Question 1:

• Hb = 76 (between 7 and 9.9) = moderate anaemia.
Normal MCH and MCV so we have normochromic anaemia.
• WBC = 1.5 (N = 0.9) = mild leukopenia with moderate neutropenia.
• Platelets = 31 (between 70 and 20) = moderate thrombocytopenia.

• SO, we have pancytopenia with normochromic anaemia.
  
  Causes of Pancytopenia:
   – Bone marrow malignancies: (Leukemia, Lymphoma, Multiple Myeloma, Myelofibrosis and myelodyplastic syndrome).
   – Medication side effects (Chemotherapy, antibiotics)
   – Infections: Viral (HIV, EBV), Overwhelming infections or Leishmaniasis.
   – SLE
   – Severe deficiencies: Vit B12, Folate (unlikely as we have normochromic anaemia here), Copper deficiency (can happen after bariatric surgery).
   – Hypersplenism.
   – Other rare causes (Gaucher’s diseases, Sako disease, chronic radiation illness,,,etc).

Causes of Intracerebral bleeding:

 Hypertensive (80% lenticulostriate, 10% pons and 10% cerebellum).
 Amyloid angiopathy (intrahemispheric).
 Coagulopathy.
 Herpes simplex encephalitis.
 Cerebral venous thrombosis.

Question 2:

1st step in managing every patient is ABC.

For patients with intracerebral haemorrhage, our goals are to rapidly control haematoma expansion (few mls can affect the survival of the patient) and to prevent secondary brain injuries.

For every patient with intracranial haemorrhage we need to control 6 processes:
 Blood pressure control
 Correction of coagulopathy
 Tight glucose control
 Temperature
 Seizures
 Intracranial pressure

1.Blood pressure control:

Try to maintain blood pressure around 140/80. Medication of choice is labetalol.
Avoid hypotension (MAP< 80) at all costs.

2.Correct Coagulopathy:
This patient has platelets count of 31, that needs to be corrected. However, it is uncommon for spontaneous bleed to occur at this level (Usually it occurs at level less than 10).

 Platelets > 50 usually is asymptomatic
 50 – 30 leads to purpura
 30 – 10 bleeding with minimal trauma
 < 10 spontaneous bleeding
We need to consider other potential coagulopathy in this patient (Look at the discussion part of the case).

3.Control of blood glucose:

Hyperglycemia is associated with poor outcome due to haematoma expansion and worsening cerebral oedema. Tight control between 4 and 10 is recommended.

Frequent measurement of blood glucose is recommended as hyperglycemia is very common in patients with intracranial haemorrhage and we should avoid hypoglycemia.

1. Fever is common in patients with intracerebral haemorrhage “Brain Blood Fever” this fever doesn’t respond to Panadol. We need to apply active cooling techniques to maintain euthermia (> 37).
   Fever is associated with poor outcomes in patients with intracranial haemorrhage.

2. Consider use of anti-epileptic medication if patient develops seizure (10 – 15%) of cases. It is not recommended to use anti-epileptic medication in all patients as their use is associated with worse clinical outcome. “different scenario to traumatic SAH”.

3. Control of high intracranial pressure

• Elevation of the head of the bed to 30°
• Good sedation and pain control
• Normocapneic ventilation (unless risk of herniation then hyperventilates the patient).
• Hypertonic solutions (Mannitol or 3% Saline).

We need to consider the pancytopenia for this patient, this patient, we need to take thorough history considering potential causes. (including medication history, travel history, extended family history….), this patient also needs blood film and urgent bone morrow aspiration and biopsy.

Case discussion:

• From the list of causes of intracranial haemorrhage, this lady can have coagulopathy or intracranial venous sinus thrombosis.
  Intracranial venous sinus thrombosis is not usually associated with pancytopenia.

Accordingly, the cause of intracerebral haemorrhage in this patient most likely due to coagulopathy.

• From the list of causes of pancytopenia, the only potential group that can cause coagulopathy is bone marrow malignancies. Among these Acute Myeloid Leukemia (M3) – ACUTE PROMYELOCYTIC LEUKEMIA (APL) is well known to be associated with coagulopathy.

Acute promyelocytic leukemia if not diagnosed and treated early it might present with life threatening blood clotting or bleeding problems. Life threatening bleeding (intracranial or pulmonary) occur as a result of increasing fibrinolytic activity. Leukemic promyelocytes express annexin II, which accelerates the conversion of plasminogen to plasmin and thus causes primary fibrinolysis. Cerebral endothelial cells also express this annexin II, which explains the high incidence of intracerebral bleeds seen in APL.
In addition to fibrinolysis, coagulopathy is further complicated by thrombocytopenia and DIC.

Coagulation profile tests may reveal overt DIC with prolongation of PT, variable aPTT, low fibrinogen levels and platelet counts, and high d-dimer due to fibrin degradation.
Urgent management of coagulopathy in Emergency department include Platelets, Cryoprecepitate and FFP. The role of tranexamic acid is not clear.
This patient needs to be referred urgently to a haematology department for definitive management of leukemia.

Special Thanks to Dr Farah Al-Marae