Angioedema after rt-PA infusion led to airway emergency: a case report of rescue treatment with fresh frozen plasma

Abstract The authors report the case of a 71-year-old woman presented to the Emergency Department with acute ischemic stroke. She was treated with rt-PA and interventional endovascular revascularization and developed rapidly progressing angioedema that led to emergency intubation. The standard treatment was not very effective and the swelling improved after infusion of fresh frozen plasma. Angioedema after rt-PA infusion could be a life-threatening emergency that requires quick airway management by skilled professionals. As this condition is triggered by several factors, such as unregulated histamine and bradykinin production, the traditional treatment recommended by the guidelines may not be sufficient and the use of FFP can be considered as a safe and valuable aid.

Perioperative blood management of a patient with coagulation factor Ⅴ deficiency and literature review / 中国输血杂志

【Objective】 To explore the perioperative blood management in patients with pancreatic pseudocyst combiend with coagulation factor Ⅴ(FⅤ) deficiency. 【Methods】 Preoperative: In order to determine the effect of cryoprecipitated antihemophilic factor and fresh frozen plasma (FFP) on the elevation level of factor Ⅴ, we alternately infused cryoprecipitate and FFP in the resting state. TEG, coagulation function and coagulation factor activity were monitored before and 1 h, 24 h and 48 h after infusion, and intraoperative and postoperative blood transfusion strategies were formulated. FFP 600 mL and cryoprecipitate 10 U were supplemented preoperatively. Intraoperative: The operation procedure was performed for 7 hours with an infusion of 600 mL FFP without significant bleeding. Postoperative: FFP was infused. 【Results】 Preoperative: The coagulation factor Ⅴ activity on pre-operation was 1.9% and 1.8%. After alternating infusion cryoprecipitate 10 U and FFP 1 200 mL, the FⅤactivity increased to 5.1% and 6.0%, respectively. There was no significant difference in TEG parameters, PT and ATPP results were decreased to varying degrees. Intraoperative: The operation was successful without obvious bleeding. Postoperative: FFP 500 mL was infused 2 h after operation, and FFP 250-500 mL was injected daily from 1 to 7 days after surgery. No significant bleeding was observed in the wound, the results of TEG, PT, APTT and hemoglobin (Hb) did not change significantly compared with those before surgery. The patient was discharged successfully 12 days after surgery. The genetic test results showed that he had inherited coagulation factor Ⅴ deficiency, which was a compound heterozygous variation. 【Conclusion】 Perioperative blood management in patients with FⅤ deficiency combined with surgical disease, requiring pre-transfusion evaluation and post-transfusion evaluation in combination with laboratory investigations and clinical manifestations, cryoprecipitate and fresh frozen plasma can be effective in supplementing coagulation factors. The TEG seems to be better than the Seven items of coagulation function in judging the clotting status of patients with FⅤ deficiency.

Progress of rebalanced hemostasis and transfusion of blood products in pediatric acute liver failure / 中国小儿急救医学

Pediatric acute liver failure(PALF)is a severe liver damage caused by multiple factors, resulting in severe impairment of hepatic synthesis, excretion, detoxification and biotransformation.It was thought that PALF patients had coagulation disorders that predisposed them to bleeding.Now it is noted that due to the simultaneous reduction of anticoagulant and procoagulant factors, the body is in a state of rebalanced hemostasis.The risk of thrombosis is nearly equal to hemorrhage.Appropriate laboratory tests can better assess the coagulation status of children with PALF and guide appropriate blood product transfusions to improve coagulation and reduce the risk of transfusion-related fluid overload and other adverse prognosis.

Progress of rebalanced hemostasis and transfusion of blood products in pediatric acute liver failure / 中国小儿急救医学

Pediatric acute liver failure(PALF)is a severe liver damage caused by multiple factors, resulting in severe impairment of hepatic synthesis, excretion, detoxification and biotransformation.It was thought that PALF patients had coagulation disorders that predisposed them to bleeding.Now it is noted that due to the simultaneous reduction of anticoagulant and procoagulant factors, the body is in a state of rebalanced hemostasis.The risk of thrombosis is nearly equal to hemorrhage.Appropriate laboratory tests can better assess the coagulation status of children with PALF and guide appropriate blood product transfusions to improve coagulation and reduce the risk of transfusion-related fluid overload and other adverse prognosis.

Prolonged Apnoea after Suxamethonium, Diagnosis & Treatment: A Case Report

Plasma Cholinesterase Deficiency is an autosomal recessive inherited blood plasma enzyme abnormality in which the Body's production of butyrylcholinesterase is impaired resulting in prolonged apnoea following depolarising muscle relaxants like Succinyl Choline (Suxamethonium) or Mivacurium. This is associated with paralysis & little or no neurological response. Individuals with plasma cholinesterase (Pseudocholinesterase) deficiency are often diagnosed only after experiencing prolonged apnoea after standard intubating dose of Succinyl Choline. Plasma Cholinesterase is not produced artificially & can be supplied through Blood & fresh frozen plasma. Hence treatment includes mechanical ventilation & supplementation of either whole blood or fresh frozen plasma

Quality of cryoprecipitated antihemophilic factor: Impact of storage time following whole blood collection, gender, ABO blood group, age, and preparation method / 中国输血杂志

【Objective】 To investigate the factors affecting the quality of cryoprecipitated antihemophilic factor. 【Methods】 The quality test results of cryoprecipitated antihemophilic factor in Xuzhou Central Blood Station from 2017 to 2020 were selected and compared. The fresh frozen plasma (FFP) was stratifying by storage time following whole blood collection: less than 2h, 2~4 h, 4~6 h, and 6~8 h; by gender: males and females; by blood group: A, B, O, and AB groups; by age: 18~30, 30~45, and 45~60 ages; by preparation method: centrifugation and siphonage. The contents of fibrinogen (FIB) and factor Ⅷ in cryoprecipitated antihemophilic factor in each group were compared. 【Results】 The content of FIB and factor Ⅷ in females were higher than those in males(P<0.05). The content of factor Ⅷ differed statically by blood groups (P<0.05), which was lower in group O than others [graup A(180.5±75.2)IU, graup B(155.1±59.4)IU, graup O(109.3±46.4)IU, graup AB(168.5±65.1)IU]. The content of factor Ⅷ increased with age statistically (P<0.05). The content of FIB prepared by centrifugation [(373.3±126.1)mg] was superior to siphonage [(309.4±85.6)mg] (P<0.05), while the content of factor Ⅷ prepared by siphonage [(172.4±71.3)IU] was superior to centrifugation [(124.0±49.1)mg] (P<0.05). 【Conclusion】 Gender and preparation method are the influencing factors of FIB. Gender, age, blood group and preparation method are the influencing factors of the content of factor Ⅷ. The FFP prepared by whole blood preserved with the ACD (citrate, sodium citrate and glucose) solution at any time within 8h after the collection has no impact on the quality of cryoprecipitated antihemophilic factor.

Efficacy in treatment of moderate to severe degree organophosphorus poisoning with fresh frozen plasma, atropine and 2-pyridine aldoxime methyl chloride as compared to treatment with atropine and 2-pyridine aldoxime methyl chloride in Western Odisha

Background: Organophosphorus (OP) compounds are one of the most common agents used for suicidal poisoning. People in the middle socioeconomic status are mainly affected. The most important determinant of death in OP poisoning is the severity. The ideal treatment of OP poisoning, this study was undertaken to compare the efficacy of fresh frozen plasma (FFP) along with the standard regimen of atropine and oximes.Methods: 80 patients were taken in this study (40 cases and 40 controls) with history and biochemical pictures suggestive of acute OP poisoning. Normality assumption and equality of variance were satisfied for most of quantitative variables. As a comparison of the baseline data of the study groups did not reveal any significant difference (p>0.05), the result at a given point of time between two groups were also compared with the same methods of assess the comparative changes.Results: Total 80 patients >15 years of age were taken for the study. Out of the total 63.7% are female and 36.3% are males. OP compounds are commonly used as suicidal agent. Salivation is the most common presenting symptoms in both cases and controls. The mean value of serum cholinesterase on day -1 in cases and controls are nearly same but the subsequent mean values as the days progresses are higher in cases than that controls.Conclusions: FFP showed its positive effect in reducing the development of intermediate syndrome/ fatality/ ventilatory support.

Audit of transfusion practices in pediatrics in a tertiary care hospital

Background: Audit of transfusion practices in pediatric patients was performed to study indications, clinical profile and whether transfusions were in accordance to guidelines.Methods: Retrospective analysis of all episodes of transfusions from a tertiary care centre was done. The study period was from January 2018 to December 2018.Patients in the age group of 4 months to 12 years were enrolled in the study. The data was reviewed according to the British Committee for Standards in Haematology guidelines for transfusion.Results: During the study period of 12 months,168 units of hemocomponents were transfused to children, 66.07% (111/168) of the total products transfused were packed red cell units, followed by 36 units (21.42%) of fresh frozen plasma and 21 units (12.5%) platelets. Overall usage of blood components was found to be appropriate in 58.33% (98/111). Red blood cells were the most appropriately transfused (64.86 %) (72 units out of 111) blood product as compared to 42.85% of platelets (9/21) and 47.22% of FFP (17/36).Conclusions: Most frequently transfused blood components are red blood cells in pediatrics. Inappropriate transfusion of blood components is hinders the utility of this valuable resource, Thus it becomes necessary to conduct regular audit of blood component transfusion for optimum utilization.

Audit of fresh frozen plasma usage, prospective study: a report from department of immunohematology and transfusion medicine, government medical college Jammu, Jammu and Kashmir, India

Background: Fresh frozen plasma is commonly used in tertiary care hospitals. These are used to manage conditions such as coagulation derangements. Unnecessary use of fresh frozen plasma (FFP) is known to increase the risk of side effects in plasma transfusing patients like anaphylaxis, transfusion related acute lung injury (TRALI) and risk of transfusion transmitted infections etc. So judicious use of plasma is extremely important where its benefits outweigh its potential risks.Methods: Prospective observational study conducted over a period of six month. The following data were collected; provisional clinical diagnosis, indication of FFP’S, coagulation profile and gender of the patients. We evaluated all FFP transfusions, classified them as appropriate or inappropriate according to fresh frozen plasma transfusion guidelines of Directorate general of health services (DGHS).Results: A total of 808 FFP units were issued (474 units to males and 334 units to females) over a period of 6 months. Out of these, 15% (122 units) of  FFP’s were issued to intensive care unit (ICU) patients, 12.87% (104 units) to paediatrics ward, 12.25%  (99 units) to emergency ward which include patients with upper GI bleed and lower GI bleed , 6.8% (55 units) to obstetrics patients, 6.18% (50 units) to orthopaedics, 4.45% (36 units)  to road traffic accident patients, 4.20% (34 units) to Hepatic failure patients, 3.09% (25 units) to Cardiothoracic and vascular surgery (CTVS), 2.97% (24 units) to oncology patients, 2.47% (20 units) to snake bite patients, 1.23 % (10 units) to dengue patients, 1.11% (9 units)  to Haemophilia  patients, 27.38% units were issued to the patients were indication for FFP transfusion was not known.Conclusions: study showed that 66.44% were appropriate and 33.56% were inappropriate use of FFP’s in patients. This highlights the pitfalls in use of FFP among clinicians and for that matter there is need of awareness and understanding the transfusion medicine by clinicians.

Evaluation of coagulation factor activity and sterility of thawed fresh frozen plasma during storage up to 5 days at 4°C

@#Introduction: Fresh frozen plasma (FFP) is a blood component containing functional quantities of all coagulation factors stored at -18°C or below. FFP has to be thawed and transfused as soon as possible to prevent the loss of certain coagulation factor activities and to minimise microbial contamination. Materials and Methods: Thirty units of FFP kept at -20°C were thawed using a 37°C water bath and immediately sampled for baseline Factor II (FII), Factor VIII (FVIII) and fibrinogen activity levels and sterility testing. Each unit was then divided into two smaller bags (i.e. Bag I and Bag II) and kept at 4°C. At 6 hours and Day 3, representative samples were taken from Bag I for coagulation factor activity assays, while at Day 5 representative samples were taken from Bag II for coagulation factor activity assays and sterility testing. Results: FII activities at the four time points were 73.43%, 73.73%, 71% and 69.8%, respectively, while FVIII activities were 177.63%, 144.37%, 80.8% and 70.97%, respectively. Fibrinogen levels at the four time points were 3.24 g/L, 3.24 g/L, 3.21 g/L and 3.20 g/L, respectively. All samples were free from microbial contamination even at Day 5. Conclusion: The mean reduction in FII and fibrinogen activities on Day 5 was 5% and 1%, respectively. However, FVIII activity declined significantly by approximately 60% at Day 5. Despite these reductions, thawed plasma stored for up to 5 days at 4°C is still suitable for use as the coagulation factor activity levels still exceed the minimum release criteria recommended in quality assurance regulations.

Hereditary angioedema caused by C1-esterase inhibitor deficiency: a case report with literature-based analysis

Hereditary angioedema (HAE) caused by C1-esterase inhibitor deficiency is an autosomal-dominant disease caused by a mutation in the C1-inhibitor gene. It is a rare disease that is often worsened during pregnancy and childbirth. HAE, though uncommon but if untreated it may lead to maternal death.  The case report presents the successful management of a 24 years old, G2P1, with hereditary angioedema caused by C1-esterase inhibitor deficiency. This patient was managed with a multidisciplinary approach by an obstetrician, an immunologist, an anaesthesiologist and a pediatrician. She had an uneventful antenatal period, labor was induced. She had precipitate delivery and soon after delivery had a flare up of the disease. It was successfully managed with fresh frozen plasma and close observation.

Pattern Of Utilization Of Platlets And Fresh Frozen Plasma In Tertiary Care Hospital With Review Of Literature

Today’s transfusion medicine practice aims at providing the specific component of the blood required; this process of transfusing only the portion of the blood needed by the patient is called blood component therapy. Transfusion of whole blood has become a rarity now except in certain situations. Blood component therapy has become an integral part of treatment of many diseases in all fields of medicine.1 In many nations whole blood transfusion is reduced and instead whole blood is separated in to components. These components are then used separately, as indicated in according to patient’s need. It is important to study the pattern of utilization of blood and blood components in the hospital. It helps to find out trend of usage which decreased the cost of treatment, reduce wastage of blood components and improves the infrastructure for storage of blood components for future.

Effects of Methylene Blue, Psoralen and Riboflavin Treatments on Fibrinogen and other Coagulation Factors Level of Fresh Frozen Plasma

@#Introduction: Photochemical treatment is one of the pathogen inactivation method to treat plasma, part of a proactive approach used for blood and blood component safety. Three photochemical treatments that have been used were methylene blue, riboflavin and psoralen treatment. This study was done on Fresh Frozen Plasma (FFP) to evaluate the treatment effects of psoralen, methylene blue and riboflavin on coagulation factors level. Methods: FFP was collected from apheresis plasma units and kept at 22oC to 24oC. A sum of 90 apheresis plasma units and segments were used, separated from each bag and a part used as controls, placed in a -30oC freezer for storage, thawed, and coagulation proteins function was evaluated before and after treatment, at immediate, 30 days and 270 days storage. Results: Significant differences in fibrinogen and coagulation factor levels between before and after treatment with methylene blue, psoralen and riboflavin. However, most of the mean values in treated plasma were within reference ranges. Methylene blue treated FFP showed the lowest changes in fibrinogen and other coagulation factors level whilst riboflavin treated FFP demonstrated the highest changes in coagulation proteins concentrations especially for fibrinogen, FV, FVIII, FIX and FXII. However, FXIII showed the best recovery for all three photochemical methods with reduction level of 3% to 8% compared to pre-treatment. Storage time comparison of immediate, 30 days and 270 days was inconclusive. Conclusion: The coagulation proteins in psoralen treated FFP and MB-FFP were adequately preserved, where MB-FFP showed better preservation than other two photochemical treatments.

Effect of fresh frozen plasma on the in vitro activation of U937 monocytes: a potential role for the age of blood donors and their underlying cytokine profile

BACKGROUND: Fresh frozen plasma (FFP) administration may increase the risk of nosocomial infections in parallel with the development of immune modulation. This could be driven by soluble mediators, possibly influencing the in vitro activation of human U937 monocyte cells, in a manner dependent on the age of the donors. METHODS: FFP donors were stratified into groups of 19-30 years, 31-40 years or 41-50 years, and U937 cells were cultured with FFP (alone or plus lipopolysaccharide-LPS) for 24 h. Both in FFP and supernatants, TNF, IL-1ß, IL-6, and IL-10 levels were measured by ELISA. Additionally, CD11B, TLR2, and CASP3 gene expression were measured by qtPCR in U937 cells. Total phagocytic activity was also assayed. RESULTS: Elevated IL-10, but low TNF and IL-1ß levels were measured in FFP from individuals aged 19-40 years, whereas in individuals aged 41-50 years FFP were characterized by equalized TNF and IL-10 levels. Elevated IL-6 levels were found in all FFP samples, especially in those from the oldest individuals. FFP stimulation was associated with striking modifications in cytokine production in an age-dependent way. Exposure to FFP attenuates the response to LPS. TLR2 and CD11B expression were enhanced regardless of the age of plasma donors, although CASP3 expression was increased only when FFP from individuals aged 19-40 years were tested. Phagocytosis decreased after exposure to FFP regardless of donor age. CONCLUSION: Our results suggest that soluble mediators in FFP may modulate the functioning of monocytes. Interestingly, this effect appears to be partially influenced by the age of donors.

Changes of coagulation factors stored for different lengths of time after fresh frozen plasma melting / 军事医学

Objective To study the changes in coagulation factors stored for different lengths of time after fresh frozen plasma(FFP)thawing.Methods Thirty-two samples of thawed FFP were detected by an automated coagulation analyzer SYSMEX CA-1500 to observe the changes in coagulation function and coagulation factors stored for different lengths of time at 4℃.Results Activated partial thromboplastin time (APTT) was significantly prolonged 12 hours after thawing.However, no significant changes were observed in prothrombin time (PT), thrombin time (TT) or fibrinogen (FIB).Coagulation factors showed varying degrees of attenuation in 24 hours.FⅤ, FⅦ and FⅧ were attenuated significantly in 6 hours by 17.2%, 9.47% and 12.5%, respectively.FⅨ began to attenuate in 12 hours and reached, the lowest rate of 21.1%, while FⅧ had the highest attenuation rate (52.0%) and showed the lowest stability.Conclusion The activity of coagulation factors is decreased with time after FFP thawing ,so it should be transfused as soon as possible to ensure the curative effect and clinical application.

The changes of fresh frozen plasma parameters after its off from the cold chain / 中国输血杂志

Objective To discuss the changes of the quality of the fresh frozen plasma,which leaved refrigerator and it was out of the cold chain.Method The fresh frozen plasma was placed at the room temperature,in six different periods,that is 0,0.5,2,4 h,8,and 12 hours.The prothrombin time,activated partial thrombin live enzymes time,fibrinogen and factor FⅤ,factor FⅧ,antithrombin(AT) and protein C were tested on each point.Results In the fourth group and the fifth group,the FⅧ,AT,and protein C were statistically lower compared with the controls (P＜0.05).But there were no obvious changes of APTT,PT,INR,Fbg and FⅤwhen placed at room temperature for 12 hours.Conclusion After the fresh frozen plasma placed at room temperature for more than 8 hours,the FⅧ ∶ C,AT and protein C were significantly lower compared with the control group.But they have no obvious changes of APTT,PT,INR,Fbg and F Ⅴ when placed at room temperature for 12 hours.

The In vitro Effects on Platelet Functions and Coagulation of Different Prime Solutions Used in Cardiopulmonary by Pass.

Purpose: To investigate the in vitro effect of human albumin (HA) and fresh frozen plasma (FFP) added to prime solution on platelet functions and coagulation in patients undergoing cardiopulmonary bypass (CPB) surgery. Methods: Sixty consecutive patients receiving elective cardiopulmonary bypass with open heart surgery were enrolled in the study. Patients were divided into three equal groups. Group 1: with 2 units of fresh frozen plasma added to prime solution. Group 2: With 100 cc 25% human albumins added to prime solution. Group 3: (control group) with no FFP or HA added to prime solution. PFA-100 platelet function analyzer and platelet aggregation tests were investigated pre-induction, during and after CPB and on the 1st day postoperatively. Results: Postoperative drainage was significantly higher in groups 2 and 3 compared to Group 1 (p<0.01). The compromise in platelet functions in groups 1 and 2 improved, while in Group 3 preoperative values were not attained at the end of the 1st day postoperatively. There was a significant difference between groups 2 and 3 in terms of erythrocyte suspension (ES) used in intensive care (p<0.01). Greater hemorrhage occurred in the postoperative period in Group 3 and more ES was used. In addition, lengths of stay in intensive care differed significantly between groups 2 and 3 (p<0.01). Conclusion: FFP used in CPB causes reduced drainage in the postoperative period and necessitates less use of blood and blood products.

Successful treatment of ligneous conjunctivitis with topical fresh frozen plasma in an infant / Sucesso do tratamento da conjuntivite lenhosa com uso tópico de plasma fresco congelado em uma criança

ABSTRACTA 6-month-old female infant presented to our clinic with bilateral eyelid swelling, yellowish-white membranes under both lids, and mucoid ocular discharge. Her aunt had similar ocular problems that were undiagnosed. The conjunctival membranes were excised and histopathological investigation of these membranes showed ligneous conjunctivitis. Further, laboratory examination revealed plasminogen deficiency. A good response was observed to topical fresh frozen plasma (FFP) treatment without systemic therapy, and the membranes did not recur during the treatment. Topical FFP treatment may facilitate rapid rehabilitation and prevent recurrence in patients with ligneous conjunctivitis.

RESUMOUma criança feminina com seis meses de idade se apresentou à nossa clínica com edema palpebral bilateral, membranas brancas amareladas sob as pálpebras de ambos os olhos e descarga mucosa. Sua tia já havia apresentado problemas oculares semelhantes que não foram diagnosticados. As membranas conjuntivais foram excisadas e a investigação histopatológica das membranas demonstraram conjuntivite lenhosa. O diagnóstico de deficiência de plasminogênio foi obtido a partir de um exame laboratorial. Tratamento tópico com plasma fresco congelado (FFP) sem qualquer terapia sistêmica mostrou boa resposta. Não foram observadas recorrências das membranas. O tratamento tópico com FFP pode ajudar a reabilitação rápida e prevenir a recorrência em pacientes com conjuntivite lenhosa.

Effectiveness of early goal-directed fluid therapy with fresh frozen plasma for severe acute pancre-atitis / 临床外科杂志

Objective To evaluate the effect of early goal-directed fluid therapy with fresh frozen plasma in severe acute pancreatitis(SAP). Methods From January 2010 to June 2014,79 SAP patients were enrolled according to the continuous sampling method. All the patients were randomly divided into a control group who accept the traditional fluid therapy(group A),an experimental group 1 who accept early goal-directed fluid therapy(group B),and an experimental group 2 who accept the early goal-directed fluid therapy with fresh frozen plasma(group C). There were no significant differences of general conditions a-mong groups. The differences of ICU admission,mortality and occurrence rate of abdominal compartment syndrome(ACS)and MODS were compared among groups. Results Compared with group A,group B and C have a shorter length of ICU admission,a lower mortality and a lower occurrence rate of ACS and MODS (P < 0. 05). Compared with group B,group C have a shorter length of ICU admission,a lower mortality and a lower occurrence rate of ACS and MODS(P < 0. 05). Conclusion The method of early goal-direct-ed fluid therapy with fresh frozen plasma will contribute to shorten the length of ICU admission and reduce mortality and occurrence rate of ACS and MODS for patients with SAP.

Extracorporeal Liver Support with Less Fresh Frozen Plasma for Treatment of Acute-on-chronic Liver Failure / 华中科技大学学报(医学版)

Objective To observe the efficacy of extracorporeal liver support by using less fresh frozen plasma in the treat‐ment of acute‐on‐chronic liver failure.Methods A total of 45 patients with acute‐on‐chronic liver failure were divided into ob‐servation group[plasma perfusion(PP) with a small amount of plasma+ plasma exchange(PE)] ,control group 1(PE) ,control group 2(PP+PE)in terms of the amount of plasma used on the day of treatment. All the patients received artificial liver treatnts 62 times totally.Results The clinical symptoms were improved in the three groups after treatments.There were significant differences in the decrease of alanine transaminase (ALT) ,aspartate transaminase(AST) and direct bilirubin(DBil)rather than the decrease of total bilirubin(TBil)and blood ammonia among the groups.No significant difference was noted in the liver and kidney function among the three groups. The improvement of the coagulation function was poor in the observation group when compared with the control group 1 and control group 2 and there were significant differences.Conclusion During the short sup‐ply of the plasma ,plasma perfusion combined with small amount of plasma can be considered to be used in artificial liver treat‐ments ,which can effectively decrease the level of TBil ,relieve symptoms and decrease the occurrence of complications.