Blood, part 3
Thrombocytes, Hemostasis, Hemostatic
Disorders, Blood Typing and Transfusions
Thrombocytes (platelets)
• Not true cells
• Cytoplasmic fragments w/purple granules that contain
chemicals for blood clotting
Activated platelet
– Enzymes
amorphous
– Serotonin
w/extensions that help
them stick to vessels
– Ca2+ ions
and each other
– 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
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
Hemostasis
• Series of reactions to
stop a bleed
• Phases:
1.
2.
3.
4.
5.
Vascular spasm
Platelet plug
Coagulation (clotting)
Clot Retraction
Fibrinolysis (Clot
Eradication)
1.
Vascular
Spasm
1. Vascular Spasm
• Constriction of damaged vessel,
triggered by:
- Endothelium
- platelets
- Pain receptors
• Slows the bleed
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)
3. Coagulation (Blood Clotting)
• Blood transformed from liquid to gel
• 3 Critical Steps:
1. 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
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
5. Fibrinolysis
• tPA (Tissue Plasminogen Activator)
– Released by endothelium around clot
– Activates plasminogen
– Plasminogen  plasmin
• Plasmin
– Digestive “clot busting” enzyme
• Remnants of clot phagocytized by WBCs
– Macrophages
– eosinophils
How are clots prevented from
becoming TOO large?
1. 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
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
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
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
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
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
Blood Typing
• anti-A or anti-B
antibody serums are
added to blood
• agglutination occurs
between the
antibody and the
corresponding
antigens
Blood Donors and Recipients
Blood
Type
Antigen
Serum
Antibody
A
A
Anti-B
A and AB A and O
B
B
Anti-A
B and AB B and O
AB
O
Donate
To
A and B
None
AB
only
None
Anti-A
Anti-B
All Types
Receive
From
All Types
O only
Rh Blood Groups
• Rh antigens:
– 8 types
– Most common: types C, D, and E
• Anti-Rh antibodies do not exist in Rhindividuals until they are exposed to
Rh+ blood (1st pregnancy)
• Leads to complications during 2nd
pregnancies, if Rh- mother is carrying
Rh+ child
Transfusions
• Blood bank:
–
–
–
–
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
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