ACQUIRED HEMOPHILIA

Lugyanti Sukrisman
Division of Hematology-Medical Oncology
Dept. of Internal, Medicine Faculty of Medicine
University of Indonesia/Cipto Mangunkusumo Hospital

ACQUIRED HEMOPHILIA A
A rare bleeding disorder, 1.5 cases/million/year
Autoantibodies directed against circulating F.VIII
Spontaneous bleeding in patients with no previous history
of a bleeding disorder.
Up to 50% of patients: underlying medical condition
(autoimmune diseases, solid tumors, lymphoproliferative
malignancies, pregnancy)
Haematologica 2009;94:4:566-75

ACQUIRED HEMOPHILIA A
Life- and limb-threatening to mild bleeding
Fatal bleeding: 22-31%
Gastrointestinal, lung, intracranial and retroperitoneal
hemorrhage.
High morbidity related to bleeding (8-22%)

BMC Res notes 2010;3:161,

Haematologica 2009;94:4:566-75, WFH
2012;38:1-9

CHARACTERISTIC SYMPTOMS
Acute onset of severe and life-threatening bleeding or
widespread subcutaneous bleeds
Bleeding sites atypical of congenital hemophilia
High mortality (early and late deaths)
Presence of underlying disease/condition
Advanced age
BMC Res notes 2010;3:161

DIAGNOSIS
Any acute or recent onset of bleeding symptoms in a
patient with no previous history of bleeding (esp. elderly
or post partum patient);
Unexplained prolonged aPTT mixing test
An isolated low F.VIII level.

International recommendation on the diagnosis and treatment

of patients with acquired hemophilia A. Haematologica 2009;94:4:566-75

HEMOSTASIS AND COAGULATION TEST

Mr. YB, 65 years,

type-2 DM + CKD,
recurrent
hemarthrosis
aPTT 58-60, F.VIII 1%

Lugyanti Sukrisman, unpublished data

ACQUIRED HEMOPHILIA A CASES (1)

No.

Patients

Symptoms &
laboratory data

Underlying
disease/comorbid

Specific
treatment

1.

Mr. A, 56
yrs

Recurrent
unexplained
hematoschezia,
aPTT 54-58, F.VIII
2%

Type-2 DM

Cryoprecipitat
e

2.

Mr. YB, 65
yrs

Recurrent
hemarthrosis, aPTT
58-60, F.VIII 1%

Type-2 DM + chronic
kidney disease (diabetic
nephropathy)

rF.VIII

3.

Mr.X1, 71
yrs

Widespread skin
bleeding, aPTT>60

Pemphigus, severe
pneumonia

Cryoprecipitat
e, F.VIII

4.

Mr. X2
(elderly)

Widespread skin
bleeding, aPTT>60

Pemphigus,
Pneumonia (late onset)

Cryoprecipitat
e, F.VIII

5.

Mrs. X3, 24
yrs

Persistent
hemarthrosis, aPTT

Post partum
Cryoprecipitat
Lugyanti Sukrisman,
unpublished data
e

ACQUIRED HEMOPHILIA A CASES (2)

No.

Patients

Symptoms &
laboratory data

Underlying
disease/como
rbid

Specific
treatment

6.

Ms. S, 25
yrs

Hematoschezia,
Papua RS Sardjito
RSCM
aPTT> (Yogyakarta)

Previous
infection in
Papua

RS Sardjito:
cryoprecipitate
before tooth
extraction
RSCM: aPTT
normal, F. VIII
normal

7.

Mrs. S, 72
yrs

Hematemesis-melena,
aPTT 65, F.VIII 1%

Type-2 DM,
F. VIII
CAD + previous
SVT,
pneumonia

8.

Mrs. TH,
66 yrs

Bleeding from skin

biopsy, melena. aPTT

Pemphigus
AHF, steroid
Lugyanti Sukrisman,
unpublished data

ANTI HEMORRHAGIC TREATMENT

Control of acute bleeding: generally the immediate priority.
Recommendation: rF.VIIa or aPCC for severe acute bleeding
symptoms, irrespective of inhibitor titer and residual F.VIII
activity.
rF.VIIa: 90 mcg/kg every 2-3 h until hemostasis is achieved.
aPCC: 50-100 IU/kg every 8-12 h to a maximum of 200 IU/kg/day
Risk of arterial thrombosis
Haematologica 2009;94:4:566-75

F. VIII

Human plasma-derived or recombinant F.VIII can only

be advocated for acute bleeding episodes associated
with AHA when:
The inhibitor titer is very low
Minor bleeding
No bypassing agent is available
A bolus loading dose to neutralize the inhibitor and to
achieve hemostatic level
20-50 IU/kg every 6-8 h, or:
3-4 IU/kg/h continuous infusion
Variable/unpredictable F.VIII level
No assurance of immediate or sustained hemostatic
effect.
No prospective, controlled clinical studies are
available
Haematologica 2009;94:4:566-75

TREATMENT FAILURE: DEFINITION

Overt bleeding: no change in blood loss/unit time
Hb unchanged or decreased despite red blood cell replacement.
Increasing dimensions of internal bleeding on imaging studies.
Evidence of continued bleeding after 48 h of appropriate (24 h
if critical site).
Bleeding at a new site while on anti-hemorrhagic treatment.
Increasing pain associated with hematoma despite treatment.
Haematologica 2009;94:4:566-75

INHIBITOR ERADICATION
Immunosuppressan should
be commenced in all
patients as soon as the
diagnosis has been made.
The optimal strategy for
inhibitor eradication:
unknown.

First line

Second line
Alternative

Not
recommended

Treatment
Corticosteroid
Corticostroid +
cyclophosphamide
Rituximab
Azathioprine
Vincristine
Mycophenolate
Cyclosporine
iv immunoglobulin

Haematologica 2009;94:4:566-75

INHIBITOR ERADICATION
The median time to remission: 5 weeks
If the F.VIII levels has not started to increase or
inhibitor decline after 2-3 weeks: an alternative
immunosuppressive regimen should be considered.

BMC Res notes 2010;3:161

CONCLUSION
Acquired hemophila A: acute or recent onset of bleeding
symptoms in a patient with no previous history of bleeding,
with an unexplained prolonged aPTT and an isolated low
F.VIII level.
High morbidity related to bleeding
rF.VIIa or aPCC for severe acute bleeding symptoms
Immunosuppressan should be commenced in all patients as
soon as the diagnosis has been made due to risk of fatal
bleeding continues until F.VIII antibody has been eradicated.