03c: Hemostasis Flashcards
What are the key steps to preventing blood loss?
- Vasoconstriction
- Platelet plug
- Fibrin clot
List the machinery involved in vasoconstriction.
- Neurogenic (fastest)
- Myogenic (fast)
- Humoral (slow)
Examples of neurogenic vasoconstriction:
Spinal reflex, pain response
Examples of myotonic vasoconstriction:
Smooth muscle contracts (response to trauma)
Examples of humoral vasoconstriction:
Substance (i.e. Serotonin) release locally
Once blood extravasates in vessel injury, which steps take place?
- Endothelial cells produce VWF factor
- VWF binds collagen
- Platelets stick to VWF
What’s the “release reaction”?
Platelet adhesion (bound to VWF) causes exocytosis of granule contents
(X) acts as a bridge in formation of platelet plug.
X = collagen
Between endothelial tissue and platelets
Release reaction involves in exocytosis of which substance(s)?
- Ca
- Serotonin
- ADP
- Enzymes targeting platelet phospholipids
Which substance released by (X) specifically aids in increasing platelet aggregation?
ADP released by
X = platelets
How does release reaction affect vasoconstriction?
- Serotonin promotes vasoconstriction
2. Enzymes act on platelet phospholipids and produce TA2 (thromboxane A2)
Thromboxane A2, released by (X), has which effect(s)
Not released directly by platelets, but formed by action of enzymes released by platelets;
- Vasoconstriction
- Increase platelet aggregation
What’s the reason behind platelet aggregation?
Platelets stuck to VWF change surface characteristics (express receptors) that bind other platelets
Easy bruising, without severe hemorrhagic issues, can be a sign of (excess/defecit):
Defecit in platelet adhesion due to decreased VWF (production issues)
What’s considered primary hemostasis?
Vasoconstriction and platelet plug formation
What’s considered secondary hemostasis?
Fibrin clot formation
What’s thrombocytopenic purpura?
Shortage of thrombocytes (platelets), resulting in medium-sized lesions under skin
Patients without primary hemostasis will show (X) on which part(s) of body?
X = lesions under skin
Usually legs/feet
Small lesions under skin are called:
Petechiae
Medium lesions under skin are called:
Purpura
Large lesions under skin are called:
Ecchymoses
In secondary hemostasis, what substance is being produced by (X) to increase platelet aggregation?
Nothing produced to increase aggregation!
Endothelial cells secrete prostacyclins to DECREASE aggregation
In clot formation, what prevents the platelet plug from continuing to spread and grow?
Prostacyclins produced by endothelial cells in secondary hemostasis
What’s hemophilia?
Lack of secondary hemostasis (incapable of forming strong, firm clot)
T/F: Fibrin is a plasma protein that’s always in the circulation.
False - fibrinogen is
Describe process that converts (X) to fibrin.
X = fibrinogen
- Thrombin cleaves it into fibrin monomers
- Monomers spontaneously polymerize into long chains (fibrin polymer)
T/F: Covalent bonds support the fibrin clot.
True
(X) reinforces fibrin clot by inserting (Y) bonds.
X = Fibrin Stabilizing Factor XIII Y = covalent
Thrombin is what kind of protein?
Protease
T/F: Thrombin is a plasma protein that’s always in the circulation.
False - Prothrombin is
Extrinsic clotting pathway stimulated by:
External trauma that causes blood to escape from the vascular system.
Intrinsic clotting pathway stimulated by:
Trauma inside the vascular system
Intrinsic pathway factors come from:
Already in blood
Extrinsic pathway factors come from:
Endothelial cells
Which post-translational modification of clotting factors must occur for successful coagulation?
- Addition of second COOH at all Glu residues
- Ionize to COO-
- Both bind Ca
Describe MOA of Warfarin.
Vit K analog (non-functional) that inhibits enzyme responsible for clotting factor post-translational modification
The (extrinsic/intrinsic) clotting pathway is faster.
Extrinsic
Removal of Fibrin after healing is carried out by:
Plasmin
Which cell(s) secrete(s) plasmin?
Not secreted by cell; inactive precursor (Plasminogen) circulates in blood.
Which factor(s) facilitate breakdown of fibrin by (X)?
X = plasmin
- Tissue plasminogen activator (tPA)
- Urokinase
tPA is used in the ER to treat:
Coronary thrombosis; enhances clearance of coronary artery clot
Aspirin has which effect on clotting? How?
Reduce clotting; inhibits cyclooxygenase (no production of TA2) and slows platelet adhesion, aggregation, vasoconstriction
Which ion is crucial for proper clotting? When taking blood samples, we prevent clotting by:
Ca; container has Ca chelator (EDTA/citrate) that binds all Ca and prevents clotting
Prompt hemolysis of many RBC will cause (increase/decrease) in circulating bilirubin for the few days following.
Increase
T/F: Sickle cell disease can cause hypo proliferative anemia.
False - RBC breakdown too fast
T/F: Renal failure can cause hypo proliferative anemia.
True
T/F: G6PD deficiency can cause hypo proliferative anemia.
False - RBC breakdown too fast
T/F: Marrow damage (chemotherapy/radiation) can cause hypo proliferative anemia.
True
(Thalassemia/hereditary spherocytosis) can cause hypo proliferative anemia.
Thalassemia
What’s thrombomodulin? How does it affect clot formation?
Epithelial transmembrane receptor that binds Thrombin; reduces coagulation
(X) is a protein that (stimulates/inhibits) coagulation by which mechanism? Its activity is enhanced over 1000x by (Y).
X = antithrombin III
Inhibits coagulation by binding and inhibiting thrombin
Y = heparin
Protein C is activated by (X) and (stimulates/inhibits) coagulation.
X = thrombin (when bound to thrombomodulin receptor)
Inhibits
