Abstract 4370840: Heparin-Resistant Massive Pulmonary Embolism in a Young Female: A Multi-Hit Thrombotic Storm

Case Description: An 18-year-old female presented to the emergency department with acute-onset dyspnea, chest pain, nausea, vomiting, and syncope after four months of oral contraceptive use and active vaping. Physical examination revealed tachycardia (135 bpm) and tachypnea, with ECG showing sinus tachycardia. Laboratory studies demonstrated dramatically elevated D-dimer (12,756), elevated proBNP (660), and troponin (299 225). Echocardiography revealed the D-sign [Image 1] classic McConnell sign - severely dilated right ventricle with hyperkinetic apex and hypokinetic basal-to-mid free wall [Image 2], confirming massive PE with acute cor pulmonale. CT angiography revealed extensive bilateral pulmonary emboli with signs of right heart strain [Image 3]. Immediate anticoagulation with heparin was initiated, followed by ICU admission where alteplase was administered for massive PE. Remarkably, the patient demonstrated complete heparin resistance with no APTT response despite escalating doses over 24 hours and the decision was made to switch to rivaroxaban 15mg twice daily. Patient symptoms significantly improved on day 3 and was eventually discharged with follow up appointment to hematology. Discussion: Thrombophilia workup revealed a multi-hit scenario: antithrombin III deficiency (68%, normal 85-135%) directly caused heparin resistance, as AT-III serves as heparin's primary cofactor. Heterozygous Factor V Leiden mutation creates activated protein C resistance, increasing VTE risk 4-8 fold. In addition to that, she was found to have PAI-1 4G/5G genotype which impairs fibrinolysis, amplifying thrombotic risk. Combined with OCPs (which increase clotting factors while decreasing natural anticoagulants) and vaping (causing endothelial dysfunction), these factors created exponential hypercoagulability in this young patient. Conclusion: This case demonstrates how multiple thrombotic risk factors can synergistically create catastrophic pulmonary embolism in young patients. Early recognition and aggressive intervention with thrombolysis can be life-saving. The identification of heparin resistance as a clinical clue to underlying thrombophilia opens new diagnostic pathways for personalized anticoagulation strategies, potentially revolutionizing PE management in the era of precision medicine.