Episode 5 - Hemostasis: Physiology, Assessment and Common Disorders

Question 1

Any local bleeding is arrested by an interaction between ____ and ____, followed by a cascade of ____.

Answer 1

platelets and blood vessel endothelial cells

coagulation factors

Question 2

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

Answer 2

Hemostasis

Question 3

Hemostasis starts with ____.

Answer 3

platelets

Question 4

Platelets are not really cells, but instead fragments of cells. They split from huge cells in the bone marrow called ____ and then enter the circulation.

Answer 4

megakaryocytes

Question 5

A single megakaryocytic can generate around ____ platelets, of which ____% are pooled in the spleen.

Answer 5

3000

20-30%

Question 6

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

Answer 6

250,000 - 400,000

Question 7

Platlets have not nucleus or organelles but contain many ____.

Answer 7

Granules (granules are required for normal platelet function)

Question 8

Platelets possess an average life span of ____ days.

Answer 8

5-20 days

Question 9

3 layers of a typical artery

Answer 9

Tunica intima
Tunica media
Tunica externa

Question 10

Compare the width of the tunicae of veins and arteries.

Answer 10

Veins have thinner tunica media

Question 11

Anatomy of a ‘typical’ capillary

Answer 11

Tunica intima only contains endothelial cells and some collagen
No tunica media or externa (very thin walled)

Question 12

3 Phases of Hemostasis

Answer 12

Vasoconstrictive Phase (Vascular Spasm)
Platelet Plug Formation
Coagulation Phase (Blood Clotting)

Question 13

Explain the vasoconstrictive phase of hemostasis

Answer 13

Smooth muscle in damaged vessels contracts immediately producing local vasoconstriction. (capillaries don’t constrict)
Triggered by injury itself and SNS

Question 14

Explain Platelet Plug Formation

Answer 14

Aggregation of platelets that stick to exposed collagen, swell and form spiked processes. Prevent blood loss in small injuries

Question 15

Collagen is found in the tunica ____ of arteries

Answer 15

intima (also found in externa but it is particularly important to know that it is in the tunica intima)

Question 16

Platelets stick to the exposed collagen of damaged endothelium via _____.

Answer 16

GPIa receptors

Question 17

____ is a protein found in plasma, platelets and the walls of blood vessels. Via ____, it specifically causes platelets to attach firmly to and spread across the damaged endothelial surface.

Answer 17

von Willebrand’s Factor (vWF)

GPIb receptors

Question 18

During adhesion, platelets will undergo major structural changes and deformations. Adhesion also triggers the secretion of multiple factors from the platelets:

These factors bind to specific receptors on other platelets making them more sticky causing aggregation.

Answer 18

ADP (adenosine diphosphate)
Thromboxane A2 (TA2; TXA2; a prostaglandin)
Serotonin (5-HT)

Question 19

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

Answer 19

GPIIb/IIIa

fibrinogen

Question 20

Explain the coagulation phase

Answer 20

occurs to either reinforce a platelet plug or stop bleeding when the platelet plug fails.

Involves numbers clotting factors

Question 21

Most clotting factors are ___ synthesized by the ___.

Answer 21

proteins

liver

Question 22

Most of the clotting factors are present in the circulation as ___ to prevent unwanted clotting.

Answer 22

inactive proteins (zymogens)

Question 23

Clotting Factor I

Answer 23

Fibrinogen

Question 24

Clotting Factor II

Answer 24

Prothrombin

Question 25

Clotting Factor III

Answer 25

Tissue Factor or thromboplastin

Question 26

Clotting Factor IV

Answer 26

Calcium

Question 27

Clotting Factor V

Answer 27

Proaccelerin (Labile factor)

Question 28

Clotting Factor VII

Answer 28

Proconvertin (Stable factor)

Question 29

Clotting Factor VIII

Answer 29

Antihemophilic factor A, | Antihemophilic globulin

Question 30

Clotting Factor IX

Answer 30

Antihemophilic factor B, Plasma thromboplastin component, Christmas factor

Question 31

Clotting Factor X

Answer 31

Stuart-Prower factor

Question 32

Clotting Factor XI

Answer 32

Plasma thromboplastin antecedent, Hemophilia C, Rosenthal syndrome

Question 33

Clotting Factor XII

Answer 33

Hageman factor

Question 34

Clotting Factor XIII

Answer 34

Fibrin stabilizing factor, Laki-Lorand factor

Question 35

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

Answer 35

II, VII, IX and X

Question 36

Blood clotting cascade comprises ___ and ___ pathways. Both of those terms are somewhat outdated. Both pathways are initiated simultaneously and lead to a "_____"

Answer 36

extrinsic and intrinsic (initiated outside and inside the blood) Final Common Pathway

Question 37

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

Answer 37

protease inhibitors

Question 38

There additionally needs to be an _____ system in place to maintain the homeostatic balance.

Answer 38

anti-coagulant

Question 39

Examples of 'natural' anti-coagulants are:

Answer 39

Thrombomodulin Antithrombin III Heparin cofactor II

Question 40

____ is a glycoprotein present on endothelial cells that combines with thrombin.

Answer 40

Thrombomodulin

Question 41

Thrombomodulin-thrombin complex activates ____.

Answer 41

Protein C

Question 42

Protein C and its cofactor ____ degrade factors V and VIII

Answer 42

Protein S

Question 43

Antithrombin is a glycoprotein produced by the liver that binds to and subsequently inhibits ____ and ____.

Answer 43

factor X and thrombin

Question 44

Heparin cofactor II is aplasma protein synthesized by the liver and inhibits ___.

Answer 44

thrombin

Question 45

Breaking down of a blood clot is initiated by the enzyme ____ which is synthesized from an inactive plasma protein from the liver called ____.

Answer 45

Plasmin | Plasminogen

Question 46

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

Answer 46

Tissue Plasminogen Activator (t-PA)

Question 47

t-PA is released into the blood very slowly by the ____ of the blood vessels. After several days, the clot is broken down because plasminogen was trapped within the clot when it formed and is slowly activated to break down the fibrin mesh.

Answer 47

damaged endothelium

Question 48

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

Answer 48

Fibrinolysis inhibitors

Question 49

Some natural fibrinolysis inhibitors:

Answer 49

Plasminogen activator inhibitor 1 Plasminogen activator inhibitor 2 alpha2-antiplasmin alpha2-macroglobulin

Question 50

____ is a low platelet count and causes an increased risk for bleeding.

Answer 50

Thrombocytopenia

Question 51

Often low platelet levels do NOT lead to clinical problems. Occasionally, there may be:

Answer 51

bruising, particularly purport in the forearms, petechia (pinpoint hemorrhages on skin and mucous membranes), nosebleeds and/or bleeding gums.

Question 52

To perform a coagulation test, blood is taken from the patient and put in tubes containing ____ which prevents clotting because it binds ____.

Answer 52

Sodium Citrate | Calcium

Question 53

Explain the Prothrombin Time (PT); Pro-Time

Answer 53

A test used to asses the extrinsic pathway. Calcium is added to replace the removed calcium and brain thromboplastin is added to substitute for tissue factor (III). Clotting is compared with the standard normal (12-15 seconds) control in a ratio.

Question 54

The ___ was devised to standardize results due to the variation of tissue factor (III). Each manufacturer gives an ____ for any tissue factor they make.

Answer 54

International Normalized Ratio (INR) | International Sensitivity Index (ISI)

Question 55

Clinically, the INR is most often used to monitor the effectiveness of drugs such as ____ which is an ____.

Answer 55

warfarin (coumadin) anti-coagulant

Question 56

Patients should have an INR of ____ for basic 'blood-thinning' needs. Some patients who have a high risk of clot formation need an INR of about ____.

Answer 56

2. 0-3.0 | 2. 5-3.5

Question 57

Explain the Activated Partial Thromboplastin Time (APPT)

Answer 57

Used to assess the intrinsic pathway. Calcium is added to plasma to replace what was removed by citrate and then kaolin and phospholipids are added to substitute for contact factor. Clotting is compared with the standard normal (25-36 seconds) control in a ratio. Clinically used to monitor Heparin therapy. Therapeutic levels of UFH will typically prolong the aPTT to 2-2.5 times that of the normal value.

Question 58

Explain Thrombin Clotting Time

Answer 58

Used to assess the common pathway. Calcium is added to plasma to replace that removed by citrate and then thrombin is added to substitute for the products of the intrinsic and extrinsic pathways. This assesses the conversion of fibrinogen to fibrin. Clinically used when a PT and/or aPTT test is prolonged, particularly if abnormal fibrinogen level or function is considered.

Question 59

Why would you do a coagulation factor assay.

Answer 59

To determine actual deficiencies of specific clotting factors.

Question 60

Hemophilia A is an X-linked disorder from mutations in factor ____ gene.

Answer 60

factor VIII

Question 61

What results would you expect from an APTT and a PT in a patient with Hemophilia A

Answer 61

Prolongation of APTT and normal PT

Question 62

___% of Hemophilia A patients have no family history; their disease is presumably caused by new mutations.

Answer 62

30%

Question 63

Hemophilia B (aka ____) is an X-linked disorder caused by mutations in factor ___ gene.

Answer 63

Christmas Disease Factor IX

Question 64

What results would you expect from an APTT and a PT in a patient with Hemophilia B

Answer 64

Prolongation of APTT and normal PT

Question 65

Hemophilia often leads to superficial bleeding but by far the most serious sites of bleeding are:

Answer 65

Joint Capsules Skeletal Muscles GI Tract Brain

Question 66

Though not life threatening, ___ bleeds are one of the most serious symptoms of hemophilia because while the blood in the joint is being broken down, the bone in the area is also degraded.

Answer 66

joint

Question 67

Patients with very low factor levels who experience repeated and painful bleeds to their joints and skeletal muscles are given ___.

Answer 67

IV(intravenous) factor replacement

Question 68

_____ is the most common inherited bleeding disorder that affects 125 per million and leads to a mild bleeding disorder affecting males and females equally.

Answer 68

Von Willebrand's Disease (vWD)

Question 69

vWF has 2 major roles:

Answer 69

1. Mediating platelet adhesion | 2. Stabilizing factor VIII

Question 70

In Von Willebrands Disease bleeding is typically seen in ___ and ___ because of the high capillary density. These tissues depend on the efficient formation of platelet plugs to stop bleeding.

Answer 70

skin and mucous membranes

Question 71

What results would you expect from an APTT and a PT in a patient with Von Willebrand's Disease and why?

Answer 71

Prolonged aPTT - reduced factor VIII clotting activity (factor VIII linked to vWF) Prolonged PT - failure in platelet-vessel wall interaction

Question 72

Thrombocytopenia can be caused by ____ or ____.

Answer 72

Impaired production of platelets (drug induced or bone marrow failure) Increased destruction of platelets (Idiopathic Thrombocytopenic Purpura - autoimmune)

Question 73

_____ are conditions associated with excessive clotting.

Answer 73

Thrombophilias

Question 74

A defect of deficiency in one of the natural anticoagulants will swing the balance towards a _____ state and potential ____.

Answer 74

hypercoagulable venous thromboembolism (VTE)

Question 75

4 Examples of inherited thrombophilias are

Answer 75

Activated Protein C Resistance (most common) Protein C Deficiency Protein S Deficiency Antithrombin III Deficiency (least common)

Question 76

Activated Protein C Resistance is not a protein C deficiency but instead a poor response by _____ to protein C

Answer 76

Factor V