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H32 Hematology
Disorders of Secondary Hemostasis Toronto Notes 2019 Factor XI Deficiency
• autosomalrecessive;morecommoninAshkenaziJewishpopulation
• usuallymild,oftendiagnosedinadulthood
• FactorXIleveldoesnotcorrelatewithbleedingrisk–riskofbleedingcorrelateswithaprevioushistory
or family history of bleeding
• treatment:antifibrinolyticagents,frozenplasma,andFactorXIconcentrate
Liver Disease
• seeGastroenterology,G31
Pathophysiology
• deficientsynthesisofallfactorsexceptVIII(alsomadeinendothelium)
• aberrantordiminishedsynthesisoffibrinogen(factorI)
• diminishedsynthesisofnaturalanticoagulantsandalteredregulationoffibrinolysis
Investigations
• peripheralbloodfilm:targetcells • primaryhemostasisaffected
■ thrombocytopenia 2o to hypersplenism, nutritional deficiency, direct bone marrow toxicity related to alcohol, diminished production from chronic viral infections (e.g. HCV), and decreased production of thrombopoietin
• secondaryhemostasisaffected
■ elevated INR (PT), aPTT, TT, and low fibrinogen in end-stage liver disease
Treatment
• supportive,treatliverdisease,bloodproductsifactivebleeding(frozenplasma,platelets, cryoprecipitate)
Vitamin K Deficiency
Etiology
• drugs
■ vitamin K antagonist (e.g. Warfarin) – diminished production of functional Factors II, VII, IX, X,
proteins C and S
■ antibiotics eradicating gut flora, altering vitamin K uptake
• poordiet(especiallyinalcoholics)e.g.prolongedfastingorstarvation
• biliaryobstruction
• chronicliverdisease(decreasedstores)
• fatmalabsorption(e.g.celiacdisease,disordersofbileorpancreaticsecretion,andintestinaldisease,CF) • hemorrhagicdiseaseofnewborn,seePediatrics,P62
Investigations
• INR(PT)iselevatedoutofproportiontoelevationoftheaPTT • decreasedFactorsII,VII,IX,X(vitaminK-dependent)
Treatment
• holdanticoagulantifvitaminKantagonistonboard
• vitaminKPOifnoactivebleeding
• ifbleeding,givevitaminK10mgIV(reversalmaytakeupto12h)
• iflife-threateningbleedingandvitaminKantagonistused,giveprothrombincomplexconcentrate
(PCC) or FP if PCC contraindicated
■ PCCs are contraindicated if there is a previous history of HIT (heparin is within the PCC product)
Disseminated Intravascular Coagulation
Definition
• excessive,dysregulatedreleaseofplasminandthrombinleadingtointravascularcoagulationand depletion of platelets, coagulation factors and fibrinogen
• riskoflife-threateninghemorrhageorthromboembolism
Etiology
• occursasacomplicationofmanyotherseveremedical,surgicalorobstetricalconditions • widespreadendothelialdamageandextensiveinflammatorycytokinerelease
Investigations in Liver Disease
Factor V, VII, VIII. Expect decreased V and VII because they have the shortest half-life. Factor VIII will be normal or increased because it is produced in the endothelium
Vitamin K Dependent Factors
Vitamin K antagonists (e.g. warfarin) affect function of these factors:
“1972 Canada vs. Soviets”
X, IX, VII, II proteins C and S
PT should improve within 24 h of adequately dosed vitamin K repletion (onset is in 6-12 h); if not, search for other causes
American Society of Hematology Choosing Wisely Recommendation
Do not administer plasma or prothrombin complex concentrates for non-emergent reversal of vitamin K antagonists (e.g. outside of the setting of major bleeding, intracranial hemorrhage, or anticipated emergent surgery)
DIC is a spectrum which may include thrombosis, bleeding, or both
Factor Levels in Acquired Coagulopathies
Factor Liver Vitamin K DIC Disease Def
ViNi VII i i i VIII N/h N i