Blood, part 3Thrombocytes, Hemostasis, Hemostatic

Disorders, Blood Typing and Transfusions

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

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. Vascular spasm 2. Platelet plug3. Coagulation (clotting)4. Clot Retraction 5. Fibrinolysis (Clot

Eradication)

1. Vascular Spasm1. 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 vesselb. Extrinsic Pathway (faster) – outer tissue around vessel

2. Prothrombin converted to Thrombin3. 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 clotCompact the clotRuptured 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 attackDeath 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

• 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

Human 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

BloodType

Antigen SerumAntibody

DonateTo

Receive From

A A Anti-B A and AB A and O

B B Anti-A B and AB B and O

AB A and B NoneAB

onlyAll Types

O None Anti-A Anti-B All Types O only

• 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

Rh Blood Groups

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

• 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

Transfusion Reactions