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1.
Braz J Cardiovasc Surg ; 34(4): 412-419, 2019 08 27.
Article in English | MEDLINE | ID: mdl-31454195

ABSTRACT

OBJECTIVE: To investigate whether low bleeding influences the early outcomes after off-pump coronary artery bypass grafting (CABG). METHODS: Retrospective analysis of ischemic heart disease patients who underwent off-pump CABG from January 2013 to December 2017. Patients were divided into low-bleeding group (n=659) and bleeding group (n=270), according to total drainage from chest tube during the first postoperative 12 hours. Clinical material and early outcomes were compared between the groups. RESULTS: Baseline was similar in the two groups. Operation time was 270±51 min in the low-bleeding group and 235±46 min in the bleeding group (P<0.0001). The low-bleeding group presented smaller drainage during the first 12 h (237±47 ml) and shorter mechanical ventilation time (6.86±3.78 h) than the bleeding group (557±169 ml and 10.66±5.19 h, respectively) (P<0.0001). Hemodynamic status was more stable in the low-bleeding group (P<0.0001) and usage rate of more than two vasoactive agents in this group was lower than in the bleeding group (P<0.0001). Number of distal anastomosis, reoperation for bleeding, suddenly increase in chest tube output, intensive care unit (ICU) stay, hospital stay, and other early outcomes had no statistical significance between the groups (P>0.05). CONCLUSION: Postoperative bleeding < 300 ml/12 h in off-pump CABG patients did not require blood product transfusion and reoperation and that would contribute to reduction in mechanical ventilation time and maintaining hemodynamic stability. Bleeding < 800 ml during the first postoperative 12 h did not increase infection rates and ICU length of stay.


Subject(s)
Coronary Artery Bypass, Off-Pump/adverse effects , Coronary Artery Disease/surgery , Postoperative Hemorrhage/blood , Aged , Blood Transfusion , Female , Hemodynamics , Hemostasis , Hospital Mortality , Humans , Intensive Care Units , Length of Stay , Male , Middle Aged , Postoperative Period , Reoperation , Respiration, Artificial , Retrospective Studies , Time Factors
2.
Rev. bras. cir. cardiovasc ; Rev. bras. cir. cardiovasc;34(4): 412-419, July-Aug. 2019. tab, graf
Article in English | LILACS | ID: biblio-1020504

ABSTRACT

Abstract Objective: To investigate whether low bleeding influences the early outcomes after off-pump coronary artery bypass grafting (CABG). Methods: Retrospective analysis of ischemic heart disease patients who underwent off-pump CABG from January 2013 to December 2017. Patients were divided into low-bleeding group (n=659) and bleeding group (n=270), according to total drainage from chest tube during the first postoperative 12 hours. Clinical material and early outcomes were compared between the groups. Results: Baseline was similar in the two groups. Operation time was 270±51 min in the low-bleeding group and 235±46 min in the bleeding group (P<0.0001). The low-bleeding group presented smaller drainage during the first 12 h (237±47 ml) and shorter mechanical ventilation time (6.86±3.78 h) than the bleeding group (557±169 ml and 10.66±5.19 h, respectively) (P<0.0001). Hemodynamic status was more stable in the low-bleeding group (P<0.0001) and usage rate of more than two vasoactive agents in this group was lower than in the bleeding group (P<0.0001). Number of distal anastomosis, reoperation for bleeding, suddenly increase in chest tube output, intensive care unit (ICU) stay, hospital stay, and other early outcomes had no statistical significance between the groups (P>0.05). Conclusion: Postoperative bleeding < 300 ml/12 h in off-pump CABG patients did not require blood product transfusion and reoperation and that would contribute to reduction in mechanical ventilation time and maintaining hemodynamic stability. Bleeding < 800 ml during the first postoperative 12 h did not increase infection rates and ICU length of stay.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Coronary Artery Disease/surgery , Postoperative Hemorrhage/blood , Coronary Artery Bypass, Off-Pump/adverse effects , Postoperative Period , Reoperation , Respiration, Artificial , Time Factors , Blood Transfusion , Retrospective Studies , Hospital Mortality , Hemodynamics , Hemostasis , Intensive Care Units , Length of Stay
3.
Rev Med Inst Mex Seguro Soc ; 56(6): 517-524, 2019 Mar 15.
Article in Spanish | MEDLINE | ID: mdl-30889339

ABSTRACT

Background: The association between coagulation profile and postpartum hemorrhage (PH) is still debated. Objective: To determine the association between hemostatic profile and PH in women with cesarean operation (CO). Methods: We included 92 patients with PH (cases) and 184 without (controls), patients were attended during 2014, at one hospital of the Instituto Mexicano del Seguro Social in Mérida, Yucatán. Demographic, clinical and laboratory data including prothrombin time (PT), activated partial thromboplastin time (aPTT), platelet count (PLC), and fibrinogen concentration were compared among cases and controls using a binary logistic regression model (LRM), from which odd ratios (OR), and 95% confidence intervals (95% CI), were obtained. Results: According to the bivariate comparison, in the LRM categorical data such as parity, any type of hypertensive comorbidity, type of anesthesia, and categorized aPTT (< 38 vs. ≥ 38 seconds), and one continuous variable (gestational age) were included. Having some hypertensive comorbidity (OR 3.55, 95% CI: 1.95-6.47), type of anesthesia (regional anesthesia, OR 0.27, 95% CI: 0.13-0.55) and aPTT (< 38 seconds, OR 0.26, 95% CI: 0.10-0.66) were all statistically significant. Categorized PT, platelet count and fibrinogen concentration, were not statistically significant. Conclusions: In this sample, having some hypertensive comorbidity increased risk of PH more than three times, while regional anesthesia and aPTT < 38 seconds reduced risk in 73% and 74%, respectively. Neither platelet count, nor fibrinogen concentration, or the PT categories modified risk of PH.


Introducción: la asociación entre el perfil hemostático y la hemorragia obstétrica posparto (HO) es controversial. Objetivo: determinar la asociación entre el perfil hemostático y la HO en pacientes con operación cesárea (OC). Métodos: se incluyeron 92 pacientes con HO (casos) y 184 sin HO (controles), atendidas durante 2014 en un hospital del Instituto Mexicano del Seguro Social de Mérida, Yucatán. Diversas variables, incluyendo la cuenta plaquetaria, el tiempo de protrombina (TP), el tiempo de tromboplastina parcial activado (TTPa) y el fibrinógeno plasmático, fueron comparadas entre casos y controles, mediante un modelo de regresión logística del que se obtuvieron razones de momios (RM) e intervalos de confianza de 95% (IC 95%). Resultados: con base en el análisis univariado se incluyeron en el modelo la paridad, comorbilidad hipertensiva (hipertensión crónica, preeclampsia, eclampsia), tipo de anestesia y el TTPa categorizado (< 38 frente a ≥ 38 segundos) y la edad gestacional (como dato continuo), resultando significativamente diferentes la presencia de comorbilidad hipertensiva (RM 3.55, IC 95%: 1.95-6.47), el tipo de anestesia (regional, RM 0.27, IC 95%: 0.13-0.55) y el TTPa (< 38 segundos, RM 0.26, IC 95%: 0.10-0.66). Conclusiones: en esta muestra, tener comorbilidad hipertensiva incrementó más de tres veces el riesgo de HO, la anestesia regional lo redujo en 73% y el TTPa < 38 segundos lo redujo en 74%. Ni el TP, ni la cuenta plaquetaria modificaron el riesgo.


Subject(s)
Cesarean Section/adverse effects , Hemostasis , Postoperative Hemorrhage/blood , Postpartum Hemorrhage/blood , Adult , Anesthesia, Obstetrical/adverse effects , Anesthesia, Obstetrical/methods , Case-Control Studies , Female , Fibrinogen/analysis , Gestational Age , Humans , Hypertension/complications , Parity , Partial Thromboplastin Time , Platelet Count/statistics & numerical data , Postoperative Hemorrhage/etiology , Postpartum Hemorrhage/etiology , Pregnancy , Prenatal Care/statistics & numerical data , Prothrombin Time , Regression Analysis , Uterine Inertia
4.
Ann Hepatol ; 17(5): 830-835, 2018 Jun 05.
Article in English | MEDLINE | ID: mdl-30145561

ABSTRACT

INTRODUCTION AND AIM: EVBL is a procedure frequently performed in cirrhotic patients for primary prophylaxis of bleeding. Patients with cirrhosis display various degrees of alteration of common coagulation parameters, and it is not known whether these alterations may predict post-EVBL bleeding. To evaluate factors predictive of post-endoscopic variceal band ligation (EVBL) bleeding in cirrhotic patients with thrombocytopenia. METHODS: We included 109 patients with cirrhosis undergoing EVBL for primary prophylaxis of variceal bleeding. Common coagulation parameters (INR, fibrinogen levels) and complete haemogram were obtained in all patients and evaluated subdividing patients in bleeders and non bleeders following EVBL. RESULTS: The incidence of post-EVBL bleeding was 5.5% (6 patients). INR and platelet counts, considered as continuous or dichotomous variables according to common cut-offs (i.e., INR>1.5, platelet count <50x109/L) were not predictors of post-EVBL bleeding. Patients who bled had significantly lower fibrinogen levels [146 mg/dL (98 - 262) versus 230 mg/dL (104 - 638), P=0.009], and no other biochemical or clinical predictors of bleeding were identified. A fibrinogen cut-off of 179 mg/dL had 98.6% negative predictive value for bleeding. CONCLUSION: low fibrinogen levels are associated with an increased risk of bleeding following prophylactic EVBL in cirrhotic patients, and might be used to stratify patients' risk. However, due to their preliminary nature, these findings need to be confirmed in larger populations.


Subject(s)
Endoscopy/adverse effects , Esophageal and Gastric Varices/surgery , Fibrinogen/metabolism , Gastrointestinal Hemorrhage/prevention & control , Liver Cirrhosis/complications , Postoperative Hemorrhage/etiology , Thrombocytopenia/etiology , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Blood Coagulation , Down-Regulation , Endoscopy/methods , Esophageal and Gastric Varices/blood , Esophageal and Gastric Varices/diagnosis , Esophageal and Gastric Varices/etiology , Female , Gastrointestinal Hemorrhage/blood , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/etiology , Humans , International Normalized Ratio , Ligation/adverse effects , Liver Cirrhosis/blood , Liver Cirrhosis/diagnosis , Male , Middle Aged , Platelet Count , Postoperative Hemorrhage/blood , Postoperative Hemorrhage/diagnosis , Risk Assessment , Risk Factors , Thrombocytopenia/blood , Thrombocytopenia/diagnosis , Time Factors , Treatment Outcome
5.
Transplantation ; 102(4): 578-592, 2018 04.
Article in English | MEDLINE | ID: mdl-29337842

ABSTRACT

We review contemporary coagulation management for patients undergoing liver transplantation. A better understanding of the complex physiologic changes that occur in patients with end-stage liver disease has resulted in significant advances in anesthetic and coagulation management. A group of internationally recognized experts have critically evaluated current approaches for coagulopathy detection and management. Strategies for blood component and factor replacement have been evaluated and recommended therapies proposed. Pharmacologic treatment and prevention of coagulopathy, management of patients receiving antiplatelet medications, and the role of transesophageal echocardiography for early detection and management of thromboses are presented.


Subject(s)
Anticoagulants/administration & dosage , Blood Coagulation/drug effects , Blood Loss, Surgical/prevention & control , Blood Transfusion/methods , End Stage Liver Disease/surgery , Liver Transplantation , Perioperative Care/methods , Postoperative Hemorrhage/prevention & control , Thrombosis/prevention & control , Animals , Anticoagulants/adverse effects , Blood Coagulation Tests , Drug Monitoring/methods , End Stage Liver Disease/blood , End Stage Liver Disease/diagnosis , Hemorrhage/chemically induced , Humans , Liver Transplantation/adverse effects , Postoperative Hemorrhage/blood , Postoperative Hemorrhage/etiology , Risk Factors , Thrombosis/blood , Thrombosis/diagnosis , Thrombosis/etiology , Treatment Outcome
6.
Clinics (Sao Paulo) ; 68(4): 531-6, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23778350

ABSTRACT

OBJECTIVE: To analyze the preoperative plasma antigenic concentration and activity of von Willebrand factor and its main cleaving protease ADAMTS-13 in pediatric patients with cyanotic congenital heart disease undergoing surgical treatment and investigate possible correlations with postoperative bleeding. METHODS: Plasma antigenic concentrations (von Willebrand factor:Ag and ADAMTS-13:Ag) were measured using enzyme-linked immunoassays. Collagen-binding assays were developed to measure biological activities (von Willebrand factor:collagen binding and ADAMTS-13 activity). The multimeric structure of von Willebrand factor was analyzed using Western immunoblotting. Demographic, diagnostic, and general and specific laboratory data and surgery-related variables were subjected to univariate, bivariate, and multivariate analysis for the prediction of postoperative bleeding. RESULTS: Forty-eight patients were enrolled, with ages ranging from 9 months to 7.6 years (median 2.5 years). The plasma concentrations of von Willebrand factor:Ag and ADAMTS-13:Ag were decreased by 65 and 82%, respectively, in the patients compared with the controls (p<0.001). An increased density of low-molecular-weight fractions of von Willebrand factor, which are suggestive of proteolytic degradation (p = 0.0081), was associated with decreased ADAMTS-13 activity, which was likely due to ADAMTS-13 consumption (71% of controls, p = 0.0029) and decreased von Willebrand factor:collagen binding (76% of controls, p = 0.0004). Significant postoperative bleeding occurred in 13 patients. The preoperative ADAMTS-13 activity of <64.6% (mean level for the group), preoperative activated partial thromboplastin time, and the need for cardiopulmonary bypass were characterized as independent risk factors for postoperative bleeding, with respective hazard ratios of 22.35 (95% CI 1.69 to 294.79), 1.096 (95% CI 1.016 to 1.183), and 37.43 (95% CI 1.79 to 782.73). CONCLUSION: Low plasma ADAMTS-13 activity is a risk factor for postoperative bleeding in children with cyanotic congenital heart disease, particularly in children undergoing cardiopulmonary bypass.


Subject(s)
ADAM Proteins/blood , Heart Defects, Congenital/blood , Postoperative Hemorrhage/blood , von Willebrand Factor/analysis , ADAM Proteins/physiology , ADAMTS13 Protein , Analysis of Variance , Blood Coagulation/physiology , Blotting, Western , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , Heart Defects, Congenital/surgery , Humans , Infant , Male , Postoperative Hemorrhage/etiology , Predictive Value of Tests , Reference Values , Risk Factors , von Willebrand Factor/physiology
7.
Clinics ; Clinics;68(4): 531-536, abr. 2013. tab, graf
Article in English | LILACS | ID: lil-674249

ABSTRACT

OBJECTIVE: To analyze the preoperative plasma antigenic concentration and activity of von Willebrand factor and its main cleaving protease ADAMTS-13 in pediatric patients with cyanotic congenital heart disease undergoing surgical treatment and investigate possible correlations with postoperative bleeding. METHODS: Plasma antigenic concentrations (von Willebrand factor:Ag and ADAMTS-13:Ag) were measured using enzyme-linked immunoassays. Collagen-binding assays were developed to measure biological activities (von Willebrand factor:collagen binding and ADAMTS-13 activity). The multimeric structure of von Willebrand factor was analyzed using Western immunoblotting. Demographic, diagnostic, and general and specific laboratory data and surgery-related variables were subjected to univariate, bivariate, and multivariate analysis for the prediction of postoperative bleeding. RESULTS: Forty-eight patients were enrolled, with ages ranging from 9 months to 7.6 years (median 2.5 years). The plasma concentrations of von Willebrand factor:Ag and ADAMTS-13:Ag were decreased by 65 and 82%, respectively, in the patients compared with the controls (p<0.001). An increased density of low-molecular-weight fractions of von Willebrand factor, which are suggestive of proteolytic degradation (p = 0.0081), was associated with decreased ADAMTS-13 activity, which was likely due to ADAMTS-13 consumption (71% of controls, p = 0.0029) and decreased von Willebrand factor:collagen binding (76% of controls, p = 0.0004). Significant postoperative bleeding occurred in 13 patients. The preoperative ADAMTS-13 activity of <64.6% (mean level for the group), preoperative activated partial thromboplastin time, and the need for cardiopulmonary bypass were characterized as independent risk factors for postoperative bleeding, with respective hazard ratios of 22.35 (95% CI 1.69 to 294.79), 1.096 (95% CI 1.016 to 1.183), and 37.43 (95% ...


Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , ADAM Proteins/blood , Heart Defects, Congenital/blood , Postoperative Hemorrhage/blood , von Willebrand Factor/analysis , ADAM Proteins/physiology , Analysis of Variance , Blotting, Western , Blood Coagulation/physiology , Enzyme-Linked Immunosorbent Assay , Heart Defects, Congenital/surgery , Predictive Value of Tests , Postoperative Hemorrhage/etiology , Reference Values , Risk Factors , von Willebrand Factor/physiology
8.
J Thorac Cardiovasc Surg ; 144(3): 663-70, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22578899

ABSTRACT

OBJECTIVES: Modified ultrafiltration (MUF) has been shown to decrease the postcardiac surgery inflammatory response and to improve respiratory function and cardiac performance in pediatric patients; however, this approach has not been well established in adults. The present study hypothesized that MUF could decrease the postsurgical inflammatory response, leading to improved respiratory and cardiac function in adults undergoing coronary artery bypass grafting. METHODS: Sixty patients undergoing coronary artery bypass grafting were randomized to the MUF or control group (n = 30 each). MUF was performed for 15 minutes at the end of bypass. The following data were recorded at the beginning of anesthesia, end of bypass, end of experimental treatment, and 24 and 48 hours after surgery: alveolar-arterial oxygen gradient, red blood cell units transfused, chest tube drainage, hemodynamic parameters, and cytokine levels (interleukin-6, P-selectin, intercellular adhesion molecule, and soluble tumor necrosis factor receptor). RESULTS: The MUF group displayed less chest tube drainage than the control group after 48 hours (598 ± 123 mL vs 848.0 ± 455 mL; P = .04) and less red blood cell transfusions (0.6 ± 0.6 units/patient vs 1.6 ± 1.1 units/patient; P = .03). Hematocrit level was higher in the MUF group than in the control group at the end of bypass (37.8% ± 1.1% vs 34.1% ± 1.1%; P < .05), but the levels were comparable at 48 hours. Similar values for interleukin-6 and P-selectin were observed at all stages. Plasma levels of intercellular adhesion molecule were higher in the MUF group than in the control group, particularly in the first sampling after experimental treatment (P = .01). Plasma levels of soluble tumor necrosis factor receptor were higher in the MUF group than in the control group at 48 hours. Hemodynamic and oxygen transport parameters were similar in both groups throughout the observation period. There were no differences in other clinical outcomes. CONCLUSIONS: Use of MUF was associated with increased inflammatory response, reduced blood loss, and less blood transfusions in adults undergoing coronary artery bypass grafting.


Subject(s)
Coronary Artery Bypass/adverse effects , Hemofiltration/adverse effects , Inflammation/etiology , Postoperative Hemorrhage/prevention & control , Analysis of Variance , Biomarkers/blood , Brazil , Cardiopulmonary Bypass/adverse effects , Chest Tubes , Drainage/instrumentation , Erythrocyte Transfusion , Female , Hemodynamics , Humans , Inflammation/blood , Inflammation Mediators/blood , Intercellular Adhesion Molecule-1/blood , Interleukin-6/blood , Lactic Acid/blood , Male , Middle Aged , Oxygen/blood , P-Selectin/blood , Postoperative Hemorrhage/blood , Postoperative Hemorrhage/etiology , Receptors, Tumor Necrosis Factor/blood , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
9.
Coron Artery Dis ; 20(2): 100-5, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19293667

ABSTRACT

OBJECTIVE: To delineate the effects of extracorporeal bypass on biomarkers of hemostasis, fibrinolysis, and inflammation and clinical sequelae. METHODS: Patients were assigned prospectively and randomly to either on-pump (n=41) or off-pump (n=51) coronary bypass surgery. The concentrations of C-reactive protein, fibrinogen, D-dimer, and plasminogen activator inhibitor type-1 in blood were quantified before and after (1 and 24 h) surgery. Similar surgical and anesthetic procedures were used for both groups. Clinical events were assessed during initial hospitalization and at the end of 1 year. RESULTS: The concentrations of plasminogen activator inhibitor type-1 and D-dimer were greater compared with preoperative values 1 and 24 h after surgery in both groups, but their concentrations increased to a greater extent 24 h after surgery in the on-pump group (P<0.01). The concentration of C-reactive protein did not change appreciably immediately after surgery in either group but increased in a parallel manner 24 h after either on-pump or off-pump surgery (P<0.01). Bypass surgery in the on-pump group was associated with greater blood loss during surgery and more bleeding after surgery (P< or =0.01). The incidence of all other complications was similar in the two groups. CONCLUSION: On-pump surgery was associated with biochemical evidence of a prothrombotic state early after surgery but no greater incidence of thrombotic events was observed. The prothrombotic state might be a consequence of extracorporeal bypass, compensation in response to more bleeding, or both in patients undergoing on-pump surgery.


Subject(s)
Blood Loss, Surgical/prevention & control , Cardiopulmonary Bypass/adverse effects , Coronary Artery Bypass, Off-Pump/adverse effects , Coronary Artery Bypass/adverse effects , Coronary Artery Disease/surgery , Hemostasis , Postoperative Hemorrhage/prevention & control , Thrombosis/blood , Aged , Biomarkers/blood , C-Reactive Protein/metabolism , Coronary Artery Disease/blood , Female , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinogen/metabolism , Fibrinolysis , Humans , Inflammation Mediators/blood , Male , Middle Aged , Plasminogen Activator Inhibitor 1/blood , Postoperative Hemorrhage/blood , Postoperative Hemorrhage/etiology , Prospective Studies , Thrombosis/etiology , Time Factors , Treatment Outcome
10.
Thromb Haemost ; 100(5): 797-802, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18989523

ABSTRACT

Patients with von Willebrand disease (VWD) frequently bleed under a challenge. The aim of our study was to identify predictive markers of perioperative major haemorrhage in type 1 (VWF:RCo = 15-30 IU dl(-1)) and possible type 1 (VWF:RCo = 31-49 IU dl(-1)) VWD patients. We recorded perioperative bleeding complications previous to diagnosis and laboratory parameters in 311 patients with 498 surgical procedures. The patients were grouped according to the absence (A) or presence (B) of perioperative major haemorrhages. Eighty-one patients (26%) and 87 surgical procedures (17.5%) presented major haemorrhages associated with surgeries. There was no difference between the percentage of type 1 and possible type 1 VWD patients who had major haemorrhages (32.6% and 24.8% respectively; p = ns). No difference in the prevalence of O blood group, age, gender, positive family history and laboratory test results (FVIII and VWF) was observed, independent of the haemorrhagic tendency. Bleeding after tooth extraction was the most frequent clinical feature observed in patients with perioperative major haemorrhages. The bleeding score and the number of bleeding sites (> or = 3) were not predictors of major haemorrhage associated with surgery. Caesarean section and adenotonsillectomy showed the highest frequency of major haemorrhages (24.6% and 22.3%, respectively). In conclusion, type 1 and possible type 1 VWD patients showed similar incidence of perioperative major haemorrhages. Laboratory tests and positive family history did not prove to be effective at predicting major haemorrhages in patients that had either type 1 or possible type 1 VWD. The history of bleeding after tooth extraction could define risk factors of major haemorrhage.


Subject(s)
Blood Loss, Surgical , Postoperative Hemorrhage/etiology , Surgical Procedures, Operative/adverse effects , von Willebrand Diseases/complications , Adenoidectomy/adverse effects , Adolescent , Adult , Aged , Biomarkers/blood , Blood Loss, Surgical/prevention & control , Cesarean Section/adverse effects , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Postoperative Hemorrhage/blood , Postoperative Hemorrhage/prevention & control , Retrospective Studies , Risk Assessment , Risk Factors , Tonsillectomy/adverse effects , Tooth Extraction/adverse effects , Young Adult , von Willebrand Diseases/blood , von Willebrand Diseases/therapy
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