Most abundant coag protein
Factor I
Factor I normal range
200-400 mg/dl
What deficiency?
Absence of fibrinogen, bleeding, thrombocytopenia
Afibrinogenemia
Factor I Hypofibrinogenemia is usually caused by?
liver disease or DIC
Hypofibrinogenemia Factor I range
20-100 mg/dl
•Proteolytic enzymes that cleave peptide bonds that have the amino acid serine in their active sites
serine proteases
•Plasma clotting defects can impair hemostasis
•Caused by?
1.Decreased synthesis of one or more factors
2.Production of abnormal molecules that interfere with the coagulation pathway
3.Loss or consumption of the coagulation factors
4.Inactivation of one or more factor by inhibition or antibodies
Factor I required to maintain normal hemostasis
•100 mg/dL
•Used to differentiate between the presence of heparin, antithrombin anticoagulants, or dysfibrinogenemia
•Reptilase Time
•Synthesized in the liver
•Most abundant factor
•Has the longest half-life of vitamin K- dependent clotting proteins
•Circulates as a zymogen
•Factor II- Prothrombin
•Single point mutation on chromosome 11
•Single base change resulting from a G (guanine) to A ( adenine) transistion at nucleotide 20210.
•Second most common cause of inherited thrombophilia
•Patients have an increased risk of venous thromboembolism
•Primarily restricted to the Caucasian population
•Prothrombin G20210A Mutation
•Second most common cause of inherited thrombophilia
•Prothrombin G20210A Mutation
•Synthesized in the liver and present on the alpha granules of platelets
•Referred to as _____ factor because of rapid deterioration of its activity in plasma at room temperature
Factor V- Labile Factor
•Catalyst in the conversion of prothrombin to thrombin, functions as a cofactor with the prothrombinase complex
Factor V- Labile Factor
•Due to a point mutation of Factor V molecule; renders Factor V molecule insensitive to the activated Protein C
•Result in continuous thrombin generation, promoting thrombosis
•Common defect
•Present in 3 to 7% of Caucasians of Northern European descent
•Factor V Leiden Mutation ( R506Q)
•Due to a point mutation of Factor V molecule; renders Factor V molecule insensitive to the activated Protein C
•Result in continuous thrombin generation, promoting thrombosis
•Common defect
•Present in 3 to 7% of Caucasians of Northern European descent
•Factor V Leiden Mutation ( R506Q)
•Known as Proconvertin for its role in coagulation
Factor VII- Stable Factor
•Known as “______ factor” -Heat and storage stable component
•Produced by the liver requiring vitamin K for its synthesis
•Circulates as an inactive zymogen
Factor VII- Stable Factor
•Extrinsic tenase Complex
•Event of vessel injury, TF ( Tissue factor) and F VII/F VIIa form a complex in the presence of calcium ions
•Known as plasma thromboplastin for its involvement in this mechanism
•Rare, AR
•Patients can present with deep muscle hematomas, hemarthroses, epistaxis, and menorrhagia
•Laboratory Findings
•PT-prolonged ( corrected by mixing pooled normal plasma)
•aPTT-normal ( F ___ not measured by aPTT)
•Homozygous congenital F VII deficiency
How is •Acquired VII deficiency, acquired..?
•Acquired with liver disease, warfarin therapy, broad spectrum antibiotic use, or dietary vitamin K deficiency
•Essential in the middle phase of coagulation
•Secreted in the plasma where is circulates as a macromolecular complex with von Willebrand factor (vWF); designated as F___:vWF
•Factor VIII
FVIII : vWF complex functions?
•1 to 2% of its complex functions as the clotting factor or coagulant F VIII:C ( aka: antihemophilic factor)
•Functions as a cofactor
•Mediates platelet adhesions
•Stabilizes FVIII:C
•Intrinsic tensase complex (function of FVIII:vWF complex)
•Accelerates the conversion of F X to F Xa
•Cleavage of thrombin activates F VIII:C to become FVIII:Ca; it then dissociates from vWF, allowing it to react with platelet phospholipids ,Ca++, and activated F IX.
•Mediates platelet adhesions
•Stabilizes FVIII:C
FVIII : vWF complex
•FVIII:vWF complex
•Serves as a carrier to concentrate FVIII:C at the site of vessel damage
•2nd in overall frequency of the inherited bleeding disorders
•Hemophilia A (Classic Hemophilia)
•Defect: molecular defect or absence of its coagulant portion, F VIII:C
•Caused by:
•A point mutation involving a single nucleotide
•Deletion of all or part of the gene
•Mutation affecting gene regulation
•Hemophilia A (Classic Hemophilia)
•Von Willebrand Disease
•Differs from Hemophilia A in three ways?
1.Autosomal inheritance rather than sex linked
2.Consistently prolonged Bleeding Times
3.Mucocutaneous bleeding rather than hemarthroses and deep muscle hemorrhages
•Most common inherited bleeding disorder
•Effect both males and females equally
•Von Willebrand Disease
