Acquired Hemophilia Medication
- Author: Sara J Grethlein, MD; Chief Editor: Emmanuel C Besa, MD more...
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).
Antihemophilic Agent; Blood Product Or Recombinant Dna Derivative
Class Summary
Recombinant products are recommended to manage bleeding in acquired hemophilia.
Antihemophilic factor (Advate, Alphanate, Helixate FS, Hemofil M, Humate-P, Koate-DVI, Kogenate FS, Monarc-M, Monoclate-P, Recombinate, ReFacto)
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.
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.
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.
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.
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.
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
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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| 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. | |||
| 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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