Family History Of Thrombosis Research Articles

Assessment of the clinical and laboratory risk factors for thrombosis in neonates admitted to neonatal intensive care unit (two Egyptian tertiary centers experience)

In neonates admitted to the neonatal intensive care unit (NICU), arterial and venous thromboembolism is a major cause of morbidity and death which could be attributed to multiple risk factors exposure. This study aimed to evaluate the clinical characteristics, laboratory and radiological assessments, predisposing risk factors, and outcomes of thrombosis in neonates admitted to NICU. This prospective cohort study was conducted at NICU, Minia, and Alexandria University Children’s Hospital. Screening of 886 patients admitted to NICU over one year with different clinical presentations, patients were classified into the thrombotic and non-thrombotic groups based on the presence or absence of thrombosis. Thrombosis was diagnosed based on clinical, laboratory and different radiologic assessments. Genetic testing for factor V Leiden mutations G1691A, prothrombin mutation G20210A, protein C, protein S, and antithrombin III gene mutations were performed for patients with a family history of thrombosis. Out of a total of 886 neonatal admissions, 36 patients were diagnosed with evident thrombosis (40 per 1000 NICU admissions). The sites of venous thrombosis detection were Portal vein thrombosis in 11 patients (30.6%), superior vena cava thrombosis in 7 patients (19.4%), deep venous thrombosis in 5 patients (13.9%), central venous thrombosis in 5 patients (13.9%), intra-cardiac thrombosis in 3 patients (8.3%) and necrotic skin patches in one patient (2.8%). Only 69% of enrolled thrombosis patients showed genetic mutations the most common of which was factor V Leiden mutation (52.3%). Sepsis, central venous line (CVL) insertion, C reactive protein (CRP), and duration of NICU admission were significantly more common in the thrombotic group (p < 0.001) and were associated with a higher risk of thrombosis (ORs: 1.02, 7.7, and 1.11, respectively) (p < 0.001). Higher mortality occurred in thrombosis neonates compared with a non-thrombotic group (52.8% versus 17.4%) (p < 0.001). NICU-admitted neonates are exposed to multiple overlapped risk factors, the detection of which is important for preventing potential thrombosis and improving the patient’s outcomes. The complexity of sepsis pathogenesis and management could potentiate multiple acquired risk factors. inherited thrombophilia detection is required for prevention of further morbidities.

COVID-19 venous thromboembolism prophylaxis guidelines in pediatrics

IntroductionSARS-CoV-2 (COVID-19) infection and multisystem inflammatory syndrome in children (MIS-C) are risk factors for venous thromboembolism (VTE). Guidelines for VTE prophylaxis were established at our institution at the beginning of the pandemic. Patients who had any VTE risk factors in addition to COVID-19 met criteria for anticoagulation prophylaxis. Patients who were diagnosed with MIS-C met criteria regardless of additional risk factors. Materials and methodsWe conducted a retrospective review of patients admitted with COVID-19 or MIS-C to determine compliance with VTE prophylaxis guidelines and to evaluate the incidence of VTE and bleeding events in our population. Results and conclusionsAmong a total of 678 patients admitted with COVID-19 or MIS-C, 519 (76 %) patients met criteria for VTE prophylaxis and 348 (65.6 %) started prophylaxis. Logistic regression analysis identified a personal or family history of thrombosis or thrombophilia, diagnosis of MIS-C, admission to the intensive care unit, and presence of a central venous catheter as significantly associated with starting VTE prophylaxis. There were 18 patients who developed VTE. Minor bleeding events occurred in 19 patients (5 %), patient important bleeding, no intervention occurred in 8 patients (2 %), clinically relevant nonmajor bleeding in 8 patients (2 %), and major bleeding in 10 patients (3 %). The incidence of VTE in our patients with COVID-19 and MIS-C is similar to VTE rates at other institutions. We found that universally recognized VTE risk factors were appropriate to include as risk factors for thrombosis in hospitalized children with COVID-19 and MIS-C.

Evaluation of an Explainable Tree-Based AI Model for Thrombophilia Diagnosis and Thrombosis Risk Stratification

Background: Thrombophilia diagnosis can often be a convoluted process involving collection and analysis of clinical data, specialized laboratory testing, and high-level decision-making. This is inherently subjective due to differences in the clinical practice philosophy of each individual practitioner and can vary depending on institutional guidelines and available resources. Patient care and clinical outcomes may be affected as a result, which in turn provides a potential opportunity for optimization of thrombophilia diagnosis using AI. Methods: This retrospective study evaluated the utility and effectiveness of an AI-powered algorithm (XGBoost) programmed to replicate the process of thrombophilia diagnosis. A total of 256 patients were referred by their clinician for thrombophilia evaluation at our ambulatory coagulation clinic between November 2019 and February 2023 and clinical and laboratory data were collected from the electronic medical record. Thrombophilia diagnosis was established (or ruled out) on the basis of the patients' personal and family history of thrombosis as well as according to the results of thrombophilia testing including established acquired and inherited thrombophilia risk factors. The XGBoost, a gradient boosting algorithm for supervised learning, was used to perform a randomized search over a predefined set of tree parameters and to find a well-performing configuration on the data using cross-validation. The dataset contained 12 clinical data parameters and 26 laboratory data parameters. The target variable was two-dimensional, consisting of the thrombophilia probability score and thrombophilia risk factors. Thrombophilia probability scores were calculated based on clinical data from the following criteria: one point assigned each for a) spontaneous thrombotic event; b) mild risk situation; c) recurrent thrombosis; d) atypical thrombosis localization; e) age &amp;lt;50 years at the time of first thrombosis; f) family history of thrombosis and/or first degree relative with an established thrombophilia diagnosis. A probability score of 0 points corresponded to “unlikely thrombophilia”; 1-2 points “thrombophilia cannot be excluded”; 3 points “likely thrombophilia”; and 4+ points “most likely thrombophilia”. Thrombophilia risk factors were categorized by a scale of 0-3 indicating no risk (0), low risk (1), intermediate risk (2), and high risk (3). Results: Six patients were excluded from analysis due to lack of availability of sufficient clinical data. Clinical and laboratory data from the remaining 250 patients were thus included in the XGBoost analysis. The resulting trees and associated feature importance rankings revealed decisive factors for the detection of thrombophilia and suggested modified thresholds (e.g. age at the first occurrence of thrombosis increased from 50 years to 51.5 years) for an objective and standardized diagnostic procedure. The relative contribution of each clinical and laboratory feature to overall performance of the algorithm is shown in the Figure. The dataset was divided into three subsets: 200 train data, 25 validation data, and 25 test data, ensuring a representative distribution across the evaluation process. The model ultimately showed a sensitivity of 100% and a specificity of 100% for the thrombophilia probability score, and a sensitivity of 75% and specificity of 98% for the thrombophilia risk factors (Table). Conclusion: These results highlight the utility of tree-based AI models to support the objective and complex diagnosis of thrombophilia and thrombosis risk stratification. Furthermore, medical professionals can gain helpful insights from this AI-powered decision-making process due to the explainable nature of the model. We expect that the algorithm will show a higher sensitivity and specificity for the thrombophilia risk factors when we repeat the tests with a larger data set, which is currently ongoing.

Development and validation of a new risk assessment model for immunomodulatory drug-associated venous thrombosis among Chinese patients with multiple myeloma

BackgroundIndividuals with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) are at risk of developing venous thromboembolism (VTE), a serious complication. There is no established clinical model for predicting VTE in the Chinese population. We develop a new risk assessment model (RAM) for IMiD-associated VTE in Chinese MM patients.MethodsWe retrospectively selected 1334 consecutive MM patients receiving IMiDs from 16 medical centers in China and classified them randomly into the derivation and validation cohorts. A multivariate Cox regression model was used for analysis.ResultsThe overall incidence of IMiD-related VTE in Chinese MM patients was 6.1%. Independent predictive factors of VTE (diabetes, ECOG performance status, erythropoietin-stimulating agent use, dexamethasone use, and VTE history or family history of thrombosis) were identified and merged to develop the RAM. The model identified approximately 30% of the patients in each cohort at high risk for VTE. The hazard ratios (HRs) were 6.08 (P < 0.001) and 6.23 (P < 0.001) for the high-risk subcohort and the low-risk subcohort, respectively, within both the derivation and validation cohorts. The RAM achieved satisfactory discrimination with a C statistic of 0.64. The stratification approach of the IMWG guidelines yielded respective HRs of 1.77 (P = 0.053) and 1.81 (P = 0.063). The stratification approach of the SAVED score resulted in HRs of 3.23 (P = 0.248) and 1.65 (P = 0.622), respectively. The IMWG guideline and the SAVED score-based method yielded C statistics of 0.58 and 0.51, respectively.ConclusionsThe new RAM outperformed the IMWG guidelines and the SAVED score and could potentially guide the VTE prophylaxis strategy for Chinese MM patients.

Thromboembolic diseases from a haemostaseologic point of view

Venous thromboembolism is one of the most common vascular diseases. Increased thrombin formation together with reduced blood flow create a hypercoagulable environment that induces thrombus formation. Anticoagulants play a pivotal role in the treatment and secondary prophylaxis of venous thromboembolism because they effectively interrupt this hypercoagulability. A personalized assessment of the thrombotic risk is essential for planning the duration and intensity of secondary prophylaxis. The occurrence of thrombosis outside a typical risk situation, an atypical localization and a family history of thrombosis indicate a thrombophilic state. In these cases, thrombophilia diagnostics are useful for extended risk assessment. If anti-phospholipid antibodies are detected, the risk of recurrence is particularly increased.

Management and outcomes of women with antiphospholipid syndrome during pregnancy.

Women with antiphospholipid syndrome (APS) have an increased risk of adverse pregnancy outcomes. To define clinical, serologic, and treatment factors that can predict outcomes in pregnant women with APS. Retrospective cohort study of pregnant women with APS evaluated at a university medical center between January 2006 and August 2021. Demographics, personal and family history of thrombosis, autoimmune disease, antithrombotic use, pregnancy outcomes, maternal and fetal complications were collected. We compared pregnancy outcomes in the presence or absence of lupus anticoagulant (LA), systemic lupus erythematosus (SLE), prior thrombosis or pregnancy losses, and antithrombotic use. There were 169 pregnancies in 50 women; 79 (46.7%) occurred after maternal diagnosis of APS. The most common antithrombotic regimen was aspirin and low molecular weight heparin (LMWH) in 26.6% of pregnancies; 55.0% of all pregnancies and 68.4% of pregnancies post-APS diagnosis resulted in a live birth. In age-adjusted analyses, aspirin plus LMWH regardless of dosage was associated with significantly higher odds of live birth compared with no antithrombotic use (OR = 7.5, p < 0.001) and compared with aspirin alone (OR = 13.2, p = 0.026). SLE increased the risk for preterm birth and preeclampsia. A positive LA did not impact the outcomes evaluated and anticardiolipin IgM decreased the risk of pre-eclampsia. The presence of SLE is a significant risk factor for adverse outcomes in pregnant women with APS. Treatment with LMWH and aspirin was superior to aspirin alone. The creation of a global registry may be useful in improving the management of these patients.

A Case Series of Immune Flare and Lupus Anticoagulant Following COVID-19 Vaccination

Background: Vaccination against COVID-19 has garnered concerns for unusual post-vaccination complications. We present 2 cases of immune flare following COVID-19 vaccination. Case Report: Our first patient was a 53-year-old male who presented with a swollen left leg, hypoxia and palpitations after a trans-Atlantic flight. Chest computed tomography showed bilateral subsegmental pulmonary emboli, with no evidence of right heart strain and Doppler ultrasonography of the lower extremities showed significant clot burden in the left femoral, popliteal, tibial and peroneal veins. Workup revealed thrombocytopenia of 81,000/μL (normal range [NR] 150,000-450,000/μL), elevated D-dimer of 6.25 μg/ml (NR < 0.5 μg/ml), elevated partial thromboplastin time at 94 seconds without heparin. Mixing studies corrected partially to 60.9 seconds (NR 22.5-39.4), indicating the presence of an inhibitor, and lupus anticoagulant was confirmed with dilute Russell viper venom ratio of 3.66 (NR 0.00-1.20) and silica clotting time ratio of 3.95 (NR 0.00-1.22). Anti-beta-2 glycoprotein and anti-cardiolipin antibodies, factor V Leiden mutation, prothrombin G20210A mutation, protein C and protein S were negative. He received 2 doses of the ChAdOx1 nCoV-19 adenoviral vaccine 6 weeks previously. Due to suspicion for vaccine-induced thrombotic thrombocytopenia, enzyme-linked immunoassay for anti-platelet-factor 4 antibody was tested, which was negative. Immediate anticoagulation therapy with low-molecular weight heparin was started and then switched to rivaroxaban. Our second patient was an 18-year-old male who presented with 2 weeks of right-sided lower chest pain. The cardiopulmonary workup was negative, with a computed tomography of the chest showing a borderline enlarged spleen at 13 cm, and hepatic steatosis. He was taking indomethacin for slipped rib pain and was less mobile than usual. One week later, he developed left posterior thigh pain extending down the posterior calf and was found to have totally occluding left leg deep venous thrombosis from femoral vein mid to distal, popliteal, posterior tibial, peroneal, gastrocnemius and soleal veins. Workup was significant for prolonged partial thromboplastin time at 78 seconds, which partially corrected to 62 seconds with mixing studies, elevated C-reactive protein of 5.4, positive antinuclear antibodies (1:1280), normal complement (C3 and C4) and negative RF, SS A/Ro, SS B/La, RNP, smooth muscle, LKM antibodies. He started anticoagulation with low-molecular weight heparin, which was transitioned to apixaban. His family history was significant for lupus in his aunt and grandmother; however, there was no family history of thrombosis. He had received the third mRNA COVID vaccine 2 weeks prior to presentation. Additional workup revealed positive lupus anticoagulant, beta-2 glycoprotein, cardiolipin antibodies, and he was started on warfarin with a target international normalized ratio of 2-3 and repeat testing 3 months later revealed persistent elevation, indicating antiphospholipid syndrome. Although there was low suspicion for vaccine induced thrombotic thrombocytopenia, heparin-induced thrombocytopenia panel was performed and was negative. Discussion: Multiple SARS-CoV-2 vaccines were rapidly developed and approved, but long-term effects are unknown. Recombinant adenoviral vector-based vaccines raised concerns for an unusual post-vaccination coagulopathic syndrome with anti-platelet-factor 4 antibodies seen in 90% of probable and definite cases of vaccine-induced thrombotic thrombocytopenia (Pavord et al). Positive lupus anticoagulant has been noted with severe COVID-19 (Tung et al); however, our first patient had no history of COVID-19. This presentation was attributed at the time to a pro-inflammatory state induced by vaccination that may have caused lupus anticoagulant titers to rise leading to thrombosis as seen in this case. Autoimmune manifestations after COVID-19 vaccination are thought to be due to molecular mimicry, autoantibodies, vaccine adjuvants and a pro-inflammatory cascade among multiple other mechanisms (Chen et al). Similar to other viral infections, COVID-19 and additionally vaccination against it may lead to flare of immune mediated diseases (Talotta et al) as what occurred in our second patient with predisposition to hypercoagulable state given his family history of systemic lupus erythematosus.

Venous thromboembolism in pediatric patients with acute lymphoblastic leukemia under chemotherapy treatment. Risk factors and usefulness of thromboprophylaxis. Results of LAL‐SEHOP‐PETHEMA‐2013

IntroductionSymptomatic venous thromboembolism (VTE) is diagnosed in 3%–14% of patients during pediatric acute lymphoblastic leukemia (ALL) therapy. There are well‐known risk factors, but the role of others as inherited thrombophilia is still controversial. Prophylaxis with low molecular weight heparin (LMWH) has been described, but its use is not globally accepted. MethodsA retrospective multicentric study in ALL patients 1–18 years old following SEHOP‐PETHEMA‐2013 treatment guideline was performed to evaluate VTE rate, anticoagulant treatment, outcome, risk factors, and safety and usefulness of LMWH administration as primary thromboprophylaxis in children with inherited thrombophilia. ResultsA total of 652 patients were included in the study. VTE incidence was 8.7%. Most of the cases occurred during induction therapy associated with central venous catheter. Univariant analysis showed that family history of thrombosis, presence of mediastinal mass, high‐risk treatment group, and inherited thrombophilia were statistically significant risk factors. LMWH administration seemed to decrease VTE rate in patients with inherited thrombophilia and those with T‐cell ALL phenotype. ConclusionMost of the VTE cases occurred in patients without inherited thrombophilia, but when it is present, the VTE risk is higher. LMWH administration was useful to decrease VTE in these patients.

Risk prediction for deep venous thrombosis after total knee arthroplasty based on modified Caprini risk assessment model:a confirmatory study

To investigate the effectiveness of modified Caprini risk assessment model(Caprini MRAM) in predicting the risk of deep venous thrombosis (DVT) after total knee arthroplasty (TKA). A case-control study was used to collect 43 patients with DVT after TKA in lower limb department of Sichuan Orthopedic Hospital from January 2016 to November 2020 in the positive group, and 172 patients without DVT after TKA in the same period according to the 1∶4 ratio between positive and control group were selected in the control group. Caprini MRAM was used to score and grade the risk of DVT. The clinical data, score and risk classification of the two groups were compared. The relationship between the risk of DVT in the patients after TKA and the risk factors in the risk ckassification and assessment of Caprini MRAM was analyzed by multivariate logistic regression model. The average score of caprini in DVT group was significantly higher than that in control group[(8.11±2.91) vs(4.07±2.12), P<0.001];DVT group was mainly at medium and high risk group(66.67%), while the control group was mainly at low risk (77.33%). There was a significant difference between the two groups in risk classification composition (P<0.001). BMI≥30 kg/m2, lower extremity edema (<1 month), severe pulmonary disease (<1 month), acute myocardial infarction (<1 month), bed rest (> 2 h), history of superficial or deep vein or pulmonary embolism and family history of thrombosis were the main risk factors for DVT in patients after TKA(all P<0.05). Preoperative D-dimer elevation (OR=4.380), BMI≥30 kg/m2(OR=2.518), lower extremity edema(<1 month)(OR=7.652), acute myocardial infarction (<1 month) (OR=1.994), bed rest (> 72 h)(OR=3.897), history of superficial or deep vein or pulmonary embolism (OR=13.517) and family history of blood embolism (OR=6.551) were independent risk factors for DVT in patients after TKA (all P<0.05). The risk of DVT was 13.457 and 2.739 times higher in high and moderate risk TKA patients with Caprini MRAM classification, respectively. Caprini MRAM can be used to predict the risk of DVT in patients after TKA, especially for patients with high risk.

High-Oxygen-Affinity Hemoglobinopathy-Associated Erythrocytosis: Clinical Outcomes and Impact of Therapy in 41 Cases

▪BackgroundApproximately 100 high oxygen affinity (HOA) hemoglobin (Hgb) variants have been reported to date; review of the Mayo Clinic laboratory database (1974-2018) identified 80 distinct variants including 12 novel variants (60 β, 20 α). One-third of HOA Hgb variants result in secondary erythrocytosis, provoking concern regarding increased risk for thrombosis. Current management guidelines lack supporting evidence regarding the utilization of phlebotomy in such cases. We describe presenting features, treatment strategies and follow-up events involving 41 consecutive cases seen at our institution.MethodsStudy patients were recruited from our institutional laboratory and clinical Hgb variant database. Initial evaluation for Hgb variants was conducted by capillary electrophoresis and high-performance liquid chromatography. Additional testing which included mass spectrometry and isoelectric focusing was pursued as necessary. Since the majority of variants were difficult to identify by protein studies, DNA sequencing of HBB, or HBA1, HBA2 genes was performed for confirmation. Symptoms and thrombosis, both at presentation and during follow up, were recorded. Therapeutic interventions were based on physician discretion and mostly included phlebotomy and/or aspirin therapy; a careful response assessment was performed to determine the impact of each therapy on symptoms and/or thrombosis.ResultsA total of 41 patients with HOA Hgb variant-associated erythrocytosis (median age 39 years, range 1-81; 54% males) were seen at our institution between January 1973 and February 2020. The majority of the patients carried β-chain variants (n=34; 83%), common variants being Hgb Malmo (n=13), Olympia (n=4), San Diego (n=3), and Wood (n=2). Among the 7 patients with α-chain variants, Hgb Dallas was the most frequent (n=4).Presenting median values (range) for Hgb/Hct, serum erythropoietin and p50 were 18 g/dl/52.9%(16-21.9g/dl/48-66%) 10.4 mIU (4-36.3 mIU), and 20 mmHg (12-25 mmHg), respectively. Family history was documented in 34 patients, of which 24 (71%) reported one or more affected family members. Family history of thrombosis was documented in 7 patients (21%). CV risk factors were present in half of the patients; by contrast, history of thrombosis prior to or at diagnosis was documented in only two patients (5%). Of 23 pregnancies reported in 12 women, live birth rate was 78% (n=18); none of the fetal losses were attributed to erythrocytosis. Active therapies at the time of initial referral consisted of phlebotomy (n=12), aspirin (n=11) and systemic anticoagulation (n=1).At a median follow-up of 10 years (range; 0.04-44), 23 patients had reported one or more symptoms, attributed to hyper-viscosity, such as headaches, fatigue, and lightheadedness. Neither Hct level at diagnosis (p=0.32) nor phlebotomy (p=0.16; 75% patients on vs 52% not on phlebotomy) or aspirin therapy (p=0.75; 55% patients on vs 60% not on aspirin) appeared to influence the occurrence of symptoms. Phlebotomy relieved symptoms in 7 (42%) symptomatic patients; however, 7 (30%) of 23 patients on phlebotomy reported one or more adverse symptoms that were attributed to phlebotomy-induced iron deficiency.Ten patients (24%) experienced thrombosis prior to or following diagnosis: 6 arterial and 4 venous. Median age at thrombotic event was 51 years and median hematocrit 52%; active therapies at the time of event included phlebotomy in 5 patients, aspirin in 4, and systemic anticoagulation in 2. Hct level at diagnosis (p=0.10) or the time of event (p=0.67) did not correlate with occurrence of thrombosis. Additionally, the incidence of thrombosis was no different among patients receiving or not receiving phlebotomy (5/23(22%) vs 5/18(28%), respectively; p=0.66). The presence of CV risk factors was predictive of arterial events (p=0.002). Two of the 4 venous events developed in the context of concomitant thrombophilia. Eight patients (20%), median age 28 years, without CV risk factors, were observed without therapy for a median of 9.5 years (range; 0.4-21) and have not experienced any thrombosis to date.ConclusionsWe found no association between Hct level and either thrombotic or non-thrombotic symptoms in HOA hemoglobinopathy-associated erythrocytosis; furthermore, implementation of aggressive phlebotomy did not provide a clear benefit with respect to thrombosis risk reduction. [Display omitted] DisclosuresPatnaik: StemLine: Research Funding; Kura Oncology: Research Funding.

Acquired and Inherited Thrombophilia Testing in Patients with Chronic Thromboembolic Pulmonary Hypertension: Value of Testing in an Academic Health Center

IntroductionChronic thromboembolic pulmonary hypertension (CTEPH) is classed as group 4 in the present classification of pulmonary hypertension. The pathophysiology of CTEPH is complex, mainly is a consequence of prior acute pulmonary embolism with failure of thrombi to resolve and the recent recognition of added small vessel changes which impacts long-term outcomes even after surgical management. The role of thrombophilia testing in this condition has been debated. Hence, we here analyzed the utility of thrombophilia testing in CTEPH from a center in a developing country.MethodsThis is a single institution (Narayana Health City, Bangalore); retrospective study including patients ≥ 18 years of age who underwent thrombophilia workup in a diagnosis of CTEPH from January 2019 till July 2021. Tests done to evaluate thrombophilia included factor V Leiden; prothrombin F20210A mutation; MTHFR gene mutation; Protein C, S, and antithrombin deficiency; lupus anticoagulant, anti-beta2 glycoprotein I (IgM and IgG) and anticardiolipin antibody (IgM and IgG); hyperhomocysteinemia and anti-nuclear antibody testing (ANA-IF). The study was approved by the ethics committee of the institute and was carried out in accordance with the principles of the declaration of Helsinki.Results and discussionThe study included 56 patients with a median age of 37 years (range 23-50), and 36 (64%) were males. Patients with recurrent venous thrombosis included 37 (66%), with the majority having thrombosis at 2 sites (53%; 22 patients with associated deep vein thrombosis). A family history of thrombosis was present in 4 patients. The majority of patients received vitamin K antagonists (76%), with the rest receiving direct oral anticoagulants (DOAC).Among the tests sent for acquired thrombophilia, ANA-IF and antiphospholipid antibody (APLA) were most frequently evaluated (94%). ANA-IF and APLA tests were positive in 5.6% and 30.1%, respectively. Among the APLA tests, Anti-beta2 glycoprotein I (IgM or IgG) was the most commonly detected antibody (13/46), followed by anticardiolipin antibody (IgG or IgM) (9/43) and lupus anticoagulant (7/40). Double and triple positive APLA were present in 3 and 4 patients, respectively. Homocysteine levels were high in 93.7% though only 16 patients were tested in this cohort.Among the tests for inherited thrombophilia, genetic tests (factor V Leiden, prothrombin F20210A mutation, and MTHFR gene mutation) were tested in only ~50%. Twenty-three percent were positive for heterozygous MTHFR followed by MTHFR compound heterozygous (10%) and heterozygous factor V Leiden heterozygous (10%). Antithrombin III, protein C, and S were tested in ~30% of patients. Antithrombin III was low in only 1 patient, with protein C and S assays being normal in all the patients.The cost analysis was calculated, showed a median of $364 (₹ 27,055) was spent per person on thrombophilia workup. The median cost incurred per patient for inherited thrombophilia workup was $232 (₹ 17,300) and for acquired thrombophilia was $132 (₹ 9814), respectively.ConclusionThis single-institution study on thrombophilia workup in CTEPH patients reveals that APLA was the most commonly performed test with high positivity rates of 30.1%. Among the inherited thrombophilia, the positivity rate of MTHFR mutation was highest (33.3%), with other tests having a low positivity rate (0-10%). Hence, we would recommend APLA testing in all patients with CTEPH considering its high positivity and clinical utility. Testing for other thrombophilias should be pursued judiciously especially in economically restrictive settings. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Management and Outcomes of Women with Antiphospholipid Antibodies or Antiphospholipid Syndrome during Pregnancy

BackgroundPregnant women with antiphospholipid antibodies (aPLs) or antiphospholipid syndrome have an increased risk for thrombosis. Although a combination of low-dose aspirin and unfractionated heparin (UFH) or low molecular weight heparin (LMWH) are usually prescribed in pregnancy, there is no consensus on optimal dosing of these agents. Despite the use of low-dose aspirin and LMWH, approximately 30% of women with a positive lupus anticoagulant (LA), underlying autoimmune disease, or a previous history of thrombosis have unfavorable outcomes.AimTo describe the management and outcomes of women with either aPLs or APS during pregnancy at a university medical center.MethodsWe conducted a retrospective cohort study of pregnant women with either aPLs or APS seen in our hematology clinic in consultation between January 2006 and August 2021. Data collected included demographics, reason for aPLs testing, personal or family history of thrombosis or autoimmune disease, and presence of other thrombophilias. Antiphospholipid antibodies included the LA, anti-cardiolipin (aCL) and anti-beta-2 glycoprotein 1 (ß2GP1) confirmed on two occasions at least 12 weeks apart. Data was collected on antithrombotic agents used during pregnancy, including aspirin, dose of LMWH, UFH and certolizumab. We recorded the following obstetric outcomes: live births, early delivery, fetal loss, early pregnancy loss <10 weeks gestational age (GA), pre-eclampsia, venous thromboembolic events (VTE), arterial thromboembolism (ATE), and post-partum hemorrhage (PPH). We compared management and outcomes in the presence or absence of LA. Statistical comparisons between groups were conducted with the Fisher's exact test.ResultsThere was a total of 202 pregnancies in 62 women with 11% of pregnancies achieved with assisted reproductive techniques. The most common reasons for aPLs testing were pregnancy loss (35%), VTE (23%), and ATE (8%). Antiphospholipid antibody profiles consisted of 56% triple positive, 8% positive LA plus either aCL or anti- ß2GP1, 13% positive LA alone and 22% with either double positive aCL and anti- ß2GP1 or single aCL or anti- ß2GP1. Twenty-tree percent of women had an additional inherited thrombophilia (Table 1). Of the 202 pregnancies, 52% resulted in live births, 20% in pregnancy loss <10 weeks, 12% in pregnancy loss >10 weeks, and 28% were either electively terminated, resulted on an ectopic pregnancy, or the outcome was unknown due to lost to follow up. Antithrombotic therapy was used in 47% of pregnancies: 26% used aspirin and LMWH, 10% used LMWH alone, and 7% used aspirin alone (Table 2). In 10% of pregnancies, patients were transitioned to UFH prior to delivery. Pre-eclampsia with or without HELLP syndrome occurred in 10% of pregnancies and maternal thromboembolic complications occurred in 6%. On analysis of outcomes stratified by LA status, there was a trend toward a higher rate of preterm births in the presence of a positive LA (Table 3). The rate of live births was increased with the use of antithrombotic therapy (Table 4).ConclusionPatients with antiphospholipid antibodies (aPLs) and antiphospholipid syndrome had elevated rates of complications and adverse outcomes during pregnancy. LA positive status was associated with a trend toward a higher rate of preterm births. Further studies are needed to clarify the factors associated with adverse outcomes and optimal anticoagulation management. [Display omitted] DisclosuresDesancho: Sanofi-Genzyme: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure:Certolizumab with the hypothesis of improving clinical outocomes

Thrombotic Risk Factors, Antithrombotic Therapy, and Outcomes of Asymptomatic Carriers of Antiphospholipid Antibodies and Patients with Antiphospholipid Syndrome

Background: There is marked heterogeneity in the clinical presentation of patients with antiphospholipid antibodies (aPL) and antiphospholipid syndrome (APS) and a variable thrombotic risk. Putative thrombotic risk factors include male gender, high titer aPL serology with IgG isotype, triple positivity and concomitant autoimmune disease. However, the evidence is conflicting for some, and the patient heterogeneity makes risk stratification challenging. Thus, long-term antithrombotic management decisions remain primarily driven by clinical judgment. Decisions such as discontinuation of therapy, use of direct oral anticoagulants (DOAC), and the role of hydroxychloroquine (HCQ) and immunosuppressive therapy remain areas of ongoing research.Objectives: To outline clinical risk factors of thrombotic events in antiphospholipid patients and describe outcomes of different antithrombotic strategies in this heterogeneous cohort.Methods: We retrospectively identified all adult patients followed at Weill Cornell Hematology with aPL or APS. Patients were included if they met laboratory criteria for APS. Data on patient demographics, concomitant thrombophilia, autoimmune disease, and family history of thrombosis, aPL isotype and titer, thrombotic events prior to and during follow-up, and antithrombotic therapies were collected. Time to event analysis was used to identify clinical risk factors for thrombosis. The time varying effects of antithrombotic therapies were also evaluated.Results: A total of 122 patients were identified with a median age of 43 (range 19-86 yrs.). Ninety-three (76%) were female and 29 (24%) were male. Eighty-four patients (69%) were diagnosed with APS prior to their initial visit and the remaining 38 (31%) were aPL positive. Of the 84 APS patients, 63 (74%) had a history of a single thrombotic event and 22 (20%) had recurring events. Those were venous thromboembolic events (VTE) in 45 patients (53%), Arterial (AT) in 19 (22%), pregnancy morbidity (PM) in 12 (14%), and combinations of VTE, AT, and PM in the remaining 9 patients (11%). Of the 38 aPL positive carriers, 25 (66%) were asymptomatic, tested mainly for prolonged aPTT (68%), and 13 (44%) had non-criteria events that prompted testing. Autoimmune disease was present in 37 (30%), of which 16 (43%) were SLE. Hereditary thrombophilia was identified in 7 (6%) and a family history of thrombosis, aPL positivity, or APS was noted in 15 (12%).During a median follow-up duration of 47 months, 19 patients had an event (16%). A significantly higher rate of thrombosis was observed in patients with autoimmune disease (HR 4.64, p<0.01), and in Blacks vs. Whites (HR 8.37 p<0.01). Triple positivity, found in 45 patients (37%), was not associated with an increased thrombotic risk. The risk of thrombosis was significantly lowest among patients on therapeutic dose anticoagulant therapy (ac) with low-molecular weight heparin (LMWH) or vitamin K antagonist (VKA) (Figure 1). In comparison, patients on antiplatelet therapy (apt) alone had 5.4 times the risk (HR 5.432, p=0.01). DOACs were used in 9 (10%) of the APS patients, with a median follow-up of 19 months (2-37) and a single event occurring in a young male without the aforementioned risk factors. Thirteen patients (11%) were on HCQ, 8 (7%) with autoimmune disease and 5 (4%) without, for a median duration of 20 months, with a single event occurring in a patient on HCQ alone.Conclusions: In this study, concomitant autoimmune disease and Black race were risk factors for thrombotic events in antiphospholipid patients. Anticoagulation with LMWH or VKA remains the most effective therapy. Deciding on who can safely discontinue anticoagulation and who may benefit from additional antithrombotic and immunosuppressive therapies remains a matter of clinical judgment until multicenter, prospective studies are carried out. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Protein C Infusion Therapy in an Adult Case of Severe Congenital Protein C Deficiency

Background: Severe congenital protein C deficiency (SCPCD) is a rare inherited disorder characterized by recurrent thrombosis, disseminated intravascular coagulation, and purpura fulminans. Due to limitations in traditional therapeutic options (anticoagulation, FFP, PCC), plasma-derived protein C concentrates have been used for both prophylactic and therapeutic indications. However, there are few reports of protein C infusion therapy in adults, with limited understanding of pharmacokinetics and no dosing guidelines available. We report the use of protein C concentrate in an individualized dose-finding study, in an adult patient in preparation for renal transplantation.Case: A 35 year old female (68 kg) with SCPCD (baseline PC activity < 0.10 U/mL) with an extensive personal and family history of thrombosis was to undergo renal transplant. Her thrombotic history included DVT and PE (age 4), recurrent DVT with PE (age 6), mesenteric vein thrombosis (age 6), arterial thrombosis in bowel (age 10), DVT (age 10), extensive superficial venous thrombosis (age 27), pregnancy-associated DVT (age 32), and internal jugular vein thrombosis (age 34), for which she was on long-term therapeutic Enoxaparin. She developed end-stage renal disease in March 2015 (age 33) in the setting of pregnancy-associated HELLP syndrome, and is currently awaiting a deceased donor renal transplant. In anticipation of her upcoming transplant, an intravenous protein C infusion trial was performed to establish a perioperative management plan.Results: The patient was admitted to hospital for this dose-finding study. She was administered Ceprotin® (human plasma-derived, virally-inactivated protein C concentrate) with an initial intravenous bolus (59 IU/kg) followed by an infusion (5 IU/kg/hr) to maintain a target PC level of 0.65-1.30 U/mL (see Table). Protein C activity was measured every 6 hours, and target levels were achieved over the 30-hour duration of the trial. The patient experienced no adverse events during the infusion trial.Conclusion: In this case report, target protein C levels were maintained using bolus and continuous infusion rates of protein C concentrate that were approximately half of those recommended by the manufacturer. This personalized trial, while resource-intensive, provided a feasible and safe method of preparing for a high-risk surgical procedure that could be adapted to other similar clinical situations. [Display omitted] DisclosuresCrowther:Leo Pharma: Research Funding; Shinogi: Consultancy; Boehringer Ingelheim: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alexion: Speakers Bureau; Pfizer: Honoraria; Portola: Consultancy.

Pulmonary Embolism in Adipsic DI: Can Desmopressin Be a Contributing Factor?

Background: Adipsic DI (ADI) is a rare disease associated with various morbidities. One of them is venous thromboembolism (VTE). In literature there are less than 10 reported cases and scarce management orientations. Classically, in ADI, VTE risk is due to dehydration and acute hypernatremia. Desmopressin should also be considered as it has a known role in blood coagulation such as increasing platelet cohesion and promoting von Willebrand factor release. Clinical Case: A 51-year woman with past medical history of obesity class 3 and a craniopharyngioma surgically intervened 8 months before, underwent a second craniotomy due to recurrent lesion. Postoperatively the patient developed an ADI, hypopituitarism and impairement of higher brain functions namely short-term memory and sleep-wake cycles impairment. She was discharged on desmopressin 0.35mg/day, levetiracetam 1500mg/day, hidrocortisone 15mg/day, levothyroxine 75mcg/day and quetiapine 25mg/day. Two weeks after discharge, the patient was admitted to the emergency room with anorexia and malaise. Tests were consistent with PE: elevated D-dimmer levels and CT angiography revealing bilateral PE. Treatment with enoxaparin was initiated. There was no hemoconcentration or polycythemia; kidney and liver function were normal, and sodium of 148 mEq/L (135-145 mEq/L). Three days before she had normal sodium levels. Respiratory insufficiency, deep vein thrombosis and infection were excluded. The patient did not present signs of dehydration. Brain CT did not show acute alterations. There was no personal history of smoking or family history of thrombosis and the patient was not on bed rest in the previous couple of weeks. During hospital stay abdominal and pelvic CT did not reveal malignancies. The patient was discharged on enoxaparin and posteriorly underwent a mammogram and colonoscopy; both exams without relevant alterations. At the last follow-up visit, she remained hypocoagulated and with desmopressin, with no further episodes of thrombosis. Conclusion: We report for the first time a case of PE in an obese patient with ADI treated with desmopressin and without overt hypernatremia or dehydration. All previously published cases of VTE in ADI have occurred in patients presenting with moderate to severe hypernatremia (sodium 157-181 mEq/L) and some degree of dehydration at the time of the event. Obesity and a recent hospitalization may have contributed to the development of VTE but desmopressin should also be taken into consideration due to its known effects on coagulation. Thromboprophylactic treatment after pituitary surgery and during acute episodes of hypernatremia and dehydration is already warranted in ADI but we additionally suggest considering at least short-term thromboprophylaxis in obese patients with recent ADI diagnosis treated with desmopressin as they might have this additional increased thrombotic risk.

Thrombosis Risk in Transgender Adolescents Receiving Gender-Affirming Hormone Therapy.

Many transgender youth experience gender dysphoria, a risk factor for suicide. Gender-affirming hormone therapy (GAHT) ameliorates this risk but may increase the risk for thrombosis, as seen from studies in adults. The aim with this study was to examine thrombosis and thrombosis risk factors among an exclusively adolescent and young adult transgender population. This retrospective chart review was conducted at a pediatric hospital-associated transgender health clinic. The primary outcome was incidence of arterial or venous thrombosis during GAHT. Secondary measures included the prevalence of thrombosis risk factors. Among 611 participants, 28.8% were transgender women and 68.1% were transgender men. Median age was 17 years at GAHT initiation. Median follow-up time was 554 and 577 days for estrogen and testosterone users, respectively. Individuals starting GAHT had estradiol and testosterone levels titrated to physiologic normal. Multiple thrombotic risk factors were noted among the cohort, including obesity, tobacco use, and personal and family history of thrombosis. Seventeen youth with risk factors for thrombosis were referred for hematologic evaluation. Five individuals were treated with anticoagulation during GAHT: 2 with a previous thrombosis and 3 for thromboprophylaxis. No participant developed thrombosis while on GAHT. In this study, we examined thrombosis and thrombosis risk factors in an exclusively adolescent and young adult population of transgender people receiving GAHT. These data suggest that GAHT in youth, titrated within physiologic range, does not carry a significant risk of thrombosis in the short-term, even with the presence of preexisting thrombosis risk factors.

Prediction Model of in-Hospital Venous Thromboembolism in Chinese Adult Patients after Hernia Surgery: The CHAT Score

BackgroundVenous thromboembolism (VTE) events after hernia surgery influence prognosis and life quality and may be preventable. This study aimed to develop a useful model for predicting in-hospital VTE in Chinese patients after hernia surgery.MethodsPatients after hernia surgery were retrospectively recruited from 58 institutions (n = 14 322). Totally, 36 potential predictors were involved in the regression analysis. Weighted points were assigned to the predictors of in-hospital VTE identified in the multivariate logistic regression analysis and a prediction model was established. Decision curve analysis was performed to evaluate the net clinical benefit between the established and Caprini models.ResultsA total of 11 707 patients were included and five variables were explored as predictors related to in-hospital VTE: varicose veins of lower extremity, history of VTE, family history of thrombosis, interruption of antithrombotic agents, and reducible hernia. The prediction model (the CHAT score) revealed a good performance metrics (c-statistic, 0.81 [95% CI, 0.80 to 0.81]; Nagelkerke R2, 0.27 [95% CI, 0.26 to 0.30]; Brier score, 0.16 [95% CI, 0.13 to 0.23]). The rate of in-hospital VTE after hernia surgery at low-risk (−4 points), intermediate-risk (0-1 points), high-risk (4 points) and very high-risk (≥5 points) were 0.05%, 0.39%, 0.73% and 8.62%, respectively. The CHAT score identified a considerable variability (from 0.05% to 8.62%) for in-hospital VTE among the overall population after hernia surgery. Decision curve analysis found a superior net benefit of the established model than the Caprini score.ConclusionsThe CHAT score is likely to be a practical 5-item supporting tool to identify patients at high risk of in-hospital VTE after hernia surgery that might assist in decision making and VTE prevention. Further validated study will strengthen this finding.

Application of Thrombomodulin-Thrombin Generation to Diverse Abnormalities of the Protein C System

Background: Increased thrombin generation is an interesting candidate as a potential indicator of hypercoagulability and thrombosis risk. Increased thrombin generation using the calibrated automated thrombogram (CAT) has been reported in antithrombin deficiency but the CAT does not reflect protein C deficiency without the addition of thrombomodulin (TM). TM activates protein C (PC) in the CAT and reduces thrombin generation. Objective: The objective of this study was to determine the capacity of the TM-augmented CAT to detect defects in various protein C system components; the lupus anticoagulant was also investigated as a cause of decreased protein C activation. Methods: The CAT-TM was performed with reagents and methods per the manufacturer's instructions using 5 pM tissue factor and TM (Stago). Other assays included: PC (chromogenic), free protein S (PS, LIA), activated protein C resistance (aPTT-based clotting assay), factor V Leiden (FVL PCR) and lupus anticoagulant (LA, dRVVT and Staclot LA, Stago). Platelet poor plasma samples were obtained from the biobank of a consented prospective inceptional cohort study of thrombosis and thrombophilia or a positive family history of either (ThromboPICS #05-0339); samples from healthy controls with no personal or family history of thrombosis or thrombophilia were collected on a consented protocol (#09-0816). Samples from participants on therapeutic inhibitors of factor Xa or thrombin were treated with appropriate neutralizers; no sample was tested on warfarin. Clinical data included gender, age (&amp;lt; 18 versus ≥ 18 years), history of thrombosis, timing of sample from most recent thrombosis (acute &amp;lt; 14 days; subacute 14-90 days; or chronic &amp;gt; 90 days) and use of anticoagulants at the time of the blood draw. Tests for violations of normality were negative. Therefore, results of cohorts versus controls were compared with independent sample t-test and subgroup analyses relative to control used One-Way ANOVA. Post-hoc comparisons of each subgroup to the controls were collected for multiple comparisons using the Bonferroni correction. Results: Ninety-nine cases and 45 normal controls were studied. Overall half of the cases had a history of thrombosis and 66% of those with thrombosis were on no anticoagulation at the time of testing. Table 1 displays results of the CAT-TM in the 2 control and 6 study groups. Control adults and children showed a mean 50% thrombin reduction in thrombin generation with CAT-TM; overall, persons with protein C system defects showed approximately 25% reduction, with the least reduction of thrombin generation in the cohort of PC deficiency at 19%. Sensitivity of the CAT-TM was 100% for PC deficiency, 81% for LA positivity, 80% for PS deficiency and 72% for FVL positivity with no difference in degree of thrombin reduction between hetero- and homozygous FVL. In addition, we identified 14 individuals with CAT-TM results similar to protein C system defects but with confirmed normal PC, PS, FVL and LA tests. Although 9 of these unknowns had a personal (7) or family (2) history of thrombosis, five came from the healthy controls. The false positive results in 3 adult and 2 pediatric controls conferred a CAT-TM test specificity of 89%. Furthermore, analyses showed no differences in CAT-TM results related to gender, age group, history of thrombosis, age of clot at blood draw (acute, subacute or chronic) or use of anticoagulation at the time of blood draw. Conclusions: The CAT-TM is a useful screening test for defects in the protein C system, including LA, although this test could not discriminate between heterozygous and homozygous FVL. The etiology of positive CAT-TM in normal individuals or individuals with a personal or family history of thrombosis without identified PC system defects is currently unknown and under ongoing investigation. Disclosures No relevant conflicts of interest to declare.

Thrombosis Risk in Transgender Adolescents Receiving Gender-Affirming Hormone Therapy

An estimated 2-3% of US youth identify as transgender or gender non-conforming (hereafter transgender). Transgender youth may suffer from gender dysphoria, a condition associated with many health risks, including high risk of suicide. Transgender individuals have a 40% greater risk of attempting suicide than cis-gender individuals. Gender-affirming hormone therapy (GAHT) is associated with improvement of gender dysphoria and amelioration of the risk of suicide. GAHT consists of either estrogen [for transgender women (TGW)] or testosterone [for transgender men (TGM)]. However, GAHT may be associated with other risks, most notably thrombosis. Numerous studies documented increased thrombosis risk in cis-gender women using exogenous estrogen for contraception or hormone replacement therapy. Studies of GAHT suggest a risk of thrombosis with estrogen use; however, this data is not uniform. Studies of testosterone replacement in cis-gender show conflicting results with respect to thrombosis risk. All previous studies examining the risk of thrombosis with GAHT have included adults exclusively. Therefore we sought to determine the risk of thrombosis in a cohort of transgender youth receiving standardized GAHT regimens. Transgender youth have potential for a much longer exposure to GAHT, thus having different life-time risk of thrombosis than patients that start GAHT at an older age. Of all 1406 patients seen at the Cincinnati Children's Medical Center Transgender Health Clinic since its inception, 611 subjects started GAHT and were eligible for inclusion in the cohort. Of these, 176 (28.8%) identified as female, 416 (68.1%) as male, and 19 (3.1%) as non-binary. Thrombosis risks were common among the cohort: 34.5% had obesity, 15.4% used tobacco, 4.6% had migraine with aura, and 8.0% had a family history of thrombosis. Three subjects had a prior history of thrombosis: 2 with venous thromboembolism (VTE) and one with a stroke. 53.7% of the cohort had previously used hormones, most commonly for menstrual suppression. Of those with prior hormone use, the vast majority had used progesterone-only methods (5.7% previously used estrogen-containing contraceptives). All patients initiating GAHT were treated according to current guidelines with monitoring of estrogen and testosterone levels and titration of GAHT doses accordingly. Overall, 29.8% initiated estrogen therapy and 70.2% started testosterone therapy. Among the cohort, 17 individuals were referred to Hematology for evaluation for thrombosis risk prior to starting GAHT. The most common laboratory abnormality for these individuals was elevated factor VIII, elevated plasminogen-activator inhibitor 1 (PAI-1), and the PAI-1 polymorphism. Two TGW and one TGM started thromboprophylaxis prior to initiating GAHT due to thrombotic risk factors. Despite the presence of preexisting risk factors, no individual in the cohort developed a thrombosis (VTE or stroke) during GAHT. This is the first study to examine thrombosis risk of GAHT in an exclusively adolescent and young adult population. While there were no incidents of thrombosis in our cohort, we found individuals at risk for thrombosis. Careful history and counseling regarding risks are needed when discussing initiation of GAHT for transgender individuals. Additionally, further studies looking at long-term risk are needed. Disclosures Mullins: Takeda, Bayer: Other: Advisory Board.

S2961 Splenic Infarction Leading to Gastrosplenic Fistula in COVID-19

INTRODUCTION: Gastrosplenic fistulas are rare with no reported cases resulting from acute infarction. Coagulopathy is commonly reported in COVID-19 infection. We present a first instance of gastrosplenic fistula as sequalae of celiac artery plexus thrombosis resulting in splenic infarction in setting of COVID-19 infection. CASE DESCRIPTION/METHODS: A 51 year-old female with chronic gastritis & no personal or family history of thrombosis, treated for COVID-19 pneumonia 1 month prior, presented 2 weeks after discharge with epigastric pain, coffee ground emesis & fever. CT with angiography showed thrombosis of celiac trunk, common hepatic, splenic & left gastric arteries, fistulation of gastric wall & splenic fossa with gastric contents in spleen, splenic abscess & complete splenic infarction. Small bowel follow-through showed contrast in spleen. EGD visualized a large gastric fistula. No specimen was collected as surgical repair was planned. Labs showed positive SAR-CoV2 RNA, negative H. pylori stool antigen, stable hemoglobin 8-9.5g/dL, thrombocytosis of 703K/µL, fibrinogen 397mg/dL, heterozygous Factor V Leiden mutation, & no antithrombin 3 deficiency, protein S deficiency, or JAK2 mutation. She remained on antibiotics, IV heparin & PPI with no further signs of GI bleed. More conservative approach was favored & a percutaneous drain was placed into splenic abscess with cultures growing 2 strains of ESBL E. coli & Candida glabrata. Patient remained stable, tolerated diet & was discharged on long term antibiotics & anticoagulation. DISCUSSION: Gastrosplenic fistulas are rare & caused by gastric or splenic pathologies causing erosion & fistulation due to proximity. Literature review shows no reported cases of splenic infarction as cause of gastrosplenic fistula. We hypothesize COVID-19 related coagulopathy & underlying Factor V Leiden heterozygosity led to arterial thrombosis & complete splenic infarction as mechanism of fistulation. While gastric lymphomas & ulcers are reported causes, EGD 3 months prior showed unremarkable biopsies throughout & EGD during hospitalization showed no gastritis or other lesions. Splenic abscesses are reported in literature as cause of gastrosplenic fistulas. While no imaging timeline is established to rule out abscess as mechanism of fistulation, they are also rare & caused most commonly by hematologic seeding. With negative blood cultures, no other source of infection & triple organism abscess culture, it is more likely fistulation occurred with seeding of spleen through fistula.Figure 1.: Axial view of the upper abdomen. A gastrosplenic fistula is noted. There is a wall defect along the greater curvature of the stomach with gastric contents and air entering a fistulous tract that extends posterolaterally to the spleen.Figure 2.: EGD visualization of non-bleeding gastric fistula in wall of gastric body.Figure 3.: Radiograph of the upper abdomen five minutes after administration of oral contrast. Oral contrast is present within the stomach and the proximal duodenum. There is abnormal contrast in the left upper quadrant of the abdomen overlying the spleen.