Clinical Pearls & Morning Reports
Published June 30, 2021
Almost any disorder that causes systemic venous thrombosis can cause cerebral venous thrombosis, converging mainly on a diverse group of hypercoagulable states, which are usually evident before cerebral venous thrombosis occurs. Read the NEJM Review Article here.
Q: What are some of the causes of cerebral venous thrombosis?
A: Causes include adenocarcinoma, polycythemia vera, thrombocythemia, leukemia, sickle cell disease, and pregnancy or the postpartum period. Other causes, such as direct cranial trauma, neurosurgical procedures in the area of a venous sinus, and bacterial meningitis, are also apparent before cerebral venous thrombosis. Disorders that may be uncovered by exploring the cause of a cerebral venous thrombosis include antiphospholipid antibody syndrome and genetic forms of hypercoagulability, including factor V Leiden, protein S and protein C deficiency, prothrombin mutation, and hyperhomocysteinemia.
Q: Name three causes of cerebral venous thrombosis that are mediated by platelet-activating antibodies to platelet factor 4.
A: Cerebral venous thrombosis can be caused by three rare but pathophysiologically related hypercoagulable states: heparin-induced thrombocytopenia (HIT); autoimmune heparin-induced thrombocytopenia (aHIT), which is not triggered by heparin and includes an even more rare variant that also is not triggered by heparin (spontaneous HIT syndrome); and vaccine-induced immune thrombotic thrombocytopenia (VITT). These three entities are all associated with thrombosis, a low platelet count, and disseminated intravascular coagulation and are mediated by platelet-activating antibodies to platelet factor 4 (PF4). HIT, aHIT, and VITT are troublesome because they can be associated with thrombosis, primary hemorrhages, and secondary hemorrhage into areas of cerebral venous infarction.
A: The presenting feature of dural sinus thrombosis is acute or subacute headache in 70 to 90% of patients, often with a normal neurologic examination. Seizures, usually focal convulsions, and stroke deficits may follow if cortical infarction occurs. The headache usually progresses during a period of hours or days to severe aching or throbbing over the entire cranium, bifrontally, or at the vertex, the last being infrequent but more specific. Coughing, bending over, or head movements tend to worsen the headache. Papilledema may develop over a period of days or weeks after dural sinus thrombosis. Other manifestations of increased intracranial pressure, such as bilateral sixth cranial nerve palsies, can occur but are uncommon. Focal neurologic deficits occur hours or days after the headache in about half of patients with cortical vein thrombosis. The common syndromes are paresis of one or both legs, hemiparesis from infarction in the frontoparietal regions surrounding the vein of Trolard, and aphasia and confusion from infarction in the temporal lobe surrounding the vein of Labbé.
A: Venous stroke appears as an edematous region with mixed infarction, hemorrhage, and contrast enhancement that does not respect arterial territories. In venous sinus thrombosis, particularly in cases accompanied by disseminated intravascular coagulation, cerebral hemorrhage may occur independent of the hemorrhagic venous infarction, and in rare cases, subarachnoid hemorrhage is the only imaging manifestation of cerebral venous thrombosis. If HIT, aHIT, or VITT is clinically suspected, special laboratory testing for anti-PF4 antibodies is indicated, along with an assay for platelet activation by the antibodies. Trials of anticoagulant therapy have used primary outcomes that included systemic venous thromboembolism and have had low event rates, making it difficult to draw conclusions about the choice or duration of anticoagulant therapy for cerebral venous thrombosis, but full-dose low-molecular-weight heparin, followed by warfarin or direct oral anticoagulants for an unspecified period, appears to be an acceptable approach except in patients with HIT, aHIT, or VITT.