Extensive Arterial Thrombosis in Covid-19.

A 70-year-old woman with hypertension and type 2 diabetes presented to the hospital with a cold, pulseless, and pale left leg. On examination, her left leg was found to have mottling and pallor to the level of the proximal left calf. There were absent left femoral, popliteal, or pedal pulses. In contrast, there were palpable pedal pulses on the right side.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction was positive. Computed tomography angiogram revealed extensive arterial thromboses including nonocclusive thrombus of the infrarenal abdominal aorta near the aortic bifurcation, occlusion of the left common iliac artery, internal iliac artery, and external iliac artery to the level of the iliac ligament with complete occlusion of the popliteal artery below the knee and its branches (Figure 1, left panel). The patient had no history of venous or arterial clots, no known vasculopathy, minimal underlying atherosclerosis, no personal or family history of hypercoagulable disease, no aortic compression as nidus for thrombus formation, and evaluation for malignancy has been negative to date. An initial hypercoagulable workup (Table 1) found a positive lupus anticoagulant by dilute Russell's viper venom time and hexagonal phase assays.

Figure 1

Computed tomography angiogram at initial presentation (left panel) and after emergent thrombectomy and thrombolysis (right panel). Consent for publication was obtained from the patient.

Table 1

Laboratory findings on admission

	Laboratory results on admission	Reference range*
Platelet count (K/L)	217	150-450
D-dimer (ng/mL)	>4000	<500
Prothrombin time (sec)	14.6	11.5-14.5
International normalized ratio	1.2	0.9-1.1
Activated partial-thromboplastin time (sec)	26.6	23.8-36.6
Fibrinogen (mg/dL)	320	200-450
Lactate dehydrogenase (U/L)	642	135-225
Ferritin (ug/L)	617	13-150
High-sensitivity C-reactive protein (mg/L)	95	0-10
B2 glycoprotein 1 Ab, IgG (CU)	<6.4	0-19
B2 glycoprotein 1 Ab, IgM (CU)	12	0-19
Cardiolipin Ab, IgG (CU)	3	0-19
Cardiolipin Ab, IgM (CU)	53	0-19
Protein C Resistance	4.2	>2.2
Dilute Russell's viper venom time	Positive	Negative
Lupus anticoagulant (hexagonal phase)	Positive	Negative

Reference values are affected by many variables, including the patient population and the laboratory methods used. The ranges used at Brigham and Women's Hospital are for adults who are not pregnant and do not have medical conditions that could affect the results. They may therefore not be appropriate for all patients.

Hypercoagulability and endothelial injury have been described as features of coronavirus disease 2019 (Covid-19). While asymptomatic or symptomatic venous thromboembolism has been frequently observed, arterial thrombosis and acute limb ischemia have less commonly been described. Lupus anticoagulant has been identified commonly in Covid-19, and if persistent, is known to be associated with thrombosis in antiphospholipid syndrome. In this case, lupus anticoagulant may have been a false-positive test result in context of acute illness and the receipt of unfractionated heparin. Critical illness and marked inflammatory response in the setting of Covid-19 likely increased propensity for thrombus formation and acute limb ischemia in this patient.

She underwent emergent thrombectomy and thrombolysis and 4-compartment fasciotomy, with limb salvage and revascularization (Figure 1, right panel). She was initially treated with unfractionated heparin and was bridged to warfarin for maintenance anticoagulation, and discharged to rehabilitation for ongoing recovery. Heightened clinical vigilance is needed for early identification of this potentially serious complication of Covid-19 to facilitate prompt intervention targeting limb salvage,3, 4, 5, 6 Further research is needed to determine the role of hypercoagulability in Covid-19, and to identify strategies to prevent and treat venous and arterial thrombosis in this setting.

Disclosures

Dr Vaduganathan is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (NIH/NCATS Award UL 1TR002541), serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa, and participates on clinical endpoint committees for studies sponsored by Novartis and the NIH. All other authors report no disclosures.