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Acquired hemophilia a nonhematologist perspective
The document discusses acquired haemophilia from the perspective of non-haematologists, detailing two case studies involving patients with this rare bleeding disorder. It highlights the challenges in diagnosing and managing acquired haemophilia, emphasizing the need for prompt diagnosis and effective treatment strategies to control bleeding and eliminate inhibitors. Awareness and collaboration among various medical specialties are essential to improve outcomes and reduce morbidity and mortality associated with the condition.
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Acquired hemophilia a nonhematologist perspective
- 1. Acquired Haemophilia A Non-HaematologistPerspective 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 • Feb20,2005 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 • Aug06, 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 suppressionstarted 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 • Sept11, 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 AcquiredHaemophilia • 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 AcquiredHaemophilia Associated Conditions
- 9. • Patients usuallypresent 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 andspecific treatment of Acquired Haemophilia patients can save their lives.
- 12. • Treatment strategyfor 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 nonhaematologist • 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 patientspresent 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 requiresspecialist 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 advancedage 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 cardiovascularco-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 managementis 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 WorkingGroup 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 WorkingGroup 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 effortsto 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 tonon 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 yourindex 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 verymuch
Editor's Notes
- #6 Upon admission, her factor VIII activity was less than 0.18, but factor VIII inhibitor was 1932 and the repeated, on 12 September 2011, was 2294. Factor IX activity was less 1 and the inhibitor was 10. Factor XI activity was 0.05.Urea and electrolytes; showed urea 35, creatinine 35, potassium 4.5, sodium 138, chloride 101, CO2 27, phosphate 1.23, glucose 4.2, magnesium 0.74Hepatic profile: bilirubin 20, ALT 47, AST 35, and LD 504. All cultures were negative.
- #7 Upon admission, her factor VIII activity was less than 0.18, but factor VIII inhibitor was 1932 and the repeated, on 12 September 2011, was 2294. Factor IX activity was less 1 and the inhibitor was 10. Factor XI activity was 0.05.Urea and electrolytes; showed urea 35, creatinine 35, potassium 4.5, sodium 138, chloride 101, CO2 27, phosphate 1.23, glucose 4.2, magnesium 0.74Hepatic profile: bilirubin 20, ALT 47, AST 35, and LD 504. All cultures were negative.Bypassing agents do not restore the normal pathways of hemostasis in hemophilia, but rather boost thrombin generation in spite of a lack of platelet surface FVIIIa-FIXa ('tenase') activity. Thus, the common clinical laboratory coagulation assays do not reflect the clinically relevant hemostatic activity of bypassing agents, and no validated assay is available with which to measure the in vivo efficacy of these agents or predict individual patient responses to treatment. Global hemostasis assays measuring overall coagulation capacity have potential for assessment of the effects of bypassing agents.
- #8 .[1] Moreover, the clinical signs and symptoms of acquired hemophilia differ from those of hereditary hemophilia. Typical signs of acquired hemophilia A include overt bleeding, epistaxis, gastrointestinal (GI) and urologic bleeding, and retroperitoneal hematomas.[1, 7, 4] Spontaneous bruising and muscle hematomas are most frequent.[2] If untreated, bleeding into the muscles may progress into a compartment syndrome, with compression of the neurovascular bundles. Subglottic hemorrhage may threaten the airway. Other frequent manifestations of acquired hemophilia include melena, hematuria, and iatrogenic bleeding, particularly after attempts to insert intravenous (IV) lines. Prolonged postpartum bleeding, excessive bleeding after trauma or surgery, and, occasionally, cerebral hemorrhage may also occur.[1]
- #10 Moreover, the clinical signs and symptoms of acquired hemophilia differ from those of hereditary hemophilia. Typical signs of acquired hemophilia A include overt bleeding, epistaxis, gastrointestinal (GI) and urologic bleeding, and retroperitoneal hematomas. Spontaneous bruising and muscle hematomas are most frequent.If untreated, bleeding into the muscles may progress into a compartment syndrome, with compression of the neurovascular bundles. Subglottic hemorrhage may threaten the airway. Other frequent manifestations of acquired hemophilia include melena, hematuria, and iatrogenic bleeding, particularly after attempts to insert intravenous (IV) lines. Prolonged postpartum bleeding, excessive bleeding after trauma or surgery, and, occasionally, cerebral hemorrhage may also occur.An interim report of the European Acquired Hemophilia Registry (EACH2) found a median delay of 3 days (3-58) from bleeding onset to diagnosis. Additionally, a 1-day (0-60) difference between first abnormal aPTT and AH diagnosis was noted.These data suggest a delay in AH identification that 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 .