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.