Baby Blues: A Rare Case of Transient Pulmonary Arteriovenous Malformation During Pregnancy

Unexplained hypoxia in a pregnant patient is an alarming finding for patient and provider. The differential for hypoxia is broad, and many imaging techniques and procedures are contraindicated in pregnancy. Transient pulmonary arteriovenous malformations (AVMs) are a rare and relatively poorly studied cause of hypoxia in pregnancy. Our patient is a 27-year-old G1P0 female with a remote history of asthma who presented to clinic with slowly progressive exertional dyspnea, exertional tachycardia, and paroxysmal nocturnal dyspnea. She reported use of a home oximeter which read in the high 80s% during exertion. Prior to presentation, the patient was evaluated in the Emergency Department and noted to have an oxygen saturation of 86% on room air. A transthoracic echocardiogram, computed tomography angiography of chest, and basic laboratories including B-type natriuretic peptide, troponin, COVID-19, and hemoglobin were unremarkable. Her clinical timeline is presented in Figure 1. Further testing was obtained, including pulmonary function testing, bubble echocardiogram, nocturnal oximetry, and shunt study. Work-up revealed a 15-20% shunt, depending on calculation, and insignificant desaturations during nocturnal oximetry. Her symptoms progressed, and repeat nocturnal oximetry showed marked overnight desaturations requiring supplemental oxygen for the remainder of her pregnancy. She delivered a healthy baby girl via cesarean section without serious complication. Repeat testing in the post-partum period showed resolution of nocturnal desaturations and decreased shunt, and her exertional dyspnea and desaturations resolved spontaneously. This case illustrates the challenging diagnosis of transient pulmonary AVM in pregnancy. Case reports of this phenomenon have been published, but as in our case, no definitive diagnosis was made secondary to testing limitations in pregnancy and quick resolution of symptoms in the post-partum period. Some reports describe pre-existing pulmonary AVM becoming worse during pregnancy causing hemothorax, fetal demise and even death. While the mechanism is not known, theories include the vasodilatory effects of progesterone on vascular smooth muscle as well as other physiologic changes in pregnancy such as increased plasma volume. These AVM are thought to be like those seen in hepatopulmonary syndrome. Similar to our case, increasing positional hypoxia has been reported as the pregnancy progresses. Further research dedicated to early and accurate detection of pulmonary AVMs in pregnancy is necessary. (Figure Presented).

Vaccine-Induced Immune Thrombocytopenia and Thrombosis Syndrome post second dose of ChAdOx1 nCov -19 vaccine: Case Presentation

We present the case of a 39-year-old female who presented to University Hospitals of Leicester 14 days after the second dose of ChAdOx1 nCov-19 vaccine. Her presenting symptoms included skin rash, nausea, intermittent abdominal pain and occasional episodes of dizziness. Her past medical history included Type 2 Diabetes Mellitus and hidradenitis suppurativa. The first dose of ChAdOx1 nCov-19 vaccine had been administered on 27th February 2021, following which the patient reported flu like symptoms that resolved after four days and did not require further medical input. Following this, a preplanned surgical procedure to incise and drain a vulval abscess was performed on 17th May 2021. Preoperative testing performed on 13th May 2021 showed a normal platelet count of 219 × 10 9 /l. The second dose of ChAdOx1 nCov-19 vaccine was subsequently administered on 23rd May 2021. On presentation, examination revealed mild epigastric tenderness and features of classical thrombocytopenic rash affecting all limbs with no other associated bleeding. Initial blood results confirmed thrombocytopenia of 11 × 10 9 /l, with D-Dimer 14.26 μg/ml and fibrinogen 2.1 g/l. Blood film microscopy revealed an occasional schistocyte and microangiopathic haemolysis was considered. Treatment with plasmapheresis of 1.5 x plasma volume using Octaplas was administered. Subsequent abdominal computed topography imaging identified extensive thrombotic events. This included bilateral pulmonary embolism, superior mesenteric vein non-occlusive thrombus and multiple soft atheromas lining the abdominal aorta causing moderate infrarenal stenosis. In view of the recent history, vaccine associated thrombosis and thrombocytopenia (VITT) was considered. Subsequent testing showed a normal ADAMTS13 level. Treatment for VITT with intravenous immunoglobulin along with oral steroids and anticoagulation using Argatroban was commenced in line with national guidance. Anti-PF4 antibody, tested using the Asserachrom HPIA ELISA assay, was positive at a level of 1.298 OD units confirming the diagnosis of VITT;the first case we are aware of in the UK following second dose administration. Given high-risk presentation, Rituximab therapy was given as an inpatient with good clinical response. Prior to discharge, anticoagulation was switched to oral apixaban with a platelet count on discharge of 170 × 10 9 /l. Subsequent follow-up has shown ongoing clinical remission with consistently negative Anti-PF4 antibody titres. This report outlines the first known definite case of VITT identified following administration of the second dose of ChAdOx1 nCov-19 vaccine in the United Kingdom. The subsequent clinical course was similar to those of patients presenting after their first dose but the atypical presentation mimicking that of Thrombotic Thrombocytopenia is noted..

PREGNANCY, VALVULAR DISEASE, AND ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS): A COLLABORATIVE APPROACH TO OUTCOMPETING COMPETING HEMODYNAMIC DEMANDS

Background: A 35-year-old G1P1 woman with a history of bioprosthetic mitral valve (MVR) and aortic valve (AVR) replacements and a tricuspid valve annuloplasty for presumed rheumatic heart disease who presented at 35 weeks gestational age with COVID-19 ARDS and shock. Case: The patient arrived with ARDS requiring intubation and distributive shock. Transthoracic echocardiogram (TTE) revealed a small left ventricular (LV) cavity with LV hypertrophy, MVR with mean gradient of 14 mmHg, and a mid-peaking transaortic gradient of 96 mmHg consistent with fixed obstruction. This gradient was likely due to LV outflow tract obstruction (LVOTO) from the combination of a small LV cavity and septal angulation of the MVR struts rather than AVR dysfunction. The patient underwent emergent cesarean section. Decision-making: The maternal and fetal risks of ARDS and distributive shock were primary considerations in undergoing cesarean section. Decisions regarding management thereafter were driven by three elements of her clinical presentation - anticipated peripartum hemodynamic shifts, multivalvular disease, and ARDS. The increased plasma volume from postpartum autotransfusion risked worsening her ARDS but also potentially benefited the LVOTO through increased preload. The effect of lower postpartum cardiac output and heart rate on valvular obstruction in series also had to be considered. To balance these hemodynamic demands, after delivery, her vasopressors were switched from norepinephrine to phenylephrine, and she was judiciously diuresed. A postpartum TTE demonstrated improved transmitral gradients (mean 5 mmHg) but ongoing LVOTO. Higher filling pressures than otherwise ideal in ARDS were tolerated given persistent gradients. She was liberated from hemodynamic and ventilator support and transferred out of ICU care. Though she died of infectious complications weeks later, close collaboration between the critical care, obstetrical, and cardiovascular teams were essential to her care. Conclusion: Care of the peripartum patient with cardiovascular disease, especially valvular disease, must take into consideration both their cardiac pathology and expected peripartum hemodynamic shifts.

Bortezomib As Frontline Therapy in the Management of TTP

Introduction The current International Society on Thrombosis and Hemostasis (ISTH) guideline of Thrombotic Thrombocytopenic Purpura (TTP) recommends Therapeutic Plasma exchange (TPE) and corticosteroid in the management of TTP, with Rituximab and Caplasizumab as additional potential therapies [X Long Zheng et al, J Thromb Haemost. 2020;18:2496-2502]. This potentially fatal condition requires prompt diagnosis and treatment but large volume plasma treatment is not without risk and in settings with limited access with sufficient compatible plasma for apheretic exchange, this can delay this emergency therapy. We have been running the first therapeutic apheresis services with an Optia instrument in Uganda at the Joint Clinical Research Centre in Kampala city and TTP is the main indication for TPE. We present 2 recent sequential cases of TTP that were successfully managed when Bortezomib was combined with plasma therapy. Case1. A 25yr woman referred to our service on 29/09/2020, with recent onset of bruising, icterus, severe anemia Hgb5.7g/dL, Severe thrombocytopenia 8 x 10 3/uL, a high LDH 3909U with schistocytes on the peripheral blood film severe thrombocytopenia and a negative Direct Antiglobulin test. She was Blood Group B+. She was managed with 3 sessions of TPE of 2.1, 1.1 and 2.0 plasma volume exchanges with 6727mL, 3026mL and 5459mL of replacement plasma respectively and oral prednisone 60mg daily without remission. Subsequent quantities of plasma were insufficient for apheresis and were instead transfused. She also received weekly Rituximab 500mg (IV) but without significant recovery in the platelet count until she received Bortezomib 2mg (SC) when there was corresponding recovery of the platelet count and with each dose to a total of 4 doses (Figure 1). Case2. A 55yr man was previously well and shopping in a mall when he had an index episode of seizures on 19.Jun.2021 and was hospitalized that day with altered consciousness and focal motor signs. He required intubation for 3 days and at the time of hospitalization, he had Hgb 9gm/dL, PLT 17 x 10 3/uL, LDH2177U, with numerous schistocytes on the peripheral blood film and a negative Direct Antiglobulin Test. The baseline blood sample functional ADAMTS13 was 3% and had Blood Group AB+. He had received the 1 st dose of the Astra-Zeneca Covid19 vaccine on 06.May.2021. It was not possible to get any AB plasma and we considered it risky to perform large volume TPE with non-AB plasma and he was instead treated with daily transfusion with Group A+ Plasma concurrent with daily Prednisone 60mg. Because of our previous experience of poor response to Rituximab, we opted to treat him upfront with 4 doses of 2mg bortezomib (SC) given 3 days apart. He made brisk recovery to complete remission and was discharged for weekly outpatient CBC and LDH monitoring. His platelet count subsequently dropped without a corresponding drop in the Hgb and no rise in the Hgb. We initially re-hospitalized him for 4 more days of plasma transfusion but without a brisk response and since the LDH was not increasing, the isolated Thrombocytopenia was considered a side effect of Bortezomib that was expected to resolve and he receive no further treatment but continued to recover to complete remission as an out-patient (figure 2). Discussion: Our findings suggest a possible role for Bortezomib in frontline therapy for TTP with potential to reduce the plasma requirement in TPE and this approach warrants a randomized clinical trial. [Formula presented] Disclosures: No relevant conflicts of interest to declare. OffLabel Disclosure: Bortezomib Indicated in the management of Multiple Myeloma and Plasma Cell Dyscrasia

Gaisbock in 2021

Case Report The purpose of the study is to explore the possible diagnosis of Gaisbock in a patient with long-standing erythrocytosis and hypertension. Methods Used Case Study Summary of Results A 40-year-old Caucasian man with obesity was admitted with recurrent leg swelling and increasing oxygen requirements two weeks after hospitalization with COVID-19 pneumonia. Upon review of the patient's history, he was found to have untreated hypertension over several medical encounters and an erythrocytosis spanning ten years. Recent medical history included a diagnosis of deep vein thrombosis (DVT) in the same leg two and a half months prior and was treated with Xarelto. The patient reported a history of low testosterone for 12 years. However, he had not used any testosterone supplementation for the last nine months. He reported daytime fatigue, frequent bouts of nighttime awakenings, and frequent snoring. The patient never had a sleep study or used a CPAP. The patient used half a can of chewing tobacco daily for thirteen years, and he smoked one pack per day for ten years but quit 12 years ago. He worked strenuous jobs in the construction industry most of his life. On this admission, the patient's lab work was notable for hemoglobin of 18.7 gm/dL (13.7-17.5) and a normal erythropoietin level of 5.7 MIU/mL (2.6-18.5) without thrombocytosis or leukocytosis and a positive factor V Leiden mutation. His blood pressure was 132/91 mmHg. On review of previous records, the patient was found to have consistently elevated hemoglobin The patient had a stocky, ruddy appearance without hepatosplenomegaly. Conclusion Erythrocytosis can be categorized as primary, secondary, or relative. Patients with relative erythrocytosis have a decreased plasma volume with a relative increase in hemoglobin. Additionally, elevated hemoglobin levels have been associated with hypertension. Gaisbock's syndrome, first described in 1905, is characterized by hypertension and erythrocytosis without splenomegaly, leukocytosis, or thrombocytosis. It is associated with mild obesity, elevated blood pressure, and increased blood viscosity, which may explain why these patients often develop cardiovascular complications. Patients with relative erythrocytosis are at a higher risk for thromboembolic complications. In this case, Gaisbock's syndrome was suspected because the patient had had a stocky, plethoric appearance with persistently elevated hemoglobin and blood pressure with a normal erythropoietin level. Gaisbock's syndrome establishes a relationship between benign erythrocytosis, hypertension, and an increased risk for cardiovascular events. (Table Presented).

Therapeutic Plasma Exchange for Apixaban Removal in the Setting of Delayed Clearance and Life-Threatening Bleeding

Introduction: The management of bleeding associated with direct oral anticoagulants (DOACs) is challenging and associated with high risk of morbidity/mortality despite the use of various reversal agents (Gomez-Outes et al. 2021). Routine tests cannot determine the level of DOAC anticoagulation and reversal agents carry potential prothrombotic complications (Garcia & Crowther 2021). We present an unusual case of a patient requiring emergent surgery with significant post-op bleeding due to profoundly delayed apixaban elimination. Case Description: A 63-year-old female presented to the emergency department (ED) with a 10-day history of worsening abdominal pain, distension, nausea and constipation. Her past medical history was notable for right sided heart failure, COVID-19 pneumonia requiring intubation, tissue mitral valve replacement, and post-op atrial fibrillation for which she was prescribed apixaban 5 mg BID. Her last dose of apixaban had been the night prior to ED presentation. In the ED, a CT of the abdomen revealed a 6 cm partially obstructing lesion involving the mid-sigmoid colon. Findings were consistent with evolving peritonitis and the patient underwent an emergent exploratory laparotomy, sigmoid resection, and end colostomy. Pre-op labs revealed WBC 12.4 x10 9/L, hemoglobin (hgb) 9.2 g/dL, and platelets 318 x10 9/L. Coagulation studies revealed a PT of 28 sec and INR of 2.5. The patient was given prothrombin complex concentrate (PCC) 25 units/kg and 1 mg of vitamin K prior to surgery. Postoperatively, the INR remained elevated, 2.0, and her hgb downtrended from 8.8 g/dL to 7.8 g/dL. On post-op day 1 the patient became hypotensive, with increased abdominal pain/distension, she also started bleeding from her ostomy. The INR was 2.4 and her hgb dropped to 6.0 g/dL. Red blood cells were given along with FFP, vitamin K and a 2 nd dose of PCC. The patient continued to decline, was transferred to the ICU where she was intubated and placed on CRRT. Hematology was consulted for the persistently prolonged PT/INR in the setting of bleeding despite multiple interventions to correct the INR. The patient's last dose of apixaban was ~48 h prior to ICU admission. A rapid heparin anti-Xa assay was performed and upon comparison with an in-house nomogram the result, 1.78 IU/mL, correlated to an apixaban dose between 180-200 ng/ml (average peak levels 2-4 h after administration are 171 ng/mL). This result was confirmed the following day by an apixaban anti-Xa assay, 190 ng/mL. A repeat test performed 11 h later showed a minimal decrease in apixaban indicating impaired clearance. Therapeutic plasma exchange (TPE) was considered for rapid removal of apixaban. We performed a 1.0 plasma volume exchange, using plasma as the replacement fluid, to remove apixaban. Pre and post TPE drug levels were 172 and 108 ng/mL, respectively. Due to an elevated apixaban level the next day, a second TPE was performed which dropped the level to 87 ng/mL. The patient began to improve clinically, with hgb stabilization ~10 g/dL. She was extubated and transferred to a medical floor for further management. Apixaban levels were still measurable, 16 ng/mL, on post op day 8, 11 days after her last dose. Discussion: Apixaban is a highly protein-bound drug (~90%) that is rapidly absorbed in the small intestine with a large Vd (21 L) and a t1/2 of ~12 h. Elimination primarily occurs through the fecal route (Byon et al. 2019). The factors impairing the elimination of the drug in this patient were the following: 1. Pre-op constipation resulting in 10 days without a bowel movement;2. Minimal bowel function post-op;and 3. Renal failure requiring CRRT after admission to the ICU. This case illustrates the profound effect intestinal obstruction/dysfunction can have on apixaban clearance. It also highlights the importance of laboratory test interpretation when managing coagulopathic patients. TPE is an effective way to remove drugs with high protein binding affinity (Mahmoud et al. 2021). TPE significantly reduced apixaban levels in our patient allowing for he ostasis and clinical improvement. To our knowledge, there are only two case reports regarding the effect of TPE on DOACs, one for apixaban, the other rivaroxaban (Hodulik et al. 2019). Conclusion: TPE can be considered as an option for rapid clearance of apixaban, or other highly protein bound anti-Xa inhibitors, in the setting of delayed elimination or when specific reversal agents are not safe/available. Disclosures: No relevant conflicts of interest to declare.

Echocardiographic changes following active heat acclimation.

Heat adaption through acclimatisation or acclimation improves cardiovascular stability by maintaining cardiac output due to compensatory increases in stroke volume. The main aim of this study was to assess whether 2D transthoracic echocardiography (TTE) could be used to confirm differences in resting echocardiographic parameters, before and after active heat acclimation (HA). Thirteen male endurance trained cyclists underwent a resting blinded TTE before and after randomisation to either 5 consecutive daily exertional heat exposures of controlled hyperthermia at 32°C with 70% relative humidity (RH) (HOT) or 5-days of exercise in temperate (21°C with 36% RH) environmental conditions (TEMP). Measures of HA included heart rate, gastrointestinal temperature, skin temperature, sweat loss, total non-urinary fluid loss (TNUFL), plasma volume and participant's ratings of perceived exertion (RPE). Following HA, the HOT group demonstrated increased sweat loss (p = 0.01) and TNUFL (p = 0.01) in comparison to the TEMP group with a significantly decreased RPE (p = 0.01). On TTE, post exposure, there was a significant comparative increase in the HOT group in left ventricular end diastolic volume (p = 0.029), SV (p = 0.009), left atrial volume (p = 0.005), inferior vena cava diameter (p = 0.041), and a significant difference in mean peak diastolic mitral annular velocity (e') (p = 0.044). Cardiovascular adaptations to HA appear to be predominantly mediated by improvements in increased preload and ventricular compliance. TTE is a useful tool to demonstrate and quantify cardiac HA.