Age: 53.0
Sex: M
Vaccine: HEP
Symptoms: Protein total normal, Protein urine present, Prothrombin time normal, Pyelogram retrograde abnormal, Red blood cell sedimentation rate normal
Clinical narrative: This case was reported by a pharmacist via other manufacturer and described the occurrence of atrial flutter in a 53-year-old male patient who received ENGERIX B adult. On 1st October 2014, the patient received the 2nd dose of ENGERIX B adult. In October 2014, less than a month after receiving ENGERIX B adult, the patient experienced deep vein thrombosis (serious criteria GSK medically significant), acute renal failure (serious criteria GSK medically significant) and hepatic cirrhosis (serious criteria GSK medically significant). On 20th October 2014, the patient experienced atrial flutter (serious criteria hospitalization and other: As per reporter), respiratory failure (serious criteria GSK medically significant), hypertension aggravated, tachycardia and chest pain. On an unknown date, the patient experienced type II diabetes mellitus (serious criteria GSK medically significant), ascites (serious criteria GSK medically significant), bladder disorder, pulmonary effusion and lethargy. The patient was treated with COUMADIN, carvedilol, VICTOZA, NOVOLOG, Sliding Scale Insulin, LANTUS, amiodarone and lisinopril. On an unknown date, the outcome of the atrial flutter, deep vein thrombosis, acute renal failure, respiratory failure, hypertension aggravated and bladder disorder were recovered/resolved and the outcome of the hepatic cirrhosis, type II diabetes mellitus, ascites, pulmonary effusion, lethargy, tachycardia and chest pain were unknown. The reporter considered the atrial flutter, acute renal failure, hepatic cirrhosis, type II diabetes mellitus, respiratory failure, hypertension aggravated and bladder disorder to be unrelated to ENGERIX B adult. The reporter considered the deep vein thrombosis to be possibly related to ENGERIX B adult. It was unknown if the reporter considered the ascites, pulmonary effusion, lethargy, tachycardia and chest pain to be related to ENGERIX B adult. Additional details were received as follows: The blinded study vaccine was confirmed to be ENGERIX B adult. The patient was 53 years old man, who was enrolled in the other manufacturer's sponsored study. Relevant medical history included chronic obstructive pulmonary disease (COPD) (1990), kidney stones (1992), osteoarthritis in bilateral hands (2009), bilateral pedal edema (2011), reactive airway disease (2011), and hypertension (2012). It was noted that the subject was homeless and lived out of his car. Relevant concomitant medications included multivitamin, ibuprofen and DULERA. On 3rd September 2014, the patient received 1st dose of blinded study vaccine (ENGERIX B adult). On 1st October 2014, the patient received 2nd dose of blinded study vaccine (ENGERIX B adult). On 20th October 2014, 19 days after the most recent dose of blinded study vaccine (ENGERIX B adult), the patient went to his primary care physician (PCP) for the evaluation of chest pain and he was advised to go to the hospital. The site confirmed that the outcome of the event cirrhosis will remain unchanged and that the subject reported that his deep vein thrombosis was asymptomatic. The deep vein thrombosis (DVT) was discovered during testing while the subject was hospitalized, that the DVT was treated with heparin while hospitalized and that the patient was discharged on COUMADIN. The site confirmed that the history of "stones" referred to kidney stones. Corrected adverse events form for the event of deep vein thrombosis, confirming the onset date as 23-Oct-2014 and the investigator's assessment of relationship to study vaccine as possibly related. The site stated that they would provide an update after the subject had completed the week 56 site visit to clarify the outcome status of the events of cirrhosis, focal thickening on the posterior wall of the urinary bladder, and type II diabetes. The updated outcome and end date for the event of focal thickening on the posterior wall of the urinary bladder (resolved on 4th December 2014), and updated outcomes for the events of cirrhosis and type II diabetes (not resolved, chronic but stable). The patient was hospitalized for atrial flutter and was subsequently diagnosed with the important medical events of acute renal failure, cirrhosis, focal thickening on the posterior wall of the urinary bladder, type II diabetes, worsening hypertension, deep vein thrombosis, and respiratory failure. Vital signs upon arrival were as follows at 11:29 am: blood pressure 136 per 106 mmHg, heart rate 165 beats per minute, temperature 97.8 degrees Fahrenheit, oxygen saturation 83 percent on room air, and oxygen saturation 93 percent on 2 liters via nasal cannula. At 3:42 pm on the day of arrival vital signs were as follows: blood pressure 164 per 87 mmHg, heart rate 148 beats per minute, body temperature 97.9 degrees Fahrenheit, and oxygen saturation 92 percent on 2 liters via nasal cannula. Laboratory test results on arrival included the following: total white blood cell count 8.8 per liter, haemoglobin 15.6 g per dL, haematocrit 49.0 percent, platelet count 131 per liter, glucose 148 mg per dl, sodium 133 mmol/L, potassium 4.8 mmol/L, blood urea nitrogen (BUN) 28 mg per dL, creatinine 1.13 m per dL, and thyroid stimulating hormone (TSH) 1.35 mcIU per mL, serial Troponin T values (0.02 ng per mL, 0.01 ng per mL, 0.01 ng per mL were within normal range, chest x-ray showed right basilar airspace disease, compatible with atelectasis versus pneumonia. The patient was admitted to the hospital with respiratory failure and was found to be in atrial flutter. He was transferred to the intensive care unit where he needed bilevel positive airway pressure (BiPAP) to improve his respiratory status. He was still in atrial flutter with a fast rate and subsequently underwent electrical cardioversion with good response. He returned to sinus rhythm, but was tachycardiac with a heart rate of 104 beats per minute at rest. Supplemental oxygen was not required. The subject was also found to have worsening hypertension. On 21st October 2014, laboratory results were notable for potassium 5.9 mmol/L, blood urea nitrogen (BUN) 36 mg per dL, creatinine 1.4 mg per dL, and glucose 212 mg per dL, sedimentation rate was 1 mm per hour, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin were all within normal range. On 22 October 2014, the subject's laboratory results included creatinine 2.52 mg per dL, blood urea nitrogen (BUN) 52 mg per dL, potassium 6.0 mmol/L, and phosphorus 7.6 mg per dL. The acute renal failure was thought to be exacerbated by Angiotensin converting enzyme inhibitors, BACTRIM and nonsteroidal anti-inflammatory drugs (NSAIDS) (the investigator assessed that it was unknown if the ACE inhibitors, BACTRIM, and NSAIDs were co-suspect medications). Additional laboratory results on that day included blood glucose 188 mg per dL and haemoglobin A1C 9.3 percent. D dimer was 559 ng per mL and heparin level was 0.40 IU per mL. IgA, IgG, IgM, total protein albumin, alpha 1 globulin, alpha 2 globulin, beta globulin, and gamma globulin were all within the reference range. Urinalysis revealed cloudy, yellow urine with pH 7.0, specified gravity 1.025, urine was negative for glucose, ketones, nitrite, and leukocyte esterase and was positive for protein 30 mg per dL, a trace amount of blood, and urobilinogen 1mg per dL. Microscopic urinalysis was notable for white blood cells 50 to 100 per hpf, red blood cells 5 to 10 per hpf, hyaline casts 20 to 50 per hpf, squamous epithelial cells 3 to 5 per hpf, and a few bacteria; mucous and amorphs were present. A renal and bladder ultrasound showed no urinary tract obstruction. A nonspecific 2.3 cm irregular lobular hypoechoic cortical defect on right kidney was indeterminate for solid or cystic mass. There was mild ascites. A chest x-ray confirmed placement of the central lines and no change cardiomegaly with pulmonary edema or heart failure. On 23rd October 2014, 23 days after the most recent dose of blinded study vaccine (ENGERIX B adult), the subject underwent a bilateral lower extremity venous ultrasound, which revealed an acute, partially occluding deep venous thrombosis of the left popliteal vein, no evidence of deep venous thrombosis of the right lower extremity, and no evidence of superficial venous thrombosis of the bilateral great saphenous veins. A lower extremity arterial duplex ultrasound showed normal artery size bilaterally throughout the lower extremities, no hemodynamically significant evidence of arterial disease in either lower extremity, and normal blood flow velocities throughout both lower extremities. The subject was asymptomatic. Heparin therapy was initiated for the deep vein thrombosis (DVT). Laboratory results included blood urea nitrogen (BUN) 48 mg per dL, creatinine 1.66 mg per dL, sodium 130 mmol/L, potassium 5.3 mmol/L and glucose 164 mg per dL. Blood cultures drawn on 22nd October 2014 were reported as negative and urine was negative for Streptococcus pneumoniae antigen. Arterial blood gases were notable for pH 7.36, PC02 61, P02 57, bicarbonate 33.5 and oxygen saturation 89.4. On 24th October 2014, a nuclear medicine ventilation perfusion scan showed no significant segmental or sub segmental defects. There was a very low probability of pulmonary thromboembolism. A Computer tomography (CT) scan of the chest and abdomen without contrast showed small moderate right pleural effusion. There was collapse of the right lower lobe and small left pleural effusion. There was consolidation and volume loss in the posterior left lower lobe. The upper lung zones were clear and minimal centrilobular emphysema was seen at the lung apices. Abnormal findings included a small amount of ascites, a well circumscribed, 2.1 by 1.4 cm hyperdense cyst at the lateral aspect of the upper right kidney. There was a 2 mm stone in the lower pole of the right kidney. No stones or masses were seen in the left kidney. There were no adrenal masses. The impression included bilateral pleural effusions with consolidation of the lower lobes of the lungs, greater on right than left consistent with atelectasis. Underlying pneumonia was not excluded. There was no evidence of pulmonary edema at this time. There was a hyperdense cyst of the lateral right kidney. The appearance of the liver was suggestive of cirrhosis, liver function test results remained within normal ranges. On 25th October 2014, 25 days after the most recent dose of study vaccine (ENGERIX B adult), Computer tomography (CT) scan of the abdomen and pelvis with and without contrast showed cirrhosis with free peritoneal fluid. Bilateral pleural effusions were noted causing bibasilar volume loss. A hyperdense lesions on the posterior lateral right kidney did not enhance and most likely represented a cyst that contained protein or blood products. There were at least two other small low-density lesions in the inferior right kidney that were too small to characterize and warranted follow up CT Scan in 6 months. A bilateral pars defect at L5 caused mild subluxation. Two rounded areas of focal thickening on the posterior wall of the urinary bladder were subtle. They could represent ureteroceles but were not typical. Bladder wall neoplasm was noted as a possibility. There was also a focal area of bladder wall thickening involving the right side of the upper right. On 27th October 2014, a chest x-ray showed persistent small bilateral pleural effusions with bibasilar atelectasis, minimal diffused interstitial congestion. A new right PICC line was visible. No pneumothorax was noted. On 30th October 2014, the subject underwent a cystoscopy with bilateral retrograde pyelograms. Findings included a partially duplicated collecting system on the right with slow drainage, mild to moderate hydronephrosis on the right, and erythematous patches in the bladder concerning for carcinoma in situ versus cystitis and irritation. Biopsies of the bladder were taken, followed by fulguration of the biopsy sites. On 3rd November 2014, the event of atrial flutter was considered resolved. The patient's blood sugars were controlled by VICTOZA, NOVOLOG sliding scale insulin (SSI), and LANTUS and the patient was provided with nutrition counseling as he usually ate a lot of candy and regular drinks. The glucose levels improved from 199 to 152 mg per dL and it was assessed that the glucose level could be controlled with carbohydrate limitations and oral medication. On 4th November 2014, laboratory test results included sodium 135 mmol per L, blood urea nitrogen (BUN) 29 mg per dL, potassium 4.6 mmol per L, glucose 100 mg per dL and repeat glucose 170 mg per dL and 124 mg per dL. The respiratory status had slowly improved, he was ambulating well. Overall left ventricular ejection fraction was approximately 40 to 50 percent. The patient was discharged with instructions to follow-up in 6 days. (Atrial flutter). Amiodarone and COUMADIN were initiated for treatment of atrial flutter. LANTUS therapy was also started for newly diagnosed type II diabetes, carvedilol and lisinopril were prescribed for hypertension and torsemide was prescribed for edema. Discharge medications included COUMADIN (confirmed as prescribed for the deep vein thrombosis (DVT), LANTUS, amiodarone, COREG, lisinopril, DEMADEX, potassium chloride, and DULERA. Discharge diagnoses included capo exacerbation, atrial flutter, respiratory failure, deep vein thrombosis and type II diabetes mellitus. The events of acute renal failure, worsening hypertension, deep vein thrombosis and respiratory failure were considered resolved on the day of discharge. The investigator noted that the bilateral effusions of lower lobes of lungs, mild ascites, capo, and lethargy were considered non-serious adverse events. On an unspecified date, the patient reported that a biopsy of the right kidney cyst was performed which was reported as benign. The patient reported this information to the study staff on 13th November 2014, and reported that he is scheduled for follow-up appointments with a cardiologist on 18th November 2014 and with an urologist on 4th December 2014. On 4th December 2014, the event of focal thickening on the posterior wall of the urinary bladder was considered resolved. On 11th December 2014, per-protocol coagulation testing was normal except for low protein C activity 41 percent, Lupus anticoagulant Ratio (-70) 1.62 and Lupus Anticonfirm (LA2) (-70) 50.9 seconds. Protein S activity was also at the low end of normal: 68 percent. It is noted that the patient was on warfarin therapy during this testing making the Lupus anticoagulant results difficult to interpret. On 28th July 2015, the site indicated that after the patient had completed the week 56 site visit, follow-up will be provided to clarify the outcomes or status of the event so cirrhosis, focal thickening on the posterior wall of the urinary bladder, and type II diabetes. On 16th September 2015, the investigator reported that the events of cirrhosis and type II diabetes were not resolved; both events were considered to be chronic but stable. The patient was withdrawn from further study vaccine administration as the result of the events, acute renal failure, cirrhosis, focal thickening on the posterior wall of the urinary bladder, type II diabetes, deep vein thrombosis, worsening hypertension, atrial flutter, and respiratory failure. The investigator assessed the atrial flutter as serious (hospitalization), and the acute renal failure, cirrhosis, focal thickening on the posterior wall of the urinary bladder, type II diabetes, worsening hypertension, deep vein thrombosis and respiratory failure as serious (important medical event) and all of severity grade 4. Atrial flutter, acute renal failure, cirrhosis, focal thickening of the posterior wall of the urinary bladder, type II diabetes, worsening hypertension, and respiratory failure were considered not related to the study vaccine. The deep vein thrombosis was considered possibly related to the study vaccine. An alternative explanation for causality of all the events reported was unknown. This case has been linked with cases US2016GSK011104, US2016GSK011105 and US2016GSK011106 reported by the same reporter.