Polycythaemia vera as a predisposing factor for systemic venous thrombosis

A 30-year-old man presented with a 3-month history of position-dependent bilateral visual blurring, visual field loss, headache, and papilledema. Prior CT and MRI brain scans were normal. Laboratory findings showed haemoglobin of 19 mmol/L and haematocrit of 0.489. The patient underwent CT head followed by CT chest, abdomen, and pelvis.

Emergency CT head demonstrated an enlarged, hyperdense left transverse sinus (Figure 1a). On contrast-enhanced CT venogram, a filling defect was shown in the left transverse sinus, confirming subacute intracranial venous thrombosis. Venous collaterals were also visualised, which is an indirect finding of venous thrombosis (Figure 1b). The patient underwent intracranial venous thrombectomy and lumbo-peritoneal shunt placement. On prior MRI, borderline prominence of CSF around the optic nerve is asymmetrically greater on the left (Figure 3a), with prominence of the optic disks and posterior scleral flattening consistent with clinical papilledema. Given the thrombotic state in a young patient with abnormal laboratory findings, this prompted concern for malignancy.

A contrast-enhanced chest, abdomen, and pelvis CT was thus indicated. There was evidence of moderate splenomegaly with absence of splenic vein (Figure 2a). Multiple collateral varices were depicted within the pancreas, stomach wall, and spleen (Figures 2a and 2b).

Polycythaemia vera (PV) is a myeloproliferative neoplasm (MPN) caused by variations of the JAK2 gene, most often the V617F variant [1]. In PV, autonomous myeloproliferation occurs, resulting in erythropoiesis [1]. Thus, a prothrombotic state is created due to increased interactions of von Willebrand factor and collagen, platelet activation, and endothelial cell activation [2]. Polycythaemia vera, therefore, results in an increased risk of thrombosis, bleeding, and disease progression to myelofibrosis and/or acute leukaemia [1,2].

While often diagnosed incidentally via complete blood count, this patient presented with symptoms due to thrombotic history. The typical presentation of PV includes vasomotor disturbances, constitutional symptoms, and iron deficiency [3]. Thrombotic events are often reported before or at diagnosis. Venous thrombosis was reported in 13.7% in one multi-centre study [4], and brain infarcts have been identified on MRI of 23% of patients with MPNs in another study [5]. Splenomegaly, in this case, was likely a result of chronic splenic venous thrombosis with secondary hypertension [3,6,7]. Collateral vessels, such as gastric varices, have been frequently identified [7,8], but intrapancreatic varices are a rare finding in portal hypertension [6,7].

Diagnosis of PV, according to the World Health Organisation, requires the fulfilment of either all three major criteria, or the first two major criteria and the minor criteria:

• Major:
  • Evidence of increased red cell volume indicated by 1 of the following:
    • Haemoglobin > 16.5 g/dL (male adults), > 16 g/dL (female adults).
    • Haematocrit > 49% (male adults), > 48% (female adults).
  • Bone marrow biopsy with hypercellularity for age with panmyelosis with prominent erythroid, granulocytic, and megakaryocytic proliferation.
  • JAK2 V617F or other mutation of similar function.
• Minor:
  • Serum erythropoietin level below normal reference range [9].

This patient fulfilled the three major criteria, with high peak haematocrit (50.1%), JAK2 mutation, and bone marrow aspiration showing pleomorphic megakaryocytic changes and increased myelopoiesis.

Though imaging does not constitute the WHO diagnostic criteria for PV, it crucially identified intracerebral thrombosis, absence of splenic vein, splenomegaly, and collateral varices in this patient case, which prompted the study of pro-thrombotic genes [1,3].

In this case, intracranial venous thrombectomy was unsuccessful, so a lumbo-peritoneal shunt was placed. However, the overall prognosis varies, with treatment options tailored to the clinical presentation. Treatment includes phlebotomy to maintain haematocrit below 45%, daily aspirin, and cytoreductive therapy [1].

All patient data have been completely anonymised throughout the entire manuscript and related files.