DISCUSSION:
The incidence of CSVT is estimated to be 0.22 to 1.57 per 100,000, with
a more observed propensity in females compared to males of a ratio of
3:1, with 70-80% of cases are female in their childbearing age. This
disproportion could be explained by one of the proposed mechanisms of
CSVT, attributed to the hypercoagulable state, which is common in
pregnancy, puerperium, and combined oral contraceptive use.2
Many proposed pathophysiological mechanisms could explain CSVT, with at
least two projected. First, thrombosis of cerebral veins or dural sinus
impeding blood drainage leading to parenchymal insult and disruption of
the blood-brain barrier, secondary to build up of venous and capillary
pressure that impairs cerebral blood flow.3 Secondly,
non-resolved venous thrombus impairing cerebrospinal fluid (CSF)
absorption via arachnoid granulation and increase intracranial pressure,
leading to cytotoxic and vasogenic edema and eventually may cause
parenchymal hemorrhage. 3 These mechanisms are
demonstrated on neuroimaging such as MRI methods, diffusion-weighted
MRI, and perfusion-weighted MRI showing cytotoxic and vasogenic edema .3
The etiology and predisposing risk factors of CSVT are several, with
Virchow triad, associated with blood stasis, hypercoagulability, and
alteration in the vessel wall, being the center of its
pathophysiology\sout, For instance, inherited or acquired
thrombophilia, Para-meningeal infection, trauma, and neurosurgical
procedures, medications, and many inflammatory diseases could attribute
as causative factors of CSVT that may exist alone or in a bundle with a
synergistic effect. For example, combined oral contraceptive (COC) with
co-existing mild to severe inherited thrombophilia such as factor
prothrombin gene mutation increases the odds of CSVT. Mutated Factor V
Leiden (R506Q) and MTHFR C677T are the most common genetically
predisposed thrombophilia, accounting for 10% and 9.3%, respectively,
of venous thromboembolism. 4 Factor VIII is a main
propagating factor in the coagulation cascade has been attributed to the
thrombotic state. One study that looked at elevated serum factor VIII
and risk of recurrence of venous showed, serum levels greater than 150
mcg/L are associated with a 5-fold risk for venous
thrombosis. 4
In a systematic review and meta-analysis on COC, thrombophilia and the
risk of venous thromboembolism, demonstrated; risk of VTE in COC users
with mild to severe thrombophilia is 6-fold higher with a rate ratio
[RR], 5.89; 95% confidence interval [CI], 4.21–8.23) and
7-fold (RR, 7.15; 95% CI, 2.93–17.45), respectively. Cochrane reviews
noted that the use of combined oral contraceptives increased the risk of
venous thrombosis (relative risk (RR) 3.5, 95% confidence interval (CI)
2.9 to 4.3). as well as arterial thrombosis (RR1.7, 95% CI 1.5 to 1.9)
compared with non‐use 5
Interestingly enough, Factor VIII is a propagating factor in both
intrinsic and extrinsic coagulation pathways, which is stabilized by the
von Willebrand factor complex (vWF). 6 Although its
level can be high in as acute phase response in the setting of acute
strokes, in a study by O’Donnell et al., half of their patients showed
elevated Factor VIII that could be attributed to vWF, which supports the
notion that elevated factor VIII remains the driving force behind
thrombotic events. 6
Factor VIII relevance in prothrombic syndrome was first recognized in
1990, where hemophiliac patients with factor VIII deficiency had a
protective effect against coronary heart diseases. 7Over the past few years, compelling evidence showed the risk of arterial
thrombosis in patients for elevated serum Factor VIII. Folsom et al.
conducted a prospective study on over 15,000 patients without
cardiovascular risk factors, reported 191 ischemic strokes events that
had Factor VIII in the uppermost quartile showed an adjusted relative
risk factor of 1.93. 8
Our patient presented with a rare combination of veno-arterial disease
(ischemic stroke with CSVT), which had elevated factor VIII of 231.7 and
243.5% provoked by OCP use. Previously, CSVT has been linked with the
use of oral contraceptives, with its risk being higher in genetically
predisposed patients with underlying thrombophilia. Furthermore, OCP is
considered a risk factor for ischemic stroke. According to the WHO, the
odds ratio for ischemic stroke in women who take oral contraceptives is
2.99 (1.65 to 5.40). 1
However, our case differs from those reported in the literature in that
the patient suffered from concomitant CSVT and ischemic stroke
(specifically PICA distribution). Her presentation resulted from
1.6-fold higher serum Factor VIII provoking a thrombotic state in the
setting of oral contraceptive use. In addition, our patient presented
with headache and nausea and was found to have cerebellar signs, and she
had quick recovery clinically and radiologically.