Hematopoiesis in the red bone
marrow
http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2/
http://www.oup.com/uk/booksites/content/0198585276/
Chemical intercellular signalling
http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2
Mazur Em, Cohen JL, Clin Pharmacol Ther, 1989, 46, 250-256
Some important trancription factors
in hematopoiesis
• GATA-2, TAL-1/SCL, and HOXB4 are
important in early phases of
hematopoiesis and stem cells functioning
• GATA-1 is important in differentiation and
development RBCs and other myeloid
blood cells.
• Data about hematopoietic gene regulation
are rapidly increasing.
Main processes of hemostasis
• 1. Platelets adhesion and aggregation,
formation of the platelet plug
• 2. Vasoconstriction
• 3. Blood clotting
• 4. Final repair by connective tissue
NB! The phases are not separated but
rather manyfold interconnected
Hemostasis
http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2
Classics of blood clotting
• Alexander Schmidt and Paul Morawitz
They discovered the enzymatic cascade nature of
blood clotting
1st phase – activation (of thrombokinase which
converts prothrombin to thrombin)
2nd phase -- coagulation (fibrinogen is converted
to soluble fibrin)
3rd phase – retraction (production of stable fibrin)
Adhesion of platelets, white
thrombus
http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2
Thrombocytes
• Production from megakaryocytes, 1,5-3,0
x 1011 in 1L blood
• Reservoirs of bioactive substances
• Serotonin (5-HT) and thromboxan A2
potent vasoconstrictors
Factors influencing platelets
adhesion
• Collageen and plasma von Willebrand
faktor (vWf) iniate adhesion.
• Adhesion is blocked by negative surface
charge of platelets, certain biochemical
regulators (e.g. NO, prostacyclin etc), and
endothelial barrier between collagen and
blood.
Platelets in “normal” state
http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html
The activated platelets
http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html
http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html
Blood clot s. “red thrombus”
http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html
http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html
Conversion of prothrombin to
thrombin
http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html
Fibrinogen
http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html
Conversion of fibrin from fibrinogen
http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html
Fibrinogen structure
http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html
Fibrin network
http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html
Initiation of coagulation
• The extrinsic pathway is critical in initiating
of blood clotting.
• The intrinsic pathway plays an important
role in maintenance of coagulation.
There is no bleeding disorders in case of
lack XII
Regulation of coagulation
• Serine protease inhibitors (antithrombin III)
• The protein C system activated by
thrombin
• The regulatory influences of intact
endothelial and blood cells
• The fibrinolytic system
Serine protease inhibitors
• Antithrombin III, tissue factor pathway
inhibitor (TFPI), alpha2-macroglobulin, C1
inhibitor jt.
• Antithrombin III inhibits mainly factor X,
and factors VII, IX, XI, XII.
• Heparin and glycosaminoglycans increase
the antithrombin III activity 1000 times.
Protein C system
• Thrombomodulin and protein C are
members of an endogenous anticoagulant
system.
• Thrombin complexed with thrombomodulin
loses its procoagulatory activity, while
readily activating protein C
• Proteiin C destroys factors V and VIII
Fibrinolysis
http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html
Endothelium and coagulation
• There is no coagulation in case of intact
endothelium
• Endothelial cells can produce under influence of
thrombin, IL-1 or TNF tissue factor, which has
procoagulatory activity
• The surface of endothelial cells contains
heparin-like compounds, which bind
antithrombin III and block thrombin formation
• Endothelial cells can produce the plasminogen
activators.
Blood cells and coagulation
• Platelets contain procoagulant
anticoagulant substances
• Polymorphonuclear leukocytes and
monocytes produce tissue factor, factor V
and present phospholipids, which all
support blood coagulation
Disturbances of blood coagulation
• Hypercoagulation – thrombi and emboli,
thrombophilia
• Hypocoagulation – bleeding disorders,
hemophilia