1. Blood, part 3
Thrombocytes, Hemostasis, Hemostatic Disorders, Blood Typing and Transfusions

2. Thrombocytes (platelets)
Not true cells
Cytoplasmic fragments w/purple granules that contain chemicals for blood clotting
Enzymes
Serotonin
Ca2+ ions
ADP
PDGF (Platelet-derived Growth Factor)
Normally kept in “inactive” state by molecules secreted by endothelial cells of blood vessels
When activated, form temporary plug that helps to seal breaks in blood vessels
Activated platelet amorphous w/extensions that help them stick to vessels and each other

3. Thrombopoiesis (Platelet formation)
Cytoplasmic fragments derived from megakaryocytes
Mega = large
Karyo = nuclei
Cyte = mature cell
Thrombopoietin promotes formation of megakaryocyte, created by multiple mitosis w/o cytokinesis
Megakaryocyte presses against sinusoid (capillary) of bone marrow and pinches off to make fragments

4. Hemostasis Series of reactions to stop a bleed Phases: Vascular spasm
Platelet plug
Coagulation (clotting)
Clot Retraction
Fibrinolysis (Clot Eradication)

5. 1. Vascular Spasm 1. Vascular Spasm
Constriction of damaged vessel, triggered by:
Endothelium
platelets
- Pain receptors
Slows the bleed

6. 2. Platelet Plug Formation
Damaged endothelium activate platelets by releasing
VWF (von Willebrand Factor)
Platelets become amorphous:
Stick to exposed collagen fibers of endothelium
Release
serotonin ( spasms)
ADP (attract more platelets)
Thromboxane ( both )
Prostacyclin (inhibits
aggregation elsewhere)

7. 3. Coagulation (Blood Clotting)
Blood transformed from liquid to gel
3 Critical Steps:
Prothrombin Activator Forms (complex series of biochemical rxns!)
- require Ca2+ ion and procoagulants to promote sequence of rxns
- Two pathways:
a. Intrinsic Pathways (slower) – within damaged vessel
b. Extrinsic Pathway (faster) – outer tissue around vessel
2. Prothrombin converted to Thrombin
3. Thrombin catalyzes joining of fibrinogen into fibrin mesh
- Glue platelets together

8. 4. Clot Retraction Clot Retraction
Platelets contract (like a muscle) to stabilize clot
Contractions pulls on fibrin
squeeze out serum from clot
Compact the clot
Ruptured ends of blood vessel drawn closer together
PDGF and VEGF released from platelets
(PDGF) Stimulates fibroblast and smooth muscle mitosis to rebuild wall
(VEGF) Promotes endothelial restoration

9. 5. Fibrinolysis tPA (Tissue Plasminogen Activator) Plasmin
Released by endothelium around clot
Activates plasminogen
Plasminogen  plasmin
Plasmin
Digestive “clot busting” enzyme
Remnants of clot phagocytized by WBCs
Macrophages
eosinophils

10. How are clots prevented from becoming TOO large?
Fast moving blood
Washes away excess Thrombin
2. Inhibition of clotting factors
Anti-thrombin III (ATIII): plasma protein inactivates thrombin
Protein C: inhibits clotting factors
Heparin: enhances ATIII

11. Hemostatic Disorders: Undesirable Clotting
Thrombus: a clot that develops in an unbroken vessel
blocks circulation
tissue death
Coronary thrombosis
Heart attack
Death of cardiac muscle

12. Hemostatic Disorders: Undesirable Clotting
Embolus: freely floating thrombus in bloodstream
Pulmonary Embolism
Impairs O2 delivery
Death of lung tissue
Cerebral Embolism
Stroke,
Death of brain tissue

13. Hemostatic Disorders: Undesirable Bleeding
Thrombocytopenia
reduced platelet count < 50,000/mm3
Bone marrow disease or destruction
petechiae on skin due to widespread hemorrhage
Treatment: blood transfusions

14. Hemostatic Disorders: Undesirable Bleeding
Hemophilia:
Hereditary
Lack of clotting factors
hp A - defective Factor VIII (83%)
hp B - defective Factor IX (10%)
Genentech. Inc. - now engineers tPA and Factor VIII  less transfusions needed

15. Human Blood Groups
glycoprotein antigens exist on external surfaces of RBCs
Antigens are:
Unique to the individual
“foreign” to other individuals
promotes agglutination
Presence or absence of these antigens is used to classify blood groups

17. Blood Typing anti-A or anti-B antibody serums are added to blood
agglutination occurs between the antibody and the corresponding antigens

18. Blood Donors and Recipients
Type
Antigen
Serum
Antibody
Donate To
Receive From A
Anti-B
A and AB
A and O B
Anti-A
B and AB
B and O AB
A and B
None
only
All Types O
Anti-A Anti-B
O only

19. Rh Blood Groups Rh antigens: 8 types Most common: types C, D, and E
Anti-Rh antibodies do not exist in Rh- individuals until they are exposed to Rh+ blood (1st pregnancy)
Leads to complications during 2nd pregnancies, if Rh- mother is carrying Rh+ child

20. Transfusions Blood bank: Whole blood: (rare)
Mix donor blood with anticoagulants that bind to Ca2+
Tested for viruses, ABO, and Rh factor
35 day shelf life at 40 C
Blood separated into component parts
Whole blood: (rare)
Only for rapid and substantial blood loss
Packed red cells (plasma removed)
To restore O2 carrying capacity

21. Transfusion Reactions
Occur when mismatched blood is infused
Donor’s blood cells are attacked by the recipient’s plasma antibodies causing:
Ruptured RBCs
Diminished O2 carrying capacity
Clumped cells (agglutination)
Blood clots
“Free” hemoglobin due to lysis of RBC
Hemoglobin solidifies in kidneys
Kidney fails