Acute flaccid paralysis (AFP) is a neurological emergency with an extremely broad

differential diagnosis encompassing pathologies of the cerebrum (such as stroke),

cerebellum (such as acute cerebellar ataxia), spinal cord (e.g. cord compression,
transverse myelitis), and the peripheral nerves (such as Guillain-Barre syndrome
and poliomyelitis).

However, the presence of exaggerated deep tendon reflexes in this patient provides
a valuable diagnostic aid; this finding is strongly against a peripheral
neuropathy, as diminished reflexes are usually encountered in these.

Note also the history of bladder and bowel dysfunction in conjunction with a
massively distended bladder (i.e. suggestive of a neuropathic bladder). This hints
that the pathology lies either in the spinal cord, or in the cerebrum.

Neuroimaging is a good next step, as this will aid in localization of the lesion
(and in some cases identify the etiology); a MRI of the brain is the modality of
choice.

This reveals the presence of cervical spinal cord compression; the compressive
lesion has characteristics suggestive of an acute epidural hematoma (as opposed to
an abscess, tumor, discal herniation or spinal stenosis).

At this point, an important question arises - if this is an acute cord compression,

shouldn't there be spinal shock ? (in which case areflexia would be expected).

However, it is important to note that there is evidence that spinal shock lasts for
a shorter time in children as compared to adults, and that the higher the level of
the lesion, the shorter the duration of spinal shock (which may be as short as a
few days).

Another important question is - how did the epidural hematoma come about ? These
are extremely uncommon in the absence of trauma (including child abuse), and there
is no evidence to suggest the latter.

Could there be an underlying bleeding disorder ? A coagulation profile is a logical

next step.

The coagulation profile in turn shows an increased clotting time, and a massively
increased activated partial thromboplastin time (APTT), suggesting that there is an
abnormality in the intrinsic pathway.

A specific factor assay subsequently shows a marked deficiency of factor VIII. This
is severe Hemophilia A (the term 'severe' is used in disease where levels are < 1%
of normal).

This case is remarkable in two ways - for one, it is rather unusual that this
infant did not develop any bleeding manifestations following birth (especially
considering that he had a difficult delivery).

This is possibly because the stress of delivery (and other neonatal problems) can
elevate factor VIII levels into the normal or near normal range.

Second, spontaneous intraspinal bleeding (in the absence of overt trauma) is

exceedingly rare in hemophiliacs.

Genetic studies should be performed later on to determine if the mother is a

carrier; this patient's mother was found to be normal, making this a case of
spontaneous mutation.
Conservative management with factor replacement will be safe and effective here,
and most likely lead to complete neurological recovery.

Surgery should be considered only if symptoms progress, or if there is no response

to conservative management; this should only be attempted once factor VIII levels
have been increased.

Platelet transfusion is not indicated here; nor are IV antibiotics.

Discussion Hemophilia is the most common inherited bleeding disorder, and is

transmitted in an X-recessive manner.

There are two main forms: Hemophilia A, where clotting factor VIII is deficient,
and Hemophilia B, where factor IX is reduced; these result from mutations at the
factor VIII or IX loci on the X chromosome respectively.

The approximate incidence is 1 in 5000 males, with no racial predilection. Around

80% of these cases are Hemophilia A, and around 15% to 20% are Hemophilia B (the
remainder are Hemophilia 'C', which is deficiency of factor XI; this is not
discussed further in this text).

In the vast majority of individuals the underlying defect is reduction in the

amount of clotting factor proteins; however in 5% to 10% of patients with
Hemophilia A and 40% to 50% of patients with Hemophilia B, dysfunctional proteins
are present.

In hemophiliacs, fibrin clot formation is delayed - resulting in both prolonged and

excessive hemorrhage in response to trauma, as well as occasional spontaneous
hemorrhage.

Note that these patients do not experience excessive bleeding following minor cuts
or abrasions -because hemostasis in these scenarios is mainly dependent on
formation of the platelet plug.

Neither factor VIII nor factor IX crosses the placenta - thus bleeding may occur at
the time of birth, or even in fetal life; however, factor VIII levels may be
artificially elevated because of the acute-phase response elicited by the birth
process.

In contrast, factor IX levels are physiologically low in the newborn.

Around 1% to 2% of affected neonates develop a spontaneous intracranial hemorrhage

(ICH) following delivery. Interestingly, only around 30% of infants bleed with
circumcision.

It is important to appreciate that due to mosaicism, the carrier mother may also
have slightly lower levels of factor VIII than normal; this may manifest as
menorrhagia or postpartum bleeding.

The clinical hallmarks of hemophilia are joint and muscle hemorrhages, easy
bruising, and prolonged and potentially fatal hemorrhage after trauma or surgery.

The joints most commonly affected include the knees, elbows, ankles, shoulders,
wrists, and hips, in decreasing order of frequency.

Hemorrhage into the central nervous system (CNS), retroperitoneum, and around or
into vital organs are the most concerning complications.

The severity of Hemophilia is classified based on the baseline factor levels.

A factor level <1% of normal (<1.0U/dl) is severe, between 1% and 5% (1-5 U/dl) is
moderate and >5% (>5U/dl) is mild disease.

Severely affected patients may experience spontaneous hemarthrosis and soft tissue
bleeding in the absence of precipitating trauma.

Moderately affected individuals bleed with minimal trauma; mildly affected patients
have very few hemorrhagic episodes, which are almost always precipitated by
significant trauma or surgery.

Hemophilia should be suspected whenever unusual bleeding is encountered in a male

patient.

This is supported when the results of screening laboratory tests include a normal
platelet count, bleeding time, thrombin time and prothrombin time but a prolonged
APTT. In severe disease this may be 2 to 3 times the upper limit of normal.

Specific factor assays are the only way to differentiate Hemophilia A from
Hemophilia B.

The management of Hemophilia requires IV replacement of the deficient clotting

factor.

There are two main approaches: on-demand therapy, where treatment is administered
only after a hemorrhagic episode. This should be done as soon as possible to raise
the factor levels to hemostatic levels(35-40%) or in case of life threatening or
major bleeds to 100% of normal.

Prophylactic therapy is the other main approach, and is of particular benefit in

individuals with severe factor VIII or IX deficiency, or in those with mild to
moderate deficiency who have recurrent joint bleeding.

In patients with mild Hemophilia A, desmopressin acetate (DDAVP) therapy may be

considered as an alternative - although not all respond to the drug. DDAVP is not
effective in the management of Hemophilia B.

During an acute mucosal bleed, Tranexamic acid (an antifibrinolytic agent) can be
administered; the exception is acute genitourinary bleeding, as there is a risk
that clots may obstruct the urinary tract. Note also that Tranexamic acid is
contraindicated in intracranial hemorrhage, and in patients with a history of clots
in the cerebrum.

The long term complications include chronic joint destruction, an increased risk of
transfusion-transmitted infections(minimized by using highly purified or
recombinant products) and the development of antibodies (inhibitors) to factor
VIII/IX in some patients.

The incidence of inhibitors appears similar in patients using either recombinant or

plasma-derived products for factor VIII replacement. Highly purified factor IX or
recombinant factor IX seems to increase the incidence of factor IX inhibitors.

Take home messages 1. The diagnosis of hemophilia should be suspected in all male
individuals who present with unexplained bleeding. 2. The absence of bleeding
manifestations at birth and in the early period following birth does not exclude
Hemophilia. 3. The myocardium and phallus are the two main tissues not prone to
bleeding. 4. The most deleterious complications are ICH, chronic arthropathy,
blood-borne infections and formation of factor inhibitors.
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