Acquired hemophilia is a rare disorder and if missed can cost lives. This presentation has been prepared keeping in view the non hematologist health care workers to broaden their index of suspicion and increase their awareness. The target people are medical residents those who work in ER and ICUs.

1. Acquired Haemophilia
A Non-Haematologist Perspective
Dr. Muhammad Asim Rana
MBBS, MRCP, MRCPS, FCCP, EDIC, SF-CCM
Dr. Ahmed F. Mady
MBBCh, MSc, MD, FCCP, SF-CCM
King Saud Medical City Riyadh, KSA

2. Case 1
• Feb 20,2005 85 yrs Saudi male H/O Cancer Prostate presented to KSMC with
haematuria and scrotal swelling. He was resuscitated with FFP and PRBCs
• March 1, 2005 anesthesiologist requested haematology consultation pre-cystoscopy
as he noticed prolonged aPTT 64.6 but normal INR 0.98
• Mixing test Requested
• Factor VIII = 12.5% (Normal 50-150) Factor IX = 70.88 % (50%-150% (0.5-1.5 IU/mL)
• Treated with Factor VIII 2000 units BID + FFP .
• Bleeding stopped and pt went to OR for biopsy of urinary bladder. (Transitional cell Ca)
• March 12, 2005 ----> had severe bleeding attack
• Didn’t respond to resuscitation and succumbed to massive bleed.

3. Case 2
• Aug 06, 2011 A 38 years Saudi female G4P3A1.
• Presented to KSMC with Rt thigh pain, ecchymosis and swelling for the last one
week, she gave no history of trauma or fever, but said that she had similar attack on
left side few months back .
• Admitted under General Surgeon , noted to have aPTT 110, INR 0.9 Hb% 6.9 .
• Aug 09, 2011 seen by haematologist who requested for mixing studies and factors
assays → ? Acquired hemophilia and started her on :
• methylprednisolone 500mg BID IV for 3 days and taper down
• Tramadol 50 mg tab / morphine 10 mg PRN
.

4. Case 2
Immuno suppression started upon confirmation by mixing test and
FVIII activity (2.5%)
• Cyclophosphamide 100 mg IV/day
• Vincristine 2 mg IV/day
• Rituximab 700 mg /day for 4 days
• She didn’t receive bypassing agents during admission.
• Aug 20, 2011
• She was slightly better & left hospital (DAMA) with prednisone 50 mg OD.

5. Case 2
• Sept 11, 2011 Presented to KFSH with sudden onset of left lower limb pain,
swelling and bruises.
• Ultrasound and MRI of the left LL showed a big hematoma 11.5 x 5.7 x 2 cm
• WBC count-- 2.95, PT 12.6, aPTT 64.8. Mixing study was +ve for inhibitors.
• F VIII activity was less than 0.18% with inhibitor was 1932 BU & 2294BU.
• F IX activity was less than 1% and the inhibitor was 10 BU.

6. Case 2
• Medications
• APCC 5500 U bid.
• IVIG
• Cyclophosphamide 1 gram stat and then 100 mg OD.
• Methyl prednisone 80 mg q.d.
• She was posted for scan to rule out any malignancy, which was negative.
• During hospital stay, the swelling decreased gradually and she started to walk.
• Therapy continued on FEIBA, cyclophosphamide and methylprednisolone.

7. Overview of Acquired Haemophilia
• Rare but potentially life-threatening bleeding disorder caused by the
development of autoantibodies directed against plasma coagulation
factors, most frequently factor VIII .
• The disorder presents with bleeding, ranging from mild subcutaneous to life
threatening in patients with no personal or family history of bleeding.
Collins et al. BMC Research Notes 2010, 3:161

8. Overview of Acquired Haemophilia
Associated Conditions

9. • Patients usually present to physicians who are not
specialists in the field and have not previously
managed a case, typically geriatricians, obstetricians,
rheumatologists, oncologists, emergency physicians,
intensive care physicians or surgeons as well as
hematologists.
Collins et al. BMC Research Notes 2010, 3:161
Z Rezaieyazdia ; Blood Coagulation and Fibrinolysis 2012, 23:71–74
Overview of Acquired Haemophilia
• Interim report of the European Acquired Hemophilia
Registry (EACH2)
• median delay of 3 days from bleeding onset to diagnosis.
• 1-day difference between first abnormal aPTT and AH
diagnosis was noted.
• This delay in diagnosis puts patients at risk for bleeding.
• Mortality rate estimated between 9-22%.
• The high overall mortality has been attributed to severe
bleeding and complications of immunosuppressive
therapy .
Problems associated with diagnosis

11. Prompt diagnosis and specific
treatment of Acquired Haemophilia
patients can save their lives.

12. • Treatment strategy for AH have 2 major objectives.
• Effective control of bleeding manifestations is the primary objective.
• Ultimate goal is to eliminate the inhibitor and cure the disease.

13. Challenges for non haematologist
• Challenges in diagnosis
• The condition is rare
• Absent family history of bleeding episodes, unlike congenital hemophilia.
• Challenges in management
• The severity of AH at clinical presentation.
• No high-level evidence to support management recommendations.

14. • That patients present to health care professionals with various specialities, many
physicians are not accustomed to identifying AH as the cause for an acute bleed.
• That Lack of familiarity with AH can result in
• Delayed diagnosis
• Suboptimal treatment
• There are no laboratory tests that have been demonstrated to be useful for
monitoring the efficacy of bypassing agents, usually best assessed clinically.
Challenges in diagnosis of AH

15. • AH requires specialist clinical and laboratory expertise and facilities for diagnosis
and treatment .
• Because it is frequently confused with other life-threatening conditions (eg,DIC)
and typically occurs in an elderly population, AH can lead to severe morbidity
and even mortality before it is correctly diagnosed
Challenges in diagnosis of AH

16. • The advanced age of patients with acquired hemophilia and co-morbid conditions
may preclude the most aggressive treatments and dose reductions (e.g. steroids in
diabetes), which may lead to a lower response rate and thus, a decreased survival
rate.
• Immunosuppressive agents are associated with multiple adverse effects, particularly
in elderly persons, and can be leading cause of morbidity and mortality.
Challenges in management of AH

17. • The cardiovascular co-morbidities associated with advanced age may put
patients at risk of thrombotic complications during haemostatic therapy.
• Sumner and colleagues reported a thrombotic event rate of 8.6% in 139 AH
patients treated with rFVIIa.Recently, an analysis of EACH2 registry data revealed
a lower thrombotic event rate (2.3%) with hemostatic therapy.
Knoebl P. (EACH2). Blood. 2010;166:abstract 716.
Sumner MJ et al. Haemophilia. 2007;13:451-461.
Challenges in management of AH

18. • Perioperative management is challenging in AH.
• Procedures should be performed only if absolutely necessary and the benefits
outweigh the risks.
• Postponement of procedures until inhibitor eradication has been achieved
should be considered, if possible.
Challenges in management of AH

19. Acquired Haemophilia Working Group Survey
• What are the most important obstacles in achieving optimal diagnosis and
treatment of Acquired haemophilia?
1) Lack of awareness about the disorder and its complications.
2) Lack of cooperation from other involved specialties when needed.
3) Lack of needed equipment for confirmation of diagnosis.
4) Unavailability of bypassing agents and/or other treatment agents.
Ahmed F Mady MD,FCCP. Basim Huwait MRCP, EDIC. Omar S Ramadan MD,FCCM. Asim Rana MRCP, EDIC, FCCP. A. Al-Harthy MD,FCCM.

20. Acquired Haemophilia Working Group Survey
• We made a questionnaire for clinicians, pharmacists and lab physicians.
• The form was structured & specified for each group.
• A first stage of our survey included MOH hospitals in Riyadh,
Ahmed F Mady MD,FCCP. Basim Huwait MRCP, EDIC. Omar S Ramadan MD,FCCM. Asim Rana MRCP, EDIC, FCCP. A. Al-Harthy MD,FCCM.

21. • Direct efforts to raise the awareness of this disorder among physicians.
• Provide practice-based guidance on how to best diagnose and treat AH.
• Empower other professionals to contribute actively in the Rx of such fatal disease.
• Establishment of centers of expertise for AH and the implementation of national or
regional haemophilia center networks that provide round the clock services for
sample assessment and diagnosis may assist in standardizing clinical practice in the
management of this patient group.
My request to haematologist colleagues

22. My message to non haematologist colleagues
SPOTCONFIRMSTOP
SPOT the bleed
Confirm Acquired haemophilia Dx
AH treatment principles
STOP Acute Bleeding
START Inhibitor eradication
Monitor & Follow up
Report case to AHN

23. • Keep your index of suspicion wide
• Seek help of an experienced hematologist regardless of the severity of disease.
• Expedite the diagnosis by sending the labs promptly .
• The priority is to control bleeding in AH by using the bypassing agents.
• Starting inhibitor eradication……. consider expert opinion
• Be aware about complications of medications and immunosuppression
• Case presentation at the local level can be very helpful to spread awareness
Take home points for non haematologists

24. Thank you very much