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 10 11 in 1L blood
• Reservoirs of bioactive substances
• Serotonin (5-HT) and thromboxan A
2 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), alpha
2
-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