A 27-year-old female presents to the Emergency Department after a collapse at work that was followed by a brief tonic-clonic seizure. She is 30 weeks pregnant with no previous pregnancies or other significant medical history. She currently localises bilaterally to painful stimulus but does not open her eyes or vocalise.
Her blood pressure is 170/50 mmHg, her urine analysis is unremarkable, and the cardiotocogram (CTG) is ‘reassuring’. A CT brain scan shows a sigmoid and transverse venous sinus thrombosis, with some temporal lobe parenchymal haemorrhage.
a) List the major risk factors, other than pregnancy, for this condition. (30% marks)
b) Briefly outline the management priorities for this patient? (70% marks)
Prothrombotic conditions – genetic or acquired Oral contraceptive
Parameningeal Infection e.g. ear, sinus
Autoimmune disease e.g. SLE, antiphospholipid
Other drugs e.g. androgens
o Consider intubation
o Check gas exchange (expect slight respiratory alkalosis)
o BP currently a bit on the high side, maybe careful hydralazine to SBP 140-160?
Specific therapy for cerebral venous sinus thrombosis
o Therapeutic anticoagulation
o Can use LMWH or UFH
o Intracranial haemorrhage with CVT is not a contraindication to anticoagulation
o Continued for remainder of pregnancy and usually for further 6-12 weeks postpartum
o Aspirin – no evidence of benefit. Occasionally used as alternative if firm CI to therapeutic anticoagulation
o Potential therapies include thrombolysis (systemic or catheter-directed), mechanical clot extraction, decompressive craniectomy
o Assess for underlying cause that may require specific therapy e.g.,
- Antiphosphoplipid syndrome
- Sinus or parameningeal infection
o May need an anticonvulsant; consider neurology input
o Involvement of obstetric service, regular CTG, ultrasound
o ? steroids to allow for early delivery if needed
o Shielding for X-ray and CT limit as able
o Blood conservation given physiological anaemia of pregnancy
o Need to keep family up to date
The following lisk of risk factors was compiled using UpToDate and Ferro et al (2004). The latter was a multinational multicentre observational study which identified 624 patients with confirmed CVT. Of this group, the following risk factors were observed:
- Genetic thrombophilia (22.4% of cases)
- Pregnancy during peripartum period or puerperium (13.8%)
- Infection, be it CNS or ENT (12.3%)
- Drugs (7.5%)
- Malignancy (7.4%)
- Pregnancy at any stage (6.3%)
- Antiphospholipid syndrome (5.9%)
- Trauma, neurosrugery or lumbar puncture (4.5%)
- Vasculitis (3%)
- Polycythaemia or thrombocytosis (2.8%)
- Surgery (2.7%)
- Vascular anomaly in the CNS like dural fistula, AVM, etc (1.9%)
- Dehydration (1.9%)
The major approaches to fixing this problem are anticoagulation, thrombolysis, endovascular thrombectomy and open clot retrieval.
- Anticoagulation has been the mainstay of treatment. Coutinho et al (2012) performed a systematic review of the practice and found it to be very helpful, with risk of death reduced by two thirds (ARR of 13%) and substantially improved neurological outcomes. As the patients usually have some sort of procoagulant state, you're going to end up anticoagulating them anyway.
- Thrombolysis for CVT is a logical extension of the use of thrombolysis for ischaemic stroke (i.e. "if its good enough for arterial clots, why not try it with venous clots"). This is the topic of the TO-ACT trial (Coutinho et al, 2013) which appears to still be recruiting. Apart from this undertaking, evidence for the use of thrombolysis in CVT consists of case series only (Ciccone et al, 2004, and Canhão et al, 2003, with about 200 patients in total). Discouraging features included a high rate of extracranial (21%) and intracranial (17%) haemorrhage, which occured in spite of the fact that in the majority of cases (88%) the thrombolytic agent was administered directly into the thrombosed sinus.
- Endovascular clot retrieval is typically reserved for situations where there is significant thrombus burden, contraindication to anticoagulation or a lack of clinical improvement or worsening of symptoms despite systemic heparin. It is the new exciting thing on this scene, and also only known from case series. As a representative example, Mokin et al (2015) report on the American experience. Thirteen patients were identified, of whom five had a favorable clinical outcome (defined as modified Rankin Scale score of 0–2) and three died. A systematic review of such case series (Siddiqui et al, 2015) found a good outcome in 84% and a mortality of 12% among a total of 185 patients, even though they represented the more severe end of the CVT spectrum (60% were in a coma).
- Open clot retrieval seems to be an end-of-the-line manoeuvre. It is known only from heroic case reports (eg. Persson et al, 1990 and Ekseth et al, 1998). In each case, the surgeons followed thrombectomy by an infusion of a thrombolytic agent.
- Decompressive craniectomy for this condition is discussed elsewhere. In brief, the results have been encouraging and full systemic anticoagulation within 24 hours of surgery seems to be safe. A 2009 review from Stroke courageously asserted that the therapy is "lifesaving" and that the outcome can be "excellent", on the basis of three cases. The AHA/ASA gudelines recommend this as a viable option.
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