Hemostasis & Blood clotting system

2 pathways to initiate coagulation: Extrinsic

Activated by external trauma that causes blood to escape from vascular system (this pathway is quicker)

Megakaryocyte

large cell in bone marrow responsible for the production of thrombocytes Thrombopoiesis -Process by which thrombocytes are formed One megakaryocyte can produce thousands or thrombocytes

Fibrinolysis : Why do we need to break down clots?

Prevents blood clots from growing and becoming problematic We don't want clots running around our blood system Two types: -Primary Fibrinolysis (Normal body process) -Secondary Fibrinolysis (medication of disease process)

thrombocytes: Thrombocytopenia

(another name for platelets) - is the reduction in number of platelets; leads to spontaneous bleeding. Primary and secondary disorders May occur as a result of generic factors, liver, dysfunction or dietary deficiency

Co-Factors: Calcium

-Binds the clotting factors together for coagulation to occur (know)

2 main components of blood

1. Plasma-liquid portion -55% of total blood volume Consist of: -water -Plasma proteins -Miscellaneous molecules 2. Blood cells -RBC, WBC, Platelets

Platelets Role in Clotting

1. Vascular phase 2. Aggregation of platelet phase 3.Coagulation phase

Three mechanisms that reduce the loss of blood from broken blood vessels

1. Vascular spasm 2. Platelet plug formation (thrombocytes agruagete and bind together to form a plug) 3. Blood clotting (coagulation)

Primary Disorders of Hemostasis: Increased destruction of consumption

1.Immume thrombocytopenia purpura (ITP) -autoimmune destruction -Spleen is major site of destruction -Chronic disease or may be self limiting Treatment -Steroids -IV immunoglobulins -Splenectomy 2. Thrombotic Thrombocytopenia purpura (TTP) is idiopathic or seconday -Ecoli -HIV -Medications -Bone marrow transplant

Thrombocytosis

>400,000 TOO MANY platelets may be primary or secondary Asymptomatic until platelet count exceeds 1 million -Myeloproliferative disorder

Thrombocytosis: Clinical manifestations

At risk for larger-vessel arterial or Venous thrombosis (Blood clots) Myocardial and renal arteries may be involed -ischemia in fingers, toes, or Cerebrovascular, Neuro -Headache & dizziness -Paresthesia's -TIA & Stoke -Seizures -Bleeding & clotting may occur simultaneously

Platelets Role in Clotting: 1. Vascular phase

Blood vessel Constricts Platelets are activated and travel to the site This phase is also known as "initiation"

Co-Factors

Calcium Vitamin K Both are required to synthesize protein C Deficiency of any of these clotting cofactors will cause inability for blood to coagulate -can contribute to excessive bleeding and hemorrhage

Primary Disorders of Hemostasis: Alterations of platelets

Disorders of platelet function Low number of platelets (Thrombocytopenia) <150,000 (150,000-450,000 is normal range) -can get spontaneous bleeding Causes: -decreased production -Increased consumption (something is consuming them) Acquired: Viral infections Autoimmune Nutritional Cancer

Secondary disorders of Hemostasis: Hemophilia

Hereditary Genetic bleeding disorder resulting from loss of select clotting factors -Lack of factor 8 (most common) -b-Def in factor 9 Pt bleeds due to inability to clot

Three mechanisms that reduce blood loss: 3. Coagulation

Involves many clotting factors (most produced by the liver) -Calcium Ions -Enzymes (to trigger one cascade to another) -Platelets if someone has liver disease they are at risk for bleeding.

Secondary disorders of Hemostasis: Hypercoagulability: DIC

Life threatening condition, proteins that control clotting become overactive -causes formation of multiple small clots, which disrupt blood supply to organs or cause serious spontaneous bleeding Significant increase in thrombin production, fibrin get activated leading to formation of numerous small clots, as clotting components are consumed the Pt is at increased risk for hemorrhage.

Fibrinolysis: Plasmin

Main enzyme that cuts the fibrin mesh at various places -leads to production of circulating fragments -Fibrin degradation products This number is reflected in the D-Dimer (non specific test, at it says is that at one point in time the PT was bleeding, ex. if post OP it should be high, if fell and scraped knee D-dimer should be high) (basically result of plasmin production to breakdown clots)

Von Willebrand Disease

Most common genetic bleeding disorder -defect in Von willebrand factor (helps platelets adhere to points of injury) Affects both genders (if you have it your platelets are not going to plug up as well, important for someone that may be going to surgery) Treatment: -for type 1 and 2 Desmopressin is used -stimulates release of Von Willebrand Factor (vWF) -plasma derived products

Secondary disorders of Hemostasis: Hypercoagulability : Sickle Cell

Nearly every aspect of hemostasis is altered -Increased thrombin levels -Abnormal activation of fibrinogen -Decrease anticoagulant proteins -Abnormal platelet activation -Increased tissue factor levels clumping of sickle cells can obstruct blood vessels and lead to tissue ischemia (resulting in a lot of pain) Thrombosis (making of a clot) frequently occurs and may lead to stoke, PE, avascualr necrosis, and leg ulcers

Platelets Role in Clotting: 2. Aggregation of platelet phase

Platelets are activated and begin to clump and form a plug important thing to note: We have drugs that can stop this (aspirin, Plavix) - antiplatelet aggregators (stop the dog pile to form the plug)

Secondary disorders of Hemostasis: Hypercoagulability

Sickle cell disease DIC Thrombocythemia

Heparin- Induced Thrombocytopenia

Type 1: Heparin causes a decrease in platelet count within the first 2-3 days of heparin therapy (usually not clinically significant) (you need to check Pt platelet count in the morning bc you can administer it) Type 2: prior exposure for heparin, caused by antibodies to platelet on the heparin complex

2 pathways to initiate coagulation: Intrinsic

activated by trauma inside the vascular system

interrelationship between the coagulation pathway and other plasma enzymes systems

activation results in generation of plasminogen activator activity - involved in fibrinolysis (clot removal) (if body forms a clot in the major blood vessels it knows that your going to die, so it has backups. when it starts to form thrombin it forms Plasminogen at the same time in order to break up the clot) SO, thrombin causes fibrinogen to become Fibrin which from the clot, at the same time plasminogen is being produced to in order to break down that clot (all of clot medications are plasminogen's which allow it to break up the clot. anticoagulants DO NOT do that, only interrupts Factor 10 to prevent Fibrin from being made) (KNOW)

Primary Disorders of Hemostasis

alterations of platelets Increases destruction of consumption

Co-Factors: Protein C

an anticoagulant that prevents excessive coagulation after cascade occurs

Thrombocytopenia: Secondary Disorders

associated with a lack of or reeducation in factors tied to coagulation

Thrombocytopenia: Primary disorder

associated with abnormalities in platelet Number or Function

Secondary disorders of Hemostasis

associated with deficits in the formation of function of coagulation factors -Hemophilia -Hypercoagulation

Hemeostasis

cessation of blood flow, particularly though the action of coagulation mechanisms -Hemostasis is necessary to stem hemorrhage. Hemorrhage: copious bleeding -may occur outside of the skin or in the skin Ecchymoses: -another term for bruising, or bleeding in the skin. Disorders of hemostasis ultimately involve excessive coagulation or excessive bleeding.

Co-Factor: Vitamin K

essential for the functioning of several proteins involved in the blood clotting cascade (if giving someone heparin, it is blocking K to prevent cascade)

Secondary disorders of Hemostasis: Thrombocythemia

platelet count greater than 600,000 if its primary then its called essential thrombocythemia associated with infection and inflammatory states: -Activation of the immune system appears to simulate platelet production -Increase palette count overwhelms the concentration of vWF, leaving platelets unable to adhere to each other and initiate clotting.

Three mechanisms that reduce blood loss: 2. Platelet plug formation

platelets encounters a damaged blood vessel they from a platelet plug to bridge together the broken end of the blood vessel 3 stages in process: -Platelet adhesion -Platelet release reaction (send signals to call more cells) -Platelet aggregation

Platelets Role in Clotting: Coagulation phase

platelets release substances/ Chem messengers that lead to formation of fibrin layer over the platelet plug (if you don't have medical providers and having a hard time for bleeding to stop, you can use a spider web and it will act as the fibrin mesh)

Hematopoiesis

process though which blood cells are formed -Begins with hematopoietic stem cell -Dev. into either a lymphoid stem cell of a myeloid stem cell

Clotting cascade

similar to complement system -coagulation pathway is a series of posive and negative feedback loops which control the activation process if someone is missing a factor then the process just stops. - ex. someone with hemophilia need to injections of factor 8 so that the cascade can continue to allow clotting process

Three mechanisms that reduce blood loss: 1. Vascular spasm

smooth muscle in blood vessels contracts immediately once the blood vessel is broken -can help for a little time to let other hemostatic mechanisms become active. i.e., when you stick a vein and it flattens out

Fibrinolysis

the enzymatic breakdown of the fibrin in blood clots. (then plasminogen cuts it up)

Fibrinolysis: Plasminogen

the inactive form of plasmin -It is produced in the liver -Requires tissue plasminogen activator (t-pa) to be converted to active form of plasmin T-PA can be made in the lab known as recombinant T-PA This drug wont discriminate and will attack any clot in there body, so they have to be screened to see if they can have it, so if they just had surgery they can use it bc the wound will open up

Ultimate goal of clotting pathway

to produce Thrombin Thrombin then converts soluble fibrinogen into fibrin - Fibrin forms the clot Generation of thrombin is divided into three phases: -Intrinsic -Extrinsic These 2 systems converge at factor X (10) to a single common pathway -Results in thrombin formation (most drug target factor X (10))