Essential thrombocythemia with CALR mutation and recurrent stroke: two case reports and literature review

Abstract

Cerebrovascular events, especially ischemic stroke, are common complications of essential thrombocythemia (ET). Compared to JAK2V617 F mutation, CALR mutation is considered as a lower risk factor of thrombosis in ET. Until now stroke in ET with CALR mutation has rarely been reported. We retrospectively investigated patients diagnosed with stroke and ET in Xijing hospital of Air Force Medical University, from 2015 to 2021. Clinical characteristics (including medical history, physical and auxiliary examination and prognosis) were recorded and associated literature was reviewed. Among the 19 patients diagnosed with both stroke and ET we retrieved, two cases were positive for CALR mutation. In case 1, a 71-year-old man developed the first ischemic event under the treatment of anagrelide, followed by a hemorrhagic stroke after receiving aspirin and clopidogrel for 4 months. Ischemic stroke reccurred and the neurological function deteriorated progressively. In case 2, a 44-year-old man presented with hypoxic-ischemic encephalopathy due to serious myocardial infarction and subsequent brain imaging indicated three times of ischemic stroke events. The patient gradually got improved through cytoreductive and antiplatelet therapy and rehabilitation. Literature review showed that cerebrovascular event is the most serious neurological complication of ET and may be the presenting symptom. Most of reported cases with ET accompanied by stroke were positive for JAK2 V617 F mutation, but with rare CALR mutation. ET with CALR mutation can cause both hemorrhagic and ischemic stroke. Identification of such rare causes of stroke is of great importance to provide precise and individualized prevention and therapy.

Keywords: CALR mutation; essential thrombocythemia; stroke.

Figure 1.

Radiological findings in case 1. Diffusion weighted imaging (DWI) showed acute cerebral infarction nearby posterior horn of left lateral ventricle as a result of the first episode of stroke (a). A hematoma located in the right frontal lobe induced by the second episode of stroke (b). Multiple scattered acute cerebral infarction lesions include left basilar ganglion region, left posterior horn of lateral ventricles,cingulate gyrus, left cerebral lobes and right centrum semiovale in the third episode of stroke (b, c, d, e). Large acute cerebral infarction lesion showed in the right occipitotemporal lobe in the fourth episode of stroke (f). T2-weighted imaging of brain magnetic resonance imaging(MRI) revealed massive white matter lesions in centrum semiovale (g). Magnetic resonance angiography(MRA) indicated intracranial cerebral atherosclerosis(h).

Figure 2.

Radiological and bone marrow biopsy findings in case 2. Brain computed tomography (CT) after episode of myocardial infarction showed a massive infarction lesion located in right temporoparieto-occipital lobe (a). Subsequent diffusion weighted imaging (DWI) revealed acute multiple acute infarcts scattered in frontoparietal lobe, bilateral occipital lobes and right paraventricular (b, c, d). Magnetic resonance angiography (MRA) indicated intracranial arteries are not remarkable. Bone marrow biopsy showed obvious proliferation of the megakaryocytes with enlarged, hyperlobulated and clustered ones on HE staining and Wright’s staining (f, g, h).