Extensive cerebral venous sinus thrombosis with hemorrhagic venous infarction as the initial presentation of acute myeloid leukemia: A case report

Abstract

Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in young adults and may present with nonspecific symptoms, leading to delayed recognition. Although CVT is associated with multiple acquired and inherited prothrombotic states, presentation as the first manifestation of acute myeloid leukemia (AML) is distinctly uncommon and poses diagnostic and therapeutic challenges, particularly when intracranial hemorrhage is present. We report the case of a 34-year-old woman with no significant past medical history who presented with sudden severe headache, vomiting, photophobia, and right-sided blurry vision. Initial noncontrast computed tomography (CT) of the brain demonstrated a right lateral occipitotemporal intraparenchymal hemorrhage with surrounding edema and hyperdense dural venous sinuses suspicious for venous thrombosis. CT venography confirmed extensive dural venous sinus thrombosis involving the straight sinus, right transverse and sigmoid sinuses, posterior superior sagittal sinus, with extension to the right internal jugular vein and involvement of the vein of Galen. Laboratory evaluation revealed leukopenia with severe neutropenia, macrocytic anemia, and borderline thrombocytopenia; peripheral smear showed circulating blasts, prompting hematologic workup. Bone marrow examination demonstrated marked blast infiltration with immunophenotypic features consistent with AML without maturation. This case underscores the importance of evaluating for underlying hematologic malignancy in patients presenting with extensive or unprovoked CVT, especially when cytopenias or abnormal peripheral blood findings are present, and highlights the need for early multidisciplinary management when thrombosis coexists with intracranial hemorrhage.

Introduction

Cerebral venous thrombosis (CVT) is an uncommon but potentially life-threatening cause of stroke that predominantly affects young and middle-aged adults, accounting for less than 1% of all cerebrovascular events [1]. Its clinical presentation is highly variable and often nonspecific, with headache being the most frequent symptom, followed by vomiting, visual disturbances related to raised intracranial pressure, focal neurological deficits, and seizures [1,2]. This heterogeneity frequently leads to delayed diagnosis; however, early recognition is crucial because prompt anticoagulation remains the cornerstone of treatment and is recommended even in the presence of venous hemorrhagic infarction or intracerebral hemorrhage [2,3].

Neuroimaging plays a pivotal role in confirming the diagnosis of CVT. Noncontrast computed tomography (CT) may demonstrate indirect signs such as hyperdense dural sinuses or parenchymal hemorrhage, whereas CT or magnetic resonance venography is required to directly visualize intraluminal filling defects and delineate the extent of venous involvement [1,4]. Extensive thrombosis involving multiple sinuses or the deep venous system, including the straight sinus and vein of Galen, has been associated with more severe clinical presentations and poorer outcomes [2,4]. In selected severe cases, endovascular treatment strategies have been evaluated, although randomized evidence has not shown clear functional benefit compared with standard medical therapy [5]. More recently, direct oral anticoagulants have been investigated as alternatives to vitamin K antagonists, demonstrating comparable safety and efficacy for secondary prevention in selected CVT patients [6].

CVT is commonly associated with acquired or inherited prothrombotic conditions, including pregnancy, oral contraceptive use, infection, autoimmune disease, and malignancy [1,2]. Cancer-associated thrombosis is a well-recognized phenomenon resulting from complex interactions between malignant cells, coagulation pathways, endothelial dysfunction, and inflammatory mediators [[7], [8]]. Hematologic malignancies, particularly acute leukemias, are associated with a substantial risk of thrombotic events both at diagnosis and during treatment [9,10]. However, CVT as the initial manifestation of acute myeloid leukemia (AML) is uncommon; this case highlights the need to consider underlying hematologic malignancy in extensive CVT without provoking factors, especially when cytopenias are present.

Case presentation

A 34-year-old previously healthy woman presented to the emergency department with a sudden-onset severe headache, rated 6-7/10 in intensity, associated with 2 episodes of vomiting and photophobia. She also reported right-sided blurry vision and bilateral lower-limb numbness ascending to the knees, which had developed shortly after receiving a vitamin B12 injection. She denied fever, weight loss, seizures, altered consciousness, focal weakness, or prior neurological symptoms. There was no history of oral contraceptive use, pregnancy, recent surgery, trauma, malignancy, or known thrombophilia. Family history was unremarkable for autoimmune, hematologic, or thrombotic disorders.

The patient had initially sought medical attention at 2 healthcare facilities, where she was discharged after triage without further investigation. Due to persistence and worsening of symptoms, she re-presented for further evaluation.

On examination, vital signs were within normal limits. The patient was alert and oriented but appeared distressed by headache and photophobic. Neurological examination revealed intact cranial nerves, normal motor strength, preserved sensation to light touch and pinprick, symmetric deep tendon reflexes, and no cerebellar signs. Fundoscopic examination was not formally performed; however, clinical suspicion for raised intracranial pressure was raised due to visual symptoms. The remainder of the systemic examination was unremarkable.

Initial noncontrast computed tomography (CT) of the brain demonstrated a right lateral occipitotemporal intraparenchymal hemorrhage measuring approximately 3.4 × 1.9 cm, with surrounding vasogenic edema and localized mass effect, without midline shift or hydrocephalus. Hyperdensity of the right transverse and sigmoid sinuses as well as the straight sinus was noted, raising suspicion for cerebral venous sinus thrombosis (Fig. 1).

Fig. 1.

Axial noncontrast computed tomography (CT) images of the brain. (A) Right occipitotemporal intraparenchymal hemorrhage with surrounding vasogenic edema (arrow). (B) Hyperdense right sigmoid sinus, consistent with the “hyperdense sinus” sign (arrow) and (C) Hyperdense right transverse sinus, suspicious for dural venous sinus thrombosis (arrow).

Subsequent CT venography confirmed extensive cerebral venous thrombosis, involving the straight sinus, right transverse sinus, right sigmoid sinus, posterior segment of the superior sagittal sinus, and partial thrombosis of the right internal jugular vein, with additional involvement of the vein of Galen (Fig. 2).

Fig. 2.

Computed tomography venography (CTV) images showing extensive cerebral venous thrombosis. (A) Axial CTV demonstrates a filling defect/lack of opacification within the right sigmoid sinus (arrow), consistent with sigmoid sinus thrombosis. (B) Sagittal reformatted CTV demonstrates a filling defect involving the superior sagittal sinus (arrow), consistent with dural venous sinus thrombosis and (C) Sagittal reformatted CTV demonstrates thrombosis of the straight sinus (upper arrow) with additional involvement of the vein of Galen (lower arrow).

The patient was managed conservatively with antiedema therapy using hypertonic saline, with close neurological monitoring. A follow-up noncontrast CT scan obtained 5 days after initiation of therapy demonstrated marked reduction of vasogenic edema and near-complete resolution of the right occipitotemporal intraparenchymal hemorrhage, with improvement in local mass effect and no evidence of hemorrhagic progression or new intracranial bleeding. A subsequent CT scan at ten days showed further interval resolution of the hemorrhage and surrounding edema, confirming continued radiologic improvement (Fig. 3).

Fig. 3.

Interval evolution of intraparenchymal hemorrhage on follow-up CT. (A) Axial noncontrast CT of the brain obtained 5 days after initiation of antiedema therapy demonstrates marked reduction of the right occipitotemporal intraparenchymal hemorrhage with decreased surrounding vasogenic edema (arrow) and (B) Axial noncontrast CT obtained 10 days after presentation shows near-complete resolution of the hemorrhage and further improvement of adjacent edema, with no evidence of hemorrhagic progression or new intracranial bleeding (arrow).

Laboratory investigations revealed leukopenia, severe neutropenia, macrocytic anemia, and borderline thrombocytopenia. Peripheral blood smear demonstrated approximately 15% circulating blasts, prompting urgent hematologic evaluation. Coagulation studies showed mild prolongation of prothrombin time and transient elevation of activated partial thromboplastin time, with normal fibrinogen levels. An extensive thrombophilia and autoimmune workup were largely unremarkable, except for a reduced protein S level, suggestive of an acquired deficiency (Table 1).

Table 1.

Key laboratory findings at presentation.

Category	Parameter	Result	Reference range
Hematology	White blood cell count	2.3-3.9 × 10³/µL	4-11 × 10³/µL
	Absolute neutrophil count	0.4 × 10³/µL	2-7.5 × 10³/µL
	Hemoglobin	9.5-10.2 g/dL	12-16 g/dL
	Mean corpuscular volume (MCV)	98-104 fL	76-96 fL
	Platelet count	130-160 × 10³/µL	150-400 × 10³/µL
	Peripheral blood smear	Blasts 15%	>15%-20%
Coagulation	Prothrombin time (PT)	15.2-15.4 s	12.3-14.7 s
	INR	1.1	0.8-1.2
	aPTT	Up to 71 s (initial)	26-40 s
	Fibrinogen	3.9 g/L	2-4 g/L
Thrombophilia	Protein S	26%	55%-140%
Bone marrow	Blast percentage	>90%	<5%
	Flow cytometry	CD34+, HLA-DR+, CD13+, CD33+, CD11b+

Bone marrow aspiration and biopsy revealed marked hypercellularity with greater than 90% myeloblasts, suppression of normal hematopoietic elements, and immunophenotypic features consistent with acute myeloid leukemia without maturation, confirming the diagnosis (Table 1). Cytogenetic and molecular studies were recommended for further classification and risk stratification.

Discussion

Cerebral venous thrombosis (CVT) can produce venous hypertension, vasogenic edema, venous infarction, and intracranial hemorrhage, which may complicate initial recognition and management [1,2]. In our patient, the combination of hemorrhagic parenchymal injury with extensive sinus occlusion (including deep venous drainage) supports a severe venous outflow disorder rather than an arterial stroke pattern, and it appropriately triggered definitive venous imaging and urgent etiologic evaluation.

A central learning point is the absence of typical provoking factors coupled with marked hematologic abnormalities, which should prompt clinicians to consider occult systemic causes. Thrombosis is increasingly recognized in AML at diagnosis and early in treatment, and disease-related coagulation activation appears to play a major role. In a Blood cohort, disseminated intravascular coagulation (DIC) at AML diagnosis was a strong predictor of thrombosis, reinforcing that clinically meaningful thrombotic risk may be present before chemotherapy begins [11].

Real-world data further support that early thrombotic events are not rare in adult AML. A retrospective study in Cancers (Basel) reported a notable incidence of thrombotic events in newly diagnosed AML and explored clinical predictors that can help identify higher-risk patients [12]. Additional evidence from European Journal of Hematology highlights that early-onset venous thromboembolism can occur during induction periods in nonpromyelocytic AML, emphasizing the need for vigilant assessment during the diagnostic and early treatment phase [13].

Our patient also demonstrated an acquired reduction in protein S. Older but relevant hematologic data show that protein C and protein S abnormalities can be present in acute leukemia, supporting an acquired prothrombotic milieu that may contribute to extensive venous thrombosis even when thrombocytopenia coexists [14]. More broadly, cancer-associated thrombosis reflects complex interactions between malignancy, inflammation, coagulation activation, and endothelial dysfunction, providing a biologically plausible framework for extensive CVT as the first manifestation of AML [15].

Management of CVT with concomitant intracranial hemorrhage requires balancing hemorrhagic risk against the dangers of thrombus propagation and worsening venous hypertension. Guideline-based care supports anticoagulation in confirmed CVT, including hemorrhagic venous infarction, with individualized consideration of bleeding risk and hematologic parameters. Prognostic evidence from the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) indicates that outcomes are heterogeneous but that severe presentations can still recover with appropriate management, supporting early diagnosis and organized care pathways [16]. Randomized evidence also supports anticoagulation in CVT: a placebo-controlled trial of low-molecular-weight heparin demonstrated benefit signals without an excess of catastrophic bleeding, providing historical support for anticoagulation even in complex cases [17]. Long-term data syntheses suggest that, overall, CVT has a relatively favorable natural history in many patients, but careful follow-up remains necessary, particularly after extensive thrombosis and hemorrhagic presentation [18].

Conclusion

This case highlights that extensive cerebral venous thrombosis with hemorrhagic venous infarction can be the initial manifestation of acute myeloid leukemia, particularly when presentation is unprovoked and accompanied by unexplained cytopenias or circulating blasts. Early recognition of this association should prompt urgent hematologic evaluation and multidisciplinary management, as timely diagnosis influences anticoagulation strategy, transfusion thresholds, and initiation of definitive leukemia therapy.

Patient consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor of this journal upon request.