430 likes | 777 Views
HEMOPHILIA. Hemophilia is a sex-linked, genetic disorder characterized by the deficiency or absence of one of the clotting proteins in plasma.The result is delayed bleeding (spontaneous or traumatic).FVIII Deficiency: Hemophilia AFIX Deficiency: Hemophilia B. Normal Coagulation. Constriction of
E N D
1. BASIC CONCEPTS IN HEMOPHILIA Regina B. Butler, R.N.
The Children’s Hospital of Philadelphia
2. HEMOPHILIA Hemophilia is a sex-linked, genetic disorder characterized by the deficiency or absence of one of the clotting proteins in plasma.
The result is delayed bleeding (spontaneous or traumatic).
FVIII Deficiency: Hemophilia A
FIX Deficiency: Hemophilia B
3. Normal Coagulation Constriction of injured vessels
Platelet plug formation
Platelets adhere to damaged vessel
Platelets aggregate , forming a primary clot
Fibrin clot formation
4. Fibrin Clot Formation Clotting proteins circulate in inactive form.
The intrinsic and extrinsic pathways function to activate clotting factors in sequence. Both pathways trigger the final, common pathway to convert fibrinogen to fibrin.
5. Fibrin Clot Formation The intrinsic pathway is activated by
contact of blood with damaged vessel wall
conversion of Factor XII to XIIa.
Subsequent factors, including VIII and IX, are activated to convert X to Xa,
6. Fibrin Clot Formation Xa activates prothrombin, which forms thrombin.
Thrombin converts fibrinogen into fibrin strands, which stabilize the clot.
7. Defect in Hemophilia
First steps in clotting function well:
immature platelet plug forms
bleeding stops
8. Defect in Hemophilia First two steps occur
If clotting protein decreased or absent, fibrin formation disrupted
Platelet plug breaks up
Repeated cycle of bleeding, stopping
9. Patterns of Inheritance
Sex-linked, recessive
Abnormal gene carried on X chromosome
10. Affected Males
Males have one X chromosome
Presence of affected X chromosome = hemophilia
Cannot transmit affected genes to sons
All daughters of affected men are obligate carriers.
11. Carrier State Females have 2 X chromosomes
Normal gene codes for factor production
May pass gene to son (hemophilia)
May pass gene to daughter (carrier)
Rarely have bleeding symptoms
12. Obligate Carriers
Two or more sons with hemophilia
One son and another relative with hemophilia
Daughter of a man with hemophilia
13. Family History Approximately 1/3 of new cases have no family history
Possible reasons for lack of family history:
inadequately reported or unknown history
mutation originating in mother’s ovum
mutation originating in maternal grandparent (most common: maternal grandfather)
14. Diagnosis of Hemophilia Presentation
Bleeding from circumcision ( in North America)
Multiple raised bruises
Testing due to family history
History
Patient history
Family history
15. Diagnosis of Hemophilia Laboratory Studies
Screening studies:
PT (normal)
PTT (prolonged)
BT (usually normal)
Specific Assays
Factor VIIIc
Factor IX assay
16. Severity of Hemophilia Severity correlates with amount of factor in plasma:
Normal levels = 50%-150%
Severe : < 1% (spontaneous bleeding)
Moderate: 1-5% (bleeding after trauma)
Mild: >5% (bleeding after serious trauma or surgery)
17. Sites of Bleeding LIFE-THREATENING BLEEDS
CNS Bleeding
intracranial hemorrhage - leading cause of death from bleeding
spontaneous
after mild or major trauma
18. Sites of Bleeding LIFE-THREATENING BLEEDS
Airway Obstruction
neck swelling
bleeding under tongue
GI hemorrhage
common in severe hemophilia
absence of demonstrable lesions
19. Sites of Bleeding Common Sites in Young Children
Head trauma
immediate treatment and evaluation
Mouth bleeding
frenulum tears
exfoliation and eruption of teeth usually not problematic
20. Common Sites of Bleeding Hemarthrosis
most common site of bleeding
knees, ankles and elbows most frequent
target joints
hemophilic arthropathy
21. Common Sites of Bleeding Muscle Bleeding
Second most frequent site
Any area of body (frequently extremities)
Large muscles: significant blood loss
thigh
iliopsoas
Closed spaces: nerve compression
22. Management of Hemophilia TRADITIONAL GOAL OF THERAPY
The goal of therapy in hemophilia is to replace the deficient factor at the first sign of bleeding to stop the bleeding and prevent resulting complications.
23. Management of Hemophilia PROPHYLAXIS
Prophylaxis is treatment on a regular basis to prevent bleeding.
GOAL: Maintain factor level > 1%
Primary prophylaxis : regular treatment, starting at an early age, to prevent bleeding
Secondary prophylaxis: regular treatment to stop the cycle of bleeding in a chronic joint
24. Prophylaxis Advantages:
decreased joint bleeding
decreased bleeding into other areas
increased participation in activities
predictable schedule of treatment
25. Prophylaxis Disadvantages:
Cost
Availability of factor
Venous access
Adherence to schedule
False sense of security
Lack of family assessment skills /appropriate interventions
26. Factor Replacement Products Infused I.V. to raise factor VIII or IX levels
Derived from human plasma prior to 1992
Safety concerns: viral transmission
All donors, products screened
All products have viral inactivation steps
No transmission of HIV, HBV, HCV reported in U.S. since 1987
27. Factor Replacement Products Plasma Derived:
Factor VIII
Factor VIII with vWF
Prothrombin Complex Concentrates
Coagulation Factor IX
Recombinant:
Factor VIII
Factor IX
28. Treatment of Bleeding Goal: raise factor level from baseline to a hemostatic level.
Stated as “desired correction” (%)
Dose depends on individual response and type and severity of bleeding
29. Dose of Factor Replacement Products
Factor VIII: 1 i.u./kg raises factor level 2%.
( % correction X wt (kg) X .5 = i.u.)
PD FIX: 1 i.u./kg raises factor level 1 %
rFactor IX: 1.2 i.u./kg raises factor level 1%
( % correction X wt (kg) X 1.2 = i.u.)
30. Factor ReplacementBiologic Half Life
Factor VIII: 8-12 hours
8-12 hours
Factor IX: 18-24 hours
31. Treatment of Bleeding Episodes
Early and appropriate treatment of each episode is critical to minimizing the complications of bleeding in patients with hemophilia. Replacement of the deficient clotting factor is the single most important step in any intervention.
32. Treatment of Serious Bleeding
Factor VIII or IX to reach high level
Treat ASAP, before diagnostic evaluation
Maintain factor VIII or IX levels above 30% until hemostasis achieved.
33. Treatment of Joint and Muscle Bleeding
Factor replacement at first sign of bleeding
Repeated dosing may be indicated
R.I.C.E.
34. Treatment of Muscle Bleeding Check hb if large muscle involved
Rest
observe for parasthesias
35. Treatment of Mouth Bleeding Factor Replacement
Antifibrinolytics
Soft diet
Avoid straws, bottles, pacifiers
Topical agents
36. Complications of Hemophilia Complications of Bleeding:
Hemophilic arthropathy: result of repeated bleeding into joint space
Anemia
CNS/ organ damage
Complications of Treatment:
Inhibitors
Hepatitis
HIV
37. Hepatitis A
Rarely transfusion related
Few cases reported in factor recipients
Vaccination recommended
38. Complications of TreatmentHepatitis B
Often transfusion related
Can become chronic
Vaccination recommended
39. Complications of TreatmentHepatitis C Most common cause of liver disease in hemophilia
Transmitted through blood (factor concentrates before 1987)
Risk:
chronic liver disease
liver carcinoma
40. Complications of TreatmentHIV Infected blood supply in late 1970’s and early 1980’s
80% of treated patients with severe hemophilia infected in U.S. by 1985
Testing and viral inactivation steps since 1985
No documented case in U.S. in factor supply since 1987
41. Future Directions Increased use of prophylaxis ?
Increased access to care worldwide
Increasing purity of products
Prolonged half-life
Affordable, available treatment products
Gene therapy
42. Patiently Waiting for a Cure