Coagulation Disorders Disease 1° Bleeding Disorders Hemophilia a Hemophilia
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Coagulation Disorders Disease Defect Characteristics 1 ° Bleeding Disorders Hemophilia A Factor VIII deficiency Can’t activate thrombin ∴ can’t clot Hemophilia B Factor IX deficiency “Christmas dz” – Can’t activate thrombin ∴ can’t clot -Platelet related vo nWille br and Dis ea se vo nWil le br and Factor vWF can’t attach to collagen ∴ platelets can’t attach injury site Bernard Soulier Syndrome GPIbα (vWF receptor) Platelets can’t attach to vWF Glanzman Thrombasthenia GPIIb-IIIa (fibrinogen receptor) Platelets can’t aggregate ∴ can’t make stable clots 2 ° Bleeding Disorders Vit amin K Def icie nc y Gl utamic ac id re si du es not add ed to factors Liver can’t produce prothrombin, factors VII, IX, X, or Protein C ∴ no coagulation reaction Liver Disease Liver can’t produce clotting factors Problems with coagulation reaction Thrombocytopenia ↓ Platelet count Bleeding from smaller vessels ∴ Punctate hemorrhages throughout body Thrombophilia Factor V Leiden APC can’t degrade factor V Increased risk to devo venous thrombosis Protein C deficiency ↓ amt APC ↓ degradation of Factors V, VIII Protein S deficiency Less APC-S complex ↓ degradation of Factors V, VIII Hypercoagulability Cancer Expression of tissue factor on surface Could trigger thromboses Pregnancy ↑↑ coagulation system to prepare for parturition Diabetes Mellitus Retinopathies d/t activation of coagulation Obesity ↑ PAI-1 Inhibits plasminogen activity Inflammation Sepsis Stasis ↓ Blood flow Accumulation of coagulation factors in small area
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Coagulation Disorders
Disease Defect Characteristics
1° Bleeding Disorders
Hemophilia A Factor VIII deficiency Can’t activate thrombin ∴ can’t clot
Hemophilia B Factor IX deficiency “Christmas dz” – Can’t activate thrombin ∴ can’t clot
-Platelet related
vonWillebrand Disease vonWillebrand Factor vWF can’t attach to collagen ∴ platelets can’t attach injury site
Bernard Soulier
SyndromeGPIbα (vWF receptor) Platelets can’t attach to vWF
Glanzman
Thrombasthenia
GPIIb-IIIa (fibrinogen receptor) Platelets can’t aggregate ∴ can’t make stable clots
2° Bleeding Disorders
Vitamin K Deficiency Glutamic acid residues not added to
factors
Liver can’t produce prothrombin, factors VII, IX, X, or Protein C
∴ no coagulation reactionLiver Disease Liver can’t produce clotting factors Problems with coagulation reaction
Thrombocytopenia ↓ Platelet count Bleeding from smaller vessels ∴ Punctate hemorrhages
throughout body
Thrombophilia
Factor V Leiden APC can’t degrade factor V Increased risk to devo venous thrombosis
Protein C deficiency ↓ amt APC ↓ degradation of Factors V, VIII
Protein S deficiency Less APC-S complex ↓ degradation of Factors V, VIII
Hypercoagulability
Cancer Expression of tissue factor on
surface
Could trigger thromboses
Pregnancy ↑↑ coagulation system to prepare
for parturition
Diabetes Mellitus Retinopathies d/t activation of coagulation
Obesity ↑ PAI-1 Inhibits plasminogen activity
Inflammation
SepsisStasis ↓ Blood flow Accumulation of coagulation factors in small area
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Coagulation System Testing
Test* Procedure
Whole Blood Clotting Time Collect blood. Invert every 30 sec. until clot forms. Norm = 6-10 min
Bleeding Time Cut and time to stoppage of bleeding. Norm = 1-6 min
PT – Prothrombin Time Oxalate blood. Add excess Ca+2 and tissue factor. Time to clot. Norm = 12 sec
Indication of prothrombin in blood – Estimates common pathwayPTT – Partial Thromboplastin Time Oxalate blood. Add excess Ca+2, kaolin, phospholipid. Time to clot.
“partial” b/c NO tissue factor Estimates intrinsic and extrinsic factors
TT – Thrombin Time Add thrombin, Ca+2
Estimates fibrinogen function
Platelet Aggregation Add agonist/activator. Measure clumping optically
*Measured in seconds. Expressed as INR
DrugsName Action
Anticoagulant
Coumadin, Warfarin Inhibit γ -carboxylation of Vitamin K dependent cofactors
Heparin ↑ antithrombin activity (↑ TAT-complexes)
Hirudin (synthetic version=hirulog) Inhibit thrombin
Antiplatelet
GPIIb-IIIa blocking Ab, RGD-mimetic Block fibrinogen receptor (GPIIb-IIIa)
Aspirin, indomethecin - Cyclooxygenase (COX) inhibitor
Steroids - Phospholipase inhibitor
Inhibit thromboxane (TXA2) synthesis
Ticlopidine, Clopidogrel Block ADP receptor
Fibrinolytic
TPA (Tissue Plasminogen Activator_
Streptokinase (Plasminogen activator)
Clot lysis
Italics = highlighted in notes
