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 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: 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: 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) Plasmin 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? 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 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

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

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

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