Hemostasis Flashcards
What is hemostasis?
The process to stop bleeding. It is the 1st stage of wound healing.
-Primary, Secondary and Tertiary
What are the processes involved in hemostasis?
- vasoconstriction
- platelet activation
- coagulation
- fibrinolysis
What is primary hemostasis?
Form weak plug.
- mediated by interaction between wall and platelets
What is secondary hemostasis?
Formation of stabilized platelet plug.
-mediated by coagulation cascade
Steps of primary hemostasis
1) Vasoconstriction
- neural stim’n and endothelin released from endothelial cells
2) Platelet adhesion
3) Platelet degranulation
4) Platelet aggregation
Steps of primary hemostasis
1) Vasoconstriction
- neural stim’n and endothelin released from endothelial cells
2) Platelet adhesion
- vWF binds to exposed collagen, platelets adhere to vWF via GP1b Rc
3) Platelet degranulation
- adhesion induces change in shape of platelets causing release: ADP, TXA and Ca++
4) Platelet aggregation
- platelets aggregate @ injured site via GPIIb/IIIa using fibrinogen to link molecules
- TXA promotes aggregation
Where does the vWF derive from?
- Endothelial cells (Weibel Palade bodies)
- alpha granules of platelets
What is thrombophilia?
Increased risk of thrombosis.
State of hypercoagulability/prothrombic state
What are the risks associated to having thrombophilia?
HEREDITARY:
- factor V (Leyden) mutation
- anti-thrombin III deficiency
ACQUIRED:
- lung immobilization
- contraceptives (estrogen increases coagulation factors in liver)
- atrial fibrillation
- smoking
- obesity
A disorder in primary hemostasis is typically due to what?
Platelet abnormalities
What’s the difference between: petechia, ecchymoses and purpura?
They are all signs of bleeding in the skin, but differ in size.
Petechia: 1-2 mm
Ecchymoses: >3 mm
Purpura: > 1 cm
What complication can occur with severe thrombocytopenia?
Intracranial bleeding
If bleeding time is prolonged, what problem does this indicate….?
Primary hemostasis problem i.e. with platelet disorders
What would be assessed in a bone marrow biopsy for primary hemostasis abnormality?
Assess megakaryoctes, because they produce thrombocytes (platelets), which is the underlying cause of 1’ hemostasis abnormalities
What is immune thrombocytopenia (aka immune thrombocytopenic purpura ITP)
An autoimmune disease where auto-antibodies produced in the spleen bind platelets, which are consumed by splenic macrophages causing thrombocytopenia.
Describe microangiopathic hemolytic anemia?
Pathologic formation of micro thrombi in vessels causing platelet consumption because platelets keep going to site of thrombi and are being used up at a higher rate than normal. Results in hemolytic anemia.
The thrombi that form cause RBCs passing by to be sheared, creating a “schistocyte” RBC (helmet-like appearance of cell)
In what conditions is microangiopathic hemolytic anemia typically seen in?
- HUS (hemolytic uremic syndrome)
- thrombotic thrombocytopenic purpura
- HELLP syndrome
- malignant hypertension
What is HUS ? What is it characterized by?
Hemolytic uremic syndrome is due to endothelial damage due to drugs or infection. Characterized by: 1) thrombocytopenia 2) microangiopathic hemolytic anemia 3) and acute renal failure
What is Bernard-Soulier syndrome?
Defect in platelet plug formation due to GpIb deficiency. This causes a problem with platelets adhering to vWF.
What is Glanzmann thrombasthenia?
GpIIb/IIIa deficiency. Platelet to platelet aggregation is impaired. Thus, no platelet plug can form.
What cascade do we measure with aPTT?
-Intrinsic + common cascade
What cascade do we measure with PTT?
Extrinsic + common cascade
What cascade do we measure with thrombin time?
Common
What is tertiary hemostasis?
Dissolution of the fibrin clot (fibrinolysis)
Which blood cells are nucleus free?
- RBCs
- Platelets
What does D-dimer measure? What is it the best screening test for?
It is released when when cross-linked fibrin is split! (NOT splitting of fibrinogen)
Best used for screening for:
-DIC
- to rule out DVT
What does alpha-2-antiplasmin do? What disease state is this reduced in?
Inhibits plasmin breaking down fibrin, thus no fibrinolysis.
Cirrhosis of liver –> reduced a2-antiplasmin
What can cause DIC?
"STOP Making New Thrombi" S-epsis (-ve gram bacteria) T-rauma O-bstetrics P-ancreatitis (Acute)
M-alignancy
N-ephrotic syndrome
T-ransfusions
- adenocarcinoma; ,mucin activates aggregation
- snake bite; venom can also induce aggregation
What is Virchow’s triad?
The 3 main categories thought to contribute to thrombosis:
1) Blood flow disruption
- stasis
- turbulence
2) Endothelial injury
3) Hypercoagulability
What are lines of zahn?
Characteristic appearance of a thrombus where there is an alternating layer between platelets/fibrin (light) and RBCs (dark)
How can you distinguish a thrombus from postmortem clot?
- look for lines of Zahn on thrombus (alternating bw light and dark, i.e. platelets/fibrin and RBCs)
- attachment to vessel wall (thrombus)
How do endothelial cells prevent thrombosis?
- block exposure to sub endothelial collagen and underlying tissue factor
- release prostacyclin and NO (blocks platelet aggregation and vasodilator)
- secrete heparin-like molecules which helps augment antithrombin (III) which inactivates thrombin and coagulation factors
- secrete tPA (tissue plasminogen activator)
- secrete thrombomodulin
What are the main causes of endothelial damage?
- vasculitis
- atherosclerosis
- high homocysteine ( Vit B12 and folate deficiency)
What happens in vit B12 and folate deficiency?
There is no conversion from homocysteine to methionine, thus there is a build-up of homocysteine causing damage to endothelial cells.
Since folate contributes to synthesis of DNA precursors, this may also be affected.
