Age: 48.0
Sex: M
Vaccine: COVID19, COVID19, COVID19, COVID19
Symptoms: Pain in extremity, Platelet count decreased, Pulmonary embolism
Clinical narrative: BILATERAL LOWER EXTREMITY PAIN; MULTIPLE ACUTE BILATERAL PULMONARY EMBOLI; PLATELET COUNT DECREASED; DEEP VEIN THROMBOSIS; VACCINE INDUCED THROMBOTIC THROMBOCYTOPENIA; ULTRASOUND DOPPLER ABNORMAL; FULL BLOOD COUNT; METABOLIC FUNCTION TESTS; MUSCLE SPAMS; SWELLING; MILD HEADACHE; This spontaneous report was received from a health care professional via a Regulatory Authority and from literature and concerned a 48 year old male. The patient's height, and weight were not reported. The patient's concurrent conditions included exercise induced asthma, and no tobacco use (both current and historically), and other pre-existing medical conditions included the patient had no known allergies. The patient was not obese, denied recent procedures, prolonged immobility, family history of bleeding or clotting disease, etc. The patient was up to date on cancer screenings based on age/family history. He was reported as being an unusually physically active and fit 48 year-old male who has enjoyed good health and exercised regularly. In 2019, his platelet count was 177 10*9/L. The patient reported flying out of town and back on 30-MAR-2021 and 04-APR-2021 respectively with the longest continuous flight lasting around 4 hours. The patient at age 48, received covid-19 vaccine ad26.cov2.s (suspension for injection, intramuscular, batch number: 201A21A, expiry: UNKNOWN) dose was not reported, 1 total administered on 07-APR-2021 for prophylactic vaccination. Concomitant medications included finasteride, and salbutamol.  On  an unspecified date in APR-2021, the patient experienced mild headache.  On 18-APR-2021, 11 days after receiving the vaccine, the patient experienced deep vein thrombosis, vaccine induced thrombotic thrombocytopenia; new pain in his big toe, bilateral leg cramping (muscle spasm), bilateral lower extremity pain, and swelling. The patient attributed soreness in the large muscle groups of his thighs to Peloton riding and exercise. The patient travelled again via airplane to an unspecified location 22-APR-2021 and 25-APR-2021 (both1 hr long flights). The patient administered Advil for the leg pain when he returned on an unspecified date. On an unspecified date he felt a leg vessel that "didn't seem right." On 26-APR-2021 the patient went to emergency department for evaluation presenting with leg pain and chest discomfort. He had normal vital signs and oxygen saturation. Additional laboratory results: Platelet count (NR 140-440  K/uL) 74;  fibrinogen (NR 150-430 mg/dL) of 254; D-dimer (NR 0-499 ng/mL FEU) 15,109 ng/mL FEU; activated partial thromboplastin time (aPTT) (NR 25.1-36.5 s)  31.8.  Venous duplex ultrasound of the lower extremities revealed non-occlusive DVT in the bilateral popliteal veins extending to the gastrocnemius veins, an occlusive DVT of the left posterior tibial vein, as well as occlusive superficial venous thrombosis in the bilateral saphenous veins.  The patient was discharged from the emergency room on rivaroxaban 15 mg twice daily with two-day follow-up with his primary care physician. He had no known exposure to heparin before the onset of symptoms and no exposure during his emergency room visit. On 28-APR-2021 (also reported as the next day), the patient complained of a new onset of chest pain (pleuritic) and presented again to the emergency room.  Chest CT showed presence of acute pulmonary embolism, with emboli present in segmental and more proximal arteries. He had already taken his rivaroxaban for the night (1800). The patient was hospitalized for further evaluation and work up. A peripheral smear showed thrombocytopenia without schistocytes. The hematology service was consulted, and a presumptive diagnosis of VITT (vaccine induced thrombotic thrombocytopenia) was made. His anti-PF4 enzyme-linked immunosorbent assay (ELISA) (LIFECODES PF4 IgG), performed on a sample collected prior to initiating IVIG therapy, demonstrated a strongly positive result of 3.323 optical density (OD) units (reference interval < 0.399), consistent with a diagnosis of VITT. The patient was immediately treated with 1 g/kg of intravenous immunoglobulins (IVIG) for 2 days, 1 mg/kg of prednisone, and switched from rivaroxaban to an intravenous argatroban infusion drip, during which he achieved therapeutic aPTT levels between 44 - 50 sec.  The patient was also treated with apixaban.  Other studies included:  Magnetic resonance venography (MRV) and angiography (MRA) of the brain, performed due to symptoms of mild headaches, were unremarkable. Platelet factor 4 (NR: not provided) strong positive at 2.9 OD; Prothrombin mutation G20210A not detected, Red blood cell count (NR: 3.98 - 5.98) 5.07 M/ microliter, Red blood cell sedimentation rate (NR: not provided) Normal, SARS-CoV-2 test was negative, Serotonin release assay was positive, and WBC (NR: 3.2 - 10.6) 5.8 K/microliter. Anticardiolipin antibodies (NR: not provided) 5 GPL, Beta-2 glycoprotein 1 antibodies (NR: 0 - 20) 0 SGU, 5 SMU, Blood homocysteine (NR: not provided) 13.4 nml (normal), C-reactive protein (NR: not provided) 2.6, Cardiolipin immunoglobulin G (NR: 0 - 12) 6 MPL, Cell marker increased was positive, EKG (NR: not provided) Normal, Hematocrit (NR: 36.9 - 52.1) 42.2 %, Hemoglobin (NR: 2.5 - 18.0) 15.0 g/dL, Lupus anticoagulant (NR: not provided) not detected, MCHC (NR: 33.4 - 35.3) 35.5 g/dL, MCV (NR: 80.6 - 97.6) 83.2 fL. On an unspecified date the serotonin release assay was no longer positive. Within a week post-discharge, the patient developed recurrent thrombocytopenia, with a platelet count that down trended to 107  10*9/L  His thrombocytopenia appeared to somewhat correlate with prednisone dose adjustments, suggesting an autoimmune-driven process, although it did not respond to repeat IVIG administration. Due to the normalized D-Dimer levels and negative SRA, it was assumed that there was no further ongoing platelet activation. The authors stated the patient had no prior risk factors for thrombosis other than the 2 recent 4-hour flights. The action taken with covid-19 vaccine ad26.cov2.s was not applicable. The patient recovered from bilateral lower extremity pain, was recovering from deep vein thrombosis, vaccine induced thrombotic thrombocytopenia, platelet count decreased, swelling, full blood count, metabolic function tests, muscle spasms, ultrasound doppler abnormal, and multiple acute bilateral pulmonary emboli, and the outcome of mild headache was not reported. This report was serious (Hospitalization Caused / Prolonged). This case is a duplicate of 20210642952.  Additional information was received from literature article on 19-JUN-2021. The following information was updated and incorporated into the case narrative: literature reference information, additional reporters, laboratory data, updated events.  It has been determined that Manufacture Report Number 20210514958 is a duplicate of deleted case 20210642952. All relevant information from Manufacture Report Number 20210642952 will be reported in this case 20210514958.; Sender's Comments: V2: Follow up consisted of a literature citation, presenting this case as a case report.  This does not change the previous assessment. This case obtained via VAERS (ID 1264060) concerns a 48-year-old male who developed symptoms of bilateral lower extremity deep vein thromboses (DVT) and thrombocytopenia 11 days after receiving Janssen Covid-19 vaccine. Concurrent conditions included exercise induced asthma. Patient was not obese, did not smoke, denied recent procedures, family history of bleeding/clotting disease & was physically active. He was up to date on cancer screenings based on age/family history. He had taken two 1-hour long flights 15 days and 18 days post-vaccination.  Concomitant medications included finasteride & salbutamol. After 1 week of bilateral leg cramping & swelling which began 11 days post-vaccination, he presented to emergency department (ED) where complete blood count showed platelets 74 k/uL, peripheral smear with giant platelets, and d-Dimer 15K. Venous duplex ultrasound showed nonocclusive DVT in the bilateral popliteal veins extending to the gastrocnemius veins, occlusive superficial vein thrombosis in the bilateral saphenous veins, and occlusive DVT of the left posterior tibial vein. He was started on rivaroxaban & was not hospitalized. Two days later, he developed new chest pain & returned to ED, where CT chest showed numerous bilateral pulmonary emboli. He was hospitalized; empiric treatment for vaccine-induced immune thrombotic thrombocytopenia was started: IVIG, steroids, & argatroban.  Anti-PF4 resulted as OD=2.9 and 3.323 (strong positive), confirming diagnosis. The patient was recovering from the events. Based on evolving knowledge of Thrombosis with Thrombocytopenia Syndrome (TTS, per definition from Brighton Collaboration), low platelet count & temporal relationship to vaccination, the events are assessed to have a plausible relationship with vaccination.