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Acquired Hemophilia Medication

  • Author: Sara J Grethlein, MD; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
 
Updated: Mar 24, 2016
 

Medication Summary

Drugs that disturb platelet function, including aspirin and nonsteroidal anti-inflammatory agents (NSAIDs), and any herbal medications that can precipitate bleeding should be avoided until the inhibitor is eradicated.

Medications used to treat acquired hemophilia include antihemophilic agents, corticosteroids, immunosuppressive agents, and monoclonal antibodies (mAbs).

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Antihemophilic Agent; Blood Product Or Recombinant DNA Derivative

Class Summary

Recombinant products are recommended to manage bleeding in acquired hemophilia.

Antihemophilic factor recombinant (Obizur)

 

Factor VIII (FVIII) is a protein in normal plasma that is necessary for clot formation and hemostasis. It activates factor X (FX) in conjunction with activated factor IX (FIX); activated FX converts prothrombin to thrombin, which converts fibrinogen to fibrin, which, with factor XIII (FXIII), forms a stable clot. The recombinant porcine sequence product (Obizur) is less likely to be affected by the antibodies against human FVIII that are present in people with acquired hemophilia A. Recombinant FVIII porcine sequence is specifically indicated for treatment of bleeding episodes in adults with acquired hemophilia.

Recombinant factor VIIa (NovoSeven, NiaStase)

 

Recombinant factor VII (rVIIa) is indicated to treat bleeding episodes in patients with hemophilia A or B and inhibitors. It promotes hemostasis by activating the extrinsic pathway of the coagulation cascade, forming complexes with tissue factor, and promoting activation of FX to factor Xa, FIX to factor IXa, and factor II (FII) to factor IIa. rVIIa is indicated for treatment of bleeding episodes and for prevention of bleeding in surgical interventions or invasive procedures in patients with acquired hemophilia.

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Antihemophilic Agent, Hemostatic Agent, Vasopressin Analog, Synthetic­

Class Summary

This agent is used to control bleeding in mild acquired hemophilia.

Desmopressin (DDAVP, Stimate)

 

Main effect is enhancement of water reabsorption in the kidney and smooth muscle constriction. Causes dose-dependent increase in plasma FVIII and plasminogen activator.

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Antihemophilic Agents

Class Summary

Antihemophilic agents are used for FVIII replacement therapy in patients with acquired hemophilia A. Appropriate monitoring is needed to manage active bleeding and to monitor and manage any allergic reactions that may develop during the infusion.

Anti-inhibitor coagulant complex (Feiba VH)

 

Anti-inhibitor coagulant complex is used in patients with FVIII inhibitors. It can temporarily correct the coagulation defect of patients with inhibitors to FVIII; it is generally used in patients with inhibitor titers of 5 BU/mL or higher.

The dose depends on patient weight, hemorrhage severity, inhibitor titer, and in vivo effect. The clinical effect on bleeding is the most important determinant of the dose and frequency of therapy. When inhibitors are present, dosage requirements are extremely variable and are determined by clinical response.

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Corticosteroids

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. They also modify the body’s immune response to diverse stimuli.

Prednisolone (Delta-Cortef, Pediapred, Prelone)

 

Prednisolone is a delta 1-derivative of the naturally occurring adrenocortical steroids. It suppresses key components of the immune system.

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Immunosuppressive Agents

Class Summary

Patients with autoimmune reactions, such as the development of inhibitors, often benefit from immunosuppression.

Cyclophosphamide (Neosar, Cytoxan)

 

Cyclophosphamide is chemically related to nitrogen mustards. It is an alkylating agent; the mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells. Cyclophosphamide may also be administered intravenously (IV) at doses up to 750 mg/m2 q3-4wk.

Cyclosporine (Neoral, Sandimmune, Gengraf)

 

Cyclosporine may control autoimmune enteropathy; it functions to downregulate T-cell activation

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Monoclonal Antibodies

Class Summary

Rituximab (anti-CD-20) monoclonal antibody binds to pre-B cells and mature B cells. It results in lymphocytotoxic effects to B cells, which should result in reduced autoantibody production. There are a small number of reports suggesting that immunosuppressed individuals receiving rituximab may be susceptible to developing progressive multifocal encephalopathy. Low leukocyte counts may also occur.

Rituximab (Rituxan)

 

Rituximab is a genetically engineered chimeric murine/human mAb directed against the CD20 antigen found on surface of normal and malignant B lymphocytes. It is an immunoglobulin G1 (IgG1) kappa immunoglobulin containing murine light- and heavy-chain variable region sequences and human constant region sequences.

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Contributor Information and Disclosures
Author

Sara J Grethlein, MD Associate Dean for Undergraduate Medical Education, Indiana University School of Medicine

Sara J Grethlein, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Coauthor(s)

Craig M Kessler, MD MACP, Professor, Department of Medicine and Pathology, Division of Hematology/Oncology, Georgetown University School of Medicine; Director, Clinical Coagulation Laboratory, Lombardi Comprehensive Cancer Center, Georgetown University Hospital

Disclosure: Received honoraria from NovoNordisk for consulting; Received grant/research funds from NovoNordisk for other; Received honoraria from Baxter-Immuno for consulting; Received honoraria from Octapharma for speaking and teaching; Received grant/research funds from Octapharma for none; Received consulting fee from Amgen for consulting; Received honoraria from Bayer for review panel membership.

Chief Editor

Srikanth Nagalla, MBBS, MS, FACP Director, Clinical Hematology, Cardeza Foundation for Hematologic Research; Assistant Professor of Medicine, Division of Hematology, Associate Program Director, Hematology/Medical Oncology Fellowship, Assistant Program Director, Internal Medicine Residency, Jefferson Medical College of Thomas Jefferson University

Srikanth Nagalla, MBBS, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Nothing to disclose.

Acknowledgements

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group

Disclosure: No financial interests None None

Pradyumna D Phatak, MBBS, MD Chair, Division of Hematology and Medical Oncology, Rochester General Hospital; Clinical Professor of Oncology, Roswell Park Cancer Institute

Pradyumna D Phatak, MBBS, MD, is a member of the following medical societies: American Society of Hematology

Disclosure: Novartis Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Clinical presentation of acquired hemophilia.
Sites of bleeding in patients with acquired hemophilia (n = 149). This research was originally published in Blood. Collins PW, Hirsch S, Baglin TP, et al. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007;109(5):1870-7. © American Society of Hematology.
Workup for acquired hemophilia.
Management of bleeding in acquired hemophilia.
Eradication of the inhibitor for acquired hemophilia.
Table 1 below illustrates the frequency of underlying diagnoses in 3 cohort studies of patients with acquired hemophilia A. [10, 13, 14, 15, 16]
Disease Association Green 1981 (N = 215), % Morrison 1993 (N = 65), % Collins 2007 (N = 172), %
Idiopathic 46.1 55.0* 63.3
Collagen, vascular, and other autoimmune diseases 18.0 17.0 16.7
Malignancy 6.7 12.0 14.7
Skin diseases 4.5 2.0 3.3
Possible drug reaction 5.6 3.0 NR
Pregnancy 7.3 11.0 2.0
Other 11.8 NR NR
*In this trial, idiopathic and other were combined.



NR—not reported.



Table 2. Acquired Bleeding Disorders Associated With Inhibitors of Factors Other Than FVIII
Coagulation Factor Inhibited Most Commonly Associated Disorders Treatment
V Lymphoproliferative disorders, adenocarcinoma, tuberculosis, aminoglycosides, topical thrombin FFP, rFVIIa
IX Systemic lupus erythematosus, acute rheumatic fever, hepatitis, collagen vascular diseases, multiple sclerosis, postprostatectomy, and postpartum FIX concentrates, APCCs, rFVIIa, corticosteroids
XI Autoimmune diseases, prostate carcinoma, chronic lymphocytic leukemia, chlorpromazine FFP, FXI concentrates, rFVIIa, tranexamic acid, fibrin glue
XIII Idiopathic, isoniazid, penicillin FXIII concentrate, FFP, stored plasma, cryoprecipitate
VWF‡ Autoimmune disorders, monoclonal gammopathies, lymphoproliferative diseases, epidermoid malignancies, hypothyroidism, myeloproliferative disorders, and certain medications Desmopressin, infusion of FVIII that contains vWF, IVIG, plasma exchange
II Topical thrombin, idiopathic, autoimmune diseases, procainamide APCC, FFP
VII Bronchogenic carcinoma, idiopathic FIX concentrates, APCC, FVIII concentrates, rFVIIa, fibrin glue, tranexamic acid
X Amyloidosis, carcinoma, acute nonlymphocytic leukemia, acute respiratory infections, fungicide exposure, idiopathic APCC, tranexamic acid, fibrin glue, FFP
APCC—activated prothrombin complex concentrate; FFP—fresh frozen plasma; IVIG—intravenous immunoglobulin; vWF—von Willebrand factor.
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