INTERNAL CAROTID ARTHERY THROMBOSIS

IN IRON DEFICIENCY ANEMIA

Ruocco I1, Bracco C2, Brignone C2, Migliore E2, Morgillo T2,
Serraino C2, Fenoglio L2
1 Post-graduate school of Internal Medicine, University of Turin, Turin, Italy
2Division of Internal Medicine, Department of Medicine, "Santa Croce e Carle" Hospital, Cuneo, Italy

We concluded for a diagnosis of ICA thrombosis in

BACKGROUND thrombocytosis due to iron deficiency anemia, having
Iron deficiency anemia is a frequent condition: it has been
excluded other thrombophilic conditions.
estimated to affect about 20% of human population at any given
time[1]. Iron deficiency anemia can lead to reactive DISCUSSION and CONCLUSIONS
thrombocytosis, a known cause of venous thromboembolism Our patient presented with severe reactive (or secondary)
(VTE). However, arterial thrombosis in the context of iron thrombocytosis, that can be caused by iron deficiency, sepsis,
deficiency anemia is rare. neoplasms, asplenia and chronic inflammatory diseases.
Here is a case of repeated internal carotid artery occlusion Thrombocytosis can occur also as a primary event in
in a young woman, which required a comprehensive evaluation myeloproliferative neoplasms, including essential
of known prothrombotic risk factors and was then attributed to thrombocythemia, polycythemia vera, chronic myeloid
leukemia and myelodysplastic syndromes. Although
thrombocytosis in iron deficiency anemia.
secondary thrombocytosis is more frequent, it carries a lower
CASE PRESENTATION risk of thrombotic events. Iron deficiency anemia has been
A 49-year-old woman was admitted to Emergency Department identified as risk factor for venous thromboembolism, but it
with acute onset of left-sided limb weakness accompanied by is seldom the cause of acute arterial thrombosis. In anemic
facial palsy, which lasted 45 minutes and reversed patients, the thrombotic risk is notably augmented by
spontaneously. Her past medical history was negative for thrombocytosis. A recent large cohort study on 6 million cases
previous thrombotic events nor cardiologic risk factors. She had with iron deficiency anemia found a rate of 32.6% increased
not yet reached menopause. She didn’t assume medications at platelet count. In this cohort, about 1 on 8 patients developed
home on regular basis. The Angio computed tomography thrombotic events, mainly of the venous type and in cases
(AngioCT) scan showed a free-floating thrombus in the with thrombocythemia (15,8% vs 7,8%) [2].
Internal carotid artery (ICA). The patient was diagnosed with a
transient ischemic attack (TIA) and underwent urgent
thromboendarterectomy. The diagnostic workup excluded
cardioembolic pathogenesis via an Holter ECG and a
transthoracic echocardiography. A patent foramen ovale was
ruled out by contrast echocardiography and transcranial
doppler. The patient started taking low-molecular weight
heparin (LMWH) at therapeutic dosing in addition to
acetylsalicylic acid (ASA) 100 mg/die and was discharged.
Heparin was interrupted at the follow-up visit at 4 weeks, when Fig. 1 – Low iron status causes megakaryocytic
differentiation. Blood 2019
results of anti-phospholipid antibodies were negative. A few
days after discontinuation of heparin, a new TIA with identical Pathogenetic mechanisms of thrombocytosis in iron
symptoms occurred. On this admission, laboratory workup deficiency are been investigated: they involve the expansion of
showed a hemoglobin level of 5.2 g/dL, mean corpuscular common progenitor cells and augmentation of
volume of 62 fL, white blood cell count of 6.58 x 10^3/uL and megakaryocyte differentiation. In-vitro studies demonstrated
platelet count of 933 x 10^9/L. Iron studies showed an iron that thrombocytosis leads to augmented thrombin generation,
level of 37 ug/dL, a ferritin level of 8.6 ng/mL, a transferrin as well as abnormal platelet activation and aggregation.
level of 425 mg/dL with a transferrin saturation of 6%, which Moreover, it has been suggested that iron deficiency may play
established the diagnosis of severe iron deficiency anemia. An a role in low-grade chronic inflammation, a known
AngioCT was repeated, which showed a small thrombotic prothrombotic status, and in endothelial damage via hypoxia.
residual on the origin of right ICA. The patient was treated non- In the comorbid typical medical patient, the increased rate of
operatively with therapeutic dose of LMWH, blood transfusion thrombotic events associated with anemia is multifactorial,
and intravenous iron supplementation with ferric resulting also from all the causes of anemia, from neoplasms
carboxymalthose. We performed a workup to rule out to chronic inflammatory conditions [3].
malignancies, including a thoracoabdominal CT scan, In conclusion, this case shows how thrombocytosis due to
gastroscopy, colonoscopy and mammography, all negative. The iron deficiency can be regarded as a rare reversible risk factor
patient’s iron deficiency anemia was attributed to chronic for arterial thrombosis. Prevention, detection and treatment
excessive menstrual losses secondary to uterine fibroid. of low iron levels in the blood are important to face the
Screening for rheumatologic conditions, homocysteine value, increasing rates of venous and arterial thrombotic events
hereditary mutations of thrombin and coagulative factor V, worldwide. References
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dosage of antithrombin and C and S proteins were negative for
thrombotic complications of thrombocytosis in iron deficiency
anemia. Am J Hematol 2020
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inflammation: a 3-year prospective analysis of the DO-
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HEALTH trial. Aging Clin Exp Res 2022
3. Paul T et al. Carotid Artery Thrombus Associated With Severe
and found negative.
Iron-Deficiency Anemia and Thrombocytosis. Stroke 1996
4. Xavier-Ferrucio J et al. Low iron promotes megakaryocytic
commitment of megakaryocytic-erythroid progenitors in
humans and mice. Blood. 2019