Episode 5- CLOTTING YO Flashcards by Austin Shackelford

_________ is designed to ensure that there is no major leakage of blood following injury and consists of a complex system of proteins and enzymes.

Hemostasis

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What are the two extremes if there is an abnormality in the homeostasis proteins?

Bleeding (not enough clotting) & Thrombosis (too much clotting)

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A single megakaryocyte can generate around _____ platelets, of which _______ are pooled in the spleen (as sort of a “reserve”).

3000!….20-30%

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A normal level of platelets is between ____________ per cubic millimeter of blood.

250,000 - 400,000

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Like RBCs, platelets have no nucleus or organelles, but contain many _______.

granules

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Platelets possess an average life span of _______ and hence must be continuously produced by the bone marrow.

5-20 days

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What is the most important layer and sublayer of the vessel we will discuss in clotting?

the connective tissue layer of the tunica intima

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When discussing the anatomy of the capillary: Tunica intima only contains _________ and small amounts of _______.

endothelial cells…..collagen

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What are the three phases of homeostasis?

1.Vascular Spasm (vasoconstrictive phase) 2.Platelet Plug Formation 3.Blood Clotting

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What is the main event of the first phase of vessel homeostasis and what ate the two ways this phase is accomplished?

The vasoconstrictive phase/vascular spasm phase occurs when smooth muscle directly around the injury contracts…it is triggered by 1.the direct injury and 2.the SymNS

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Phase 2 of homeostasis: ___________. Characterized by the aggregation of platelets. Platelets stick to exposed ______, swell, and form spiked process. Platelet _____ are effective in preventing blood loss due to ______ injuries.

collagen….plugs….small

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HOW DO THOSE platelets stick to collagen to form a plug?! Platelets stick to the exposed collagen of damaged endothelium (or an artificial surface) via _____ receptors.

GPIa receptors (GP = glycoprotein)

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HOW DO THOSE platelets stick?!?! ______________ is a protein found in plasma, platelets and the walls of blood vessels – via _____ receptors, it specifically causes platelets to attach firmly to and spread across the damaged endothelial surface.

von Willebrand’s Factor (vWF)…..GPIb receptors

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What are the three secretions of the platelets during plug formation? What do theses secretions bind to?

1.ADP (adensosine diphosphate) 2.Thromboxane A2 (a prostaglandin) 3.Serotonin…..They bind to OTHER PLATELETS!

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Aggregation of platelets occurs as a consequence of another platelet glycoprotein receptor called _______ onto which _______ and other macromolecules bind tightly.

GPIIb/IIIa….fibrinogen

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Most of the clotting factors are present in the circulation as __________ (_______) to prevent unwanted clotting.

inactive proteins (zymogens)

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Factors __, __, __, and __ are vitamin K-dependent clotting factors.

II,VII,IX,X…2,7,9,10….Two,Seven,Nine, Ten.

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Clotting Factor: I…. Name and Origin Plez

I…Fibrinogen…Liver

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Clotting Factor: II…. Name and Origin Plez

II…ProThrombin…Liver

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Clotting Factor: III… Name and Origin Plez

III…Tissue Factor or ThromboPlastin….PeriVascular Tissue

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Clotting Factor: IV….Name and Origin Plez

IV…Calcium…Plasma

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Clotting Factor: V Name and Origin Plez

V…ProAccelerin (Labile Factor)…Liver

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Clotting Factor: VII Name and Origin Plez

VII….ProConvertin (Stable Factor)…Liver

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Clotting Factor: VIII Name and Origin Plez

VIII….AntiHemophilic factor A, Antihemophilic globulin…Liver

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Clotting Factor: IX Name and Origin Plez

IX...AntiHemophilic factor B, Plasma thromboplastin compontent, CHRISTMAS factor!!!...Liver

Clotting Factor: X Name and Origin Plez

X....Stuart-Prower factor(weird)....Liver

Clotting Factor: XI Name and Origin Plez

XI...Plasma thromboplastin antecedent, Hemophilia C, Rosenthal Syndrome...Liver

Clotting Factor: XII Name and Origin Plez

XII....Hageman Factor....Liver,Platelets

Clotting Factor: XIII Name and Origin Plez

XIII....Fibrin stabilizing factor, Laki-Lorand factor....Platelets, Plasma

In addition to coagulation factors, the plasma contains several ____________ that rapidly inactivate coagulation factors that escape the site of injury.

protease inhibitors

What are the three examples of the "anti-coagulant" system that balances coagulation?

1.Thrombo-Modulin 2.Anti-thrombin III (aka Anti-Thrombin) 3.Heparin cofactor II

ThromboModulin: A glycoprotein present on endothelial cells that combines with _______.

thrombin

The thrombomodulin-thrombin complex activates _________.

PROTEIN C

Protein C and its cofactor, _________, degrade factors __ and __

PROTEIN S....V and VIII.

___________ is a glycoprotein produced by the liver that binds to and subsequently inhibits factor X and thrombin

Antithrombin III

____________ is a plasma protein synthesized by the liver and inhibits thrombin.

Heparin cofactor II

The Fibrolytic system is initiated by the enzyme _______ which is synthesized from an inactive plasma protein synthesized by the liver called ________.

PLASMIN........PLASMINOGEN

___________ converts plasminogen to the active plasmin, thus allowing fibrinolysis to occur.

TISSUE PLASMINOGEN ACTIVATOR (t-PA)

___________ is released into the blood very slowly by the damaged endothelium of the blood vessels, such that, after several days (when the bleeding has stopped), the clot is broken down.

TISSUE PLASMINOGEN ACTIVATOR (t-PA)

Clots are broken down several days after bleeding has stopped. This occurs because _________ became entrapped within the clot when it formed; as it is slowly activated, it breaks down the fibrin mesh.

plasminogen

____________ are required in vivo to prevent prolonged or unwanted degradation of fibrinogen.

Fibrinolysis inhibitors

What are the four natural fibrinolysis inhibitors?

1.Plasminogen Activator Inhibitor 1 2.Plasminogen Activator inhibitor 2 3.alpha2-antiplasmin 4.alpha2-macroglobulin

Review! _________ is a low platelet count with an increased risk for bleeding.

Thrombocytopenia

Low platelet levels do not lead to clinical problems. Occasionally, there may be bruising, particularly purpura in the forearms, ________, (pinpoint hemorrhages on skin and mucous membranes), ________ and/or _________.

petechia....nosebleeds.....bleeding gums

What breaks down Fibrin?

Plasmin

What Activates plasminogen to plasmin?

tPA

What inhibits tPA?

Plasminogen activator inhibitors 1 and 2 :) funny name

What are the two drugs that attack plasmin and there for KEEP blood clots strong?

alpha 2 antiplasmin (tough name!), alpha2-macroglobulin

Some inherited platelet disorders are associated with _____ platelets

large

How do we prevent blood from clotting when taking and keeping a pt sample?

Sodium Citrate! It binds to the Ca2+ in the blood. The blood will not clot until MORE Ca2+ is added.

What are the 5 Coagulation tests?

*****1. Prothrombin Time (PT) WITH 2. International Normalized Ratio (INR)**** ((((Extrinsic pathway)))3. Activated Partial Thromboplastin Time (APTT) (((Intrinsic Pathway))) 4.Thrombin Clotting Time (TT) (((Common Pathway))) 5.Coagulation Factor Assays

Which Coagulation test is used to assess the extrinsic pathway?

Prothrombin Time (PT)

In the Prothrombin Test: Calcium is added to plasma to replace that removed by citrate and ____ ________ is added to substitute for tissue factor.

brain thromboplastin..WHAAA?!

In the Prothrombin Test: Clotting normally takes ___________ and the test time is compared with a standard normal control in a ratio.

12-15 seconds

In the Prothrombin Test: Because of differences between different batches and manufacturers of tissue factor (it is a biologically obtained product), the _____________ was devised to standardize the results.

INTERNATIONAL NORMALIZED RATIO (INR)

Each manufacturer gives an ______________ for any tissue factor they make. This ____ says how their tissue factor compares to other company's. The INR is the ratio of _______ prothrombin time to __________ prothrombin time, raised to the power of the ____.

ISI (International Sensitivity Index)......ISI....Patient/a normal (control) sample....ISI

Clinically, the ____ is most often used to monitor the effectiveness of drugs such as warfarin (Coumadin).

INR

Most laboratories report PT results that have been adjusted to the INR for patients on anti-coagulant drugs. These patients should have an INR of ___to____ for basic "blood-thinning" needs. For some patients who have a high risk of clot formation, the INR needs to be higher - about ___ to ___.

2.0 to 3.0......2.5 to 3.5

Which coagulation test is used to assess the intrinsic pathway?

Activated Partial Thromboplastin Time

In the APTT: Calcium is added to plasma to replace that removed by citrate and then ______ and _________ are added to substitute for contact factor.

kaolin "Kay-o-lin" and phospholipids

In the APTT clotting normally takes _______.

25-36 seconds

Clinically, the APTT is most often used to monitor _______therapy. Therapeutic levels of ________ will typically prolong the APTT to _____ times that of the normal value.

HEPARIN...Unfractionated Heparin (UFH)....2-2.5 times

Where is Heparin usually administered?

Hospitals...surgeries n such

Which coagulation test is used to assess the common pathway?

Thrombin Clotting Time (TT)

In the TT: Calcium is added to plasma to replace that removed by citrate and then ________ is added to substitute for the products of the intrinsic and extrinsic pathways. This assesses the conversion of _______ to ____.

thrombin.....fibrinogen to fibrin

Clinically, TT is used when a ___ and/or _____ test is prolonged, particularly if abnormal fibrinogen level or function is considered.

PT and/or APTT

______________ are used to determine actual deficiencies of specific clotting factors (e.g. a hemophiliac).

COAGULATION FACTOR ASSAYS

Which inherited clotting factor disorder is due to a mutation in factor VIII? What type of genetic disorder is it?

Hemophilia A...it is X linked

For a Hemophilia A pt the ____ test will be prolonged and the ____ will be normal.

APTT is prolonged(intrinsic pathway not working properly)...PT is normal (extrinsic pathway is fine)

Hemophilia A affects ~ __ in ____ males; Males (who have only 1 X chromosome) are the main sufferer of this condition.

1:5000

In Hemophilia A: Approx. __% of patients have no family history; their disease is presumably caused by new mutations.

30%

Which inherited clotting factor disorder is due to a mutation in factor IX? What type of genetic disorder?

Hemophilia B or Christmas disease....X linked

In Hemophila B/Christmas: the ____ test will be prolonged and the ____ test will be normal.

APTT prolonged...PT is normal

Hemophilia B/Christmas affects ~ __ in ____ males; Males (who have only 1 X chromosome) are the main sufferer of this condition, with females generally only having one of their X chromosomes affected

1 in 30,000

_________ leads to an increased risk of prolonged bleeding from common injuries, or in severe cases bleeds may be spontaneous and without obvious cause. Bleeding may occur anywhere in the body.

Hemophilia

In a hemophiliac superficial bleeding such as those cause by abrasions, or shallow lacerations may be prolonged and the scab may easily be broken up due to the lack of _____, which may cause re-bleeding.

fibrin

What are the 4 most serious sites of bleeding for a hemophiliac?

1.Joint Capsules 2.Skeletal Muscles 3.GI Tract 4.Brain

In Hemophilia, repeated bleeds into a joint capsule can cause permanent joint damage and disfigurement resulting in _________ and disability.

chronic arthritis

In Hemophila, joint damage is not a result of blood in the capsule but rather the healing process. When blood in the joint is broken down by enzymes in the body, the ____ in that area is also degraded. Therefore, this exerts massive amounts of ____ the person afflicted with the disease.

bone...pain

Patients with very low factor levels (hemophiliacs), who experience repeated and painful bleeds into their joints and skeletal muscles, are given ______ replacement. (Done w/ surgery and after trauma on normal people too).

The specific factors the Pt does not make can be given IntraVeinously (haha not IV Calcium)

_____________ is the most common inherited bleeding disorder. It affects 125 per million & leads to a mild bleeding disorder affecting _________.

Von Willebrand’s Disease (vWD)....Males AND females frequently

What are the two major roles of Von Willebrand factor?

1.Mediating Platelet Adhesion (GP Ib) 2. Stabilizing Factor VIII

For Von Willebrand Disease, bleeding is typically seen in _____ & __________ because of high capillary density; these tissues particularly depend on the efficient formation of platelet plugs to stop bleeding.

skin & mucous membranes

Because of Van Willebrand's links to factor VIII, low levels of vWF, like hemophilia A, also result in a ________ APTT & reduced factor VIII clotting activity. Unlike hemophilia A, patients have ________ PT because of a failure in platelet-vessel wall interaction.

prolonged....prolonged

What are the two causes for thrombocytopenia?

1.Impared production of platelets or 2. Decreased production of platelets

In thrombocytopenia, why might the production of platelets be impaired? (2)

1.Drug induced 2.bone marrow failure

In thrombocytopenia, why might platelets have an increase in destruction?

Idiopathic Thrombocytopenic Pur-Pur-A (ITP): AUTO IMMUNE response which removes platelets early!

__________ are conditions associated with excessive clotting.

Thrombophilias

As we have seen, the coagulation system is a delicately balanced series of cogaulation and fibrinolyic events and a defect or deficiency in one of the natural anticoagulants will swing the balance towards a ____________ and _______________.

HYPERCOAGULABLE STATE........potential venous thromboemolism (VTE)

What are the 4 causes for thrombophilia? Order of frequency...

1. Factor V Leiden Mutation (protein C resistance) 2. Protein S deficiency 3. Protein C Deficiency 4.Antithrombin III deficiency

In the body's natural anti-coagulation what does thrombin join to inhibit clots? What is the rest of this natural anti-coagulation story?

Thrombin + ThromboModulin= Thrombin-Thrombomodulin complex Which then activated Proteins C and S which deactivate V and VIII :)

What percentage of caucasians in north america are factor V leiden leading to thrombophilia?

5%! thats a pretty large number! No wonder why anti-coagulants are popular!

What are the clotting factors NOT made in the liver?

III, IV, XII,XIII.....3,4,12,13