Doria and Saxena Flashcards
Thrombophilia
Inappropriate activation of hemostatic system with excessive thrombus formation. Most common cause of death is the U.S. Abnormalities can be acquired or hereditary. Complications secondary to ischemia or necrosis of distal organs.
Define thrombus
Intravascular mass of platelets, fibrin and entrapped cells and is attached to a vessel and can grow or be dislodged at distant sites as an embolus.
Define Hemostasis
Carefully balanced process task maintenance of fluid blood flow to ultimately keep internal body environment constant. Process of clot formation and lysis and vessel repair and involves series of complex and regulated events.
Coagulation
Concerned with the formation of insoluble fibrin clot from proteins present in the blood that are in an inactive state (zymogen)
Coagulation deficiencies
Slow rate of coagulation, prolonged clot formation, bleeding tendencies
3 majors facets that act simultaneously in hemostasis
Vasculature: contracture and dilation - diminish or increase flow, localize the reaction.
Platelets: form aggregate plugs and aid in secondary coagulation.
Coagulation factors: support the unstable platelet plug with fibrin formation and late breakdown.
Where are coagulation factors produced
Mostly in the liver, 8 (vWF) in megakaryocytes and endothelial cells of the liver, 8 (C) in macrophages and 13 in megakaryocytes.
Nomenclature of factors
Factor I Fibrinogen
Factor II Prothrombin
Factor III Tissue thromboplastin (tissue factor)
Factor IV Calcium
Factor V Labile factor (proaccelerin)
Factor VI Not assigned (was activated Factor V)
Factor VII Stable factor (serum prothrombin conversion accelerator or SPCA)
Factor VIII Antihemophilic factor, von Willebrand factor
Factor IX Christmas factor (plasma thromboplastin component or PTC)
Factor X Stuart Prower factor
Factor XI Plasma thromboplastic antecedent (PTA)
Factor XII Hageman factor (contact factor)
Factor XIII Fibrin stabilizing factor (FSP)
Fitzgerald factor HMWK (high molecular weight kininogen)
Fletcher factor Prekallikrien
Factor 1 ( fibrinogen)
chromosome 4, produced in liver, normal level is 250 mg, substrate, in all pathways.
Factor 2 (prothrombin)
chromosome 11, produced in liver, vitamin K dependent, serine protease, thrombin precursor, in all pathways.
Factor 3 ( tissue thromboplastin)
Chromosome 1, transmembrane glycoprotein found in most nonvascular cells, not in plasma, cofactor of factor 7 in the extrinsic and common pathway.
Factor 4 ( calcium)
required in many coag reactions
Factor 5 ( proaccelerin)
Labile factor, chromosome 1, produced in liver, cofactor in prothrombinase complex in all pathways.
Factor 7 ( proconvertin, stable)
chromosome 1, produced in liver, vitamin k dependent, serine protease, component of extrinsic Xase complex in extrinsic only.
Factor 8 ( antihemophilic factor, von Willebrand factor)
chromosome X, produced in the megakaryocytes, cofactor in intrinsic xase complex in intrinsic only.
Factor 9 ( plasma thromboplastin component, Christmas factor)
Chromosome X, produced in the liver, vitamin K dependent, cofactor in intrinsic Xase complex, intrinsic only.
factor 10 ( Stuart Prower factor)
Chromosome 13, produced in liver, vitamin k dependent, serine protease, component of prothrombinase complex, in all pathways.
Factor 11 ( plasma thromboplastin antecedent)
chromosome 4, produced in liver, most bound to HK in circulation, serine protease, contact factor, intrinsic only
Factor 12 ( Hageman factor)
Chromosome 5, produced in liver, serine protease, contact factor, intrinsic only.
Factor 13 ( fibrin stabilizing factor)
Chromosome 6 and 1, produced in liver or megakaryocytes, transglutamase in all pathways.
Fitzgerald Factor
HK, High molecular weight kininogen, Williams factor. Chromosome 3, produced in liver, contact factor, complex with prekallekrein and FXI, in intrinsic.
Fletcher factor ( Prekallekrein)
chromosome 4, bound to HK in circulation, serine protease, complex with PK, in intrinsic
Co - factors
Factors 5, 8, HK. no enzymatic activity and enhances reactivity of associated protease. substrate is fibrinogen, enzymes are activated by conformational change or proteolytic cleavage of zymogen peptide bonds.
Prothrombin group
factors 2, 7, 9 AND 10, requires calcium and vitamin K, attaches -COOH group to glutamic acid, deficient proteins PIVKA. Vitamin K deficiency in parenteral feeding, neonate, liver disease, gut surgery, antibiotic therapy.
Fibrinogen group
Factors 1, 5, 8, and 13. Consumed during clotting, absent from serum, responds to thrombin. Acute phase proteins
Contact group
Factors 11, 12, PK, HK. Involved in initial activation and requires negatively charged surface. Stable and found in serum. No bleeding associated with deficiency except for factor 11.
How is intrinsic pathway activated
Factor 12 is activated by autoactivation, by a foreign substance or other charge dependent, glass, acid, cellite, plasmin, kallikrein. Factor 12a and HK activates prekallikrein to kallikrein to produce more factor 12. Complex with factors 9a, 8a, platelet factor 3 and calcium activates the common pathway.
Extrinsic Pathway
Factor 3 is a cell membrane protein found almost subendothelial cells and when exposed to injury, factor 3 is exposed and binds factor 7 and factor 7a and with calcium activate factor 7. The activated Factor 7 complex can activate the common pathway via Factor 10 and the intrinsic pathway via Factor 9.
Common Pathway
Factor 1 0activated by extrisnic and intrinsic pathways, factor 5 activated by thrombin. Complex with 10a, 5a, factor 3, and calcium activates factor 2 to thrombin. Thrombin acts on fibrinogen to produce fibrin. Factor 13a acts on fibrin clot.
Fibrinogen
Most abundant factor in serum and responsible for ESR. Thrombin cleaves portions of alpha and beta chains at the arginine-glycine bonds of the E nodule and converts it to a net positive charge.
What converts fibrinogen to fibrin
Thrombin. Thrombin also degrades factor 5 and 8. Aggregate platelets and initiates thrombolysis, and involved in inflammation.
Fibrinolysis
Main function is the removal of excessive fibrin from the circulation in a controlled manner and prevent expansion of coag, and allow progression of vascular and tissue repair and restoration of function. Activated in response to initiation of coag. Key enzyme is plasmin, which degrades fibrin.
Plasmin
Degrades fibrin, fibrinogen, 5 and 8. Enhance 11 and 11a, enhance prekallekrein to kallekrein. Cleave C3 to fragments.
Liver clearance
Major site of factor production and primary site for removal of activated factors with their inhibitors and degradation products. LDL receptor related protein found on hepatocytes and live macrophages and degrades activated factors.
Antithrombin
Most important anti - coagulant and all degrades serine proteases, especially thrombin and also plasmin. HSP localizes reaction
