2. Sub specialty case presentation
Haematology Sub specialty case presentation
Maamoun Alsermani MD MRCP SBIM ABIM SFAH
Consultant Haematologist
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3. Case presentation
•
History :
32 year female mother of 3 children not known to have any medical illness.
2 months postpartum develop spontaneous ecchymosis some are large size
and small subcutaneous hematoma
No other bleeding manifestation ,
• No previous personnel or family history of bleeding
• previous labor not complicated with bleeding
• No other systemic symptoms , no history of fever or weight loss
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4. • the symptoms persist for 5 months now she is 7 months postpartum ,
• not taking any medication except on and of diclofenac for nonspecific
musculoskeletal pain ,
• did not required blood transfusion
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5. Physical examination
Vitally stable
not pale , small ecchymosis in the rt wrist and soft tissue swelling in the rt
foot
no lymphadenopathy , no hepatosplenomegaly
joints full range of motion
screening neurological exam normal
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6. Investigations
• WBC : 9.5 with normal diff , HB : 12.8 , Plt : 313
PTT : 81 , PT 10 , fibrinogen : 3.6
• Normal hepatic & renal profile
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7. Investigations
• mixing study : patient plasma, control plasma, mixing plasma
immediate 83 29 36
1 hr 85 29 49
2 hr 86 30 53
Rosner index for 2 hr mix = 26 percent correction 58%
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8. Investigations
• prolonged PTT that correct with initial mixing study but after 2 hr
incubation start to prolonged ,
• factor 8 level was 5%, Hb normal , platelet normal , PT and fibrinogen
normal
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9. Investigations
• factor 8 activity 5%
• inhibitor not done
• factor 9 normal
• repeated PTT in our hospital 95
Assessment : mixing study showed time dependent inhibitor and low
factor 8
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11. • ackground
• Acquired hemophilia A (AHA) is a bleeding disorder caused by an
autoantibody to factor VIII [1-4]. It must be distinguished from
congenital hemophilia, which is an inherited disorder caused by
mutations in the FVIII gene that presents at a young age and is
characterized by a distinct bleeding phenotype.
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12. • AHA has an estimated incidence of 1.5/million/year and
predominantly affects older patients [5-7]. The disorder presents with
bleeding, ranging from life- and limb-threatening to mild in patients
with no personal or family history of bleeding, and has a high
mortality, estimated at between 9-22% [
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13. • Mixing tests
• . In these studies patient plasma is mixed with pooled normal plasma
in a ratio of 1:1. If the patient plasma has a prolonged aPTT secondary
to a deficiency of a patient has an inhibitor to factor VIII, then the
factor VIII in the normal plasma will be inhibited and the aPTT will not
correct. Failure of normal plasma to correct the aPTT by more than
50% is usually taken as evidence that an inhibitor is present [17],
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14. • FVIII inhibitors, however, are time- and temperature-dependent
because the inhibitor does not inhibit the factor VIII in the normal
plasma immediately. Therefore, mixing studies must be incubated for
1-2 h at 37°C [10,18]. A mixing study performed without incubation
for 1-2 hours or at a lower temperature may result in correction of
the aPTT and the diagnosis of AHA potentially missed. If mixing tests
are compatible with an inhibitor, or the clinical picture is suggestive of
AHA, the sample should be urgently referred to a specialist
hemostasis laboratory for further investigation by Bethesda assay to
measure the strength of the factor VIII inhibitor
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15. treatment of bleeding
• First-line treatment of bleeding in AHA is with a bypassing agent. The
two available licensed treatments are recombinant factor VIIa (rFVIIa,
NovoSeven®) [21,22] and the activated prothrombin complex
concentrate (aPCC) (FEIBA®; Factor VIII inhibitor bypassing activity
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16. Treatment to eradicate the inhibitor
• The two most common regimens are corticosteroids alone or
corticosteroids combined with cyclophosphamide . Some experts
recommend the combination of steroids and cyclophosphamide as
initial treatment, asserting that the inhibitor is eradicated more
rapidly [20]. However, the published evidence from retrospective
studies suggests that neither strategy leads to a superior outcome
[1,5,9] and the only randomized study comparing the two regimens
did not recruit sufficient patients to be interpretable [34]. Reviews of
published data and large cohorts suggest that about 70-80% of
patients achieve remission with steroids alone or steroids combined
with cyclosphosphamide
16
