Perioperative management of von Willebrand disease: a review for the anesthesiologist

von Willebrand disease (VWD) is the most common hereditary bleeding disorder in humans, with an estimated prevalence of 0.5% to 1%. Patients with VWD are at increased risk of perioperative bleeding complications. This review provides an evidence-based overview of VWD and its management during the perioperative period.     

Neuraxial anesthesia for cesarean delivery in a parturient with type 1 von Willebrand disease and scoliosis

We present the case of a parturient with von Willebrand disease and scoliosis who required cesarean delivery. Neuraxial anesthesia was used for the patient. The indications for neuraxial anesthesia with regard to type 1 von Willebrand disease are reviewed.     

Closure of a ventricular septal defect in a patient with von Willebrand disease

Few reports of open heart surgery being performed in patients with von Willebrand disease (vWD) have been documented. We describe, herein the case of a 5-year-old girl with a ventricular septal defect (VSD) and vWD who underwent patch closure under cardiopulmonary bypass (CPB). The hematological parameters relating to vWD, namely, factor VIII, von Willebrand factor, and factor VIII-related antigen were monitored perioperatively. These laboratory findings were elevated after the termination of CPB, and consistently maintained within the normal range for 4 months postoperatively. The operation was successfully completed without the administration of factor VIII concentrates or homologous blood products.     

Perioperative management of a patient with an acquired von Willebrand syndrome

We report the case of a man suffering from a monoclonal gammapathy with an acquired von Willebrand disease in a perioperative context. This pathology is rare, but is important to diagnose because of the possible haemorrhagic complications encountered. We describe the main therapeutic options available today to prevent bleeding during major surgery.     

Spinal anesthesia for a cesarean delivery in a woman with type-2M von Willebrand disease: case report and mini-review

Von Willebrand disease is the most common inherited bleeding disorder. No consensus exists about the use of neuraxial analgesia or anesthesia in patients with von Willebrand disease. We report on a 38-year-old multiparous woman who presented at 36 weeks’ of gestation with spontaneous rupture of membranes for urgent cesarean delivery. Preoperative coagulation tests were normal except for prolonged platelet adhesion and aggregation tests. The cesarean delivery was performed under spinal anesthesia with hyperbaric bupivacaine, fentanyl and morphine sulfate. Desmopressin was administered immediately after delivery. No perioperative complications were observed.     

Multiple gastrointestinal stromal tumors and pheochromocytoma in a patient with von Recklinghausen's disease

INTRODUCTIONNeurofibromatosis type 1 is a genetic disease characterized by neoplastic and non neoplastic disorders involving tissues of neuroectodermal and mesenchymal origin. Herein, we present a case with von Recklinghausen's disease, right adrenal heochromocytoma and multiple gastrointestinal stromal tumors.PRESENTATION OF CASEA forty-eight year old male patient was admitted to our Emergency Department with melena. His physical examination revealed multiple neurofibromas all over the skin, kyphosis, multiple cafe au lait spots and Lisch nodules on the eye and, melena on digital rectal examination. Abdominal computerized tomography scan showed a mass on right adrenal gland and multiple soft tissue mass lesions between distal part of pancreas and small bowel. Adrenal mass was determined as a pheochromocytoma and small bowel lesions were verified as stromal tumors.DISCUSSIONIn patients with NF1, pheochromocytomas and GISTs are well known neoplasms seen with increased incidence than the general population.CONCLUSIONIn patients with NF1, any symptoms with other systems should be managed carefully for underlying malignity.     

Anesthetic management of super-morbidly obese parturients for cesarean delivery with a double neuraxial catheter technique: a case series

Parturients with super-morbid obesity, defined as body mass index greater than 50 kg/m², represent a growing segment of patients who require anesthetic care for labor and delivery. Severe obesity and its comorbid conditions place the parturient and fetus at greater risk for pregnancy complications and cesarean delivery, as well as surgical and anesthetic complications. The surgical approach for cesarean delivery in these patients may require a supra-umbilical vertical midline incision due to a large pannus. The dense T4-level of spinal anesthesia can cause difficulties with ventilation for the obese patient during the procedure, which can be prolonged. Patients also may have respiratory complications in the postoperative period due to pain from the incision. We describe the anesthetic management of three parturients with body mass index ranging from 73 to 95 kg/m² who had a cesarean delivery via a supra-umbilical vertical midline incision. Continuous lumbar spinal and low thoracic epidural catheters were placed in each patient for intraoperative anesthesia and postoperative analgesia, respectively. Continuous spinal catheters were dosed with incremental bupivacaine boluses to achieve surgical anesthesia. In one case, the patient required respiratory support with non-invasive positive pressure ventilation. Two cases were complicated by intraoperative hemorrhage. All patients had satisfactory postoperative analgesia with a thoracic epidural infusion. None suffered postoperative respiratory complications or postdural puncture headache. The use of a continuous lumbar spinal catheter and a low thoracic epidural provides several advantages in the anesthetic management of super-morbidly obese parturients for cesarean delivery.     

Anaesthetic management of a parturient with pulmonary stenosis and aortic incompetence for Caesarean section

Anaesthetic management of Caesarean section in a parturientwith severe pulmonary stenosis and aortic regurgitation is described.The valvular sequelae resulted from previous unsuccessful surgicalcorrection (Ross procedure) of congenital aortic stenosis. Thiscase demonstrates the importance of multi-disciplinary assessmentand careful anaesthetic planning, to avoid deterioration inperioperative cardiac performance in parturients with complexvalvular disease. Br J Anaesth 2003; 90: 241–3     

Anesthetic management of cesarean section in a patient with type II von Willebrand disease

von Willebrand disease is one of the inherited bleeding disorders, and caused by the deficiency or the abnormality of von Willebrand factor. A 28-year-old woman with von Willebrand disease (type II) was scheduled for cesarean section under general anesthesia. Platelet count was within normal limits. However, the prolongation of both APTT and bleeding time was confirmed. The level of von Willbrand factor was within normal ranges, but its activity was about 55%. The platelet aggregation was below 1.3%. We managed to administer factor VIII concentrate to her intravenously before and after operation. We did not perform epidural catheterization because we cannot forecast the amount of bleeding. We could successfully manage this case without any complications. Intravenous patient controlled analgesia was given for postoperative pain. The perioperative course was uneventful and the patient was discharged 7 days after the operation.     

Endothelial dysfunction as a predictor of cardiovascular disease in type 1 diabetes

Macro and microvascular disease are the main cause of morbi-mortality in type 1 diabetes(T1DM).Although there is a clear association between endothelial dysfunction and atherosclerosis in type 2 diabetes,a cause-effect relationship is less clear in T1 DM.Although endothelial dysfunction(ED) precedes atherosclerosis,it is not clear weather,in recent onset T1 DM,it may progress to clinical macrovascular disease.Moreover,endothelial dysfunction may either be reversed spontaneously or in response to intensive glycemic control,long-term exercise training and use of statins.Acute,long-term and post-prandial hyperglycemia as well as duration of diabetes and microalbuminuria are all conditions associated with ED in T1 DM.The pathogenesis of endothelial dysfunction is closely related to oxidative-stress.NAD(P)H oxidase over activity induces excessive superoxide production inside the mitochondrial oxidative chain of endothelial cells,thus reducing nitric oxide bioavailability and resulting in peroxynitrite formation,a potent oxidant agent.Moreover,oxidative stress also uncouples endothelial nitric oxide synthase,which becomes dysfunctional,inducing formation of superoxide.Other important mechanisms are the activation of both the polyol and protein kinase C pathways as well as the presence of advanced glycation end-products.Future studies are needed to evaluate the potential clinical applicability of endothelial dysfunction as a marker for early vascular complications in T1 DM.     

Anaesthetic management of a parturient with the postural orthostatic tachycardia syndrome: a case report

Postural orthostatic tachycardia syndrome encompasses a groupof disorders characterized by orthostatic intolerance. We describethe anaesthetic management of analgesia for labour and of Caesareansection in a parturient suffering from this disorder. Worseningof her symptoms during pregnancy was managed with an increasein the dose of ß-blockers taken by the patient. Epiduralanalgesia was instigated early to attenuate the stress of labourand avoid consequent triggering of a tachycardic response. Slowtitration of epidural analgesia and anaesthesia after an adequatefluid preload was undertaken to minimize hypotension and subsequenttachycardia. Neuraxial opioid, combined with non-steroidal anti-inflammatorydrugs and bilateral iliohypogastric and ilioinguinal nerve blockswere used to optimize postoperative analgesia.     

Elevated levels of plasma von Willebrand factor and the risk of macro- and microvascular disease in type 2 diabetic patients with microalbuminuria.

BACKGROUND: The purpose of this study was to examine the concept suggesting that microalbuminuria in combination with high levels of plasma von Willebrand factor is a stronger predictor for cardiovascular disease and microvascular complications than microalbuminuria alone in type 2 diabetic patients. METHODS: One hundred and sixty patients with type 2 diabetes mellitus and persistent microalbuminuria were followed for an average of 3.8 (SD 0.3) years. 70% of the patients were treated with angiotensin converting enzyme (ACE)-inhibitors. Patients in this subanalysis were divided into two groups according to baseline plasma von Willebrand factor levels below or above the median. The main outcome was cardiovascular disease (cardiovascular mortality, non-fatal stroke, non-fatal myocardial infarction, coronary artery bypass graft and revascularization or amputation of legs), progression to diabetic nephropathy or progression in diabetic retinopathy. RESULTS: At baseline the two groups were comparable for HbA(1c), fasting levels of s-total-cholesterol, s-HDL-cholesterol and s-triglycerides, systolic and diastolic blood pressure, gender, known diabetes duration, smoking habits, previous cardiovascular disease and antihypertensive therapy as well as retinopathy. Odds ratio for cardiovascular disease was 1.11 (95% CI 0.45-2.73, P=0.82) (multiple logistic regression), odds ratio for progression to nephropathy was 1.08 (0.41-2.85, P=0.87) and odds ratio for progression in retinopathy was 0.96 (0.46-2.00, P=0.92), all with plasma von Willebrand factor levels above the median. CONCLUSIONS: Our results do not support the suggestion that the combination of high plasma levels of von Willebrand factor and microalbuminuria is a stronger predictor for cardiovascular disease, progression to diabetic nephropathy or progression in diabetic retinopathy than microalbuminuria alone in patients with type 2 diabetes and persistent microalbuminuria.     

Severe thrombotic and bleeding complications in a baby with heterozygous factor V Leiden and acquired von Willebrand disease on ECMO

We aim to present the case of a 5-week-old girl with severe respiratory failure placed on veno-venous extracorporeal membrane oxygenation (ECMO) that was then switched to veno-arterial ECMO. She required up to 60 units/kg/hr of heparin to keep her heparin level within the target range at .3-.7 units/mL. During the ECMO course, substantial thrombus formation was observed within the venous site of the ECMO cannula, which led to two circuit changes on ECMO day 9 and day 20. On ECMO day 15, she was noticed to have purpuric lesions on her chest and her right hand with no obvious arterial or venous clot detected by Doppler ultrasound. She was also noted to have remarkable hemolysis as the plasma free hemoglobin levels were substantially elevated up to 700 mg/dL. She was noted to have continuous oozing from the catheter insertion sites despite adequate underlying coagulation status. Her subsequent platelet function analysis, the thromboelastography, and thromboelastography platelet mapping suggested substantial platelet dysfunction. Her von Willebrand panel revealed absence of high molecular weight multimers. Further coagulation workup was prompted which revealed heterozygosity for factor V Leiden. The patient developed severe pulmonary hemorrhages and ECMO was discontinued on day 40.     

胰肾联合移植治疗1型糖尿病合并终末期肾病1例报告并文献复习

目的探讨胰肾联合移植治疗糖尿病合并终末期肾病的手术方式及移植效果。方法对1例1型糖尿病合并糖尿病肾病、尿毒症患者施行胰肾联合移植手术,将肾脏移植于左侧髂窝,胰腺移植于右侧髂窝,胰腺移植采用胰腺外分泌肠道引流、内分泌体循环系统回流的术式(肠道-体循环回流术式);术后常规给予免疫抑制、防治感染、支持等治疗。结果受者手术顺利。联合移植后胰、肾均发挥正常功能,血清肌酐逐渐恢复正常水平,血糖趋于稳定,第14日完全停用胰岛素及降糖药物。无严重手术并发症发生,受者健康存活,门诊随访移植胰腺、肾脏功能正常。结论胰肾联合移植是治疗1型糖尿病合并终末期肾病的理想方法 。     

Co-occurrence of type 1 diabetes mellitus and celiac disease

The co-occurrence of celiac disease(CD) and type 1 diabetes(T1DM) has been reported as 5-7 times more prevalent than CD alone.The clinical presentation and natural history of CD in patients with T1 DM may vary considerably.Less than 10% of patients with T1 DM and CD show gastrointestinal symptoms.Therefore,experts support screening for CD in T1 DM patients,though there is no consensus as to the recommended frequency of screening.When stratified by time since CD diagnosis,longer follow-up and coexistence of CD are associated with significant increased risk of diabetic associated morbidity and mortality.Early CD diagnosis and treatment with a gluten-free diet are essential.     

Anaesthetic management of a pregnant patient with Takayasu’s disease undergoing abdominal aortic aneurysm repair

We report the successful anaesthetic management of repair of an abdominal aortic aneurysm in a patient with Takayasu’s disease at 14 weeks’ gestation. Anaesthesia was managed with combined epidural and general anaesthesia. During the intraoperative period haemodynamic parameters were well maintained. There were no episodes of haemodynamic fluctuations, oxygen desaturation or metabolic acidosis. Aortic cross-clamp time was 105 min, blood loss around 1200 mL, and central venous pressure maintained between 8 and 10 cm H₂O. There were no sudden changes in cardiac parameters, base deficit or urine output before or after cross clamping. The patient later delivered a full term, normal fetus.     

Prognostic implications of retinopathy and a high plasma von Willebrand factor concentration in type 2 diabetic subjects with microalbuminuria.

BACKGROUND: Microalbuminuria in subjects with type 2 diabetes may be heterogeneous with respect to clinical features, renal histology, and prognosis. There may be at least two types of microalbuminuria in diabetes, namely with and without generalized endothelial dysfunction. We investigated whether, among microalbuminuric subjects with type 2 diabetes, the presence of generalized endothelial dysfunction, as indicated by the presence of retinopathy or a high plasma von Willebrand factor (vWf) level, has prognostic implications. METHODS: In 173 type 2 diabetic subjects of a population-based cohort, we assessed the urinary albumin-to-creatinine ratio, the plasma vWf level, and the presence of retinopathy. The main outcome was cardiovascular mortality. RESULTS: The absolute difference in 7 years' cardiovascular mortality between microalbuminuric (albumin-to-creatinine ratio 2.0-30.0 mg/mmol) and normoalbuminuric subjects was higher in the presence as compared to the absence of retinopathy (55.6 vs 11.1%). The age- and sex-adjusted relative risk (95% confidence interval) of cardiovascular mortality, as compared to normoalbuminuric subjects without retinopathy, was 1.1 (0.1-9.2) for normoalbuminuric subjects with retinopathy, 1.8 (0.5-6.7) for microalbuminuric subjects without retinopathy, and 9.8 (3.1-30.9) for microalbuminuric subjects with retinopathy. The absolute difference in risk of 7 years' cardiovascular mortality between microalbuminuric and normoalbuminuric subjects was higher in the presence as compared to the absence of a high (>1.89 IU/ml) vWf level (49.8 vs 16.4%). The age- and sex-adjusted relative risk of cardiovascular mortality, as compared to normoalbuminuric subjects without a high vWf level, was 1.5 (0.4-5.5) for normoalbuminuric subjects with a high vWf level, 2.6 (0.7-9.6) for microalbuminuric subjects without a high vWf level, and 12.0 (2.9-49.5) for microalbuminuric subjects with a high vWf level. These differences in risk of cardiovascular mortality did not change materially after further adjustment for known duration of diabetes, hypertension, creatinine clearance, level of glycated haemoglobin and high-density lipoprotein cholesterol, and presence of cardiovascular disease. Analysis of all-cause instead of cardiovascular mortality showed a similar difference in risk of mortality between microalbuminuric subjects with or without retinopathy or a high vWf level. CONCLUSIONS: Among type 2 diabetic subjects with microalbuminuria, the presence of retinopathy or a high plasma vWf level affects the risk of cardiovascular death. Although larger studies are necessary, these findings support the concept that microalbuminuria in type 2 diabetes can occur in the absence or the presence of generalized endothelial dysfunction, and that the latter is a much more 'malignant' condition than the former.     

Aneurysmal rupture of the costo-cervical trunk in a patient with neurofibromatosis type 1: A case report

INTRODUCTION

Rupture of blood vessels associated with neurofibromatosis type 1 (NF-1) is a rare but life threatening complication. We report the first case of an aneurysmal rupture from the costocervical trunk in a NF-1 patient treated by endovascular embolisation.

PRESENTATION OF CASE

A 43 year-old gentleman with a past medical history of NF-1 presented with sudden onset left sided neck swelling. A computed tomography (CT) revealed a large cervical haematoma, which was causing airway compromise, requiring the patient to be intubated. Percutaneous embolisation of the bleeding vessel from the costo-cervical trunk was performed with successful haemostasis and no immediate complications. A repeat CT scan showed a reduction in the original cervical haematoma. However, six days post embolisation, the patient arrested with complete whiteout of the left hemithorax.

DISCUSSION

CT angiography is the gold standard for diagnosis of an aneurysmal rupture in NF-1 patients, and percutaneous embolisation is the preferred modality in patients who are haemodynamically stable due to arterial fragility and high intra operative mortality rates. The increasing haemothorax could be explained by the original cervical haematoma draining down into the pleural space, or the possibility of a new second bleed.

CONCLUSION

This is the first reported episode of bleeding from the costocervical trunk in NF-1 patients. Ruptured aneurysms require urgent CT angiography, if haemodynamically stable, and further input from the vascular surgeons and vascular radiologists.     

慢性丙型肝炎合并2型糖尿病患者基因型特征分析

目的：了解慢性丙型肝炎并2型糖尿病患者基因型及相应的临床特征。方法检测88例慢性丙型肝炎并2型糖尿病患者与770例慢性丙型肝炎患者基因分型,分析88例慢性丙型肝炎并2型糖尿病患者的糖化血红蛋白、空腹血糖、空腹胰岛素、天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、γ-谷氨酰转肽酶（GGT）、总胆红素（TBil）、HCV RNA病毒载量及血甘油三酯等临床相关指标,并调查患者糖尿病确诊时间及抗病毒治疗情况。结果慢性丙型肝炎并2型糖尿病患者3a基因型占11.36%（10/88）,高于未合并2型糖尿病者3a基因型3.38%（26/770）,差异具有统计学意义（χ2=7.248,P=0.002）;并2型糖尿病的3a基因型患者的甘油三酯高于其他基因型（t=2.271,P =0.028）;糖尿病诊断时间多在抗病毒治疗前,部分患者控制血糖同时抗病毒治疗。结论感染丙型肝炎病毒3a基因型的患者更易并2型糖尿病,应监测血糖情况,尽早筛查糖尿病,早期诊治。