre-anesthetic evaluation should be done before any invasive or surgical procedure, with the knowledge of the main disorders and syndromes, in order to reduce anesthetic and surgical risks.

REFERENCES

Submitted em 31 de outubro de 2006

Accepted para publicação em 07 de agosto de 2007

• 01. Kessler CM Deficiências dos Fatores da Coagulação, em: Goldman L, Bennett JC Cecil: Tratado de Medicina Interna, 21Ş Ed., Rio de Janeiro, Guanabara Koogan, 2001;1121-1123.
• 02. Abreu MP, Porto AM, Minari AL et al. Anestesia para septoplastia e turbinectomia em paciente portador de doença de von Willebrand. Relato de caso. Rev Bras Anestesiol, 2003; 53:382-387.
• 03. Whalley ICN Retrospective review of the management of elective surgery with desmopressin and clotting factor concentrates in patients with von Willebrand disease. Am J Hematol, 2001;66:280-284.
• 04. Ramos MRF, Rotbande IS, Ramos RRM Complicação da anestesia subdural utilizada em artroscopia de joelho em paciente com doença de von Willebrand. Rev Bras Ortop, 2000;35:419-421.
• 05. Balle VR, Machado SB, Gomes MEW et al. Cesariana em paciente com doença de von Willebrand associada à infecção pelo HIV. Relato de caso. Rev Bras Anestesiol, 2004;54:788-793.
• 06. D'Amico EA, Villaça PR Doença de Von Willebrand, em: Zago MA, Falcão RP, Pasquini R Hematologia Fundamentos e Prática. São Paulo, Atheneu, 2001;819-831.
• 07. Manucci PM How I treat patients with von Willebrand disease. Blood, 2001;97:1915-1919.

*

Received from Hospital e Maternidade Celso Pierro (HMCP/PUC) – Campinas, SP

Publication Dates

• Publication in this collection
  30 Nov 2007
• Date of issue
  Dec 2007

History

• Received
  31 Oct 2006
• Accepted
  07 Aug 2007