Blood Transfusion in Covid-19 Patients: One Year Survey

Introduction: Due to the COVID-19 outbreak, many chronic patients and elective surgical procedures have been postponed to create spaces for the hospitalization of COVID-19 patients, raising issues related to this change. The objective of this study is to assess the effect of the COVID-19 pandemic on the demand for blood products transfusion. Materials ant methods: The study presents the results of a retrospective study of blood transfusions in COVID-19 patients admitted to the Constanta County Emergency Clinical Hospital. The period of study was January-December 2021. We compared the transfusion requirement for each type of blood component in COVID 19 patients versus patients with non-COVID pathology. Results and discussions: During 2021, we transfused 282 COVID-19 patients;150 patients had only Covid pneumonia (of which 19 patients with severe forms needed intensive care in ICU-Covid), and 132 patients had various co-morbidities. The maximum blood requests was registered in the period February - April 2021, with a peak of 63 patients in April 2021. The main co-morbidities in patients with Covid 19 were: severe anemia in patients with malignant hemopathies. Anemia at admission in patients with Covid pneumonia is reported in more than 40% of patients. Moderate anemia (Hb <11 g/dL) is considered as an independent risk factor for the severe course of COVID-19 infection and mortality in these patients. The transfusion requirement in these patients was greater than 1.43 RBC (units/patient), 0.81 Plasma units/patient, 0.40 Platelets concentrate units + single donor platelet concentrate units/patient, in accordance with the associated pathology. Conclusion(s): The most requested product was packed red blood cells, the correction of anaemia being an important factor in preventing the severe course of the disease. The platelet requirement was 0.15 units/patient, thrombocytopenia being present in patients with severe evolution of the infection (hospitalized in ICU-COVID). The most requested blood groups were O+ and A+. COVID-19 transfusion data will help plan and prepare for the use of blood resources during the pandemic.Copyright © 2022 Sevigean Ali et al., published by Sciendo.

Clinical Profile of Congenital Factor XIII Deficiency in Children.

OBJECTIVES: Congenital Factor 13 Deficiency (FXIIID) is a rare bleeding disorder (RBD) of autosomal recessive inheritance, with an incidence of 1 in 3-5 million. The clinical symptomatology, diagnosis, and management of FXIIID are described. METHODS: A retrospective chart review of children with FXIIID was performed from January 2000 through October 2021 at a tertiary care center in Southern India. The diagnosis was performed by the Urea clot solubility test (UCST) and Factor XIII antigen assay. RESULTS: Twenty children (representing 16 families) were included. Male: Female ratio was 1.5:1. The median age of symptom onset was 6 mo, and the median age of diagnosis was 1 y, demonstrating a delay in diagnosis. Consanguinity was present in 15 (75%) with 4 children having affected siblings. Clinical symptomatology ranged from mucosal bleeds to intracranial bleeds and hemarthrosis, with many children having a history of prolonged umbilical bleeding in their neonatal period. Fourteen children were on cryoprecipitate prophylaxis. Four children had breakthrough bleeds due to irregular prophylaxis, including one intracranial bleed due to a delay in cryoprecipitate prophylaxis during the covid pandemic. CONCLUSIONS: Congenital FXIIID presents with a wide range of bleeding manifestations. The high prevalence of consanguinity in Southern India can be a cause of FXIIID's high prevalence in this region. There is a propensity for intracranial bleeding with a significant number having this at first presentation. Regular prophylaxis is required and feasible to prevent potentially fatal bleeds.

Management of Acquired von Willebrand Syndrome During Prolonged VV-ECMO

Acquired von Willebrand syndrome (AVWS) contributes to bleeding during extracorporeal membrane oxygenation (ECMO) support. Although it is recognized that AVWS rapidly resolves after ECMO decannulation, this approach may often be clinically unsuitable. In such cases, optimal AVWS management during ECMO support is not well established. We report our approach to managing AVWS in a patient on veno-venous (VV) ECMO for 59 days. A 19-year-old male developed hypoxemic respiratory failure from SARS-CoV-2 pneumonia. Following intubation, he progressed to VV-ECMO support for refractory hypoxemia and was started on bivalirudin for systemic anticoagulation. Two days later, he developed refractory gastrointestinal and oro-nasopharyngeal bleeding despite blood product transfusions and discontinuing bivalirudin. He was started on pantoprazole along with infusions of octreotide and aminocaproic acid. Upper endoscopy on ECMO day 5 revealed an ulcerative bleeding vessel in the duodenum that was clipped. Recurrent mucosal bleeding precluded resumption of systemic anticoagulation. On ECMO day 23, AVWS was diagnosed based on elevated von Willebrand factor (VWF) activity (207%, normal 55-189%) and antigen (234%, normal 50-210%) levels with abnormally low VWF high-molecular-weight multimers. Factor VIII complex was administered twice over the following week. Between doses, the ECMO circuit was exchanged to empirically mitigate suspected shear-related VWF consumption from the fibrin burden, and a repeat endoscopy controlled additional intestinal bleeding with local hemostatic agents. He received 36 units of red blood cells, 2 units of platelets, 2 units of plasma, and 7 pooled units of cryoprecipitate over 31 days leading into these combined interventions. In the 28 days afterwards, he received 3 units of red blood cells, 3.5 pooled units of cryoprecipitate, and no additional platelets or plasma. Our patient was maintained off systemic anticoagulation for 54 of 59 days of VV-ECMO support without any thrombotic complications occurring. With no subsequent clinical evidence of bleeding, repeat VWF testing was done two months post-decannulation and showed near-normal VWF activity (54%) and normal multimer distribution. Our patient rehabilitated well without any neurologic deficits and on discharge was requiring supplemental oxygen with sleep and strenuous activity. Avoiding systemic anticoagulation, repleting VWF, maintaining circuit integrity, and providing local hemostasis, when possible, may be a safe and effective management strategy of AVWS on ECMO support when decannulation is not a viable option.

Rationale for supporting stepwise access to safe plasma proteins through local production in low- and middle-income countries: A commentary of an international workshop.

This document provides a commentary and further elaboration on the conclusions reached during a recent international workshop on plasma protein therapies organized by the Working Party for Global Safety of the International Society of Blood Transfusion (ISBT). The workshop addressed the profound deficiency in access to safe plasma protein therapies that persists in low- and middle-income countries (LMICs). We provide additional factual economic and technological information that highlights why local production of small-scale virus-inactivated concentrates of clotting factors and immune globulins from domestic recovered plasma through stepwise introduction of available validated technologies is a pragmatic approach to gradually improve the care of patients with bleeding disorders and immune deficiencies in LMIC while supporting progress toward fractionation of plasma. This strategy is in line with a recent WHO guidance. We stress that the active involvement of international blood donor and blood transfusion organizations, patient organizations, governments and industry will be essential in supporting stepwise and sustainable improvements in access to safe, effective, and quality assured plasma protein therapies.

A Comparative Analysis of the Blood Products used in the Emergency Room and other Clinics with the Pre-pandemic Period

Aim: In this study, we evaluated the blood transfusion statistics by determining the frequency of blood component transfusions by year and the total number of transfusions administered in emergency departments (EDs) and all inpatient clinics across Turkey, to provide a foresight of the future and to guide planning. Method(s): The study was conducted retrospectively, covering the period between January 1, 2016, and January 1, 2022. The numerical data of the blood transfusions applied in the 2nd and 3rd level public hospitals in Turkey were collected as the number of units, and the data were used by obtaining the necessary permissions from the Ministry of Health. The most frequently used blood components in EDsand inpatient clinics in our country were examined. The total number of transfusions in EDs and all inpatient clinics was calculated, and the frequency changes over time were investigated. In the study, the 4-year period of 2016-2019 was specified as the prepandemic period. The 2-year data for 2020 and 2021 are also stated as the pandemic period. The mean values of the data belonging to both periods were taken, and their significance was evaluated with Fisher's exact test. Blood transfusion statistics for each year were recorded on the tabulation software, and the frequency changes were calculated using the statistical formulas of the tabulation software. Patient consent was waived because of the study. Result(s): The most common types of blood components transfused in Turkey were packed red blood cell (PRBC), fresh frozen plasma (FFP), platelet concentrate, whole blood, and cryoprecipitate. When the blood component transfusion rates in the EDs were evaluated, the most frequently transfused blood component was found to be PRBC, followed by FFP (64.4% and 29.8%, respectively). Platelet concentrate, cryoprecipitate, and whole blood transfusion rates were found to be 5.5%, 0.17%, and 0.13%, respectively. 6.6% of all blood transfusions were administered in EDs. The use of all blood and blood products, except PRBC, has decreased in the ED. In all departments, there was a decrease in the use of platelets and whole blood and an increase in the use of cryoprecipitate. Conclusion(s): Since the current study shows blood and blood product replacement and includes a broad comparison with the pandemic and pre-pandemic periods, it can guide the blood replacement strategies of the ED and all departments. Copyright © 2022 by The Medical Bulletin of Istanbul Haseki Training and Research Hospital The Medical Bulletin of Haseki published by Galenos Yayinevi.

Successful cesarean section in a woman with coronavirus and scleroderma: a case report

Background: The incidence of adverse perinatal outcomes including increased risk of miscarriage, preeclampsia, preterm birth and stillbirth is higher in pregnant women with coronavirus. Pregnant women who are infected with the coronavirus have placentas that are abnormal compared to the placentas of healthy women. Examples of these adverse effects have been observed before and include reduced fetal growth, pre-eclampsia, premature birth and stillbirth. Scleroderma is an uncommon connective tissue disease and its most obvious manifestation is skin fibrosis. Patients may also have involvement of visceral organs, as a result, their digestive system, kidney and heart are affected. Scleroderma also exacerbates miscarriage, fetal growth retardation, intrauterine fetal death, and preterm delivery. Pregnant women with these problems need special measures, so this study was performed to report a successful cesarean section in a woman with coronavirus and scleroderma. Case presentation: The patient was a 31-year-old pregnant woman with a gestational age of 29 weeks who presented to Sanandaj Besat Hospital in November 2021 with symptoms of shortness of breath and dyspnea. HRCT-positive, PCR-positive, bilateral pleural effusion, and pulmonary dilatation corona were diagnosed. Due to 3 liters of vaginal bleeding and diagnosis of Decollement 60% and severe preeclampsia underwent emergency cesarean section. The live baby was born weighing 1300 g with Apgar 7. During surgery, he received 3 units of FFB and 3 units of Cryoprecipitate. Microcalcifications and fibrin thrombi were reported in the pathology of intermittent nodules. The diagnosis and treatment of this patient has significant points that are mentioned below. Conclusion(s): Complications of pregnancy and childbirth in pregnant women infected with Corona virus include an increase in premature birth and an increase in the rate of cesarean section. Pregnancy in women with scleroderma at the right time and careful delivery monitoring will increase the probability of successful pregnancy outcome and all patients need counseling. Copyright © 2022 Zare et al. Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.

ISTH Abstract

The proceedings contain 1875 papers. The topics discussed include: Dynamic changes in activated protein C during major hemorrhage protocol and associated fibrinolytic response;changes in fibrinolysis during extracorporeal membrane oxygenation in critically ill adult patients;national incidence of bleeding-related hospitalizations and mortality by anatomical and ISTH site classification in England 2014-2019;functional characterization of coagulopathy in isolated traumatic brain injury;synergy of red blood cells and tranexamic acid in the inhibition of fibrinolysis;modest performance of available risk prediction models when used to predict hemorrhage in patients with chronic liver disease;thrombosis and major bleeding in patients with severe COVID-19 supported by extracorporeal membrane oxygenation (ECMO) - multicenter observational study in UK;risk factors for bleeding after recent medical hospitalization: The Medical Inpatient Thrombosis and Hemostasis Study (MITH);cryoprecipitate transfusion in trauma patients attenuates hyperfibrinolysis and restores normal clot structure and strength;results from a sub-study of the FEISTY trial;and factor XIII levels correlate with fibrinogen concentrations in patients with venous malformations and chronic disseminated intravascular coagulopathy.

Severe progression of autoimmune hepatitis in a young COVID-19 adult patient: A case report

Rationale: The impact of COVID-19 in patients with autoimmune liver disease treated with immunosuppressive therapy has not been described so far. This case report describes the clinical course of a patient with autoimmune hepatitis (AIH) who developed COVID-19 and the features of cytokine syndrome leading to its deterioration in our intensive care unit. Patient's Concern: A 28-year-old male presented with generalized anasarca for two weeks and chronic liver disease for 8 months. Diagnosis: AIH and Covid-19 with features of cytokine storm syndrome. Interventions: Intravenous furosemide, mannitol, syrup lactulose, steroids (prednisolone 40 mg), azathioprine 1 mg/kg body weight, rifaximin, vitamin K, and blood products. Outcomes: The patient had hepatic encephalopathy and AIH and died on the 10th day after admission despite ventilatory support, sustained low-efficiency hemodialysis, and resuscition. Lessons: The dramatic release of cytokines and the inflammatory-immune responses not only alter the pathophysiology but also affects the onset and severity of disease progression in patients with AIH.

Experience of managing abnormally invasive placenta over an eight-year period in a UK centre

Introduction: Abnormally invasive placenta (AIP) has a significant risk of mortality and morbidity. International recommendations support management in specialist centres [1]. North Bristol Trust (NBT) is a large obstetric unit providing regional management since 2014 this service evaluation shows changing management over an eight year period, in line with local experience and published recommendations. Methods: Retrospective database analysis (with local audit approval) of AIP cases at NBT 2014–2021 were performed. Antenatal and perioperative management was reviewed via electronic patient records. Results: Sixty-one patients presented with AIP. Mean maternal age was 35.2 years and mean gestation at delivery was 34 + 2 weeks. Average paritywas 2.5 (range 0–7). No maternal deathswere recorded. Sixty women were identified pre-operatively and one unexpected intraoperatively. Postoperatively 60 cases were managed on our level- 2 obstetric critical care unit, one required level-3 critical care. Anaesthetic technique has evolved including: general anaesthetic (GA) plus low-dose spinal 36%;GA alone 36%;combined spinalepidural (CSE) 23%;CSE converted to GA 3%;epidurals 1.5%;and spinals 1.5%. Forty-five cases (72%) delivered via elective CS and 28% required urgent CS. Invasive arterial blood pressure monitoring was used in 84%. The hysterectomy rate was 67% (59% elective vs 100% urgent cases). Of 16 cases in the hybrid theatre, only four internal iliac artery balloons (IAB) were inflated (25%), for a mean of 62 min. One complication occurred, a femoral artery thrombus requiring embolectomy at the end of case. Mean estimated blood loss for all cases was 3.5 L (range 0.5–14 L). No statistical differencewas noted in blood loss with or without IAB (3.6 vs 3.1 L), nor planned vs urgent surgery. Intraoperative cell salvagewas used 97%;mean volume of cell salvaged blood (CSB) reinfused was 0.7 L (range 0–3.3 L). Packed red blood cells were transfused in 44%, fresh frozen plasma in 34%, platelets in 18%, and cryoprecipitate in 44%. ROTEM was utilised in 56% of cases and TXA given in 82%. Discussion: IAB have not been used in AIP management for 2 years in our institution. This does not appear to affect blood loss, transfusion rate, or requirement for critical care. Our GA rate has remained high compared to other centres [2], due to hybrid theatre ergonomics and Covid-19 PPE requirements. Use of autologous blood transfusion via cell salvage with rapid processing is central to our care.

Blood beyond borders: Strategy to ensure blood availability during COVID-19 pandemic

Background: It's more than 2 years since the strike of a COVID-19 pandemic caused by severe acute respiratory syndrome Coronavirus 2. It had infected nearly 400 million populations globally and affected several important sectors worldwide such as the economy, social and healthcare services. To date, Malaysia recorded more than 3 million confirmed cases of COVID-19. The first nationwide Movement Control Order (MCO) started on 18th March 2020 then followed by multiple series of targeted MCOs on several states with a high surge up of cases. The National Blood Center (NBC) and State Blood Transfusion Services (SBTS) experienced significant reduction of blood collection, the shortage of blood availability and supply. The total blood collection in the year 2020 was 655,069 units, showing a 12% reduction compared with the year 2019. Blood supply management requires an integrated and holistic planning from all stakeholders to ensure the judicious use of blood and blood components in the normal situations, pandemics, crises, or during blood shortages. Aims: This study was to determine the characteristic of blood components mobilized during the COVID-19 Pandemic and to assess the coordination of inter-regional blood availability, supply, and transportation between the blood inventory of NBC, SBTS, or Hospital Blood Bank. Methods: A retrospective study was conducted from 18th March 2020 until 18th August 2021 where multiple series of MCOs were instated. Data from the blood inventory during the 18 months were analysed. All data were retrieved from Blood Bank Information System from NBC and SBTS. Results: A total of 17,144 units of blood components have been mobilized and distributed, comprised of 15,591 units of red cell, 1107 units of platelet concentrates, 299 units of Fresh Frozen Plasma, 125 units of Cryoprecipitate and 22 units of Convalescent Plasma. Overall, there were 20 blood collection centers comprised of NBC, state hospitals, and major hospitals involve as blood providers to the (Table Presented) several affected blood collection centers, beyond the state border. The states with major contributions for blood component mobilization were Kuala Lumpur, Sarawak and Johor while the collection centres that provided the most blood were National Blood Centre (4542 bags), Sultanah Aminah Hospital in Johor (1714 bags) and Malacca Hospital (1630 bags). The blood products have been shipped via hospitals' land transportation, air transportation by courier service and collaborative mercy flight by the Malaysian Air Force to the Malaysia East. The validated blood packaging and transportation procedure have been implemented to preserve the blood cold chain during blood mobilization through the air or by land transportation. Summary/Conclusions: The challenges during a pandemic are to deliver adequate, safe, and quality blood to the patient who needs blood transfusion for life-saving. Dynamic inter-state blood availability, supply and mobilization are essential to overcome the shortfall during a pandemic. Effective communication among NBC, SBTS, interagencies, governmental organizations, and postal service companies were among the great factors of success in transporting blood beyond borders to ensure blood availability. The plan was designed in response to the threat to the national blood supply from any untoward events that lead to blood shortages in a state, regional, or nationwide in Malaysia.

Effect of SARS-CoV-2 pandemic in the routine of a hospital-based blood bank

Background: Since the beginning of SARS-CoV-2 pandemic, several restrictions on mass gatherings were necessary to be implemented due to the pan-lockdown, so the blood supply chain was considerably affected. Many issues were raised concerning maintaining an adequate and safe blood supply according to the demand and with minimum discard percentage. Aims: The study investigated the impact of the pandemic in blood donation and transfusion process and also the discard rate. Methods: We studied a period before (May 2018-February 2020) and after the beginning of lockdown (March 2020-December 2021), where several strategies had to be implemented in our hospital, like physical distancing measures, postponement of elective surgeries and priority in urgency medical and surgery admissions. In relation to the blood bank, our goal was to maintain a buffer stock of blood to a 2-week level, collecting blood donations only at the blood center and cancelling mobile blood donations. The blood donor recruitment was basically performed by phone, e-mail, WhatsApp and blood donations were scheduled in such a way to prevent any risk of people's agglomeration. The following collection data were analysed: number of blood donations, rates of repeated blood donors and mobile blood donations, number of red blood cells (RBC), plasma, platelets (random donor platelet-RDP and apheresis) and cryoprecipitate transfusions, discard rates by expiration or due to reactive serological screening. Results: Surprisingly, we noticed a 14% increase in blood donations after the beginning of lockdown (12,977 donations before pandemic and 14,793 after), with an important decrease for mobile blood donations (from 29.6% to 14.3%;p < 0.05). However, in the period before pandemic, there were 84.1% repeated blood donor whereas after the beginning of pandemic it declined to 82% (p < 0.05). No changes were observed in the percentages of reactive serological screenings in both periods: 1.32% and 1.42%, respectively (p = 0.47). As for discard due to expiration, we observed a decrease for both apheresis and RDP with 3.75% ± 1.62% for apheresis before and after pandemic, respectively (p < 0.05), 0.78% ± 0.17% for RDP before and after pandemic (p = 0.001). For RBC, there were no statistical difference in both periods;306/10,972 (2.78%) ± 378/12,563 (3.00%) units (p = 0.31). The transfusional demand in the studied periods demonstrated an increase from 18,672 to 22,007 (17.86%) transfusions, especially because of an increase for plasma transfusions requests: from 1727 to 2907 units (p < 0.05) due to patients undergoing therapeutic plasma exchange (1804 or 62% of units), Covid-19 convalescent plasma (381 or 13.1%), and 722 (24.8%) units, due to other causes. We also had a significantly increasing demand for platelets (from 5420 to 6091;p < 0.05) and for RBC (from 11,047 to 12,567, p < 0.05) units, and a drop for cryoprecipitate (from 478 to 442;p < 0.05) doses. Summary/Conclusions: Besides all global restrictive measures adopted related to Covid-19 pandemic, we could maintain our inventory well enough to attend our transfusional demand, including when an increase was required, since we were a reference center for severe Covid-19 cases. Finally, in times of pandemic, it is crucial to maintain a buffer stock of blood besides a pro-active management through a strict surveillance between the recruitment team and coordinator staff, according to daily transfusional demand.

Approach to management of cryoprecipitate inventory during pandemic-related shortages

Background: A surprising and disturbing feature of blood shortages in the United States during the COVID-19 pandemic is that they include Cryoprecipitate, a component that was not historically affected by seasonal shortages. Our blood suppliers provide Cryoprecipitate primarily as 5-unit pools. A few individual whole blood-derived units of Cryoprecipitate are also provided for use for infants and young children. The adult dose of Cryoprecipitate, standardized many years ago, has been two pools (10 units). In an average-sized adult, this dose is expected to increase plasma fibrinogen by 50-100 mg/dl. Over the 10-year period 2011- 2020, the number of single units transfused at our 1000 bed tertiary care hospital remained small and relatively stable, but the number of transfused pools increased approximately 60%, from a monthly average of 322-522. During the pandemic, Cryoprecipitate usage at our hospital remained high, possibly because high-use surgeries, such as urgent cardiovascular and liver transplant procedures, were not restricted. In the face of donor- and manufacturing-related shortages, our blood bank has been challenged to maintain an adequate inventory to support these services. Aims: To develop and implement a plan for ensuring sufficient availability of Cryoprecipitate units to meet our patients' needs. Methods: As with other blood components, the shortage of Cryoprecipitate was initially managed through prospective review and modification (if appropriate) of orders by the Transfusion Medicine resident physician, and regular communications with the blood suppliers regarding inventory requirements. Additional steps for Cryoprecipitate were: re-evaluating the standard dose of Cryoprecipitate, and exploring alternatives to the use of Cryoprecipitate pools. Results: Quality control data from our blood suppliers provided evidence that the fibrinogen content of Cryoprecipitate currently averages 524 mg per unit, more than twice the value of 250 mg per unit that is generally used for dosing calculations. These data justified halving the standard adult dose to 1 pool. An explanatory document was distributed to the clinical services, with comparisons of plasma fibrinogen increments expected with two pools versus one pool. An update to the electronic ordering system is in process, to change the default Cryoprecipitate order for adults from two pools to one pool. We increased the stock of single Cryoprecipitate units, whenever these were available, to build a buffer for adult use in case of ongoing shortage. We collaborated with the hospital pharmacy to maintain a reserve of purified fibrinogen concentrate, and develop a dosing and administration protocol for off-label use of this product. So far, there has not been an occasion to use either alternative. The efforts above have been supplemented with frequent, structured communication with the clinical services and hospital leaders regarding inventory levels of blood components, and the measures taken and requested to safeguard this precious resource. Summary/Conclusions: Meeting the challenge of extreme and prolonged blood shortages requires a multi-pronged approach that may include questioning assumptions, considering alternatives, and improving inter-disciplinary communications.

Safe and effective administration of multiple recombinant factors on VA-ECMO via post-oxygenator pigtail during acute massive pulmonary hemorrhage

Introduction: Massive bleeding on extracorporeal membrane oxygenation (ECMO) is associated with multiple coagulation defects, including depletion of coagulation factors and development of acquired von Willebrand syndrome (AVWS). The use of recombinant factors, in particular recombinant activated factor VII (rFVIIa, Novoseven), to treat severe refractory hemorrhage in ECMO has been described. However, the use of multiple recombinant factors has been avoided in large part due to concern for circuit complications and thrombosis. Here, we describe the safe and effective administration of rFVIIa and recombinant von Willebrand factor complex (vWF/ FVIII, Humate-P) via post-oxygenator pigtail catheter on VA-ECMO for the treatment of massive pulmonary hemorrhage. Case Description: A 21-month-old (13.4 kg) girl with a recent history of COVID-19 infection presented to an outside hospital with parainfluenza bronchiolitis resulting in acute refractory hypoxemic respiratory failure (oxygenation index 58), refractory septic shock, and myocardial dysfunction. She was cannulated to VA-ECMO and subsequently diagnosed with necrotizing pneumonia from Pseudomonas and herpes simplex infections. Her course was complicated by a large left-sided pneumatocele and bronchopleural fistula requiring multiple chest tubes. She also had right mainstem bronchus obstruction from necrotic airway debris and complete right lung atelectasis. She was noted to have prolonged episodes of mucosal and cutaneous bleeding (oropharynx, chest tube insertion sites, peripheral IV insertion sites) associated with absent high molecular weight von Willebrand multimers consistent with AVWS. Tranexamic acid infusion was initiated and bivalirudin anticoagulation was discontinued. VA-ECMO flows were escalated to 140-160 ml/kg/min to maintain circuit integrity and meet high patient metabolic demand in the absence of anticoagulation. On ECMO day 26, she underwent bronchoscopy to clear necrotic debris from her airway to assist with lung recruitment. The procedure was notable for mucosal bleeding requiring topical epinephrine and rFVIIa. Post-procedure, she developed acute hemorrhage from her right mainstem bronchus, resulting in significant hemothorax (estimated 950 ml) with mediastinal shift, increased venous pressures, desaturation and decreased ECMO blood flow rate, necessitating massive transfusion of 2,050 ml (150 ml/kg) of packed red blood cells, platelets, plasma and cryoprecipitate. An airway blocker was placed in the mid-trachea to control bleeding. In addition to transfusion of appropriate blood products and continuation of tranexamic acid infusion, she was given both rFVIIa (100mcg/kg) and vWF-FVIII (70 units vWF/kg loading dose on the day of hemorrhage, followed by 40 units vWF/kg every 12 hours for 3 additional doses). Both products were administered over 10 minutes through a post-oxygenator pigtail to allow the product to circulate throughout the patient prior to entering the ECMO circuit. The circuit was closely monitored during administration and no changes to circuit integrity were noted in the subsequent hours while hemostasis was achieved. The ECMO circuit remained without thrombosis for 9 days after the bleeding event. Discussion: Balancing anticoagulation and hemostasis is a central challenge in maintaining ECMO support, especially given the prevalence of acquired coagulopathies such as AVWS. For our patient, AVWS contributed to mucosal bleeding necessitating cessation of anticoagulation and utilization of a high ECMO blood flow strategy to minimize circuit clot burden. This was further complicated by absent native lung function and minimal myocardial function, resulting in complete dependence on ECMO. An acute massive pulmonary hemorrhage was treated with multiple recombinant factors (rFVIIa and vWF/FVIII), that are often avoided on ECMO. To minimize clotting risk to the circuit and to maximize transit of these factors to our patient, we added a post-oxygenator pigtail for administration. While this approach was the result of extreme circumstances, th use of a post-oxygenator pigtail for administration of recombinant factors may represent a viable strategy for refractory hemorrhage while on ECMO.

A Case Series of Acquired Factor Inhibitor Following Sars-COV2-Vaccination

[Formula presented] : Autoimmune disorders post viral illness and post vaccination are some of the known complications. COVID 19 is known to cause complement dysregulation and possible reactivation of known autoimmune disorders. New data are emerging on the possible autoimmune reactivation and cases of de novo ITP and vaccine induced immune thrombotic thrombocytopenia are reported. We are presenting two cases of factor deficiencies due to acquired factor inhibitor in patients who had no apparent cause but who had recently received the Moderna COVID-19 vaccine. We hypothesize that just like native COVID 19 infection can be associated with development of acquired inhibitors, so can the COVID 19 vaccination. Cases:An 83 year old Caucasian Male with history of Arrhythmia, Coronary artery disease, H/O heart artery stent and hypertension, had received the second dose of Moderna covid vaccine one month prior to presentation. Presented with new onset headache and noted to have large right sub insular acute intra parenchymal hemorrhage. He was managed conservatively, and this bleed was attributed to his h/o hypertension. Post treatment was discharged to rehab, where he had worsening neurological status and repeat imaging showed slightly expanded size of a parenchymal hemorrhage centered in the right sub insular region and increasing surrounding edema with new tiny right frontal cortical parenchymal hemorrhage. Initial admission labs reveled a prolonged APTT of 70 and PT normal after his readmission from rehab, his PTT remained elevated to 70 and PT became prolonged to 17. PT. APTT mixing studies demonstrated only partial correction of PT and no correction of APTT. All factor levels were normal except Factor IX low at 8% and Factor XI low at 2.4%. Bethesda titer was positive at 11 BU to specific to factor IX. Further work up demonstrated no oncologic or rheumatological etiology for the coagulation inhibitor. The only possible etiology had been his age and patient had received SARS COV2 moderna vaccine. The patient was treated with rituximab, prednisone and cyclophosphamide with improvement in the inhibitor titer. A 77-year-old Caucasian female with history of hypertension, obesity, steroid induced psychosis, and Moderna Covid-19 vaccination four months prior. She presented to the hospital with epigastric pain, hematochezia, hematuria, epistaxis, and significant bruising without trauma. Laboratory studies showed hemoglobin drop from baseline of 13.8 to 11.8 to 8.2 g/dL. Significant coagulopathy, with elevated PT 130 sec, PTT 108.7. All factor levels were normal except Factor X levels low at <2%. Mixing study of the prolonged prothrombin time mainly demonstrates an inhibitory pattern, with incomplete correction. (1:1 mix PT 22.7 sec;normal 9.4-12.5 sec). Bethesda titers could not be demonstrated. No neoplastic or rheumatologic etiology of her inhibitor was found. She was given cryoprecipitate and vitamin K with no improvement in her coagulation studies. She received factor X infusion for 3 doses 2500 units during day 3 of her hospitalization. She was treated with prednisone and weekly rituximab with complete normalization of her Factor X levels at 132%. Discussion:Acquired inhibitors to coagulation factors are rare disorders that can be related to infections, malignancy, autoimmune conditions, and pregnancy and sometimes seen spontaneously in older individuals. There have been several individual case reports of acquired coagulation inhibitors with COVID 19 infection including inhibitors to III, Factor XI, Factor V and Thrombin. To our knowledge there have been no acquired inhibitors described to the COVID vaccine however, it would seem conceptually possible. Acquired factor deficiencies should be suspected when a patient presents with no previous history of bleeding, use of anticoagulation and unexplained prolonged prothrombin, and activated partial thromboplastin time. It is vital to have high index of suspicious for prompt recognition as it can have a high mortality. Treatment would involve resuscitation and eradic ting the inhibitor with immunosuppression. It would be interesting to follow this patient long term for any relapse. In the above mentioned cases, no other etiologies could be attributed to the abnormal coagulopathy and could be related to the SARS-COV-2 vaccine. Disclosures: No relevant conflicts of interest to declare.