Hemostasis and Coagulation Flashcards
Aspirin function
Inhibits platelet thromboxane (TXA2) formation
-Irreversible inhibitor of cyclooxygenase (COX)
-Decreases TXA2: PGI2 ratio
Heparin
Activates antithrombin III and inactivates thrombin
Warfarin (oral anticoagulant)
Blocks vitamin K epoxide reductase (VKOR) in liver and prevents regeneration of the active form of vitamin K
-Inhibits synthesis of mature vitamin K dependent clotting factors
Streptokinase/Urokinase
Thrombolytic agent; plasminogen activator
-Converts plasminogen to plasmin enabling dissolution of clots
Tissue Plasminogen activator
Used to dissolve a thrombus
-Converts plasminogen to plasmin enabling dissolution of clots.
Test to detect the von Willebrand disease
Ristocetin cofactor assay which determines reduced platelet aggregation in von Willebrand disease
Test to determine which type of platelet glycoprotein disease
Flow cytometry to distinguish Bernard-Soulier syndrome vs. Glanzmann thrombasthenia
Disorders of the clotting pathway (coagulation cascade) include:
1) Hemophilia A and B
2) Vitamin K deficiency
Disorders caused by defects in platelet plug formation:
1) Von Willebrand disease
2) Platelet defects: Thrombocytopenia, Bernard-Soulier syndrome, Glanzmann thrombasthenia
Tests for primary hemostasis/platelet plug formation:
Bleeding time
Platelet count
vWF levels
Platelet aggregation studies (ADP, thrombin, ristocetin)
Flow Cytometry
Tests for secondary hemostasis/clotting cascade:
Prothombin time (PT/INR)
APTT
Function of Endothelial PGI2 (prostacyclin) and nitric oxide:
Prevent platelet aggregation
Function of PGI2:
Increases platelet cAMP levels and inhibits activation (Thromboxane antagonist)
Function of Antithrombin III
-Inactivates thrombin and factor Xa and prevents clotting
Which molecule activates Antithrombin-III?
Heparin (glycosaminoglycan)
Which vitamin is Protein C and S dependent on?
Vitamin K
What activates protein C and protein S?
Binding of thrombomodulin to thrombin
Function of proteins C and S
Inactivation of Va and VIIIa of the coagulation cascade
Elevated levels of what indicates a high risk for pulmonary embolism?
Highly elevated D-dimer levels
Primary hemostasis
Platelet plug formation
Secondary hemostasis
Blood coagulation
Steps in Hemostasis
- Vascular spasm/vasoconstriction
- Platelet plug formation/primary hemostasis
- Blood coagulation/secondary hemostasis
- Clot stabilization and resorption
Defect is which protein causes Bernard-Soulier syndrome?
Platelet receptor Gp1b: this binds collagen which allows adhesion of von Willebrand factor biding to allow for adhesion to the subendothelial collagen layer
Factor [ ] levels are low in hemophilia A
Factor VIII
Factor [ ] levels are low in hemophilia B
Factor IX
Disease characterized by: instability of Factor VIII
-Increased mucosal bleeding
-Easy bruising
-Epistaxis
-Increased post-operative bleeding
-Prolonged bleeding following tooth extraction
von Willebrand Disease
Abnormal lab findings in von Willebrand Disease
- Primary hemostasis: prolonged bleeding time, abnormal Ristocetin assay
- Secondary hemostasis: prolonged APTT
Features of Thrombocytopenia
Increased bleeding time and low platelet count
Disease that is due to GpIIb/IIIa defect
Glanzmann Thrombasthenia
EDTA (in-vitro)
Calcium chelator
Warfarin (Coumadin)
Inhibits gamma-carboxylation of vitamin K dependent clotting factors; Inhibits regeneration of vitamin K; inhibits vitamin K epoxide reductase
Erythropoietin (EPO)
Produced by the kidneys to increase erythrocyte precursors.
Thrombopoietin (TPO)
Hormone from liver stimulates thrombocyte formation
Cytokines
Local hormones of bone marrow
Which factors stimulate leukocyte production?
Colony-stimulating factor (CSF) and interleukin
Life span of Erythrocytes
120 days (removed by spleen macrophages)
Individuals that express N-acetylgalactosamine transferase have which blood group?
A
Individuals that express galactose transferase have which blood group?
B
For individuals that express the necessary enzymes within the blood have which blood group?
O
What is the main stimulus for erythropoiesis?
Hypoxia
Poikilocytosis
The presence of poikilocytes in the blood: RBCs of distorted shape
-Various shapes can be due to membrane abnormalities or due to traumatic conditions
Anisocytosis
Blood abnormality where the RBCs are of unequal sizes
-Can be detected in peripheral smears
-Can signify conditions such as anemia and thalassemia
Hereditary spherocytosis
Caused by molecular defects in genes that code for spectrin, ankyrin, band 3 and band 4 proteins. This results in a spherical shape of RBC than the biconcave nature of it.
The shape of RBCs in patients with beta-Thalassemia:
Target cells
Beta-thalassemia
Indicates decreased or absent beta chains. Hereditary hypochromic anemia
Sickle cell anemia
Genetic defect in hemoglobin molecule (Hb-S) where a single point mutation causes hydrophobic glutamic acid replaced by hydrophobic valine at point 6 in the beta chain
T cells
Cell mediated immunity: differentiate in the thymus
-Long life span
-Attack viruses, fungi, transplanted organs, cancer cells and some bacteria
B cells
First recognized in the bone marrow:
-Production of antibodies
-Destroy bacteria and their toxins
-Turn into plasma cells that produces antibodies
-Variable life span
Natural killer cells (NK): programmed during development
-Attack many different microbes and some tumor cells
-Destroy foreign invaders by direct attack
Redness following injury site such as wound or cut is due to:
Hyperemia: increased diameter of vessels at the site
Pain following inflammation of injury site is due to:
The release of bradykinin and PGE2
Which mediators of acute inflammation cause vasodilation?
Prostaglandins, nitric oxide, histamine
Which mediators of acute inflammation cause increased vascular permeability?
Histamine, serotonin, bradykinin, leukotrienes
Which mediators of acute inflammation cause fever?
Cytokines (IL-1, TNF), prostaglandins
What increases the production of free radicals (Reactive oxygen species)?
Oxidant drugs (Sulfa drugs/Primaquine) or infection or fava beans
-Defect in the pentose phosphate pathway leads to the accumulation of hydrogen peroxide accumulation that damage RBC membrane that leads to hemolysis
G6PD deficiency results in the formation of:
Heinz bodies (denatured insoluble proteins) due to the inappropriate disulfide bond formation
