Narrative:  48 Y F with PMH of, menorrhagia with uterine fibroids (home estrogen/progesterone-has been on for >10 years), HTN, asthma, allergic rhinitis, DJD, and iron deficiency anemia (baseline Hgb 8-9) who presented to ED from home on 4/10/21 with complaints of SOB, nausea, generalized weakness, bilateral leg swelling, and presyncope. No recent travel. Non-smoker. COVID-19 negative (4/10/21). No family hx of DVTs/PEs. The patient received her 1st Pfizer COVID-19 vaccine on 4/5/21. CT demonstrated distal L main pulmonary artery extensive PE (as well as smaller branches L, R lobar PA branches) and R heart strain. BLE DVT US on 4/11/21 notable for RLE DVT. She was admitted and heparin gtt was started, went for catheter directed thrombolysis on 4/11/21, received systemic alteplase. During the procedure, multiple PEA arrests and was cannulated for ECMO (4/11-4/20) with notable low flows (c/f RP bleed with RF sheath pull), vent dyssynchrony, high pressor requirements. Transferred to outside Hospital for ECMO management on 4/12/21. Course at outside hospital notable for AF w/ RVR s/p cardioversion, AKI on dialysis, small falcine subdural hematoma, right iliac artery stent, left leg weakness i/s/o L groin hemorrhage. On 4/22/21, Patient returned (extubated) to agency hospital ICU. HIT panel negative on 4/23/2021-patient transition back to heparin from argatroban. S/p emergent repair of left groin hemorrhage on 5/2/21. On 5/18/21, She was admitted to the acute rehabilitation unit. Per 7/29/21 Infectious Disease consult, "TTS can begin as early as 4 days post vaccination, and up to 42 days after. Some of the initial patients had prior risks for hypercoagulability. Thrombosis most often occurs in atypical locations (cerebral, abdominal) but can be pulmonary. There is almost always thrombocytopenia, and almost always a positive test for PF4 (platelet factor 4) antibodies, as with heparin-induced thrombocytopenia (but without exposure to heparin)--which turn out to be activating antibodies in this particular syndrome. Heparin should not be used in this syndrome, but rather IVIG and nonheparin anticoagulation. She could have had TTS (female, typical age, OCP use, documented major arerial thrombosis, and documented thrombocytopenia--albeit after receiving heparin. Unfortunately, it will be tough to know if she did--unless a lab saved some serum from the initial blood draw in ED before she received heparin. If so, a PF4 (HIT) antibody screen should be run on that saved sample. Without PF4 antibody confirmation TTS cannot be confirmed. A serotonin release assay would also be informative. If she did have TTS, there are very little data on which to base a decision about whether she should receive another dose of a COVID vaccine. Nearly all of the very limited experience with TTS has been with single dose vaccines. My sense about this however is that until it is better understood how to risk stratify individuals for COVID vaccine-associated TTS, I would not give her another dose of COVID vaccine. She may have risks (in addition to OCP) that we don't recognize that create a high likelihood of another post-COVID vaccine major thrombotic event. Given that she essentially died and was then resuscitated from the last one, I would not place her at repeated risk of the same until we understand more about how to predict or mitigate." On 8/3/2021, COVID-19 vaccine was added to the patient's allergy/adverse drug reaction coversheet in the electronic medical record system indicating that the patient should not receive a 2nd covid-19 per infectious disease and to re-evaluate for vaccine candidacy in the future once more data is available. Per 8/3/2021 Hematology consult, "Hypercoagulable work-up performed: APLS sceen at facility negative for ACA Abs, LAC (though on apixaban), aPS/PT Abs, B2G Abs Factor V Leiden negative on 6/7 Prothrombin negative on 6/7 antiphospholipid panel performed 7/22 was unremarkable (see imaging) Protein C returned elevated, though on apixaban. Protein S and ATIII not sent since on AC. A PF4 antibody was sent at hospital and was negative." "Given the severity of her pulmonary embolism with PEA arrest and requiring ECMO, would recommend that she remains on lifelong anticoagulation. Her hypercoagulable workup has been unrevealing thus far. LAC, protein C and S, and ATIII cannot be accurately assessed on anticoagulation however would not stop her anticoagulation to test for them at this time, since it would not change her management and put her at higher risk of worsening VTE." In terms of the relation to the COVID vaccine, it seems like the vaccine could be a provoking factor particularly in terms of the timing; however, there has not been a clear association between the mRNA vaccines and VTE. Vaccine-induced thrombotic thrombocytopenia has been described in relation to the adenovirus vector vaccines (JnJ, AstraZaneca) rather than mRNA vaccines, in which there has been sparse case reports and has not been found to be associated with VITT at this current time. This patient's platelets on admission were normal and only one reading was low at any time during her admission. In addition, her PF4 antibody was normal at hospital even after heparin exposure; this was positive in almost all patients diagnosed with VITT. Given that she had an mRNA vaccine with mostly normal platelet counts and negative PF4 antibody, this is unlikely to be vaccine-induced thrombotic thrombocytopenia. We would defer to infectious disease as to whether to pursue second dose of vaccine with this information."