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Toronto Notes 2019
Disorders of Secondary Hemostasis
Hematology H31
Table 25. Investigations in vWD
Test
PTT
Factor VIII
Plt Count Ristocetin Activity
Treatment
Expected Result
N/h
N/i
N/i
i(cofactor for vWF-Plt binding)
Test
von Willebrand antigen Blood group
vWF multimer analysis
Expected Result
i
Affects antigen quantification (i in group O) Multimer variants
• desmopressin(DDAVP®)iseffectivetreatmentfor85-90%ofpatientswithtype1vWDandforsome subtypes of type 2 vWD
■ causes release of vWF and Factor VIII from endothelial cells
■ variable efficacy depending on disease type; tachyphylaxis occurs after 4 consecutive doses ■ need to document responsiveness with “DDAVP® challenge”
■ caution in children due to hyponatremia
• tranexamicacid(Cyklokapron®,antifibrinolytic)tostabilizeclotformation
• vWF:FVIIIconcentrate(HumateP®,Wilate®)ifDDAVP®unresponsive/clinicallyineffectiveorfor
severe bleeding episode
■ need to monitor vWF and factor VIII levels (very high factor VIII level can be prothrombotic)
• gynecologicfocusedcareforheavymenstrualbleeding(NBestrogenshavetheaddedbenefitof increasing vWF levels)
Prognosis
• patientswithmildtype1vWDhaveauto-correctionofvWFdeficiencyinpregnancy
• patientsarebestmanagedbyahematologist,ideallyonewhoworksinaHemophiliaTreatmentCentre
(HTC)
Disorders of Secondary Hemostasis
Definition
• inabilitytoformanadequatefibrinclot
■ disorders of clotting factors or co-factors
■ disorders of proteins associated with fibrinolysis
• characterizedbydelayedbleeding,deepmuscularbleeding,andspontaneoushemarthroses
Table 26. Classification of Secondary Hemostasis Disorders
Consider vWD in all women with menorrhagia
vWD is the most common inheritable couagulation abnormality
Hereditary
Factor VIII: Hemophilia A, vWD
Factor IX: Hemophilia B (Christmas Disease) Factor XI
Other factor deficiencies are rare
Acquired
Liver disease
DIC
Vitamin K deficiency
Acquired inhibitors (FVIII most common)
Hemophilia A (Factor VIII Deficiency)
Pathophysiology
• X-linkedrecessive,1/5,000males
• mild(>5%ofnormalfactorlevel),moderate(1-5%),severe(<1%)
Clinical Features
• seeTable19–SignsandSymptomsofDisordersofHemostasis,H26
• olderpatientsmayalsohaveHIVorHCVfromcontaminatedbloodproducts
Investigations
• prolongedaPTT,normalINR(PT)
• decreasedFactorVIII(<40%ofnormal)
Treatment
• desmopressin(DDAVP®)inmildhemophiliaA
• FactorVIIIconcentratefor:
■ prophylaxis
■ on-demand (i.e. to treat a bleed)
• anti-fibrinolyticagents(e.g.tranexamicacid)
Hemophilia B (Factor IX Deficiency)
• X-linkedrecessive,1/30,000males;approximatelyhalfhaveseveredisease(factorIXactivity<1%of normal)
• clinicalandlaboratoryfeaturesidenticaltohemophiliaA(exceptdecreasedFactorIX)
• treatment:FactorIXconcentrate(prophylaxisoron-demand),anti-fibrinolyticagents