3. Hemophilia A
• Hemophilia A is an X-linked, recessive disorder caused by deficiency
of functional plasma clotting factor VIII (FVIII), which may be inherited
or arise from spontaneous mutation.
• The development of inhibitory alloantibodies to FVIII can severely
complicate the treatment of genetic cases.
• Rarely, development of autoantibodies to FVIII results in acquired
hemophilia A.
4. Management
• Management of hemostasis
• Management of bleeding episodes including hemostatic support and
pain mangagement
• Use of factor replacement products and adjuvant medications
• Treatment of patients with factor inhibitors
• Treatment and rehabilitation of patients with hemophilia synovitis
5. Pharmacotherapy
• FVIII concentrates
• Desmopressin vasopressin analog, or 1-deamino-8-D-arginine
vasopressin (DDAVP). Not effective in the treatment of severe
hemophilia. Given by intravenously. Peak effect is observed in 30-60
minutes. DDAVP leads to free water retention, which can lead to
hyponatremia. A concentrated DDAVP intranasal spray is available for
outpatient use.
• Antifibrinolytics used for oral mucosal hemorrhage and prophylaxis.
Examples Epsilon aminocaproic acid and Tranexamic acid
6. Pharmacotherapy cont.
Treatments used in patients with inhibitors of FVII
• High doses of FVIII for low-titer inhibitors
• Activated prothrombin complex concentrate (aPCC)Activated
recombinant FVII (rFVIIa)
• Monoclonal antibodies directed toward restoring FVIII function (eg,
emicizumab, rituximab)
• Porcine FVIII, which has low cross-reactivity with human FVIII
antibody
7. Hemophilia B
• Hemophilia B, or Christmas disease, is an inherited, recessive disorder
that involves deficiency of functional coagulation factor IX (FIX) in
plasma.
• Hemophilia B is caused by a variety of defects in the F9 gene.[1]As
this gene is carried on the X chromosome, the disease usually
manifests in males and is transmitted by females who carry the
causative mutation on one of their X chromosomes.
8. Management
• Control of hemostasis
• Treatment of bleeding episodes
• Administration of factor replacement products and medications
• Use of factor inhibitors
• Rehabilitation of patients with hemophilia synovitis
• Primary and/or secondary prophylaxis
9. Pharmacotherapy
• Factor IX-containing products (eg, factor IX, recombinant factor IX, factor
IX complex).
• Recombinant coagulation factor VIIa
• Recombinant coagulation factor IX
• Antifibrinolytics (eg, epsilon aminocaproic acid, tranexamic acid)
• Antihemophilic agents (eg, desmopressin, anti-inhibitor coagulant
complex, human antihemophilic factor, recombinant human antihemophilic
factor, plasma-derived prothrombin complex concentrates/factor IX
complex concentrates, plasma-derived coagulation factor IX concentrate)
• Monoclonal antibodies (eg, rituximab)
• Analgesics (eg, narcotic agents, NSAIDS, acetaminophen with codeine or
synthetic codeine analogs)
• Gene therapy (ie, etranacogene dezaparvovec [Hemgenix])
10. Hemophilia c
• deficiency of factor XI
• ometimes called Rosenthal syndrome
• Unlike the bleeding tendency in hemophilia A or hemophilia B,
which is clearly related to the factor level, some patients with
severe deficiency of factor XI do not have a bleeding tendency.
• On the other hand, some patients with mild deficiency of factor
XI bleed excessively, and this unpredictability, which is not fully
understood, makes hemophilia C more difficult to manage
11. Management of hemophilia C
• In patients with hemophilia C undergoing a surgical procedure,
replacement with plasma products may be needed in the preoperative,
intraoperative, and postoperative periods, depending on the procedure,
the patient's history with other surgical procedures, and the person's
bleeding tendency, if any.
• antifibrinolytics;
• fresh-frozen plasma (FFP),
• ideally pathogen-inactivated (eg, solvent-detergent treated FFP);
• factor XI concentrates.
• Adjunctive measures include the use of fibrin glue and desmopressin
(DDAVP)
12. Acquired hemophilia
• Acquired hemophilia is a rare but potentially life-threatening
bleeding disorder caused by the development of autoantibodies
(inhibitors) directed against plasma coagulation factors, most
frequently factor VIII (FVIII).
13. Management
• Treatment of the underlying disorder or discontinuation of an
offending drug
• Recombinant FVIII porcine sequence (rpFVIII), if the baseline anti-
porcine FVIII inhibitor titer is ≤ 20 BU; recombinant activated factor
VII (rFVIIa); or activated prothrombin complex concentrate (APCC).
• Human FVIII concentrates may be used to control bleeding
• Hemostatic prophylaxis can be with rpFVIII, rFVIIa, APCC, or
emicizumab
• Eradication of the inhibitor with immunosuppression with
corticosteroids alone (first line) or combined with rituximab or
cyclophosphamide.
• Salvage therapy with cyclosporine is particularly effective in patients
with underlying systemic lupus erythematosus.
15. Antihemophilic factor recombinant (Advate,
Adynovate, Afstyla, Eloctate, Helixate FS, Jivi,
Kogenate FS, Kovaltry, NovoEight, Nuwiq, Obizur,
Recombinate, Xyntha)
• Mechanism of Action
• Temporarily replaces missing clotting factor VIII which corrects
&/or prevents bleeding
• Adverse Effects
• Factor VIII inhibitor disorder (31.7%)
• Pyrexia (5.9%)
• Nausea (1-4.4%)
• Dizziness (3.5%)
• Headache (3.5%)
• Taste disorder (2.7%)
• Contraindications
• Hypersensitivity to mouse or hamster protein
16. Factor VIII, human plasma derived
(Monoclate-P, Hemofil M, Koate DVI)
• Mechanism of Action
• Factor VIII derived from pooled human
plasma, temporarily replaces missing clotting
factor VIII which corrects and/or prevents
bleeding in patients with hemophilia A
• Adverse Effects
• Headache, Somnolence, Lethargy, Fever,
Blurred vision
• Contraindications
• Hypersensitivity
17. Anti-inhibitor coagulant complex (Feiba NF,
Feiba VH Immuno)
• Mechanism of Action
• Provides activated blood coagulation factors II,
VII, IX and X from pooled human plasma
• May shorten the activated partial
thromboplastin time of plasma containing
factor VIII inhibitors
• Adverse Effects: Headache, Lethargy,
Nausea, Chest discomfort, Chills, Rash,
Urticaria
• Contraindications
• Treatment of bleeding occurrences resulting
from deficiencies in coagulation factors VIII or
IX
18. Antihemophilic factor/von Willebrand
factor complex (Alphanate, Humate P,
Wilate)
• Mechanism of Action
• Temporarily increases the plasma level of FVIII, thus
minimizing the hazard of hemorrhage in patients with
hemophilia A; FVIII is an essential cofactor in
activation of factor X leading to formation of thrombin
and fibrin
• VWF promotes platelet aggregation and platelet
adhesion on damaged vascular endothelium; it also
serves as a stabilizing carrier protein for the
procoagulant protein FVIII
• Adverse Effects: Pain, Respiratory distress, Pruritus,
Rash, Urticaria, Face edema, Paresthesia, Pain.
• Contraindications: Hypersensitivity
19. Factor VIIa, recombinant (NovoSeven
RT)
• Recombinant activated factor VII (rFVIIa) 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. rFVIIa is indicated for
treatment of bleeding episodes and for prevention
of bleeding in surgical interventions or invasive
procedures in patients with acquired hemophilia.
20. Fresh frozen plasma
Mechanism of Action
• Each unit provides all plasma proteins and clotting factors to
support adequate hemostasis to treat or prevent bleeding or to
treat other protein deficiencies that cannot be replaced with
protein specific concentrates.
Adverse Effects
• Nervous system: Headache, paresthesia
• Gastrointestinal: Nausea
• Skin and subcutaneous tissue disorders: Pruritus, urticaria
Contraindications
• IgA deficiency
• Severe protein S deficiency
• History of hypersensitivity to FFPs or Octaplas
21. Human coagulation factor Xl
• Factor XI concentrates provide the best source
for factor XI replacement.
• Advantages of factor XI concentrates include
selective delivery of the deficient factor, a
reduced volume of infusion, and viral safety.
• Issuess: Hemoleven (LFB) and factor XI
concentrate (BPL), are activation of the
coagulation system and some thrombotic
events, especially in patients with preexisting
vascular disease.
22. Fibrin sealant (Tisseel, Artiss, Evicel)
Mechanism of Action
• Forms fibrin clot from fibrinogen to achieve hemostasis
• fibrinogen (sealer protein) as the main active ingredient and fibrinolysis inhibitor
(aprotinin)
• Used in dental extractions without blood product replacement.
Contraindications
• Hypersensitivity to product or other components
• Massive or brisk arterial bleeding
• Intravascular use - risk of life-threatening thromboembolic events
• Do not spray product where the minimum recommended distance from the applicator
tip to the target site cannot be assured
Administration
• The glue is applied with a pair of syringes, one containing calcium and thrombin and
one containing fibrinogen, factor XIII, and aprotinin.
23. Aminocaproic acid (Amicar)
MOA: Inhibits fibrinolysis through inhibition of plasminogen binding to
fibrin and subsequent conversion to plasmin, which in turn inhibits
fibrinolysis
• Exhibits antiplasmin activity
• Adverse Effects: Confusion, Vision decrease, Vomiting, Headache,
Convulsions, Malaise,etc
Contraindications
• In presence of DIC without concomitant heparin
• Evidence of active intravascular clotting process
IV Administration
• Initial 5 g in 250 mL over 1 hr, each subsequent gram in 50-100 mL at 1
g/hr
• Rapid injection undiluted into a vein is not recommended
• Continue for about 8 hr or until bleeding has been controlled
24. Tranexamic acid (Cyklokapron, Lysteda)
• Mechanism of Action
• Inhibits fibrinolysis by displacing plasminogen from fibrin
• Reduces plasmin activity, which in turn reduces activation of
complement and consumption of C1 esterase inhibitor (C1-
NH) and subsequently decreases inflammation associated
with hereditary angioedema
• Adverse Effects
• Visual abnormalities, Hypotension (with rapid injection)
• Nausea, Vomiting, Diarrhea, Anaphylaxis
• Contraindications
• Hypersensitivity, Acquired defective color vision
• Subarachnoid hemorrhage, Active intravascular clotting
25. Desmopressin (DDAVP, Stimate)
• Increase in von Willebrand factor VIII
and t-PA levels; this shortens activated
partial thromboplastin time (aPTT), as
well as bleeding time.
• Adverse Effects: Dry mouth,
Headache, Hyponatremia, Dizziness.
• Contraindications: Hypersensitivity,
Hyponatremia or history of
hyponatremia, Moderate to severe
renal impairment (CrCl <50 mL/min).
26. Anti-inhibitor coagulant complex (Feiba
VH)
• Mechanism of Action
• Provides activated blood coagulation factors II, VII, IX
and X from pooled human plasma
• May shorten the activated partial thromboplastin time
of plasma containing factor VIII inhibitors
• Adverse Effects: Headache, Lethargy, Nausea, Chest
discomfort, Chills, Rash
• Contraindications
• Treatment of bleeding occurrences resulting from
deficiencies in coagulation factors VIII or IX
• DIC
• Normal coagulation mechanisms present
27. Factor IX, recombinant (BeneFIX,
Rixubis, Alprolix, Ixinity, Rebinyn)
Mechanism of Action
• Temporarily replaces missing clotting factor IX which corrects and/or
prevents bleeding.
Adverse Effects
• Headache (10.8%)
• Dizziness (7.7%)
• Injection site reaction (7.7%)
• Injection site pain (6.2%)
• Nausea (6.2%)
• Rash (6.2%)
• Taste perversion
Contraindications
Hypersensitivity to product or its
excipients including hamster protein
Disseminated intravascular coagulation
(DIC)
Signs of fibrinolysis
28. Prednisolone
• Mechanism of Action
• Glucocorticosteroid; elicits mild mineralocorticoid
activity and moderate anti-inflammatory effects;
controls or prevents inflammation by controlling rate of
protein synthesis, suppressing migration of
polymorphonuclear leukocytes (PMNs) and
fibroblasts, reversing capillary permeability, and
stabilizing lysosomes at cellular level
• Adverse Effects: Acne, Adrenal suppression,
Delayed wound healing, Diabetes mellitus, GI
perforation, Glucose intolerance.
• Contraindications: Documented hypersensitivity,
Systemic fungal infection, varicella, superficial herpes
simplex keratitis, Receipt of live or attenuated live
vaccine
29. Cyclophosphamide (Neosar, Cytoxan)
• Mechanism of Action
• Metabolites interfere with malignant cell growth by cross-
linking tumor cell DNA; drug does not have specificity for
any phase of the cell cycle; also has potent
immunosuppressive activity
• Adverse Effects: NVD, Hemorrhagic colitis, Oral mucosal
ulceration, Jaundice, Alopecia, Skin rash
• Contraindications
• Severe myelosuppression
• Hypersensitivity
• Urinary outflow obstruction
31. Emicizumab (Hemlibra, emicizumab-
kxwh)
• Mechanism of Action
• Bispecific factor IXa- and factor X-directed antibody
that bridges activated factor IX and factor X in order to
restore the function of missing activated factor VIII
necessary for effective hemostasis
• Adverse Effects
• Injection site reaction (22%)
• Headache (15%)
• Arthralgia (15%)
• Injection site erythema (11%)
• Contraindications: None
32. Rituximab (Rituxan)
• Mechanism of Action
• Humanized monoclonal antibody, binds to CD20
antigen on surface of normal and malignant B
lymphocytes, inducing complement- or antibody-
mediated cytolysis. This results in reduced
autoantibody production.
• Adverse Effects
• Angioedema (11%)
• Asthenia (26%), chills (33%), dizziness (10%), fever
(53%), headache (19%)
• Pruritus (14%), rash (15%)
• Abdominal pain (14%), diarrhea (10%), nausea
(23%), vomiting (10%)
• Contraindications: None
Editor's Notes
View full drug information
View full drug information
View full drug information
View full drug information
Antihemophilic Factor (FVIII) and von Willebrand Factor (VWF) are constituents of normal plasma, which are required for clotting
View full drug information
View full drug information
This is the product of choice when factor XI concentrates are not available. FFP is easily available. It can be infused over a short period. Disadvantages include large infusion volumes to achieve appropriate control of bleeding, a potential for transmitting infective agents, and the possibility of allergic reactions.
