Thrombotic thrombocytopenic purpura as the initial presentation of COVID‐19

We read the article “The ADAMTS13‐von Willebrand factor axis in COVID‐19 patients”¹ with interest and hereby present a relevant clinical case.

Thromboembolism predominates coronavirus disease 2019 (COVID‐19)'s coagulopathy, but there is a paucity of reported arterial events and microangiopathy.² Acute infections are associated with thrombotic thrombocytopenic purpura (TTP), caused by an autoantibody that inhibits the ADAMTS‐13 metalloprotease, responsible for cleaving von Willebrand factor (VWF).³ We describe the case of an asymptomatic patient positive for severe acute respiratory coronavirus 2 (SARS‐CoV‐2) presenting with TTP.

A 70‐year‐old man known for peripheral artery disease and dyslipidemia presented to the hospital for confusion. Home medication were aspirin and a statin. He had tested positive for COVID‐19 19 days prior, based on nasopharyngeal reverse transcription polymerase chain reaction that had detected SARS‐CoV‐2. He was completely asymptomatic for COVID‐19 upon presentation to the emergency room, where he thereafter had a prolonged seizure requiring sedation and intubation. Physical examination revealed no purpura or other relevant findings. A computed tomography of the head and a chest radiograph were normal. The initial complete blood count showed a platelet count of 18 × 10⁹/L (normal value: 130‐400 × 10⁹/l) and hemoglobin of 60 g/l (normal value: 130‐170 g/l). Features of hemolysis were found (high total bilirubin, high lactate dehydrogenase, and low haptoglobin) with schistocytes on the blood smear. Renal function and coagulation parameters were normal. He later mentioned having had dark urine 5 days before hospitalization (Table 1 ).

TABLE 1.

Evolution of laboratory findings from presentation until the end of plasma exchange therapy

	Day 1	Day 2	Day 3	Day 4	Day 7	Day 9
Plasma exchange	+	+	+	+	+	−
Hemoglobin (g/l) (130‐170)	60	74	73	75	81	79
Platelets (×109/l) (130‐400)	18	49	115	200	367	405
Leukocytes (×109/l) (4‐10)	8	10.5	13.7	10.6	7.7	6.2
Reticulocytes (×109/l) (20‐84)	—	—	—	254.5	207.9	169.6
Schistocytes on blood smear	+	+	+	—	—	—
Creatinine (μmol/l) (53‐112)	106	102	91	77	76	67
LDH (U/l) (104‐205)	1422	417	—	295	232	183
Total bilirubin (μmol/l) (7‐23)	38	23	—	14	—	—
Haptoglobin (g/l) (0.46‐1.46)	<0.3	0.48	—	0.79	0.67	0.69
Fibrinogen (g/l) (2‐4.5)	5.35	2.3	—	—	—	—
ADAMTS‐13 (%) (56‐133)	<10	—	—	—	—	43
ADAMTS‐13 IgG antibody	+ Titer 1/2	—	—	—	—	—
INR (0.8‐1.15)	1.07	1.05	1	1	0.93	0.98
PTT (22‐31)	24	23	22	22	22	23
SARS‐CoV‐2 (negative)	+	—	—	—	—	—

Abbreviations: ADAMTS‐13, disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; INR, international normalized ratio; LDH, lactate dehydrogenase; PTT, partial thromboplastin time.

A microangiopathic episode was confirmed and TTP was suspected. Anti‐ADAMTS‐13 immunoglobulin G antibody was weakly positive (titer 1/2) and ADAMTS‐13 activity was low (<10%). Treatment was initiated with transfusion of 2 U of plasma before transfer to the apheresis center. Methylprednisolone was given at a dose of 1 mg/kg daily for 2 days followed by oral prednisone at 50 mg daily. Daily plasma exchange was initiated (1.5 volume exchange; Spectra Optia, TERUMOBCT) with plasma replacement. Clinically, the patient recovered rapidly without neurologic sequelae and was extubated after 24 h. Platelet count improved gradually and then rapidly after the second plasma exchange. Treatment was stopped after the seventh plasma exchange as platelet count and lactate dehydrogenase had normalized for more than 48 h. ADAMTS‐13 activity at discharge normalized (43%). A diagnosis of COVID‐19–induced TTP was made because no other causes could be associated with the episode.

Previous cases of COVID‐19–associated TTP mostly included patients with other classic COVID‐19 symptoms.4., 5. To our knowledge, this is the first case of an initial presentation of a COVID‐19 infection with a severe microangiopathic episode and neurological symptoms in an otherwise asymptomatic patient. Interestingly, this severe microangiopathic activity was present despite a low titer of anti‐ADAMTS‐13 immunoglobulin G antibody. Studies have shown that SARS‐COV‐2 causes endothelial damage that could release higher amounts of VWF independently of the ADAMTS‐13 activity. ADAMTS‐13 activity also tends to be decreased in inflammatory states.1., 6., 7. This could possibly explain the severity of the initial presentation, even with low antibody activity, as well as the fast recovery.2., 7. Full mechanisms remain incompletely understood.

In conclusion, this is a unique case of severe COVID‐19–induced TTP with microangiopathy and cerebral arterial ischemic events. Pathophysiology probably implies a combination of immune dysregulation and inflammation.1., 2., 8., 9., 10.

CONFLICT OF INTEREST

The authors have no disclosures to declare.

AUTHOR CONTRIBUTION

Marie‐Claude Beaulieu and Danny Sebastien Mettelus contributed to the study design, data collection, literature review, and case report redaction. Michèle Mahone and Benjamin Rioux‐Massé also designed the study. They revised all intellectual content and gave their approval for final version to be submitted.