Rivaroxiban approved for afib stroke risk

Rivaroxaban, a factor Xa inhibitor, is now FDA approved for stroke prophylaxis in non-valvular atrial fibrillation. Rivaroxaban is marketed as Xaletro and has previously been approved for post operative DVT prophylaxis after knee or hip surgery.

The Rocket AF trial (industry sponsered and published in NEJM) showed non-inferiority in stroke prophylaxis compared to warfarin. I have previously posted about treating life threatening bleeding in patients on rivaroxaban. Rivaroxaban is a factor Xa inhibitor, and bleeding can be treated with prothrombin complex concentrate which contains Xa.

Add rivaroxaban to your list of drugs that can cause and exacerbate bleeding, and remember to look for rivaroxaban or Xaletro on the meds list of patients with trauma, and especially minor head trauma.

High Risk: Stroke Mimics and TPA

The decision to offer or withhold thrombolytic therapy for acute stroke is full of both legal and medical risk. Since the publication of ECASS-3 in 2008 and the extension of the thrombolytic timeline to 4.5 hours the proportion of stroke patients who potentially qualify for thrombolysis has markedly increased. In community hospitals (like mine) thrombolytic decisions are owned entirely by the emergency physician. Neurologists are only a phone call away, but they are only a phone call, never able to evaluate the patient in person and therefore of limited help. Radiology is available but again often limited to interpretation of a non-contrast CT head (with CT-angiography often not available after hours, and MRI never available acutely).

In this sort of environment (and make no mistake, this is the environment in most mid-sized community hospitals) how does a prudent emergency physician offer TPA safely?

I will start by saying that I am not sure it is safe to offer TPA in these circumstances, and if we are to offer TPA we should do so within the confines of a protocol with single minded attention to inclusion and exclusion criteria. If we rely on outsourced or night-hawk radiology reads we should get used to re-reading all of these CT’s ourselves, and reviewing any sort of inconsistency with the radiologist before proceeding. We should use our telephone-neurologists, but realize that this particular telephone consultation frequently offers little except diffusion of legal liability.

There are a number of papers that proclaim that thrombolysis in stroke mimics is generally safe, the most recent of these is in the October Annals of Emergency Medicine. These studies are usually done in large academic centres with good neurology access and very well established protocols. I don’t think this translates well to the community hospital with no neurology team available. Some of these mimics are difficult to pick up, by history, examination and imaging, and the less experienced and specialized we are the easier it will be for mimics to recieve thrombolysis.

Although thrombolysis is considered safe in some stroke mimics, such as hemiplegic migraine, it is most certainly not in others such as intercranial neoplasm, subtle intercranial hemmorhage and brain abscess. Although these conditions are comparatively rare they warrant consideration because in these cases thrombolysis is potentially lethal.

Lets consider some specific stroke mimics and how we can potentially recognize them and avoid thrombolysis and it’s associated risks.

Hypoglycemia: This seems simple and completely avoidable but any experienced emergency physician has been caught out at least once by hypoglycemia. Everyone with anything that might possibly be a neurological symptom requires a rapid fingerstick glucose.

Hemiplegic Migraine: Hemiplegic migraine is a difficult diagnosis. There should be an aura, and a headache associated with the symptoms of motor weakness. The patient may be able to describe a previous episode or a similar episode in a family member. The patient may have nausea, vomitting or photo/phonophobia in addition to motor symptoms. Familial hemiplegic migraine is thought to be an autosomal dominant genetic disorder and some types are associated with cerebellar degeneration. Cerebellar degeneration on CT scan may be a clue to this diagnosis.

Seizures and Postictal States: Seizures and status epilepticus may present in bizarre ways that resemble stroke with decreased level of consciousness. Postictal states can closely resemble stroke, and in particular Todd’s paresis can fool even an astute clinician who does not have access to a full history. Any history of a seizure disorder or any hint of a seizure at the time of symptom onset should worry the emergency physician that this stroke mimic is in play.

Intercerebral hemmorhage: Intercerebral hemmorhage is what we are screening for with the CT scan that is part of every stroke protocol. We do not expect to see changes associated with an acute stroke and really we are looking for a reason to not administer TPA. Intercerebral hemmorhage should be easy to find, but subtle bleeds can be missed. Emergency physicians should re-read the CT scan of any patient they are considering treating with thrombolysis. Particular attention should be paid to areas that can show subtle bleeds, such as the 4th ventricle which is a dependant area in the supine patient and an area where a small volume of intraventricular blood might collect. Additionally the emergency physician should be on the lookout for concomitant subacute subdural hemmorhages which can be difficult to identify as they are often isodense to brain tissue. While these are not the cause of the patients acute stroke, they are common in older patients in particular and preclude thrombolysis.

Subacute Stroke: This is definitely a mimic of acute stroke. We try to determine this from history, but at times we can be fooled. Maybe grandpa didn’t get up from his chair all day, but when he finally did he had right sided weakness and fell to the floor. The onset seems discrete to the family, but it may not be. On the initial CT scan we expect to see no changes associated with an acute stroke aside from a hyperdense artery sign. If there is visible edema in the predicted area of the stroke the patient is in all likelihood out of the window for thrombolysis.

Mass lesions and neoplasms: Any sort of primary or metastatic lesion can cause seizures and edema mimicking stroke. When thrombolysis is potentially an option including a cancer history is a good idea. If the patient has a history of cancer, or recent symptoms that might be attributable to cancer caution should be exercised. A CT scan showing early stroke changes could also be showing edema from a mass lesion, and a small amount of midline shift may be the only clue to a subtle mass lesion on non-contrast CT.

Brain Abscess: Brain abscess can also act as a stroke mimic from either local tissue injury or surrounding edema. A history of immunosupression, HIV, endocarditis or IV drug use should raise suspicion of this mimic. On a non-contrast CT there may be a small area of low attenuation mimicking early stroke changes. Again, any changes at all on CT should raise the possibility of an acute stroke mimic, for the purposes of thrombolysis what we expect to see is a normal CT scan.

Conversion Disorder: Although rare conversion disorder presenting as an acute stroke syndrome, usually a unilateral hemiparesis, has been reported. A detailed neurological exam with findings that cannot be explained anatomically or a previous history of conversion disorder may be the only clues the physician has to this mimic.

Encephalopathies: Although encephalopathies typically cause global deficits, they can cause more focal symptoms. Hypoglycemia has been previously discussed. Both severe hyponatremia and hepatic encephalopathy have been reported to cause focal deficits. A very low sodium on initial bloodwork may prompt this as a consideration, as should stigmata of liver disease.

Cerebral Venous Sinus Thrombosis: CVST may present with a hemiparesis or other neurological findings. Luckily it should typically be proceeded by a severe headache and should be accompanied by papilledema, which will raise the emergency physicians suspicion for this mimic.

Thoracic Aortic Dissection: Although unusual TAD can present with primary neurologic symptoms. Chest pain or syncope at symptom onset (even if no longer present), and diminished or assymetrical pulses in the arms, carotids or femorals may be clues to this difficult mimic.

When acute stroke patients present to community hospitals the emergency physicians are faced with a quandary. There are often protocols for thrombolysis in place, but insufficient resources to support the use of this potentially dangerous drug. When community emergency physicians consider thrombolysis they should consider the usual inclusion and exclusion criteria and follow these rigorously. A thorough history and physical examination should allow the physician to predict the anatomic location of the stroke. On CT scan the only positive finding expected is a hyperdense artery sign in the anatomic region predicted by the patient’s deficit. Any other abnormality should raise suspicion for a stroke mimic. The physician should look at all CT scans themselves in addition to the radiology read. In particular attention they should look for subtle bleeding and evidence of mass lesion or abscess. Any discrepancy should be reviewed with the radiologist. In particular, if there is the possibility of a mass lesion a CT with contrast should be complete prior to any consideration of thrombolysis. Finally, if the history physical and CT scan just don’t seem to quite add up it is reasonable to obtain a CT-angiogram demonstrating a filling defect prior to consideration of thrombolysis. Finally the physician should consider stroke mimics as a possibility prior to offering thrombolysis.

Thrombolysis for acute stroke continues to be a hotly debated topic in emergency medicine. In large academic centres this is a multi disciplinary decision undertaken by the emergency physician and the stroke team. In community hospitals the story is different. Often with the support of distant neurologists and the community at large stroke thrombolysis protocols have been put in place, though the resources to support these protocols are lacking. In the community the emergency physician is the stroke physician, and if thrombolysis is part of the services offered by these hospitals it is the emergency physician who must ensure they are offered safely.

Factoid: Stroke Syndromes

History and physical examination of the suspected ischemic stroke patient allows localization of the suspected lesion. Discussing the suspected lesion, or stroke syndrome, with the radiologist reading the CT scan can help them to look for early stroke signs in that territory (like the hyper dense MCA sign).

Describe the features of each stroke syndrome listed below:

  • Contralateral hemiparesis
  • Contralateral lower face weakness
  • Ipselateral gaze preference
  • Aphasia

  • Disinhibition
  • Contralateral leg weakness
  • Ataxia
  • Presence of primitive reflexes
  • Urinary incontinance

  • Homonymous hemianopsia
  • Altered mental status
  • Impaired memory

  • Vertigo
  • Nystagmus
  • Diplopia
  • Dysphagia
  • Dysarthria
  • Ataxia
  • Ipselateral cranial nerve defect
  • Contralateral motor deficit