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 GPIbα (vWF receptor) Platelets can’t attach to vWF
Syndrome
Glanzman GPIIb-IIIa (fibrinogen receptor) Platelets can’t aggregate ∴ can’t make stable clots
Thrombasthenia

2° Bleeding Disorders
Vitamin K Deficiency Glutamic acid residues not added to Liver can’t produce prothrombin, factors VII, IX, X, or Protein C
factors ∴ 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 Could trigger thromboses
surface
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
Coagulation System Testing
Test*
Whole Blood Clotting Time
Bleeding Time
PT – Prothrombin Time
PTT – Partial Thromboplastin Time
TT – Thrombin Time
Platelet Aggregation
*Measured in seconds. Expressed as INR
Drugs
Name
Anticoagulant
Coumadin, Warfarin
Heparin
Hirudin (synthetic version=hirulog)
Antiplatelet
GPIIb-IIIa blocking Ab, RGD-mimetic
Aspirin, indomethecin - Cyclooxygenase (COX) inhibitor
Steroids - Phospholipase inhibitor
Ticlopidine, Clopidogrel
Fibrinolytic
TPA (Tissue Plasminogen Activator_
Streptokinase (Plasminogen activator)
Italics = highlighted in notes
Procedure
Collect blood. Invert every 30 sec. until clot forms. Norm = 6-10 min
Cut and time to stoppage of bleeding. Norm = 1-6 min
Oxalate blood. Add excess Ca+2 and tissue factor. Time to clot. Norm = 12 sec
Indication of prothrombin in blood – Estimates common pathway
Oxalate blood. Add excess Ca+2, kaolin, phospholipid. Time to clot.
“partial” b/c NO tissue factor
Estimates intrinsic and extrinsic factors
Add thrombin, Ca+2
Estimates fibrinogen function
Add agonist/activator. Measure clumping optically
Action
Inhibit γ-carboxylation of Vitamin K dependent cofactors
↑ antithrombin activity (↑ TAT-complexes)
Inhibit thrombin
Block fibrinogen receptor (GPIIb-IIIa)
Inhibit thromboxane (TXA2) synthesis
Block ADP receptor
Clot lysis