bleeding disorders january 19, 2012 erin m. kwolek
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Bleeding DisordersBleeding Disorders
JANUARY 19, 2012JANUARY 19, 2012Erin M. KwolekErin M. Kwolek
3 important questions…3 important questions…
Is the bleeding significant?Is the bleeding significant?
Is the bleeding likely related to an Is the bleeding likely related to an underlying health problem or to underlying health problem or to medication/chemical ingestion?medication/chemical ingestion?
Is there a family history of a Is there a family history of a bleeding disorder?bleeding disorder?
Important historical Important historical informationinformation
The nature of bruisingThe nature of bruising
Site of bleedingSite of bleeding
Bleeding with traumaBleeding with trauma
Duration of bleeding tendencyDuration of bleeding tendency
General healthGeneral health
Drug and chemical ingestionDrug and chemical ingestion
Family history of bleedingFamily history of bleeding
hemophiliahemophilia
1.1. HemophiliaHemophilia
2.2. PorphyriaPorphyria
3.3. HIV/AIDSHIV/AIDS
4.4. SmallpoxSmallpox
5.5. PlaguePlague
6.6. CholeraCholera
7.7. TuberculosisTuberculosis
8.8. SyphillisSyphillis
9.9. InfluenzaInfluenza
10.10. MalariaMalaria
11.11. Yellow FeverYellow Fever
12.12. Irish Potato BlightIrish Potato Blight
Hemophilia AHemophilia Ahistoryhistory
Talmud – babies did not have to be Talmud – babies did not have to be circumcised if two brothers had circumcised if two brothers had died from the proceduredied from the procedure
1803 – “hemorrhagic disposition 1803 – “hemorrhagic disposition existing in certain families”existing in certain families”
1828 - hemophilia1828 - hemophilia
HemophiliaHemophiliaseverityseverity
Factor VII or IX level
Severity Type of bleeding
<0.01 IU/mL Severe Spontaneous, minimal trauma, young age
0.01 – 0.05 IU/mL(1-5%)
Moderate With trauma or surgery, can be spontaneous
0.06 – 0.40 IU/mL(6-40%)
Mild Only with trauma or surgery, can present in adulthood
Hemophilia AHemophilia AFactor VIIIFactor VIII
1:10,0001:10,000
Classic hemophilia, Royal diseaseClassic hemophilia, Royal disease
Hemophilia BHemophilia BFactor iXFactor iX
1:60,0001:60,000
Christmas diseaseChristmas disease
Hemophilia Hemophilia treatmenttreatment
Replace missing clotting factorsReplace missing clotting factors
Education and lifestyleEducation and lifestyle
On demand vs. ProphylacticOn demand vs. Prophylactic
Clotting factors in Clotting factors in canadacanada
Product Introduction in Canada
Fresh whole blood 1947
Cryoprecipitate (Factor VIII) 1965
Factor VIII (lyophilized, unheated) 1968
Factor VIII (lyophilized, dry heat-treated)Factor IX (lyophilized, dry heat-treated)
19851985
Factor VIII (viral inactivation: vapour heat, solvent detergent)
1987
High purity factor VIII (monoclonal antibody purified)Purity factor IX
19871991
GE recombinant factor VIII concentrateGE recombinant factor IX concentrate
19931998
Von willebrandVon willebrand
Von Willebrand factor is made and Von Willebrand factor is made and stored in endothelial cellsstored in endothelial cells
Anchors platelets to subendotheliumAnchors platelets to subendothelium
Factor is made up of protein multimers Factor is made up of protein multimers – the more repeating units the – the more repeating units the “stickier” (more effective) the factor “stickier” (more effective) the factor is is
Stabilizes factor VIII in plasmaStabilizes factor VIII in plasma
VW Dx severityVW Dx severity
TYPE 1 – partial quantitative TYPE 1 – partial quantitative deficiencydeficiency• 80% of people with VW Dx have type 180% of people with VW Dx have type 1
TYPE 2 – qualitative defectTYPE 2 – qualitative defect
TYPE 3 – virtually complete TYPE 3 – virtually complete quantitative deficiencyquantitative deficiency• Very rareVery rare• First type describedFirst type described
Variable expressivity and incomplete penetranceVariable expressivity and incomplete penetrance
Von willebrandVon willebrandtreatmenttreatment
Exogenous - DesmopressinExogenous - Desmopressin• ~3x increase in plasma VWF and factor ~3x increase in plasma VWF and factor
VIIIVIII• Not useful if qualitative abnormality (type Not useful if qualitative abnormality (type
2)2)• Not useful if complete deficiency (type 3)Not useful if complete deficiency (type 3)
Endogenous – factorsEndogenous – factors• Plasma derived VWF concentrate – Plasma derived VWF concentrate –
contains VWF and factor VIIIcontains VWF and factor VIII
Hemophilia A Hemophilia B Von Willebrand
Inheritance X-linked X-linked autosomal dominant
Deficiency Factor VIII Factor IV VW factor, VIIIC
Bleeding sites muscle, joint muscle, joint mucous membranes, skin, menstrual
PT normal normal normal
PTT prolonged prolonged prolonged or normal
Bleeding time normal normal prolonged or normal
Factor VIII activity
low normal low or normal
VW factor antigen
normal normal low
VW factor activity
normal normal low
Factor IX normal low normal
Platelet aggregation
normal normal normal
Hemophilia A Hemophilia B Von Willebrand
Inheritance X-linked X-linked autosomal dominant
Deficiency Factor VIII Factor IV VW factor, VIIIC
Bleeding sites muscle, joint muscle, joint mucous membranes, skin, menstrual
PT normal normal normal
PTT prolonged prolonged prolonged or normal
Bleeding time normal normal prolonged or normal
Factor VIII activity
low normal low or normal
VW factor antigen
normal normal low
VW factor activity
normal normal low
Factor IX normal low normal
Platelet aggregation
normal normal normal
Hemorrhagic disease of Hemorrhagic disease of the newbornthe newborn
Normal PTT, prolonged PTNormal PTT, prolonged PT
VKDB – early, classic, lateVKDB – early, classic, late
Prophylactic Vitamin KProphylactic Vitamin K
Intracranial VKDBIntracranial VKDB
•<
10
< 1
0 se
vere
muco
sal/in
tern
al b
leedin
g se
vere
muco
sal/in
tern
al b
leedin
g
•10-3
010-3
0 p
ete
chia
e, p
urp
ura
, ecch
ym
ose
s p
ete
chia
e, p
urp
ura
, ecch
ym
ose
s
•30-5
030-5
0 e
asy
bru
ising
easy
bru
ising
•>
50
> 5
0 a
sym
pto
matic
asy
mpto
matic
ThrombocytopeniaThrombocytopenia
Decreased productionDecreased production
Increased destructionIncreased destruction
Abnormal sequestrationAbnormal sequestration
Normal value – 150-400 x 10Normal value – 150-400 x 1099/L/L
Lifespan 7-10dLifespan 7-10d
ThrombocytopeniaThrombocytopeniadecreased productiondecreased production
Toxins/drugs/alcoholToxins/drugs/alcohol
Aplastic anemiaAplastic anemia
Intrinsic bone marrowIntrinsic bone marrow
DisplacementDisplacement
Nutritional deficiencyNutritional deficiency
Hereditary thrombocytopeniasHereditary thrombocytopenias
ThrombocytopeniaThrombocytopeniaIncreased destructionIncreased destruction
Auto Immune - ITPAuto Immune - ITP
ThrombocytopeniaThrombocytopenianon-immunenon-immune
DICDIC
TTPTTP
VasculitisVasculitis
HELLPHELLP
DICDIC
Activation of coagulation – failure of Activation of coagulation – failure of homeostasis with bleeding and/or homeostasis with bleeding and/or thrombosis; consumption of clotting thrombosis; consumption of clotting factors and plateletsfactors and platelets
InfectionInfection
TraumaTrauma
Abnormal endothelial surfaceAbnormal endothelial surface
CancerCancer
Obstetrical complicationsObstetrical complications
ThrombocytopeniaThrombocytopeniaIncreased sequestrationIncreased sequestration
SplenomegalySplenomegaly
Platelet dysfunctionPlatelet dysfunction
Congenital causes are rare!Congenital causes are rare!• Glanzmann thrombastheniaGlanzmann thrombasthenia
• Glycoprotein IIb/IIIaGlycoprotein IIb/IIIa• Bernard-Soulier syndromeBernard-Soulier syndrome
• Glycoprotein Ib/IX/VGlycoprotein Ib/IX/V
AcquiredAcquired• DrugsDrugs• Renal diseaseRenal disease• Bone marrow disordersBone marrow disorders
3 important questions…3 important questions…
Is the bleeding significant?Is the bleeding significant?
Is the bleeding likely related to an Is the bleeding likely related to an underlying health problem or to underlying health problem or to medication/chemical ingestion?medication/chemical ingestion?
Is there a family history of a Is there a family history of a bleeding disorder?bleeding disorder?
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