COVID19 Associated Thrombotic Angiopathy Improved After Plasma Exchange
Natalie Elkayam, M.D.1; Gagan Raju, M.D.1; Bluth, Martin, M.D. Ph.D.2; Huang, Yiwu, M.D.1; Lipshitz, Jay, M.D.1; Peeke, Stephen, M.D. 1
1Department of Hematology and Oncology, Maimonides Medical Center, Brooklyn, NY, USA
2Department of Pathology, Maimonides Medical Center, Brooklyn, NY, USA
Corresponding author: Gagan Raju, MD (gagan.raju@gmail.com)
Case presentation:
A 44-year-old Chinese woman with no known medical history presented to the emergency department for evaluation of shortness of breath. The patient reported fevers, chills and a dry cough which had progressively worsened during the preceding week. Her husband was also sick at home with similar symptoms. Upon arrival to the emergency room, she was afebrile (36.4℃) with a blood pressure of 132/87 mmHg, tachycardic (122 beats/minute) and tachypneic (25 breaths/minute). Her oxygen saturation was 80% on 6 L of oxygen via nasal cannula requiring escalation to a non-rebreather mask on which her oxygen saturation declined to 75%. Due to progressive dyspnea and hypoxia refractory to oxygen supplementation, she was endotracheally intubated and mechanically ventilated on account of acute respiratory failure. Initial laboratory studies demonstrated creatinine of 1.0 mg/dL, lactate dehydrogenase (LDH) was 2334IU/L and liver function tests (LFT) were aspartate transaminase (AST)/alanine transaminase (ALT) 79/63 IU/L with bilirubin levels within normal limits. Coronavirus-2019 (COVID19) PCR was reactive. C-reactive protein (CRP) was 38.6mg/dL and ferritin was found to be 297.9 ng/ml. Her complete blood count (CBC) on presentation demonstrated the following: white blood cell (WBC) 13.4 cells/L, hemoglobin (Hgb) of 11.7 g/dL and platelet count of 243k/uL. Coagulation profile including international normalized ratio (INR), activated partial thromboplastin time (aPTT) and fibrinogen were all in normal range. Patient was admitted to the medical intensive care unit for management of septic shock and acute respiratory failure secondary to acute COVID19 infection. She underwent CT angiography of the chest, which demonstrated no pulmonary embolism and bilateral, predominantly ground glass opacities consistent with COVID19 infection changes.
The patient received dexamethasone therapy as indicated in the standard of care for management of severe COVID19 infection. Within one day of her hospitalization, her laboratory findings demonstrated worsening renal function (blood urea nitrogen (BUN)/creatinine 45/2.2 mg/dL), and worsening total bilirubin up to 4.0 mL/dL within 3 days of her admission. The patient underwent continuous venovenous hemodiafiltration (CVVHD) for acute renal failure. Her troponin trended up to 1.41 ng/mL, which was attributed to demand ischemia due to underlying infectious process. Her WBC count remained stable throughout her admission. Her hemoglobin decreased to 6.8 g/dL and she received PRBC transfusion. Her platelet count within one day of admission dropped from 243 to 65k/µL and further decreased to 23k/µL. Poly Coombs test was negative. Heparin induced thrombocytopenia (HIT) antibody was negative.
Due to dropping hemoglobin and platelet values, hematology evaluation was obtained for assessment of possible thrombotic thrombocytopenic purpura (TTP). Peripheral smear demonstrated normochromic red blood cells (RBC) with some polychromasia, numerous nucleated RBCs, occasional basophilic stippling with many schistocytes identified (approximately 5-6/high power field). No platelet clumps were identified though some large platelets were observed and manual platelet count estimated around 30-50k. Polymorphonuclear cells with toxic granules, many band cells and some large activated lymphocytes were identified. ADAMTS13 testing was sent.
On account of high clinical suspicion for thrombotic angiopathy, a decision was made to commence empiric plasma exchange in advance of receipt of ADAMTS13 level. The patient underwent plasma exchange with one blood volume of fresh frozen plasma (FFP) for five consecutive days.
After initiation of plasma exchange, the patient’s laboratory values demonstrated significant improvement: LDH level improved from 3802 to 945 within one day of plasma exchange initiation. Total bilirubin levels improved from 4.0 to 2.9 within one day of plasma exchange. After the initial plasma volume exchange, her platelet count increased from 18k to 68k and continued to increase and eventually normalize thereafter, concurrent with daily plasma exchange. The patient also showed significant clinical improvement with declining vasopressor requirement after the second day of plasma exchange and subsequently required antihypertensives due to elevated blood pressure on the third day of plasma exchange. Peripheral smear on the fourth day of plasma exchange demonstrated a significant decrease in schistocytes per high power field. The presumption was that the rapid clinical improvement concurrent with plasma exchange was consistent with the diagnosis of TTP. However after five consecutive plasma exchanges, the ADAMTS13 level (drawn before initiation of plasma exchange) resulted at 50.7%, subsequently plasma exchange was discontinued. The patient no longer required renal replacement therapy.